Bruce Jancin

NEW ORLEANS – Stung by disappointing long-term outcomes for evidence-based intensive behavioral weight loss interventions that are often marked by late backsliding, researchers are turning the standard treatment programs upside down, with encouraging preliminary results.

One example of the new outside-the-box thinking regarding achieving sustained weight loss is the just-completed, 18-month, randomized FRESH START trial. Obese subjects in the novel “maintenance first” study arm spent the first 8 weeks of the intensive 6-month treatment program under orders not to lose any weight. If they did happen to lose a few pounds, they were instructed to gain them right back.

Participants were also encouraged to enjoy their favorite high-fat, high-calorie foods during the initial 8 weeks, albeit mindfully and in moderation, while searching for healthy replacement foods that tasted as good. Toward the end of the 8-week, maintenance-first part of the intervention, participants even took a “vacation week” in which they were instructed to eat five high-fat/high-calorie meals.

Sound counterintuitive? Actually, it’s an approach that’s solidly grounded in behavioral theory, according to Michaela Kiernan, Ph.D., senior research scientist at the center for research in disease prevention at Stanford (Calif.) University.

The emphasis during those first eight weekly 90-minute sessions was on avoiding self-deprivation while mastering the self-monitoring “stability skills” that she and her coinvestigators consider crucial to keeping lost weight off in the long term. The vacation week, for example, afforded an opportunity to practice navigating the dietary disruptions that are inevitable in any weight-loss effort.

In contrast, standard intensive behavioral weight loss programs place the initial emphasis on losing weight; maintenance skills are taught only after the weight loss has already occurred. But that approach hasn’t worked out so well. At the end of the standard, state-of-the-art behavioral and lifestyle intervention, patients have typically lost 15-20 pounds, but they regain 30%-50% of that during the next 12 months. The FRESH START approach was designed to curb that weight regain, she explained at the annual meeting of the Society of Behavioral Medicine.

And it worked. The 267 obese participants in FRESH START were randomized to a maintenance-skills-first group or to a standard, evidence-based, behavioral weight loss program. Both groups got 28 weekly 90-minute group sessions, with identical content for the weight-loss component in both arms. At the end of the intensive 6-month intervention, the mean weight loss was 16.1 pounds in the maintenance-first group, and – as expected – similar at 17.1 pounds in the control arm. But the control group regained 7.0 pounds during the next 12 months, significantly more than the mean 3.0 pounds regained in the maintenance-first arm.

Moreover, nearly twice as many women in the maintenance-first group displayed what behavioral therapists consider a model pattern of weight change: loss of at least 5% of initial weight at 6 months and a gain of less than 5 pounds at any time from 6 to 18 months. This pattern was achieved by 33% in the maintenance-first group, compared with 18% of controls. These FRESH START results have exciting practical as well as theoretical implications for long-term health behavior change, Dr. Kiernan asserted.

Another innovative study presented at the conference took a stepped-care approach to weight loss. The STEP-UP trial was a multicenter, randomized trial involving 363 obese, sedentary subjects who were assigned to a standard, evidence-based, 18-month, group-class behavioral intervention or to a lower-intensity approach in which patients were bumped up to more intensive interventions – phone calls, face-to-face individual counseling, meal replacements – only if they failed to achieve predetermined weight loss goals set at 3-month intervals. Those goals included a 5% weight loss at 3 months, 7% at 6 months, and 10% at 9, 12, and 15 months.

Deborah F. Tate, Ph.D., reported that the two groups achieved similar weight loss at 18 months: an average of 7.6 kg in the standard therapy group and 6.2 kg with the stepped-care approach. Weight loss of at least 5% was achieved among 58% of the control group and 56% of the stepped-care group at 18 months. Blood pressure, resting heart rate, and physical fitness didn’t differ between the two groups at any point.

Although outcomes in the two groups were similar, the costs to achieve those results were not. The stepped-care program cost an average total of $785 for combined payer and participant costs per patient, compared with $1,335 per participant in the standard behavioral therapy group, noted Dr. Tate of the University of North Carolina at Chapel Hill.

The explanation for the substantially lower per-patient total cost in the stepped-care group is that subjects in that study arm achieved their weight loss in an average of 12 group sessions, whereas those in the control arm had an average of 42 sessions. The incremental cost per kilogram of weight loss in the standard program was $409, she added.

Discussant Michael G. Perri, Ph.D., a pioneer in developing intensive behavioral weight loss programs, said he really likes the stepped-care approach because it’s practical and efficient, and it lends itself to implementation in a variety of health care settings.

“I can tell you, one of the biggest barriers to dissemination is that the length and intensity of the kinds of programs we do is too high for adoption in most community settings. We have to find ways to make them more efficient,” said Dr. Perri, professor of clinical and health psychology and dean of the college of public health and health professions at the University of Florida, Gainesville.

Another “terrific” aspect of the STEP-UP trial, he continued, is that the weight loss was achieved with lower cost and markedly fewer sessions than were entailed in standard therapy.

“It tells us that maybe we need to be looking at more of a triage kind of approach: You could set it up so that if somebody doesn’t do well, they get more care, and if they do worse they get even more care. But at some point, I think it really needs to be triage, where we say, ‘Enough is enough – this person is not going to benefit from anything more and we don’t waste more resources on him,’ ” Dr. Perri commented.

As for the FRESH START trial, in which he was a coinvestigator, Dr. Perri raised the possibility that the novel, maintenance-first intervention merely delayed weight regain rather than preventing it. This is suggested by the weight loss trend over time: During months 6-12, the maintenance-first group gained a mean of only 0.4 pounds, whereas in months 12-18, the group put on 2.5 pounds, which wasn’t significantly different from the mean 3.3-pound gain in the control group during that late phase of the study.

Still, delaying weight regain is not to be shrugged off. It confers long-term health benefits, as was recently shown in the 10-year follow-up of the landmark Diabetes Prevention Program (DPP), the psychologist asserted.

The DPP randomized more than 3,000 subjects with impaired glucose tolerance to an intensive diet and exercise lifestyle intervention, to metformin, or to placebo. The results were truly heartening: At 4 years of follow-up, the biggest average weight loss – about 4 kg – was seen in the lifestyle modification group. Moreover, the primary study end point, which was the development of type 2 diabetes, was reduced by 58% in the lifestyle intervention group, compared with placebo, which was a significantly greater benefit than the 31% risk reduction with metformin (N. Engl. J. Med. 2002;346:393-403).

Then came the initially disheartening DPP 10-year follow-up report. At 10 years, there was no longer any difference between the three study arms in terms of weight loss, which stood at about 2 kg in each group. Yet, surprisingly, there was still a 34% reduction in the incidence of type 2 diabetes in the lifestyle arm, compared with placebo, and an 18% reduction with metformin. The incidence was 11.0 cases per 100 person-years with placebo, 7.8 with metformin, and 4.8 with lifestyle modification (Lancet 2009;374:1677-86).

“One of the things that’s instructive about this is that even though we’re worried about the maintenance problem, the DPP shows that if somebody is able to lose weight and keep it off for a few years, that’s likely to have some beneficial impact on their health that can be observed long term, even if they do regain weight,” Dr. Perri observed.

The FRESH START and STEP-UP trials were funded by the National Institutes of Health. Dr. Kiernan, Dr. Tate, and Dr. Perri reported having no financial conflicts.

NEW ORLEANS – Stung by disappointing long-term outcomes for evidence-based intensive behavioral weight loss interventions that are often marked by late backsliding, researchers are turning the standard treatment programs upside down, with encouraging preliminary results.

One example of the new outside-the-box thinking regarding achieving sustained weight loss is the just-completed, 18-month, randomized FRESH START trial. Obese subjects in the novel “maintenance first” study arm spent the first 8 weeks of the intensive 6-month treatment program under orders not to lose any weight. If they did happen to lose a few pounds, they were instructed to gain them right back.

Participants were also encouraged to enjoy their favorite high-fat, high-calorie foods during the initial 8 weeks, albeit mindfully and in moderation, while searching for healthy replacement foods that tasted as good. Toward the end of the 8-week, maintenance-first part of the intervention, participants even took a “vacation week” in which they were instructed to eat five high-fat/high-calorie meals.

Sound counterintuitive? Actually, it’s an approach that’s solidly grounded in behavioral theory, according to Michaela Kiernan, Ph.D., senior research scientist at the center for research in disease prevention at Stanford (Calif.) University.

The emphasis during those first eight weekly 90-minute sessions was on avoiding self-deprivation while mastering the self-monitoring “stability skills” that she and her coinvestigators consider crucial to keeping lost weight off in the long term. The vacation week, for example, afforded an opportunity to practice navigating the dietary disruptions that are inevitable in any weight-loss effort.

In contrast, standard intensive behavioral weight loss programs place the initial emphasis on losing weight; maintenance skills are taught only after the weight loss has already occurred. But that approach hasn’t worked out so well. At the end of the standard, state-of-the-art behavioral and lifestyle intervention, patients have typically lost 15-20 pounds, but they regain 30%-50% of that during the next 12 months. The FRESH START approach was designed to curb that weight regain, she explained at the annual meeting of the Society of Behavioral Medicine.

And it worked. The 267 obese participants in FRESH START were randomized to a maintenance-skills-first group or to a standard, evidence-based, behavioral weight loss program. Both groups got 28 weekly 90-minute group sessions, with identical content for the weight-loss component in both arms. At the end of the intensive 6-month intervention, the mean weight loss was 16.1 pounds in the maintenance-first group, and – as expected – similar at 17.1 pounds in the control arm. But the control group regained 7.0 pounds during the next 12 months, significantly more than the mean 3.0 pounds regained in the maintenance-first arm.

Moreover, nearly twice as many women in the maintenance-first group displayed what behavioral therapists consider a model pattern of weight change: loss of at least 5% of initial weight at 6 months and a gain of less than 5 pounds at any time from 6 to 18 months. This pattern was achieved by 33% in the maintenance-first group, compared with 18% of controls. These FRESH START results have exciting practical as well as theoretical implications for long-term health behavior change, Dr. Kiernan asserted.

Another innovative study presented at the conference took a stepped-care approach to weight loss. The STEP-UP trial was a multicenter, randomized trial involving 363 obese, sedentary subjects who were assigned to a standard, evidence-based, 18-month, group-class behavioral intervention or to a lower-intensity approach in which patients were bumped up to more intensive interventions – phone calls, face-to-face individual counseling, meal replacements – only if they failed to achieve predetermined weight loss goals set at 3-month intervals. Those goals included a 5% weight loss at 3 months, 7% at 6 months, and 10% at 9, 12, and 15 months.

Deborah F. Tate, Ph.D., reported that the two groups achieved similar weight loss at 18 months: an average of 7.6 kg in the standard therapy group and 6.2 kg with the stepped-care approach. Weight loss of at least 5% was achieved among 58% of the control group and 56% of the stepped-care group at 18 months. Blood pressure, resting heart rate, and physical fitness didn’t differ between the two groups at any point.

Although outcomes in the two groups were similar, the costs to achieve those results were not. The stepped-care program cost an average total of $785 for combined payer and participant costs per patient, compared with $1,335 per participant in the standard behavioral therapy group, noted Dr. Tate of the University of North Carolina at Chapel Hill.

The explanation for the substantially lower per-patient total cost in the stepped-care group is that subjects in that study arm achieved their weight loss in an average of 12 group sessions, whereas those in the control arm had an average of 42 sessions. The incremental cost per kilogram of weight loss in the standard program was $409, she added.

Discussant Michael G. Perri, Ph.D., a pioneer in developing intensive behavioral weight loss programs, said he really likes the stepped-care approach because it’s practical and efficient, and it lends itself to implementation in a variety of health care settings.

“I can tell you, one of the biggest barriers to dissemination is that the length and intensity of the kinds of programs we do is too high for adoption in most community settings. We have to find ways to make them more efficient,” said Dr. Perri, professor of clinical and health psychology and dean of the college of public health and health professions at the University of Florida, Gainesville.

Another “terrific” aspect of the STEP-UP trial, he continued, is that the weight loss was achieved with lower cost and markedly fewer sessions than were entailed in standard therapy.

“It tells us that maybe we need to be looking at more of a triage kind of approach: You could set it up so that if somebody doesn’t do well, they get more care, and if they do worse they get even more care. But at some point, I think it really needs to be triage, where we say, ‘Enough is enough – this person is not going to benefit from anything more and we don’t waste more resources on him,’ ” Dr. Perri commented.

As for the FRESH START trial, in which he was a coinvestigator, Dr. Perri raised the possibility that the novel, maintenance-first intervention merely delayed weight regain rather than preventing it. This is suggested by the weight loss trend over time: During months 6-12, the maintenance-first group gained a mean of only 0.4 pounds, whereas in months 12-18, the group put on 2.5 pounds, which wasn’t significantly different from the mean 3.3-pound gain in the control group during that late phase of the study.

Still, delaying weight regain is not to be shrugged off. It confers long-term health benefits, as was recently shown in the 10-year follow-up of the landmark Diabetes Prevention Program (DPP), the psychologist asserted.

The DPP randomized more than 3,000 subjects with impaired glucose tolerance to an intensive diet and exercise lifestyle intervention, to metformin, or to placebo. The results were truly heartening: At 4 years of follow-up, the biggest average weight loss – about 4 kg – was seen in the lifestyle modification group. Moreover, the primary study end point, which was the development of type 2 diabetes, was reduced by 58% in the lifestyle intervention group, compared with placebo, which was a significantly greater benefit than the 31% risk reduction with metformin (N. Engl. J. Med. 2002;346:393-403).

Then came the initially disheartening DPP 10-year follow-up report. At 10 years, there was no longer any difference between the three study arms in terms of weight loss, which stood at about 2 kg in each group. Yet, surprisingly, there was still a 34% reduction in the incidence of type 2 diabetes in the lifestyle arm, compared with placebo, and an 18% reduction with metformin. The incidence was 11.0 cases per 100 person-years with placebo, 7.8 with metformin, and 4.8 with lifestyle modification (Lancet 2009;374:1677-86).

“One of the things that’s instructive about this is that even though we’re worried about the maintenance problem, the DPP shows that if somebody is able to lose weight and keep it off for a few years, that’s likely to have some beneficial impact on their health that can be observed long term, even if they do regain weight,” Dr. Perri observed.

The FRESH START and STEP-UP trials were funded by the National Institutes of Health. Dr. Kiernan, Dr. Tate, and Dr. Perri reported having no financial conflicts.

NEW ORLEANS – Stung by disappointing long-term outcomes for evidence-based intensive behavioral weight loss interventions that are often marked by late backsliding, researchers are turning the standard treatment programs upside down, with encouraging preliminary results.

One example of the new outside-the-box thinking regarding achieving sustained weight loss is the just-completed, 18-month, randomized FRESH START trial. Obese subjects in the novel “maintenance first” study arm spent the first 8 weeks of the intensive 6-month treatment program under orders not to lose any weight. If they did happen to lose a few pounds, they were instructed to gain them right back.

Participants were also encouraged to enjoy their favorite high-fat, high-calorie foods during the initial 8 weeks, albeit mindfully and in moderation, while searching for healthy replacement foods that tasted as good. Toward the end of the 8-week, maintenance-first part of the intervention, participants even took a “vacation week” in which they were instructed to eat five high-fat/high-calorie meals.

Sound counterintuitive? Actually, it’s an approach that’s solidly grounded in behavioral theory, according to Michaela Kiernan, Ph.D., senior research scientist at the center for research in disease prevention at Stanford (Calif.) University.

The emphasis during those first eight weekly 90-minute sessions was on avoiding self-deprivation while mastering the self-monitoring “stability skills” that she and her coinvestigators consider crucial to keeping lost weight off in the long term. The vacation week, for example, afforded an opportunity to practice navigating the dietary disruptions that are inevitable in any weight-loss effort.

In contrast, standard intensive behavioral weight loss programs place the initial emphasis on losing weight; maintenance skills are taught only after the weight loss has already occurred. But that approach hasn’t worked out so well. At the end of the standard, state-of-the-art behavioral and lifestyle intervention, patients have typically lost 15-20 pounds, but they regain 30%-50% of that during the next 12 months. The FRESH START approach was designed to curb that weight regain, she explained at the annual meeting of the Society of Behavioral Medicine.

And it worked. The 267 obese participants in FRESH START were randomized to a maintenance-skills-first group or to a standard, evidence-based, behavioral weight loss program. Both groups got 28 weekly 90-minute group sessions, with identical content for the weight-loss component in both arms. At the end of the intensive 6-month intervention, the mean weight loss was 16.1 pounds in the maintenance-first group, and – as expected – similar at 17.1 pounds in the control arm. But the control group regained 7.0 pounds during the next 12 months, significantly more than the mean 3.0 pounds regained in the maintenance-first arm.

Moreover, nearly twice as many women in the maintenance-first group displayed what behavioral therapists consider a model pattern of weight change: loss of at least 5% of initial weight at 6 months and a gain of less than 5 pounds at any time from 6 to 18 months. This pattern was achieved by 33% in the maintenance-first group, compared with 18% of controls. These FRESH START results have exciting practical as well as theoretical implications for long-term health behavior change, Dr. Kiernan asserted.

Another innovative study presented at the conference took a stepped-care approach to weight loss. The STEP-UP trial was a multicenter, randomized trial involving 363 obese, sedentary subjects who were assigned to a standard, evidence-based, 18-month, group-class behavioral intervention or to a lower-intensity approach in which patients were bumped up to more intensive interventions – phone calls, face-to-face individual counseling, meal replacements – only if they failed to achieve predetermined weight loss goals set at 3-month intervals. Those goals included a 5% weight loss at 3 months, 7% at 6 months, and 10% at 9, 12, and 15 months.

Deborah F. Tate, Ph.D., reported that the two groups achieved similar weight loss at 18 months: an average of 7.6 kg in the standard therapy group and 6.2 kg with the stepped-care approach. Weight loss of at least 5% was achieved among 58% of the control group and 56% of the stepped-care group at 18 months. Blood pressure, resting heart rate, and physical fitness didn’t differ between the two groups at any point.

Although outcomes in the two groups were similar, the costs to achieve those results were not. The stepped-care program cost an average total of $785 for combined payer and participant costs per patient, compared with $1,335 per participant in the standard behavioral therapy group, noted Dr. Tate of the University of North Carolina at Chapel Hill.

The explanation for the substantially lower per-patient total cost in the stepped-care group is that subjects in that study arm achieved their weight loss in an average of 12 group sessions, whereas those in the control arm had an average of 42 sessions. The incremental cost per kilogram of weight loss in the standard program was $409, she added.

Discussant Michael G. Perri, Ph.D., a pioneer in developing intensive behavioral weight loss programs, said he really likes the stepped-care approach because it’s practical and efficient, and it lends itself to implementation in a variety of health care settings.

“I can tell you, one of the biggest barriers to dissemination is that the length and intensity of the kinds of programs we do is too high for adoption in most community settings. We have to find ways to make them more efficient,” said Dr. Perri, professor of clinical and health psychology and dean of the college of public health and health professions at the University of Florida, Gainesville.

Another “terrific” aspect of the STEP-UP trial, he continued, is that the weight loss was achieved with lower cost and markedly fewer sessions than were entailed in standard therapy.

“It tells us that maybe we need to be looking at more of a triage kind of approach: You could set it up so that if somebody doesn’t do well, they get more care, and if they do worse they get even more care. But at some point, I think it really needs to be triage, where we say, ‘Enough is enough – this person is not going to benefit from anything more and we don’t waste more resources on him,’ ” Dr. Perri commented.

As for the FRESH START trial, in which he was a coinvestigator, Dr. Perri raised the possibility that the novel, maintenance-first intervention merely delayed weight regain rather than preventing it. This is suggested by the weight loss trend over time: During months 6-12, the maintenance-first group gained a mean of only 0.4 pounds, whereas in months 12-18, the group put on 2.5 pounds, which wasn’t significantly different from the mean 3.3-pound gain in the control group during that late phase of the study.

Still, delaying weight regain is not to be shrugged off. It confers long-term health benefits, as was recently shown in the 10-year follow-up of the landmark Diabetes Prevention Program (DPP), the psychologist asserted.

The DPP randomized more than 3,000 subjects with impaired glucose tolerance to an intensive diet and exercise lifestyle intervention, to metformin, or to placebo. The results were truly heartening: At 4 years of follow-up, the biggest average weight loss – about 4 kg – was seen in the lifestyle modification group. Moreover, the primary study end point, which was the development of type 2 diabetes, was reduced by 58% in the lifestyle intervention group, compared with placebo, which was a significantly greater benefit than the 31% risk reduction with metformin (N. Engl. J. Med. 2002;346:393-403).

Then came the initially disheartening DPP 10-year follow-up report. At 10 years, there was no longer any difference between the three study arms in terms of weight loss, which stood at about 2 kg in each group. Yet, surprisingly, there was still a 34% reduction in the incidence of type 2 diabetes in the lifestyle arm, compared with placebo, and an 18% reduction with metformin. The incidence was 11.0 cases per 100 person-years with placebo, 7.8 with metformin, and 4.8 with lifestyle modification (Lancet 2009;374:1677-86).

“One of the things that’s instructive about this is that even though we’re worried about the maintenance problem, the DPP shows that if somebody is able to lose weight and keep it off for a few years, that’s likely to have some beneficial impact on their health that can be observed long term, even if they do regain weight,” Dr. Perri observed.

The FRESH START and STEP-UP trials were funded by the National Institutes of Health. Dr. Kiernan, Dr. Tate, and Dr. Perri reported having no financial conflicts.

RALEIGH, N.C. – A population-based total-body skin cancer screening program reduces melanoma mortality, according to the results of a landmark German project presented at the annual meeting of the Society for Investigative Dermatology.

"I would argue that this is the most important presentation anywhere at this meeting," Dr. Martin A. Weinstock said during his presentation of the SCREEN (Skin Cancer Research to Provide Evidence for Effectiveness of Screening in Northern Germany) project.

"The reason I make that argument is very simply because melanoma accounts for more deaths than anything else in the dermatology world. If we want to reduce that number of deaths, the best way is [through] early detection – and SCREEN provides the best evidence to date that we can do that," explained Dr. Weinstock, professor of dermatology and epidemiology at Brown University, Providence, R.I., and a SCREEN project organizer.

SCREEN was a population-based skin cancer screening program in which all residents over age 20 in the German federal state of Schleswig-Holstein were encouraged to undergo a standardized whole-body skin examination between July 2003 and June 2004. Nineteen percent of the state’s eligible population – 360,288 individuals – participated. Half of the 1,169 melanomas diagnosed in Schleswig-Holstein during the study period were detected via the SCREEN program.

Before the skin cancer screening period (1998-1999), the melanoma mortality rate was 1.9 per 100,000 men and 1.4 per 100,000 women. The key study finding was that melanoma mortality fell by 48% in Schleswig-Holstein by 2008-2009 to 1.0 per 100,000 men to 0.7 per 100,000 women.

Nothing parallel occurred in the rest of Germany, or in Schleswig-Holstein’s neighbor to the north, Denmark.

The observed melanoma mortality rate in Schleswig-Holstein during 2008-2009 was 1.0 per 100,000 for men and 0.7 per 100,000 for women, compared with 1.8 and 1.2, respectively, in Germany as a whole excluding Schleswig-Holstein.

During 2000-2009, the most recent 10-year period for which official German mortality statistics are available, melanoma mortality in Schleswig-Holstein declined by 7.4% annually. In contrast, melanoma mortality rates were stable over time in each of the four adjacent states to the north, south, east, and west, none of which had a skin cancer screening program.

A bump in the incidence of melanoma was recorded in Schleswig-Holstein during the screening year, but not elsewhere, according to Dr. Weinstock.

The standardized total-body skin examinations were performed by physicians, who had to complete an 8-hour, day-long training course in order to participate. Of note, 116 of the 118 dermatologists practicing in Schleswig-Holstein participated in SCREEN, as did 64% of primary care physicians. Physicians were paid to perform the screens, and the public was encouraged to undergo screening via an extensive multimedia campaign.

The screening had a two-tiered structure. More than three-quarters of individuals were initially screened by primary care physicians. Participants with suspicious findings were sent to a dermatologist, who performed a second whole-body skin examination and performed biopsies as warranted.

Total-body skin examination as a means of reducing melanoma mortality has long been a controversial issue. The U.S. Preventive Services Task Force has recommended that there is not enough evidence to recommend screening the general adult population (Ann. Intern. Med. 2009;150:188-93). However, according to Dr. Weinstock, the recommendation will need to be revisited in light of the new evidence from Germany.

He observed that although SCREEN was an observational study, and, hence, doesn’t constitute absolute proof that a skin cancer screening program saves lives, it was the most ambitious effort to screen for melanoma ever conducted anywhere in the world. And it provides what is probably the strongest evidence that will ever be available, in his view, given the great expense and many years of follow-up required for a randomized controlled trial of skin cancer screening.

As he and his coauthors wrote in a new report from the SCREEN project, "In the public health arena, absolute proof is not necessarily required when lives are at stake" (Cancer 2012 April 19 [doi: 10.1002/cncr.27566]).

German dermatologists, flush with the SCREEN success, had proposed to follow-up the project with a definitive randomized controlled trial of melanoma screening, but were overruled. Federal health officials found the SCREEN results so persuasive that they launched an ongoing national skin cancer screening program. All 45 million Germans aged 35 years and older are now eligible for a total-body skin examination every 2 years.

The SCREEN investigators ruled out improvements in melanoma therapy as a potential explanation for the observed reduction in mortality, since there were none during the study years. Nor were there any changes in coding practices in the Schleswig-Holstein statistics office. And no major melanoma primary prevention programs were introduced.

Melanoma mortality rates in Schleswig-Holstein were fairly constant from 1990 to 2003, then dropped during and immediately after introduction of the statewide SCREEN program. All of which points to the skin cancer screening program as the almost-certain explanation for the melanoma mortality reduction, he said.

Dr. Weinstock promised there will be much more information and analysis to come from the SCREEN project, including tumor thickness–specific incidence rates. Also, by examining the incidence of melanoma in Schleswig-Holstein in the years following the screening program, it will be possible to create models that provide an idea of the optimal screening interval.

In a presentation at the Hawaii Dermatology Seminar sponsored by the Skin Disease Education Foundation (SDEF) in Waikoloa, Hawaii, Dr. Andreas Blum noted that while the main purpose of whole-body skin examination is to save lives through early detection of melanoma, the SCREEN project also detected basal cell carcinomas at a rate of 5.4 malignancies per 1,000 persons screened, and squamous cell carcinomas at a rate of 1.1 per 1,000.

Five lesion excisions had to be performed in order to detect one malignancy, according to Dr. Blum, professor of dermatology at the University of Tübingen (Germany).

He predicted that the cost involved in routine total-body skin examinations is likely to be a critical source of controversy. Using the U.S. National Cancer Institute’s estimate that 12.5% of melanomas are fatal, and assuming the cost of a total-body skin exam to be $50 per person, he estimated that routine total-body skin exams in the SCREEN project cost $240,000 per melanoma death avoided.

Meanwhile, in a recently reported multicenter study in which more than 14,000 subjects underwent a total-body skin exam, 400 patients had to be screened in order to find 1 melanoma (J. Am. Acad. Dermatol. 2012;66:212-9). Again, assuming a cost of $50 per total-body skin exam, that would work out to roughly $140,000 per melanoma death avoided, Dr. Blum said.

He added that in his own specialized skin cancer clinic, where he and his colleagues see a relatively select patient population, routine total-body skin exams cost an estimated $65,000 per melanoma death avoided. And when he plugged in the numbers provided by session chair Dr. Ashfaq A. Margoob from the skin cancer clinic at Memorial Sloan-Kettering Cancer Center in New York, Dr. Blum once again came up with a figure of roughly $65,000 per melanoma death avoided, which is close to one-fourth of the estimated cost per melanoma death avoided in the SCREEN project.

"The range is quite large. I think the cost debate will continue," Dr. Blum said.

Dr. Weinstock and Dr. Blum reported having no financial conflicts.

SDEF and this news organization are owned by Elsevier.

RALEIGH, N.C. – A population-based total-body skin cancer screening program reduces melanoma mortality, according to the results of a landmark German project presented at the annual meeting of the Society for Investigative Dermatology.

"I would argue that this is the most important presentation anywhere at this meeting," Dr. Martin A. Weinstock said during his presentation of the SCREEN (Skin Cancer Research to Provide Evidence for Effectiveness of Screening in Northern Germany) project.

"The reason I make that argument is very simply because melanoma accounts for more deaths than anything else in the dermatology world. If we want to reduce that number of deaths, the best way is [through] early detection – and SCREEN provides the best evidence to date that we can do that," explained Dr. Weinstock, professor of dermatology and epidemiology at Brown University, Providence, R.I., and a SCREEN project organizer.

SCREEN was a population-based skin cancer screening program in which all residents over age 20 in the German federal state of Schleswig-Holstein were encouraged to undergo a standardized whole-body skin examination between July 2003 and June 2004. Nineteen percent of the state’s eligible population – 360,288 individuals – participated. Half of the 1,169 melanomas diagnosed in Schleswig-Holstein during the study period were detected via the SCREEN program.

Before the skin cancer screening period (1998-1999), the melanoma mortality rate was 1.9 per 100,000 men and 1.4 per 100,000 women. The key study finding was that melanoma mortality fell by 48% in Schleswig-Holstein by 2008-2009 to 1.0 per 100,000 men to 0.7 per 100,000 women.

Nothing parallel occurred in the rest of Germany, or in Schleswig-Holstein’s neighbor to the north, Denmark.

The observed melanoma mortality rate in Schleswig-Holstein during 2008-2009 was 1.0 per 100,000 for men and 0.7 per 100,000 for women, compared with 1.8 and 1.2, respectively, in Germany as a whole excluding Schleswig-Holstein.

During 2000-2009, the most recent 10-year period for which official German mortality statistics are available, melanoma mortality in Schleswig-Holstein declined by 7.4% annually. In contrast, melanoma mortality rates were stable over time in each of the four adjacent states to the north, south, east, and west, none of which had a skin cancer screening program.

A bump in the incidence of melanoma was recorded in Schleswig-Holstein during the screening year, but not elsewhere, according to Dr. Weinstock.

The standardized total-body skin examinations were performed by physicians, who had to complete an 8-hour, day-long training course in order to participate. Of note, 116 of the 118 dermatologists practicing in Schleswig-Holstein participated in SCREEN, as did 64% of primary care physicians. Physicians were paid to perform the screens, and the public was encouraged to undergo screening via an extensive multimedia campaign.

The screening had a two-tiered structure. More than three-quarters of individuals were initially screened by primary care physicians. Participants with suspicious findings were sent to a dermatologist, who performed a second whole-body skin examination and performed biopsies as warranted.

Total-body skin examination as a means of reducing melanoma mortality has long been a controversial issue. The U.S. Preventive Services Task Force has recommended that there is not enough evidence to recommend screening the general adult population (Ann. Intern. Med. 2009;150:188-93). However, according to Dr. Weinstock, the recommendation will need to be revisited in light of the new evidence from Germany.

He observed that although SCREEN was an observational study, and, hence, doesn’t constitute absolute proof that a skin cancer screening program saves lives, it was the most ambitious effort to screen for melanoma ever conducted anywhere in the world. And it provides what is probably the strongest evidence that will ever be available, in his view, given the great expense and many years of follow-up required for a randomized controlled trial of skin cancer screening.

As he and his coauthors wrote in a new report from the SCREEN project, "In the public health arena, absolute proof is not necessarily required when lives are at stake" (Cancer 2012 April 19 [doi: 10.1002/cncr.27566]).

German dermatologists, flush with the SCREEN success, had proposed to follow-up the project with a definitive randomized controlled trial of melanoma screening, but were overruled. Federal health officials found the SCREEN results so persuasive that they launched an ongoing national skin cancer screening program. All 45 million Germans aged 35 years and older are now eligible for a total-body skin examination every 2 years.

The SCREEN investigators ruled out improvements in melanoma therapy as a potential explanation for the observed reduction in mortality, since there were none during the study years. Nor were there any changes in coding practices in the Schleswig-Holstein statistics office. And no major melanoma primary prevention programs were introduced.

Melanoma mortality rates in Schleswig-Holstein were fairly constant from 1990 to 2003, then dropped during and immediately after introduction of the statewide SCREEN program. All of which points to the skin cancer screening program as the almost-certain explanation for the melanoma mortality reduction, he said.

Dr. Weinstock promised there will be much more information and analysis to come from the SCREEN project, including tumor thickness–specific incidence rates. Also, by examining the incidence of melanoma in Schleswig-Holstein in the years following the screening program, it will be possible to create models that provide an idea of the optimal screening interval.

In a presentation at the Hawaii Dermatology Seminar sponsored by the Skin Disease Education Foundation (SDEF) in Waikoloa, Hawaii, Dr. Andreas Blum noted that while the main purpose of whole-body skin examination is to save lives through early detection of melanoma, the SCREEN project also detected basal cell carcinomas at a rate of 5.4 malignancies per 1,000 persons screened, and squamous cell carcinomas at a rate of 1.1 per 1,000.

Five lesion excisions had to be performed in order to detect one malignancy, according to Dr. Blum, professor of dermatology at the University of Tübingen (Germany).

He predicted that the cost involved in routine total-body skin examinations is likely to be a critical source of controversy. Using the U.S. National Cancer Institute’s estimate that 12.5% of melanomas are fatal, and assuming the cost of a total-body skin exam to be $50 per person, he estimated that routine total-body skin exams in the SCREEN project cost $240,000 per melanoma death avoided.

Meanwhile, in a recently reported multicenter study in which more than 14,000 subjects underwent a total-body skin exam, 400 patients had to be screened in order to find 1 melanoma (J. Am. Acad. Dermatol. 2012;66:212-9). Again, assuming a cost of $50 per total-body skin exam, that would work out to roughly $140,000 per melanoma death avoided, Dr. Blum said.

He added that in his own specialized skin cancer clinic, where he and his colleagues see a relatively select patient population, routine total-body skin exams cost an estimated $65,000 per melanoma death avoided. And when he plugged in the numbers provided by session chair Dr. Ashfaq A. Margoob from the skin cancer clinic at Memorial Sloan-Kettering Cancer Center in New York, Dr. Blum once again came up with a figure of roughly $65,000 per melanoma death avoided, which is close to one-fourth of the estimated cost per melanoma death avoided in the SCREEN project.

"The range is quite large. I think the cost debate will continue," Dr. Blum said.

Dr. Weinstock and Dr. Blum reported having no financial conflicts.

SDEF and this news organization are owned by Elsevier.

RALEIGH, N.C. – A population-based total-body skin cancer screening program reduces melanoma mortality, according to the results of a landmark German project presented at the annual meeting of the Society for Investigative Dermatology.

"I would argue that this is the most important presentation anywhere at this meeting," Dr. Martin A. Weinstock said during his presentation of the SCREEN (Skin Cancer Research to Provide Evidence for Effectiveness of Screening in Northern Germany) project.

"The reason I make that argument is very simply because melanoma accounts for more deaths than anything else in the dermatology world. If we want to reduce that number of deaths, the best way is [through] early detection – and SCREEN provides the best evidence to date that we can do that," explained Dr. Weinstock, professor of dermatology and epidemiology at Brown University, Providence, R.I., and a SCREEN project organizer.

SCREEN was a population-based skin cancer screening program in which all residents over age 20 in the German federal state of Schleswig-Holstein were encouraged to undergo a standardized whole-body skin examination between July 2003 and June 2004. Nineteen percent of the state’s eligible population – 360,288 individuals – participated. Half of the 1,169 melanomas diagnosed in Schleswig-Holstein during the study period were detected via the SCREEN program.

Before the skin cancer screening period (1998-1999), the melanoma mortality rate was 1.9 per 100,000 men and 1.4 per 100,000 women. The key study finding was that melanoma mortality fell by 48% in Schleswig-Holstein by 2008-2009 to 1.0 per 100,000 men to 0.7 per 100,000 women.

Nothing parallel occurred in the rest of Germany, or in Schleswig-Holstein’s neighbor to the north, Denmark.

The observed melanoma mortality rate in Schleswig-Holstein during 2008-2009 was 1.0 per 100,000 for men and 0.7 per 100,000 for women, compared with 1.8 and 1.2, respectively, in Germany as a whole excluding Schleswig-Holstein.

During 2000-2009, the most recent 10-year period for which official German mortality statistics are available, melanoma mortality in Schleswig-Holstein declined by 7.4% annually. In contrast, melanoma mortality rates were stable over time in each of the four adjacent states to the north, south, east, and west, none of which had a skin cancer screening program.

A bump in the incidence of melanoma was recorded in Schleswig-Holstein during the screening year, but not elsewhere, according to Dr. Weinstock.

The standardized total-body skin examinations were performed by physicians, who had to complete an 8-hour, day-long training course in order to participate. Of note, 116 of the 118 dermatologists practicing in Schleswig-Holstein participated in SCREEN, as did 64% of primary care physicians. Physicians were paid to perform the screens, and the public was encouraged to undergo screening via an extensive multimedia campaign.

The screening had a two-tiered structure. More than three-quarters of individuals were initially screened by primary care physicians. Participants with suspicious findings were sent to a dermatologist, who performed a second whole-body skin examination and performed biopsies as warranted.

Total-body skin examination as a means of reducing melanoma mortality has long been a controversial issue. The U.S. Preventive Services Task Force has recommended that there is not enough evidence to recommend screening the general adult population (Ann. Intern. Med. 2009;150:188-93). However, according to Dr. Weinstock, the recommendation will need to be revisited in light of the new evidence from Germany.

He observed that although SCREEN was an observational study, and, hence, doesn’t constitute absolute proof that a skin cancer screening program saves lives, it was the most ambitious effort to screen for melanoma ever conducted anywhere in the world. And it provides what is probably the strongest evidence that will ever be available, in his view, given the great expense and many years of follow-up required for a randomized controlled trial of skin cancer screening.

As he and his coauthors wrote in a new report from the SCREEN project, "In the public health arena, absolute proof is not necessarily required when lives are at stake" (Cancer 2012 April 19 [doi: 10.1002/cncr.27566]).

German dermatologists, flush with the SCREEN success, had proposed to follow-up the project with a definitive randomized controlled trial of melanoma screening, but were overruled. Federal health officials found the SCREEN results so persuasive that they launched an ongoing national skin cancer screening program. All 45 million Germans aged 35 years and older are now eligible for a total-body skin examination every 2 years.

The SCREEN investigators ruled out improvements in melanoma therapy as a potential explanation for the observed reduction in mortality, since there were none during the study years. Nor were there any changes in coding practices in the Schleswig-Holstein statistics office. And no major melanoma primary prevention programs were introduced.

Melanoma mortality rates in Schleswig-Holstein were fairly constant from 1990 to 2003, then dropped during and immediately after introduction of the statewide SCREEN program. All of which points to the skin cancer screening program as the almost-certain explanation for the melanoma mortality reduction, he said.

Dr. Weinstock promised there will be much more information and analysis to come from the SCREEN project, including tumor thickness–specific incidence rates. Also, by examining the incidence of melanoma in Schleswig-Holstein in the years following the screening program, it will be possible to create models that provide an idea of the optimal screening interval.

In a presentation at the Hawaii Dermatology Seminar sponsored by the Skin Disease Education Foundation (SDEF) in Waikoloa, Hawaii, Dr. Andreas Blum noted that while the main purpose of whole-body skin examination is to save lives through early detection of melanoma, the SCREEN project also detected basal cell carcinomas at a rate of 5.4 malignancies per 1,000 persons screened, and squamous cell carcinomas at a rate of 1.1 per 1,000.

Five lesion excisions had to be performed in order to detect one malignancy, according to Dr. Blum, professor of dermatology at the University of Tübingen (Germany).

He predicted that the cost involved in routine total-body skin examinations is likely to be a critical source of controversy. Using the U.S. National Cancer Institute’s estimate that 12.5% of melanomas are fatal, and assuming the cost of a total-body skin exam to be $50 per person, he estimated that routine total-body skin exams in the SCREEN project cost $240,000 per melanoma death avoided.

Meanwhile, in a recently reported multicenter study in which more than 14,000 subjects underwent a total-body skin exam, 400 patients had to be screened in order to find 1 melanoma (J. Am. Acad. Dermatol. 2012;66:212-9). Again, assuming a cost of $50 per total-body skin exam, that would work out to roughly $140,000 per melanoma death avoided, Dr. Blum said.

He added that in his own specialized skin cancer clinic, where he and his colleagues see a relatively select patient population, routine total-body skin exams cost an estimated $65,000 per melanoma death avoided. And when he plugged in the numbers provided by session chair Dr. Ashfaq A. Margoob from the skin cancer clinic at Memorial Sloan-Kettering Cancer Center in New York, Dr. Blum once again came up with a figure of roughly $65,000 per melanoma death avoided, which is close to one-fourth of the estimated cost per melanoma death avoided in the SCREEN project.

"The range is quite large. I think the cost debate will continue," Dr. Blum said.

Dr. Weinstock and Dr. Blum reported having no financial conflicts.

SDEF and this news organization are owned by Elsevier.

RALEIGH, N.C. – Once-daily application of an emollient from birth through age 6 months has shown considerable promise as a means of preventing atopic dermatitis, according to the Barrier Enhancement for Eczema Prevention study.

BEEP was a multicenter, international, randomized controlled pilot study assessing the feasibility, safety, and effectiveness of a novel approach to the prevention of atopic dermatitis. The study hypothesis was that protecting the skin barrier early in life can prevent this common skin disease, explained Dr. Eric L. Simpson of Oregon Health and Science University, Portland.

The rationale for this approach lies in previous work demonstrating that skin barrier dysfunction precedes eczema development. And emollients can be effective in treating mild disease and preventing flares, he said at the annual meeting of the Society for Investigative Dermatology.

BEEP involved 124 infants in Portland and at four medical centers in the United Kingdom. All were deemed high risk for atopic dermatitis because they had one or more first-degree relatives with a history of asthma, hay fever, or atopic dermatitis. Participating families were randomized to either once-daily application of an emollient to the baby’s entire body except the scalp and diaper area starting before age 3 weeks and continuing for 6 months, or to a control group that agreed to refrain from regular use of emollients. All families received advice on best-practice skin care, namely to minimize the use of harsh cleansers and hot water bathing.

The 6-month cumulative incidence of investigator-diagnosed eczema was 21.8% in the daily emollient group, compared with 43.3% in controls, for a 67% reduction in risk. It was a considerably more dramatic effect than what the investigators had anticipated.

"This was kind of a surprising finding to us," Dr. Simpson admitted. Patients will be followed up at 1 and 2 years to learn whether the early-life treatment actually prevented or simply delayed onset of atopic dermatitis.

In a subanalysis, skin barrier function studies were carried out in 15 patients divided between a control and intervention arm. Children in the control arm showed favorable albeit nonsignificant trends for less transepidermal water loss and a lower skin pH.

Parents in the intervention arm were given a choice of three emollients of various viscosities: sunflower seed oil; Cetaphil cream in the United States or Doublebase gel in the United Kingdom; or Aquaphor in the United States or 50-50 ointment, a white soft paraffin/liquid paraffin product marketed in the United Kingdom. More than two-thirds of families opted for Cetaphil cream or Doublebase gel.

Ninety-six percent of families in the intervention arm found their emollient acceptable, and 80% indicated they used it at least 5 days per week.

No cases of irritant or contact dermatitis occurred in the emollient group. Three mild skin infections occurred in each study arm.

Dr. Simpson’s BEEP coinvestigators included atopic dermatitis experts such as Dr. Hywel C. Williams, professor of dermatology at the University of Nottingham (England) and Dr. Jon M. Hanifin, professor emeritus of dermatology at Oregon Health and Science University.

The researchers are now planning a larger, definitive, randomized controlled trial of emollient therapy early in life as a means of preventing the development of atopic dermatitis. This study will be powered to look at the relative efficacy of different emollients. Also, it will include objective measures of adherence, such as volume of emollient used, rather than simply relying upon parental report.

Audience members expressed enthusiasm over the BEEP findings. The prevalence of atopic dermatitis has been rising for decades; the disease exacts a steep toll in terms of quality of life; and to date, there has been no established eczema prevention strategy. Moreover, there is the prospect that by preventing eczema via a simple topical therapy it will be possible to halt the "atopic march" to asthma and other comorbidities.

Dr. Simpson noted that BEEP was a small-scale feasibility study carried out because investigators were initially unsure if families would be willing to participate in a clinical trial where they could be randomized to avoiding emollients. But 28%-59% of the families approached at the participating centers agreed to enroll.

BEEP was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the Oregon Clinical and Translational Research Institute, and the U.K. National Institute for Health Research.

Dr. Simpson reported having no financial conflicts of interest.

RALEIGH, N.C. – Once-daily application of an emollient from birth through age 6 months has shown considerable promise as a means of preventing atopic dermatitis, according to the Barrier Enhancement for Eczema Prevention study.

BEEP was a multicenter, international, randomized controlled pilot study assessing the feasibility, safety, and effectiveness of a novel approach to the prevention of atopic dermatitis. The study hypothesis was that protecting the skin barrier early in life can prevent this common skin disease, explained Dr. Eric L. Simpson of Oregon Health and Science University, Portland.

The rationale for this approach lies in previous work demonstrating that skin barrier dysfunction precedes eczema development. And emollients can be effective in treating mild disease and preventing flares, he said at the annual meeting of the Society for Investigative Dermatology.

BEEP involved 124 infants in Portland and at four medical centers in the United Kingdom. All were deemed high risk for atopic dermatitis because they had one or more first-degree relatives with a history of asthma, hay fever, or atopic dermatitis. Participating families were randomized to either once-daily application of an emollient to the baby’s entire body except the scalp and diaper area starting before age 3 weeks and continuing for 6 months, or to a control group that agreed to refrain from regular use of emollients. All families received advice on best-practice skin care, namely to minimize the use of harsh cleansers and hot water bathing.

The 6-month cumulative incidence of investigator-diagnosed eczema was 21.8% in the daily emollient group, compared with 43.3% in controls, for a 67% reduction in risk. It was a considerably more dramatic effect than what the investigators had anticipated.

"This was kind of a surprising finding to us," Dr. Simpson admitted. Patients will be followed up at 1 and 2 years to learn whether the early-life treatment actually prevented or simply delayed onset of atopic dermatitis.

In a subanalysis, skin barrier function studies were carried out in 15 patients divided between a control and intervention arm. Children in the control arm showed favorable albeit nonsignificant trends for less transepidermal water loss and a lower skin pH.

Parents in the intervention arm were given a choice of three emollients of various viscosities: sunflower seed oil; Cetaphil cream in the United States or Doublebase gel in the United Kingdom; or Aquaphor in the United States or 50-50 ointment, a white soft paraffin/liquid paraffin product marketed in the United Kingdom. More than two-thirds of families opted for Cetaphil cream or Doublebase gel.

Ninety-six percent of families in the intervention arm found their emollient acceptable, and 80% indicated they used it at least 5 days per week.

No cases of irritant or contact dermatitis occurred in the emollient group. Three mild skin infections occurred in each study arm.

Dr. Simpson’s BEEP coinvestigators included atopic dermatitis experts such as Dr. Hywel C. Williams, professor of dermatology at the University of Nottingham (England) and Dr. Jon M. Hanifin, professor emeritus of dermatology at Oregon Health and Science University.

The researchers are now planning a larger, definitive, randomized controlled trial of emollient therapy early in life as a means of preventing the development of atopic dermatitis. This study will be powered to look at the relative efficacy of different emollients. Also, it will include objective measures of adherence, such as volume of emollient used, rather than simply relying upon parental report.

Audience members expressed enthusiasm over the BEEP findings. The prevalence of atopic dermatitis has been rising for decades; the disease exacts a steep toll in terms of quality of life; and to date, there has been no established eczema prevention strategy. Moreover, there is the prospect that by preventing eczema via a simple topical therapy it will be possible to halt the "atopic march" to asthma and other comorbidities.

Dr. Simpson noted that BEEP was a small-scale feasibility study carried out because investigators were initially unsure if families would be willing to participate in a clinical trial where they could be randomized to avoiding emollients. But 28%-59% of the families approached at the participating centers agreed to enroll.

BEEP was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the Oregon Clinical and Translational Research Institute, and the U.K. National Institute for Health Research.

Dr. Simpson reported having no financial conflicts of interest.

RALEIGH, N.C. – Once-daily application of an emollient from birth through age 6 months has shown considerable promise as a means of preventing atopic dermatitis, according to the Barrier Enhancement for Eczema Prevention study.

BEEP was a multicenter, international, randomized controlled pilot study assessing the feasibility, safety, and effectiveness of a novel approach to the prevention of atopic dermatitis. The study hypothesis was that protecting the skin barrier early in life can prevent this common skin disease, explained Dr. Eric L. Simpson of Oregon Health and Science University, Portland.

The rationale for this approach lies in previous work demonstrating that skin barrier dysfunction precedes eczema development. And emollients can be effective in treating mild disease and preventing flares, he said at the annual meeting of the Society for Investigative Dermatology.

BEEP involved 124 infants in Portland and at four medical centers in the United Kingdom. All were deemed high risk for atopic dermatitis because they had one or more first-degree relatives with a history of asthma, hay fever, or atopic dermatitis. Participating families were randomized to either once-daily application of an emollient to the baby’s entire body except the scalp and diaper area starting before age 3 weeks and continuing for 6 months, or to a control group that agreed to refrain from regular use of emollients. All families received advice on best-practice skin care, namely to minimize the use of harsh cleansers and hot water bathing.

The 6-month cumulative incidence of investigator-diagnosed eczema was 21.8% in the daily emollient group, compared with 43.3% in controls, for a 67% reduction in risk. It was a considerably more dramatic effect than what the investigators had anticipated.

"This was kind of a surprising finding to us," Dr. Simpson admitted. Patients will be followed up at 1 and 2 years to learn whether the early-life treatment actually prevented or simply delayed onset of atopic dermatitis.

In a subanalysis, skin barrier function studies were carried out in 15 patients divided between a control and intervention arm. Children in the control arm showed favorable albeit nonsignificant trends for less transepidermal water loss and a lower skin pH.

Parents in the intervention arm were given a choice of three emollients of various viscosities: sunflower seed oil; Cetaphil cream in the United States or Doublebase gel in the United Kingdom; or Aquaphor in the United States or 50-50 ointment, a white soft paraffin/liquid paraffin product marketed in the United Kingdom. More than two-thirds of families opted for Cetaphil cream or Doublebase gel.

Ninety-six percent of families in the intervention arm found their emollient acceptable, and 80% indicated they used it at least 5 days per week.

No cases of irritant or contact dermatitis occurred in the emollient group. Three mild skin infections occurred in each study arm.

Dr. Simpson’s BEEP coinvestigators included atopic dermatitis experts such as Dr. Hywel C. Williams, professor of dermatology at the University of Nottingham (England) and Dr. Jon M. Hanifin, professor emeritus of dermatology at Oregon Health and Science University.

The researchers are now planning a larger, definitive, randomized controlled trial of emollient therapy early in life as a means of preventing the development of atopic dermatitis. This study will be powered to look at the relative efficacy of different emollients. Also, it will include objective measures of adherence, such as volume of emollient used, rather than simply relying upon parental report.

Audience members expressed enthusiasm over the BEEP findings. The prevalence of atopic dermatitis has been rising for decades; the disease exacts a steep toll in terms of quality of life; and to date, there has been no established eczema prevention strategy. Moreover, there is the prospect that by preventing eczema via a simple topical therapy it will be possible to halt the "atopic march" to asthma and other comorbidities.

Dr. Simpson noted that BEEP was a small-scale feasibility study carried out because investigators were initially unsure if families would be willing to participate in a clinical trial where they could be randomized to avoiding emollients. But 28%-59% of the families approached at the participating centers agreed to enroll.

BEEP was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the Oregon Clinical and Translational Research Institute, and the U.K. National Institute for Health Research.

Dr. Simpson reported having no financial conflicts of interest.

NEW ORLEANS – Think ‘chronic gastric volvulus’ when a patient with a history of hiatal hernia presents with nonspecific symptoms such as difficulty in swallowing food and uncomfortable fullness after eating.

Gastric volvulus – a torsional twisting of the stomach – is an underrecognized complication of hiatal hernia. It occurs most often in patients with a large paraesophageal hiatal hernia or with an intrathoracic stomach that has come loose from its abdominal moorings, Dr. Conor G. Loftus explained at the conference.

Acute gastric volvulus is a surgical emergency. It typically presents suddenly with severe pain in the lower chest or upper abdomen, often accompanied by persistent nonproductive retching. It’s often mistaken for an acute MI. Yet acute gastric volvulus is no less serious an event, according to Dr. Loftus, a gastroenterologist at the Mayo Clinic, Rochester, Minn.

In contrast, chronic gastric volvulus is characterized by considerably milder, nonspecific symptoms. When clinical suspicion focuses on this possible diagnosis, the best confirmatory test is a barium esophagram.

Dr. Loftus presented an illustrative case: a 70-year-old man who presents complaining of nonpainful difficulty in swallowing solid food but not liquids for the past several years. He has a history of hiatal hernia as well as long-standing gastroesophageal reflux disease controlled with once-daily proton pump inhibitor therapy. He hasn’t lost weight. A gastroenterologist performed upper endoscopy with grossly normal findings, albeit with a notation that it was somewhat difficult to pass the probe across a tortuous esophagus and stomach.

In this vignette, Dr. Loftus observed, the clinical presentation and endoscopic findings raise a red flag for chronic gastric volvulus. In particular, the reported earlier difficulty in passing the endoscope suggests a mechanical problem.

Ordering esophageal manometry would be the right choice if a dysmotility disorder were suspected; however, a recent-onset dysmotility disorder would be unusual in an aged individual and, in any case, it would typically present with both liquid and solid food dysphagia.

Endoscopic ultrasound of the gastroesophageal junction or CT scan of the chest would be the appropriate imaging study if a malignancy was suspected. But the lack of weight loss in a patient with a 3-year history of symptoms argues strongly against that possibility, he continued.

Repeating the earlier upper endoscopy, this time obtaining esophageal biopsies, would be a good move if eosinophilic esophagitis was suspected; however, this disorder is uncommon at an advanced age, Dr. Loftus noted.

He reported having no financial conflicts.

NEW ORLEANS – Think ‘chronic gastric volvulus’ when a patient with a history of hiatal hernia presents with nonspecific symptoms such as difficulty in swallowing food and uncomfortable fullness after eating.

Gastric volvulus – a torsional twisting of the stomach – is an underrecognized complication of hiatal hernia. It occurs most often in patients with a large paraesophageal hiatal hernia or with an intrathoracic stomach that has come loose from its abdominal moorings, Dr. Conor G. Loftus explained at the conference.

Acute gastric volvulus is a surgical emergency. It typically presents suddenly with severe pain in the lower chest or upper abdomen, often accompanied by persistent nonproductive retching. It’s often mistaken for an acute MI. Yet acute gastric volvulus is no less serious an event, according to Dr. Loftus, a gastroenterologist at the Mayo Clinic, Rochester, Minn.

In contrast, chronic gastric volvulus is characterized by considerably milder, nonspecific symptoms. When clinical suspicion focuses on this possible diagnosis, the best confirmatory test is a barium esophagram.

Dr. Loftus presented an illustrative case: a 70-year-old man who presents complaining of nonpainful difficulty in swallowing solid food but not liquids for the past several years. He has a history of hiatal hernia as well as long-standing gastroesophageal reflux disease controlled with once-daily proton pump inhibitor therapy. He hasn’t lost weight. A gastroenterologist performed upper endoscopy with grossly normal findings, albeit with a notation that it was somewhat difficult to pass the probe across a tortuous esophagus and stomach.

In this vignette, Dr. Loftus observed, the clinical presentation and endoscopic findings raise a red flag for chronic gastric volvulus. In particular, the reported earlier difficulty in passing the endoscope suggests a mechanical problem.

Ordering esophageal manometry would be the right choice if a dysmotility disorder were suspected; however, a recent-onset dysmotility disorder would be unusual in an aged individual and, in any case, it would typically present with both liquid and solid food dysphagia.

Endoscopic ultrasound of the gastroesophageal junction or CT scan of the chest would be the appropriate imaging study if a malignancy was suspected. But the lack of weight loss in a patient with a 3-year history of symptoms argues strongly against that possibility, he continued.

Repeating the earlier upper endoscopy, this time obtaining esophageal biopsies, would be a good move if eosinophilic esophagitis was suspected; however, this disorder is uncommon at an advanced age, Dr. Loftus noted.

He reported having no financial conflicts.

NEW ORLEANS – Think ‘chronic gastric volvulus’ when a patient with a history of hiatal hernia presents with nonspecific symptoms such as difficulty in swallowing food and uncomfortable fullness after eating.

Gastric volvulus – a torsional twisting of the stomach – is an underrecognized complication of hiatal hernia. It occurs most often in patients with a large paraesophageal hiatal hernia or with an intrathoracic stomach that has come loose from its abdominal moorings, Dr. Conor G. Loftus explained at the conference.

Acute gastric volvulus is a surgical emergency. It typically presents suddenly with severe pain in the lower chest or upper abdomen, often accompanied by persistent nonproductive retching. It’s often mistaken for an acute MI. Yet acute gastric volvulus is no less serious an event, according to Dr. Loftus, a gastroenterologist at the Mayo Clinic, Rochester, Minn.

In contrast, chronic gastric volvulus is characterized by considerably milder, nonspecific symptoms. When clinical suspicion focuses on this possible diagnosis, the best confirmatory test is a barium esophagram.

Dr. Loftus presented an illustrative case: a 70-year-old man who presents complaining of nonpainful difficulty in swallowing solid food but not liquids for the past several years. He has a history of hiatal hernia as well as long-standing gastroesophageal reflux disease controlled with once-daily proton pump inhibitor therapy. He hasn’t lost weight. A gastroenterologist performed upper endoscopy with grossly normal findings, albeit with a notation that it was somewhat difficult to pass the probe across a tortuous esophagus and stomach.

In this vignette, Dr. Loftus observed, the clinical presentation and endoscopic findings raise a red flag for chronic gastric volvulus. In particular, the reported earlier difficulty in passing the endoscope suggests a mechanical problem.

Ordering esophageal manometry would be the right choice if a dysmotility disorder were suspected; however, a recent-onset dysmotility disorder would be unusual in an aged individual and, in any case, it would typically present with both liquid and solid food dysphagia.

Endoscopic ultrasound of the gastroesophageal junction or CT scan of the chest would be the appropriate imaging study if a malignancy was suspected. But the lack of weight loss in a patient with a 3-year history of symptoms argues strongly against that possibility, he continued.

Repeating the earlier upper endoscopy, this time obtaining esophageal biopsies, would be a good move if eosinophilic esophagitis was suspected; however, this disorder is uncommon at an advanced age, Dr. Loftus noted.

He reported having no financial conflicts.

CHICAGO – The new oral anticoagulants for stroke prevention in atrial fibrillation may be garnering all the buzz, but don’t count out warfarin.

"It’s not just a knee-jerk reaction that all patients should be switched to the new agents. It’s dependent upon how well you as a physician are managing your patients on warfarin," Dr. Jack E. Ansell asserted at the annual meeting of the American College of Cardiology.

"Warfarin therapy is all about management. If it’s not managed well, you can compare it to anything, and anything is going to be better. And if it’s managed very well, then it’s very difficult to beat warfarin therapy," said Dr. Ansell, chairman of the department of medicine at Lenox Hill Hospital in New York.

A growing body of evidence indicates that the new standard in high-quality management of warfarin therapy involves patient self-testing of International Normalized Ratios at home using a fingerstick blood sample and portable point-of-care device.

Case in point: Dr. Ansell presented highlights of the new STABLE study, in which he and his coinvestigators conducted a retrospective analysis of the real-world experience of more than 29,000 warfarin-treated patients enrolled in a national commercial comprehensive self-test support service (JACC 2012 March 27 [doi: 10.1016/S0735-1097(12)61865-8]).

Patients who performed frequent self-testing – meaning more than 80% of their self-testing was done on a weekly basis had a mean time spent in the therapeutic INR range (TTR) of 74%. That’s unprecedented, he said.

By comparison, in the pivotal RE-LY randomized trial for dabigatran (Pradaxa), the control group on warfarin had a TTR of 64% (N. Engl. J. Med. 2009;361:1139-51). In the ROCKET-AF trial of rivaroxaban (Xarelto), warfarin controls had a TTR of 55% (N. Engl. J. Med. 2011;365:883-91). And in the ARISTOTLE study of apixaban (Eliquis), an agent expected to soon receive Food and Drug Administration marketing approval, the warfarin control group had a TTR of 62% (N. Engl. J. Med. 2011;365:981-92). In all these major randomized trials involving the novel oral anticoagulants, patients assigned to warfarin were closely managed, but in traditional fashion – home self-testing wasn’t involved.

In contrast, in the STABLE study, the overall TTR, including those patients who self-tested variably and inconsistently, was still 69.7%.

"This is important because the cost-effectiveness analyses done with dabigatran and the other new anticoagulants suggest that when you get up to a TTR above 70% with warfarin, the cost-effectiveness of the new agents diminishes and warfarin actually becomes more cost-effective," according to Dr. Ansell.

A particularly impressive finding in STABLE was that patients who did weekly self-testing had a 2.3% incidence of critical value INR results, defined as an INR below 1.5 or greater than 5.0. "This is really a phenomenally low result," he commented. It represented a 48% reduction from the 4.4% incidence in patients with variable self-testing frequency.

Participants in the STABLE study tested themselves at home, but their warfarin dosing was managed by their referring physicians or anticoagulation clinics. Thus, an individual’s TTR reflected the warfarin management expertise of the referral source.

There are several reasons why home monitoring achieves better TTRs and – as shown in other studies – lower major bleeding and thrombotic event rates than with usual care or anticoagulation clinics not utilizing patient self-monitoring, Dr. Ansell said. Home testing is more frequent, timely, and consistent, and the immediate feedback regarding INR results is likely to promote adherence.

A variant of patient self-testing starting to catch on in the United States is patient self-management. This entails teaching patients how to manage their own warfarin dose on the basis of their home INR measurements.

The most recent American College of Chest Physicians clinical practice guidelines on antithrombotic therapy for atrial fibrillation give patient self-management of warfarin therapy a class 2B recommendation, stating, "For patients treated with vitamin K antagonists who are motivated and can demonstrate competency in self-management strategies, including the self-testing equipment, we suggest patient self-management rather than the usual outpatient INR monitoring" (CHEST 2012;141: 2 suppl. e531S-e575S [doi: 10.1378/chest.11-2304]).

Session cochair Dr. Samuel Z. Goldhaber agreed with Dr. Ansell that warfarin still has a place in anticoagulation therapy. The fact that it costs as little as $4 per month while dabigatran, for example, retails for 60 times that amount, is not to be shrugged off in an era of runaway health care spending. Plus, warfarin, for all its drawbacks, is a known quantity backed by more than a half century of clinical experience.

"Even though warfarin can cause horrible complications, there are no more surprises left about what warfarin can do," observed Dr. Goldhaber, professor of medicine at Harvard Medical School and director of the venous thromboembolism research group at Brigham and Women’s Hospital, Boston.

A potential game changer for warfarin is the possibility that rapid pharmacogenetic testing will enable physicians to improve upon the current method of warfarin dosing.

One advantage warfarin has is that bleeding episodes can be reversed by administration of vitamin K. In contrast, there is as yet no reliable means of reversing major bleeding in patients on the novel anticoagulants. But Dr. Lars Wallentin said this limitation of the new agents is outweighed by the consistent finding that they have lower rates of intracranial hemorrhage than those of warfarin.

"There is no antidote to warfarin that has proven to have any effect in patients with ICH. And there is no evidence as far as I can see that however you control INR you can reach as low a level of ICH as with these new agents. I think this is a specific downside of warfarin that we can’t get away from," said Dr. Wallentin, professor of cardiology at Uppsala (Sweden) University.

The STABLE study was funded by Alere Home Monitoring, Inc. Dr. Ansell is a consultant to the company.

Dr. Goldhaber has served as a consultant to numerous pharmaceutical companies developing cardiovascular medications.

Dr. Wallentin was principal investigator in the ARISTOTLE study of apixaban, funded by Pfizer and Bristol Myers Squibb, and has served as a consultant to those and other pharmaceutical companies.

CHICAGO – The new oral anticoagulants for stroke prevention in atrial fibrillation may be garnering all the buzz, but don’t count out warfarin.

"It’s not just a knee-jerk reaction that all patients should be switched to the new agents. It’s dependent upon how well you as a physician are managing your patients on warfarin," Dr. Jack E. Ansell asserted at the annual meeting of the American College of Cardiology.

"Warfarin therapy is all about management. If it’s not managed well, you can compare it to anything, and anything is going to be better. And if it’s managed very well, then it’s very difficult to beat warfarin therapy," said Dr. Ansell, chairman of the department of medicine at Lenox Hill Hospital in New York.

A growing body of evidence indicates that the new standard in high-quality management of warfarin therapy involves patient self-testing of International Normalized Ratios at home using a fingerstick blood sample and portable point-of-care device.

Case in point: Dr. Ansell presented highlights of the new STABLE study, in which he and his coinvestigators conducted a retrospective analysis of the real-world experience of more than 29,000 warfarin-treated patients enrolled in a national commercial comprehensive self-test support service (JACC 2012 March 27 [doi: 10.1016/S0735-1097(12)61865-8]).

Patients who performed frequent self-testing – meaning more than 80% of their self-testing was done on a weekly basis had a mean time spent in the therapeutic INR range (TTR) of 74%. That’s unprecedented, he said.

By comparison, in the pivotal RE-LY randomized trial for dabigatran (Pradaxa), the control group on warfarin had a TTR of 64% (N. Engl. J. Med. 2009;361:1139-51). In the ROCKET-AF trial of rivaroxaban (Xarelto), warfarin controls had a TTR of 55% (N. Engl. J. Med. 2011;365:883-91). And in the ARISTOTLE study of apixaban (Eliquis), an agent expected to soon receive Food and Drug Administration marketing approval, the warfarin control group had a TTR of 62% (N. Engl. J. Med. 2011;365:981-92). In all these major randomized trials involving the novel oral anticoagulants, patients assigned to warfarin were closely managed, but in traditional fashion – home self-testing wasn’t involved.

In contrast, in the STABLE study, the overall TTR, including those patients who self-tested variably and inconsistently, was still 69.7%.

"This is important because the cost-effectiveness analyses done with dabigatran and the other new anticoagulants suggest that when you get up to a TTR above 70% with warfarin, the cost-effectiveness of the new agents diminishes and warfarin actually becomes more cost-effective," according to Dr. Ansell.

A particularly impressive finding in STABLE was that patients who did weekly self-testing had a 2.3% incidence of critical value INR results, defined as an INR below 1.5 or greater than 5.0. "This is really a phenomenally low result," he commented. It represented a 48% reduction from the 4.4% incidence in patients with variable self-testing frequency.

Participants in the STABLE study tested themselves at home, but their warfarin dosing was managed by their referring physicians or anticoagulation clinics. Thus, an individual’s TTR reflected the warfarin management expertise of the referral source.

There are several reasons why home monitoring achieves better TTRs and – as shown in other studies – lower major bleeding and thrombotic event rates than with usual care or anticoagulation clinics not utilizing patient self-monitoring, Dr. Ansell said. Home testing is more frequent, timely, and consistent, and the immediate feedback regarding INR results is likely to promote adherence.

A variant of patient self-testing starting to catch on in the United States is patient self-management. This entails teaching patients how to manage their own warfarin dose on the basis of their home INR measurements.

The most recent American College of Chest Physicians clinical practice guidelines on antithrombotic therapy for atrial fibrillation give patient self-management of warfarin therapy a class 2B recommendation, stating, "For patients treated with vitamin K antagonists who are motivated and can demonstrate competency in self-management strategies, including the self-testing equipment, we suggest patient self-management rather than the usual outpatient INR monitoring" (CHEST 2012;141: 2 suppl. e531S-e575S [doi: 10.1378/chest.11-2304]).

Session cochair Dr. Samuel Z. Goldhaber agreed with Dr. Ansell that warfarin still has a place in anticoagulation therapy. The fact that it costs as little as $4 per month while dabigatran, for example, retails for 60 times that amount, is not to be shrugged off in an era of runaway health care spending. Plus, warfarin, for all its drawbacks, is a known quantity backed by more than a half century of clinical experience.

"Even though warfarin can cause horrible complications, there are no more surprises left about what warfarin can do," observed Dr. Goldhaber, professor of medicine at Harvard Medical School and director of the venous thromboembolism research group at Brigham and Women’s Hospital, Boston.

A potential game changer for warfarin is the possibility that rapid pharmacogenetic testing will enable physicians to improve upon the current method of warfarin dosing.

One advantage warfarin has is that bleeding episodes can be reversed by administration of vitamin K. In contrast, there is as yet no reliable means of reversing major bleeding in patients on the novel anticoagulants. But Dr. Lars Wallentin said this limitation of the new agents is outweighed by the consistent finding that they have lower rates of intracranial hemorrhage than those of warfarin.

"There is no antidote to warfarin that has proven to have any effect in patients with ICH. And there is no evidence as far as I can see that however you control INR you can reach as low a level of ICH as with these new agents. I think this is a specific downside of warfarin that we can’t get away from," said Dr. Wallentin, professor of cardiology at Uppsala (Sweden) University.

The STABLE study was funded by Alere Home Monitoring, Inc. Dr. Ansell is a consultant to the company.

Dr. Goldhaber has served as a consultant to numerous pharmaceutical companies developing cardiovascular medications.

Dr. Wallentin was principal investigator in the ARISTOTLE study of apixaban, funded by Pfizer and Bristol Myers Squibb, and has served as a consultant to those and other pharmaceutical companies.

CHICAGO – The new oral anticoagulants for stroke prevention in atrial fibrillation may be garnering all the buzz, but don’t count out warfarin.

"It’s not just a knee-jerk reaction that all patients should be switched to the new agents. It’s dependent upon how well you as a physician are managing your patients on warfarin," Dr. Jack E. Ansell asserted at the annual meeting of the American College of Cardiology.

"Warfarin therapy is all about management. If it’s not managed well, you can compare it to anything, and anything is going to be better. And if it’s managed very well, then it’s very difficult to beat warfarin therapy," said Dr. Ansell, chairman of the department of medicine at Lenox Hill Hospital in New York.

A growing body of evidence indicates that the new standard in high-quality management of warfarin therapy involves patient self-testing of International Normalized Ratios at home using a fingerstick blood sample and portable point-of-care device.

Case in point: Dr. Ansell presented highlights of the new STABLE study, in which he and his coinvestigators conducted a retrospective analysis of the real-world experience of more than 29,000 warfarin-treated patients enrolled in a national commercial comprehensive self-test support service (JACC 2012 March 27 [doi: 10.1016/S0735-1097(12)61865-8]).

Patients who performed frequent self-testing – meaning more than 80% of their self-testing was done on a weekly basis had a mean time spent in the therapeutic INR range (TTR) of 74%. That’s unprecedented, he said.

By comparison, in the pivotal RE-LY randomized trial for dabigatran (Pradaxa), the control group on warfarin had a TTR of 64% (N. Engl. J. Med. 2009;361:1139-51). In the ROCKET-AF trial of rivaroxaban (Xarelto), warfarin controls had a TTR of 55% (N. Engl. J. Med. 2011;365:883-91). And in the ARISTOTLE study of apixaban (Eliquis), an agent expected to soon receive Food and Drug Administration marketing approval, the warfarin control group had a TTR of 62% (N. Engl. J. Med. 2011;365:981-92). In all these major randomized trials involving the novel oral anticoagulants, patients assigned to warfarin were closely managed, but in traditional fashion – home self-testing wasn’t involved.

In contrast, in the STABLE study, the overall TTR, including those patients who self-tested variably and inconsistently, was still 69.7%.

"This is important because the cost-effectiveness analyses done with dabigatran and the other new anticoagulants suggest that when you get up to a TTR above 70% with warfarin, the cost-effectiveness of the new agents diminishes and warfarin actually becomes more cost-effective," according to Dr. Ansell.

A particularly impressive finding in STABLE was that patients who did weekly self-testing had a 2.3% incidence of critical value INR results, defined as an INR below 1.5 or greater than 5.0. "This is really a phenomenally low result," he commented. It represented a 48% reduction from the 4.4% incidence in patients with variable self-testing frequency.

Participants in the STABLE study tested themselves at home, but their warfarin dosing was managed by their referring physicians or anticoagulation clinics. Thus, an individual’s TTR reflected the warfarin management expertise of the referral source.

There are several reasons why home monitoring achieves better TTRs and – as shown in other studies – lower major bleeding and thrombotic event rates than with usual care or anticoagulation clinics not utilizing patient self-monitoring, Dr. Ansell said. Home testing is more frequent, timely, and consistent, and the immediate feedback regarding INR results is likely to promote adherence.

A variant of patient self-testing starting to catch on in the United States is patient self-management. This entails teaching patients how to manage their own warfarin dose on the basis of their home INR measurements.

The most recent American College of Chest Physicians clinical practice guidelines on antithrombotic therapy for atrial fibrillation give patient self-management of warfarin therapy a class 2B recommendation, stating, "For patients treated with vitamin K antagonists who are motivated and can demonstrate competency in self-management strategies, including the self-testing equipment, we suggest patient self-management rather than the usual outpatient INR monitoring" (CHEST 2012;141: 2 suppl. e531S-e575S [doi: 10.1378/chest.11-2304]).

Session cochair Dr. Samuel Z. Goldhaber agreed with Dr. Ansell that warfarin still has a place in anticoagulation therapy. The fact that it costs as little as $4 per month while dabigatran, for example, retails for 60 times that amount, is not to be shrugged off in an era of runaway health care spending. Plus, warfarin, for all its drawbacks, is a known quantity backed by more than a half century of clinical experience.

"Even though warfarin can cause horrible complications, there are no more surprises left about what warfarin can do," observed Dr. Goldhaber, professor of medicine at Harvard Medical School and director of the venous thromboembolism research group at Brigham and Women’s Hospital, Boston.

A potential game changer for warfarin is the possibility that rapid pharmacogenetic testing will enable physicians to improve upon the current method of warfarin dosing.

One advantage warfarin has is that bleeding episodes can be reversed by administration of vitamin K. In contrast, there is as yet no reliable means of reversing major bleeding in patients on the novel anticoagulants. But Dr. Lars Wallentin said this limitation of the new agents is outweighed by the consistent finding that they have lower rates of intracranial hemorrhage than those of warfarin.

"There is no antidote to warfarin that has proven to have any effect in patients with ICH. And there is no evidence as far as I can see that however you control INR you can reach as low a level of ICH as with these new agents. I think this is a specific downside of warfarin that we can’t get away from," said Dr. Wallentin, professor of cardiology at Uppsala (Sweden) University.

The STABLE study was funded by Alere Home Monitoring, Inc. Dr. Ansell is a consultant to the company.

Dr. Goldhaber has served as a consultant to numerous pharmaceutical companies developing cardiovascular medications.

Dr. Wallentin was principal investigator in the ARISTOTLE study of apixaban, funded by Pfizer and Bristol Myers Squibb, and has served as a consultant to those and other pharmaceutical companies.

DENVER – Morphine sulfate can be readily formulated into a gel for effective topical analgesia in patients with painful skin ulcers and other wounds.

All that’s necessary is for a compounding pharmacist to mix 10 mg of intravenous morphine sulfate in 8 g of IntraSite Gel, a hydrogel widely used in wound care. The morphine gel can be applied to the wound one to three times daily, according to Mary Lynn McPherson, professor and vice chair of the department of pharmacy practice and science at the University of Maryland, Baltimore.

There is very little systemic absorption of the morphine. External irritation that manifests as burning or itching is the only side effect. This therapy works despite the limited systemic absorption because there are both central and peripheral opioid receptors.

Dressing changes can be excruciating for hospice patients. Administering an oral dose of ketamine beforehand provides effective pain relief.

"We’ve been doing this frequently in our inpatient hospice unit for patients who have these horrific, horrific wounds. We’ll give them 10, 20, or even 30 mg of ketamine orally 15-20 minutes before wound care. It has made absolutely all the difference in the world. The results have been spectacular," she said at the meeting.

The oral dose consists of intravenous ketamine solution, the only form in which the drug is available. The taste is awful, so the medication should be mixed with cherry syrup, spearmint, orange juice, or another masking flavor.

Dr. McPherson reported having no financial conflicts.

DENVER – Morphine sulfate can be readily formulated into a gel for effective topical analgesia in patients with painful skin ulcers and other wounds.

All that’s necessary is for a compounding pharmacist to mix 10 mg of intravenous morphine sulfate in 8 g of IntraSite Gel, a hydrogel widely used in wound care. The morphine gel can be applied to the wound one to three times daily, according to Mary Lynn McPherson, professor and vice chair of the department of pharmacy practice and science at the University of Maryland, Baltimore.

There is very little systemic absorption of the morphine. External irritation that manifests as burning or itching is the only side effect. This therapy works despite the limited systemic absorption because there are both central and peripheral opioid receptors.

Dressing changes can be excruciating for hospice patients. Administering an oral dose of ketamine beforehand provides effective pain relief.

"We’ve been doing this frequently in our inpatient hospice unit for patients who have these horrific, horrific wounds. We’ll give them 10, 20, or even 30 mg of ketamine orally 15-20 minutes before wound care. It has made absolutely all the difference in the world. The results have been spectacular," she said at the meeting.

The oral dose consists of intravenous ketamine solution, the only form in which the drug is available. The taste is awful, so the medication should be mixed with cherry syrup, spearmint, orange juice, or another masking flavor.

Dr. McPherson reported having no financial conflicts.

DENVER – Morphine sulfate can be readily formulated into a gel for effective topical analgesia in patients with painful skin ulcers and other wounds.

All that’s necessary is for a compounding pharmacist to mix 10 mg of intravenous morphine sulfate in 8 g of IntraSite Gel, a hydrogel widely used in wound care. The morphine gel can be applied to the wound one to three times daily, according to Mary Lynn McPherson, professor and vice chair of the department of pharmacy practice and science at the University of Maryland, Baltimore.

There is very little systemic absorption of the morphine. External irritation that manifests as burning or itching is the only side effect. This therapy works despite the limited systemic absorption because there are both central and peripheral opioid receptors.

Dressing changes can be excruciating for hospice patients. Administering an oral dose of ketamine beforehand provides effective pain relief.

"We’ve been doing this frequently in our inpatient hospice unit for patients who have these horrific, horrific wounds. We’ll give them 10, 20, or even 30 mg of ketamine orally 15-20 minutes before wound care. It has made absolutely all the difference in the world. The results have been spectacular," she said at the meeting.

The oral dose consists of intravenous ketamine solution, the only form in which the drug is available. The taste is awful, so the medication should be mixed with cherry syrup, spearmint, orange juice, or another masking flavor.

Dr. McPherson reported having no financial conflicts.

NEW ORLEANS  – Noninvasive transcranial direct current stimulation of the pain-modulating areas of the cerebral cortex markedly reduced postoperative pain and opioid use in a randomized trial involving total knee arthroplasty recipients.

Transcranial direct current stimulation (tDCS), a novel and apparently safe form of neurostimulation for analgesia, also is in planned or ongoing clinical trials for various forms of chronic pain.

In tDCS, two saline-soaked electrodes are placed over different areas of the brain so that a 2.0 mA direct current can be run through the brain for about 20 minutes. This electrical current increases activity in one target area of the brain while decreasing activity in another. In the total knee arthroplasty study, for example, the cathode was placed over the right dorsolateral prefrontal cortex, and the anode was placed over the knee representation of the motor strip.

There is intense research interest in extending tDCS beyond the arena of pain control and exploring its potential for nonpharmacologic treatment of mood and anxiety disorders, according to Jeffrey J. Borckardt, Ph.D., a psychologist at the Medical University of South Carolina, Charleston.

"This whole area of minimally invasive brain stimulation technologies is growing rapidly. Psychotherapy changes the electrical patterns that are realized in the brain, as shown by good-quality functional MRI studies. And tDCS is another way to do that," he explained. "We’ve just started playing with an idea that has real interesting potential: If we can enhance cortical excitability in targeted brain regions and we also have an idea what we’re doing to brain regions with psychotherapy, we may be able to get a synergistic effect by combining these brain stimulation technologies with psychotherapy. Perhaps we can increase the longevity and even the intensity of the clinical impact we have."

He and his coinvestigators selected total knee arthroplasty for a pilot clinical trial of tDCS for acute pain because it’s one of the most frequently performed orthopedic surgeries and the postoperative pain is severe. Many patients experience continued marked pain despite opioids and nerve blocks. The result is slowed recovery, increased hospital length of stay, and difficulty in completing the recommended postop physical therapy program.

Dr. Borckardt reported on 40 patients undergoing unilateral total knee arthroplasty who were randomized to receive four 20-minute sessions of real or sham tDCS. The first session was immediately after the surgery, the second 4 hours later, the third on the morning of postoperative day 1, and the fourth that afternoon.

Subjects who received real tDCS used 44% less patient-controlled opioid analgesia during the first 48 hours post surgery. And despite having significantly fewer opioids on board, they rated their pain as significantly less than controls did: an average of 9 out of a possible 100 points on a visual analog scale, compared with 34 points in the sham tDCS group.

In an earlier randomized, sham-controlled pilot study of tDCS for postprocedural pain in 21 women undergoing endoscopic retrograde cholangiopancreatography for pancreatitis-related pain, the patients who received a single 20-minute session of real tDCS used an average of 22% less patient-controlled opioid analgesia (Gastrointest. Endosc. 2011;73:1158-64).

Transcranial direct current stimulation, like the much more extensively studied transcranial magnetic stimulation (TMS), falls under the heading of neurostimulatory therapies for pain control. All rely upon the gate theory of pain, which holds that bombarding pain-signaling pathways with stimuli prevents the pain signals from getting through.

The best-known neurostimulation technology is transcutaneous electrical nerve stimulation (TENS). Invasive neurostimulation technologies include spinal cord stimulation; vagus nerve stimulation, which is Food and Drug Administration–approved for treatment of both epilepsy and depression; and motor cortex stimulation, involving a small craniotomy and implantation of electrodes into the brain.

Dr. Borckardt and his South Carolina colleagues have been heavily involved in studies of both TMS and tDCS. These are noninvasive technologies in that they don’t entail implantation of electrodes or generators. Both can be performed on patients who are awake.

Transcranial magnetic stimulation uses a cone-shaped magnetic field generated by a figure-eight–shaped coil placed above the patient’s head. The magnetic field passes unimpeded through the hair and skull to depolarize neurons in a dime-sized target area. However, if the magnetic field intensity or frequency is too high, the therapy can induce seizures. The therapy also causes bone pain or discomfort. Although Dr. Borckardt characterized TMS as "reasonably safe," tDCS is a considerably safer procedure because it doesn’t depolarize neurons and thus doesn’t cause seizures or other adverse effects.

It is also much easier to perform tDCS than TMS. Among other attractive features of the nonpharmacologic therapy is that electricity has no metabolite or other residue, the psychologist noted. But he was quick to add that research into the modern clinical applications of this technology is a recent development.

"We’re not really sure of the best way to do tDCS: the best targets, best intensities, best frequencies. But we’re getting there quickly," Dr. Borckardt said.

He reported having no financial conflicts.

NEW ORLEANS  – Noninvasive transcranial direct current stimulation of the pain-modulating areas of the cerebral cortex markedly reduced postoperative pain and opioid use in a randomized trial involving total knee arthroplasty recipients.

Transcranial direct current stimulation (tDCS), a novel and apparently safe form of neurostimulation for analgesia, also is in planned or ongoing clinical trials for various forms of chronic pain.

In tDCS, two saline-soaked electrodes are placed over different areas of the brain so that a 2.0 mA direct current can be run through the brain for about 20 minutes. This electrical current increases activity in one target area of the brain while decreasing activity in another. In the total knee arthroplasty study, for example, the cathode was placed over the right dorsolateral prefrontal cortex, and the anode was placed over the knee representation of the motor strip.

There is intense research interest in extending tDCS beyond the arena of pain control and exploring its potential for nonpharmacologic treatment of mood and anxiety disorders, according to Jeffrey J. Borckardt, Ph.D., a psychologist at the Medical University of South Carolina, Charleston.

"This whole area of minimally invasive brain stimulation technologies is growing rapidly. Psychotherapy changes the electrical patterns that are realized in the brain, as shown by good-quality functional MRI studies. And tDCS is another way to do that," he explained. "We’ve just started playing with an idea that has real interesting potential: If we can enhance cortical excitability in targeted brain regions and we also have an idea what we’re doing to brain regions with psychotherapy, we may be able to get a synergistic effect by combining these brain stimulation technologies with psychotherapy. Perhaps we can increase the longevity and even the intensity of the clinical impact we have."

He and his coinvestigators selected total knee arthroplasty for a pilot clinical trial of tDCS for acute pain because it’s one of the most frequently performed orthopedic surgeries and the postoperative pain is severe. Many patients experience continued marked pain despite opioids and nerve blocks. The result is slowed recovery, increased hospital length of stay, and difficulty in completing the recommended postop physical therapy program.

Dr. Borckardt reported on 40 patients undergoing unilateral total knee arthroplasty who were randomized to receive four 20-minute sessions of real or sham tDCS. The first session was immediately after the surgery, the second 4 hours later, the third on the morning of postoperative day 1, and the fourth that afternoon.

Subjects who received real tDCS used 44% less patient-controlled opioid analgesia during the first 48 hours post surgery. And despite having significantly fewer opioids on board, they rated their pain as significantly less than controls did: an average of 9 out of a possible 100 points on a visual analog scale, compared with 34 points in the sham tDCS group.

In an earlier randomized, sham-controlled pilot study of tDCS for postprocedural pain in 21 women undergoing endoscopic retrograde cholangiopancreatography for pancreatitis-related pain, the patients who received a single 20-minute session of real tDCS used an average of 22% less patient-controlled opioid analgesia (Gastrointest. Endosc. 2011;73:1158-64).

Transcranial direct current stimulation, like the much more extensively studied transcranial magnetic stimulation (TMS), falls under the heading of neurostimulatory therapies for pain control. All rely upon the gate theory of pain, which holds that bombarding pain-signaling pathways with stimuli prevents the pain signals from getting through.

The best-known neurostimulation technology is transcutaneous electrical nerve stimulation (TENS). Invasive neurostimulation technologies include spinal cord stimulation; vagus nerve stimulation, which is Food and Drug Administration–approved for treatment of both epilepsy and depression; and motor cortex stimulation, involving a small craniotomy and implantation of electrodes into the brain.

Dr. Borckardt and his South Carolina colleagues have been heavily involved in studies of both TMS and tDCS. These are noninvasive technologies in that they don’t entail implantation of electrodes or generators. Both can be performed on patients who are awake.

Transcranial magnetic stimulation uses a cone-shaped magnetic field generated by a figure-eight–shaped coil placed above the patient’s head. The magnetic field passes unimpeded through the hair and skull to depolarize neurons in a dime-sized target area. However, if the magnetic field intensity or frequency is too high, the therapy can induce seizures. The therapy also causes bone pain or discomfort. Although Dr. Borckardt characterized TMS as "reasonably safe," tDCS is a considerably safer procedure because it doesn’t depolarize neurons and thus doesn’t cause seizures or other adverse effects.

It is also much easier to perform tDCS than TMS. Among other attractive features of the nonpharmacologic therapy is that electricity has no metabolite or other residue, the psychologist noted. But he was quick to add that research into the modern clinical applications of this technology is a recent development.

"We’re not really sure of the best way to do tDCS: the best targets, best intensities, best frequencies. But we’re getting there quickly," Dr. Borckardt said.

He reported having no financial conflicts.

NEW ORLEANS  – Noninvasive transcranial direct current stimulation of the pain-modulating areas of the cerebral cortex markedly reduced postoperative pain and opioid use in a randomized trial involving total knee arthroplasty recipients.

Transcranial direct current stimulation (tDCS), a novel and apparently safe form of neurostimulation for analgesia, also is in planned or ongoing clinical trials for various forms of chronic pain.

In tDCS, two saline-soaked electrodes are placed over different areas of the brain so that a 2.0 mA direct current can be run through the brain for about 20 minutes. This electrical current increases activity in one target area of the brain while decreasing activity in another. In the total knee arthroplasty study, for example, the cathode was placed over the right dorsolateral prefrontal cortex, and the anode was placed over the knee representation of the motor strip.

There is intense research interest in extending tDCS beyond the arena of pain control and exploring its potential for nonpharmacologic treatment of mood and anxiety disorders, according to Jeffrey J. Borckardt, Ph.D., a psychologist at the Medical University of South Carolina, Charleston.

"This whole area of minimally invasive brain stimulation technologies is growing rapidly. Psychotherapy changes the electrical patterns that are realized in the brain, as shown by good-quality functional MRI studies. And tDCS is another way to do that," he explained. "We’ve just started playing with an idea that has real interesting potential: If we can enhance cortical excitability in targeted brain regions and we also have an idea what we’re doing to brain regions with psychotherapy, we may be able to get a synergistic effect by combining these brain stimulation technologies with psychotherapy. Perhaps we can increase the longevity and even the intensity of the clinical impact we have."

He and his coinvestigators selected total knee arthroplasty for a pilot clinical trial of tDCS for acute pain because it’s one of the most frequently performed orthopedic surgeries and the postoperative pain is severe. Many patients experience continued marked pain despite opioids and nerve blocks. The result is slowed recovery, increased hospital length of stay, and difficulty in completing the recommended postop physical therapy program.

Dr. Borckardt reported on 40 patients undergoing unilateral total knee arthroplasty who were randomized to receive four 20-minute sessions of real or sham tDCS. The first session was immediately after the surgery, the second 4 hours later, the third on the morning of postoperative day 1, and the fourth that afternoon.

Subjects who received real tDCS used 44% less patient-controlled opioid analgesia during the first 48 hours post surgery. And despite having significantly fewer opioids on board, they rated their pain as significantly less than controls did: an average of 9 out of a possible 100 points on a visual analog scale, compared with 34 points in the sham tDCS group.

In an earlier randomized, sham-controlled pilot study of tDCS for postprocedural pain in 21 women undergoing endoscopic retrograde cholangiopancreatography for pancreatitis-related pain, the patients who received a single 20-minute session of real tDCS used an average of 22% less patient-controlled opioid analgesia (Gastrointest. Endosc. 2011;73:1158-64).

Transcranial direct current stimulation, like the much more extensively studied transcranial magnetic stimulation (TMS), falls under the heading of neurostimulatory therapies for pain control. All rely upon the gate theory of pain, which holds that bombarding pain-signaling pathways with stimuli prevents the pain signals from getting through.

The best-known neurostimulation technology is transcutaneous electrical nerve stimulation (TENS). Invasive neurostimulation technologies include spinal cord stimulation; vagus nerve stimulation, which is Food and Drug Administration–approved for treatment of both epilepsy and depression; and motor cortex stimulation, involving a small craniotomy and implantation of electrodes into the brain.

Dr. Borckardt and his South Carolina colleagues have been heavily involved in studies of both TMS and tDCS. These are noninvasive technologies in that they don’t entail implantation of electrodes or generators. Both can be performed on patients who are awake.

Transcranial magnetic stimulation uses a cone-shaped magnetic field generated by a figure-eight–shaped coil placed above the patient’s head. The magnetic field passes unimpeded through the hair and skull to depolarize neurons in a dime-sized target area. However, if the magnetic field intensity or frequency is too high, the therapy can induce seizures. The therapy also causes bone pain or discomfort. Although Dr. Borckardt characterized TMS as "reasonably safe," tDCS is a considerably safer procedure because it doesn’t depolarize neurons and thus doesn’t cause seizures or other adverse effects.

It is also much easier to perform tDCS than TMS. Among other attractive features of the nonpharmacologic therapy is that electricity has no metabolite or other residue, the psychologist noted. But he was quick to add that research into the modern clinical applications of this technology is a recent development.

"We’re not really sure of the best way to do tDCS: the best targets, best intensities, best frequencies. But we’re getting there quickly," Dr. Borckardt said.

He reported having no financial conflicts.

NEW ORLEANS – Excessive daytime sleepiness in patients with obstructive sleep apnea remains a common and often debilitating problem, despite optimal use of continuous positive airway pressure treatment, according to Dr. Janine R.E. Vintch.

The two drugs most beneficial as adjunctive therapy for these patients are modafinil (Provigil) and armodafinil (Nuvigil). Both are approved by the Food and Drug Administration for the management of persistent sleepiness and fatigue in patients with sleep apnea who are compliant with their CPAP therapy, Dr. Vintch said at the annual meeting of the American College of Physicians.

In one study, 22% of patients with obstructive sleep apnea using effective CPAP – that is, CPAP for more than 6 hours per night – still had impaired daytime functioning because of excessive daytime sleepiness documented on objective tests, including the Multiple Sleep Latency Test. This persistent daytime somnolence can manifest as cognitive impairment, diminished vigilance, and increased rates of workplace and motor vehicle accidents.

Before turning to drug therapy, however, it’s crucial to rule out other causes of persistent daytime sleepiness. The No. 1 reason is the patient is less adherent to CPAP than claimed. Other possible explanations include an improperly fitting CPAP mask, poor sleep hygiene, depression, and additional sleep disorders, such as restless legs, said Dr. Vintch of the University of California, Los Angeles.

Modafinil is a novel wake-promoting agent approved in 2004 for the management of residual sleepiness in CPAP-compliant patients. In 2006 the American Academy of Sleep Medicine published a practice parameter on the medical therapy of obstructive sleep apnea that endorsed modafinil as a standard recommendation for this indication (Sleep 2006;29:1031-5). It has a low abuse potential. Its mechanism of action remains controversial. Modafinil is cleared by both the liver and kidneys, so lower doses are appropriate in patients with either hepatic or renal dysfunction.

Modafinil has several important interactions with other drugs. These medications include propranolol, diltiazem, phenytoin, carbamazepine, and diazepam; the levels of all these drugs are increased in patients on modafinil. Also, women of childbearing age who are on ethinyl estradiol need to be given an alternative method of contraception, she said.

The most common side effects attributed to modafinil are headache, nausea, and nervousness. The headaches typically disappear after the first 3 days of treatment.

Armodafinil is the R-isomer of modafinil. Its 10- to 15-hour half-life is slightly longer than modafinil’s. It has the same side effects as modafinil.

Long-term studies of both drugs have documented good safety and tolerability along with improved objective and subjective measures of wakefulness and cognition.

Dr. Vintch reported having no relevant financial relationships.

NEW ORLEANS – Excessive daytime sleepiness in patients with obstructive sleep apnea remains a common and often debilitating problem, despite optimal use of continuous positive airway pressure treatment, according to Dr. Janine R.E. Vintch.

The two drugs most beneficial as adjunctive therapy for these patients are modafinil (Provigil) and armodafinil (Nuvigil). Both are approved by the Food and Drug Administration for the management of persistent sleepiness and fatigue in patients with sleep apnea who are compliant with their CPAP therapy, Dr. Vintch said at the annual meeting of the American College of Physicians.

In one study, 22% of patients with obstructive sleep apnea using effective CPAP – that is, CPAP for more than 6 hours per night – still had impaired daytime functioning because of excessive daytime sleepiness documented on objective tests, including the Multiple Sleep Latency Test. This persistent daytime somnolence can manifest as cognitive impairment, diminished vigilance, and increased rates of workplace and motor vehicle accidents.

Before turning to drug therapy, however, it’s crucial to rule out other causes of persistent daytime sleepiness. The No. 1 reason is the patient is less adherent to CPAP than claimed. Other possible explanations include an improperly fitting CPAP mask, poor sleep hygiene, depression, and additional sleep disorders, such as restless legs, said Dr. Vintch of the University of California, Los Angeles.

Modafinil is a novel wake-promoting agent approved in 2004 for the management of residual sleepiness in CPAP-compliant patients. In 2006 the American Academy of Sleep Medicine published a practice parameter on the medical therapy of obstructive sleep apnea that endorsed modafinil as a standard recommendation for this indication (Sleep 2006;29:1031-5). It has a low abuse potential. Its mechanism of action remains controversial. Modafinil is cleared by both the liver and kidneys, so lower doses are appropriate in patients with either hepatic or renal dysfunction.

Modafinil has several important interactions with other drugs. These medications include propranolol, diltiazem, phenytoin, carbamazepine, and diazepam; the levels of all these drugs are increased in patients on modafinil. Also, women of childbearing age who are on ethinyl estradiol need to be given an alternative method of contraception, she said.

The most common side effects attributed to modafinil are headache, nausea, and nervousness. The headaches typically disappear after the first 3 days of treatment.

Armodafinil is the R-isomer of modafinil. Its 10- to 15-hour half-life is slightly longer than modafinil’s. It has the same side effects as modafinil.

Long-term studies of both drugs have documented good safety and tolerability along with improved objective and subjective measures of wakefulness and cognition.

Dr. Vintch reported having no relevant financial relationships.

NEW ORLEANS – Excessive daytime sleepiness in patients with obstructive sleep apnea remains a common and often debilitating problem, despite optimal use of continuous positive airway pressure treatment, according to Dr. Janine R.E. Vintch.

The two drugs most beneficial as adjunctive therapy for these patients are modafinil (Provigil) and armodafinil (Nuvigil). Both are approved by the Food and Drug Administration for the management of persistent sleepiness and fatigue in patients with sleep apnea who are compliant with their CPAP therapy, Dr. Vintch said at the annual meeting of the American College of Physicians.

In one study, 22% of patients with obstructive sleep apnea using effective CPAP – that is, CPAP for more than 6 hours per night – still had impaired daytime functioning because of excessive daytime sleepiness documented on objective tests, including the Multiple Sleep Latency Test. This persistent daytime somnolence can manifest as cognitive impairment, diminished vigilance, and increased rates of workplace and motor vehicle accidents.

Before turning to drug therapy, however, it’s crucial to rule out other causes of persistent daytime sleepiness. The No. 1 reason is the patient is less adherent to CPAP than claimed. Other possible explanations include an improperly fitting CPAP mask, poor sleep hygiene, depression, and additional sleep disorders, such as restless legs, said Dr. Vintch of the University of California, Los Angeles.

Modafinil is a novel wake-promoting agent approved in 2004 for the management of residual sleepiness in CPAP-compliant patients. In 2006 the American Academy of Sleep Medicine published a practice parameter on the medical therapy of obstructive sleep apnea that endorsed modafinil as a standard recommendation for this indication (Sleep 2006;29:1031-5). It has a low abuse potential. Its mechanism of action remains controversial. Modafinil is cleared by both the liver and kidneys, so lower doses are appropriate in patients with either hepatic or renal dysfunction.

Modafinil has several important interactions with other drugs. These medications include propranolol, diltiazem, phenytoin, carbamazepine, and diazepam; the levels of all these drugs are increased in patients on modafinil. Also, women of childbearing age who are on ethinyl estradiol need to be given an alternative method of contraception, she said.

The most common side effects attributed to modafinil are headache, nausea, and nervousness. The headaches typically disappear after the first 3 days of treatment.

Armodafinil is the R-isomer of modafinil. Its 10- to 15-hour half-life is slightly longer than modafinil’s. It has the same side effects as modafinil.

Long-term studies of both drugs have documented good safety and tolerability along with improved objective and subjective measures of wakefulness and cognition.

Dr. Vintch reported having no relevant financial relationships.

NEW ORLEANS – Both probiotics and antibiotics can be considered legitimate, evidence-based treatments for irritable bowel syndrome.

The gut flora of patients with irritable bowel syndrome (IBS) differs both quantitatively and qualitatively from that of unaffected individuals. The proposed mechanism of the demonstrated benefit for probiotics and antibiotics lies in the controversial notion that bacterial overgrowth in the small intestines may account for some cases of IBS.

"The thought is that if you can restore a balanced intestinal flora in somebody with IBS, you may be able to eliminate the symptoms. So a better biome may mean a better life," explained Cmdr. Patrick E. Young, USN, a gastroenterologist at Walter Reed National Military Medical Center in Bethesda, Md.

By far the best-studied probiotic in the treatment of IBS is Bifidobacterium infantis. It is supported by "very powerful" data showing reductions in bloating, abdominal pain, and passing of gas, as well as easing of bowel movement difficulty and normalization of aberrant peripheral cytokine levels, according to Dr. Young.

The effective dose as demonstrated in a 362-patient, multicenter, randomized trial is 1 × 10⁸ CFU/mL (Am. J. Gastroenterol. 2006;101:1581-90). Bifidobacterium infantis is commercially available as a nutritional supplement in fortified yogurt or in capsule form. Long-term efficacy data are lacking, but the probiotic is devoid of significant side effects, the gastroenterologist said.

He noted that a recent meta-analysis concluded that oral rifaximin (Xifaxan) provides significant short-term relief of bloating as well as improved global quality of life scores in patients with IBS. The meta-analysis included five randomized, placebo-controlled clinical trials with a total of 1,803 patients. The number needed to treat was roughly 10 for both outcomes. The outcomes were better in older female patients.

The investigators characterized the 10% therapeutic gain over placebo as "modest" and similar to that provided by other accepted therapies for IBS (Am. J. Gastroenterol. 2012;107:28-35).

To this Dr. Young added his own caveat: The longest study of rifaximin followed patients for only 12 weeks.

"I would caution you in using antibiotics for a benign, incurable condition in general. These typically 20- to 30-year-old patients are going to live for another 40-50 years with the consequences of repetitive antibiotic exposure. This is a relatively new agent, and we don’t know what the long-term effect is going to be. That being said, there have been cases where I have used this with some success," Dr. Young said.

The standard dosing is 550 mg TID for 14 days, he said.

Dr. Young reported having no financial conflicts.

NEW ORLEANS – Both probiotics and antibiotics can be considered legitimate, evidence-based treatments for irritable bowel syndrome.

The gut flora of patients with irritable bowel syndrome (IBS) differs both quantitatively and qualitatively from that of unaffected individuals. The proposed mechanism of the demonstrated benefit for probiotics and antibiotics lies in the controversial notion that bacterial overgrowth in the small intestines may account for some cases of IBS.

"The thought is that if you can restore a balanced intestinal flora in somebody with IBS, you may be able to eliminate the symptoms. So a better biome may mean a better life," explained Cmdr. Patrick E. Young, USN, a gastroenterologist at Walter Reed National Military Medical Center in Bethesda, Md.

By far the best-studied probiotic in the treatment of IBS is Bifidobacterium infantis. It is supported by "very powerful" data showing reductions in bloating, abdominal pain, and passing of gas, as well as easing of bowel movement difficulty and normalization of aberrant peripheral cytokine levels, according to Dr. Young.

The effective dose as demonstrated in a 362-patient, multicenter, randomized trial is 1 × 10⁸ CFU/mL (Am. J. Gastroenterol. 2006;101:1581-90). Bifidobacterium infantis is commercially available as a nutritional supplement in fortified yogurt or in capsule form. Long-term efficacy data are lacking, but the probiotic is devoid of significant side effects, the gastroenterologist said.

He noted that a recent meta-analysis concluded that oral rifaximin (Xifaxan) provides significant short-term relief of bloating as well as improved global quality of life scores in patients with IBS. The meta-analysis included five randomized, placebo-controlled clinical trials with a total of 1,803 patients. The number needed to treat was roughly 10 for both outcomes. The outcomes were better in older female patients.

The investigators characterized the 10% therapeutic gain over placebo as "modest" and similar to that provided by other accepted therapies for IBS (Am. J. Gastroenterol. 2012;107:28-35).

To this Dr. Young added his own caveat: The longest study of rifaximin followed patients for only 12 weeks.

"I would caution you in using antibiotics for a benign, incurable condition in general. These typically 20- to 30-year-old patients are going to live for another 40-50 years with the consequences of repetitive antibiotic exposure. This is a relatively new agent, and we don’t know what the long-term effect is going to be. That being said, there have been cases where I have used this with some success," Dr. Young said.

The standard dosing is 550 mg TID for 14 days, he said.

Dr. Young reported having no financial conflicts.

NEW ORLEANS – Both probiotics and antibiotics can be considered legitimate, evidence-based treatments for irritable bowel syndrome.

The gut flora of patients with irritable bowel syndrome (IBS) differs both quantitatively and qualitatively from that of unaffected individuals. The proposed mechanism of the demonstrated benefit for probiotics and antibiotics lies in the controversial notion that bacterial overgrowth in the small intestines may account for some cases of IBS.

"The thought is that if you can restore a balanced intestinal flora in somebody with IBS, you may be able to eliminate the symptoms. So a better biome may mean a better life," explained Cmdr. Patrick E. Young, USN, a gastroenterologist at Walter Reed National Military Medical Center in Bethesda, Md.

By far the best-studied probiotic in the treatment of IBS is Bifidobacterium infantis. It is supported by "very powerful" data showing reductions in bloating, abdominal pain, and passing of gas, as well as easing of bowel movement difficulty and normalization of aberrant peripheral cytokine levels, according to Dr. Young.

The effective dose as demonstrated in a 362-patient, multicenter, randomized trial is 1 × 10⁸ CFU/mL (Am. J. Gastroenterol. 2006;101:1581-90). Bifidobacterium infantis is commercially available as a nutritional supplement in fortified yogurt or in capsule form. Long-term efficacy data are lacking, but the probiotic is devoid of significant side effects, the gastroenterologist said.

He noted that a recent meta-analysis concluded that oral rifaximin (Xifaxan) provides significant short-term relief of bloating as well as improved global quality of life scores in patients with IBS. The meta-analysis included five randomized, placebo-controlled clinical trials with a total of 1,803 patients. The number needed to treat was roughly 10 for both outcomes. The outcomes were better in older female patients.

The investigators characterized the 10% therapeutic gain over placebo as "modest" and similar to that provided by other accepted therapies for IBS (Am. J. Gastroenterol. 2012;107:28-35).

To this Dr. Young added his own caveat: The longest study of rifaximin followed patients for only 12 weeks.

"I would caution you in using antibiotics for a benign, incurable condition in general. These typically 20- to 30-year-old patients are going to live for another 40-50 years with the consequences of repetitive antibiotic exposure. This is a relatively new agent, and we don’t know what the long-term effect is going to be. That being said, there have been cases where I have used this with some success," Dr. Young said.

The standard dosing is 550 mg TID for 14 days, he said.

Dr. Young reported having no financial conflicts.

NEW ORLEANS – Patient visits involving prescription of opiates for chronic pain can be among the most cringe-producing encounters in primary care medicine.

These visits place physicians in the difficult position of determining whether a patient is lying or in chronic pain, said Dr. Barak Gaster, a general internist at the University of Washington, Seattle.

The goal is to help slow the arc of the pendulum of opiate prescribing. Fueled by recent reports of overdose deaths from opiates being greater than those from heroin and cocaine combined, the pendulum is rapidly swinging away from a period of overprescribing, which fed the nation’s huge prescription drug misuse problem, and is now headed back towards undertreatment of chronic pain.

"I think if we all get too freaked out by the [risk of] fatal overdoses and too frustrated by what a difficult area this is, more and more doctors will say, ‘I just don’t [prescribe opiates] anymore.’ And that would be a shame because there are definitely people who benefit from being on chronic opiates," he said at the annual meeting of the American College of Physicians.

A few practical tools make opiate prescribing safer and more efficient in a busy primary care practice, according to Dr. Gaster. Here are his recommendations for safer, more manageable opiate prescribing:

Establish a clear upper limit on dosing: An upper limit is, quite simply, the most important thing physicians can do to limit inappropriate opiate prescribing. The epidemiologic literature indicates that the risk of unintentional fatal overdose jumps at more than 120 milliequivalents of morphine per day, a value that "exceeds my comfort zone," Dr. Gaster said. But wherever the line is drawn – say, 60 or 80 milliequivalents per day – stay the course no matter what the patient says.

"What little research has been done in this area suggests that opiates have mild to moderate efficacy for chronic pain, that very low doses are about as likely to work as very high doses, and that in situations where you’re not achieving adequate pain control at lower doses the idea that you can just go to higher and higher doses is wrong and you’ll end up causing harm," he said.

The notion that dosing should continue to increase until pain control is achieved is appropriate for cancer pain, which is the setting where most physicians-in-training learned to use opiates, but it’s all wrong for noncancer chronic pain, he noted.

Have your patter down: Physicians need to have a pre-rehearsed response in mind for when they walk into the examination room and patients say that the maximum dose isn’t getting the job done. That ready-made response will keep the office visit moving briskly along. Here’s what Dr. Gaster suggested: "Honestly, I don’t believe that higher doses would be safe for you. This is the maximum dose that I feel comfortable prescribing in a safe way."

Make smart use of written care agreements: Many physicians try to list every possible aberrant behavior and transgression in the care agreement. That’s a mistake, Dr. Gaster said. The document ends up becoming a multipage contract, and nobody except lawyers read multipage contracts. Keep the agreement short.

"The main value of a care agreement is to quickly communicate what the rules of opiate prescribing are in your clinic. If you’ve effectively communicated those rules and patients are not able to follow them, that is when you have actionable information to identify those at high risk for prescription drug abuse," he explained. "If you’re confident that you’ve been clear, and yet the rules aren’t being followed, that’s when you can feel okay about saying, ‘This isn’t safe. It needs to stop.’ "

To be an effective communication tool, the care agreement needs to say that the medication cannot be refilled early, refills are done by clinic appointment only, and appointments for refills must be requested at least two business days in advance. Also, lost or stolen medications can’t be refilled.

"The number of lost or stolen opioid scripts, compared to the number of lost or stolen blood pressure medication scripts, is pretty impressive," he noted. "You have to be up front with people and say, ‘This bottle of pills is like cash and if you lose it I can’t replace it.’ "

The clear message must be that failure to follow these rules will result in discontinuation of opiates.

And don’t simply tuck the signed care agreement away in the patient’s file.

"Repeating what the rules of opiate prescribing are in your clinic at least two, three, or even four times on different occasions is absolutely essential, just so that you feel really confident that the patient got the message," Dr. Gaster continued.

Keep track of red flags for prescription drug misuse in one place in the patient’s file: That’s how to prevent signs of a pattern of problematic behavior from slipping through the cracks. One major red flag is a history of substance abuse.

"It’s super important to at least ask about alcohol or substance abuse and document it in the chart, recognizing that you may not get an honest answer," Dr. Gaster advised.

"Anyone with a history of substance abuse should be treated with opiates for bad somatic pain only with extreme caution. The risk of prescription drug abuse in someone who has a history of substance abuse is dramatically higher. This is a completely different class of prescribing. It’s hard to say such people should never be on chronic opiates, but a much, much higher level of caution is required," he said.

As for patients with an ongoing substance abuse problem who also have obvious severe somatic pain, on balance the risk of harm in prescribing chronic opiates exceeds the potential benefit.

"These are terrible situations. I’d say primary care doctors shouldn’t be doing this at all. Such patients should be offered a referral for substance abuse treatment," he said.

Hepatitis C infection is another major red flag because it’s an important epidemiologic indicator of past illicit drug use.

Use a urine toxicology screen: An "absolutely essential part of the tool kit" because it’s the only source of hard data regarding whether a patient is abusing or diverting prescription drugs. Do it randomly but fairly frequently, and let the patient know that any time a urine screen is ordered, leaving the clinic without providing a urine sample that day will be considered tantamount to a positive test and will result in discontinuation of opiate therapy.

"If you were to pick out the one thing on a urine toxicology screen that’s most informative, I’d say it’s a positive result for cocaine. Cocaine use has a very, very high correlation with prescription drug abuse, and there are virtually no false-positive results for cocaine," the internist said.

In contrast, false-positive results for amphetamines are a real problem. The ELISA assay for amphetamines turns out to have cross-reactivity with at least 20 prescription drugs, including bupropion, phenergan, and legitimate medications for attention-deficit/hyperactivity disorder. Having the lab run a gas chromatography test will differentiate prescription stimulant medications from illicit street amphetamines.

Another key point about urine toxicology screens is they don’t reliably detect synthetic opiates such as fentanyl, or semisynthetic opiates such as oxycodone.

"Patients taking oxycodone may very well have a negative toxicology result, so you always need to make sure to order a separate oxycodone assay as part of your toxicology screen," he advised.

Also, before bringing up the need for a urine screen that very day, be sure to ask when the patient took his last opiate pill. That will be most helpful in interpreting a negative result.

For patients on dialysis who are anuric, use serum drug testing.

Utilize the statewide prescription monitoring system: It’s an essential tool for detection of patients who are sneaking around and obtaining opiate prescriptions from multiple physicians and then selling them.

"The giant street market for prescription opiates is, to some extent, happening from pharmacies and warehouses being robbed, but the vast majority of those pills are coming from doctors’ offices," Dr. Gaster noted.

Stop chronic opiates in response to red flags: This is one of the most difficult and emotion-charged interactions that occur between physicians and patients. "I rank it right up there with having to deliver a cancer diagnosis," Dr. Gaster said.

Patients seldom take this news well, so it’s a good idea to practice this straightforward phrasing beforehand: "In my medical opinion, this type of pain medication is simply not safe for you and I cannot prescribe it for you anymore."

To avoid legal and ethical problems, it’s important to emphasize that patients are not being fired or abandoned. Explain that you’re willing to continue as the patient’s physician, but not in prescribing opiates, he said.

Dr. Gaster reported having no financial conflicts.

NEW ORLEANS – Patient visits involving prescription of opiates for chronic pain can be among the most cringe-producing encounters in primary care medicine.

These visits place physicians in the difficult position of determining whether a patient is lying or in chronic pain, said Dr. Barak Gaster, a general internist at the University of Washington, Seattle.

The goal is to help slow the arc of the pendulum of opiate prescribing. Fueled by recent reports of overdose deaths from opiates being greater than those from heroin and cocaine combined, the pendulum is rapidly swinging away from a period of overprescribing, which fed the nation’s huge prescription drug misuse problem, and is now headed back towards undertreatment of chronic pain.

"I think if we all get too freaked out by the [risk of] fatal overdoses and too frustrated by what a difficult area this is, more and more doctors will say, ‘I just don’t [prescribe opiates] anymore.’ And that would be a shame because there are definitely people who benefit from being on chronic opiates," he said at the annual meeting of the American College of Physicians.

A few practical tools make opiate prescribing safer and more efficient in a busy primary care practice, according to Dr. Gaster. Here are his recommendations for safer, more manageable opiate prescribing:

Establish a clear upper limit on dosing: An upper limit is, quite simply, the most important thing physicians can do to limit inappropriate opiate prescribing. The epidemiologic literature indicates that the risk of unintentional fatal overdose jumps at more than 120 milliequivalents of morphine per day, a value that "exceeds my comfort zone," Dr. Gaster said. But wherever the line is drawn – say, 60 or 80 milliequivalents per day – stay the course no matter what the patient says.

"What little research has been done in this area suggests that opiates have mild to moderate efficacy for chronic pain, that very low doses are about as likely to work as very high doses, and that in situations where you’re not achieving adequate pain control at lower doses the idea that you can just go to higher and higher doses is wrong and you’ll end up causing harm," he said.

The notion that dosing should continue to increase until pain control is achieved is appropriate for cancer pain, which is the setting where most physicians-in-training learned to use opiates, but it’s all wrong for noncancer chronic pain, he noted.

Have your patter down: Physicians need to have a pre-rehearsed response in mind for when they walk into the examination room and patients say that the maximum dose isn’t getting the job done. That ready-made response will keep the office visit moving briskly along. Here’s what Dr. Gaster suggested: "Honestly, I don’t believe that higher doses would be safe for you. This is the maximum dose that I feel comfortable prescribing in a safe way."

Make smart use of written care agreements: Many physicians try to list every possible aberrant behavior and transgression in the care agreement. That’s a mistake, Dr. Gaster said. The document ends up becoming a multipage contract, and nobody except lawyers read multipage contracts. Keep the agreement short.

"The main value of a care agreement is to quickly communicate what the rules of opiate prescribing are in your clinic. If you’ve effectively communicated those rules and patients are not able to follow them, that is when you have actionable information to identify those at high risk for prescription drug abuse," he explained. "If you’re confident that you’ve been clear, and yet the rules aren’t being followed, that’s when you can feel okay about saying, ‘This isn’t safe. It needs to stop.’ "

To be an effective communication tool, the care agreement needs to say that the medication cannot be refilled early, refills are done by clinic appointment only, and appointments for refills must be requested at least two business days in advance. Also, lost or stolen medications can’t be refilled.

"The number of lost or stolen opioid scripts, compared to the number of lost or stolen blood pressure medication scripts, is pretty impressive," he noted. "You have to be up front with people and say, ‘This bottle of pills is like cash and if you lose it I can’t replace it.’ "

The clear message must be that failure to follow these rules will result in discontinuation of opiates.

And don’t simply tuck the signed care agreement away in the patient’s file.

"Repeating what the rules of opiate prescribing are in your clinic at least two, three, or even four times on different occasions is absolutely essential, just so that you feel really confident that the patient got the message," Dr. Gaster continued.

Keep track of red flags for prescription drug misuse in one place in the patient’s file: That’s how to prevent signs of a pattern of problematic behavior from slipping through the cracks. One major red flag is a history of substance abuse.

"It’s super important to at least ask about alcohol or substance abuse and document it in the chart, recognizing that you may not get an honest answer," Dr. Gaster advised.

"Anyone with a history of substance abuse should be treated with opiates for bad somatic pain only with extreme caution. The risk of prescription drug abuse in someone who has a history of substance abuse is dramatically higher. This is a completely different class of prescribing. It’s hard to say such people should never be on chronic opiates, but a much, much higher level of caution is required," he said.

As for patients with an ongoing substance abuse problem who also have obvious severe somatic pain, on balance the risk of harm in prescribing chronic opiates exceeds the potential benefit.

"These are terrible situations. I’d say primary care doctors shouldn’t be doing this at all. Such patients should be offered a referral for substance abuse treatment," he said.

Hepatitis C infection is another major red flag because it’s an important epidemiologic indicator of past illicit drug use.

Use a urine toxicology screen: An "absolutely essential part of the tool kit" because it’s the only source of hard data regarding whether a patient is abusing or diverting prescription drugs. Do it randomly but fairly frequently, and let the patient know that any time a urine screen is ordered, leaving the clinic without providing a urine sample that day will be considered tantamount to a positive test and will result in discontinuation of opiate therapy.

"If you were to pick out the one thing on a urine toxicology screen that’s most informative, I’d say it’s a positive result for cocaine. Cocaine use has a very, very high correlation with prescription drug abuse, and there are virtually no false-positive results for cocaine," the internist said.

In contrast, false-positive results for amphetamines are a real problem. The ELISA assay for amphetamines turns out to have cross-reactivity with at least 20 prescription drugs, including bupropion, phenergan, and legitimate medications for attention-deficit/hyperactivity disorder. Having the lab run a gas chromatography test will differentiate prescription stimulant medications from illicit street amphetamines.

Another key point about urine toxicology screens is they don’t reliably detect synthetic opiates such as fentanyl, or semisynthetic opiates such as oxycodone.

"Patients taking oxycodone may very well have a negative toxicology result, so you always need to make sure to order a separate oxycodone assay as part of your toxicology screen," he advised.

Also, before bringing up the need for a urine screen that very day, be sure to ask when the patient took his last opiate pill. That will be most helpful in interpreting a negative result.

For patients on dialysis who are anuric, use serum drug testing.

Utilize the statewide prescription monitoring system: It’s an essential tool for detection of patients who are sneaking around and obtaining opiate prescriptions from multiple physicians and then selling them.

"The giant street market for prescription opiates is, to some extent, happening from pharmacies and warehouses being robbed, but the vast majority of those pills are coming from doctors’ offices," Dr. Gaster noted.

Stop chronic opiates in response to red flags: This is one of the most difficult and emotion-charged interactions that occur between physicians and patients. "I rank it right up there with having to deliver a cancer diagnosis," Dr. Gaster said.

Patients seldom take this news well, so it’s a good idea to practice this straightforward phrasing beforehand: "In my medical opinion, this type of pain medication is simply not safe for you and I cannot prescribe it for you anymore."

To avoid legal and ethical problems, it’s important to emphasize that patients are not being fired or abandoned. Explain that you’re willing to continue as the patient’s physician, but not in prescribing opiates, he said.

Dr. Gaster reported having no financial conflicts.

NEW ORLEANS – Patient visits involving prescription of opiates for chronic pain can be among the most cringe-producing encounters in primary care medicine.

These visits place physicians in the difficult position of determining whether a patient is lying or in chronic pain, said Dr. Barak Gaster, a general internist at the University of Washington, Seattle.

The goal is to help slow the arc of the pendulum of opiate prescribing. Fueled by recent reports of overdose deaths from opiates being greater than those from heroin and cocaine combined, the pendulum is rapidly swinging away from a period of overprescribing, which fed the nation’s huge prescription drug misuse problem, and is now headed back towards undertreatment of chronic pain.

"I think if we all get too freaked out by the [risk of] fatal overdoses and too frustrated by what a difficult area this is, more and more doctors will say, ‘I just don’t [prescribe opiates] anymore.’ And that would be a shame because there are definitely people who benefit from being on chronic opiates," he said at the annual meeting of the American College of Physicians.

A few practical tools make opiate prescribing safer and more efficient in a busy primary care practice, according to Dr. Gaster. Here are his recommendations for safer, more manageable opiate prescribing:

Establish a clear upper limit on dosing: An upper limit is, quite simply, the most important thing physicians can do to limit inappropriate opiate prescribing. The epidemiologic literature indicates that the risk of unintentional fatal overdose jumps at more than 120 milliequivalents of morphine per day, a value that "exceeds my comfort zone," Dr. Gaster said. But wherever the line is drawn – say, 60 or 80 milliequivalents per day – stay the course no matter what the patient says.

"What little research has been done in this area suggests that opiates have mild to moderate efficacy for chronic pain, that very low doses are about as likely to work as very high doses, and that in situations where you’re not achieving adequate pain control at lower doses the idea that you can just go to higher and higher doses is wrong and you’ll end up causing harm," he said.

The notion that dosing should continue to increase until pain control is achieved is appropriate for cancer pain, which is the setting where most physicians-in-training learned to use opiates, but it’s all wrong for noncancer chronic pain, he noted.

Have your patter down: Physicians need to have a pre-rehearsed response in mind for when they walk into the examination room and patients say that the maximum dose isn’t getting the job done. That ready-made response will keep the office visit moving briskly along. Here’s what Dr. Gaster suggested: "Honestly, I don’t believe that higher doses would be safe for you. This is the maximum dose that I feel comfortable prescribing in a safe way."

Make smart use of written care agreements: Many physicians try to list every possible aberrant behavior and transgression in the care agreement. That’s a mistake, Dr. Gaster said. The document ends up becoming a multipage contract, and nobody except lawyers read multipage contracts. Keep the agreement short.

"The main value of a care agreement is to quickly communicate what the rules of opiate prescribing are in your clinic. If you’ve effectively communicated those rules and patients are not able to follow them, that is when you have actionable information to identify those at high risk for prescription drug abuse," he explained. "If you’re confident that you’ve been clear, and yet the rules aren’t being followed, that’s when you can feel okay about saying, ‘This isn’t safe. It needs to stop.’ "

To be an effective communication tool, the care agreement needs to say that the medication cannot be refilled early, refills are done by clinic appointment only, and appointments for refills must be requested at least two business days in advance. Also, lost or stolen medications can’t be refilled.

"The number of lost or stolen opioid scripts, compared to the number of lost or stolen blood pressure medication scripts, is pretty impressive," he noted. "You have to be up front with people and say, ‘This bottle of pills is like cash and if you lose it I can’t replace it.’ "

The clear message must be that failure to follow these rules will result in discontinuation of opiates.

And don’t simply tuck the signed care agreement away in the patient’s file.

"Repeating what the rules of opiate prescribing are in your clinic at least two, three, or even four times on different occasions is absolutely essential, just so that you feel really confident that the patient got the message," Dr. Gaster continued.

Keep track of red flags for prescription drug misuse in one place in the patient’s file: That’s how to prevent signs of a pattern of problematic behavior from slipping through the cracks. One major red flag is a history of substance abuse.

"It’s super important to at least ask about alcohol or substance abuse and document it in the chart, recognizing that you may not get an honest answer," Dr. Gaster advised.

"Anyone with a history of substance abuse should be treated with opiates for bad somatic pain only with extreme caution. The risk of prescription drug abuse in someone who has a history of substance abuse is dramatically higher. This is a completely different class of prescribing. It’s hard to say such people should never be on chronic opiates, but a much, much higher level of caution is required," he said.

As for patients with an ongoing substance abuse problem who also have obvious severe somatic pain, on balance the risk of harm in prescribing chronic opiates exceeds the potential benefit.

"These are terrible situations. I’d say primary care doctors shouldn’t be doing this at all. Such patients should be offered a referral for substance abuse treatment," he said.

Hepatitis C infection is another major red flag because it’s an important epidemiologic indicator of past illicit drug use.

Use a urine toxicology screen: An "absolutely essential part of the tool kit" because it’s the only source of hard data regarding whether a patient is abusing or diverting prescription drugs. Do it randomly but fairly frequently, and let the patient know that any time a urine screen is ordered, leaving the clinic without providing a urine sample that day will be considered tantamount to a positive test and will result in discontinuation of opiate therapy.

"If you were to pick out the one thing on a urine toxicology screen that’s most informative, I’d say it’s a positive result for cocaine. Cocaine use has a very, very high correlation with prescription drug abuse, and there are virtually no false-positive results for cocaine," the internist said.

In contrast, false-positive results for amphetamines are a real problem. The ELISA assay for amphetamines turns out to have cross-reactivity with at least 20 prescription drugs, including bupropion, phenergan, and legitimate medications for attention-deficit/hyperactivity disorder. Having the lab run a gas chromatography test will differentiate prescription stimulant medications from illicit street amphetamines.

Another key point about urine toxicology screens is they don’t reliably detect synthetic opiates such as fentanyl, or semisynthetic opiates such as oxycodone.

"Patients taking oxycodone may very well have a negative toxicology result, so you always need to make sure to order a separate oxycodone assay as part of your toxicology screen," he advised.

Also, before bringing up the need for a urine screen that very day, be sure to ask when the patient took his last opiate pill. That will be most helpful in interpreting a negative result.

For patients on dialysis who are anuric, use serum drug testing.

Utilize the statewide prescription monitoring system: It’s an essential tool for detection of patients who are sneaking around and obtaining opiate prescriptions from multiple physicians and then selling them.

"The giant street market for prescription opiates is, to some extent, happening from pharmacies and warehouses being robbed, but the vast majority of those pills are coming from doctors’ offices," Dr. Gaster noted.

Stop chronic opiates in response to red flags: This is one of the most difficult and emotion-charged interactions that occur between physicians and patients. "I rank it right up there with having to deliver a cancer diagnosis," Dr. Gaster said.

Patients seldom take this news well, so it’s a good idea to practice this straightforward phrasing beforehand: "In my medical opinion, this type of pain medication is simply not safe for you and I cannot prescribe it for you anymore."

To avoid legal and ethical problems, it’s important to emphasize that patients are not being fired or abandoned. Explain that you’re willing to continue as the patient’s physician, but not in prescribing opiates, he said.

Dr. Gaster reported having no financial conflicts.