Original Research

Among National Football League (NFL) and National Collegiate Athletic Association (NCAA) team physicians, there is no consensus on the management of various injuries. At national and regional meetings, the management of football injuries often is debated.

Given the high level of interest in the treatment of elite football players, we wanted to determine treatment patterns by surveying orthopedic team physicians. We conducted a study to determine the demographics of NFL and NCAA team physicians and to identify patterns and variations in the management of common injuries in these groups of elite football players.

Materials and Methods

The study was reviewed by an Institutional Review Board before data collection and was classified as exempt. The study population consisted of head orthopedic team physicians for NFL teams and NCAA Division I universities. The survey (Appendix),

Chi-square tests were used to determine significant differences between groups. P < .05 was considered statistically significant.

Results

Responses were received from 31 (97%) of the 32 NFL and 111 (93%) of the 119 NCAA team physicians. The 2 groups’ surveys were identical with the exception of question 3, regarding NFL division or NCAA conference.

Team Physician Demographics

All survey respondents were the head orthopedic physicians for their teams. Seventy-one percent were the head team physicians as well; another 25% named a primary care physician as the head team physician. Thirty-nine percent of the NFL team physicians had been a team physician at the NFL level for more than 15 years, and 58% of the NCAA team physicians had been a team physician at the Division I level for more than 15 years. Eighty-one percent of NFL and 66% of NCAA team physicians had fellowship training in sports medicine. For away games, 10% of NFL vs 65% of NCAA teams traveled with 2 physicians; 90% of NFL and 28% of NCAA teams traveled with 3 or more physicians.

Only a small percentage of respondents (NFL, 10%; NCAA, 14%) indicated they had received advertising in exchange for services. Most respondents (NFL, 93%; NCAA, 89%) did not pay to provide team coverage. In contrast, 97% of NFL vs only 31% of NCAA physicians indicated they received a monetary stipend for providing orthopedic coverage.

Anterior Cruciate Ligament Reconstructions

Eighty-seven percent of NFL and 67% of NCAA respondents indicated that patellar tendon autograft was their preferred graft choice (Table 1).

Anterior Shoulder Dislocations (Without Bony Bankart)

Sling use after reduction of anterior shoulder dislocation was varied, with most physicians using a sling 2 weeks or less (Table 2).

Acromioclavicular Joint Injuries

Roughly two-thirds of respondents (NFL, 60%; NCAA, 69%) indicated that, during a game, they managed acute acromioclavicular (AC) joint injuries (type I/II) with injection of a local anesthetic that allowed return to play. In addition, a majority (NFL, 90%; NCAA, 87%) indicated they gave such athletes pregame injections that allowed them to play. About half the physicians (NFL, 57%; NCAA, 52%) injected the AC joint with cortisone during the acute/subacute period (<1 month) to decrease inflammation.

No significant difference was found between the 2 groups in terms of proportion of surgeons electing to treat type III AC joint injuries operatively versus nonoperatively (Table 4).

Medial Collateral Ligament Injuries

There was a significant (P < .0001) difference in use of prophylactic bracing for medial collateral ligament (MCL) injuries (NFL, 28%; NCAA, 89%).

Posterior Cruciate Ligament Injuries

The percentage of physicians who allowed athletes to return to play after a grade I/II posterior cruciate ligament (PCL) injury was significantly (P = .01) higher in NFL physicians (22%) than in NCAA physicians (7%). The amount of time varied up to more than 4 weeks (Figure 4).

Elbow Ulnar Collateral Ligament Tears

A majority of respondents indicated they would treat a complete elbow ulnar collateral ligament (UCL) tear in a quarterback; a much smaller percentage preferred operative repair in athletes playing other positions (Table 6).

Thumb Ulnar Collateral Ligament Tears

For athletes with in-season thumb UCL tears, 63% of NFL and 54% of NCAA physicians indicated they cast the thumb and allowed return to play. Others recommended operative repair and either cast the thumb and allowed return to play (NFL, 30%; NCAA, 41%) or let the thumb heal before allowing return to play (NFL, 7%; NCAA, 5%).

Fifth Metatarsal Fractures

For a large majority of physicians (NFL, 100%; NCAA, 94%), the preferred treatment for fifth metatarsal fractures was screw fixation.

Tibia Fractures

In the 5-year period before the survey, 43% of NFL and 75% of NCAA physicians managed at least one tibia fracture (P < .001) (Figure 7).

Ketorolac Injections

Intramuscular ketorolac injections were frequently given to elite football players, significantly (P < .01) more so in the NFL (93%) than in the NCAA (62%). The average number of injections varied among physicians, though a significantly (P < .0001) higher percentage of NFL (79%) than NCAA (13%) physicians gave 5 or more injections per game.

Discussion

This survey on managing common injuries in elite football players had an overall response rate of 94%. All NFL divisions and NCAA conferences were represented in physicians’ responses. Ninety percent of NFL and 65% of NCAA head team physicians were orthopedists. These findings differ from those of Stockard¹ (1997), who surveyed athletic directors at Division I schools and reported 45% of head team physicians were family medicine-trained and 41% were orthopedists.

Given the high visibility of team coverage and the economics of college football’s highest division, one might expect team physicians to receive financial remuneration. This was not the case, according to our survey: Only 30% of physicians received a monetary stipend for team coverage, and only 14% received advertising in exchange for their services. Twelve NCAA team physicians indicated they pay to be allowed to provide team coverage.

Injury Management

Anterior Cruciate Ligament Injuries. For NFL and NCAA team physicians, the preferred graft choice for ACL reconstruction was patellar tendon autograft. This finding is similar to what Erickson and colleagues² reported from a survey of NFL and NCAA team physicians: 86% of surgeons preferred bone–patellar tendon–bone (BPTB) autograft. However, only 1 surgeon (0.7%) in that study, vs 16% in ours, preferred allograft. Allograft use may be somewhat controversial, as relevant data on competitive athletes are lacking, and it has been shown that the graft rupture rate³ is higher for BPTB allograft than for BPTB autograft in young patients. However, much of the data on higher failure rates with use of allograft in young patients^4,5 has appeared since our data were collected.

Our return-to-play data are similar to data from other studies.^2,6 According to our survey, the most common length of time from ACL reconstruction to return to football was 6 months, and 94% of team physicians allowed return to football by 9 months. In the survey by Erickson and colleagues,² 55% of surgeons waited a minimum of 6 months before returning athletes to play, and only 12% waited at least 9 months. In the study by Bradley and colleagues⁶ (2002), 84% of surgeons waited at least 6 months before returning athletes to play. Of note, we found a significantly higher percentage of NCAA football players than NFL players returning within 6 months after surgery. The difference may be attributable to a more cautious approach being taken with NFL players, whereas most NCAA players are limited in the time remaining in their football careers and want to return to the playing field as soon as possible.

Shoulder Dislocations. Responses to the 5 survey questions on anterior shoulder dislocation showed little consensus with respect to management. The exception pertained to use of a harness for in-season return to play with a dislocation—92% of physicians preferred management with a harness. Of note, 7 of 10 team surgeons performed anterior stabilization through an arthroscopic approach. Despite historical recommendations to perform open anterior stabilization in collision athletes, NFL and NCAA physicians’ practice patterns have evolved.⁷ Although return to contact activity was varied among responses, 94% of physicians allowed return to contact within 6 months.

Acromioclavicular Joint Injuries. For college football players, AC joint injuries are the most common shoulder injuries.⁸ In the NFL Combine, the incidence of AC joint injuries was 15.7 per 100 players.⁸ Several studies have cited favorable results with nonoperative management of type III AC joint injuries.^9-12 Nonoperative management was the preferred treatment in our study as well, yet 26% of surgeons still preferred operative treatment in quarterbacks. Opinions about operative repair of type III injuries in overhead athletes vary,¹³ but nonoperative management clearly is the preferred method for elite football players. A 2013 study by Lynch and colleagues¹⁴ found that only 2 of 40 NFL players with type III AC joint injuries underwent surgery.

For type I and II AC joint injuries that occur during a game, more than two-thirds of the NCAA team physicians in our study favored injecting a local anesthetic to reduce pain and allow return to play in the same game. An even larger majority indicated they gave a pregame injection of an anesthetic to allow play. Similar use of injections for AC joint injuries has been reported in Australian-rules football and rugby.¹⁵Medial Collateral Ligament Injuries. Whether bracing is prophylactic against MCL injuries is controversial.¹⁶ Some studies have found it effective.^17,18 According to our survey, 89% of Division I football teams used prophylactic knee bracing, mainly in offensive linemen but frequently in defensive linemen, too. No schools used bracing in athletes who played skill positions, except quarterbacks. Six schools used bracing on a quarterback’s front leg.

The percentage of teams that used prophylactic MCL bracing was significantly higher in the NCAA than in the NFL. NCAA team physicians generally have more control over players and therefore can implement widespread use of this bracing.

Posterior Cruciate Ligament Injuries. These injuries are infrequent. According to Parolie and Bergfeld,¹⁹ only 2% of college football players at the NFL Combine had a PCL injury. Treatment in athletes remains controversial. Our survey showed physicians’ willingness to return players to competition within 4 weeks after grade I/II PCL injuries. There is no consensus on management or on postinjury bracing. In operative cases, however, the preferred graft is allograft, and the preferred repair method is the arthroscopic single-bundle technique. These findings mirror those of a 2004 survey of the Herodicus Society by Dennis and colleagues.²⁰ Elbow Ulnar Collateral Ligament Tears. In throwing athletes with UCL tears, operative treatment has been recommended.^21,22 A majority of our survey respondents preferred operative treatment for quarterbacks. However, operative treatment is still controversial, and quarterbacks differ from baseball players in their throwing motions and in the stresses acting on the UCLs during throwing. Two systematic reviews of UCL reconstruction have affirmed the positive outcomes of operative treatment in throwing athletes.^21,22 However, most of the studies covered by these reviews focused on baseball players. In athletes playing positions other than quarterback, these injuries were typically treated nonoperatively.

Thumb Ulnar Collateral Ligament Tears. Our survey respondents differed in their opinions on treating thumb UCL tears. About half recommended cast treatment, and the other half recommended operative treatment. Previous data suggest that delaying surgical treatment may be deleterious to the eventual outcome.^23,24Fifth Metatarsal Fractures. For fifth metatarsal fractures, screw fixation was preferred by 90% of our survey respondents—vs 73% of NFL team physicians in a 2004 study by Low and colleagues.²⁵ What remains controversial is the length of time before return to play. Our most frequent response was 4 to 6 weeks, and 46% of our respondents indicated they would wait 7 weeks or longer. These times differ significantly from what Low and colleagues²⁵ reported: 86% of their physicians allowed return to competition after 6 to 12 weeks.

Tibia Fractures. Management of tibia fractures in US football players has not been reported. Chang and colleagues²⁶ described 24 tibial shaft fractures in UK soccer players. Eleven fractures (~50%) were treated with intramedullary nails, 2 with plating, and 11 with conservative management. All players returned to activity, the operative group at 23.3 weeks and the nonoperative group at 27.6 weeks. Our respondents reported treating at least 150 tibial shaft fractures in the 5-year period before our survey, demonstrating the incidence and importance of this type of injury. A vast majority of team surgeons (96%) opted for treatment with intramedullary nailing. This choice may reflect an ability to return to play earlier—the ability to move the knee and maintain strength in the legs. Some have suggested it is important to remove the nail before the player returns to the football field, but this was not common practice among our groups of team surgeons. Other studies have not found any advantage to tibial nail removal.²⁷Ketorolac Injections. Authors have described using ketorolac for the treatment of acute or pregame pain in professional football players.^28-30 According to a 2000 survey, 93% of NFL teams used intramuscular ketorolac, and on average 15 players per team were treated, primarily on game day. Our survey found frequent use of ketorolac, with almost two-thirds of team orthopedists indicating pregame use. Ketorolac use was popular, particularly because of its effect in reducing postoperative pain and its potent effect in reducing pain on game day. However, injections by football team physicians have declined significantly in recent years, ever since an NFL Physician Society task force published recommendations on ketorolac use.³¹

Conclusion

There is a wide variety of patterns in treating athletes who play football at the highest levels of competition. Our findings can initiate further discussion on these topics and assist orthopedists providing game coverage at all levels of play in their decision-making process by helping to define the standard of care for their injured players.

Am J Orthop. 2016;45(6):E319-E327. Copyright Frontline Medical Communications Inc. 2016. All rights reserved.

Among National Football League (NFL) and National Collegiate Athletic Association (NCAA) team physicians, there is no consensus on the management of various injuries. At national and regional meetings, the management of football injuries often is debated.

Given the high level of interest in the treatment of elite football players, we wanted to determine treatment patterns by surveying orthopedic team physicians. We conducted a study to determine the demographics of NFL and NCAA team physicians and to identify patterns and variations in the management of common injuries in these groups of elite football players.

Materials and Methods

The study was reviewed by an Institutional Review Board before data collection and was classified as exempt. The study population consisted of head orthopedic team physicians for NFL teams and NCAA Division I universities. The survey (Appendix),

Chi-square tests were used to determine significant differences between groups. P < .05 was considered statistically significant.

Results

Responses were received from 31 (97%) of the 32 NFL and 111 (93%) of the 119 NCAA team physicians. The 2 groups’ surveys were identical with the exception of question 3, regarding NFL division or NCAA conference.

Team Physician Demographics

All survey respondents were the head orthopedic physicians for their teams. Seventy-one percent were the head team physicians as well; another 25% named a primary care physician as the head team physician. Thirty-nine percent of the NFL team physicians had been a team physician at the NFL level for more than 15 years, and 58% of the NCAA team physicians had been a team physician at the Division I level for more than 15 years. Eighty-one percent of NFL and 66% of NCAA team physicians had fellowship training in sports medicine. For away games, 10% of NFL vs 65% of NCAA teams traveled with 2 physicians; 90% of NFL and 28% of NCAA teams traveled with 3 or more physicians.

Only a small percentage of respondents (NFL, 10%; NCAA, 14%) indicated they had received advertising in exchange for services. Most respondents (NFL, 93%; NCAA, 89%) did not pay to provide team coverage. In contrast, 97% of NFL vs only 31% of NCAA physicians indicated they received a monetary stipend for providing orthopedic coverage.

Anterior Cruciate Ligament Reconstructions

Eighty-seven percent of NFL and 67% of NCAA respondents indicated that patellar tendon autograft was their preferred graft choice (Table 1).

Anterior Shoulder Dislocations (Without Bony Bankart)

Sling use after reduction of anterior shoulder dislocation was varied, with most physicians using a sling 2 weeks or less (Table 2).

Acromioclavicular Joint Injuries

Roughly two-thirds of respondents (NFL, 60%; NCAA, 69%) indicated that, during a game, they managed acute acromioclavicular (AC) joint injuries (type I/II) with injection of a local anesthetic that allowed return to play. In addition, a majority (NFL, 90%; NCAA, 87%) indicated they gave such athletes pregame injections that allowed them to play. About half the physicians (NFL, 57%; NCAA, 52%) injected the AC joint with cortisone during the acute/subacute period (<1 month) to decrease inflammation.

No significant difference was found between the 2 groups in terms of proportion of surgeons electing to treat type III AC joint injuries operatively versus nonoperatively (Table 4).

Medial Collateral Ligament Injuries

There was a significant (P < .0001) difference in use of prophylactic bracing for medial collateral ligament (MCL) injuries (NFL, 28%; NCAA, 89%).

Posterior Cruciate Ligament Injuries

The percentage of physicians who allowed athletes to return to play after a grade I/II posterior cruciate ligament (PCL) injury was significantly (P = .01) higher in NFL physicians (22%) than in NCAA physicians (7%). The amount of time varied up to more than 4 weeks (Figure 4).

Elbow Ulnar Collateral Ligament Tears

A majority of respondents indicated they would treat a complete elbow ulnar collateral ligament (UCL) tear in a quarterback; a much smaller percentage preferred operative repair in athletes playing other positions (Table 6).

Thumb Ulnar Collateral Ligament Tears

For athletes with in-season thumb UCL tears, 63% of NFL and 54% of NCAA physicians indicated they cast the thumb and allowed return to play. Others recommended operative repair and either cast the thumb and allowed return to play (NFL, 30%; NCAA, 41%) or let the thumb heal before allowing return to play (NFL, 7%; NCAA, 5%).

Fifth Metatarsal Fractures

For a large majority of physicians (NFL, 100%; NCAA, 94%), the preferred treatment for fifth metatarsal fractures was screw fixation.

Tibia Fractures

In the 5-year period before the survey, 43% of NFL and 75% of NCAA physicians managed at least one tibia fracture (P < .001) (Figure 7).

Ketorolac Injections

Intramuscular ketorolac injections were frequently given to elite football players, significantly (P < .01) more so in the NFL (93%) than in the NCAA (62%). The average number of injections varied among physicians, though a significantly (P < .0001) higher percentage of NFL (79%) than NCAA (13%) physicians gave 5 or more injections per game.

Discussion

This survey on managing common injuries in elite football players had an overall response rate of 94%. All NFL divisions and NCAA conferences were represented in physicians’ responses. Ninety percent of NFL and 65% of NCAA head team physicians were orthopedists. These findings differ from those of Stockard¹ (1997), who surveyed athletic directors at Division I schools and reported 45% of head team physicians were family medicine-trained and 41% were orthopedists.

Given the high visibility of team coverage and the economics of college football’s highest division, one might expect team physicians to receive financial remuneration. This was not the case, according to our survey: Only 30% of physicians received a monetary stipend for team coverage, and only 14% received advertising in exchange for their services. Twelve NCAA team physicians indicated they pay to be allowed to provide team coverage.

Injury Management

Anterior Cruciate Ligament Injuries. For NFL and NCAA team physicians, the preferred graft choice for ACL reconstruction was patellar tendon autograft. This finding is similar to what Erickson and colleagues² reported from a survey of NFL and NCAA team physicians: 86% of surgeons preferred bone–patellar tendon–bone (BPTB) autograft. However, only 1 surgeon (0.7%) in that study, vs 16% in ours, preferred allograft. Allograft use may be somewhat controversial, as relevant data on competitive athletes are lacking, and it has been shown that the graft rupture rate³ is higher for BPTB allograft than for BPTB autograft in young patients. However, much of the data on higher failure rates with use of allograft in young patients^4,5 has appeared since our data were collected.

Our return-to-play data are similar to data from other studies.^2,6 According to our survey, the most common length of time from ACL reconstruction to return to football was 6 months, and 94% of team physicians allowed return to football by 9 months. In the survey by Erickson and colleagues,² 55% of surgeons waited a minimum of 6 months before returning athletes to play, and only 12% waited at least 9 months. In the study by Bradley and colleagues⁶ (2002), 84% of surgeons waited at least 6 months before returning athletes to play. Of note, we found a significantly higher percentage of NCAA football players than NFL players returning within 6 months after surgery. The difference may be attributable to a more cautious approach being taken with NFL players, whereas most NCAA players are limited in the time remaining in their football careers and want to return to the playing field as soon as possible.

Shoulder Dislocations. Responses to the 5 survey questions on anterior shoulder dislocation showed little consensus with respect to management. The exception pertained to use of a harness for in-season return to play with a dislocation—92% of physicians preferred management with a harness. Of note, 7 of 10 team surgeons performed anterior stabilization through an arthroscopic approach. Despite historical recommendations to perform open anterior stabilization in collision athletes, NFL and NCAA physicians’ practice patterns have evolved.⁷ Although return to contact activity was varied among responses, 94% of physicians allowed return to contact within 6 months.

Acromioclavicular Joint Injuries. For college football players, AC joint injuries are the most common shoulder injuries.⁸ In the NFL Combine, the incidence of AC joint injuries was 15.7 per 100 players.⁸ Several studies have cited favorable results with nonoperative management of type III AC joint injuries.^9-12 Nonoperative management was the preferred treatment in our study as well, yet 26% of surgeons still preferred operative treatment in quarterbacks. Opinions about operative repair of type III injuries in overhead athletes vary,¹³ but nonoperative management clearly is the preferred method for elite football players. A 2013 study by Lynch and colleagues¹⁴ found that only 2 of 40 NFL players with type III AC joint injuries underwent surgery.

For type I and II AC joint injuries that occur during a game, more than two-thirds of the NCAA team physicians in our study favored injecting a local anesthetic to reduce pain and allow return to play in the same game. An even larger majority indicated they gave a pregame injection of an anesthetic to allow play. Similar use of injections for AC joint injuries has been reported in Australian-rules football and rugby.¹⁵Medial Collateral Ligament Injuries. Whether bracing is prophylactic against MCL injuries is controversial.¹⁶ Some studies have found it effective.^17,18 According to our survey, 89% of Division I football teams used prophylactic knee bracing, mainly in offensive linemen but frequently in defensive linemen, too. No schools used bracing in athletes who played skill positions, except quarterbacks. Six schools used bracing on a quarterback’s front leg.

The percentage of teams that used prophylactic MCL bracing was significantly higher in the NCAA than in the NFL. NCAA team physicians generally have more control over players and therefore can implement widespread use of this bracing.

Posterior Cruciate Ligament Injuries. These injuries are infrequent. According to Parolie and Bergfeld,¹⁹ only 2% of college football players at the NFL Combine had a PCL injury. Treatment in athletes remains controversial. Our survey showed physicians’ willingness to return players to competition within 4 weeks after grade I/II PCL injuries. There is no consensus on management or on postinjury bracing. In operative cases, however, the preferred graft is allograft, and the preferred repair method is the arthroscopic single-bundle technique. These findings mirror those of a 2004 survey of the Herodicus Society by Dennis and colleagues.²⁰ Elbow Ulnar Collateral Ligament Tears. In throwing athletes with UCL tears, operative treatment has been recommended.^21,22 A majority of our survey respondents preferred operative treatment for quarterbacks. However, operative treatment is still controversial, and quarterbacks differ from baseball players in their throwing motions and in the stresses acting on the UCLs during throwing. Two systematic reviews of UCL reconstruction have affirmed the positive outcomes of operative treatment in throwing athletes.^21,22 However, most of the studies covered by these reviews focused on baseball players. In athletes playing positions other than quarterback, these injuries were typically treated nonoperatively.

Thumb Ulnar Collateral Ligament Tears. Our survey respondents differed in their opinions on treating thumb UCL tears. About half recommended cast treatment, and the other half recommended operative treatment. Previous data suggest that delaying surgical treatment may be deleterious to the eventual outcome.^23,24Fifth Metatarsal Fractures. For fifth metatarsal fractures, screw fixation was preferred by 90% of our survey respondents—vs 73% of NFL team physicians in a 2004 study by Low and colleagues.²⁵ What remains controversial is the length of time before return to play. Our most frequent response was 4 to 6 weeks, and 46% of our respondents indicated they would wait 7 weeks or longer. These times differ significantly from what Low and colleagues²⁵ reported: 86% of their physicians allowed return to competition after 6 to 12 weeks.

Tibia Fractures. Management of tibia fractures in US football players has not been reported. Chang and colleagues²⁶ described 24 tibial shaft fractures in UK soccer players. Eleven fractures (~50%) were treated with intramedullary nails, 2 with plating, and 11 with conservative management. All players returned to activity, the operative group at 23.3 weeks and the nonoperative group at 27.6 weeks. Our respondents reported treating at least 150 tibial shaft fractures in the 5-year period before our survey, demonstrating the incidence and importance of this type of injury. A vast majority of team surgeons (96%) opted for treatment with intramedullary nailing. This choice may reflect an ability to return to play earlier—the ability to move the knee and maintain strength in the legs. Some have suggested it is important to remove the nail before the player returns to the football field, but this was not common practice among our groups of team surgeons. Other studies have not found any advantage to tibial nail removal.²⁷Ketorolac Injections. Authors have described using ketorolac for the treatment of acute or pregame pain in professional football players.^28-30 According to a 2000 survey, 93% of NFL teams used intramuscular ketorolac, and on average 15 players per team were treated, primarily on game day. Our survey found frequent use of ketorolac, with almost two-thirds of team orthopedists indicating pregame use. Ketorolac use was popular, particularly because of its effect in reducing postoperative pain and its potent effect in reducing pain on game day. However, injections by football team physicians have declined significantly in recent years, ever since an NFL Physician Society task force published recommendations on ketorolac use.³¹

Conclusion

There is a wide variety of patterns in treating athletes who play football at the highest levels of competition. Our findings can initiate further discussion on these topics and assist orthopedists providing game coverage at all levels of play in their decision-making process by helping to define the standard of care for their injured players.

Am J Orthop. 2016;45(6):E319-E327. Copyright Frontline Medical Communications Inc. 2016. All rights reserved.

Among National Football League (NFL) and National Collegiate Athletic Association (NCAA) team physicians, there is no consensus on the management of various injuries. At national and regional meetings, the management of football injuries often is debated.

Given the high level of interest in the treatment of elite football players, we wanted to determine treatment patterns by surveying orthopedic team physicians. We conducted a study to determine the demographics of NFL and NCAA team physicians and to identify patterns and variations in the management of common injuries in these groups of elite football players.

Materials and Methods

The study was reviewed by an Institutional Review Board before data collection and was classified as exempt. The study population consisted of head orthopedic team physicians for NFL teams and NCAA Division I universities. The survey (Appendix),

Chi-square tests were used to determine significant differences between groups. P < .05 was considered statistically significant.

Results

Responses were received from 31 (97%) of the 32 NFL and 111 (93%) of the 119 NCAA team physicians. The 2 groups’ surveys were identical with the exception of question 3, regarding NFL division or NCAA conference.

Team Physician Demographics

All survey respondents were the head orthopedic physicians for their teams. Seventy-one percent were the head team physicians as well; another 25% named a primary care physician as the head team physician. Thirty-nine percent of the NFL team physicians had been a team physician at the NFL level for more than 15 years, and 58% of the NCAA team physicians had been a team physician at the Division I level for more than 15 years. Eighty-one percent of NFL and 66% of NCAA team physicians had fellowship training in sports medicine. For away games, 10% of NFL vs 65% of NCAA teams traveled with 2 physicians; 90% of NFL and 28% of NCAA teams traveled with 3 or more physicians.

Only a small percentage of respondents (NFL, 10%; NCAA, 14%) indicated they had received advertising in exchange for services. Most respondents (NFL, 93%; NCAA, 89%) did not pay to provide team coverage. In contrast, 97% of NFL vs only 31% of NCAA physicians indicated they received a monetary stipend for providing orthopedic coverage.

Anterior Cruciate Ligament Reconstructions

Eighty-seven percent of NFL and 67% of NCAA respondents indicated that patellar tendon autograft was their preferred graft choice (Table 1).

Anterior Shoulder Dislocations (Without Bony Bankart)

Sling use after reduction of anterior shoulder dislocation was varied, with most physicians using a sling 2 weeks or less (Table 2).

Acromioclavicular Joint Injuries

Roughly two-thirds of respondents (NFL, 60%; NCAA, 69%) indicated that, during a game, they managed acute acromioclavicular (AC) joint injuries (type I/II) with injection of a local anesthetic that allowed return to play. In addition, a majority (NFL, 90%; NCAA, 87%) indicated they gave such athletes pregame injections that allowed them to play. About half the physicians (NFL, 57%; NCAA, 52%) injected the AC joint with cortisone during the acute/subacute period (<1 month) to decrease inflammation.

No significant difference was found between the 2 groups in terms of proportion of surgeons electing to treat type III AC joint injuries operatively versus nonoperatively (Table 4).

Medial Collateral Ligament Injuries

There was a significant (P < .0001) difference in use of prophylactic bracing for medial collateral ligament (MCL) injuries (NFL, 28%; NCAA, 89%).

Posterior Cruciate Ligament Injuries

The percentage of physicians who allowed athletes to return to play after a grade I/II posterior cruciate ligament (PCL) injury was significantly (P = .01) higher in NFL physicians (22%) than in NCAA physicians (7%). The amount of time varied up to more than 4 weeks (Figure 4).

Elbow Ulnar Collateral Ligament Tears

A majority of respondents indicated they would treat a complete elbow ulnar collateral ligament (UCL) tear in a quarterback; a much smaller percentage preferred operative repair in athletes playing other positions (Table 6).

Thumb Ulnar Collateral Ligament Tears

For athletes with in-season thumb UCL tears, 63% of NFL and 54% of NCAA physicians indicated they cast the thumb and allowed return to play. Others recommended operative repair and either cast the thumb and allowed return to play (NFL, 30%; NCAA, 41%) or let the thumb heal before allowing return to play (NFL, 7%; NCAA, 5%).

Fifth Metatarsal Fractures

For a large majority of physicians (NFL, 100%; NCAA, 94%), the preferred treatment for fifth metatarsal fractures was screw fixation.

Tibia Fractures

In the 5-year period before the survey, 43% of NFL and 75% of NCAA physicians managed at least one tibia fracture (P < .001) (Figure 7).

Ketorolac Injections

Intramuscular ketorolac injections were frequently given to elite football players, significantly (P < .01) more so in the NFL (93%) than in the NCAA (62%). The average number of injections varied among physicians, though a significantly (P < .0001) higher percentage of NFL (79%) than NCAA (13%) physicians gave 5 or more injections per game.

Discussion

This survey on managing common injuries in elite football players had an overall response rate of 94%. All NFL divisions and NCAA conferences were represented in physicians’ responses. Ninety percent of NFL and 65% of NCAA head team physicians were orthopedists. These findings differ from those of Stockard¹ (1997), who surveyed athletic directors at Division I schools and reported 45% of head team physicians were family medicine-trained and 41% were orthopedists.

Given the high visibility of team coverage and the economics of college football’s highest division, one might expect team physicians to receive financial remuneration. This was not the case, according to our survey: Only 30% of physicians received a monetary stipend for team coverage, and only 14% received advertising in exchange for their services. Twelve NCAA team physicians indicated they pay to be allowed to provide team coverage.

Injury Management

Anterior Cruciate Ligament Injuries. For NFL and NCAA team physicians, the preferred graft choice for ACL reconstruction was patellar tendon autograft. This finding is similar to what Erickson and colleagues² reported from a survey of NFL and NCAA team physicians: 86% of surgeons preferred bone–patellar tendon–bone (BPTB) autograft. However, only 1 surgeon (0.7%) in that study, vs 16% in ours, preferred allograft. Allograft use may be somewhat controversial, as relevant data on competitive athletes are lacking, and it has been shown that the graft rupture rate³ is higher for BPTB allograft than for BPTB autograft in young patients. However, much of the data on higher failure rates with use of allograft in young patients^4,5 has appeared since our data were collected.

Our return-to-play data are similar to data from other studies.^2,6 According to our survey, the most common length of time from ACL reconstruction to return to football was 6 months, and 94% of team physicians allowed return to football by 9 months. In the survey by Erickson and colleagues,² 55% of surgeons waited a minimum of 6 months before returning athletes to play, and only 12% waited at least 9 months. In the study by Bradley and colleagues⁶ (2002), 84% of surgeons waited at least 6 months before returning athletes to play. Of note, we found a significantly higher percentage of NCAA football players than NFL players returning within 6 months after surgery. The difference may be attributable to a more cautious approach being taken with NFL players, whereas most NCAA players are limited in the time remaining in their football careers and want to return to the playing field as soon as possible.

Shoulder Dislocations. Responses to the 5 survey questions on anterior shoulder dislocation showed little consensus with respect to management. The exception pertained to use of a harness for in-season return to play with a dislocation—92% of physicians preferred management with a harness. Of note, 7 of 10 team surgeons performed anterior stabilization through an arthroscopic approach. Despite historical recommendations to perform open anterior stabilization in collision athletes, NFL and NCAA physicians’ practice patterns have evolved.⁷ Although return to contact activity was varied among responses, 94% of physicians allowed return to contact within 6 months.

Acromioclavicular Joint Injuries. For college football players, AC joint injuries are the most common shoulder injuries.⁸ In the NFL Combine, the incidence of AC joint injuries was 15.7 per 100 players.⁸ Several studies have cited favorable results with nonoperative management of type III AC joint injuries.^9-12 Nonoperative management was the preferred treatment in our study as well, yet 26% of surgeons still preferred operative treatment in quarterbacks. Opinions about operative repair of type III injuries in overhead athletes vary,¹³ but nonoperative management clearly is the preferred method for elite football players. A 2013 study by Lynch and colleagues¹⁴ found that only 2 of 40 NFL players with type III AC joint injuries underwent surgery.

For type I and II AC joint injuries that occur during a game, more than two-thirds of the NCAA team physicians in our study favored injecting a local anesthetic to reduce pain and allow return to play in the same game. An even larger majority indicated they gave a pregame injection of an anesthetic to allow play. Similar use of injections for AC joint injuries has been reported in Australian-rules football and rugby.¹⁵Medial Collateral Ligament Injuries. Whether bracing is prophylactic against MCL injuries is controversial.¹⁶ Some studies have found it effective.^17,18 According to our survey, 89% of Division I football teams used prophylactic knee bracing, mainly in offensive linemen but frequently in defensive linemen, too. No schools used bracing in athletes who played skill positions, except quarterbacks. Six schools used bracing on a quarterback’s front leg.

The percentage of teams that used prophylactic MCL bracing was significantly higher in the NCAA than in the NFL. NCAA team physicians generally have more control over players and therefore can implement widespread use of this bracing.

Posterior Cruciate Ligament Injuries. These injuries are infrequent. According to Parolie and Bergfeld,¹⁹ only 2% of college football players at the NFL Combine had a PCL injury. Treatment in athletes remains controversial. Our survey showed physicians’ willingness to return players to competition within 4 weeks after grade I/II PCL injuries. There is no consensus on management or on postinjury bracing. In operative cases, however, the preferred graft is allograft, and the preferred repair method is the arthroscopic single-bundle technique. These findings mirror those of a 2004 survey of the Herodicus Society by Dennis and colleagues.²⁰ Elbow Ulnar Collateral Ligament Tears. In throwing athletes with UCL tears, operative treatment has been recommended.^21,22 A majority of our survey respondents preferred operative treatment for quarterbacks. However, operative treatment is still controversial, and quarterbacks differ from baseball players in their throwing motions and in the stresses acting on the UCLs during throwing. Two systematic reviews of UCL reconstruction have affirmed the positive outcomes of operative treatment in throwing athletes.^21,22 However, most of the studies covered by these reviews focused on baseball players. In athletes playing positions other than quarterback, these injuries were typically treated nonoperatively.

Thumb Ulnar Collateral Ligament Tears. Our survey respondents differed in their opinions on treating thumb UCL tears. About half recommended cast treatment, and the other half recommended operative treatment. Previous data suggest that delaying surgical treatment may be deleterious to the eventual outcome.^23,24Fifth Metatarsal Fractures. For fifth metatarsal fractures, screw fixation was preferred by 90% of our survey respondents—vs 73% of NFL team physicians in a 2004 study by Low and colleagues.²⁵ What remains controversial is the length of time before return to play. Our most frequent response was 4 to 6 weeks, and 46% of our respondents indicated they would wait 7 weeks or longer. These times differ significantly from what Low and colleagues²⁵ reported: 86% of their physicians allowed return to competition after 6 to 12 weeks.

Tibia Fractures. Management of tibia fractures in US football players has not been reported. Chang and colleagues²⁶ described 24 tibial shaft fractures in UK soccer players. Eleven fractures (~50%) were treated with intramedullary nails, 2 with plating, and 11 with conservative management. All players returned to activity, the operative group at 23.3 weeks and the nonoperative group at 27.6 weeks. Our respondents reported treating at least 150 tibial shaft fractures in the 5-year period before our survey, demonstrating the incidence and importance of this type of injury. A vast majority of team surgeons (96%) opted for treatment with intramedullary nailing. This choice may reflect an ability to return to play earlier—the ability to move the knee and maintain strength in the legs. Some have suggested it is important to remove the nail before the player returns to the football field, but this was not common practice among our groups of team surgeons. Other studies have not found any advantage to tibial nail removal.²⁷Ketorolac Injections. Authors have described using ketorolac for the treatment of acute or pregame pain in professional football players.^28-30 According to a 2000 survey, 93% of NFL teams used intramuscular ketorolac, and on average 15 players per team were treated, primarily on game day. Our survey found frequent use of ketorolac, with almost two-thirds of team orthopedists indicating pregame use. Ketorolac use was popular, particularly because of its effect in reducing postoperative pain and its potent effect in reducing pain on game day. However, injections by football team physicians have declined significantly in recent years, ever since an NFL Physician Society task force published recommendations on ketorolac use.³¹

Conclusion

There is a wide variety of patterns in treating athletes who play football at the highest levels of competition. Our findings can initiate further discussion on these topics and assist orthopedists providing game coverage at all levels of play in their decision-making process by helping to define the standard of care for their injured players.

Am J Orthop. 2016;45(6):E319-E327. Copyright Frontline Medical Communications Inc. 2016. All rights reserved.

From the Ochsner Diabetes Clinical Research Unit, Frank Riddick Diabetes Institute, Department of Endocrinology, Ochsner Medical Center, New Orleans, LA (Dr. Blonde), and AstraZeneca, Gaithersburg, MD (Drs. Sheehan, Barrett, and Garcia-Sanchez).

Abstract

• Objective: To evaluate diabetes care quality measure attainment, specifically, blood glucose and blood pressure (BP) control, with saxagliptin, a dipeptidyl peptidase-4 inhibitor, and dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, added singly or as dual add-on therapy in patients with type 2 diabetes inadequately controlled with metformin alone.
• Methods: Analysis of a phase 3, randomized, double-blind, active-controlled, parallel-group trial was conducted. Patients were randomized 1:1:1 to receive saxagliptin 5 mg/d plus dapagliflozin 10 mg/d, saxagliptin 5 mg/d, or dapagliflozin 10 mg/d as add-on to metformin 1500 to 2000 mg/d. Assessments included attainment of individual and composite glycated hemoglobin (A1C) and BP measures at 24 weeks of treatment.
• Results: Compared with single add-on saxagliptin or dapagliflozin, dual add-on saxagliptin plus dapagliflozin to metformin was associated with significantly more patients attaining the individual quality measures of A1C < 7% and A1C < 8%. Similarly, dual add-on saxagliptin plus dapagliflozin was associated with significantly more patients attaining the composite quality measures A1C < 7% and BP < 140/90 mm Hg and A1C < 8% and BP < 140/90 mmHg (vs saxagliptin plus metformin).
• Conclusion: Dual add-on saxagliptin plus dapagliflozin to metformin was associated with a higher proportion of patients achieving glycemic and BP quality measures compared with single add-on saxagliptin or dapagliflozin.

Assessment of performance is a focus of many health care organizations as a means to evaluate and improve the quality of health care. Standardized performance measures have been developed to improve quality of care as well as to allow for comparative assessment of health plans and to support pay for performance models [1]. A widely used set of performance measures is the Healthcare Effectiveness Data and Information Set or HEDIS [2,3], measures that are maintained by the National Committee for Quality Assurance [4,5] and used by most US health plans [6].

Type 2 diabetes (T2D) is a focus of quality measure assessment and performance improvement because of its high prevalence, substantial personal and economic impact on society, high morbidity and mortality, and because it is a condition that requires coordinated care. Important outcome measures for diabetes include blood glucose control and blood pressure (BP) control. HEDIS measures for T2D include a glycated hemoglobin (A1C) > 9%, indicating poor glucose control, < 8%, indicating good control, and < 7%, a more stringent measure of good glycemic control. The HEDIS measure for BP in T2D is < 140/90 mm Hg, which is considered good BP control. All of these HEDIS measures are currently or were previously (A1C < 7%) endorsed by the National Quality Forum [1,7–10]. Endorsement of a quality measure by the NQF indicates that the measure has been thoroughly evaluated, meets specific criteria, and is based on recognized standards of care grounded in evidence-based medicine [1].

A number of oral agents are utilized in the treatment of diabetes. Saxagliptin, an oral dipeptidyl peptidase-4 (DPP-4) inhibitor, and dapagliflozin, an oral sodium-glucose cotransporter-2 (SGLT-2) inhibitor, are indicated as adjuncts to diet and exercise in adults with T2D [11,12]. Saxagliptin inhibits DPP-4, and thereby reduces fasting and postprandial glucose concentrations by preventing degradation of the incretin hormones, glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide [13]. Dapagliflozin reduces blood glucose concentrations by inhibiting glucose reabsorption in the proximal tubule of the kidney, which results in enhanced urinary glucose excretion [14]. Because their mechanisms of action are glucose-dependent, both saxagliptin and dapagliflozin have a low intrinsic potential to cause hypoglycemia [13,14]. In a randomized, double-blind study of patients with T2D inadequately controlled with metformin, Rosenstock et al assessed the efficacy and safety of dual add-on of saxagliptin plus dapagliflozin versus saxagliptin and dapagliflozin added on alone (ClinicalTrials.gov identifier, NCT01606007) [15]. The dual add-on therapy resulted in a greater adjusted mean reduction from baseline in A1C at week 24 (–1.47%) compared with either saxagliptin (–0.88%) or dapagliflozin (–1.20%) alone added to metformin; the difference for dual add-on saxagliptin plus dapagliflozin to metformin vs. single add-on saxagliptin and single add-on dapagliflozin was –0.59% (P < 0.001) and –0.27% (P = 0.0166), respectively. The incidence of adverse events was similar across the 3 treatment groups, and hypo-glycemia was infrequent (1%), with no reports of severe hypoglycemia events (symptomatic events with glucose ≤ 54 mg/dL requiring assistance).

In this paper, we assess the attainment of diabetes quality measures among patients in this study, specifically, measures of glycemic and BP control.

Methods

Study Design and Patients

Quality Measure Assessment

Individual measures assessed included the proportion of patients with A1C < 7%, A1C < 8%, A1C > 9%, and BP < 140/90 mm Hg. Composite measures assessed includedthe proportion of patients with A1C < 7% and BP < 140/90 mm Hg and the proportion of patients with A1C < 8% and BP < 140/90 mm Hg.

Antihypertensive or cholesterol-lowering medication use was not controlled for in this study. Patients were maintained on their prescribed dosing regimen for antihypertensive and cholesterol-lowering medications, with adjustments as needed per the standard of care for their diagnosis. Treatment outcomes for A1C < 7%, < 8%, or > 9% were prespecified. The BP treatment outcome was also prespecified per the statistical analysis plan; however, a change to the HEDIS quality measure treatment outcome for BP during the clinical study resulted in this analysis being no longer relevant. Therefore, analyses of the currently endorsed quality measures for BP were conducted post hoc. Quality measure assessments for A1C and BP treatment outcomes were conducted using data from the 24-week, double-blind treatment period.

Statistical Analysis

P values for the differences in proportion of patients with individual treatment outcomes and composite treatment outcomes with saxagliptin plus dapagliflozin plus metformin versus saxagliptin plus metformin or dapagliflozin plus metformin were calculated using Fisher’s exact test. The numerator and denominator for each percentage are the number of responders and the number of patients with non-missing values in the treatment group at the corresponding baseline category, respectively, and are not corrected for baseline A1C. Because some patients experienced improvement in A1C during the lead-in period and could have already been at treatment goal at baseline, a sensitivity analysis excluding these patients was completed. Results are presented for the total number of patients with non-missing values in the treatment group, as well as patients with non-missing values in the treatment group who did not meet quality measure criteria at baseline. The number needed to treat (NNT) was calculated for all comparisons reaching statistical significance.

Results

Patients

Individual Quality Measures

The dual addition of saxagliptin plus dapagliflozin to metformin resulted in a significantly greater proportion of patients achieving A1C < 8.0% compared with saxagliptin plus metformin (71.2% vs 49.1%; P < 0.001; NNT 5 [95% CI 3–8]) or dapagliflozin plus metformin (60.1%; P = 0.033; NNT 9 [95% CI 5–85]; Figure 2). Similar results (proportions of patients: 66.4% vs 40.0% vs 51.9%; P ≤ 0.02; NNTs 4 [95% CI 3–7]) and 7 [95% CI 4–34]) were attained when the analysis excluded patients with baseline A1C < 8.0%.

Significantly fewer patients had A1C > 9% (a measure of poor glycemic control) with saxagliptin plus dapagliflozin plus metformin (12.4%) compared with saxagliptin plus metformin (22.3%; P = 0.017; NNT –10 [95% CI –50 to –6]; Figure 2). The proportion of patients with A1C > 9% was similar for both regimens that included dapagliflozin (12.4% vs 10.4%; P = 0.616).

No significant difference was observed among treatment groups in the proportion of patients with BP < 140/90 mm Hg (Figure 2). However, most patients had BP < 140/90 mm Hg (72%–82%) at baseline, which was generally maintained at week 24.

Composite Quality Measures

Discussion

This post hoc analysis evaluated attainment of glycemic and BP quality measures for diabetes. A significantly greater proportion of patients achieved the individual quality measures of A1C < 7% and A1C < 8% with dual add-on saxagliptin plus dapagliflozin to metformin compared with single add-on saxagliptin or dapagliflozin to metformin after 24 weeks. Similar results were seen when the analysis excluded patients with A1C < 7% and < 8% at baseline. All measures of good glycemic control had clinically relevant NNTs ≤ 10 after 24 weeks with saxagliptin plus dapagliflozin plus metformin compared with saxagliptin or dapagliflozin plus metformin, regardless of baseline status. Very few patients experienced lackof improvement in glycemic control, evidenced by small proportions of patients with A1C > 9%.

There was little difference in BP between dual add-on saxagliptin plus dapagliflozin or single add-on saxagliptin or dapagliflozin to metformin. The proportion of patients who attained the BP quality measure of BP < 140/90 mm Hg was similar across the 3 treatments, as might be expected because most patients already met this target at baseline. However, as might be expected based on the mild diuretic effect and weight loss associated with SGLT-2 inhibitors [16,17], trends in BP favored groups treated with dapagliflozin.

Attainment of multiple treatment targets is desirable in reducing complications of diabetes. A significantly greater proportion of patients achieved both A1C < 7% and BP < 140/90 mm Hg when both saxagliptin and dapagliflozin were added to metformin compared with single-agent addition of either saxagliptin or dapagliflozin plus metformin. Similarly, a significantly greater proportion of patients achieved both A1C < 8% and BP < 140/90 mm Hg with dual addition of saxagliptin and dapagliflozin plus metformin compared with saxagliptin plus metformin. There was also a numerically greater number of patients who achieved both of these goals with triple therapy compared with dapagliflozin plus metformin, but this finding did not reach statistical significance. Clinically relevant NNT values ≤ 10 were observed for both composite outcomes for saxagliptin plus dapagliflozin plus metformin compared with saxagliptin plus metformin or dapagliflozin plus metformin after 24 weeks.

Despite advances in the medical management of T2D, a report published in 2013 showed that between 2007 and 2010, only 53% of patients achieved an A1C < 7.0% and only 19% simultaneously achieved all 3 American Diabetes Association (ADA) goals recommended for most patients at that time: A1C < 7.0%, BP < 130/80 mm Hg, and low-density lipoprotein cholesterol LDL-C < 100 mg/dL [18]. These data highlight a need for new approaches to help patients attain glycemic, BP, and cholesterol goals. Our results demonstrated that a higher proportion of patients attained glycemic and BP quality measures with dual add-on saxagliptin plus dapagliflozin compared with single add-on saxagliptin or dapagliflozin to metformin. As a result of recent updates for cholesterol management from the American College of Cardiology and the American Heart Association [19], attainment of a cholesterol level was retired as a diabetes quality measure and replaced with a recommendation for statin therapy use [20,21]. Although the current analysis did not include assessment of LDL, DPP-4 inhibitors have demonstrated neutral effects on lipids [22,23], and SGLT-2 inhibitors have demonstrated generally modest increases in LDL-C (placebo-adjusted change from baseline: 4.5%–8.0% for canagliflozin 100 and 300 mg/d, 3.9% for dapagliflozin 10 mg, and 2.3%–4.2% for empagliflozin 10 and 25 mg/d) [12,24,25], as well as increases in high-density lipoprotein cholesterol and reductions in triglycerides [26].

Current ADA guidelines recommend an individualized, stepwise approach to treatment with sequential addition of single oral antihyperglycemic agents for patients who do not achieve their glycemic goal in 3 months [27]. Although T2D may progress at different rates in different patients, T2D does generally progress over time [28], and the ADA and American Association of Clinical Endocrinologists treatment guidelines recommend initial dual add-on therapy for individuals with higher A1C, which is suggestive of more advanced disease [27,29]. For individuals requiring initial combination therapy, guidelines note that antihyperglycemic agents that have a low risk of hypoglycemia and low potential for weight gain should be preferentially selected [29]. Attainment of A1C ≤ 7%, the guideline recommendation considered appropriate for many patients, is associated with reductions in microvascular disease and, if attained soon after diagnosis of diabetes, studies have shown reductions in macrovascular disease with long-term follow-up [27,30,31]. However, it may be challenging to achieve A1C < 7% with the addition of single oral antihyperglycemic agents, especially in patients with higher A1C [32]. Less stringent A1C goals (eg, A1C < 8%) may be appropriate in individuals with a long duration of diabetes that is difficult to control, history of severe hypoglycemia, limited life expectancy, numerous comorbidities, and extensive complications or comorbidities, especially cardiovascular disease [27]. Given the shift toward individualized treatment plans with patient-specific treatment goals, it is valuable to understand how different treatment strategies effect attainment of guideline-recommended less stringent and more stringent glycemic targets that may be appropriate for certain patients.

In addition to quality measures that assess glucose lowering with pharmacotherapy, it is important to consider measures that assess other aspects of diabetes care. For example, quality measures related to hypoglycemia and hyperglycemia may help avoid potentially adverse glucose levels, and quality measures related to weight may provide insight on treatment and lifestyle efforts directed at weight loss and management. NQF-endorsed measures of hypoglycemia and hyperglycemia are currently moving through annual review and are paired measures, intended to be interpreted with respect to one another to ensure balanced outcomes [33,34]. This underscores the value of efficacious antihyperglycemic agents with low intrinsic potential for hypoglycemia. Although this analysis did not include quality measures related to hypoglycemia or weight, future studies evaluating these aspects of diabetes care will likely further contribute to a more comprehensive and holistic treatment approach.

In addition to assessing a broad range of quality measures, an important aspect of care to consider is patient affordability. Affordability for an individual patient will depend on access in the patient’s individual plan, the financial resources of the patient, and the potential for medical cost offsets from improved control of the patient’s disease. For example, fixed-dose combination products are associated with increased patient adherence and may increase pharmacy costs but decrease medical costs [35].

Limitations of this study include the post hoc design and that quality measure attainment was assessed over a shorter duration of time (24 weeks) than is commonly assessed in the real-world/community setting (~12 months).

Dual add-on therapy with oral antihyperglycemic agents that have complementary mechanisms of action should lead to enhanced reductions in A1C. The results reported here and from the primary study, in which saxagliptin and dapagliflozin added to metformin significantly reduced mean A1C from baseline to week 24 compared with single add-on saxagliptin or dapagliflozin [15], showed that greater reductions in A1C were attained with the coadministration of saxagliptin and dapagliflozin. The glucuretic effect of SGLT-2 inhibitors has been associated with increased plasma glucagon concentrations and increased endogenous glucose production, which may impair the full glucose-lowering potential of SGLT-2 inhibitors [36,37]. Administering saxagliptin with dapagliflozin as dual therapy was shown to blunt the rise in plasma glucagon caused by dapagliflozin [38], and this may have contributed to the greater glucose control achieved with dual add-on of these 2 antihyperglycemic drugs [15].

By targeting multiple aspects of the underlying pathophysiology in T2D, greater improvements in A1C can be achieved. Dual add-on saxagliptin plus dapagliflozin to metformin resulted in a greater proportion of patients achieving NQF-endorsed HEDIS quality measures, as well as A1C < 7% (no longer an NQF-endorsed measure). As health care shifts to a more value-based payment structure, measuring quality outcomes will assume a greater role in guiding decision making and influence the care that patients receive. Understanding how antihyperglycemic medication regimens affect quality measures can help clinicians make informed decisions.

Corresponding author: Lawrence Blonde, MD, Ochsner Diabetes Clinical Research Unit, Frank Riddick Diabetes Institute, Department of Endocrinology, Ochsner Medical Center, New Orleans, LA.

Funding/support: This study was supported by AstraZeneca. Medical writing support for the preparation of this manuscript was provided by Lauren D’Angelo, PhD, and Janet Matsuura, PhD, from Complete Healthcare Communications, LLC (Chadds Ford, PA), with funding from AstraZeneca.

Financial disclosures: Dr. Blonde has received grant and research support from AstraZeneca, Jansen Pharmaceuticals, Lexicon Pharmaceuticals, Merck, Novo Nordisk, and Sanofi-Aventis and has received honoraria for participating as a speaker from AstraZeneca, Janssen Pharmaceuticals, Merck, Novo Nordisk, and Sanofi-Aventis as well as honoraria for consultant work from AstraZeneca, GlaxoSmithKline, Intarcia Therapeutics, Janssen Pharmaceuticals, Merck, Novo Nordisk, and Sanofi-Aventis. R. Garcia-Sanchez is an employee of AstraZeneca. J. Sheehan and Y. C. Barrett were employees of AstraZeneca at the time of this research.

From the Ochsner Diabetes Clinical Research Unit, Frank Riddick Diabetes Institute, Department of Endocrinology, Ochsner Medical Center, New Orleans, LA (Dr. Blonde), and AstraZeneca, Gaithersburg, MD (Drs. Sheehan, Barrett, and Garcia-Sanchez).

Abstract

• Objective: To evaluate diabetes care quality measure attainment, specifically, blood glucose and blood pressure (BP) control, with saxagliptin, a dipeptidyl peptidase-4 inhibitor, and dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, added singly or as dual add-on therapy in patients with type 2 diabetes inadequately controlled with metformin alone.
• Methods: Analysis of a phase 3, randomized, double-blind, active-controlled, parallel-group trial was conducted. Patients were randomized 1:1:1 to receive saxagliptin 5 mg/d plus dapagliflozin 10 mg/d, saxagliptin 5 mg/d, or dapagliflozin 10 mg/d as add-on to metformin 1500 to 2000 mg/d. Assessments included attainment of individual and composite glycated hemoglobin (A1C) and BP measures at 24 weeks of treatment.
• Results: Compared with single add-on saxagliptin or dapagliflozin, dual add-on saxagliptin plus dapagliflozin to metformin was associated with significantly more patients attaining the individual quality measures of A1C < 7% and A1C < 8%. Similarly, dual add-on saxagliptin plus dapagliflozin was associated with significantly more patients attaining the composite quality measures A1C < 7% and BP < 140/90 mm Hg and A1C < 8% and BP < 140/90 mmHg (vs saxagliptin plus metformin).
• Conclusion: Dual add-on saxagliptin plus dapagliflozin to metformin was associated with a higher proportion of patients achieving glycemic and BP quality measures compared with single add-on saxagliptin or dapagliflozin.

Assessment of performance is a focus of many health care organizations as a means to evaluate and improve the quality of health care. Standardized performance measures have been developed to improve quality of care as well as to allow for comparative assessment of health plans and to support pay for performance models [1]. A widely used set of performance measures is the Healthcare Effectiveness Data and Information Set or HEDIS [2,3], measures that are maintained by the National Committee for Quality Assurance [4,5] and used by most US health plans [6].

Type 2 diabetes (T2D) is a focus of quality measure assessment and performance improvement because of its high prevalence, substantial personal and economic impact on society, high morbidity and mortality, and because it is a condition that requires coordinated care. Important outcome measures for diabetes include blood glucose control and blood pressure (BP) control. HEDIS measures for T2D include a glycated hemoglobin (A1C) > 9%, indicating poor glucose control, < 8%, indicating good control, and < 7%, a more stringent measure of good glycemic control. The HEDIS measure for BP in T2D is < 140/90 mm Hg, which is considered good BP control. All of these HEDIS measures are currently or were previously (A1C < 7%) endorsed by the National Quality Forum [1,7–10]. Endorsement of a quality measure by the NQF indicates that the measure has been thoroughly evaluated, meets specific criteria, and is based on recognized standards of care grounded in evidence-based medicine [1].

A number of oral agents are utilized in the treatment of diabetes. Saxagliptin, an oral dipeptidyl peptidase-4 (DPP-4) inhibitor, and dapagliflozin, an oral sodium-glucose cotransporter-2 (SGLT-2) inhibitor, are indicated as adjuncts to diet and exercise in adults with T2D [11,12]. Saxagliptin inhibits DPP-4, and thereby reduces fasting and postprandial glucose concentrations by preventing degradation of the incretin hormones, glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide [13]. Dapagliflozin reduces blood glucose concentrations by inhibiting glucose reabsorption in the proximal tubule of the kidney, which results in enhanced urinary glucose excretion [14]. Because their mechanisms of action are glucose-dependent, both saxagliptin and dapagliflozin have a low intrinsic potential to cause hypoglycemia [13,14]. In a randomized, double-blind study of patients with T2D inadequately controlled with metformin, Rosenstock et al assessed the efficacy and safety of dual add-on of saxagliptin plus dapagliflozin versus saxagliptin and dapagliflozin added on alone (ClinicalTrials.gov identifier, NCT01606007) [15]. The dual add-on therapy resulted in a greater adjusted mean reduction from baseline in A1C at week 24 (–1.47%) compared with either saxagliptin (–0.88%) or dapagliflozin (–1.20%) alone added to metformin; the difference for dual add-on saxagliptin plus dapagliflozin to metformin vs. single add-on saxagliptin and single add-on dapagliflozin was –0.59% (P < 0.001) and –0.27% (P = 0.0166), respectively. The incidence of adverse events was similar across the 3 treatment groups, and hypo-glycemia was infrequent (1%), with no reports of severe hypoglycemia events (symptomatic events with glucose ≤ 54 mg/dL requiring assistance).

In this paper, we assess the attainment of diabetes quality measures among patients in this study, specifically, measures of glycemic and BP control.

Methods

Study Design and Patients

Quality Measure Assessment

Individual measures assessed included the proportion of patients with A1C < 7%, A1C < 8%, A1C > 9%, and BP < 140/90 mm Hg. Composite measures assessed includedthe proportion of patients with A1C < 7% and BP < 140/90 mm Hg and the proportion of patients with A1C < 8% and BP < 140/90 mm Hg.

Antihypertensive or cholesterol-lowering medication use was not controlled for in this study. Patients were maintained on their prescribed dosing regimen for antihypertensive and cholesterol-lowering medications, with adjustments as needed per the standard of care for their diagnosis. Treatment outcomes for A1C < 7%, < 8%, or > 9% were prespecified. The BP treatment outcome was also prespecified per the statistical analysis plan; however, a change to the HEDIS quality measure treatment outcome for BP during the clinical study resulted in this analysis being no longer relevant. Therefore, analyses of the currently endorsed quality measures for BP were conducted post hoc. Quality measure assessments for A1C and BP treatment outcomes were conducted using data from the 24-week, double-blind treatment period.

Statistical Analysis

P values for the differences in proportion of patients with individual treatment outcomes and composite treatment outcomes with saxagliptin plus dapagliflozin plus metformin versus saxagliptin plus metformin or dapagliflozin plus metformin were calculated using Fisher’s exact test. The numerator and denominator for each percentage are the number of responders and the number of patients with non-missing values in the treatment group at the corresponding baseline category, respectively, and are not corrected for baseline A1C. Because some patients experienced improvement in A1C during the lead-in period and could have already been at treatment goal at baseline, a sensitivity analysis excluding these patients was completed. Results are presented for the total number of patients with non-missing values in the treatment group, as well as patients with non-missing values in the treatment group who did not meet quality measure criteria at baseline. The number needed to treat (NNT) was calculated for all comparisons reaching statistical significance.

Results

Patients

Individual Quality Measures

The dual addition of saxagliptin plus dapagliflozin to metformin resulted in a significantly greater proportion of patients achieving A1C < 8.0% compared with saxagliptin plus metformin (71.2% vs 49.1%; P < 0.001; NNT 5 [95% CI 3–8]) or dapagliflozin plus metformin (60.1%; P = 0.033; NNT 9 [95% CI 5–85]; Figure 2). Similar results (proportions of patients: 66.4% vs 40.0% vs 51.9%; P ≤ 0.02; NNTs 4 [95% CI 3–7]) and 7 [95% CI 4–34]) were attained when the analysis excluded patients with baseline A1C < 8.0%.

Significantly fewer patients had A1C > 9% (a measure of poor glycemic control) with saxagliptin plus dapagliflozin plus metformin (12.4%) compared with saxagliptin plus metformin (22.3%; P = 0.017; NNT –10 [95% CI –50 to –6]; Figure 2). The proportion of patients with A1C > 9% was similar for both regimens that included dapagliflozin (12.4% vs 10.4%; P = 0.616).

No significant difference was observed among treatment groups in the proportion of patients with BP < 140/90 mm Hg (Figure 2). However, most patients had BP < 140/90 mm Hg (72%–82%) at baseline, which was generally maintained at week 24.

Composite Quality Measures

Discussion

This post hoc analysis evaluated attainment of glycemic and BP quality measures for diabetes. A significantly greater proportion of patients achieved the individual quality measures of A1C < 7% and A1C < 8% with dual add-on saxagliptin plus dapagliflozin to metformin compared with single add-on saxagliptin or dapagliflozin to metformin after 24 weeks. Similar results were seen when the analysis excluded patients with A1C < 7% and < 8% at baseline. All measures of good glycemic control had clinically relevant NNTs ≤ 10 after 24 weeks with saxagliptin plus dapagliflozin plus metformin compared with saxagliptin or dapagliflozin plus metformin, regardless of baseline status. Very few patients experienced lackof improvement in glycemic control, evidenced by small proportions of patients with A1C > 9%.

There was little difference in BP between dual add-on saxagliptin plus dapagliflozin or single add-on saxagliptin or dapagliflozin to metformin. The proportion of patients who attained the BP quality measure of BP < 140/90 mm Hg was similar across the 3 treatments, as might be expected because most patients already met this target at baseline. However, as might be expected based on the mild diuretic effect and weight loss associated with SGLT-2 inhibitors [16,17], trends in BP favored groups treated with dapagliflozin.

Attainment of multiple treatment targets is desirable in reducing complications of diabetes. A significantly greater proportion of patients achieved both A1C < 7% and BP < 140/90 mm Hg when both saxagliptin and dapagliflozin were added to metformin compared with single-agent addition of either saxagliptin or dapagliflozin plus metformin. Similarly, a significantly greater proportion of patients achieved both A1C < 8% and BP < 140/90 mm Hg with dual addition of saxagliptin and dapagliflozin plus metformin compared with saxagliptin plus metformin. There was also a numerically greater number of patients who achieved both of these goals with triple therapy compared with dapagliflozin plus metformin, but this finding did not reach statistical significance. Clinically relevant NNT values ≤ 10 were observed for both composite outcomes for saxagliptin plus dapagliflozin plus metformin compared with saxagliptin plus metformin or dapagliflozin plus metformin after 24 weeks.

Despite advances in the medical management of T2D, a report published in 2013 showed that between 2007 and 2010, only 53% of patients achieved an A1C < 7.0% and only 19% simultaneously achieved all 3 American Diabetes Association (ADA) goals recommended for most patients at that time: A1C < 7.0%, BP < 130/80 mm Hg, and low-density lipoprotein cholesterol LDL-C < 100 mg/dL [18]. These data highlight a need for new approaches to help patients attain glycemic, BP, and cholesterol goals. Our results demonstrated that a higher proportion of patients attained glycemic and BP quality measures with dual add-on saxagliptin plus dapagliflozin compared with single add-on saxagliptin or dapagliflozin to metformin. As a result of recent updates for cholesterol management from the American College of Cardiology and the American Heart Association [19], attainment of a cholesterol level was retired as a diabetes quality measure and replaced with a recommendation for statin therapy use [20,21]. Although the current analysis did not include assessment of LDL, DPP-4 inhibitors have demonstrated neutral effects on lipids [22,23], and SGLT-2 inhibitors have demonstrated generally modest increases in LDL-C (placebo-adjusted change from baseline: 4.5%–8.0% for canagliflozin 100 and 300 mg/d, 3.9% for dapagliflozin 10 mg, and 2.3%–4.2% for empagliflozin 10 and 25 mg/d) [12,24,25], as well as increases in high-density lipoprotein cholesterol and reductions in triglycerides [26].

Current ADA guidelines recommend an individualized, stepwise approach to treatment with sequential addition of single oral antihyperglycemic agents for patients who do not achieve their glycemic goal in 3 months [27]. Although T2D may progress at different rates in different patients, T2D does generally progress over time [28], and the ADA and American Association of Clinical Endocrinologists treatment guidelines recommend initial dual add-on therapy for individuals with higher A1C, which is suggestive of more advanced disease [27,29]. For individuals requiring initial combination therapy, guidelines note that antihyperglycemic agents that have a low risk of hypoglycemia and low potential for weight gain should be preferentially selected [29]. Attainment of A1C ≤ 7%, the guideline recommendation considered appropriate for many patients, is associated with reductions in microvascular disease and, if attained soon after diagnosis of diabetes, studies have shown reductions in macrovascular disease with long-term follow-up [27,30,31]. However, it may be challenging to achieve A1C < 7% with the addition of single oral antihyperglycemic agents, especially in patients with higher A1C [32]. Less stringent A1C goals (eg, A1C < 8%) may be appropriate in individuals with a long duration of diabetes that is difficult to control, history of severe hypoglycemia, limited life expectancy, numerous comorbidities, and extensive complications or comorbidities, especially cardiovascular disease [27]. Given the shift toward individualized treatment plans with patient-specific treatment goals, it is valuable to understand how different treatment strategies effect attainment of guideline-recommended less stringent and more stringent glycemic targets that may be appropriate for certain patients.

In addition to quality measures that assess glucose lowering with pharmacotherapy, it is important to consider measures that assess other aspects of diabetes care. For example, quality measures related to hypoglycemia and hyperglycemia may help avoid potentially adverse glucose levels, and quality measures related to weight may provide insight on treatment and lifestyle efforts directed at weight loss and management. NQF-endorsed measures of hypoglycemia and hyperglycemia are currently moving through annual review and are paired measures, intended to be interpreted with respect to one another to ensure balanced outcomes [33,34]. This underscores the value of efficacious antihyperglycemic agents with low intrinsic potential for hypoglycemia. Although this analysis did not include quality measures related to hypoglycemia or weight, future studies evaluating these aspects of diabetes care will likely further contribute to a more comprehensive and holistic treatment approach.

In addition to assessing a broad range of quality measures, an important aspect of care to consider is patient affordability. Affordability for an individual patient will depend on access in the patient’s individual plan, the financial resources of the patient, and the potential for medical cost offsets from improved control of the patient’s disease. For example, fixed-dose combination products are associated with increased patient adherence and may increase pharmacy costs but decrease medical costs [35].

Limitations of this study include the post hoc design and that quality measure attainment was assessed over a shorter duration of time (24 weeks) than is commonly assessed in the real-world/community setting (~12 months).

Dual add-on therapy with oral antihyperglycemic agents that have complementary mechanisms of action should lead to enhanced reductions in A1C. The results reported here and from the primary study, in which saxagliptin and dapagliflozin added to metformin significantly reduced mean A1C from baseline to week 24 compared with single add-on saxagliptin or dapagliflozin [15], showed that greater reductions in A1C were attained with the coadministration of saxagliptin and dapagliflozin. The glucuretic effect of SGLT-2 inhibitors has been associated with increased plasma glucagon concentrations and increased endogenous glucose production, which may impair the full glucose-lowering potential of SGLT-2 inhibitors [36,37]. Administering saxagliptin with dapagliflozin as dual therapy was shown to blunt the rise in plasma glucagon caused by dapagliflozin [38], and this may have contributed to the greater glucose control achieved with dual add-on of these 2 antihyperglycemic drugs [15].

By targeting multiple aspects of the underlying pathophysiology in T2D, greater improvements in A1C can be achieved. Dual add-on saxagliptin plus dapagliflozin to metformin resulted in a greater proportion of patients achieving NQF-endorsed HEDIS quality measures, as well as A1C < 7% (no longer an NQF-endorsed measure). As health care shifts to a more value-based payment structure, measuring quality outcomes will assume a greater role in guiding decision making and influence the care that patients receive. Understanding how antihyperglycemic medication regimens affect quality measures can help clinicians make informed decisions.

Corresponding author: Lawrence Blonde, MD, Ochsner Diabetes Clinical Research Unit, Frank Riddick Diabetes Institute, Department of Endocrinology, Ochsner Medical Center, New Orleans, LA.

Funding/support: This study was supported by AstraZeneca. Medical writing support for the preparation of this manuscript was provided by Lauren D’Angelo, PhD, and Janet Matsuura, PhD, from Complete Healthcare Communications, LLC (Chadds Ford, PA), with funding from AstraZeneca.

Financial disclosures: Dr. Blonde has received grant and research support from AstraZeneca, Jansen Pharmaceuticals, Lexicon Pharmaceuticals, Merck, Novo Nordisk, and Sanofi-Aventis and has received honoraria for participating as a speaker from AstraZeneca, Janssen Pharmaceuticals, Merck, Novo Nordisk, and Sanofi-Aventis as well as honoraria for consultant work from AstraZeneca, GlaxoSmithKline, Intarcia Therapeutics, Janssen Pharmaceuticals, Merck, Novo Nordisk, and Sanofi-Aventis. R. Garcia-Sanchez is an employee of AstraZeneca. J. Sheehan and Y. C. Barrett were employees of AstraZeneca at the time of this research.

From the Ochsner Diabetes Clinical Research Unit, Frank Riddick Diabetes Institute, Department of Endocrinology, Ochsner Medical Center, New Orleans, LA (Dr. Blonde), and AstraZeneca, Gaithersburg, MD (Drs. Sheehan, Barrett, and Garcia-Sanchez).

Abstract

• Objective: To evaluate diabetes care quality measure attainment, specifically, blood glucose and blood pressure (BP) control, with saxagliptin, a dipeptidyl peptidase-4 inhibitor, and dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, added singly or as dual add-on therapy in patients with type 2 diabetes inadequately controlled with metformin alone.
• Methods: Analysis of a phase 3, randomized, double-blind, active-controlled, parallel-group trial was conducted. Patients were randomized 1:1:1 to receive saxagliptin 5 mg/d plus dapagliflozin 10 mg/d, saxagliptin 5 mg/d, or dapagliflozin 10 mg/d as add-on to metformin 1500 to 2000 mg/d. Assessments included attainment of individual and composite glycated hemoglobin (A1C) and BP measures at 24 weeks of treatment.
• Results: Compared with single add-on saxagliptin or dapagliflozin, dual add-on saxagliptin plus dapagliflozin to metformin was associated with significantly more patients attaining the individual quality measures of A1C < 7% and A1C < 8%. Similarly, dual add-on saxagliptin plus dapagliflozin was associated with significantly more patients attaining the composite quality measures A1C < 7% and BP < 140/90 mm Hg and A1C < 8% and BP < 140/90 mmHg (vs saxagliptin plus metformin).
• Conclusion: Dual add-on saxagliptin plus dapagliflozin to metformin was associated with a higher proportion of patients achieving glycemic and BP quality measures compared with single add-on saxagliptin or dapagliflozin.

Assessment of performance is a focus of many health care organizations as a means to evaluate and improve the quality of health care. Standardized performance measures have been developed to improve quality of care as well as to allow for comparative assessment of health plans and to support pay for performance models [1]. A widely used set of performance measures is the Healthcare Effectiveness Data and Information Set or HEDIS [2,3], measures that are maintained by the National Committee for Quality Assurance [4,5] and used by most US health plans [6].

Type 2 diabetes (T2D) is a focus of quality measure assessment and performance improvement because of its high prevalence, substantial personal and economic impact on society, high morbidity and mortality, and because it is a condition that requires coordinated care. Important outcome measures for diabetes include blood glucose control and blood pressure (BP) control. HEDIS measures for T2D include a glycated hemoglobin (A1C) > 9%, indicating poor glucose control, < 8%, indicating good control, and < 7%, a more stringent measure of good glycemic control. The HEDIS measure for BP in T2D is < 140/90 mm Hg, which is considered good BP control. All of these HEDIS measures are currently or were previously (A1C < 7%) endorsed by the National Quality Forum [1,7–10]. Endorsement of a quality measure by the NQF indicates that the measure has been thoroughly evaluated, meets specific criteria, and is based on recognized standards of care grounded in evidence-based medicine [1].

A number of oral agents are utilized in the treatment of diabetes. Saxagliptin, an oral dipeptidyl peptidase-4 (DPP-4) inhibitor, and dapagliflozin, an oral sodium-glucose cotransporter-2 (SGLT-2) inhibitor, are indicated as adjuncts to diet and exercise in adults with T2D [11,12]. Saxagliptin inhibits DPP-4, and thereby reduces fasting and postprandial glucose concentrations by preventing degradation of the incretin hormones, glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide [13]. Dapagliflozin reduces blood glucose concentrations by inhibiting glucose reabsorption in the proximal tubule of the kidney, which results in enhanced urinary glucose excretion [14]. Because their mechanisms of action are glucose-dependent, both saxagliptin and dapagliflozin have a low intrinsic potential to cause hypoglycemia [13,14]. In a randomized, double-blind study of patients with T2D inadequately controlled with metformin, Rosenstock et al assessed the efficacy and safety of dual add-on of saxagliptin plus dapagliflozin versus saxagliptin and dapagliflozin added on alone (ClinicalTrials.gov identifier, NCT01606007) [15]. The dual add-on therapy resulted in a greater adjusted mean reduction from baseline in A1C at week 24 (–1.47%) compared with either saxagliptin (–0.88%) or dapagliflozin (–1.20%) alone added to metformin; the difference for dual add-on saxagliptin plus dapagliflozin to metformin vs. single add-on saxagliptin and single add-on dapagliflozin was –0.59% (P < 0.001) and –0.27% (P = 0.0166), respectively. The incidence of adverse events was similar across the 3 treatment groups, and hypo-glycemia was infrequent (1%), with no reports of severe hypoglycemia events (symptomatic events with glucose ≤ 54 mg/dL requiring assistance).

In this paper, we assess the attainment of diabetes quality measures among patients in this study, specifically, measures of glycemic and BP control.

Methods

Study Design and Patients

Quality Measure Assessment

Individual measures assessed included the proportion of patients with A1C < 7%, A1C < 8%, A1C > 9%, and BP < 140/90 mm Hg. Composite measures assessed includedthe proportion of patients with A1C < 7% and BP < 140/90 mm Hg and the proportion of patients with A1C < 8% and BP < 140/90 mm Hg.

Antihypertensive or cholesterol-lowering medication use was not controlled for in this study. Patients were maintained on their prescribed dosing regimen for antihypertensive and cholesterol-lowering medications, with adjustments as needed per the standard of care for their diagnosis. Treatment outcomes for A1C < 7%, < 8%, or > 9% were prespecified. The BP treatment outcome was also prespecified per the statistical analysis plan; however, a change to the HEDIS quality measure treatment outcome for BP during the clinical study resulted in this analysis being no longer relevant. Therefore, analyses of the currently endorsed quality measures for BP were conducted post hoc. Quality measure assessments for A1C and BP treatment outcomes were conducted using data from the 24-week, double-blind treatment period.

Statistical Analysis

P values for the differences in proportion of patients with individual treatment outcomes and composite treatment outcomes with saxagliptin plus dapagliflozin plus metformin versus saxagliptin plus metformin or dapagliflozin plus metformin were calculated using Fisher’s exact test. The numerator and denominator for each percentage are the number of responders and the number of patients with non-missing values in the treatment group at the corresponding baseline category, respectively, and are not corrected for baseline A1C. Because some patients experienced improvement in A1C during the lead-in period and could have already been at treatment goal at baseline, a sensitivity analysis excluding these patients was completed. Results are presented for the total number of patients with non-missing values in the treatment group, as well as patients with non-missing values in the treatment group who did not meet quality measure criteria at baseline. The number needed to treat (NNT) was calculated for all comparisons reaching statistical significance.

Results

Patients

Individual Quality Measures

The dual addition of saxagliptin plus dapagliflozin to metformin resulted in a significantly greater proportion of patients achieving A1C < 8.0% compared with saxagliptin plus metformin (71.2% vs 49.1%; P < 0.001; NNT 5 [95% CI 3–8]) or dapagliflozin plus metformin (60.1%; P = 0.033; NNT 9 [95% CI 5–85]; Figure 2). Similar results (proportions of patients: 66.4% vs 40.0% vs 51.9%; P ≤ 0.02; NNTs 4 [95% CI 3–7]) and 7 [95% CI 4–34]) were attained when the analysis excluded patients with baseline A1C < 8.0%.

Significantly fewer patients had A1C > 9% (a measure of poor glycemic control) with saxagliptin plus dapagliflozin plus metformin (12.4%) compared with saxagliptin plus metformin (22.3%; P = 0.017; NNT –10 [95% CI –50 to –6]; Figure 2). The proportion of patients with A1C > 9% was similar for both regimens that included dapagliflozin (12.4% vs 10.4%; P = 0.616).

No significant difference was observed among treatment groups in the proportion of patients with BP < 140/90 mm Hg (Figure 2). However, most patients had BP < 140/90 mm Hg (72%–82%) at baseline, which was generally maintained at week 24.

Composite Quality Measures

Discussion

This post hoc analysis evaluated attainment of glycemic and BP quality measures for diabetes. A significantly greater proportion of patients achieved the individual quality measures of A1C < 7% and A1C < 8% with dual add-on saxagliptin plus dapagliflozin to metformin compared with single add-on saxagliptin or dapagliflozin to metformin after 24 weeks. Similar results were seen when the analysis excluded patients with A1C < 7% and < 8% at baseline. All measures of good glycemic control had clinically relevant NNTs ≤ 10 after 24 weeks with saxagliptin plus dapagliflozin plus metformin compared with saxagliptin or dapagliflozin plus metformin, regardless of baseline status. Very few patients experienced lackof improvement in glycemic control, evidenced by small proportions of patients with A1C > 9%.

There was little difference in BP between dual add-on saxagliptin plus dapagliflozin or single add-on saxagliptin or dapagliflozin to metformin. The proportion of patients who attained the BP quality measure of BP < 140/90 mm Hg was similar across the 3 treatments, as might be expected because most patients already met this target at baseline. However, as might be expected based on the mild diuretic effect and weight loss associated with SGLT-2 inhibitors [16,17], trends in BP favored groups treated with dapagliflozin.

Attainment of multiple treatment targets is desirable in reducing complications of diabetes. A significantly greater proportion of patients achieved both A1C < 7% and BP < 140/90 mm Hg when both saxagliptin and dapagliflozin were added to metformin compared with single-agent addition of either saxagliptin or dapagliflozin plus metformin. Similarly, a significantly greater proportion of patients achieved both A1C < 8% and BP < 140/90 mm Hg with dual addition of saxagliptin and dapagliflozin plus metformin compared with saxagliptin plus metformin. There was also a numerically greater number of patients who achieved both of these goals with triple therapy compared with dapagliflozin plus metformin, but this finding did not reach statistical significance. Clinically relevant NNT values ≤ 10 were observed for both composite outcomes for saxagliptin plus dapagliflozin plus metformin compared with saxagliptin plus metformin or dapagliflozin plus metformin after 24 weeks.

Despite advances in the medical management of T2D, a report published in 2013 showed that between 2007 and 2010, only 53% of patients achieved an A1C < 7.0% and only 19% simultaneously achieved all 3 American Diabetes Association (ADA) goals recommended for most patients at that time: A1C < 7.0%, BP < 130/80 mm Hg, and low-density lipoprotein cholesterol LDL-C < 100 mg/dL [18]. These data highlight a need for new approaches to help patients attain glycemic, BP, and cholesterol goals. Our results demonstrated that a higher proportion of patients attained glycemic and BP quality measures with dual add-on saxagliptin plus dapagliflozin compared with single add-on saxagliptin or dapagliflozin to metformin. As a result of recent updates for cholesterol management from the American College of Cardiology and the American Heart Association [19], attainment of a cholesterol level was retired as a diabetes quality measure and replaced with a recommendation for statin therapy use [20,21]. Although the current analysis did not include assessment of LDL, DPP-4 inhibitors have demonstrated neutral effects on lipids [22,23], and SGLT-2 inhibitors have demonstrated generally modest increases in LDL-C (placebo-adjusted change from baseline: 4.5%–8.0% for canagliflozin 100 and 300 mg/d, 3.9% for dapagliflozin 10 mg, and 2.3%–4.2% for empagliflozin 10 and 25 mg/d) [12,24,25], as well as increases in high-density lipoprotein cholesterol and reductions in triglycerides [26].

Current ADA guidelines recommend an individualized, stepwise approach to treatment with sequential addition of single oral antihyperglycemic agents for patients who do not achieve their glycemic goal in 3 months [27]. Although T2D may progress at different rates in different patients, T2D does generally progress over time [28], and the ADA and American Association of Clinical Endocrinologists treatment guidelines recommend initial dual add-on therapy for individuals with higher A1C, which is suggestive of more advanced disease [27,29]. For individuals requiring initial combination therapy, guidelines note that antihyperglycemic agents that have a low risk of hypoglycemia and low potential for weight gain should be preferentially selected [29]. Attainment of A1C ≤ 7%, the guideline recommendation considered appropriate for many patients, is associated with reductions in microvascular disease and, if attained soon after diagnosis of diabetes, studies have shown reductions in macrovascular disease with long-term follow-up [27,30,31]. However, it may be challenging to achieve A1C < 7% with the addition of single oral antihyperglycemic agents, especially in patients with higher A1C [32]. Less stringent A1C goals (eg, A1C < 8%) may be appropriate in individuals with a long duration of diabetes that is difficult to control, history of severe hypoglycemia, limited life expectancy, numerous comorbidities, and extensive complications or comorbidities, especially cardiovascular disease [27]. Given the shift toward individualized treatment plans with patient-specific treatment goals, it is valuable to understand how different treatment strategies effect attainment of guideline-recommended less stringent and more stringent glycemic targets that may be appropriate for certain patients.

In addition to quality measures that assess glucose lowering with pharmacotherapy, it is important to consider measures that assess other aspects of diabetes care. For example, quality measures related to hypoglycemia and hyperglycemia may help avoid potentially adverse glucose levels, and quality measures related to weight may provide insight on treatment and lifestyle efforts directed at weight loss and management. NQF-endorsed measures of hypoglycemia and hyperglycemia are currently moving through annual review and are paired measures, intended to be interpreted with respect to one another to ensure balanced outcomes [33,34]. This underscores the value of efficacious antihyperglycemic agents with low intrinsic potential for hypoglycemia. Although this analysis did not include quality measures related to hypoglycemia or weight, future studies evaluating these aspects of diabetes care will likely further contribute to a more comprehensive and holistic treatment approach.

In addition to assessing a broad range of quality measures, an important aspect of care to consider is patient affordability. Affordability for an individual patient will depend on access in the patient’s individual plan, the financial resources of the patient, and the potential for medical cost offsets from improved control of the patient’s disease. For example, fixed-dose combination products are associated with increased patient adherence and may increase pharmacy costs but decrease medical costs [35].

Limitations of this study include the post hoc design and that quality measure attainment was assessed over a shorter duration of time (24 weeks) than is commonly assessed in the real-world/community setting (~12 months).

Dual add-on therapy with oral antihyperglycemic agents that have complementary mechanisms of action should lead to enhanced reductions in A1C. The results reported here and from the primary study, in which saxagliptin and dapagliflozin added to metformin significantly reduced mean A1C from baseline to week 24 compared with single add-on saxagliptin or dapagliflozin [15], showed that greater reductions in A1C were attained with the coadministration of saxagliptin and dapagliflozin. The glucuretic effect of SGLT-2 inhibitors has been associated with increased plasma glucagon concentrations and increased endogenous glucose production, which may impair the full glucose-lowering potential of SGLT-2 inhibitors [36,37]. Administering saxagliptin with dapagliflozin as dual therapy was shown to blunt the rise in plasma glucagon caused by dapagliflozin [38], and this may have contributed to the greater glucose control achieved with dual add-on of these 2 antihyperglycemic drugs [15].

By targeting multiple aspects of the underlying pathophysiology in T2D, greater improvements in A1C can be achieved. Dual add-on saxagliptin plus dapagliflozin to metformin resulted in a greater proportion of patients achieving NQF-endorsed HEDIS quality measures, as well as A1C < 7% (no longer an NQF-endorsed measure). As health care shifts to a more value-based payment structure, measuring quality outcomes will assume a greater role in guiding decision making and influence the care that patients receive. Understanding how antihyperglycemic medication regimens affect quality measures can help clinicians make informed decisions.

Corresponding author: Lawrence Blonde, MD, Ochsner Diabetes Clinical Research Unit, Frank Riddick Diabetes Institute, Department of Endocrinology, Ochsner Medical Center, New Orleans, LA.

Funding/support: This study was supported by AstraZeneca. Medical writing support for the preparation of this manuscript was provided by Lauren D’Angelo, PhD, and Janet Matsuura, PhD, from Complete Healthcare Communications, LLC (Chadds Ford, PA), with funding from AstraZeneca.

Financial disclosures: Dr. Blonde has received grant and research support from AstraZeneca, Jansen Pharmaceuticals, Lexicon Pharmaceuticals, Merck, Novo Nordisk, and Sanofi-Aventis and has received honoraria for participating as a speaker from AstraZeneca, Janssen Pharmaceuticals, Merck, Novo Nordisk, and Sanofi-Aventis as well as honoraria for consultant work from AstraZeneca, GlaxoSmithKline, Intarcia Therapeutics, Janssen Pharmaceuticals, Merck, Novo Nordisk, and Sanofi-Aventis. R. Garcia-Sanchez is an employee of AstraZeneca. J. Sheehan and Y. C. Barrett were employees of AstraZeneca at the time of this research.

Papulopustular rosacea (PPR) is characterized by centrofacial papules, pustules, erythema, and occasionally telangiectasia.^1,2 A myriad of factors, including genetic predisposition³ and environmental triggers,⁴ have been associated with dysregulated inflammatory responses,⁵ contributing to the disease pathogenesis and symptoms. Inflammation associated with PPR may decrease skin barrier function, increase transepidermal water loss, and reduce stratum corneum hydration,^6,7 resulting in heightened skin sensitivity, pain, burning, and/or stinging.^5,8

Azelaic acid (AzA), which historically has only been available in gel or cream formulations, is well established for the treatment of rosacea⁹; however, these formulations have been associated with application-site adverse events (AEs)(eg, burning, erythema, irritation), limited cosmetic acceptability, and reduced compliance or efficacy.¹⁰

For select skin conditions, active agents delivered in foam vehicles may offer superior tolerability with improved outcomes.¹¹ An AzA foam 15% formulation was approved for the treatment of mild to moderate PPR. Primary outcomes from a phase 3 trial demonstrated the efficacy and safety of AzA foam in improving inflammatory lesion counts (ILCs) and disease severity in participants with PPR. The trial also evaluated additional secondary end points, including the effect of AzA foam on erythema, inflammatory lesions, treatment response, and other manifestations of PPR.¹² The current study evaluated investigator-reported efficacy outcomes for these secondary end points for AzA foam 15% versus vehicle foam.

Methods

Study Design

This phase 3 multicenter, randomized, double-blind, vehicle-controlled, parallel-group clinical trial was conducted from September 2012 to January 2014 at 48 US study centers comparing the efficacy of AzA foam versus vehicle foam in patients with PPR. Eligible participants were 18 years and older with PPR rated as moderate or severe according to investigator global assessment (IGA), plus 12 to 50 inflammatory lesions and persistent erythema with or without telangiectasia. Exclusion criteria included known nonresponse to AzA, current or prior use (within 6 weeks of randomization) of noninvestigational products to treat rosacea, and presence of other dermatoses that could interfere with rosacea evaluation.

Participants were randomized into the AzA foam or vehicle group (1:1 ratio). The study medication was applied in 0.5-g doses twice daily until the end of treatment (EoT) at 12 weeks. Efficacy and safety parameters were evaluated at baseline and at 4, 8, and 12 weeks of treatment, and at a follow-up visit 4 weeks after EoT (week 16).

Results for the coprimary efficacy end points—therapeutic success rate according to IGA and nominal change in ILC—were previously reported.¹²

Investigator-Reported Secondary Efficacy Outcomes

The secondary efficacy end points were grouped change in erythema rating, grouped change in telangiectasia rating, grouped change in IGA score, therapeutic response rate according to IGA, percentage change in ILC from baseline, and facial skin color rating at EoT.

Grouped change for all secondary end points was measured as improved, no change, or worsened relative to baseline. For grouped change in erythema and telangiectasia ratings, a participant was considered improved if the rating at the postbaseline visit was lower than the baseline rating, no change if the postbaseline and baseline ratings were identical, and worsened if the postbaseline rating was higher than at baseline. For grouped change in IGA score, a participant was considered improved if a responder showed at least a 1-step improvement postbaseline compared to baseline, no change if postbaseline and baseline ratings were identical, and worsened if the postbaseline rating was higher than at baseline.

For the therapeutic response rate, a participant was considered a treatment responder if the IGA score improved from baseline and resulted in clear, minimal, or mild disease severity at EoT.

Safety

Adverse events also were assessed.

Statistical Analyses

Secondary efficacy and safety end points were assessed for all randomized participants who were dispensed the study medication. Missing data were imputed using last observation carried forward.

For the percentage change in ILC from baseline, therapeutic response rate, and grouped change in erythema rating, confirmatory analyses were conducted in a hierarchical manner (in the order listed), with testing stopped as soon as a null hypothesis of superior treatment effect could not be rejected. Analyses without significance level were exploratory. The Cochran-Mantel-Haenszel van Elteren test stratified by study center was used for grouped change in erythema rating (1-tailed, 2.5%) and IGA score (2-tailed, 5%); Wilcoxon rank sum tests also were performed. Percentage change in ILC from baseline was evaluated using the Student t test and F test of analysis of covariance (1-tailed, 2.5%). Therapeutic response rate was evaluated using the Cochran-Mantel-Haenszel van Elteren test stratified by study center and the Pearson χ² test. Facial skin color and grouped change in telangiectasia rating were evaluated using the Wilcoxon rank sum test.

Adverse events beginning or worsening after the first dose of the study drug were considered treatment emergent and were coded using the Medical Dictionary for Regulatory Activities (MedDRA) Version 16.1. Statistical analyses were performed using SAS software version 9.2.

Results

Study Participants

The study included 961 total participants; 483 were randomized to the AzA foam group and 478 to the vehicle group (Figure 1). Overall, 803 participants completed follow-up; however, week 16 results for the efficacy outcomes include data for 4 additional patients (2 per study arm) who did not formally meet all requirements for follow-up completion. The mean age was 51.5 years, and the majority of the participants were white and female (Table 1). Most participants (86.8%) had moderate PPR at baseline, with the remaining rated as having severe disease (13.2%). The majority (76.4%) had more than 14 inflammatory lesions with moderate (76.4%) or severe (15.1%) erythema at baseline.

Efficacy

Significantly more participants in the AzA group than in the vehicle group showed an improved erythema rating at EoT (61.5% vs 51.3%; P<.001)(Figure 2), with more participants in the AzA group showing improvement at weeks 4 (P=.022) and 8 (P=.002).

A significantly greater mean percentage reduction in ILC from baseline to EoT was observed in the AzA group versus the vehicle group (61.6% vs 50.8%; P<.001)(Figure 3), and between-group differences were observed at week 4 (P<.001), week 8 (P=.003), and week 16 (end of study/follow-up)(P=.002).

A significantly higher proportion of participants treated with AzA foam versus vehicle were considered responders at week 12/EoT (66.3% vs 54.4%; P<.001)(Figure 4). Differences in responder rate also were observed at week 4 (P=.026) and week 8 (P=.026).

Differences in grouped change in IGA score were observed between groups at every evaluation during the treatment phase (Figure 5). Specifically, IGA score was improved at week 12/EoT relative to baseline in 71.2% of participants in the AzA group versus 58.8% in the vehicle group (P<.001).

For grouped change in telangiectasia rating at EoT, the majority of participants in both treatment groups showed no change (Table 2). Regarding facial skin color, the majority of participants in both the AzA and vehicle treatment groups (80.1% and 78.7%, respectively) showed normal skin color compared to nontreated skin EoT; no between-group differences were detected for facial skin color rating (P=.315, Wilcoxon rank sum test).

Safety

The incidence of drug-related AEs was greater in the AzA group than the vehicle group (7.7% vs 4.8%)(Table 3). Drug-related AEs occurring in at least 1% of the AzA group were pain at application site (eg, tenderness, stinging, burning)(AzA group, 3.5%; vehicle group, 1.3%), application-site pruritus (1.4% vs 0.4%), and application-site dryness (1.0% vs 0.6%). A single drug-related AE of severe intensity (ie, application-site dermatitis) was observed in the vehicle group; all other drug-related AEs were mild or moderate. The incidence of withdrawals due to AEs was lower in the AzA group than the vehicle group (1.2% vs 2.5%). This AE profile correlated with a treatment compliance (the percentage of expected doses that were actually administered) of 97.0% in the AzA group and 95.9% in the vehicle group. One participant in the vehicle group died due to head trauma unrelated to administration of the study drug.

Comment

The results of this study further support the efficacy of AzA foam for the treatment of PPR. The percentage reduction in ILC was consistent with nominal decreases in ILC, a coprimary efficacy end point of this study.¹² Almost two-thirds of participants treated with AzA foam achieved a therapeutic response, indicating that many participants who did not strictly achieve the primary outcome of therapeutic success nevertheless attained notable reductions in disease severity. The number of participants who showed any improvement on the IGA scale increased throughout the course of treatment (63.8% AzA foam vs 55.0% vehicle at week 8) up to EoT (71.2% vs 58.8%)(Figure 5). In addition, the number of participants showing any improvement at week 8 (63.8% AzA foam vs 55.0% vehicle)(Figure 5) was comparable to the number of participants achieving therapeutic response at week 12/EoT (66.3% vs 54.4%)(Figure 4). These data suggest that increasing time of treatment increases the likelihood of achieving better results.

Erythema also appeared to respond to AzA foam, with 10.2% more participants in the AzA group demonstrating improvement at week 12/EoT compared to vehicle. The difference in grouped change in erythema rating also was statistically significant and favored AzA foam, sustained up to 4 weeks after EoT.

The outcomes for percentage change in ILC, therapeutic response rate, and grouped change in erythema rating consequently led to the rejection of all 3 null hypotheses in hierarchical confirmatory analyses, underscoring the benefits of AzA foam treatment.

The therapeutic effects of AzA foam were apparent at the first postbaseline evaluation and persisted throughout treatment. Differences favoring AzA foam were observed at every on-treatment evaluation for grouped change in erythema rating, percentage change in ILC, therapeutic response rate, and grouped change in IGA score. Symptoms showed minimal resurgence after treatment cessation, and there were no signs of disease flare-up within the 4 weeks of observational follow-up. In addition, the percentage reduction in ILC remained higher in the AzA foam group during follow-up.

These results also show that AzA foam was well tolerated with a low incidence of discontinuation because of drug-related AEs. No serious drug-related AEs were reported for this study or in the preceding phase 2 trial.^12,13 Although not directly evaluated, the low incidence of cutaneous AEs suggests that AzA foam may be better tolerated than prior formulations of AzA^14,15 and correlates with high compliance observed during the study.¹² Azelaic acid foam appeared to have minimal to no effect on skin color, with more than 88% of participants reporting barely visible or no skin lightening.

Interestingly, the vehicle foam showed appreciable efficacy independent of AzA. Improvements in erythema were recorded in approximately half of the vehicle group at week 12/EoT. A similar proportion attained a therapeutic response, and ILC was reduced by 50.8% at week 12/EoT. Comparable results also were evident in the vehicle group for the primary end points of this study.¹² Vehicles in dermatologic trials frequently exert effects on diseased skin^16,17 via a skin care regimen effect (eg, moisturization and other vehicle-related effects that may improve skin barrier integrity and function) and thus should not be regarded as placebo controls. The mechanism underlying this efficacy may be due to the impact of vehicle composition on skin barrier integrity and transepidermal water loss.¹⁸ The hydrophilic emulsion or other constituents of AzA foam (eg, fatty alcohols) may play a role.

A notable strength of our study is detailed clinical characterization using carefully chosen parameters and preplanned analyses that complement the primary end points. As the latter are often driven by regulatory requirements, opportunities to characterize other outcomes of interest to clinicians may be missed. The additional analyses reported here hopefully will aid dermatologists in both assessing the role of AzA foam in the treatment armamentarium for PPR and counseling patients.

Because participants with lighter skin pigmentation dominated our study population, the impact of AzA foam among patients with darker skin complexions is unknown. Although AzA is unlikely to cause hypopigmentation in normal undiseased skin, patients should be monitored for early signs of hypopigmentation.^19,20 Our data also do not allow assessment of the differential effect, if any, of AzA foam on erythema of different etiologies in PPR, as corresponding information was not collected in the trial.

Conclusion

Azelaic acid foam 15% combines a well-established treatment of PPR with new vehicle technology to deliver effective therapy across multiple disease dimensions. In addition, the vehicle foam appears to demonstrate inherent therapeutic properties independent of AzA. The availability of this novel, efficacious, and well-tolerated option for PPR has the potential to improve patient care, reduce disease burden, and minimize unnecessary costs through increased tolerability and compliance.²¹

Acknowledgment

Editorial support through inVentiv Medical Communications (New York, New York) was provided by Bayer Pharmaceuticals.

Papulopustular rosacea (PPR) is characterized by centrofacial papules, pustules, erythema, and occasionally telangiectasia.^1,2 A myriad of factors, including genetic predisposition³ and environmental triggers,⁴ have been associated with dysregulated inflammatory responses,⁵ contributing to the disease pathogenesis and symptoms. Inflammation associated with PPR may decrease skin barrier function, increase transepidermal water loss, and reduce stratum corneum hydration,^6,7 resulting in heightened skin sensitivity, pain, burning, and/or stinging.^5,8

Azelaic acid (AzA), which historically has only been available in gel or cream formulations, is well established for the treatment of rosacea⁹; however, these formulations have been associated with application-site adverse events (AEs)(eg, burning, erythema, irritation), limited cosmetic acceptability, and reduced compliance or efficacy.¹⁰

For select skin conditions, active agents delivered in foam vehicles may offer superior tolerability with improved outcomes.¹¹ An AzA foam 15% formulation was approved for the treatment of mild to moderate PPR. Primary outcomes from a phase 3 trial demonstrated the efficacy and safety of AzA foam in improving inflammatory lesion counts (ILCs) and disease severity in participants with PPR. The trial also evaluated additional secondary end points, including the effect of AzA foam on erythema, inflammatory lesions, treatment response, and other manifestations of PPR.¹² The current study evaluated investigator-reported efficacy outcomes for these secondary end points for AzA foam 15% versus vehicle foam.

Methods

Study Design

This phase 3 multicenter, randomized, double-blind, vehicle-controlled, parallel-group clinical trial was conducted from September 2012 to January 2014 at 48 US study centers comparing the efficacy of AzA foam versus vehicle foam in patients with PPR. Eligible participants were 18 years and older with PPR rated as moderate or severe according to investigator global assessment (IGA), plus 12 to 50 inflammatory lesions and persistent erythema with or without telangiectasia. Exclusion criteria included known nonresponse to AzA, current or prior use (within 6 weeks of randomization) of noninvestigational products to treat rosacea, and presence of other dermatoses that could interfere with rosacea evaluation.

Participants were randomized into the AzA foam or vehicle group (1:1 ratio). The study medication was applied in 0.5-g doses twice daily until the end of treatment (EoT) at 12 weeks. Efficacy and safety parameters were evaluated at baseline and at 4, 8, and 12 weeks of treatment, and at a follow-up visit 4 weeks after EoT (week 16).

Results for the coprimary efficacy end points—therapeutic success rate according to IGA and nominal change in ILC—were previously reported.¹²

Investigator-Reported Secondary Efficacy Outcomes

The secondary efficacy end points were grouped change in erythema rating, grouped change in telangiectasia rating, grouped change in IGA score, therapeutic response rate according to IGA, percentage change in ILC from baseline, and facial skin color rating at EoT.

Grouped change for all secondary end points was measured as improved, no change, or worsened relative to baseline. For grouped change in erythema and telangiectasia ratings, a participant was considered improved if the rating at the postbaseline visit was lower than the baseline rating, no change if the postbaseline and baseline ratings were identical, and worsened if the postbaseline rating was higher than at baseline. For grouped change in IGA score, a participant was considered improved if a responder showed at least a 1-step improvement postbaseline compared to baseline, no change if postbaseline and baseline ratings were identical, and worsened if the postbaseline rating was higher than at baseline.

For the therapeutic response rate, a participant was considered a treatment responder if the IGA score improved from baseline and resulted in clear, minimal, or mild disease severity at EoT.

Safety

Adverse events also were assessed.

Statistical Analyses

Secondary efficacy and safety end points were assessed for all randomized participants who were dispensed the study medication. Missing data were imputed using last observation carried forward.

For the percentage change in ILC from baseline, therapeutic response rate, and grouped change in erythema rating, confirmatory analyses were conducted in a hierarchical manner (in the order listed), with testing stopped as soon as a null hypothesis of superior treatment effect could not be rejected. Analyses without significance level were exploratory. The Cochran-Mantel-Haenszel van Elteren test stratified by study center was used for grouped change in erythema rating (1-tailed, 2.5%) and IGA score (2-tailed, 5%); Wilcoxon rank sum tests also were performed. Percentage change in ILC from baseline was evaluated using the Student t test and F test of analysis of covariance (1-tailed, 2.5%). Therapeutic response rate was evaluated using the Cochran-Mantel-Haenszel van Elteren test stratified by study center and the Pearson χ² test. Facial skin color and grouped change in telangiectasia rating were evaluated using the Wilcoxon rank sum test.

Adverse events beginning or worsening after the first dose of the study drug were considered treatment emergent and were coded using the Medical Dictionary for Regulatory Activities (MedDRA) Version 16.1. Statistical analyses were performed using SAS software version 9.2.

Results

Study Participants

The study included 961 total participants; 483 were randomized to the AzA foam group and 478 to the vehicle group (Figure 1). Overall, 803 participants completed follow-up; however, week 16 results for the efficacy outcomes include data for 4 additional patients (2 per study arm) who did not formally meet all requirements for follow-up completion. The mean age was 51.5 years, and the majority of the participants were white and female (Table 1). Most participants (86.8%) had moderate PPR at baseline, with the remaining rated as having severe disease (13.2%). The majority (76.4%) had more than 14 inflammatory lesions with moderate (76.4%) or severe (15.1%) erythema at baseline.

Efficacy

Significantly more participants in the AzA group than in the vehicle group showed an improved erythema rating at EoT (61.5% vs 51.3%; P<.001)(Figure 2), with more participants in the AzA group showing improvement at weeks 4 (P=.022) and 8 (P=.002).

A significantly greater mean percentage reduction in ILC from baseline to EoT was observed in the AzA group versus the vehicle group (61.6% vs 50.8%; P<.001)(Figure 3), and between-group differences were observed at week 4 (P<.001), week 8 (P=.003), and week 16 (end of study/follow-up)(P=.002).

A significantly higher proportion of participants treated with AzA foam versus vehicle were considered responders at week 12/EoT (66.3% vs 54.4%; P<.001)(Figure 4). Differences in responder rate also were observed at week 4 (P=.026) and week 8 (P=.026).

Differences in grouped change in IGA score were observed between groups at every evaluation during the treatment phase (Figure 5). Specifically, IGA score was improved at week 12/EoT relative to baseline in 71.2% of participants in the AzA group versus 58.8% in the vehicle group (P<.001).

For grouped change in telangiectasia rating at EoT, the majority of participants in both treatment groups showed no change (Table 2). Regarding facial skin color, the majority of participants in both the AzA and vehicle treatment groups (80.1% and 78.7%, respectively) showed normal skin color compared to nontreated skin EoT; no between-group differences were detected for facial skin color rating (P=.315, Wilcoxon rank sum test).

Safety

The incidence of drug-related AEs was greater in the AzA group than the vehicle group (7.7% vs 4.8%)(Table 3). Drug-related AEs occurring in at least 1% of the AzA group were pain at application site (eg, tenderness, stinging, burning)(AzA group, 3.5%; vehicle group, 1.3%), application-site pruritus (1.4% vs 0.4%), and application-site dryness (1.0% vs 0.6%). A single drug-related AE of severe intensity (ie, application-site dermatitis) was observed in the vehicle group; all other drug-related AEs were mild or moderate. The incidence of withdrawals due to AEs was lower in the AzA group than the vehicle group (1.2% vs 2.5%). This AE profile correlated with a treatment compliance (the percentage of expected doses that were actually administered) of 97.0% in the AzA group and 95.9% in the vehicle group. One participant in the vehicle group died due to head trauma unrelated to administration of the study drug.

Comment

The results of this study further support the efficacy of AzA foam for the treatment of PPR. The percentage reduction in ILC was consistent with nominal decreases in ILC, a coprimary efficacy end point of this study.¹² Almost two-thirds of participants treated with AzA foam achieved a therapeutic response, indicating that many participants who did not strictly achieve the primary outcome of therapeutic success nevertheless attained notable reductions in disease severity. The number of participants who showed any improvement on the IGA scale increased throughout the course of treatment (63.8% AzA foam vs 55.0% vehicle at week 8) up to EoT (71.2% vs 58.8%)(Figure 5). In addition, the number of participants showing any improvement at week 8 (63.8% AzA foam vs 55.0% vehicle)(Figure 5) was comparable to the number of participants achieving therapeutic response at week 12/EoT (66.3% vs 54.4%)(Figure 4). These data suggest that increasing time of treatment increases the likelihood of achieving better results.

Erythema also appeared to respond to AzA foam, with 10.2% more participants in the AzA group demonstrating improvement at week 12/EoT compared to vehicle. The difference in grouped change in erythema rating also was statistically significant and favored AzA foam, sustained up to 4 weeks after EoT.

The outcomes for percentage change in ILC, therapeutic response rate, and grouped change in erythema rating consequently led to the rejection of all 3 null hypotheses in hierarchical confirmatory analyses, underscoring the benefits of AzA foam treatment.

The therapeutic effects of AzA foam were apparent at the first postbaseline evaluation and persisted throughout treatment. Differences favoring AzA foam were observed at every on-treatment evaluation for grouped change in erythema rating, percentage change in ILC, therapeutic response rate, and grouped change in IGA score. Symptoms showed minimal resurgence after treatment cessation, and there were no signs of disease flare-up within the 4 weeks of observational follow-up. In addition, the percentage reduction in ILC remained higher in the AzA foam group during follow-up.

These results also show that AzA foam was well tolerated with a low incidence of discontinuation because of drug-related AEs. No serious drug-related AEs were reported for this study or in the preceding phase 2 trial.^12,13 Although not directly evaluated, the low incidence of cutaneous AEs suggests that AzA foam may be better tolerated than prior formulations of AzA^14,15 and correlates with high compliance observed during the study.¹² Azelaic acid foam appeared to have minimal to no effect on skin color, with more than 88% of participants reporting barely visible or no skin lightening.

Interestingly, the vehicle foam showed appreciable efficacy independent of AzA. Improvements in erythema were recorded in approximately half of the vehicle group at week 12/EoT. A similar proportion attained a therapeutic response, and ILC was reduced by 50.8% at week 12/EoT. Comparable results also were evident in the vehicle group for the primary end points of this study.¹² Vehicles in dermatologic trials frequently exert effects on diseased skin^16,17 via a skin care regimen effect (eg, moisturization and other vehicle-related effects that may improve skin barrier integrity and function) and thus should not be regarded as placebo controls. The mechanism underlying this efficacy may be due to the impact of vehicle composition on skin barrier integrity and transepidermal water loss.¹⁸ The hydrophilic emulsion or other constituents of AzA foam (eg, fatty alcohols) may play a role.

A notable strength of our study is detailed clinical characterization using carefully chosen parameters and preplanned analyses that complement the primary end points. As the latter are often driven by regulatory requirements, opportunities to characterize other outcomes of interest to clinicians may be missed. The additional analyses reported here hopefully will aid dermatologists in both assessing the role of AzA foam in the treatment armamentarium for PPR and counseling patients.

Because participants with lighter skin pigmentation dominated our study population, the impact of AzA foam among patients with darker skin complexions is unknown. Although AzA is unlikely to cause hypopigmentation in normal undiseased skin, patients should be monitored for early signs of hypopigmentation.^19,20 Our data also do not allow assessment of the differential effect, if any, of AzA foam on erythema of different etiologies in PPR, as corresponding information was not collected in the trial.

Conclusion

Azelaic acid foam 15% combines a well-established treatment of PPR with new vehicle technology to deliver effective therapy across multiple disease dimensions. In addition, the vehicle foam appears to demonstrate inherent therapeutic properties independent of AzA. The availability of this novel, efficacious, and well-tolerated option for PPR has the potential to improve patient care, reduce disease burden, and minimize unnecessary costs through increased tolerability and compliance.²¹

Acknowledgment

Editorial support through inVentiv Medical Communications (New York, New York) was provided by Bayer Pharmaceuticals.

Papulopustular rosacea (PPR) is characterized by centrofacial papules, pustules, erythema, and occasionally telangiectasia.^1,2 A myriad of factors, including genetic predisposition³ and environmental triggers,⁴ have been associated with dysregulated inflammatory responses,⁵ contributing to the disease pathogenesis and symptoms. Inflammation associated with PPR may decrease skin barrier function, increase transepidermal water loss, and reduce stratum corneum hydration,^6,7 resulting in heightened skin sensitivity, pain, burning, and/or stinging.^5,8

Azelaic acid (AzA), which historically has only been available in gel or cream formulations, is well established for the treatment of rosacea⁹; however, these formulations have been associated with application-site adverse events (AEs)(eg, burning, erythema, irritation), limited cosmetic acceptability, and reduced compliance or efficacy.¹⁰

For select skin conditions, active agents delivered in foam vehicles may offer superior tolerability with improved outcomes.¹¹ An AzA foam 15% formulation was approved for the treatment of mild to moderate PPR. Primary outcomes from a phase 3 trial demonstrated the efficacy and safety of AzA foam in improving inflammatory lesion counts (ILCs) and disease severity in participants with PPR. The trial also evaluated additional secondary end points, including the effect of AzA foam on erythema, inflammatory lesions, treatment response, and other manifestations of PPR.¹² The current study evaluated investigator-reported efficacy outcomes for these secondary end points for AzA foam 15% versus vehicle foam.

Methods

Study Design

This phase 3 multicenter, randomized, double-blind, vehicle-controlled, parallel-group clinical trial was conducted from September 2012 to January 2014 at 48 US study centers comparing the efficacy of AzA foam versus vehicle foam in patients with PPR. Eligible participants were 18 years and older with PPR rated as moderate or severe according to investigator global assessment (IGA), plus 12 to 50 inflammatory lesions and persistent erythema with or without telangiectasia. Exclusion criteria included known nonresponse to AzA, current or prior use (within 6 weeks of randomization) of noninvestigational products to treat rosacea, and presence of other dermatoses that could interfere with rosacea evaluation.

Participants were randomized into the AzA foam or vehicle group (1:1 ratio). The study medication was applied in 0.5-g doses twice daily until the end of treatment (EoT) at 12 weeks. Efficacy and safety parameters were evaluated at baseline and at 4, 8, and 12 weeks of treatment, and at a follow-up visit 4 weeks after EoT (week 16).

Results for the coprimary efficacy end points—therapeutic success rate according to IGA and nominal change in ILC—were previously reported.¹²

Investigator-Reported Secondary Efficacy Outcomes

The secondary efficacy end points were grouped change in erythema rating, grouped change in telangiectasia rating, grouped change in IGA score, therapeutic response rate according to IGA, percentage change in ILC from baseline, and facial skin color rating at EoT.

Grouped change for all secondary end points was measured as improved, no change, or worsened relative to baseline. For grouped change in erythema and telangiectasia ratings, a participant was considered improved if the rating at the postbaseline visit was lower than the baseline rating, no change if the postbaseline and baseline ratings were identical, and worsened if the postbaseline rating was higher than at baseline. For grouped change in IGA score, a participant was considered improved if a responder showed at least a 1-step improvement postbaseline compared to baseline, no change if postbaseline and baseline ratings were identical, and worsened if the postbaseline rating was higher than at baseline.

For the therapeutic response rate, a participant was considered a treatment responder if the IGA score improved from baseline and resulted in clear, minimal, or mild disease severity at EoT.

Safety

Adverse events also were assessed.

Statistical Analyses

Secondary efficacy and safety end points were assessed for all randomized participants who were dispensed the study medication. Missing data were imputed using last observation carried forward.

For the percentage change in ILC from baseline, therapeutic response rate, and grouped change in erythema rating, confirmatory analyses were conducted in a hierarchical manner (in the order listed), with testing stopped as soon as a null hypothesis of superior treatment effect could not be rejected. Analyses without significance level were exploratory. The Cochran-Mantel-Haenszel van Elteren test stratified by study center was used for grouped change in erythema rating (1-tailed, 2.5%) and IGA score (2-tailed, 5%); Wilcoxon rank sum tests also were performed. Percentage change in ILC from baseline was evaluated using the Student t test and F test of analysis of covariance (1-tailed, 2.5%). Therapeutic response rate was evaluated using the Cochran-Mantel-Haenszel van Elteren test stratified by study center and the Pearson χ² test. Facial skin color and grouped change in telangiectasia rating were evaluated using the Wilcoxon rank sum test.

Adverse events beginning or worsening after the first dose of the study drug were considered treatment emergent and were coded using the Medical Dictionary for Regulatory Activities (MedDRA) Version 16.1. Statistical analyses were performed using SAS software version 9.2.

Results

Study Participants

The study included 961 total participants; 483 were randomized to the AzA foam group and 478 to the vehicle group (Figure 1). Overall, 803 participants completed follow-up; however, week 16 results for the efficacy outcomes include data for 4 additional patients (2 per study arm) who did not formally meet all requirements for follow-up completion. The mean age was 51.5 years, and the majority of the participants were white and female (Table 1). Most participants (86.8%) had moderate PPR at baseline, with the remaining rated as having severe disease (13.2%). The majority (76.4%) had more than 14 inflammatory lesions with moderate (76.4%) or severe (15.1%) erythema at baseline.

Efficacy

Significantly more participants in the AzA group than in the vehicle group showed an improved erythema rating at EoT (61.5% vs 51.3%; P<.001)(Figure 2), with more participants in the AzA group showing improvement at weeks 4 (P=.022) and 8 (P=.002).

A significantly greater mean percentage reduction in ILC from baseline to EoT was observed in the AzA group versus the vehicle group (61.6% vs 50.8%; P<.001)(Figure 3), and between-group differences were observed at week 4 (P<.001), week 8 (P=.003), and week 16 (end of study/follow-up)(P=.002).

A significantly higher proportion of participants treated with AzA foam versus vehicle were considered responders at week 12/EoT (66.3% vs 54.4%; P<.001)(Figure 4). Differences in responder rate also were observed at week 4 (P=.026) and week 8 (P=.026).

Differences in grouped change in IGA score were observed between groups at every evaluation during the treatment phase (Figure 5). Specifically, IGA score was improved at week 12/EoT relative to baseline in 71.2% of participants in the AzA group versus 58.8% in the vehicle group (P<.001).

For grouped change in telangiectasia rating at EoT, the majority of participants in both treatment groups showed no change (Table 2). Regarding facial skin color, the majority of participants in both the AzA and vehicle treatment groups (80.1% and 78.7%, respectively) showed normal skin color compared to nontreated skin EoT; no between-group differences were detected for facial skin color rating (P=.315, Wilcoxon rank sum test).

Safety

The incidence of drug-related AEs was greater in the AzA group than the vehicle group (7.7% vs 4.8%)(Table 3). Drug-related AEs occurring in at least 1% of the AzA group were pain at application site (eg, tenderness, stinging, burning)(AzA group, 3.5%; vehicle group, 1.3%), application-site pruritus (1.4% vs 0.4%), and application-site dryness (1.0% vs 0.6%). A single drug-related AE of severe intensity (ie, application-site dermatitis) was observed in the vehicle group; all other drug-related AEs were mild or moderate. The incidence of withdrawals due to AEs was lower in the AzA group than the vehicle group (1.2% vs 2.5%). This AE profile correlated with a treatment compliance (the percentage of expected doses that were actually administered) of 97.0% in the AzA group and 95.9% in the vehicle group. One participant in the vehicle group died due to head trauma unrelated to administration of the study drug.

Comment

The results of this study further support the efficacy of AzA foam for the treatment of PPR. The percentage reduction in ILC was consistent with nominal decreases in ILC, a coprimary efficacy end point of this study.¹² Almost two-thirds of participants treated with AzA foam achieved a therapeutic response, indicating that many participants who did not strictly achieve the primary outcome of therapeutic success nevertheless attained notable reductions in disease severity. The number of participants who showed any improvement on the IGA scale increased throughout the course of treatment (63.8% AzA foam vs 55.0% vehicle at week 8) up to EoT (71.2% vs 58.8%)(Figure 5). In addition, the number of participants showing any improvement at week 8 (63.8% AzA foam vs 55.0% vehicle)(Figure 5) was comparable to the number of participants achieving therapeutic response at week 12/EoT (66.3% vs 54.4%)(Figure 4). These data suggest that increasing time of treatment increases the likelihood of achieving better results.

Erythema also appeared to respond to AzA foam, with 10.2% more participants in the AzA group demonstrating improvement at week 12/EoT compared to vehicle. The difference in grouped change in erythema rating also was statistically significant and favored AzA foam, sustained up to 4 weeks after EoT.

The outcomes for percentage change in ILC, therapeutic response rate, and grouped change in erythema rating consequently led to the rejection of all 3 null hypotheses in hierarchical confirmatory analyses, underscoring the benefits of AzA foam treatment.

The therapeutic effects of AzA foam were apparent at the first postbaseline evaluation and persisted throughout treatment. Differences favoring AzA foam were observed at every on-treatment evaluation for grouped change in erythema rating, percentage change in ILC, therapeutic response rate, and grouped change in IGA score. Symptoms showed minimal resurgence after treatment cessation, and there were no signs of disease flare-up within the 4 weeks of observational follow-up. In addition, the percentage reduction in ILC remained higher in the AzA foam group during follow-up.

These results also show that AzA foam was well tolerated with a low incidence of discontinuation because of drug-related AEs. No serious drug-related AEs were reported for this study or in the preceding phase 2 trial.^12,13 Although not directly evaluated, the low incidence of cutaneous AEs suggests that AzA foam may be better tolerated than prior formulations of AzA^14,15 and correlates with high compliance observed during the study.¹² Azelaic acid foam appeared to have minimal to no effect on skin color, with more than 88% of participants reporting barely visible or no skin lightening.

Interestingly, the vehicle foam showed appreciable efficacy independent of AzA. Improvements in erythema were recorded in approximately half of the vehicle group at week 12/EoT. A similar proportion attained a therapeutic response, and ILC was reduced by 50.8% at week 12/EoT. Comparable results also were evident in the vehicle group for the primary end points of this study.¹² Vehicles in dermatologic trials frequently exert effects on diseased skin^16,17 via a skin care regimen effect (eg, moisturization and other vehicle-related effects that may improve skin barrier integrity and function) and thus should not be regarded as placebo controls. The mechanism underlying this efficacy may be due to the impact of vehicle composition on skin barrier integrity and transepidermal water loss.¹⁸ The hydrophilic emulsion or other constituents of AzA foam (eg, fatty alcohols) may play a role.

A notable strength of our study is detailed clinical characterization using carefully chosen parameters and preplanned analyses that complement the primary end points. As the latter are often driven by regulatory requirements, opportunities to characterize other outcomes of interest to clinicians may be missed. The additional analyses reported here hopefully will aid dermatologists in both assessing the role of AzA foam in the treatment armamentarium for PPR and counseling patients.

Because participants with lighter skin pigmentation dominated our study population, the impact of AzA foam among patients with darker skin complexions is unknown. Although AzA is unlikely to cause hypopigmentation in normal undiseased skin, patients should be monitored for early signs of hypopigmentation.^19,20 Our data also do not allow assessment of the differential effect, if any, of AzA foam on erythema of different etiologies in PPR, as corresponding information was not collected in the trial.

Conclusion

Azelaic acid foam 15% combines a well-established treatment of PPR with new vehicle technology to deliver effective therapy across multiple disease dimensions. In addition, the vehicle foam appears to demonstrate inherent therapeutic properties independent of AzA. The availability of this novel, efficacious, and well-tolerated option for PPR has the potential to improve patient care, reduce disease burden, and minimize unnecessary costs through increased tolerability and compliance.²¹

Acknowledgment

Editorial support through inVentiv Medical Communications (New York, New York) was provided by Bayer Pharmaceuticals.

Spectators at baseball games may be exposed to excess solar UV radiation (UVR), which has been linked to the development of both melanoma and nonmelanoma skin cancers.^1,2 Although baseball hats traditionally are worn to demonstrate team support, they also may provide some sun protection for the head and face where skin cancers are commonly found.

The importance of protecting the skin from solar UVR has led to sun-protection programs and community education as well as efforts to evaluate the impact of these programs. Major League Baseball (MLB) has partnered with the American Academy of Dermatology since 1999 to promote the importance of sun protection and raise skin cancer awareness through its Play Sun Smart program.³ A study conducted 10 years ago (N=2030) evaluated hat use in spectators at MLB games and noted that less than half of all spectators in seating sections exposed to direct sunlight wore hats.⁴ The purpose of the current study was to evaluate how public education about sun protection has impacted the use of hats by spectators at MLB games in 2015 compared to the prior study in 2006.

Methods

Data were collected during a 3-game series (2 day games, 1 night game) in August 2015 in New York, New York. During one of the day games, 18,000 fans received a free wide-brimmed hat. High-resolution digital photographs of seating sections were obtained using a camera with a 300-mm lens. Using the same methodology as the prior study,⁴ sunny and shaded seating sections were photographed during all 3 games (Figure). Photographs of each section were analyzed by an independent reviewer using a high-resolution computer screen. Spectators wearing head coverings—baseball hats, visors, or hats with circumferential brims—were defined as using hats. The number of spectators wearing hats versus not wearing hats was recorded for all identical sections of interest. Bleacher seating was analyzed separately, as spectators presumably knew in advance of the continuous direct sun exposure during day games, and a subset of young children in the bleachers (<10 years of age) also was assessed. A continuously sunny section also was evaluated at the second and sixth innings to see if hats were presumably purchased during exposure. Statistical significance was determined using χ² tests with P<.05 indicating statistical significance.

Results

This analysis consisted of 3539 spectators. In both the sunny and shaded sections of a day game, there were more spectators wearing hats (49% and 37%, respectively)(P<.001) than in the same sections at night games (35% and 29%, respectively)(Table 1). During the day game, more spectators wore hats in the sunny section than in the adjacent shaded section (49% vs 37%; P<.001). Analysis of the same 2 sections during the night game revealed no significant differences.

Spectators sitting in the bleachers during a day game who presumably knew to anticipate direct sun exposure showed no significant differences in hat-wearing patterns versus the sunny section (44% vs 49%) but were more likely to wear hats compared to those sitting in the bleachers at the night game (44% vs 33%)(P<.001)(Table 1). There was no significant difference in the number of hats worn by spectators in the sunny section in the second inning (43%) versus the same section after continuous sun exposure at the sixth inning (44%)(Table 2). Significantly more children seated in the bleachers during the day game wore hats compared to adults in the same section (64% vs 42%; P<.001)(Table 3). During the hat giveaway day, significantly more spectators wore hats (the majority of which were the free giveaway hats) across all sections studied (P<.001)(Table 4).

Comment

More than 23 million spectators attended daytime MLB games in 2015, with millions more attending minor league and amateur events.⁵Although sun-protection messages tend to be well understood and received by society, many choose to ignore them.⁶

In partnership with the American Academy of Dermatology, the MLB’s Play Sun Smart program has promoted UVR risk awareness at sporting events since 1999.³ Those affiliated with MLB teams also receive annual skin cancer screenings in conjunction with a public education effort in May of each season. However, despite the years of sun-protection education, our study found that less than half of attendees wore hats for UVR protection. In fact, there were no significant differences noted across all of the hat-wearing parameters studied (day vs night game, sunny vs shaded section, sunny section over course of game) between the current study compared to the results from 10 years prior⁴ (Tables 1 and 2). For spectators in the bleacher section, even presumably knowing in advance that seating would be in the sun did not significantly increase hat-wearing behavior. Although skin cancer rates continue to rise, hat-wearing trends remain stable, revealing a concerning trend.

Increased availability of sunscreen has led to improved sun-protective behaviors in many populations.⁷ In our study, the free hat giveaway had the greatest impact on hat wearing, which suggests that improved availability and access to hats can lead to an important opportunity for sun-protection programs to partner with hat manufacturers to augment their use and protective impact.

Sun avoidance during childhood and adolescence has been shown to decrease the risk for melanoma.¹ Young children had the highest rate of hat usage in the current study, possibly due to parental example or dictates. Research has shown the importance of role models in promoting sun safety to young children,^8,9 so perhaps use of hats by parents or MLB players contributed to the hat-wearing behavior observed in this subpopulation.

Given the limited change observed in hat-wearing behaviors over the last decade, a knowledge and behavioral gap appears to exist that may be able to be exploited to enhance future sun protection. Also, based on our findings, the MLB and other sun-protection education campaigns may wish to augment their UVR protective messages by offering hat giveaways, which appear to have a notable impact.

Acknowledgment

The authors thank Jessie Skapik, BS (New York, New York), for her independent review of the spectator photographs.

Spectators at baseball games may be exposed to excess solar UV radiation (UVR), which has been linked to the development of both melanoma and nonmelanoma skin cancers.^1,2 Although baseball hats traditionally are worn to demonstrate team support, they also may provide some sun protection for the head and face where skin cancers are commonly found.

The importance of protecting the skin from solar UVR has led to sun-protection programs and community education as well as efforts to evaluate the impact of these programs. Major League Baseball (MLB) has partnered with the American Academy of Dermatology since 1999 to promote the importance of sun protection and raise skin cancer awareness through its Play Sun Smart program.³ A study conducted 10 years ago (N=2030) evaluated hat use in spectators at MLB games and noted that less than half of all spectators in seating sections exposed to direct sunlight wore hats.⁴ The purpose of the current study was to evaluate how public education about sun protection has impacted the use of hats by spectators at MLB games in 2015 compared to the prior study in 2006.

Methods

Data were collected during a 3-game series (2 day games, 1 night game) in August 2015 in New York, New York. During one of the day games, 18,000 fans received a free wide-brimmed hat. High-resolution digital photographs of seating sections were obtained using a camera with a 300-mm lens. Using the same methodology as the prior study,⁴ sunny and shaded seating sections were photographed during all 3 games (Figure). Photographs of each section were analyzed by an independent reviewer using a high-resolution computer screen. Spectators wearing head coverings—baseball hats, visors, or hats with circumferential brims—were defined as using hats. The number of spectators wearing hats versus not wearing hats was recorded for all identical sections of interest. Bleacher seating was analyzed separately, as spectators presumably knew in advance of the continuous direct sun exposure during day games, and a subset of young children in the bleachers (<10 years of age) also was assessed. A continuously sunny section also was evaluated at the second and sixth innings to see if hats were presumably purchased during exposure. Statistical significance was determined using χ² tests with P<.05 indicating statistical significance.

Results

This analysis consisted of 3539 spectators. In both the sunny and shaded sections of a day game, there were more spectators wearing hats (49% and 37%, respectively)(P<.001) than in the same sections at night games (35% and 29%, respectively)(Table 1). During the day game, more spectators wore hats in the sunny section than in the adjacent shaded section (49% vs 37%; P<.001). Analysis of the same 2 sections during the night game revealed no significant differences.

Spectators sitting in the bleachers during a day game who presumably knew to anticipate direct sun exposure showed no significant differences in hat-wearing patterns versus the sunny section (44% vs 49%) but were more likely to wear hats compared to those sitting in the bleachers at the night game (44% vs 33%)(P<.001)(Table 1). There was no significant difference in the number of hats worn by spectators in the sunny section in the second inning (43%) versus the same section after continuous sun exposure at the sixth inning (44%)(Table 2). Significantly more children seated in the bleachers during the day game wore hats compared to adults in the same section (64% vs 42%; P<.001)(Table 3). During the hat giveaway day, significantly more spectators wore hats (the majority of which were the free giveaway hats) across all sections studied (P<.001)(Table 4).

Comment

More than 23 million spectators attended daytime MLB games in 2015, with millions more attending minor league and amateur events.⁵Although sun-protection messages tend to be well understood and received by society, many choose to ignore them.⁶

In partnership with the American Academy of Dermatology, the MLB’s Play Sun Smart program has promoted UVR risk awareness at sporting events since 1999.³ Those affiliated with MLB teams also receive annual skin cancer screenings in conjunction with a public education effort in May of each season. However, despite the years of sun-protection education, our study found that less than half of attendees wore hats for UVR protection. In fact, there were no significant differences noted across all of the hat-wearing parameters studied (day vs night game, sunny vs shaded section, sunny section over course of game) between the current study compared to the results from 10 years prior⁴ (Tables 1 and 2). For spectators in the bleacher section, even presumably knowing in advance that seating would be in the sun did not significantly increase hat-wearing behavior. Although skin cancer rates continue to rise, hat-wearing trends remain stable, revealing a concerning trend.

Increased availability of sunscreen has led to improved sun-protective behaviors in many populations.⁷ In our study, the free hat giveaway had the greatest impact on hat wearing, which suggests that improved availability and access to hats can lead to an important opportunity for sun-protection programs to partner with hat manufacturers to augment their use and protective impact.

Sun avoidance during childhood and adolescence has been shown to decrease the risk for melanoma.¹ Young children had the highest rate of hat usage in the current study, possibly due to parental example or dictates. Research has shown the importance of role models in promoting sun safety to young children,^8,9 so perhaps use of hats by parents or MLB players contributed to the hat-wearing behavior observed in this subpopulation.

Given the limited change observed in hat-wearing behaviors over the last decade, a knowledge and behavioral gap appears to exist that may be able to be exploited to enhance future sun protection. Also, based on our findings, the MLB and other sun-protection education campaigns may wish to augment their UVR protective messages by offering hat giveaways, which appear to have a notable impact.

Acknowledgment

The authors thank Jessie Skapik, BS (New York, New York), for her independent review of the spectator photographs.

Spectators at baseball games may be exposed to excess solar UV radiation (UVR), which has been linked to the development of both melanoma and nonmelanoma skin cancers.^1,2 Although baseball hats traditionally are worn to demonstrate team support, they also may provide some sun protection for the head and face where skin cancers are commonly found.

The importance of protecting the skin from solar UVR has led to sun-protection programs and community education as well as efforts to evaluate the impact of these programs. Major League Baseball (MLB) has partnered with the American Academy of Dermatology since 1999 to promote the importance of sun protection and raise skin cancer awareness through its Play Sun Smart program.³ A study conducted 10 years ago (N=2030) evaluated hat use in spectators at MLB games and noted that less than half of all spectators in seating sections exposed to direct sunlight wore hats.⁴ The purpose of the current study was to evaluate how public education about sun protection has impacted the use of hats by spectators at MLB games in 2015 compared to the prior study in 2006.

Methods

Data were collected during a 3-game series (2 day games, 1 night game) in August 2015 in New York, New York. During one of the day games, 18,000 fans received a free wide-brimmed hat. High-resolution digital photographs of seating sections were obtained using a camera with a 300-mm lens. Using the same methodology as the prior study,⁴ sunny and shaded seating sections were photographed during all 3 games (Figure). Photographs of each section were analyzed by an independent reviewer using a high-resolution computer screen. Spectators wearing head coverings—baseball hats, visors, or hats with circumferential brims—were defined as using hats. The number of spectators wearing hats versus not wearing hats was recorded for all identical sections of interest. Bleacher seating was analyzed separately, as spectators presumably knew in advance of the continuous direct sun exposure during day games, and a subset of young children in the bleachers (<10 years of age) also was assessed. A continuously sunny section also was evaluated at the second and sixth innings to see if hats were presumably purchased during exposure. Statistical significance was determined using χ² tests with P<.05 indicating statistical significance.

Results

This analysis consisted of 3539 spectators. In both the sunny and shaded sections of a day game, there were more spectators wearing hats (49% and 37%, respectively)(P<.001) than in the same sections at night games (35% and 29%, respectively)(Table 1). During the day game, more spectators wore hats in the sunny section than in the adjacent shaded section (49% vs 37%; P<.001). Analysis of the same 2 sections during the night game revealed no significant differences.

Spectators sitting in the bleachers during a day game who presumably knew to anticipate direct sun exposure showed no significant differences in hat-wearing patterns versus the sunny section (44% vs 49%) but were more likely to wear hats compared to those sitting in the bleachers at the night game (44% vs 33%)(P<.001)(Table 1). There was no significant difference in the number of hats worn by spectators in the sunny section in the second inning (43%) versus the same section after continuous sun exposure at the sixth inning (44%)(Table 2). Significantly more children seated in the bleachers during the day game wore hats compared to adults in the same section (64% vs 42%; P<.001)(Table 3). During the hat giveaway day, significantly more spectators wore hats (the majority of which were the free giveaway hats) across all sections studied (P<.001)(Table 4).

Comment

More than 23 million spectators attended daytime MLB games in 2015, with millions more attending minor league and amateur events.⁵Although sun-protection messages tend to be well understood and received by society, many choose to ignore them.⁶

In partnership with the American Academy of Dermatology, the MLB’s Play Sun Smart program has promoted UVR risk awareness at sporting events since 1999.³ Those affiliated with MLB teams also receive annual skin cancer screenings in conjunction with a public education effort in May of each season. However, despite the years of sun-protection education, our study found that less than half of attendees wore hats for UVR protection. In fact, there were no significant differences noted across all of the hat-wearing parameters studied (day vs night game, sunny vs shaded section, sunny section over course of game) between the current study compared to the results from 10 years prior⁴ (Tables 1 and 2). For spectators in the bleacher section, even presumably knowing in advance that seating would be in the sun did not significantly increase hat-wearing behavior. Although skin cancer rates continue to rise, hat-wearing trends remain stable, revealing a concerning trend.

Increased availability of sunscreen has led to improved sun-protective behaviors in many populations.⁷ In our study, the free hat giveaway had the greatest impact on hat wearing, which suggests that improved availability and access to hats can lead to an important opportunity for sun-protection programs to partner with hat manufacturers to augment their use and protective impact.

Sun avoidance during childhood and adolescence has been shown to decrease the risk for melanoma.¹ Young children had the highest rate of hat usage in the current study, possibly due to parental example or dictates. Research has shown the importance of role models in promoting sun safety to young children,^8,9 so perhaps use of hats by parents or MLB players contributed to the hat-wearing behavior observed in this subpopulation.

Given the limited change observed in hat-wearing behaviors over the last decade, a knowledge and behavioral gap appears to exist that may be able to be exploited to enhance future sun protection. Also, based on our findings, the MLB and other sun-protection education campaigns may wish to augment their UVR protective messages by offering hat giveaways, which appear to have a notable impact.

Acknowledgment

The authors thank Jessie Skapik, BS (New York, New York), for her independent review of the spectator photographs.

In the U.S., 4.5 million ambulatory care visits occur annually due to adverse drug reactions (ADRs) of prescription medications.¹ Many ADRs are severe, and they result in more than 100,000 death per year.² A significant number of these ADRs are preventable and are a result of inappropriate prescribing.³ It is well-documented that inappropriate prescribing is exacerbated by the number of patients who see multiple prescribers and use many different prescription medications.⁴ This situation results in many versions of a patient’s medication list and in discrepancies across data sources.⁵

Medication list discrepancies have been researched in the context of care transitions between the hospital and home.^6,7 However, less attention has been given to community-dwelling adults who use multiple outpatient prescribers, a practice common among older adults with chronic conditions who see a primary care provider and several specialists.⁴ Also, veterans are a growing patient population who use providers from multiple health care systems.⁸ Up to 70% of veterans enrolled in VA health care use both VA and non-VA providers. These patients are referred to as dual users.^9,10

There has been an increasing push for patients to be more actively engaged in their own health care, including maintenance of their medication list and other personal health information.^11-13 Providers have realized that patients have important experiences and preferences to share about how they use medications at home.^14,15 Research suggests that patient interest and ability to use patient portals is variable and dependent on age, technical abilities, health literacy, and endorsement by their providers.¹⁶ Greater patient engagement in the medication management process is potentially advantageous, especially because providers from different health care systems often lack the capability to share medication list information.^12,17

My HealtheVet, the VA’s patient portal, offers veterans several features. For example, users can securely message providers, refill prescriptions, check appointments, self-enter information, and download their VA health record (including medication history) using the Blue Button (BB) feature. The BB is managed by the HHS to provide consistency across electronic health record platforms.^18,19

This BB medication list gives VA patients the tool they need to inform their providers about the medications they take, particularly dual users. VA patients that use multiple prescribers are subject to medication list discrepancies because of the fragmentation of information.^4,20

Objectives

The objectives of this study were to (1) describe discrepancies between VA medication lists and non-VA provider medication lists for a group of veteran dual users; (2) identify therapeutic duplications in these lists; and (3) contextualize discrepancies by interviewing non-VA providers about their medication reconciliation processes and management of dual use patients.

Methods

This analysis is based on data collected as part of a pilot randomized controlled trial by Turvey and colleagues.²¹ Veterans with a diagnosis of ≥ 1 chronic health condition (eg, diabetes, hypertension) were invited by letter to participate in a study about using online management of their health information. Interested patients were screened to meet additional inclusion criteria, such as taking ≥ 5 medications, receiving care from a non-VA provider, an appointment with a non-VA provider within the study time frame, and access to a computer, online access, and printer. 

Eligible veterans were randomized to receive either (1) BB training (intervention group) instructing patients to download the Continuity of Care Document and bring it to their non-VA provider visit; or (2) a training evaluating medical information online (control group). Training information was mailed, including written materials and phone support, to both groups. The intervention group could also access an online training link.

One of the objectives was to test whether downloading and bringing the health information to a non-VA appointment decreased medication list discrepancies. The sample was small, and differences in discrepancy rates between groups were not significant. Therefore, groups were combined for the present analysis. Visits occurred between December 2013 and December 2014. Greater detail about study design and primary results are available in the study by Turvey and colleagues.²¹

Study procedures were approved by the University of Iowa Institutional Review Board and the Iowa City VA Health Care System Research and Development Committee. All participants provided consent.

Identifying Discrepancies

A 4-phase process was used to address medication discrepancies.^22,23 The first phase defined medication discrepancy categories. The mutually exclusive categories were dose, frequency, and missing discrepancies. In cases where a medication was both dose and frequency discrepant, only dose discrepancy was applied. For missing medications, entities on only the VA list were marked as “non-VA missing” and medications appearing on only the non-VA list would be denoted as “VA missing.” Medications with no discrepancy were marked as such.

Phase 2 involved collecting medication data. Medication lists from the VA medical record were printed at the time of the non-VA provider appointment. Non-VA medication lists were obtained by sending a medical record request for the visit note, medication list, and any associated visit test results to the non-VA provider office within 2 to 3 weeks of the appointment. Patient names from both lists were replaced with unique patient identifiers.

In phase 3, a research assistant abstracted the hard copy medication lists into a database and identified discrepancies. Variables included medication name, dose, frequency, and administration route. Although administration routes were collected, discrepancies were not assessed because this information commonly was not specified. Medications also were coded as prescription or over-the-counter (OTC). Durable medical equipment often was present on VA lists (eg, syringes, test strips) and was excluded from all analyses. Medications also were not coded as discrepant if they were referenced in a visit note as being changed by the non-VA provider. These combined lists were evaluated by the research assistant based on the discrepancy categories specified in phase 1 and were verified by a pharmacist.

Phase 4 involved counting medication discrepancies. Medication discrepancy rates were calculated at the patient level, both descriptively (mean number of discrepancies per patient) and as a proportion of medications discrepant (number of discrepancies divided by total medications).

Identifying Duplications and High-Risk Medications

A pharmacist examined each combined medication list to identify therapeutic duplications, defined as a patient using ≥ 2 medications from the same medication class (eg, patient taking 2 statin drugs) but not 2 drugs for the same condition (eg, fish oil and atorvastatin for dyslipidemia). High-risk medications also were noted, including anticoagulants, certain nonsteroidal anti-inflammatory drugs, oral and injectable hypoglycemics, opioids, sedatives, and hypnotics.^24-26 These medications received special focus because of their link to a high risk for ADRs.²⁷

Descriptive statistics were calculated for patient characteristics and for each discrepancy type, both overall and according to prescription OTC, and high-risk medications. The proportion of discrepant medications was calculated for each category. Bivariate correlations were calculated for select variables to understand potential relationships.

Interviews With Non-VA Providers

All patients were instructed to bring a consent letter and the 1-page questionnaire to their non-VA provider appointment. The questionnaire contained an item asking whether non-VA providers could be contacted for a 15- to 30-minute follow-up interview. The semistructured, qualitative interviews assessed their experiences working with VA providers and VA patients, experiences with VA documents or records, preferences for receiving information from the VA, experience with personal health records, and sharing information with the VA. Eight interviews were conducted, audio-recorded, and transcribed. The goal of the interviews was to explore and understand provider perspectives on managing dual use veterans, including medication reconciliation processes to add context to the interpretation of medication list analysis. Because the data set was relatively small, summaries of each interview were created to highlight main points. These main points were sorted into topics, summarized, and representative quotes were selected.

Results

Fifty veterans were included in the analysis (Table 1). The mean age was 68.5 (SD 6.2); 90% were men. On average, they reported having 6 chronic health conditions and a fair-to-good health status. Based on the combined medication lists from VA and non-VA providers, veterans took an average of 15.8 (SD 7.0) unique medications (combined prescription and OTC/vitamins) and had an average of 10.0 (SD 6.1) all-type discrepancies (Table 2).

Overall, 58% of the prescription medications were discrepant: The most common discrepancy between the 2 lists was medication missing on one of the lists, which occurred 3.9 times per patient on average for prescription medications and 2.8 times per patient for OTCs. Frequency or dose discrepancies also were common between the lists at a rate of 1.9 discrepancies per patient for prescription medications and 1.2 discrepancies per patient for OTCs.

For high-risk medications, opiates and sedative medications had the most discrepancies between the lists because the VA practitioner may not have known that the patient was taking an opiate, although other discrepancies were present (Table 3). Anticoagulant discrepancies were the most consistent, most of these occurring with aspirin. Last, insulin commonly was dose discrepant between the 2 lists, although it also was missing from one list for a number of patients. Overall, high-risk medications shared a discrepancy rate (46.9%) similar to the overall rate.

Twelve therapeutic duplications were identified in the sample.Ten were between-list duplications, that is, “provider A” thought the patient was on a particular medication and “provider B” thought that the patient was on a different medication (Table 4). In 6 instances, within-list duplications were identified (ie, a provider had 2 medications on the list that should not be taken together because they were in the same drug class). In 4 cases, both between- and within-list duplications were present.

Interview Summaries

Veterans and medication. Multiple non-VA providers said that the primary reason veteran patients were going to a VA provider was to obtain discounted medications. The use of the VA for medications also was a way for the non-VA provider to discover that the patient was a veteran. One non-VA provider was particularly concerned about the impact of new or different medications from VA prescribers on efforts to stabilize the patient’s chronic condition.

Several non-VA providers reported that veterans often brought a medication list to the appointment, and several providers recommended the practice to their patients. Non-VA providers preferred to have patients transfer information from VA, sometimes requesting that veterans bring in their records from recent appointments rather than the non-VA provider obtain the information directly from the VA.

Information sharing. Non-VA providers generally preferred hard copies of medication lists and other documents rather than scans because they were more likely to be included in decision making if the documents were presented during the visit. Also, document scans may be buried in the electronic medical record. Some providers mentioned their interest in electronic transfer of medical information like medication lists if the technology were more developed and better integrated.

“I think the long-term vision would be that it should be electronic… it wouldn’t necessarily be feasible at this time. Our system scans paper documents in to an e-version. … but when the patient comes to their encounter 10 days later, you don’t realize the stuff’s there… Having the patient bring them in is probably a more certain way to make sure that it’s actually included in your decision making as a provider.”

Most non-VA providers welcomed more information such as imaging studies because they reported rarely receiving this information from the VA system. Two mentioned the potential for too much information and wanted concise reports should the flow of information increase. Providers had little interest in logging in to a patient’s online health record portal as a delegate for reasons related to complexity, time, privacy, and lack of mechanism to document the information accessed.

Medication reconciliation. Non-VA providers generally reported that patients bringing their own or an outside medication list would prompt a process of medication reconciliation. The providers were interested in making changes to their records based on other lists, but outside data were verified against a patient self-report of actual use before adopting changes.

“I print out my med list of what I have in the computer and then I just check off my list against their list. And then whatever’s remaining, we talk about what the differences are, when they were changed, what they were changed for, if they were taken off of something, and if I don’t agree, then I’ll tell the patient, ‘look, there’s a disagreement here, they’ve told you not to be on this. I want you on this.”

Should a discrepancy arise, non-VA providers generally had a negative view of attempting to contact VA providers. Other mechanisms such as calling a local pharmacy would be done first.

Discussion

This study provided initial evidence that medication list discrepancies exist for dual use veterans. Other studies of medication list discrepancies have linked such inconsistencies to medication-related problems and negative outcomes for patients.²⁷ Although efforts to increase access to care for veterans have advantages related to expediency, consequences to fragmenting care exist. More robust mechanisms for establishing and maintaining medication list consistency are needed, especially given the lack of a universally accepted medical record format or repository. A multifaceted approach, including patient engagement, seems necessary.

This study also showed that discrepancies of high-risk medications are common for veteran participants, placing them at risk for medication-related problems and harm. These risks included dose and frequency discrepancies that could result in over- or underdosing of medications and in medication omissions, which could cause duplicative therapies and unnecessary risks. For example, aspirin frequently was listed on non-VA lists but was omitted from VA medication lists. This could be problematic for patients who present to the VA for a procedure in which no information about aspirin could jeopardize their safety. Insulin doses also were commonly discrepant, which could impact glycemic control.

Many providers also had incomplete prescribing information for opiates. Those prescriptions are particularly relevant given the link between veterans, posttraumatic stress disorder, depression, and substance abuse.^28-30 However, it was beyond the scope of this pilot study to link these discrepancies to ADRs, such as emergency department visits or hospital admissions. Other studies have demonstrated that discrepancies at hospital discharge can result in these types of negative outcomes.^27,31 Subsequent research should determine the clinical significance of discrepancies that occur when veterans are dual users.

The qualitative interviews provided some initial context on prescriber perspectives about the role of veterans participating in the medication list sharing process and personal health records. It seemed that for the portion of patients who brought a list to their non-VA provider appointment, the information was welcomed but fell outside the usual visit workflow. Many provider visits are dominated by current patient symptoms, and issues of reconciling medications may be a lower priority.³² Also, some providers may delegate medication reconciliation functions to a nurse or other support staff. One physician offered that he delegated logging in to a patient’s online medication information to a health coach on staff. These findings were consistent with perspectives shared by non-VA family practice physicians about personal health records.³³

The most common way to integrate outside medication lists into the non-VA provider’s medical record seemed to be scanning the document. Scanning had its limitations because the provider might be unaware of the scanned document, and there were no mechanisms to import medication names and doses. However, the process may improve only the non-VA providers’ records, as they reported that they had no easy or consistent way to transmit medication changes to notes to the VA.

In general, communicating with VA providers was seen as not feasible and not worth their time or effort. It may be beneficial to address this non-VA provider concern because it seems to inhibit the transfer of important health information and the maintenance of a concordant medication record. Information transfer is particularly relevant for veterans who are primarily cared for by non-VA providers and use the VA only to get prescription medications.

In the current approach, non-VA providers have no simple, direct way to update the VA medication list. Transmitting updates carries the risk of inappropriate changes and is concerning if neither or both prescribers consider themselves to be responsible for the patient’s medications. Also, the potential exists for all medication lists to be inaccurate if the lists do not reflect the medications patients take when left on their own. Patient nonadherence rates can exceed 50%, depending on the medication.^34,35 Several interviewed non-VA physicians stressed the importance of asking patients to list the medications they were using during the medication reconciliation process.

This study offers several areas for additional inquiry, including understanding how providers make sense of medication lists from other sources and what technologies can be applied to increase list consistency without increasing the burden on providers.

Practice Implications

Although patient involvement in medication list sharing has the potential to improve information consistency, health systems, providers, and other stakeholders should be cautious in assuming that other prescribers will work to combat medication list entropy, especially if no systems exist to seamlessly incorporate this information into clinic workflow. Devising standardized procedures when patients bring in their records from other providers increases the likelihood that this information will be incorporated into clinical decision making and maintaining up-to-date medication information for patients who use multiple prescribers.

Limitations

These analyses are based on a small sample size (n = 50 for chart review) and (n = 8 for the semistructured interviews) from a single Midwestern state. These findings should be used as evidence for further inquiry.

Conclusion

This study illuminates the level of discrepancies between the medication lists of veteran dual users, including high rates of discrepancies for high-risk medications, such as anticoagulants and opiates. This study also provides evidence of deficiencies in the health care system to decrease medication list entropy that may place veterans at an elevated risk for adverse medication events.

In the U.S., 4.5 million ambulatory care visits occur annually due to adverse drug reactions (ADRs) of prescription medications.¹ Many ADRs are severe, and they result in more than 100,000 death per year.² A significant number of these ADRs are preventable and are a result of inappropriate prescribing.³ It is well-documented that inappropriate prescribing is exacerbated by the number of patients who see multiple prescribers and use many different prescription medications.⁴ This situation results in many versions of a patient’s medication list and in discrepancies across data sources.⁵

Medication list discrepancies have been researched in the context of care transitions between the hospital and home.^6,7 However, less attention has been given to community-dwelling adults who use multiple outpatient prescribers, a practice common among older adults with chronic conditions who see a primary care provider and several specialists.⁴ Also, veterans are a growing patient population who use providers from multiple health care systems.⁸ Up to 70% of veterans enrolled in VA health care use both VA and non-VA providers. These patients are referred to as dual users.^9,10

There has been an increasing push for patients to be more actively engaged in their own health care, including maintenance of their medication list and other personal health information.^11-13 Providers have realized that patients have important experiences and preferences to share about how they use medications at home.^14,15 Research suggests that patient interest and ability to use patient portals is variable and dependent on age, technical abilities, health literacy, and endorsement by their providers.¹⁶ Greater patient engagement in the medication management process is potentially advantageous, especially because providers from different health care systems often lack the capability to share medication list information.^12,17

My HealtheVet, the VA’s patient portal, offers veterans several features. For example, users can securely message providers, refill prescriptions, check appointments, self-enter information, and download their VA health record (including medication history) using the Blue Button (BB) feature. The BB is managed by the HHS to provide consistency across electronic health record platforms.^18,19

This BB medication list gives VA patients the tool they need to inform their providers about the medications they take, particularly dual users. VA patients that use multiple prescribers are subject to medication list discrepancies because of the fragmentation of information.^4,20

Objectives

The objectives of this study were to (1) describe discrepancies between VA medication lists and non-VA provider medication lists for a group of veteran dual users; (2) identify therapeutic duplications in these lists; and (3) contextualize discrepancies by interviewing non-VA providers about their medication reconciliation processes and management of dual use patients.

Methods

This analysis is based on data collected as part of a pilot randomized controlled trial by Turvey and colleagues.²¹ Veterans with a diagnosis of ≥ 1 chronic health condition (eg, diabetes, hypertension) were invited by letter to participate in a study about using online management of their health information. Interested patients were screened to meet additional inclusion criteria, such as taking ≥ 5 medications, receiving care from a non-VA provider, an appointment with a non-VA provider within the study time frame, and access to a computer, online access, and printer. 

Eligible veterans were randomized to receive either (1) BB training (intervention group) instructing patients to download the Continuity of Care Document and bring it to their non-VA provider visit; or (2) a training evaluating medical information online (control group). Training information was mailed, including written materials and phone support, to both groups. The intervention group could also access an online training link.

One of the objectives was to test whether downloading and bringing the health information to a non-VA appointment decreased medication list discrepancies. The sample was small, and differences in discrepancy rates between groups were not significant. Therefore, groups were combined for the present analysis. Visits occurred between December 2013 and December 2014. Greater detail about study design and primary results are available in the study by Turvey and colleagues.²¹

Study procedures were approved by the University of Iowa Institutional Review Board and the Iowa City VA Health Care System Research and Development Committee. All participants provided consent.

Identifying Discrepancies

A 4-phase process was used to address medication discrepancies.^22,23 The first phase defined medication discrepancy categories. The mutually exclusive categories were dose, frequency, and missing discrepancies. In cases where a medication was both dose and frequency discrepant, only dose discrepancy was applied. For missing medications, entities on only the VA list were marked as “non-VA missing” and medications appearing on only the non-VA list would be denoted as “VA missing.” Medications with no discrepancy were marked as such.

Phase 2 involved collecting medication data. Medication lists from the VA medical record were printed at the time of the non-VA provider appointment. Non-VA medication lists were obtained by sending a medical record request for the visit note, medication list, and any associated visit test results to the non-VA provider office within 2 to 3 weeks of the appointment. Patient names from both lists were replaced with unique patient identifiers.

In phase 3, a research assistant abstracted the hard copy medication lists into a database and identified discrepancies. Variables included medication name, dose, frequency, and administration route. Although administration routes were collected, discrepancies were not assessed because this information commonly was not specified. Medications also were coded as prescription or over-the-counter (OTC). Durable medical equipment often was present on VA lists (eg, syringes, test strips) and was excluded from all analyses. Medications also were not coded as discrepant if they were referenced in a visit note as being changed by the non-VA provider. These combined lists were evaluated by the research assistant based on the discrepancy categories specified in phase 1 and were verified by a pharmacist.

Phase 4 involved counting medication discrepancies. Medication discrepancy rates were calculated at the patient level, both descriptively (mean number of discrepancies per patient) and as a proportion of medications discrepant (number of discrepancies divided by total medications).

Identifying Duplications and High-Risk Medications

A pharmacist examined each combined medication list to identify therapeutic duplications, defined as a patient using ≥ 2 medications from the same medication class (eg, patient taking 2 statin drugs) but not 2 drugs for the same condition (eg, fish oil and atorvastatin for dyslipidemia). High-risk medications also were noted, including anticoagulants, certain nonsteroidal anti-inflammatory drugs, oral and injectable hypoglycemics, opioids, sedatives, and hypnotics.^24-26 These medications received special focus because of their link to a high risk for ADRs.²⁷

Descriptive statistics were calculated for patient characteristics and for each discrepancy type, both overall and according to prescription OTC, and high-risk medications. The proportion of discrepant medications was calculated for each category. Bivariate correlations were calculated for select variables to understand potential relationships.

Interviews With Non-VA Providers

All patients were instructed to bring a consent letter and the 1-page questionnaire to their non-VA provider appointment. The questionnaire contained an item asking whether non-VA providers could be contacted for a 15- to 30-minute follow-up interview. The semistructured, qualitative interviews assessed their experiences working with VA providers and VA patients, experiences with VA documents or records, preferences for receiving information from the VA, experience with personal health records, and sharing information with the VA. Eight interviews were conducted, audio-recorded, and transcribed. The goal of the interviews was to explore and understand provider perspectives on managing dual use veterans, including medication reconciliation processes to add context to the interpretation of medication list analysis. Because the data set was relatively small, summaries of each interview were created to highlight main points. These main points were sorted into topics, summarized, and representative quotes were selected.

Results

Fifty veterans were included in the analysis (Table 1). The mean age was 68.5 (SD 6.2); 90% were men. On average, they reported having 6 chronic health conditions and a fair-to-good health status. Based on the combined medication lists from VA and non-VA providers, veterans took an average of 15.8 (SD 7.0) unique medications (combined prescription and OTC/vitamins) and had an average of 10.0 (SD 6.1) all-type discrepancies (Table 2).

Overall, 58% of the prescription medications were discrepant: The most common discrepancy between the 2 lists was medication missing on one of the lists, which occurred 3.9 times per patient on average for prescription medications and 2.8 times per patient for OTCs. Frequency or dose discrepancies also were common between the lists at a rate of 1.9 discrepancies per patient for prescription medications and 1.2 discrepancies per patient for OTCs.

For high-risk medications, opiates and sedative medications had the most discrepancies between the lists because the VA practitioner may not have known that the patient was taking an opiate, although other discrepancies were present (Table 3). Anticoagulant discrepancies were the most consistent, most of these occurring with aspirin. Last, insulin commonly was dose discrepant between the 2 lists, although it also was missing from one list for a number of patients. Overall, high-risk medications shared a discrepancy rate (46.9%) similar to the overall rate.

Twelve therapeutic duplications were identified in the sample.Ten were between-list duplications, that is, “provider A” thought the patient was on a particular medication and “provider B” thought that the patient was on a different medication (Table 4). In 6 instances, within-list duplications were identified (ie, a provider had 2 medications on the list that should not be taken together because they were in the same drug class). In 4 cases, both between- and within-list duplications were present.

Interview Summaries

Veterans and medication. Multiple non-VA providers said that the primary reason veteran patients were going to a VA provider was to obtain discounted medications. The use of the VA for medications also was a way for the non-VA provider to discover that the patient was a veteran. One non-VA provider was particularly concerned about the impact of new or different medications from VA prescribers on efforts to stabilize the patient’s chronic condition.

Several non-VA providers reported that veterans often brought a medication list to the appointment, and several providers recommended the practice to their patients. Non-VA providers preferred to have patients transfer information from VA, sometimes requesting that veterans bring in their records from recent appointments rather than the non-VA provider obtain the information directly from the VA.

Information sharing. Non-VA providers generally preferred hard copies of medication lists and other documents rather than scans because they were more likely to be included in decision making if the documents were presented during the visit. Also, document scans may be buried in the electronic medical record. Some providers mentioned their interest in electronic transfer of medical information like medication lists if the technology were more developed and better integrated.

“I think the long-term vision would be that it should be electronic… it wouldn’t necessarily be feasible at this time. Our system scans paper documents in to an e-version. … but when the patient comes to their encounter 10 days later, you don’t realize the stuff’s there… Having the patient bring them in is probably a more certain way to make sure that it’s actually included in your decision making as a provider.”

Most non-VA providers welcomed more information such as imaging studies because they reported rarely receiving this information from the VA system. Two mentioned the potential for too much information and wanted concise reports should the flow of information increase. Providers had little interest in logging in to a patient’s online health record portal as a delegate for reasons related to complexity, time, privacy, and lack of mechanism to document the information accessed.

Medication reconciliation. Non-VA providers generally reported that patients bringing their own or an outside medication list would prompt a process of medication reconciliation. The providers were interested in making changes to their records based on other lists, but outside data were verified against a patient self-report of actual use before adopting changes.

“I print out my med list of what I have in the computer and then I just check off my list against their list. And then whatever’s remaining, we talk about what the differences are, when they were changed, what they were changed for, if they were taken off of something, and if I don’t agree, then I’ll tell the patient, ‘look, there’s a disagreement here, they’ve told you not to be on this. I want you on this.”

Should a discrepancy arise, non-VA providers generally had a negative view of attempting to contact VA providers. Other mechanisms such as calling a local pharmacy would be done first.

Discussion

This study provided initial evidence that medication list discrepancies exist for dual use veterans. Other studies of medication list discrepancies have linked such inconsistencies to medication-related problems and negative outcomes for patients.²⁷ Although efforts to increase access to care for veterans have advantages related to expediency, consequences to fragmenting care exist. More robust mechanisms for establishing and maintaining medication list consistency are needed, especially given the lack of a universally accepted medical record format or repository. A multifaceted approach, including patient engagement, seems necessary.

This study also showed that discrepancies of high-risk medications are common for veteran participants, placing them at risk for medication-related problems and harm. These risks included dose and frequency discrepancies that could result in over- or underdosing of medications and in medication omissions, which could cause duplicative therapies and unnecessary risks. For example, aspirin frequently was listed on non-VA lists but was omitted from VA medication lists. This could be problematic for patients who present to the VA for a procedure in which no information about aspirin could jeopardize their safety. Insulin doses also were commonly discrepant, which could impact glycemic control.

Many providers also had incomplete prescribing information for opiates. Those prescriptions are particularly relevant given the link between veterans, posttraumatic stress disorder, depression, and substance abuse.^28-30 However, it was beyond the scope of this pilot study to link these discrepancies to ADRs, such as emergency department visits or hospital admissions. Other studies have demonstrated that discrepancies at hospital discharge can result in these types of negative outcomes.^27,31 Subsequent research should determine the clinical significance of discrepancies that occur when veterans are dual users.

The qualitative interviews provided some initial context on prescriber perspectives about the role of veterans participating in the medication list sharing process and personal health records. It seemed that for the portion of patients who brought a list to their non-VA provider appointment, the information was welcomed but fell outside the usual visit workflow. Many provider visits are dominated by current patient symptoms, and issues of reconciling medications may be a lower priority.³² Also, some providers may delegate medication reconciliation functions to a nurse or other support staff. One physician offered that he delegated logging in to a patient’s online medication information to a health coach on staff. These findings were consistent with perspectives shared by non-VA family practice physicians about personal health records.³³

The most common way to integrate outside medication lists into the non-VA provider’s medical record seemed to be scanning the document. Scanning had its limitations because the provider might be unaware of the scanned document, and there were no mechanisms to import medication names and doses. However, the process may improve only the non-VA providers’ records, as they reported that they had no easy or consistent way to transmit medication changes to notes to the VA.

In general, communicating with VA providers was seen as not feasible and not worth their time or effort. It may be beneficial to address this non-VA provider concern because it seems to inhibit the transfer of important health information and the maintenance of a concordant medication record. Information transfer is particularly relevant for veterans who are primarily cared for by non-VA providers and use the VA only to get prescription medications.

In the current approach, non-VA providers have no simple, direct way to update the VA medication list. Transmitting updates carries the risk of inappropriate changes and is concerning if neither or both prescribers consider themselves to be responsible for the patient’s medications. Also, the potential exists for all medication lists to be inaccurate if the lists do not reflect the medications patients take when left on their own. Patient nonadherence rates can exceed 50%, depending on the medication.^34,35 Several interviewed non-VA physicians stressed the importance of asking patients to list the medications they were using during the medication reconciliation process.

This study offers several areas for additional inquiry, including understanding how providers make sense of medication lists from other sources and what technologies can be applied to increase list consistency without increasing the burden on providers.

Practice Implications

Although patient involvement in medication list sharing has the potential to improve information consistency, health systems, providers, and other stakeholders should be cautious in assuming that other prescribers will work to combat medication list entropy, especially if no systems exist to seamlessly incorporate this information into clinic workflow. Devising standardized procedures when patients bring in their records from other providers increases the likelihood that this information will be incorporated into clinical decision making and maintaining up-to-date medication information for patients who use multiple prescribers.

Limitations

These analyses are based on a small sample size (n = 50 for chart review) and (n = 8 for the semistructured interviews) from a single Midwestern state. These findings should be used as evidence for further inquiry.

Conclusion

This study illuminates the level of discrepancies between the medication lists of veteran dual users, including high rates of discrepancies for high-risk medications, such as anticoagulants and opiates. This study also provides evidence of deficiencies in the health care system to decrease medication list entropy that may place veterans at an elevated risk for adverse medication events.

In the U.S., 4.5 million ambulatory care visits occur annually due to adverse drug reactions (ADRs) of prescription medications.¹ Many ADRs are severe, and they result in more than 100,000 death per year.² A significant number of these ADRs are preventable and are a result of inappropriate prescribing.³ It is well-documented that inappropriate prescribing is exacerbated by the number of patients who see multiple prescribers and use many different prescription medications.⁴ This situation results in many versions of a patient’s medication list and in discrepancies across data sources.⁵

Medication list discrepancies have been researched in the context of care transitions between the hospital and home.^6,7 However, less attention has been given to community-dwelling adults who use multiple outpatient prescribers, a practice common among older adults with chronic conditions who see a primary care provider and several specialists.⁴ Also, veterans are a growing patient population who use providers from multiple health care systems.⁸ Up to 70% of veterans enrolled in VA health care use both VA and non-VA providers. These patients are referred to as dual users.^9,10

There has been an increasing push for patients to be more actively engaged in their own health care, including maintenance of their medication list and other personal health information.^11-13 Providers have realized that patients have important experiences and preferences to share about how they use medications at home.^14,15 Research suggests that patient interest and ability to use patient portals is variable and dependent on age, technical abilities, health literacy, and endorsement by their providers.¹⁶ Greater patient engagement in the medication management process is potentially advantageous, especially because providers from different health care systems often lack the capability to share medication list information.^12,17

My HealtheVet, the VA’s patient portal, offers veterans several features. For example, users can securely message providers, refill prescriptions, check appointments, self-enter information, and download their VA health record (including medication history) using the Blue Button (BB) feature. The BB is managed by the HHS to provide consistency across electronic health record platforms.^18,19

This BB medication list gives VA patients the tool they need to inform their providers about the medications they take, particularly dual users. VA patients that use multiple prescribers are subject to medication list discrepancies because of the fragmentation of information.^4,20

Objectives

The objectives of this study were to (1) describe discrepancies between VA medication lists and non-VA provider medication lists for a group of veteran dual users; (2) identify therapeutic duplications in these lists; and (3) contextualize discrepancies by interviewing non-VA providers about their medication reconciliation processes and management of dual use patients.

Methods

This analysis is based on data collected as part of a pilot randomized controlled trial by Turvey and colleagues.²¹ Veterans with a diagnosis of ≥ 1 chronic health condition (eg, diabetes, hypertension) were invited by letter to participate in a study about using online management of their health information. Interested patients were screened to meet additional inclusion criteria, such as taking ≥ 5 medications, receiving care from a non-VA provider, an appointment with a non-VA provider within the study time frame, and access to a computer, online access, and printer. 

Eligible veterans were randomized to receive either (1) BB training (intervention group) instructing patients to download the Continuity of Care Document and bring it to their non-VA provider visit; or (2) a training evaluating medical information online (control group). Training information was mailed, including written materials and phone support, to both groups. The intervention group could also access an online training link.

One of the objectives was to test whether downloading and bringing the health information to a non-VA appointment decreased medication list discrepancies. The sample was small, and differences in discrepancy rates between groups were not significant. Therefore, groups were combined for the present analysis. Visits occurred between December 2013 and December 2014. Greater detail about study design and primary results are available in the study by Turvey and colleagues.²¹

Study procedures were approved by the University of Iowa Institutional Review Board and the Iowa City VA Health Care System Research and Development Committee. All participants provided consent.

Identifying Discrepancies

A 4-phase process was used to address medication discrepancies.^22,23 The first phase defined medication discrepancy categories. The mutually exclusive categories were dose, frequency, and missing discrepancies. In cases where a medication was both dose and frequency discrepant, only dose discrepancy was applied. For missing medications, entities on only the VA list were marked as “non-VA missing” and medications appearing on only the non-VA list would be denoted as “VA missing.” Medications with no discrepancy were marked as such.

Phase 2 involved collecting medication data. Medication lists from the VA medical record were printed at the time of the non-VA provider appointment. Non-VA medication lists were obtained by sending a medical record request for the visit note, medication list, and any associated visit test results to the non-VA provider office within 2 to 3 weeks of the appointment. Patient names from both lists were replaced with unique patient identifiers.

In phase 3, a research assistant abstracted the hard copy medication lists into a database and identified discrepancies. Variables included medication name, dose, frequency, and administration route. Although administration routes were collected, discrepancies were not assessed because this information commonly was not specified. Medications also were coded as prescription or over-the-counter (OTC). Durable medical equipment often was present on VA lists (eg, syringes, test strips) and was excluded from all analyses. Medications also were not coded as discrepant if they were referenced in a visit note as being changed by the non-VA provider. These combined lists were evaluated by the research assistant based on the discrepancy categories specified in phase 1 and were verified by a pharmacist.

Phase 4 involved counting medication discrepancies. Medication discrepancy rates were calculated at the patient level, both descriptively (mean number of discrepancies per patient) and as a proportion of medications discrepant (number of discrepancies divided by total medications).

Identifying Duplications and High-Risk Medications

A pharmacist examined each combined medication list to identify therapeutic duplications, defined as a patient using ≥ 2 medications from the same medication class (eg, patient taking 2 statin drugs) but not 2 drugs for the same condition (eg, fish oil and atorvastatin for dyslipidemia). High-risk medications also were noted, including anticoagulants, certain nonsteroidal anti-inflammatory drugs, oral and injectable hypoglycemics, opioids, sedatives, and hypnotics.^24-26 These medications received special focus because of their link to a high risk for ADRs.²⁷

Descriptive statistics were calculated for patient characteristics and for each discrepancy type, both overall and according to prescription OTC, and high-risk medications. The proportion of discrepant medications was calculated for each category. Bivariate correlations were calculated for select variables to understand potential relationships.

Interviews With Non-VA Providers

All patients were instructed to bring a consent letter and the 1-page questionnaire to their non-VA provider appointment. The questionnaire contained an item asking whether non-VA providers could be contacted for a 15- to 30-minute follow-up interview. The semistructured, qualitative interviews assessed their experiences working with VA providers and VA patients, experiences with VA documents or records, preferences for receiving information from the VA, experience with personal health records, and sharing information with the VA. Eight interviews were conducted, audio-recorded, and transcribed. The goal of the interviews was to explore and understand provider perspectives on managing dual use veterans, including medication reconciliation processes to add context to the interpretation of medication list analysis. Because the data set was relatively small, summaries of each interview were created to highlight main points. These main points were sorted into topics, summarized, and representative quotes were selected.

Results

Fifty veterans were included in the analysis (Table 1). The mean age was 68.5 (SD 6.2); 90% were men. On average, they reported having 6 chronic health conditions and a fair-to-good health status. Based on the combined medication lists from VA and non-VA providers, veterans took an average of 15.8 (SD 7.0) unique medications (combined prescription and OTC/vitamins) and had an average of 10.0 (SD 6.1) all-type discrepancies (Table 2).

Overall, 58% of the prescription medications were discrepant: The most common discrepancy between the 2 lists was medication missing on one of the lists, which occurred 3.9 times per patient on average for prescription medications and 2.8 times per patient for OTCs. Frequency or dose discrepancies also were common between the lists at a rate of 1.9 discrepancies per patient for prescription medications and 1.2 discrepancies per patient for OTCs.

For high-risk medications, opiates and sedative medications had the most discrepancies between the lists because the VA practitioner may not have known that the patient was taking an opiate, although other discrepancies were present (Table 3). Anticoagulant discrepancies were the most consistent, most of these occurring with aspirin. Last, insulin commonly was dose discrepant between the 2 lists, although it also was missing from one list for a number of patients. Overall, high-risk medications shared a discrepancy rate (46.9%) similar to the overall rate.

Twelve therapeutic duplications were identified in the sample.Ten were between-list duplications, that is, “provider A” thought the patient was on a particular medication and “provider B” thought that the patient was on a different medication (Table 4). In 6 instances, within-list duplications were identified (ie, a provider had 2 medications on the list that should not be taken together because they were in the same drug class). In 4 cases, both between- and within-list duplications were present.

Interview Summaries

Veterans and medication. Multiple non-VA providers said that the primary reason veteran patients were going to a VA provider was to obtain discounted medications. The use of the VA for medications also was a way for the non-VA provider to discover that the patient was a veteran. One non-VA provider was particularly concerned about the impact of new or different medications from VA prescribers on efforts to stabilize the patient’s chronic condition.

Several non-VA providers reported that veterans often brought a medication list to the appointment, and several providers recommended the practice to their patients. Non-VA providers preferred to have patients transfer information from VA, sometimes requesting that veterans bring in their records from recent appointments rather than the non-VA provider obtain the information directly from the VA.

Information sharing. Non-VA providers generally preferred hard copies of medication lists and other documents rather than scans because they were more likely to be included in decision making if the documents were presented during the visit. Also, document scans may be buried in the electronic medical record. Some providers mentioned their interest in electronic transfer of medical information like medication lists if the technology were more developed and better integrated.

“I think the long-term vision would be that it should be electronic… it wouldn’t necessarily be feasible at this time. Our system scans paper documents in to an e-version. … but when the patient comes to their encounter 10 days later, you don’t realize the stuff’s there… Having the patient bring them in is probably a more certain way to make sure that it’s actually included in your decision making as a provider.”

Most non-VA providers welcomed more information such as imaging studies because they reported rarely receiving this information from the VA system. Two mentioned the potential for too much information and wanted concise reports should the flow of information increase. Providers had little interest in logging in to a patient’s online health record portal as a delegate for reasons related to complexity, time, privacy, and lack of mechanism to document the information accessed.

Medication reconciliation. Non-VA providers generally reported that patients bringing their own or an outside medication list would prompt a process of medication reconciliation. The providers were interested in making changes to their records based on other lists, but outside data were verified against a patient self-report of actual use before adopting changes.

“I print out my med list of what I have in the computer and then I just check off my list against their list. And then whatever’s remaining, we talk about what the differences are, when they were changed, what they were changed for, if they were taken off of something, and if I don’t agree, then I’ll tell the patient, ‘look, there’s a disagreement here, they’ve told you not to be on this. I want you on this.”

Should a discrepancy arise, non-VA providers generally had a negative view of attempting to contact VA providers. Other mechanisms such as calling a local pharmacy would be done first.

Discussion

This study provided initial evidence that medication list discrepancies exist for dual use veterans. Other studies of medication list discrepancies have linked such inconsistencies to medication-related problems and negative outcomes for patients.²⁷ Although efforts to increase access to care for veterans have advantages related to expediency, consequences to fragmenting care exist. More robust mechanisms for establishing and maintaining medication list consistency are needed, especially given the lack of a universally accepted medical record format or repository. A multifaceted approach, including patient engagement, seems necessary.

This study also showed that discrepancies of high-risk medications are common for veteran participants, placing them at risk for medication-related problems and harm. These risks included dose and frequency discrepancies that could result in over- or underdosing of medications and in medication omissions, which could cause duplicative therapies and unnecessary risks. For example, aspirin frequently was listed on non-VA lists but was omitted from VA medication lists. This could be problematic for patients who present to the VA for a procedure in which no information about aspirin could jeopardize their safety. Insulin doses also were commonly discrepant, which could impact glycemic control.

Many providers also had incomplete prescribing information for opiates. Those prescriptions are particularly relevant given the link between veterans, posttraumatic stress disorder, depression, and substance abuse.^28-30 However, it was beyond the scope of this pilot study to link these discrepancies to ADRs, such as emergency department visits or hospital admissions. Other studies have demonstrated that discrepancies at hospital discharge can result in these types of negative outcomes.^27,31 Subsequent research should determine the clinical significance of discrepancies that occur when veterans are dual users.

The qualitative interviews provided some initial context on prescriber perspectives about the role of veterans participating in the medication list sharing process and personal health records. It seemed that for the portion of patients who brought a list to their non-VA provider appointment, the information was welcomed but fell outside the usual visit workflow. Many provider visits are dominated by current patient symptoms, and issues of reconciling medications may be a lower priority.³² Also, some providers may delegate medication reconciliation functions to a nurse or other support staff. One physician offered that he delegated logging in to a patient’s online medication information to a health coach on staff. These findings were consistent with perspectives shared by non-VA family practice physicians about personal health records.³³

The most common way to integrate outside medication lists into the non-VA provider’s medical record seemed to be scanning the document. Scanning had its limitations because the provider might be unaware of the scanned document, and there were no mechanisms to import medication names and doses. However, the process may improve only the non-VA providers’ records, as they reported that they had no easy or consistent way to transmit medication changes to notes to the VA.

In general, communicating with VA providers was seen as not feasible and not worth their time or effort. It may be beneficial to address this non-VA provider concern because it seems to inhibit the transfer of important health information and the maintenance of a concordant medication record. Information transfer is particularly relevant for veterans who are primarily cared for by non-VA providers and use the VA only to get prescription medications.

In the current approach, non-VA providers have no simple, direct way to update the VA medication list. Transmitting updates carries the risk of inappropriate changes and is concerning if neither or both prescribers consider themselves to be responsible for the patient’s medications. Also, the potential exists for all medication lists to be inaccurate if the lists do not reflect the medications patients take when left on their own. Patient nonadherence rates can exceed 50%, depending on the medication.^34,35 Several interviewed non-VA physicians stressed the importance of asking patients to list the medications they were using during the medication reconciliation process.

This study offers several areas for additional inquiry, including understanding how providers make sense of medication lists from other sources and what technologies can be applied to increase list consistency without increasing the burden on providers.

Practice Implications

Although patient involvement in medication list sharing has the potential to improve information consistency, health systems, providers, and other stakeholders should be cautious in assuming that other prescribers will work to combat medication list entropy, especially if no systems exist to seamlessly incorporate this information into clinic workflow. Devising standardized procedures when patients bring in their records from other providers increases the likelihood that this information will be incorporated into clinical decision making and maintaining up-to-date medication information for patients who use multiple prescribers.

Limitations

These analyses are based on a small sample size (n = 50 for chart review) and (n = 8 for the semistructured interviews) from a single Midwestern state. These findings should be used as evidence for further inquiry.

Conclusion

This study illuminates the level of discrepancies between the medication lists of veteran dual users, including high rates of discrepancies for high-risk medications, such as anticoagulants and opiates. This study also provides evidence of deficiencies in the health care system to decrease medication list entropy that may place veterans at an elevated risk for adverse medication events.

Acne vulgaris predominantly occurs during puberty and can persist beyond 25 years of age, most commonly in women.^1,2 Although acne does not cause physical impairment, it can be associated with a considerable psychosocial burden including increased levels of anxiety, anger, depression, and frustration, which in turn can affect vocational and academic performance, quality of life (QOL), and self-esteem.³

Quality of life measures provide valuable insight into the debilitating effects of acne.¹ It has been suggested that acne patients may experience poor body image and low self-esteem as well as social isolation and constriction of activities.⁴ Self-esteem is a favorable and unfavorable attitude toward oneself.⁵ A marked emphasis has been placed on body image in society, fueled by external cues such as the media.^3,6 This study was carried out to assess QOL and self-esteem in acne patients.

Methods

This prospective, hospital-based, cross-sectional, case-control study was conducted at The Oxford Medical College, Hospital & Research Center (Bangalore, India), over a period of 3 months. One hundred consecutive acne cases (age range, 12–45 years) and 100 age- and gender-matched controls who did not have any skin disease provided consent and were included in the analysis. Guardians gave consent for individuals who were younger than 18 years. Exclusion criteria for cases included a medical disorder (eg, epilepsy, diabetes mellitus, hypertension) or medications that would likely interfere with acne assessment.

The cases and controls were administered a semistructured questionnaire to collect sociodemographic details. Acne was graded for the predominant lesions, QOL was assessed using the Cardiff Acne Disability Index (CADI) and World Health Organization Quality of Life–BREF (WHOQOL-BREF) scale, and self-esteem was measured using the Rosenberg self-esteem scale (RSES). The study was approved by the institutional review board.

Acne Grading

Acne was graded according to the predominant lesions using the following criteria: grade 1=comedones and occasional papules; grade 2=papules, comedones, and few pustules; grade 3=predominant pustules, nodules, and abscesses; and grade 4=mainly cysts, abscesses, and widespread scarring.¹

Quality of Life Assessment

The CADI questionnaire was used to assess the level of disability caused by acne.⁶ It is a 5-item questionnaire with scores ranging from 0 to 3 for a total maximum score of 15 and minimum score of 0. Total scores were classified as low (0–4), medium (5–9), and high (10–15).⁷

The WHOQOL-BREF is a self-reported questionnaire containing 26 items that make up the 4 domains of physical health (7 items), psychological health (6 items), social relationships (3 items), and environment (8 items); there also are 2 single questions regarding the overall perception of QOL and health. Questions were scored on aseries of 5-point scales with higher scores denoting better QOL.⁸

Self-esteem Assessment

The RSES uses a 5-point Likert scale from strongly agree to strongly disagree to rate a series of 10 statements. The total score ranges from 0 to 30. Scores less than 15 suggest low self-esteem, while scores of 15 and greater indicate high self-esteem.⁵

Statistical Analysis

Results were analyzed using descriptive and inferential statistical methods. A χ² test was used for categorical data, and a Student t test and an analysis of variance were used for continuous data.

Results

The study consisted of 100 cases and 100 controls. The mean age was 21 years. The majority of cases reported an age of onset of acne of 11 to 20 years (66%), were predominantly female (58%) from rural backgrounds, and had a family history of acne (68%). The majority of lesions ceased within 24 months (60%). The face was the most commonly involved area (80%) and papules were the most prevalent lesion type (62%).

Cases predominantly had grade 2 acne (46%), and there was medium to high impairment in QOL according to CADI scores.

The scores for all the domains of the WHOQOL-BREF as well as the total score were lower in cases compared to controls (Table). There was a statistically significant difference between the 2 groups in the psychological (P=.0402) and environment (P=.006) domains.

The RSES mean (SD) score was higher in controls (19.74 [4.23]) than in cases (15.72 [5.06]) and was statistically significant (P<.0001). Low self-esteem was noted in 38% of cases and 16% of controls, and high self-esteem was noted in 62% and 84%, respectively.

In reviewing the correlation between acne severity, CADI, WHOQOL-BREF, and RSES scores, we found a positive correlation between acne severity and CADI scores (R=0.51), which implies that as the severity of acne worsens, the QOL impairment increases. There was a negative correlation between acne severity, WHOQOL-BREF score (R=–0.13), and RSES score (R=–0.18), which showed that as the severity of acne increases, QOL and self-esteem decrease. We observed that as the grade of acne increases, there is a statistically significant impairment in the QOL according to CADI (P<.001), while there is a reduction in QOL and self-esteem according to WHOQOL-BREF and RSES, respectively (P>.05).

Comment

Patients are more likely to develop acne than any other skin disease in their lifetime. Only in recent years has the psychodermatologic literature begun to address the possibility of acne having a psychological and emotional impact.⁴ Although the cause-and-effect relationship between acne and psychological trauma has been debated for decades, only recently has the measurement focus shifted from psychological correlates (eg, personality) and emotional triggers (eg, stress) to the effect of acne on patients’ QOL and self-esteem. This shift occurred as validated instruments for measuring disability, QOL, and self-esteem, specifically in patients with skin diseases, became available.⁹

In our study, the age of onset of acne was 11 to 20 years and it affected predominantly females (58%), which is in concordance with other studies, as acne develops in adolescence and subsides in adulthood.^1,10 Acne is more common in females due to hormonal factors and use of cosmetics. We observed that the face (80%) was most frequently affected, followed by the back (14%) and chest (6%), which is similar to prior studies.^1,10 Because the face plays an important role in body image, the presence of facial lesions may be unacceptable for patients and therefore they may present more frequently to dermatologists.

In our study, 68% of cases and 22% of controls had a family history of acne. A similar correlation also was noted in other studies, which suggests acne has an inherited predisposition due to involvement of the cytochrome P450-1A1 gene, CYP1A1, and steroid 21-hydroxylase, P-450-c21.^1,11 We found 46% of cases had grade 2 acne and 36% had grade 1 acne, which was congruent with prior studies.^12,13 Patients with severe acne are more likely to seek medical intervention in hospitals.

In our study, 58% of the cases had medium to high impairment in QOL according to CADI scores. We noticed as the severity of acne increased there was severe impairment in QOL. Similar findings have been found in studies that used other scales to assess QOL.^1,6,9

In our study, 38% of cases and 16% of controls had low self-esteem, which was statistically significant (P<.0001). There was a negative correlation between the severity of acne and self-esteem. In a prior study of 240 professional college students, 53% had feelings of low self-esteem and 40% revealed they avoided social gatherings and interactions with the opposite sex because of their acne.¹⁴ In a questionnaire-based survey of 3775 students, it was observed that the presence of acne correlated with poor self-attitude in boys and poor self-worth in girls.³ We found patients with grade 1 acne had higher self-esteem as compared to other grades of acne. Similarly, a cross-sectional study by Uslu et al¹⁵ found a direct correlation between acne severity and lower self-esteem using the RSES questionnaire. Although acne may be viewed as a minor cosmetic issue, it can have a negative impact on self-esteem and interpersonal relationships. Many of the studies had not used a validated structured questionnaire to assess self-esteem and there is a paucity of literature in relation to acne and self-esteem.^3,16,17

According to the WHOQOL-BREF, the psychological domain was affected more in cases than in controls, which was a statistically significant difference. One study observed that patients experience immediate psychological consequences of acne such as reduced self-esteem, poor self-image, self-consciousness, and embarrassment.³ These effects are exacerbated by taunting, stigmatization, and perceptions of scrutiny and being judged, causing patients to avoid interaction and social situations. Similarly, Pruthi and Babu¹⁸ observed that acne had an impact on the psychosocial aspects of adult females using the Dermatology Life Quality Index and CADI.

Financial resources, health and social care accessibility, and opportunities for acquiring new information and skills were the factors that were considered in the environment domain of the WHOQOL-BREF.⁸ We noted that the environment domain scores were significantly lower in cases than in controls. The cases could have had a detrimental effect on the latest opportunities in occupational functioning due to acne, and as most of the population was from a rural area, they were having less favorable circumstances in acquiring new information about the management of acne.

There was no statistically significant difference between cases and controls in the social and physical domains of the WHOQOL-BREF, which suggests that these fields do not influence QOL. Similarly, patients in Sarawak, Malaysia, were least affected in the domain of social functioning, which was likely attributed to the upbringing of this population encouraging stoicism.¹⁹

In the current study, QOL impairment showed a positive correlation with acne severity according to CADI scores; however, there was no significant difference between WHOQOL-BREF score and acne grading, which suggests that QOL impairment does not depend on severity of acne alone. Physical, psychological, social, and environment domains play an important role in impaired QOL. Hence, by using the WHOQOL-BREF we can evaluate the actual domain that is adversely affected by acne and can be treated with a holistic approach. This point must be stressed in the training of medical faculty, as the treatment of acne should not be based on acne severity alone but also on the degree of QOL impairment.¹⁹

These results indicate that more data are required and there is a need to consider other variables that could play a role. This study was a hospital-based, cross-sectional study with a small sample group that cannot be generalized, which are limitations. Longitudinal follow-up of the cases before and after treatment was not done. The questionnaires helped us to detect psychosocial aspects but were insufficient to diagnose psychiatric comorbidity.

The strengths of this study include the use of a specific scale for the assessment of self-esteem. The usage of comprehensive (WHOQOL-BREF) and specific (CADI) scales to evaluate QOL has mutual advantage.

Conclusion

Acne vulgaris is a disease that can adversely affect an individual’s QOL and self-esteem. This study suggested the importance of screening for psychosocial problems in those who present for management of acne. It is important for dermatologists to be cautious about psychological problems in acne patients and be aware of the importance of basic psychosomatic treatment in conjunction with medical treatment in the management of acne.

Acne vulgaris predominantly occurs during puberty and can persist beyond 25 years of age, most commonly in women.^1,2 Although acne does not cause physical impairment, it can be associated with a considerable psychosocial burden including increased levels of anxiety, anger, depression, and frustration, which in turn can affect vocational and academic performance, quality of life (QOL), and self-esteem.³

Quality of life measures provide valuable insight into the debilitating effects of acne.¹ It has been suggested that acne patients may experience poor body image and low self-esteem as well as social isolation and constriction of activities.⁴ Self-esteem is a favorable and unfavorable attitude toward oneself.⁵ A marked emphasis has been placed on body image in society, fueled by external cues such as the media.^3,6 This study was carried out to assess QOL and self-esteem in acne patients.

Methods

This prospective, hospital-based, cross-sectional, case-control study was conducted at The Oxford Medical College, Hospital & Research Center (Bangalore, India), over a period of 3 months. One hundred consecutive acne cases (age range, 12–45 years) and 100 age- and gender-matched controls who did not have any skin disease provided consent and were included in the analysis. Guardians gave consent for individuals who were younger than 18 years. Exclusion criteria for cases included a medical disorder (eg, epilepsy, diabetes mellitus, hypertension) or medications that would likely interfere with acne assessment.

The cases and controls were administered a semistructured questionnaire to collect sociodemographic details. Acne was graded for the predominant lesions, QOL was assessed using the Cardiff Acne Disability Index (CADI) and World Health Organization Quality of Life–BREF (WHOQOL-BREF) scale, and self-esteem was measured using the Rosenberg self-esteem scale (RSES). The study was approved by the institutional review board.

Acne Grading

Acne was graded according to the predominant lesions using the following criteria: grade 1=comedones and occasional papules; grade 2=papules, comedones, and few pustules; grade 3=predominant pustules, nodules, and abscesses; and grade 4=mainly cysts, abscesses, and widespread scarring.¹

Quality of Life Assessment

The CADI questionnaire was used to assess the level of disability caused by acne.⁶ It is a 5-item questionnaire with scores ranging from 0 to 3 for a total maximum score of 15 and minimum score of 0. Total scores were classified as low (0–4), medium (5–9), and high (10–15).⁷

The WHOQOL-BREF is a self-reported questionnaire containing 26 items that make up the 4 domains of physical health (7 items), psychological health (6 items), social relationships (3 items), and environment (8 items); there also are 2 single questions regarding the overall perception of QOL and health. Questions were scored on aseries of 5-point scales with higher scores denoting better QOL.⁸

Self-esteem Assessment

The RSES uses a 5-point Likert scale from strongly agree to strongly disagree to rate a series of 10 statements. The total score ranges from 0 to 30. Scores less than 15 suggest low self-esteem, while scores of 15 and greater indicate high self-esteem.⁵

Statistical Analysis

Results were analyzed using descriptive and inferential statistical methods. A χ² test was used for categorical data, and a Student t test and an analysis of variance were used for continuous data.

Results

The study consisted of 100 cases and 100 controls. The mean age was 21 years. The majority of cases reported an age of onset of acne of 11 to 20 years (66%), were predominantly female (58%) from rural backgrounds, and had a family history of acne (68%). The majority of lesions ceased within 24 months (60%). The face was the most commonly involved area (80%) and papules were the most prevalent lesion type (62%).

Cases predominantly had grade 2 acne (46%), and there was medium to high impairment in QOL according to CADI scores.

The scores for all the domains of the WHOQOL-BREF as well as the total score were lower in cases compared to controls (Table). There was a statistically significant difference between the 2 groups in the psychological (P=.0402) and environment (P=.006) domains.

The RSES mean (SD) score was higher in controls (19.74 [4.23]) than in cases (15.72 [5.06]) and was statistically significant (P<.0001). Low self-esteem was noted in 38% of cases and 16% of controls, and high self-esteem was noted in 62% and 84%, respectively.

In reviewing the correlation between acne severity, CADI, WHOQOL-BREF, and RSES scores, we found a positive correlation between acne severity and CADI scores (R=0.51), which implies that as the severity of acne worsens, the QOL impairment increases. There was a negative correlation between acne severity, WHOQOL-BREF score (R=–0.13), and RSES score (R=–0.18), which showed that as the severity of acne increases, QOL and self-esteem decrease. We observed that as the grade of acne increases, there is a statistically significant impairment in the QOL according to CADI (P<.001), while there is a reduction in QOL and self-esteem according to WHOQOL-BREF and RSES, respectively (P>.05).

Comment

Patients are more likely to develop acne than any other skin disease in their lifetime. Only in recent years has the psychodermatologic literature begun to address the possibility of acne having a psychological and emotional impact.⁴ Although the cause-and-effect relationship between acne and psychological trauma has been debated for decades, only recently has the measurement focus shifted from psychological correlates (eg, personality) and emotional triggers (eg, stress) to the effect of acne on patients’ QOL and self-esteem. This shift occurred as validated instruments for measuring disability, QOL, and self-esteem, specifically in patients with skin diseases, became available.⁹

In our study, the age of onset of acne was 11 to 20 years and it affected predominantly females (58%), which is in concordance with other studies, as acne develops in adolescence and subsides in adulthood.^1,10 Acne is more common in females due to hormonal factors and use of cosmetics. We observed that the face (80%) was most frequently affected, followed by the back (14%) and chest (6%), which is similar to prior studies.^1,10 Because the face plays an important role in body image, the presence of facial lesions may be unacceptable for patients and therefore they may present more frequently to dermatologists.

In our study, 68% of cases and 22% of controls had a family history of acne. A similar correlation also was noted in other studies, which suggests acne has an inherited predisposition due to involvement of the cytochrome P450-1A1 gene, CYP1A1, and steroid 21-hydroxylase, P-450-c21.^1,11 We found 46% of cases had grade 2 acne and 36% had grade 1 acne, which was congruent with prior studies.^12,13 Patients with severe acne are more likely to seek medical intervention in hospitals.

In our study, 58% of the cases had medium to high impairment in QOL according to CADI scores. We noticed as the severity of acne increased there was severe impairment in QOL. Similar findings have been found in studies that used other scales to assess QOL.^1,6,9

In our study, 38% of cases and 16% of controls had low self-esteem, which was statistically significant (P<.0001). There was a negative correlation between the severity of acne and self-esteem. In a prior study of 240 professional college students, 53% had feelings of low self-esteem and 40% revealed they avoided social gatherings and interactions with the opposite sex because of their acne.¹⁴ In a questionnaire-based survey of 3775 students, it was observed that the presence of acne correlated with poor self-attitude in boys and poor self-worth in girls.³ We found patients with grade 1 acne had higher self-esteem as compared to other grades of acne. Similarly, a cross-sectional study by Uslu et al¹⁵ found a direct correlation between acne severity and lower self-esteem using the RSES questionnaire. Although acne may be viewed as a minor cosmetic issue, it can have a negative impact on self-esteem and interpersonal relationships. Many of the studies had not used a validated structured questionnaire to assess self-esteem and there is a paucity of literature in relation to acne and self-esteem.^3,16,17

According to the WHOQOL-BREF, the psychological domain was affected more in cases than in controls, which was a statistically significant difference. One study observed that patients experience immediate psychological consequences of acne such as reduced self-esteem, poor self-image, self-consciousness, and embarrassment.³ These effects are exacerbated by taunting, stigmatization, and perceptions of scrutiny and being judged, causing patients to avoid interaction and social situations. Similarly, Pruthi and Babu¹⁸ observed that acne had an impact on the psychosocial aspects of adult females using the Dermatology Life Quality Index and CADI.

Financial resources, health and social care accessibility, and opportunities for acquiring new information and skills were the factors that were considered in the environment domain of the WHOQOL-BREF.⁸ We noted that the environment domain scores were significantly lower in cases than in controls. The cases could have had a detrimental effect on the latest opportunities in occupational functioning due to acne, and as most of the population was from a rural area, they were having less favorable circumstances in acquiring new information about the management of acne.

There was no statistically significant difference between cases and controls in the social and physical domains of the WHOQOL-BREF, which suggests that these fields do not influence QOL. Similarly, patients in Sarawak, Malaysia, were least affected in the domain of social functioning, which was likely attributed to the upbringing of this population encouraging stoicism.¹⁹

In the current study, QOL impairment showed a positive correlation with acne severity according to CADI scores; however, there was no significant difference between WHOQOL-BREF score and acne grading, which suggests that QOL impairment does not depend on severity of acne alone. Physical, psychological, social, and environment domains play an important role in impaired QOL. Hence, by using the WHOQOL-BREF we can evaluate the actual domain that is adversely affected by acne and can be treated with a holistic approach. This point must be stressed in the training of medical faculty, as the treatment of acne should not be based on acne severity alone but also on the degree of QOL impairment.¹⁹

These results indicate that more data are required and there is a need to consider other variables that could play a role. This study was a hospital-based, cross-sectional study with a small sample group that cannot be generalized, which are limitations. Longitudinal follow-up of the cases before and after treatment was not done. The questionnaires helped us to detect psychosocial aspects but were insufficient to diagnose psychiatric comorbidity.

The strengths of this study include the use of a specific scale for the assessment of self-esteem. The usage of comprehensive (WHOQOL-BREF) and specific (CADI) scales to evaluate QOL has mutual advantage.

Conclusion

Acne vulgaris is a disease that can adversely affect an individual’s QOL and self-esteem. This study suggested the importance of screening for psychosocial problems in those who present for management of acne. It is important for dermatologists to be cautious about psychological problems in acne patients and be aware of the importance of basic psychosomatic treatment in conjunction with medical treatment in the management of acne.

Acne vulgaris predominantly occurs during puberty and can persist beyond 25 years of age, most commonly in women.^1,2 Although acne does not cause physical impairment, it can be associated with a considerable psychosocial burden including increased levels of anxiety, anger, depression, and frustration, which in turn can affect vocational and academic performance, quality of life (QOL), and self-esteem.³

Quality of life measures provide valuable insight into the debilitating effects of acne.¹ It has been suggested that acne patients may experience poor body image and low self-esteem as well as social isolation and constriction of activities.⁴ Self-esteem is a favorable and unfavorable attitude toward oneself.⁵ A marked emphasis has been placed on body image in society, fueled by external cues such as the media.^3,6 This study was carried out to assess QOL and self-esteem in acne patients.

Methods

This prospective, hospital-based, cross-sectional, case-control study was conducted at The Oxford Medical College, Hospital & Research Center (Bangalore, India), over a period of 3 months. One hundred consecutive acne cases (age range, 12–45 years) and 100 age- and gender-matched controls who did not have any skin disease provided consent and were included in the analysis. Guardians gave consent for individuals who were younger than 18 years. Exclusion criteria for cases included a medical disorder (eg, epilepsy, diabetes mellitus, hypertension) or medications that would likely interfere with acne assessment.

The cases and controls were administered a semistructured questionnaire to collect sociodemographic details. Acne was graded for the predominant lesions, QOL was assessed using the Cardiff Acne Disability Index (CADI) and World Health Organization Quality of Life–BREF (WHOQOL-BREF) scale, and self-esteem was measured using the Rosenberg self-esteem scale (RSES). The study was approved by the institutional review board.

Acne Grading

Acne was graded according to the predominant lesions using the following criteria: grade 1=comedones and occasional papules; grade 2=papules, comedones, and few pustules; grade 3=predominant pustules, nodules, and abscesses; and grade 4=mainly cysts, abscesses, and widespread scarring.¹

Quality of Life Assessment

The CADI questionnaire was used to assess the level of disability caused by acne.⁶ It is a 5-item questionnaire with scores ranging from 0 to 3 for a total maximum score of 15 and minimum score of 0. Total scores were classified as low (0–4), medium (5–9), and high (10–15).⁷

The WHOQOL-BREF is a self-reported questionnaire containing 26 items that make up the 4 domains of physical health (7 items), psychological health (6 items), social relationships (3 items), and environment (8 items); there also are 2 single questions regarding the overall perception of QOL and health. Questions were scored on aseries of 5-point scales with higher scores denoting better QOL.⁸

Self-esteem Assessment

The RSES uses a 5-point Likert scale from strongly agree to strongly disagree to rate a series of 10 statements. The total score ranges from 0 to 30. Scores less than 15 suggest low self-esteem, while scores of 15 and greater indicate high self-esteem.⁵

Statistical Analysis

Results were analyzed using descriptive and inferential statistical methods. A χ² test was used for categorical data, and a Student t test and an analysis of variance were used for continuous data.

Results

The study consisted of 100 cases and 100 controls. The mean age was 21 years. The majority of cases reported an age of onset of acne of 11 to 20 years (66%), were predominantly female (58%) from rural backgrounds, and had a family history of acne (68%). The majority of lesions ceased within 24 months (60%). The face was the most commonly involved area (80%) and papules were the most prevalent lesion type (62%).

Cases predominantly had grade 2 acne (46%), and there was medium to high impairment in QOL according to CADI scores.

The scores for all the domains of the WHOQOL-BREF as well as the total score were lower in cases compared to controls (Table). There was a statistically significant difference between the 2 groups in the psychological (P=.0402) and environment (P=.006) domains.

The RSES mean (SD) score was higher in controls (19.74 [4.23]) than in cases (15.72 [5.06]) and was statistically significant (P<.0001). Low self-esteem was noted in 38% of cases and 16% of controls, and high self-esteem was noted in 62% and 84%, respectively.

In reviewing the correlation between acne severity, CADI, WHOQOL-BREF, and RSES scores, we found a positive correlation between acne severity and CADI scores (R=0.51), which implies that as the severity of acne worsens, the QOL impairment increases. There was a negative correlation between acne severity, WHOQOL-BREF score (R=–0.13), and RSES score (R=–0.18), which showed that as the severity of acne increases, QOL and self-esteem decrease. We observed that as the grade of acne increases, there is a statistically significant impairment in the QOL according to CADI (P<.001), while there is a reduction in QOL and self-esteem according to WHOQOL-BREF and RSES, respectively (P>.05).

Comment

Patients are more likely to develop acne than any other skin disease in their lifetime. Only in recent years has the psychodermatologic literature begun to address the possibility of acne having a psychological and emotional impact.⁴ Although the cause-and-effect relationship between acne and psychological trauma has been debated for decades, only recently has the measurement focus shifted from psychological correlates (eg, personality) and emotional triggers (eg, stress) to the effect of acne on patients’ QOL and self-esteem. This shift occurred as validated instruments for measuring disability, QOL, and self-esteem, specifically in patients with skin diseases, became available.⁹

In our study, the age of onset of acne was 11 to 20 years and it affected predominantly females (58%), which is in concordance with other studies, as acne develops in adolescence and subsides in adulthood.^1,10 Acne is more common in females due to hormonal factors and use of cosmetics. We observed that the face (80%) was most frequently affected, followed by the back (14%) and chest (6%), which is similar to prior studies.^1,10 Because the face plays an important role in body image, the presence of facial lesions may be unacceptable for patients and therefore they may present more frequently to dermatologists.

In our study, 68% of cases and 22% of controls had a family history of acne. A similar correlation also was noted in other studies, which suggests acne has an inherited predisposition due to involvement of the cytochrome P450-1A1 gene, CYP1A1, and steroid 21-hydroxylase, P-450-c21.^1,11 We found 46% of cases had grade 2 acne and 36% had grade 1 acne, which was congruent with prior studies.^12,13 Patients with severe acne are more likely to seek medical intervention in hospitals.

In our study, 58% of the cases had medium to high impairment in QOL according to CADI scores. We noticed as the severity of acne increased there was severe impairment in QOL. Similar findings have been found in studies that used other scales to assess QOL.^1,6,9

In our study, 38% of cases and 16% of controls had low self-esteem, which was statistically significant (P<.0001). There was a negative correlation between the severity of acne and self-esteem. In a prior study of 240 professional college students, 53% had feelings of low self-esteem and 40% revealed they avoided social gatherings and interactions with the opposite sex because of their acne.¹⁴ In a questionnaire-based survey of 3775 students, it was observed that the presence of acne correlated with poor self-attitude in boys and poor self-worth in girls.³ We found patients with grade 1 acne had higher self-esteem as compared to other grades of acne. Similarly, a cross-sectional study by Uslu et al¹⁵ found a direct correlation between acne severity and lower self-esteem using the RSES questionnaire. Although acne may be viewed as a minor cosmetic issue, it can have a negative impact on self-esteem and interpersonal relationships. Many of the studies had not used a validated structured questionnaire to assess self-esteem and there is a paucity of literature in relation to acne and self-esteem.^3,16,17

According to the WHOQOL-BREF, the psychological domain was affected more in cases than in controls, which was a statistically significant difference. One study observed that patients experience immediate psychological consequences of acne such as reduced self-esteem, poor self-image, self-consciousness, and embarrassment.³ These effects are exacerbated by taunting, stigmatization, and perceptions of scrutiny and being judged, causing patients to avoid interaction and social situations. Similarly, Pruthi and Babu¹⁸ observed that acne had an impact on the psychosocial aspects of adult females using the Dermatology Life Quality Index and CADI.

Financial resources, health and social care accessibility, and opportunities for acquiring new information and skills were the factors that were considered in the environment domain of the WHOQOL-BREF.⁸ We noted that the environment domain scores were significantly lower in cases than in controls. The cases could have had a detrimental effect on the latest opportunities in occupational functioning due to acne, and as most of the population was from a rural area, they were having less favorable circumstances in acquiring new information about the management of acne.

There was no statistically significant difference between cases and controls in the social and physical domains of the WHOQOL-BREF, which suggests that these fields do not influence QOL. Similarly, patients in Sarawak, Malaysia, were least affected in the domain of social functioning, which was likely attributed to the upbringing of this population encouraging stoicism.¹⁹

In the current study, QOL impairment showed a positive correlation with acne severity according to CADI scores; however, there was no significant difference between WHOQOL-BREF score and acne grading, which suggests that QOL impairment does not depend on severity of acne alone. Physical, psychological, social, and environment domains play an important role in impaired QOL. Hence, by using the WHOQOL-BREF we can evaluate the actual domain that is adversely affected by acne and can be treated with a holistic approach. This point must be stressed in the training of medical faculty, as the treatment of acne should not be based on acne severity alone but also on the degree of QOL impairment.¹⁹

These results indicate that more data are required and there is a need to consider other variables that could play a role. This study was a hospital-based, cross-sectional study with a small sample group that cannot be generalized, which are limitations. Longitudinal follow-up of the cases before and after treatment was not done. The questionnaires helped us to detect psychosocial aspects but were insufficient to diagnose psychiatric comorbidity.

The strengths of this study include the use of a specific scale for the assessment of self-esteem. The usage of comprehensive (WHOQOL-BREF) and specific (CADI) scales to evaluate QOL has mutual advantage.

Conclusion

Acne vulgaris is a disease that can adversely affect an individual’s QOL and self-esteem. This study suggested the importance of screening for psychosocial problems in those who present for management of acne. It is important for dermatologists to be cautious about psychological problems in acne patients and be aware of the importance of basic psychosomatic treatment in conjunction with medical treatment in the management of acne.

The incidence of skin cancer, along with its effects on patients and the economy, has continued to increase and therefore requires particular attention from dermatologists. UV light has been shown to be of etiopathologic importance in the development of various types of skin cancer.^1-3 Studies have shown that there is a direct correlation between the incidence of skin cancer and average annual amounts of UV radiation exposure.³ Accordingly, in 2009 the International Agency for Research on Cancer classified UV light as carcinogenic to humans.⁴ Therefore, the general public must be made aware of the danger of exposure to UV radiation.

In Australia, government initiatives to educate the population on causes of skin cancer development and its relationship to UV radiation have already caused the public to change their way of thinking and to deal with sunlight in a conscious and responsible manner.⁵ A large proportion of the Australian population with light skin is at a particularly high risk for developing skin cancer due to intense exposure to UV radiation. Numerous campaigns in Germany and other countries have attempted to sensitize the public to this issue by emphasizing a reduction in UV exposure (primary prevention) or highlighting the importance of early diagnosis (secondary prevention).^6,7

For a good prognosis, it is crucial that skin cancer, particularly melanoma, is discovered at an early or precancerous stage.⁸ For this reason, self-examination of the skin and skin cancer screening are important factors that can contribute to ensuring early and curative treatment.^9-11 Since July 1, 2008, skin cancer screenings have been included in the preventative health care program by statutory health insurance providers in Germany. As part of this program, the cost of screening once every 2 years for individuals 35 years and older is covered by statutory health insurance.¹² Several studies have shown a decline in the melanoma mortality rate since the introduction of skin cancer screening programs in Germany.^11,13,14

Employee skin cancer screening programs are an important method of examining high numbers of individuals quickly and effectively. These programs have been carried out in Germany and other countries.^15,16 Studies have shown that skin cancer screening carried out selectively on defined groups can be an effective form of secondary prevention, particularly for those who work outdoors.¹⁷

An employee skin cancer screening program was carried out as part of this study. The findings are interpreted and discussed in relation to other employee screening programs that have been reported as well as those introduced by statutory health insurance providers in Germany. The aim of this study was to determine the importance and effectiveness of employee skin cancer screening programs and the role they play in secondary prevention of skin cancer.

Methods

Study Population

Employees of a technical company in Bavaria, Germany, were offered a skin cancer screening program by the employer’s occupational health service and health insurance provider in collaboration with the Department of Dermatology at the University Hospital Erlangen (Erlangen, Germany). Skin examinations were performed exclusively by 5 trained dermatologists. Only direct employees of the company at 3 of its locations in the Erlangen area were eligible to participate. The total number of employees varied by location (1072–5126 employees). The majority of employees had a university education or had completed technical training. Family members and other individuals who were not members of the company were excluded. There were no further inclusion or exclusion criteria. Over a period of 13 days, 783 of 7823 total employees (10.0%) were examined and included in the study. The study was approved by the Responsible Ethics Commission of the Faculty of Medicine at Friedrich-Alexander-University Erlangen-Nürnberg, Germany.

Study Design

Employees signed a consent form for participation in the study and completed a standardized questionnaire. The questionnaire was based on surveys used in a prior study¹⁸ and collected information on current and prior skin lesions, prior dermatological screening, personal and family history of skin tumors, frequency of UV exposure, and type of UV protection used. For the question on measures taken for protection from UV radiation, possible answers included with sunscreen cream, with suitable sun-protective clothing, and by staying in the shade, or no measures were taken. In contrast to the other questions, multiple answers were accepted for this question. Answering no automatically excluded other possible answers. Participants also were asked to assess their own Fitzpatrick skin type¹⁹; the questionnaire included explanations of each skin type (I–IV).

The participants were then called in for examination by the dermatologist at 15-minute intervals. All clothing was removed and the skin was examined. Dermatoscopes were used for closer examination of suspicious skin lesions. The clinical results of the examinations were recorded on a standardized form.

An estimation of the number of melanocytic nevi—≤20, 21–49, or ≥50—was recorded for each patient. Suspicious skin lesions were assigned to one of the following categories: nevus requiring future checkup (Nc), nevus requiring excision (Ne), suspected malignant melanoma (MM), suspected squamous cell carcinoma, suspected basal cell carcinoma (BCC), suspected other skin tumor, and precancerous lesion. Fitzpatrick skin type also was assessed for all participants and recorded by the dermatologist carrying out the examination. Each participant was assigned to a risk group—low, moderate, or high risk—based on their individual risk for developing a skin tumor. Factors that were considered when determining participants’ risk for developing skin cancer included Fitzpatrick skin type, number of melanocytic nevi, personal and family history, leisure activities, UV protection used, and current clinical diagnosis of skin lesions.

After the skin examination, participants were informed of recommended treatment but were not given any additional dermatologic advice. Participants could arrange an appointment at the Department of Dermatology, University Hospital Erlangen, for the excision and histological analysis of the skin lesions. All recorded data were collected in a computerized spreadsheet program. When evaluating the questionnaires, questions that were not answered or were answered incorrectly (participant chose more than 1 answer) were ignored.

Statistical Analysis

Statistical analysis was carried out using SPSS software version 16.0. The majority of the data were nominal or ordinal. Metric data were checked for normal distribution using the Shapiro-Wilk test before carrying out parametric tests. Statistical tests were carried out using the χ² test and the t test for independent samples. Non-nominal distributed data were checked using the Mann-Whitney U test. P<.05 was considered statistically significant in the exploratory data analysis.

Results

Of 783 employees included in the study, 288 (36.8%) were female and 495 (63.2%) were male (Table 1). In comparison with the total workforce, a significantly higher proportion of women than men took part in the cross-sectional study (P<.01). The average age (SD) was 42.3 (9.5) years (range, 18–64 years). Female participants (average age [SD], 39.8 [10.2] years) were significantly younger than male participants (average age [SD], 43.8 [8.8] years; P<.01). Forty-one percent of participants had a prior skin cancer screening. One percent of participants had a personal history of skin cancer, with 1 participant reporting a history of MM; 6.5% had a family history of skin cancer, of which 39.2% had a family history of MM.

The results of the clinical examinations showed that 43.8% of participants had 20 or fewer melanocytic nevi, 43.4% had 21 to 49 melanocytic nevi, and 12.8% had 50 or more melanocytic nevi. Significantly more women than men had 20 or fewer melanocytic nevi (P<.05).

Approximately 92% of participants assessed themselves as having Fitzpatrick skin types II (35.2%) or III (56.7%), while only approximately 3.6% and 4.5% assessed themselves as having skin types I and IV, respectively. The results of the Fitzpatrick skin type assessments made by dermatologists were similar: 96.9% of participants were assessed as having Fitzpatrick skin types II (43.0%) and III (53.8%); approximately 1.9% and 1.3% were assessed as having Fitzpatrick skin types I and IV, respectively. Results showed that 80.2% of all participants assessed their skin type in the same way as the dermatologist; 13.5% assessed their skin type as darker and 6.3% (49/783) assessed it as lighter. A quantitative analysis of Fitzpatrick skin type and sex showed that significantly more male participants than female participants assessed their Fitzpatrick skin type darker than their actual skin type (P<.01).

Overall, 47.6% of participants reported having had sunburn rarely in the past, while 36.9% and 14.0% had experienced sunburn once per year and several times per year, respectively. Approximately 1.4% of participants reported never having a sunburn. More of the male participants made use of comprehensive sun protection using all methods listed (34.5%; P<.05) or a combination of sunscreen and sun-protective clothing (14.9%; P<.01) than the female participants who relied more frequently on sunscreen alone (29.5%; P<.01) or a combination of sunscreen and staying in the shade (29.5%; P<.01)

In general it was clear that sunscreen, either alone or in combination with other sun-protection methods, was used most frequently (88.0%); 58.0% protected themselves by staying in the shade, while 48.0% used suitable sun-protective clothing. Only 3.6% of participants did not protect themselves using any of the suggested methods.

A total of 661 categorized skin lesions were found in 377 participants. Of these lesions, 491 were Nc and 121 were Ne. Twenty-four of the skin lesions were suspected precancerous lesions, 13 were suspected BCC, 2 were suspected MM, and 10 were suspected other skin tumor (Table 2). Overall, male participants who were diagnosed with at least 1 skin lesion (average age, 44.0 years) were significantly older than the women (average age, 39.3 years)(P<.01). Similar findings were observed in participants with at least 1 Nc (men, 43.3 years; women, 38.7 years; P<.01) and at least 1 Ne (men, 44.2 years; women, 38.0 years; P<.05). With regard to the individual risk for developing skin cancer, 32.6% of participants were considered to be at low risk, 64.9% were at moderate risk, and 2.6% were at high risk.

Approximately 61.5% of 377 participants who were diagnosed with at least 1 categorized skin lesion were advised to have a specific skin lesion checked by a dermatologist or to have a full examination for skin cancer once every 12 months. Furthermore, 22.5% were advised to follow-up biannually and 11.7% were advised to follow-up once every 2 years. Of the remaining participants who were advised to have follow-ups, 0.3% were advised to have a skin examination once every 3 months after having had MM, and 4.0% were advised to have follow-up once every 18 months. Overall, follow-up was recommended within 1 year in 84.4% of cases and within 1 to 2 years in 15.6% (Table 3).

Subsequent histological analysis of the excised tissue resulted in a diagnosis of only 21 clinically significant skin conditions. One case of Bowen disease and 1 case of BCC was confirmed. Histological analysis identified the remaining 19 excised skin lesions, which included the 2 suspected MMs, as dysplastic nevi.

Comment

The aim of this cross-sectional study was to examine the importance and effectiveness of employee skin cancer screening programs. In comparison with the total workforce, significantly more women took part than men. Female participants were significantly younger than male participants, which mirrors the findings of prior studies showing that screening programs reach women more frequently than men and that women who participate in screenings are also younger on average in comparison to men.^7-13 Men and older individuals usually are underrepresented.^7,13 The average age of participants in our study was 42.3 years, which is lower than in the SCREEN (Skin Cancer Research to Provide Evidence for Effectiveness of Screening in Northern Germany) study (average age, 49.7 years).¹³ The average age in our study also is likely to be lower than patients who undergo skin cancer screenings offered by statutory health insurance providers in Germany, which has a minimum age restriction of 35 years; however, it is comparable to the average age of participants in other employee screening programs and therefore represents the average age of individuals employed in Germany.^15,16

The employee skin cancer screening program in this study generated a high level of interest, indicated by the fact that all available appointments had been booked just 36 hours after the screening was announced. Furthermore, there was a waiting list of approximately 300 employees who were not able to undergo a skin examination. For logistical reasons, the number of participants was limited to 10% of the workforce. The high level of interest is an indication of increased awareness of the importance of recognizing skin tumors early and the associated need for information as well as the need to undergo screening for skin cancer as a precaution. This observation also can be made with regard to the skin cancer screening introduced by statutory health insurance providers in Germany. Studies published by Augustin et al²⁰ and Kornek et al^21,22 confirm that skin cancer screenings have gained wide acceptance in Germany because they were introduced by statutory health insurance providers in 2008. The number of skin cancer screenings carried out by dermatologists in Germany also is increasing.^20-22 Although approximately 19% of those eligible to participate took part in the SCREEN pilot project,¹³ approximately 31% of individuals who were eligible to participate took part in skin cancer screenings offered by statutory health insurance providers in Germany in 2012, and the percentage is rising.²³ Two important factors affecting the high level of interest in the employee screening program used in our study were undoubtedly the advantages of the examination taking place during working hours and being held on the occupational health services’ premises in the workplace, which helped participants avoid the cost of travel and wait times associated with visiting a medical practice.

Of 783 participants included in this study, 377 displayed at least 1 categorized skin lesion; the majority were suspicious melanocytic nevi. This high incidence rate suggested that regular skin cancer screenings are useful, as it has been shown that there is a correlation between higher numbers of melanocytic nevi and increased risk for developing melanoma.²⁴

In a study by Winkler et al,²⁵ a skin cancer screening of 1658 bank and insurance employees found that 33.8% of those examined displayed at least 1 atypical melanocytic nevus and 27.2% displayed more than 50 melanocytic nevi (compared to 12.8% with ≥50 melanocytic nevi in the current study). The risk for developing skin cancer was classified as intermediate or high in 54.5% (compared to 67.5% at moderate or high risk in the current study).²⁵ Therefore, the rate of suspicious skin lesions was lower in the population of the study by Winkler et al²⁵ in comparison to the population of the current study. As the overall number of melanocytic nevi and the individual risk for skin cancer, however, was underestimated by the majority of the bank and insurance employees,²⁵ employee skin cancer screening programs can be used as a potentially effective tool to make employees aware of the issue and sensitizing them to it. Employee screening in addition to a final diagnosis can contribute to ensuring suitable treatment is started. For example, in the large-scale employee screening published by Schaefer et al¹⁵ and Augustin et al,¹⁶ 48,665 and 90,880 employees, respectively, were screened for inflammatory and noninflammatory skin diseases, and 19% and 27% of participants, respectively, were diagnosed with skin lesions that required treatment.

Participants in the current study were given no further treatment or advice. Recommendations were made that participants monitor suspicious skin lesions or have them removed. With regard to future screening, 84.4% of participants with at least 1 categorized skin lesion were advised to have a regular follow-up within 1 year, while 15.6% were advised to follow-up within 1 to 2 years. Therefore, a period of 2 years before the next checkup, the period between screenings offered by statutory health insurance providers in Germany,¹² was considered too long for the majority of participants, according to the dermatologists involved with our study.

Conclusion

The high rate of suspicious skin lesions diagnosed demonstrated the effectiveness of skin cancer screenings organized in the workplace, which should be recommended for all employees, not only those who are at high risk for developing skin cancer due to the nature of their work, such as those who work outdoors. It should be noted that the study group examined in the current study was a homogeneous group of employees of a technical company only and is therefore relatively selective. Nevertheless, despite the comparatively selective and young participant group, these examinations provide evidence of the importance of skin cancer screening programs for a wider population.

Acknowledgments

The authors thank Heidi Seybold, MD; Petra Wörl, MD; Sybille Thoma-Uszynski, MD; and Jens Bussmann, MD (all from Erlangen, Germany), for their support and active assistance in the practical implementation of this study.

The incidence of skin cancer, along with its effects on patients and the economy, has continued to increase and therefore requires particular attention from dermatologists. UV light has been shown to be of etiopathologic importance in the development of various types of skin cancer.^1-3 Studies have shown that there is a direct correlation between the incidence of skin cancer and average annual amounts of UV radiation exposure.³ Accordingly, in 2009 the International Agency for Research on Cancer classified UV light as carcinogenic to humans.⁴ Therefore, the general public must be made aware of the danger of exposure to UV radiation.

In Australia, government initiatives to educate the population on causes of skin cancer development and its relationship to UV radiation have already caused the public to change their way of thinking and to deal with sunlight in a conscious and responsible manner.⁵ A large proportion of the Australian population with light skin is at a particularly high risk for developing skin cancer due to intense exposure to UV radiation. Numerous campaigns in Germany and other countries have attempted to sensitize the public to this issue by emphasizing a reduction in UV exposure (primary prevention) or highlighting the importance of early diagnosis (secondary prevention).^6,7

For a good prognosis, it is crucial that skin cancer, particularly melanoma, is discovered at an early or precancerous stage.⁸ For this reason, self-examination of the skin and skin cancer screening are important factors that can contribute to ensuring early and curative treatment.^9-11 Since July 1, 2008, skin cancer screenings have been included in the preventative health care program by statutory health insurance providers in Germany. As part of this program, the cost of screening once every 2 years for individuals 35 years and older is covered by statutory health insurance.¹² Several studies have shown a decline in the melanoma mortality rate since the introduction of skin cancer screening programs in Germany.^11,13,14

Employee skin cancer screening programs are an important method of examining high numbers of individuals quickly and effectively. These programs have been carried out in Germany and other countries.^15,16 Studies have shown that skin cancer screening carried out selectively on defined groups can be an effective form of secondary prevention, particularly for those who work outdoors.¹⁷

An employee skin cancer screening program was carried out as part of this study. The findings are interpreted and discussed in relation to other employee screening programs that have been reported as well as those introduced by statutory health insurance providers in Germany. The aim of this study was to determine the importance and effectiveness of employee skin cancer screening programs and the role they play in secondary prevention of skin cancer.

Methods

Study Population

Employees of a technical company in Bavaria, Germany, were offered a skin cancer screening program by the employer’s occupational health service and health insurance provider in collaboration with the Department of Dermatology at the University Hospital Erlangen (Erlangen, Germany). Skin examinations were performed exclusively by 5 trained dermatologists. Only direct employees of the company at 3 of its locations in the Erlangen area were eligible to participate. The total number of employees varied by location (1072–5126 employees). The majority of employees had a university education or had completed technical training. Family members and other individuals who were not members of the company were excluded. There were no further inclusion or exclusion criteria. Over a period of 13 days, 783 of 7823 total employees (10.0%) were examined and included in the study. The study was approved by the Responsible Ethics Commission of the Faculty of Medicine at Friedrich-Alexander-University Erlangen-Nürnberg, Germany.

Study Design

Employees signed a consent form for participation in the study and completed a standardized questionnaire. The questionnaire was based on surveys used in a prior study¹⁸ and collected information on current and prior skin lesions, prior dermatological screening, personal and family history of skin tumors, frequency of UV exposure, and type of UV protection used. For the question on measures taken for protection from UV radiation, possible answers included with sunscreen cream, with suitable sun-protective clothing, and by staying in the shade, or no measures were taken. In contrast to the other questions, multiple answers were accepted for this question. Answering no automatically excluded other possible answers. Participants also were asked to assess their own Fitzpatrick skin type¹⁹; the questionnaire included explanations of each skin type (I–IV).

The participants were then called in for examination by the dermatologist at 15-minute intervals. All clothing was removed and the skin was examined. Dermatoscopes were used for closer examination of suspicious skin lesions. The clinical results of the examinations were recorded on a standardized form.

An estimation of the number of melanocytic nevi—≤20, 21–49, or ≥50—was recorded for each patient. Suspicious skin lesions were assigned to one of the following categories: nevus requiring future checkup (Nc), nevus requiring excision (Ne), suspected malignant melanoma (MM), suspected squamous cell carcinoma, suspected basal cell carcinoma (BCC), suspected other skin tumor, and precancerous lesion. Fitzpatrick skin type also was assessed for all participants and recorded by the dermatologist carrying out the examination. Each participant was assigned to a risk group—low, moderate, or high risk—based on their individual risk for developing a skin tumor. Factors that were considered when determining participants’ risk for developing skin cancer included Fitzpatrick skin type, number of melanocytic nevi, personal and family history, leisure activities, UV protection used, and current clinical diagnosis of skin lesions.

After the skin examination, participants were informed of recommended treatment but were not given any additional dermatologic advice. Participants could arrange an appointment at the Department of Dermatology, University Hospital Erlangen, for the excision and histological analysis of the skin lesions. All recorded data were collected in a computerized spreadsheet program. When evaluating the questionnaires, questions that were not answered or were answered incorrectly (participant chose more than 1 answer) were ignored.

Statistical Analysis

Statistical analysis was carried out using SPSS software version 16.0. The majority of the data were nominal or ordinal. Metric data were checked for normal distribution using the Shapiro-Wilk test before carrying out parametric tests. Statistical tests were carried out using the χ² test and the t test for independent samples. Non-nominal distributed data were checked using the Mann-Whitney U test. P<.05 was considered statistically significant in the exploratory data analysis.

Results

Of 783 employees included in the study, 288 (36.8%) were female and 495 (63.2%) were male (Table 1). In comparison with the total workforce, a significantly higher proportion of women than men took part in the cross-sectional study (P<.01). The average age (SD) was 42.3 (9.5) years (range, 18–64 years). Female participants (average age [SD], 39.8 [10.2] years) were significantly younger than male participants (average age [SD], 43.8 [8.8] years; P<.01). Forty-one percent of participants had a prior skin cancer screening. One percent of participants had a personal history of skin cancer, with 1 participant reporting a history of MM; 6.5% had a family history of skin cancer, of which 39.2% had a family history of MM.

The results of the clinical examinations showed that 43.8% of participants had 20 or fewer melanocytic nevi, 43.4% had 21 to 49 melanocytic nevi, and 12.8% had 50 or more melanocytic nevi. Significantly more women than men had 20 or fewer melanocytic nevi (P<.05).

Approximately 92% of participants assessed themselves as having Fitzpatrick skin types II (35.2%) or III (56.7%), while only approximately 3.6% and 4.5% assessed themselves as having skin types I and IV, respectively. The results of the Fitzpatrick skin type assessments made by dermatologists were similar: 96.9% of participants were assessed as having Fitzpatrick skin types II (43.0%) and III (53.8%); approximately 1.9% and 1.3% were assessed as having Fitzpatrick skin types I and IV, respectively. Results showed that 80.2% of all participants assessed their skin type in the same way as the dermatologist; 13.5% assessed their skin type as darker and 6.3% (49/783) assessed it as lighter. A quantitative analysis of Fitzpatrick skin type and sex showed that significantly more male participants than female participants assessed their Fitzpatrick skin type darker than their actual skin type (P<.01).

Overall, 47.6% of participants reported having had sunburn rarely in the past, while 36.9% and 14.0% had experienced sunburn once per year and several times per year, respectively. Approximately 1.4% of participants reported never having a sunburn. More of the male participants made use of comprehensive sun protection using all methods listed (34.5%; P<.05) or a combination of sunscreen and sun-protective clothing (14.9%; P<.01) than the female participants who relied more frequently on sunscreen alone (29.5%; P<.01) or a combination of sunscreen and staying in the shade (29.5%; P<.01)

In general it was clear that sunscreen, either alone or in combination with other sun-protection methods, was used most frequently (88.0%); 58.0% protected themselves by staying in the shade, while 48.0% used suitable sun-protective clothing. Only 3.6% of participants did not protect themselves using any of the suggested methods.

A total of 661 categorized skin lesions were found in 377 participants. Of these lesions, 491 were Nc and 121 were Ne. Twenty-four of the skin lesions were suspected precancerous lesions, 13 were suspected BCC, 2 were suspected MM, and 10 were suspected other skin tumor (Table 2). Overall, male participants who were diagnosed with at least 1 skin lesion (average age, 44.0 years) were significantly older than the women (average age, 39.3 years)(P<.01). Similar findings were observed in participants with at least 1 Nc (men, 43.3 years; women, 38.7 years; P<.01) and at least 1 Ne (men, 44.2 years; women, 38.0 years; P<.05). With regard to the individual risk for developing skin cancer, 32.6% of participants were considered to be at low risk, 64.9% were at moderate risk, and 2.6% were at high risk.

Approximately 61.5% of 377 participants who were diagnosed with at least 1 categorized skin lesion were advised to have a specific skin lesion checked by a dermatologist or to have a full examination for skin cancer once every 12 months. Furthermore, 22.5% were advised to follow-up biannually and 11.7% were advised to follow-up once every 2 years. Of the remaining participants who were advised to have follow-ups, 0.3% were advised to have a skin examination once every 3 months after having had MM, and 4.0% were advised to have follow-up once every 18 months. Overall, follow-up was recommended within 1 year in 84.4% of cases and within 1 to 2 years in 15.6% (Table 3).

Subsequent histological analysis of the excised tissue resulted in a diagnosis of only 21 clinically significant skin conditions. One case of Bowen disease and 1 case of BCC was confirmed. Histological analysis identified the remaining 19 excised skin lesions, which included the 2 suspected MMs, as dysplastic nevi.

Comment

The aim of this cross-sectional study was to examine the importance and effectiveness of employee skin cancer screening programs. In comparison with the total workforce, significantly more women took part than men. Female participants were significantly younger than male participants, which mirrors the findings of prior studies showing that screening programs reach women more frequently than men and that women who participate in screenings are also younger on average in comparison to men.^7-13 Men and older individuals usually are underrepresented.^7,13 The average age of participants in our study was 42.3 years, which is lower than in the SCREEN (Skin Cancer Research to Provide Evidence for Effectiveness of Screening in Northern Germany) study (average age, 49.7 years).¹³ The average age in our study also is likely to be lower than patients who undergo skin cancer screenings offered by statutory health insurance providers in Germany, which has a minimum age restriction of 35 years; however, it is comparable to the average age of participants in other employee screening programs and therefore represents the average age of individuals employed in Germany.^15,16

The employee skin cancer screening program in this study generated a high level of interest, indicated by the fact that all available appointments had been booked just 36 hours after the screening was announced. Furthermore, there was a waiting list of approximately 300 employees who were not able to undergo a skin examination. For logistical reasons, the number of participants was limited to 10% of the workforce. The high level of interest is an indication of increased awareness of the importance of recognizing skin tumors early and the associated need for information as well as the need to undergo screening for skin cancer as a precaution. This observation also can be made with regard to the skin cancer screening introduced by statutory health insurance providers in Germany. Studies published by Augustin et al²⁰ and Kornek et al^21,22 confirm that skin cancer screenings have gained wide acceptance in Germany because they were introduced by statutory health insurance providers in 2008. The number of skin cancer screenings carried out by dermatologists in Germany also is increasing.^20-22 Although approximately 19% of those eligible to participate took part in the SCREEN pilot project,¹³ approximately 31% of individuals who were eligible to participate took part in skin cancer screenings offered by statutory health insurance providers in Germany in 2012, and the percentage is rising.²³ Two important factors affecting the high level of interest in the employee screening program used in our study were undoubtedly the advantages of the examination taking place during working hours and being held on the occupational health services’ premises in the workplace, which helped participants avoid the cost of travel and wait times associated with visiting a medical practice.

Of 783 participants included in this study, 377 displayed at least 1 categorized skin lesion; the majority were suspicious melanocytic nevi. This high incidence rate suggested that regular skin cancer screenings are useful, as it has been shown that there is a correlation between higher numbers of melanocytic nevi and increased risk for developing melanoma.²⁴

In a study by Winkler et al,²⁵ a skin cancer screening of 1658 bank and insurance employees found that 33.8% of those examined displayed at least 1 atypical melanocytic nevus and 27.2% displayed more than 50 melanocytic nevi (compared to 12.8% with ≥50 melanocytic nevi in the current study). The risk for developing skin cancer was classified as intermediate or high in 54.5% (compared to 67.5% at moderate or high risk in the current study).²⁵ Therefore, the rate of suspicious skin lesions was lower in the population of the study by Winkler et al²⁵ in comparison to the population of the current study. As the overall number of melanocytic nevi and the individual risk for skin cancer, however, was underestimated by the majority of the bank and insurance employees,²⁵ employee skin cancer screening programs can be used as a potentially effective tool to make employees aware of the issue and sensitizing them to it. Employee screening in addition to a final diagnosis can contribute to ensuring suitable treatment is started. For example, in the large-scale employee screening published by Schaefer et al¹⁵ and Augustin et al,¹⁶ 48,665 and 90,880 employees, respectively, were screened for inflammatory and noninflammatory skin diseases, and 19% and 27% of participants, respectively, were diagnosed with skin lesions that required treatment.

Participants in the current study were given no further treatment or advice. Recommendations were made that participants monitor suspicious skin lesions or have them removed. With regard to future screening, 84.4% of participants with at least 1 categorized skin lesion were advised to have a regular follow-up within 1 year, while 15.6% were advised to follow-up within 1 to 2 years. Therefore, a period of 2 years before the next checkup, the period between screenings offered by statutory health insurance providers in Germany,¹² was considered too long for the majority of participants, according to the dermatologists involved with our study.

Conclusion

The high rate of suspicious skin lesions diagnosed demonstrated the effectiveness of skin cancer screenings organized in the workplace, which should be recommended for all employees, not only those who are at high risk for developing skin cancer due to the nature of their work, such as those who work outdoors. It should be noted that the study group examined in the current study was a homogeneous group of employees of a technical company only and is therefore relatively selective. Nevertheless, despite the comparatively selective and young participant group, these examinations provide evidence of the importance of skin cancer screening programs for a wider population.

Acknowledgments

The authors thank Heidi Seybold, MD; Petra Wörl, MD; Sybille Thoma-Uszynski, MD; and Jens Bussmann, MD (all from Erlangen, Germany), for their support and active assistance in the practical implementation of this study.

The incidence of skin cancer, along with its effects on patients and the economy, has continued to increase and therefore requires particular attention from dermatologists. UV light has been shown to be of etiopathologic importance in the development of various types of skin cancer.^1-3 Studies have shown that there is a direct correlation between the incidence of skin cancer and average annual amounts of UV radiation exposure.³ Accordingly, in 2009 the International Agency for Research on Cancer classified UV light as carcinogenic to humans.⁴ Therefore, the general public must be made aware of the danger of exposure to UV radiation.

In Australia, government initiatives to educate the population on causes of skin cancer development and its relationship to UV radiation have already caused the public to change their way of thinking and to deal with sunlight in a conscious and responsible manner.⁵ A large proportion of the Australian population with light skin is at a particularly high risk for developing skin cancer due to intense exposure to UV radiation. Numerous campaigns in Germany and other countries have attempted to sensitize the public to this issue by emphasizing a reduction in UV exposure (primary prevention) or highlighting the importance of early diagnosis (secondary prevention).^6,7

For a good prognosis, it is crucial that skin cancer, particularly melanoma, is discovered at an early or precancerous stage.⁸ For this reason, self-examination of the skin and skin cancer screening are important factors that can contribute to ensuring early and curative treatment.^9-11 Since July 1, 2008, skin cancer screenings have been included in the preventative health care program by statutory health insurance providers in Germany. As part of this program, the cost of screening once every 2 years for individuals 35 years and older is covered by statutory health insurance.¹² Several studies have shown a decline in the melanoma mortality rate since the introduction of skin cancer screening programs in Germany.^11,13,14

Employee skin cancer screening programs are an important method of examining high numbers of individuals quickly and effectively. These programs have been carried out in Germany and other countries.^15,16 Studies have shown that skin cancer screening carried out selectively on defined groups can be an effective form of secondary prevention, particularly for those who work outdoors.¹⁷

An employee skin cancer screening program was carried out as part of this study. The findings are interpreted and discussed in relation to other employee screening programs that have been reported as well as those introduced by statutory health insurance providers in Germany. The aim of this study was to determine the importance and effectiveness of employee skin cancer screening programs and the role they play in secondary prevention of skin cancer.

Methods

Study Population

Employees of a technical company in Bavaria, Germany, were offered a skin cancer screening program by the employer’s occupational health service and health insurance provider in collaboration with the Department of Dermatology at the University Hospital Erlangen (Erlangen, Germany). Skin examinations were performed exclusively by 5 trained dermatologists. Only direct employees of the company at 3 of its locations in the Erlangen area were eligible to participate. The total number of employees varied by location (1072–5126 employees). The majority of employees had a university education or had completed technical training. Family members and other individuals who were not members of the company were excluded. There were no further inclusion or exclusion criteria. Over a period of 13 days, 783 of 7823 total employees (10.0%) were examined and included in the study. The study was approved by the Responsible Ethics Commission of the Faculty of Medicine at Friedrich-Alexander-University Erlangen-Nürnberg, Germany.

Study Design

Employees signed a consent form for participation in the study and completed a standardized questionnaire. The questionnaire was based on surveys used in a prior study¹⁸ and collected information on current and prior skin lesions, prior dermatological screening, personal and family history of skin tumors, frequency of UV exposure, and type of UV protection used. For the question on measures taken for protection from UV radiation, possible answers included with sunscreen cream, with suitable sun-protective clothing, and by staying in the shade, or no measures were taken. In contrast to the other questions, multiple answers were accepted for this question. Answering no automatically excluded other possible answers. Participants also were asked to assess their own Fitzpatrick skin type¹⁹; the questionnaire included explanations of each skin type (I–IV).

The participants were then called in for examination by the dermatologist at 15-minute intervals. All clothing was removed and the skin was examined. Dermatoscopes were used for closer examination of suspicious skin lesions. The clinical results of the examinations were recorded on a standardized form.

An estimation of the number of melanocytic nevi—≤20, 21–49, or ≥50—was recorded for each patient. Suspicious skin lesions were assigned to one of the following categories: nevus requiring future checkup (Nc), nevus requiring excision (Ne), suspected malignant melanoma (MM), suspected squamous cell carcinoma, suspected basal cell carcinoma (BCC), suspected other skin tumor, and precancerous lesion. Fitzpatrick skin type also was assessed for all participants and recorded by the dermatologist carrying out the examination. Each participant was assigned to a risk group—low, moderate, or high risk—based on their individual risk for developing a skin tumor. Factors that were considered when determining participants’ risk for developing skin cancer included Fitzpatrick skin type, number of melanocytic nevi, personal and family history, leisure activities, UV protection used, and current clinical diagnosis of skin lesions.

After the skin examination, participants were informed of recommended treatment but were not given any additional dermatologic advice. Participants could arrange an appointment at the Department of Dermatology, University Hospital Erlangen, for the excision and histological analysis of the skin lesions. All recorded data were collected in a computerized spreadsheet program. When evaluating the questionnaires, questions that were not answered or were answered incorrectly (participant chose more than 1 answer) were ignored.

Statistical Analysis

Statistical analysis was carried out using SPSS software version 16.0. The majority of the data were nominal or ordinal. Metric data were checked for normal distribution using the Shapiro-Wilk test before carrying out parametric tests. Statistical tests were carried out using the χ² test and the t test for independent samples. Non-nominal distributed data were checked using the Mann-Whitney U test. P<.05 was considered statistically significant in the exploratory data analysis.

Results

Of 783 employees included in the study, 288 (36.8%) were female and 495 (63.2%) were male (Table 1). In comparison with the total workforce, a significantly higher proportion of women than men took part in the cross-sectional study (P<.01). The average age (SD) was 42.3 (9.5) years (range, 18–64 years). Female participants (average age [SD], 39.8 [10.2] years) were significantly younger than male participants (average age [SD], 43.8 [8.8] years; P<.01). Forty-one percent of participants had a prior skin cancer screening. One percent of participants had a personal history of skin cancer, with 1 participant reporting a history of MM; 6.5% had a family history of skin cancer, of which 39.2% had a family history of MM.

The results of the clinical examinations showed that 43.8% of participants had 20 or fewer melanocytic nevi, 43.4% had 21 to 49 melanocytic nevi, and 12.8% had 50 or more melanocytic nevi. Significantly more women than men had 20 or fewer melanocytic nevi (P<.05).

Approximately 92% of participants assessed themselves as having Fitzpatrick skin types II (35.2%) or III (56.7%), while only approximately 3.6% and 4.5% assessed themselves as having skin types I and IV, respectively. The results of the Fitzpatrick skin type assessments made by dermatologists were similar: 96.9% of participants were assessed as having Fitzpatrick skin types II (43.0%) and III (53.8%); approximately 1.9% and 1.3% were assessed as having Fitzpatrick skin types I and IV, respectively. Results showed that 80.2% of all participants assessed their skin type in the same way as the dermatologist; 13.5% assessed their skin type as darker and 6.3% (49/783) assessed it as lighter. A quantitative analysis of Fitzpatrick skin type and sex showed that significantly more male participants than female participants assessed their Fitzpatrick skin type darker than their actual skin type (P<.01).

Overall, 47.6% of participants reported having had sunburn rarely in the past, while 36.9% and 14.0% had experienced sunburn once per year and several times per year, respectively. Approximately 1.4% of participants reported never having a sunburn. More of the male participants made use of comprehensive sun protection using all methods listed (34.5%; P<.05) or a combination of sunscreen and sun-protective clothing (14.9%; P<.01) than the female participants who relied more frequently on sunscreen alone (29.5%; P<.01) or a combination of sunscreen and staying in the shade (29.5%; P<.01)

In general it was clear that sunscreen, either alone or in combination with other sun-protection methods, was used most frequently (88.0%); 58.0% protected themselves by staying in the shade, while 48.0% used suitable sun-protective clothing. Only 3.6% of participants did not protect themselves using any of the suggested methods.

A total of 661 categorized skin lesions were found in 377 participants. Of these lesions, 491 were Nc and 121 were Ne. Twenty-four of the skin lesions were suspected precancerous lesions, 13 were suspected BCC, 2 were suspected MM, and 10 were suspected other skin tumor (Table 2). Overall, male participants who were diagnosed with at least 1 skin lesion (average age, 44.0 years) were significantly older than the women (average age, 39.3 years)(P<.01). Similar findings were observed in participants with at least 1 Nc (men, 43.3 years; women, 38.7 years; P<.01) and at least 1 Ne (men, 44.2 years; women, 38.0 years; P<.05). With regard to the individual risk for developing skin cancer, 32.6% of participants were considered to be at low risk, 64.9% were at moderate risk, and 2.6% were at high risk.

Approximately 61.5% of 377 participants who were diagnosed with at least 1 categorized skin lesion were advised to have a specific skin lesion checked by a dermatologist or to have a full examination for skin cancer once every 12 months. Furthermore, 22.5% were advised to follow-up biannually and 11.7% were advised to follow-up once every 2 years. Of the remaining participants who were advised to have follow-ups, 0.3% were advised to have a skin examination once every 3 months after having had MM, and 4.0% were advised to have follow-up once every 18 months. Overall, follow-up was recommended within 1 year in 84.4% of cases and within 1 to 2 years in 15.6% (Table 3).

Subsequent histological analysis of the excised tissue resulted in a diagnosis of only 21 clinically significant skin conditions. One case of Bowen disease and 1 case of BCC was confirmed. Histological analysis identified the remaining 19 excised skin lesions, which included the 2 suspected MMs, as dysplastic nevi.

Comment

The aim of this cross-sectional study was to examine the importance and effectiveness of employee skin cancer screening programs. In comparison with the total workforce, significantly more women took part than men. Female participants were significantly younger than male participants, which mirrors the findings of prior studies showing that screening programs reach women more frequently than men and that women who participate in screenings are also younger on average in comparison to men.^7-13 Men and older individuals usually are underrepresented.^7,13 The average age of participants in our study was 42.3 years, which is lower than in the SCREEN (Skin Cancer Research to Provide Evidence for Effectiveness of Screening in Northern Germany) study (average age, 49.7 years).¹³ The average age in our study also is likely to be lower than patients who undergo skin cancer screenings offered by statutory health insurance providers in Germany, which has a minimum age restriction of 35 years; however, it is comparable to the average age of participants in other employee screening programs and therefore represents the average age of individuals employed in Germany.^15,16

The employee skin cancer screening program in this study generated a high level of interest, indicated by the fact that all available appointments had been booked just 36 hours after the screening was announced. Furthermore, there was a waiting list of approximately 300 employees who were not able to undergo a skin examination. For logistical reasons, the number of participants was limited to 10% of the workforce. The high level of interest is an indication of increased awareness of the importance of recognizing skin tumors early and the associated need for information as well as the need to undergo screening for skin cancer as a precaution. This observation also can be made with regard to the skin cancer screening introduced by statutory health insurance providers in Germany. Studies published by Augustin et al²⁰ and Kornek et al^21,22 confirm that skin cancer screenings have gained wide acceptance in Germany because they were introduced by statutory health insurance providers in 2008. The number of skin cancer screenings carried out by dermatologists in Germany also is increasing.^20-22 Although approximately 19% of those eligible to participate took part in the SCREEN pilot project,¹³ approximately 31% of individuals who were eligible to participate took part in skin cancer screenings offered by statutory health insurance providers in Germany in 2012, and the percentage is rising.²³ Two important factors affecting the high level of interest in the employee screening program used in our study were undoubtedly the advantages of the examination taking place during working hours and being held on the occupational health services’ premises in the workplace, which helped participants avoid the cost of travel and wait times associated with visiting a medical practice.

Of 783 participants included in this study, 377 displayed at least 1 categorized skin lesion; the majority were suspicious melanocytic nevi. This high incidence rate suggested that regular skin cancer screenings are useful, as it has been shown that there is a correlation between higher numbers of melanocytic nevi and increased risk for developing melanoma.²⁴

In a study by Winkler et al,²⁵ a skin cancer screening of 1658 bank and insurance employees found that 33.8% of those examined displayed at least 1 atypical melanocytic nevus and 27.2% displayed more than 50 melanocytic nevi (compared to 12.8% with ≥50 melanocytic nevi in the current study). The risk for developing skin cancer was classified as intermediate or high in 54.5% (compared to 67.5% at moderate or high risk in the current study).²⁵ Therefore, the rate of suspicious skin lesions was lower in the population of the study by Winkler et al²⁵ in comparison to the population of the current study. As the overall number of melanocytic nevi and the individual risk for skin cancer, however, was underestimated by the majority of the bank and insurance employees,²⁵ employee skin cancer screening programs can be used as a potentially effective tool to make employees aware of the issue and sensitizing them to it. Employee screening in addition to a final diagnosis can contribute to ensuring suitable treatment is started. For example, in the large-scale employee screening published by Schaefer et al¹⁵ and Augustin et al,¹⁶ 48,665 and 90,880 employees, respectively, were screened for inflammatory and noninflammatory skin diseases, and 19% and 27% of participants, respectively, were diagnosed with skin lesions that required treatment.

Participants in the current study were given no further treatment or advice. Recommendations were made that participants monitor suspicious skin lesions or have them removed. With regard to future screening, 84.4% of participants with at least 1 categorized skin lesion were advised to have a regular follow-up within 1 year, while 15.6% were advised to follow-up within 1 to 2 years. Therefore, a period of 2 years before the next checkup, the period between screenings offered by statutory health insurance providers in Germany,¹² was considered too long for the majority of participants, according to the dermatologists involved with our study.

Conclusion

The high rate of suspicious skin lesions diagnosed demonstrated the effectiveness of skin cancer screenings organized in the workplace, which should be recommended for all employees, not only those who are at high risk for developing skin cancer due to the nature of their work, such as those who work outdoors. It should be noted that the study group examined in the current study was a homogeneous group of employees of a technical company only and is therefore relatively selective. Nevertheless, despite the comparatively selective and young participant group, these examinations provide evidence of the importance of skin cancer screening programs for a wider population.

Acknowledgments

The authors thank Heidi Seybold, MD; Petra Wörl, MD; Sybille Thoma-Uszynski, MD; and Jens Bussmann, MD (all from Erlangen, Germany), for their support and active assistance in the practical implementation of this study.