Original Research

An antimicrobial stewardship program (ASP) is designed to provide guidance for the safe andcost-effective use of antimicrobial agents. This evidence-based approach addresses the correct selection of antimicrobial agents, dosages, routes of administration, and duration of therapy. In other words, the ASP necessitates the right drug, the right time, the right amount, and the right duration.¹ The ASP reduces the development of multidrug-resistant organisms (MDROs), adverse drug events (such as antibiotic-associated diarrhea and renal toxicity), hospital length of stay, collateral damage (development of Clostridium difficile colitis), and health care costs. Review of the literature has shown the ASP reduces hospital stays among patients with acute bacterial-skin and skin-structure infections along with other costly infections.² 

The ASP is not a new concept, but it is a hot topic. A successful ASP cannot be achieved without the support of the hospital leadership to determine and provide the needed resources. Its success stems from being a joint collaborative effort between pharmacy, medicine, infection control (IC), microbiology, and information technology. The purpose of the ASP is to ensure proper use of antimicrobials within the health care system through the development of a formal, interdisciplinary team. The primary goal of the ASP is to optimize clinical outcomes while minimizing unintended consequences related to antimicrobial usage, such as toxicities or the emergence of resistance. 

In today’s world, health care clinicians are dealing with a global challenge of MDROs such as Enterococcus faecium, Staphylococcus aureus (S aureus), Klebsiella pneumonia, Acinetobacter baumanii, Pseudomonas aeruginosa, and Enterobacter species (ESKAPE), better known as “bugs without borders.”³ According to the CDC, antibiotic-resistant infections affect at least 2 million people in the U.S. annually and result in > 23,000 deaths.² According to Thomas Frieden, director of the CDC, the pipeline of new antibiotics is nearly empty for the short term, and new drugs could be a decade away from discovery and approval by the FDA.²

Literature Review

Pasquale and colleagues conducted a retrospective, observational chart review on 62 patients who were admitted for bacterial-skin and skin-structure infections (S aureus, MRSA, MSSA, and Pseudomonas aeruginosa).⁴ The data examined patient demographic characteristics, comorbidities, specific type of skin infection (the most common being cellulitis, major or deep abscesses, and surgical site infections), microbiology, surgical interventions, and recommendations obtained from the ASP committee.

The primary goal of the antimicrobial stewardship program is to optimize clinical outcomes while minimizing unintended consequences related to antimicrobial usage, such as toxicities or the emergence of resistance.The ASP recommendations were divided into 5 categories, including dosage changes, de-escalation, antibiotic regimen changes, infectious disease (ID) consults, and other (not described). The ASP offered 85 recommendations, and acceptance of the ASP recommendations by physicians was 95%. The intervention group had a significantly lower length of stay (4.4 days vs 6.2 days, P < .001); and the 30-day all-cause readmission rate was also significantly lower (6.5% vs 16.71%, P = .05). However, the skin and skin-related structures readmission rate did not differ significantly (3.33% vs 6.27%). It was impossible for the investigators to determine exact differences in the amount of antimicrobials used in the intervention group vs the historical controls, because the historical data were based on ICD-9 codes, which may explain the nonsignificant finding.⁴

D’Agata reviewed the antimicrobial usage and ASP programs in dialysis centers.⁵ Chronic hemodialysis patients with central lines were noted to have the greatest rate of infections and antibiotic usage (6.4 per 100 patient months). The next highest group was dialysis patients with grafts (2.4 per 100 patient months), followed by patients with fistulas (1.8 per 100 patient months). Vancomycin was most commonly chosen for all antibiotic starts (73%). Interestingly, vancomycin was followed by cefazolin and third- and/or fourth-generation cephalosporin, which are risk factors for the emergence of multidrug-resistant, Gram-negative bacteria that are highly linked to increased morbidity and mortality rates. The U.S. Renal Data System stated in its 2009 report that the use of antibiotic therapy has increased from 31% in 1994 to 41% in 2007.⁵

In reviewing inappropriate choices of antimicrobial prescribing, D’Agata compared prescriptions given to the Healthcare Infection Control Practices Advisory Committee to determine whether the correct antibiotic was chosen. In 164 vancomycin prescriptions, 20% were categorized as inappropriate.⁵ In another study done by Zvonar and colleagues, 163 prescriptions of vancomycin were reviewed, and 12% were considered inappropriate.⁶

Snyder and colleagues examined 278 patients on hemodialysis, and over a 1-year period, 32% of these patients received ≥ 1 antimicrobial with 29.8% of the doses classified as inappropriate.⁷ The most common category for inappropriate prescribing of antimicrobials was not meeting the criteria for diagnosing infections (52.9% of cases). The second leading cause of inappropriate prescription for infections was not meeting criteria for diagnosing specific skin and skin-structure infections (51.6% of cases). Another common category was failure to choose a narrower spectrum antimicrobial prescription (26.8%).⁷ Attention to the indications and duration of antimicrobial treatment accounted for 20.3% of all inappropriate doses. Correction of these problems with use of an ASP could reduce the patient’s exposure to unneeded or inappropriate antibiotics by 22% to 36% and decrease hospital costs between $200,000 to $900,000.⁵

Rosa and colleagues discussed adherence to an ASP and the effects on mortality in hospitalized cancer patients with febrile neutropenia (FN).⁸ A prospective cohort study was performed in a single facility over a 2-year period. Patients admitted with cancer and FN were followed for 28 days. The mortality rates of those treated with ASP protocol antibiotics were compared with those treated with other antibiotic regimens. One hundred sixty-nine patients with 307 episodes of FN were included. The rate of adherence to ASP recommendations was 53% with the mortality of this cohort 9.4% (29 patients).⁸

Older patients were more likely to be treated according to ASP recommendations, whereas patients with comorbidities were not treated with ASP guidelines, Rosa and colleagues noted.⁸ No explanation was given, but statistical testing did uphold these findings, ensuring that the results were correctly interpreted. The 28-day mortality during FN was related to several factors, including nonadherence with ASP recommendations (P = .001) relapsing diseases stages (P = .001), and time to antibiotic start therapy > 1 hour (P = .001). Adherence to the ASP was independently associated with a higher survival rate (P = .03), whereas mortality was attributable to infection in all 29 patients who died.

Nowak and colleagues reviewed the clinical and economic benefits of an ASP using a pre- and postanalysis of potential patients who might benefit from recommendations of the ASP.⁹ Subjects included adult inpatients with pneumonia or abdominal sepsis. Recommendations from ASP that were followed decreased expenditures by 9.75% during the first year and remained stable in the following years. The cumulative cost savings was about $1.7 million. Rates of nosocomial infections decreased, and pre- and postcomparison of survival and lengths of stay for patients with pneumonia (n = 2,186) or abdominal sepsis (n = 225) revealed no significant differences. Investigators argued that this finding may have been due to the hospital’s initiation of other concurrent IC programs.

Doron and colleagues conducted a survey identifying characteristics of ASP practices and factors associated with the presence of an ASP.¹⁰ Surveys were received from 48 states (North and South Dakota were not included) and Puerto Rico. Surveys were received from 406 providers, and 96.4% identified some form of ASP. Barriers to implementation included staffing constraints (69.4%) and insufficient funding (0.6%).¹⁰

About 38% of the responses stated ASP was being used for adults and pediatric patients, whereas 58.8% were used for adults only.¹⁰ The ASP teams were composed of a variety of providers, including infectious disease (ID) physicians (70.7%), IC professionals (51.1%), and clinical microbiologists (38.6%). Additional barriers to implementing an ASP were found as insufficient medical staff buy-in (32.8%), not high on the priority list (22.2%), and too many other things to consider or deal with at the time (42.8%). Interestingly, 41.1% of the subjects in facilities without an ASP responded that providers agree with limiting the use of antimicrobials compared with 66.9% of subjects in hospitals with an ASP. Factors linked to having an ASP included having an ID consultation service, an ID fellowship program, an ID pharmacist, larger hospitals, annual admissions > 10,000, having a published antibiogram, and being a teaching hospital.

Establishment of an ASP

The Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA) issued guidelines in 2007 for developing an institutional ASP to enhance antimicrobial stewardship and help prevent antimicrobial resistance in hospitals.¹¹ The ASP may vary among facilities based on available resources.

When developing an ASP, 2 core strategies are necessary. The core measures are proactive and are usually conducted by an ID clinical pharmacist assigned to the ASP in collaboration with the ID physician. These strategies are not mutually exclusive and include a prospective audit with interventions provided to the clinicians, resulting in decreased inappropriate use of antimicrobials or a formulary restriction and preauthorization to help reduce antimicrobial usage and related cost.

Supplemental elements may be considered and prioritized as to the core antimicrobial stewardship strategies based on local practice pattern and resources.¹¹ Factors to consider include education, which is considered to be an essential element of the ASP. Although education is important, it alone is only somewhat effective in changing clinicians’ prescribing practices. Guidelines and clinical pathways are elements set forth in institutional management protocols for common and potentially serious infections such as intravascular catheter-related infections, hospital- and community-acquired pneumonia, bloodstream infections, and complicated urinary tract infections among other types.

Another consideration is antimicrobial cycling. This process refers to the specific schedule of alternating specific antimicrobials or antimicrobial classes to prevent or reverse the development of antimicrobial resistance. Insufficient data on antimicrobial cycling currently exist to affect major changes in practice. This element, however, could be implemented in certain institutions if needed based on the reported bacterial resistance pattern.

Antimicrobial order forms can be used to help monitor the implementation of formulated institutional clinical practice pathways. However, the authors feel that documenting this indication in the clinician notes may be adequate and save time for everyone involved; additionally, reviewing combination therapy, which if avoided, may prevent the emergence of resistance. Although combination therapy is needed in certain clinical diagnostic situations, careful consideration of its use is essential.

Using the appropriate antimicrobial dose based on the specific pathogen, patient characteristic, source of infection, along with the pharmacokinetic and pharmacodynamics should be reviewed to prevent antimicrobial overuse.Streamlining or de-escalation of therapy by using a narrower spectrum agent, based on culture and sensitivity results, prevents duplicative therapy with a patient when double coverage is not indicated or intended. Another goal is the discontinuation of therapy based on negative culture results and lack of supporting clinical signs and symptoms of infection. Dose optimization and adjustment should also be reviewed. Using the appropriate antimicrobial dose based on the specific pathogen, patient characteristic, source of infection, along with the pharmacokinetic and pharmacodynamics should be reviewed to prevent antimicrobial overuse and subsequent potentially avoidable adverse effects.

Parenteral to oral conversion from IV to oral administration (IV to oral) antimicrobials must be considered when the patient is clinically and hemodynamically stable, thus limiting the length of hospital stays and health care costs. However, it is important to keep in mind pharmacokinetic studies examining the bioavailability of antibiotics are usually conducted with healthy volunteers. Therefore, when treating patients who are elderly, on multiple medications, or severely ill, proper usage of these antibiotics is required. Also, having antibiotics with excellent bioavailability does not necessarily mean switching from IV to oral routes when treating serious infections such as bacteremia. Special consideration should be given when changing the route of administration. In addition, approval—or at least notification by the treating physician or ID specialist—should be included in the absence of an institutional policy, allowing for automatic IV to oral conversion.

The ASP Team

The participation of specific clinicians has been suggested as key to having a successful ASP team.¹² Members should include an ID physician (director) who serves as the lead physician and supervises the overall function of the ASP, makes recommendations to the ASP team, and contributes to the educational activities. A clinical ID pharmacist (codirector) provides suggestions to clinicians on preferred first-line antimicrobials and reviews medication orders for antimicrobials and resistance patterns, microbiological data, patient data, and clinical information. The codirector also tracks any ASP-related data and submits monitoring reports on a regular basis.

If accessible, an IC professional should participate, implementing and monitoring prevention strategies that decrease health care-associated infections. These infections play a significant role in reducing MDROs and decreasing the use of antibiotics. Additionally, the IC professional can assist in the early identification of patients with MDROs, aid patient placement on transmission-based precautions, and flag a patient in the medical record for hightened awareness. Also, IC professionals promote hand hygiene, standard precautions, and contribute to infection prevention strategies, such as hospital bundle practices, to prevent catheter-associated bloodstream infections and ventilator-associated pneumonias, among others.

If possible, a microbiologist who can prepare culture and susceptibility data to optimize antimicrobial management and conduct timely documentation of microbial pathogens should be a member of the team. Microbiologists can report organism susceptibility, assist in the surveillance of specific organisms, and provide early identification of patients with MDROs that require transmission-based precautions. The microbiologist can perform a semiannual update of a local antibiogram while reporting antimicrobial susceptibility profiles. Based on the information gathered, microbiologists can provide new drug panels to the members of the ASP, who will decide which antibiotic panel will be used. Another possible member of the ASP team is a program analyst who provides data retrieval, performs data analysis, and delivers necessary reports to the team.

It is the responsibility of medical staff to review and implement suggestions made by the ASP when appropriate. However, these suggestions are not considered a substitute for clinical decisions, and discretion is required when treating individual patients. The VHA, in response to the IDSA/SHEA published guidelines, chartered an antimicrobial stewardship task force in May 2011 with the sole purpose “To optimize the care of Veterans by developing, deploying and monitoring a national-level strategic plan for improvements in antimicrobial therapy management.”¹ In 2011, the Office of Inspector General in a combined assessment program summary report for management of MDROs in VHA facilities recommended that “the Under Secretary for Health, in conjunction with VISN and facility senior managers, ensures that facilities develop policies and programs that control and reduce antimicrobial agent use.”¹³

In 2012, the VHA conducted a survey to obtain baseline data regarding ASP activities, presence of dedicated personnel, current related practice policies, available resources, and outcomes. There were 140 voluntary participating VA facilities, of which 130 had inpatient services. The survey found that 26 facilities (20%) did not have an attending ID physician, 49 facilities (38%) reported having an ASP, 19 facilities (15%) had developed policy in place addressing de-escalation of antimicrobials, 87 facilities (67%) had not developed a business plan for an ASP, and 61 facilities (47%) had completed a medication usage evaluation.¹⁴ Feedback following the analysis of the survey data recommended integrating more ID personnel as needed, along with the development of ASP teams for all facilities with inpatient services, who would have the authority to change the antimicrobial therapy selection and have policies in place related to ASP principles.

Conclusions

Increased MDROs and decreased anti-infective development requires stricter management of antibiotics. An ASP is essential in any hospital or health care facility to decrease the incidence of resistance and improve patient care. The ASP is a collaborative effort that involves multiple specialties and departments. A successful ASP is one that changes based on local prescribing trends and resistance patterns while focusing on a patient as an individual. 

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

An antimicrobial stewardship program (ASP) is designed to provide guidance for the safe andcost-effective use of antimicrobial agents. This evidence-based approach addresses the correct selection of antimicrobial agents, dosages, routes of administration, and duration of therapy. In other words, the ASP necessitates the right drug, the right time, the right amount, and the right duration.¹ The ASP reduces the development of multidrug-resistant organisms (MDROs), adverse drug events (such as antibiotic-associated diarrhea and renal toxicity), hospital length of stay, collateral damage (development of Clostridium difficile colitis), and health care costs. Review of the literature has shown the ASP reduces hospital stays among patients with acute bacterial-skin and skin-structure infections along with other costly infections.² 

The ASP is not a new concept, but it is a hot topic. A successful ASP cannot be achieved without the support of the hospital leadership to determine and provide the needed resources. Its success stems from being a joint collaborative effort between pharmacy, medicine, infection control (IC), microbiology, and information technology. The purpose of the ASP is to ensure proper use of antimicrobials within the health care system through the development of a formal, interdisciplinary team. The primary goal of the ASP is to optimize clinical outcomes while minimizing unintended consequences related to antimicrobial usage, such as toxicities or the emergence of resistance. 

In today’s world, health care clinicians are dealing with a global challenge of MDROs such as Enterococcus faecium, Staphylococcus aureus (S aureus), Klebsiella pneumonia, Acinetobacter baumanii, Pseudomonas aeruginosa, and Enterobacter species (ESKAPE), better known as “bugs without borders.”³ According to the CDC, antibiotic-resistant infections affect at least 2 million people in the U.S. annually and result in > 23,000 deaths.² According to Thomas Frieden, director of the CDC, the pipeline of new antibiotics is nearly empty for the short term, and new drugs could be a decade away from discovery and approval by the FDA.²

Literature Review

Pasquale and colleagues conducted a retrospective, observational chart review on 62 patients who were admitted for bacterial-skin and skin-structure infections (S aureus, MRSA, MSSA, and Pseudomonas aeruginosa).⁴ The data examined patient demographic characteristics, comorbidities, specific type of skin infection (the most common being cellulitis, major or deep abscesses, and surgical site infections), microbiology, surgical interventions, and recommendations obtained from the ASP committee.

The primary goal of the antimicrobial stewardship program is to optimize clinical outcomes while minimizing unintended consequences related to antimicrobial usage, such as toxicities or the emergence of resistance.The ASP recommendations were divided into 5 categories, including dosage changes, de-escalation, antibiotic regimen changes, infectious disease (ID) consults, and other (not described). The ASP offered 85 recommendations, and acceptance of the ASP recommendations by physicians was 95%. The intervention group had a significantly lower length of stay (4.4 days vs 6.2 days, P < .001); and the 30-day all-cause readmission rate was also significantly lower (6.5% vs 16.71%, P = .05). However, the skin and skin-related structures readmission rate did not differ significantly (3.33% vs 6.27%). It was impossible for the investigators to determine exact differences in the amount of antimicrobials used in the intervention group vs the historical controls, because the historical data were based on ICD-9 codes, which may explain the nonsignificant finding.⁴

D’Agata reviewed the antimicrobial usage and ASP programs in dialysis centers.⁵ Chronic hemodialysis patients with central lines were noted to have the greatest rate of infections and antibiotic usage (6.4 per 100 patient months). The next highest group was dialysis patients with grafts (2.4 per 100 patient months), followed by patients with fistulas (1.8 per 100 patient months). Vancomycin was most commonly chosen for all antibiotic starts (73%). Interestingly, vancomycin was followed by cefazolin and third- and/or fourth-generation cephalosporin, which are risk factors for the emergence of multidrug-resistant, Gram-negative bacteria that are highly linked to increased morbidity and mortality rates. The U.S. Renal Data System stated in its 2009 report that the use of antibiotic therapy has increased from 31% in 1994 to 41% in 2007.⁵

In reviewing inappropriate choices of antimicrobial prescribing, D’Agata compared prescriptions given to the Healthcare Infection Control Practices Advisory Committee to determine whether the correct antibiotic was chosen. In 164 vancomycin prescriptions, 20% were categorized as inappropriate.⁵ In another study done by Zvonar and colleagues, 163 prescriptions of vancomycin were reviewed, and 12% were considered inappropriate.⁶

Snyder and colleagues examined 278 patients on hemodialysis, and over a 1-year period, 32% of these patients received ≥ 1 antimicrobial with 29.8% of the doses classified as inappropriate.⁷ The most common category for inappropriate prescribing of antimicrobials was not meeting the criteria for diagnosing infections (52.9% of cases). The second leading cause of inappropriate prescription for infections was not meeting criteria for diagnosing specific skin and skin-structure infections (51.6% of cases). Another common category was failure to choose a narrower spectrum antimicrobial prescription (26.8%).⁷ Attention to the indications and duration of antimicrobial treatment accounted for 20.3% of all inappropriate doses. Correction of these problems with use of an ASP could reduce the patient’s exposure to unneeded or inappropriate antibiotics by 22% to 36% and decrease hospital costs between $200,000 to $900,000.⁵

Rosa and colleagues discussed adherence to an ASP and the effects on mortality in hospitalized cancer patients with febrile neutropenia (FN).⁸ A prospective cohort study was performed in a single facility over a 2-year period. Patients admitted with cancer and FN were followed for 28 days. The mortality rates of those treated with ASP protocol antibiotics were compared with those treated with other antibiotic regimens. One hundred sixty-nine patients with 307 episodes of FN were included. The rate of adherence to ASP recommendations was 53% with the mortality of this cohort 9.4% (29 patients).⁸

Older patients were more likely to be treated according to ASP recommendations, whereas patients with comorbidities were not treated with ASP guidelines, Rosa and colleagues noted.⁸ No explanation was given, but statistical testing did uphold these findings, ensuring that the results were correctly interpreted. The 28-day mortality during FN was related to several factors, including nonadherence with ASP recommendations (P = .001) relapsing diseases stages (P = .001), and time to antibiotic start therapy > 1 hour (P = .001). Adherence to the ASP was independently associated with a higher survival rate (P = .03), whereas mortality was attributable to infection in all 29 patients who died.

Nowak and colleagues reviewed the clinical and economic benefits of an ASP using a pre- and postanalysis of potential patients who might benefit from recommendations of the ASP.⁹ Subjects included adult inpatients with pneumonia or abdominal sepsis. Recommendations from ASP that were followed decreased expenditures by 9.75% during the first year and remained stable in the following years. The cumulative cost savings was about $1.7 million. Rates of nosocomial infections decreased, and pre- and postcomparison of survival and lengths of stay for patients with pneumonia (n = 2,186) or abdominal sepsis (n = 225) revealed no significant differences. Investigators argued that this finding may have been due to the hospital’s initiation of other concurrent IC programs.

Doron and colleagues conducted a survey identifying characteristics of ASP practices and factors associated with the presence of an ASP.¹⁰ Surveys were received from 48 states (North and South Dakota were not included) and Puerto Rico. Surveys were received from 406 providers, and 96.4% identified some form of ASP. Barriers to implementation included staffing constraints (69.4%) and insufficient funding (0.6%).¹⁰

About 38% of the responses stated ASP was being used for adults and pediatric patients, whereas 58.8% were used for adults only.¹⁰ The ASP teams were composed of a variety of providers, including infectious disease (ID) physicians (70.7%), IC professionals (51.1%), and clinical microbiologists (38.6%). Additional barriers to implementing an ASP were found as insufficient medical staff buy-in (32.8%), not high on the priority list (22.2%), and too many other things to consider or deal with at the time (42.8%). Interestingly, 41.1% of the subjects in facilities without an ASP responded that providers agree with limiting the use of antimicrobials compared with 66.9% of subjects in hospitals with an ASP. Factors linked to having an ASP included having an ID consultation service, an ID fellowship program, an ID pharmacist, larger hospitals, annual admissions > 10,000, having a published antibiogram, and being a teaching hospital.

Establishment of an ASP

The Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA) issued guidelines in 2007 for developing an institutional ASP to enhance antimicrobial stewardship and help prevent antimicrobial resistance in hospitals.¹¹ The ASP may vary among facilities based on available resources.

When developing an ASP, 2 core strategies are necessary. The core measures are proactive and are usually conducted by an ID clinical pharmacist assigned to the ASP in collaboration with the ID physician. These strategies are not mutually exclusive and include a prospective audit with interventions provided to the clinicians, resulting in decreased inappropriate use of antimicrobials or a formulary restriction and preauthorization to help reduce antimicrobial usage and related cost.

Supplemental elements may be considered and prioritized as to the core antimicrobial stewardship strategies based on local practice pattern and resources.¹¹ Factors to consider include education, which is considered to be an essential element of the ASP. Although education is important, it alone is only somewhat effective in changing clinicians’ prescribing practices. Guidelines and clinical pathways are elements set forth in institutional management protocols for common and potentially serious infections such as intravascular catheter-related infections, hospital- and community-acquired pneumonia, bloodstream infections, and complicated urinary tract infections among other types.

Another consideration is antimicrobial cycling. This process refers to the specific schedule of alternating specific antimicrobials or antimicrobial classes to prevent or reverse the development of antimicrobial resistance. Insufficient data on antimicrobial cycling currently exist to affect major changes in practice. This element, however, could be implemented in certain institutions if needed based on the reported bacterial resistance pattern.

Antimicrobial order forms can be used to help monitor the implementation of formulated institutional clinical practice pathways. However, the authors feel that documenting this indication in the clinician notes may be adequate and save time for everyone involved; additionally, reviewing combination therapy, which if avoided, may prevent the emergence of resistance. Although combination therapy is needed in certain clinical diagnostic situations, careful consideration of its use is essential.

Using the appropriate antimicrobial dose based on the specific pathogen, patient characteristic, source of infection, along with the pharmacokinetic and pharmacodynamics should be reviewed to prevent antimicrobial overuse.Streamlining or de-escalation of therapy by using a narrower spectrum agent, based on culture and sensitivity results, prevents duplicative therapy with a patient when double coverage is not indicated or intended. Another goal is the discontinuation of therapy based on negative culture results and lack of supporting clinical signs and symptoms of infection. Dose optimization and adjustment should also be reviewed. Using the appropriate antimicrobial dose based on the specific pathogen, patient characteristic, source of infection, along with the pharmacokinetic and pharmacodynamics should be reviewed to prevent antimicrobial overuse and subsequent potentially avoidable adverse effects.

Parenteral to oral conversion from IV to oral administration (IV to oral) antimicrobials must be considered when the patient is clinically and hemodynamically stable, thus limiting the length of hospital stays and health care costs. However, it is important to keep in mind pharmacokinetic studies examining the bioavailability of antibiotics are usually conducted with healthy volunteers. Therefore, when treating patients who are elderly, on multiple medications, or severely ill, proper usage of these antibiotics is required. Also, having antibiotics with excellent bioavailability does not necessarily mean switching from IV to oral routes when treating serious infections such as bacteremia. Special consideration should be given when changing the route of administration. In addition, approval—or at least notification by the treating physician or ID specialist—should be included in the absence of an institutional policy, allowing for automatic IV to oral conversion.

The ASP Team

The participation of specific clinicians has been suggested as key to having a successful ASP team.¹² Members should include an ID physician (director) who serves as the lead physician and supervises the overall function of the ASP, makes recommendations to the ASP team, and contributes to the educational activities. A clinical ID pharmacist (codirector) provides suggestions to clinicians on preferred first-line antimicrobials and reviews medication orders for antimicrobials and resistance patterns, microbiological data, patient data, and clinical information. The codirector also tracks any ASP-related data and submits monitoring reports on a regular basis.

If accessible, an IC professional should participate, implementing and monitoring prevention strategies that decrease health care-associated infections. These infections play a significant role in reducing MDROs and decreasing the use of antibiotics. Additionally, the IC professional can assist in the early identification of patients with MDROs, aid patient placement on transmission-based precautions, and flag a patient in the medical record for hightened awareness. Also, IC professionals promote hand hygiene, standard precautions, and contribute to infection prevention strategies, such as hospital bundle practices, to prevent catheter-associated bloodstream infections and ventilator-associated pneumonias, among others.

If possible, a microbiologist who can prepare culture and susceptibility data to optimize antimicrobial management and conduct timely documentation of microbial pathogens should be a member of the team. Microbiologists can report organism susceptibility, assist in the surveillance of specific organisms, and provide early identification of patients with MDROs that require transmission-based precautions. The microbiologist can perform a semiannual update of a local antibiogram while reporting antimicrobial susceptibility profiles. Based on the information gathered, microbiologists can provide new drug panels to the members of the ASP, who will decide which antibiotic panel will be used. Another possible member of the ASP team is a program analyst who provides data retrieval, performs data analysis, and delivers necessary reports to the team.

It is the responsibility of medical staff to review and implement suggestions made by the ASP when appropriate. However, these suggestions are not considered a substitute for clinical decisions, and discretion is required when treating individual patients. The VHA, in response to the IDSA/SHEA published guidelines, chartered an antimicrobial stewardship task force in May 2011 with the sole purpose “To optimize the care of Veterans by developing, deploying and monitoring a national-level strategic plan for improvements in antimicrobial therapy management.”¹ In 2011, the Office of Inspector General in a combined assessment program summary report for management of MDROs in VHA facilities recommended that “the Under Secretary for Health, in conjunction with VISN and facility senior managers, ensures that facilities develop policies and programs that control and reduce antimicrobial agent use.”¹³

In 2012, the VHA conducted a survey to obtain baseline data regarding ASP activities, presence of dedicated personnel, current related practice policies, available resources, and outcomes. There were 140 voluntary participating VA facilities, of which 130 had inpatient services. The survey found that 26 facilities (20%) did not have an attending ID physician, 49 facilities (38%) reported having an ASP, 19 facilities (15%) had developed policy in place addressing de-escalation of antimicrobials, 87 facilities (67%) had not developed a business plan for an ASP, and 61 facilities (47%) had completed a medication usage evaluation.¹⁴ Feedback following the analysis of the survey data recommended integrating more ID personnel as needed, along with the development of ASP teams for all facilities with inpatient services, who would have the authority to change the antimicrobial therapy selection and have policies in place related to ASP principles.

Conclusions

Increased MDROs and decreased anti-infective development requires stricter management of antibiotics. An ASP is essential in any hospital or health care facility to decrease the incidence of resistance and improve patient care. The ASP is a collaborative effort that involves multiple specialties and departments. A successful ASP is one that changes based on local prescribing trends and resistance patterns while focusing on a patient as an individual. 

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

An antimicrobial stewardship program (ASP) is designed to provide guidance for the safe andcost-effective use of antimicrobial agents. This evidence-based approach addresses the correct selection of antimicrobial agents, dosages, routes of administration, and duration of therapy. In other words, the ASP necessitates the right drug, the right time, the right amount, and the right duration.¹ The ASP reduces the development of multidrug-resistant organisms (MDROs), adverse drug events (such as antibiotic-associated diarrhea and renal toxicity), hospital length of stay, collateral damage (development of Clostridium difficile colitis), and health care costs. Review of the literature has shown the ASP reduces hospital stays among patients with acute bacterial-skin and skin-structure infections along with other costly infections.² 

The ASP is not a new concept, but it is a hot topic. A successful ASP cannot be achieved without the support of the hospital leadership to determine and provide the needed resources. Its success stems from being a joint collaborative effort between pharmacy, medicine, infection control (IC), microbiology, and information technology. The purpose of the ASP is to ensure proper use of antimicrobials within the health care system through the development of a formal, interdisciplinary team. The primary goal of the ASP is to optimize clinical outcomes while minimizing unintended consequences related to antimicrobial usage, such as toxicities or the emergence of resistance. 

In today’s world, health care clinicians are dealing with a global challenge of MDROs such as Enterococcus faecium, Staphylococcus aureus (S aureus), Klebsiella pneumonia, Acinetobacter baumanii, Pseudomonas aeruginosa, and Enterobacter species (ESKAPE), better known as “bugs without borders.”³ According to the CDC, antibiotic-resistant infections affect at least 2 million people in the U.S. annually and result in > 23,000 deaths.² According to Thomas Frieden, director of the CDC, the pipeline of new antibiotics is nearly empty for the short term, and new drugs could be a decade away from discovery and approval by the FDA.²

Literature Review

Pasquale and colleagues conducted a retrospective, observational chart review on 62 patients who were admitted for bacterial-skin and skin-structure infections (S aureus, MRSA, MSSA, and Pseudomonas aeruginosa).⁴ The data examined patient demographic characteristics, comorbidities, specific type of skin infection (the most common being cellulitis, major or deep abscesses, and surgical site infections), microbiology, surgical interventions, and recommendations obtained from the ASP committee.

The primary goal of the antimicrobial stewardship program is to optimize clinical outcomes while minimizing unintended consequences related to antimicrobial usage, such as toxicities or the emergence of resistance.The ASP recommendations were divided into 5 categories, including dosage changes, de-escalation, antibiotic regimen changes, infectious disease (ID) consults, and other (not described). The ASP offered 85 recommendations, and acceptance of the ASP recommendations by physicians was 95%. The intervention group had a significantly lower length of stay (4.4 days vs 6.2 days, P < .001); and the 30-day all-cause readmission rate was also significantly lower (6.5% vs 16.71%, P = .05). However, the skin and skin-related structures readmission rate did not differ significantly (3.33% vs 6.27%). It was impossible for the investigators to determine exact differences in the amount of antimicrobials used in the intervention group vs the historical controls, because the historical data were based on ICD-9 codes, which may explain the nonsignificant finding.⁴

D’Agata reviewed the antimicrobial usage and ASP programs in dialysis centers.⁵ Chronic hemodialysis patients with central lines were noted to have the greatest rate of infections and antibiotic usage (6.4 per 100 patient months). The next highest group was dialysis patients with grafts (2.4 per 100 patient months), followed by patients with fistulas (1.8 per 100 patient months). Vancomycin was most commonly chosen for all antibiotic starts (73%). Interestingly, vancomycin was followed by cefazolin and third- and/or fourth-generation cephalosporin, which are risk factors for the emergence of multidrug-resistant, Gram-negative bacteria that are highly linked to increased morbidity and mortality rates. The U.S. Renal Data System stated in its 2009 report that the use of antibiotic therapy has increased from 31% in 1994 to 41% in 2007.⁵

In reviewing inappropriate choices of antimicrobial prescribing, D’Agata compared prescriptions given to the Healthcare Infection Control Practices Advisory Committee to determine whether the correct antibiotic was chosen. In 164 vancomycin prescriptions, 20% were categorized as inappropriate.⁵ In another study done by Zvonar and colleagues, 163 prescriptions of vancomycin were reviewed, and 12% were considered inappropriate.⁶

Snyder and colleagues examined 278 patients on hemodialysis, and over a 1-year period, 32% of these patients received ≥ 1 antimicrobial with 29.8% of the doses classified as inappropriate.⁷ The most common category for inappropriate prescribing of antimicrobials was not meeting the criteria for diagnosing infections (52.9% of cases). The second leading cause of inappropriate prescription for infections was not meeting criteria for diagnosing specific skin and skin-structure infections (51.6% of cases). Another common category was failure to choose a narrower spectrum antimicrobial prescription (26.8%).⁷ Attention to the indications and duration of antimicrobial treatment accounted for 20.3% of all inappropriate doses. Correction of these problems with use of an ASP could reduce the patient’s exposure to unneeded or inappropriate antibiotics by 22% to 36% and decrease hospital costs between $200,000 to $900,000.⁵

Rosa and colleagues discussed adherence to an ASP and the effects on mortality in hospitalized cancer patients with febrile neutropenia (FN).⁸ A prospective cohort study was performed in a single facility over a 2-year period. Patients admitted with cancer and FN were followed for 28 days. The mortality rates of those treated with ASP protocol antibiotics were compared with those treated with other antibiotic regimens. One hundred sixty-nine patients with 307 episodes of FN were included. The rate of adherence to ASP recommendations was 53% with the mortality of this cohort 9.4% (29 patients).⁸

Older patients were more likely to be treated according to ASP recommendations, whereas patients with comorbidities were not treated with ASP guidelines, Rosa and colleagues noted.⁸ No explanation was given, but statistical testing did uphold these findings, ensuring that the results were correctly interpreted. The 28-day mortality during FN was related to several factors, including nonadherence with ASP recommendations (P = .001) relapsing diseases stages (P = .001), and time to antibiotic start therapy > 1 hour (P = .001). Adherence to the ASP was independently associated with a higher survival rate (P = .03), whereas mortality was attributable to infection in all 29 patients who died.

Nowak and colleagues reviewed the clinical and economic benefits of an ASP using a pre- and postanalysis of potential patients who might benefit from recommendations of the ASP.⁹ Subjects included adult inpatients with pneumonia or abdominal sepsis. Recommendations from ASP that were followed decreased expenditures by 9.75% during the first year and remained stable in the following years. The cumulative cost savings was about $1.7 million. Rates of nosocomial infections decreased, and pre- and postcomparison of survival and lengths of stay for patients with pneumonia (n = 2,186) or abdominal sepsis (n = 225) revealed no significant differences. Investigators argued that this finding may have been due to the hospital’s initiation of other concurrent IC programs.

Doron and colleagues conducted a survey identifying characteristics of ASP practices and factors associated with the presence of an ASP.¹⁰ Surveys were received from 48 states (North and South Dakota were not included) and Puerto Rico. Surveys were received from 406 providers, and 96.4% identified some form of ASP. Barriers to implementation included staffing constraints (69.4%) and insufficient funding (0.6%).¹⁰

About 38% of the responses stated ASP was being used for adults and pediatric patients, whereas 58.8% were used for adults only.¹⁰ The ASP teams were composed of a variety of providers, including infectious disease (ID) physicians (70.7%), IC professionals (51.1%), and clinical microbiologists (38.6%). Additional barriers to implementing an ASP were found as insufficient medical staff buy-in (32.8%), not high on the priority list (22.2%), and too many other things to consider or deal with at the time (42.8%). Interestingly, 41.1% of the subjects in facilities without an ASP responded that providers agree with limiting the use of antimicrobials compared with 66.9% of subjects in hospitals with an ASP. Factors linked to having an ASP included having an ID consultation service, an ID fellowship program, an ID pharmacist, larger hospitals, annual admissions > 10,000, having a published antibiogram, and being a teaching hospital.

Establishment of an ASP

The Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA) issued guidelines in 2007 for developing an institutional ASP to enhance antimicrobial stewardship and help prevent antimicrobial resistance in hospitals.¹¹ The ASP may vary among facilities based on available resources.

When developing an ASP, 2 core strategies are necessary. The core measures are proactive and are usually conducted by an ID clinical pharmacist assigned to the ASP in collaboration with the ID physician. These strategies are not mutually exclusive and include a prospective audit with interventions provided to the clinicians, resulting in decreased inappropriate use of antimicrobials or a formulary restriction and preauthorization to help reduce antimicrobial usage and related cost.

Supplemental elements may be considered and prioritized as to the core antimicrobial stewardship strategies based on local practice pattern and resources.¹¹ Factors to consider include education, which is considered to be an essential element of the ASP. Although education is important, it alone is only somewhat effective in changing clinicians’ prescribing practices. Guidelines and clinical pathways are elements set forth in institutional management protocols for common and potentially serious infections such as intravascular catheter-related infections, hospital- and community-acquired pneumonia, bloodstream infections, and complicated urinary tract infections among other types.

Another consideration is antimicrobial cycling. This process refers to the specific schedule of alternating specific antimicrobials or antimicrobial classes to prevent or reverse the development of antimicrobial resistance. Insufficient data on antimicrobial cycling currently exist to affect major changes in practice. This element, however, could be implemented in certain institutions if needed based on the reported bacterial resistance pattern.

Antimicrobial order forms can be used to help monitor the implementation of formulated institutional clinical practice pathways. However, the authors feel that documenting this indication in the clinician notes may be adequate and save time for everyone involved; additionally, reviewing combination therapy, which if avoided, may prevent the emergence of resistance. Although combination therapy is needed in certain clinical diagnostic situations, careful consideration of its use is essential.

Using the appropriate antimicrobial dose based on the specific pathogen, patient characteristic, source of infection, along with the pharmacokinetic and pharmacodynamics should be reviewed to prevent antimicrobial overuse.Streamlining or de-escalation of therapy by using a narrower spectrum agent, based on culture and sensitivity results, prevents duplicative therapy with a patient when double coverage is not indicated or intended. Another goal is the discontinuation of therapy based on negative culture results and lack of supporting clinical signs and symptoms of infection. Dose optimization and adjustment should also be reviewed. Using the appropriate antimicrobial dose based on the specific pathogen, patient characteristic, source of infection, along with the pharmacokinetic and pharmacodynamics should be reviewed to prevent antimicrobial overuse and subsequent potentially avoidable adverse effects.

Parenteral to oral conversion from IV to oral administration (IV to oral) antimicrobials must be considered when the patient is clinically and hemodynamically stable, thus limiting the length of hospital stays and health care costs. However, it is important to keep in mind pharmacokinetic studies examining the bioavailability of antibiotics are usually conducted with healthy volunteers. Therefore, when treating patients who are elderly, on multiple medications, or severely ill, proper usage of these antibiotics is required. Also, having antibiotics with excellent bioavailability does not necessarily mean switching from IV to oral routes when treating serious infections such as bacteremia. Special consideration should be given when changing the route of administration. In addition, approval—or at least notification by the treating physician or ID specialist—should be included in the absence of an institutional policy, allowing for automatic IV to oral conversion.

The ASP Team

The participation of specific clinicians has been suggested as key to having a successful ASP team.¹² Members should include an ID physician (director) who serves as the lead physician and supervises the overall function of the ASP, makes recommendations to the ASP team, and contributes to the educational activities. A clinical ID pharmacist (codirector) provides suggestions to clinicians on preferred first-line antimicrobials and reviews medication orders for antimicrobials and resistance patterns, microbiological data, patient data, and clinical information. The codirector also tracks any ASP-related data and submits monitoring reports on a regular basis.

If accessible, an IC professional should participate, implementing and monitoring prevention strategies that decrease health care-associated infections. These infections play a significant role in reducing MDROs and decreasing the use of antibiotics. Additionally, the IC professional can assist in the early identification of patients with MDROs, aid patient placement on transmission-based precautions, and flag a patient in the medical record for hightened awareness. Also, IC professionals promote hand hygiene, standard precautions, and contribute to infection prevention strategies, such as hospital bundle practices, to prevent catheter-associated bloodstream infections and ventilator-associated pneumonias, among others.

If possible, a microbiologist who can prepare culture and susceptibility data to optimize antimicrobial management and conduct timely documentation of microbial pathogens should be a member of the team. Microbiologists can report organism susceptibility, assist in the surveillance of specific organisms, and provide early identification of patients with MDROs that require transmission-based precautions. The microbiologist can perform a semiannual update of a local antibiogram while reporting antimicrobial susceptibility profiles. Based on the information gathered, microbiologists can provide new drug panels to the members of the ASP, who will decide which antibiotic panel will be used. Another possible member of the ASP team is a program analyst who provides data retrieval, performs data analysis, and delivers necessary reports to the team.

It is the responsibility of medical staff to review and implement suggestions made by the ASP when appropriate. However, these suggestions are not considered a substitute for clinical decisions, and discretion is required when treating individual patients. The VHA, in response to the IDSA/SHEA published guidelines, chartered an antimicrobial stewardship task force in May 2011 with the sole purpose “To optimize the care of Veterans by developing, deploying and monitoring a national-level strategic plan for improvements in antimicrobial therapy management.”¹ In 2011, the Office of Inspector General in a combined assessment program summary report for management of MDROs in VHA facilities recommended that “the Under Secretary for Health, in conjunction with VISN and facility senior managers, ensures that facilities develop policies and programs that control and reduce antimicrobial agent use.”¹³

In 2012, the VHA conducted a survey to obtain baseline data regarding ASP activities, presence of dedicated personnel, current related practice policies, available resources, and outcomes. There were 140 voluntary participating VA facilities, of which 130 had inpatient services. The survey found that 26 facilities (20%) did not have an attending ID physician, 49 facilities (38%) reported having an ASP, 19 facilities (15%) had developed policy in place addressing de-escalation of antimicrobials, 87 facilities (67%) had not developed a business plan for an ASP, and 61 facilities (47%) had completed a medication usage evaluation.¹⁴ Feedback following the analysis of the survey data recommended integrating more ID personnel as needed, along with the development of ASP teams for all facilities with inpatient services, who would have the authority to change the antimicrobial therapy selection and have policies in place related to ASP principles.

Conclusions

Increased MDROs and decreased anti-infective development requires stricter management of antibiotics. An ASP is essential in any hospital or health care facility to decrease the incidence of resistance and improve patient care. The ASP is a collaborative effort that involves multiple specialties and departments. A successful ASP is one that changes based on local prescribing trends and resistance patterns while focusing on a patient as an individual. 

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

The Mental Health Residential Rehabilitation Treatment Program (MHRRTP) is an essential part of the mental health services offered at the Clement J. Zablocki VAMC (ZVAMC) in Milwaukee, Wisconsin. Across the nation, there are about 250 MHRRTPs, which are designed to provide rehabilitation and treatment services to veterans ranging in age from 18 to 80 years, with medical conditions, mental illness, addiction, or psychosocial deficits.¹ About 900 patients were admitted to the ZVAMC MHRRTP in 2013.

Background

Prior to 2010, pharmacy administrators recognized that many MHRRTP patients were inappropriately using emergency care services (ECS) to obtain treatments for simple ailments that often required only the use of over-the-counter medications. This was likely associated with the Safe Medication Management (SMM) Policy as defined in Professional Services Memorandum VII-29.^2,3 This policy states that MHRRTP patients are not allowed to bring in any home medications—all medications are reconciled and readministered on admission in an effort to reduce diversion.

A lack of 24-hour-per-day provider availability forced patients to find treatment elsewhere. A 6-month review was completed in 2010, which identified all of the MHRRTP patients who used ECS, their chief medical condition, and the medication(s) that were administered to each patient. This review identified a total of 254 ECS visits made by MHRRTP patients during this period. Twenty percent of these visits resulted in prescriptions for over-the-counter medications. As a result, an as needed (PRN) medication list was created for patients to have medications readily available for simple ailments with nursing oversight (Box). The goal of the PRN medication list is to reduce the amount of unnecessary ECS visits, decrease unnecessary cost, and improve treatment efficiency and overall patient care.

Treatment Programs

The ZVAMC MHRRTP has 189 beds divided among 7 different 6-week treatment programs, including General Men’s Program (GEN), Substance Abuse Rehabilitation (SAR), Posttraumatic Stress Disorder (PTSD), Women’s Program (WOM), Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn (OEF/OIF/OND), Domiciliary Care for Homeless Veterans (DCHV), and Individualized Addiction Consultation Team (I-ACT).⁴

The treatment programs within the MHRRTP at the ZVAMC address goals of rehabilitation, recovery, health maintenance, improved quality of life, and community integration in addition to specific treatment of medical conditions, mental illnesses, addictive disorders, and homelessness. Various levels of care are available through the program, based on the needs of each veteran. This care generally provides methods to enhance patients’ functional status and psychosocial rehabilitation.

A SMM program is used to ensure safe and effective medication use for all patients in the MHRRTP.² As a result, the patients are admitted to the MHRRTP with inpatient status, and the medication delivery procedure varies based on the veteran’s ability to take medication independently. Veterans are assisted in developing self-care skills, which include comprehensive medication education. The goal of the SMM program is to give patients the assistance to eventually manage their medications independently.

MHRRTP Staffing

The MHRRTP must have adequate staffing in order to provide safe and effective patient care. Program staffing patterns are based on workload indicators and a bed-to-staff ratio.⁴ The MHRRTP is a multidisciplinary program; however, the only providers who can address medication issues are the 1.2 full-time employee equivalent MHRRTP psychiatrists. Unfortunately, the psychiatrists are not available for triage on nights, weekends, or holidays.

The role of the psychiatrist is to focus on the mental health needs of the MHRRTP patients, not the primary care medical concerns, which are the main reason for ECS visits. With the current model, providers are sometimes unavailable to meet the emergent needs of patients in the MHRRTP, and patients may be forced to choose between using ECS or leaving the concern unaddressed. Patients’ needs vary from mild to serious emergent needs but may not necessarily require full emergency assessments. For example, if a patient has a headache and a physician is not available to write an order for acetaminophen, the patient may need to visit the ECS to obtain a medication that otherwise would have been readily available at home. The restrictions are designed to promote medication safety, prevent medication diversion and misuse, and be in compliance with regulatory agencies (eg, The Joint Commission and the Commission on Accreditation of Rehabilitation Facilities).

ECS Use

During fiscal year 2010, pharmacy administrators discovered that many patients were using ECS to obtain medications for nonemergent conditions. Inappropriate and unnecessary use of ECS by MHRRTP patients delayed treatment, increased wait times for veterans in need of emergent care, and increased the cost of caring for simple ailments. To put this into perspective, the average cost of all conditions at the ZVAMC during the 2013 fiscal year was $657 per ECS visit, while the total cost of ECS was about $14 million.

In response to the inappropriate ECS use, the ZVAMC created a PRN medication list in 2010, which is offered to all MHRRTP patients, with the goal of reducing the number of patients inappropriately using ECS for minor ailments and providing more efficient and cost-effective patient care.² The MHRRTP PRN medication list is initially evaluated by the admitting psychiatrist or nurse practitioner and mental health clinical pharmacy specialist completing the admission orders for appropriateness based on each patient’s comorbidities, medication regimen, and past medical history. For example, if a new patient with liver dysfunction is admitted to the MHRRTP, acetaminophen would not be made available due to an increased risk of hepatotoxicity. The other PRN medications would still be available for the patient if clinically appropriate.

Once the PRN medications are ordered, the MHRRTP nurse can assess a patient’s condition and administer the medication(s) to the patient as indicated. For instance, if a patient requests ibuprofen for pain, the nurse will document an initial pain score and administer the ibuprofendose. As a result, the patient obtains more efficient and convenient care and does not need to wait for a provider to become available or use ECS. Per ZVAMC policy, the nurse has 96 hours to reassess the PRN medication effectiveness; however, this is typically done within the same shift. Since the implementation of the PRN medication list, no formal assessment has been completed.

To the authors’ knowledge, the ZVAMC is the only MHRRTP in the VHA system that incorporates a PRN medication list in the admission orders to reduce unnecessary ECS visits. After completing a thorough literature review and contacting the national VA mental health pharmacist listserve, no studies discussing the use of PRN medication lists in this setting were identified, and no sites offered information as to a similar practice in place.

Methods

A randomized, retrospective case-controlled study involving a chart review was completed for patients admitted to the MHRRTP at the ZVAMC pre- and postimplementation of the MHRRTP PRN medication list between April 2010 and August 2010 and between April 2013 and August 2013, respectively. The ZVAMC is a teaching institution. This study was approved by the ZVAMC institutional review board.

Patients were eligible for the study if they were male, aged > 18 years, and admitted during the study period for treatment in the GEN or SAR programs at the ZVAMC for at least 4 weeks. Patients were excluded if they were female, admitted to the hospital after being seen by ECS, or if they were receiving treatment in the following programs: PTSD, WOM, OEF/OIF/OND, DCHV, and I-ACT. Patients studied in 2010 served as the control group, and patients studied in 2013 were the treatment group.

Objectives

The primary objective of this study was to evaluate the use of the current PRN medication list. Secondary objectives included the evaluation of the use of ECS by patients admitted to the MHRRTP pre- and postimplementation of the PRN medication list, the potential cost reduction due to avoided ECS use, and nurse and patient satisfaction with the PRN medication list.

Data

A list of all patients admitted to the MHRRTP at the ZVAMC between April and August of 2010 and 2013 was generated using the Veterans Health Information Systems and Technology Architecture (VISTA)system. The Computerized Patient Record System (CPRS) was used to evaluate the patient for inclusion and collect pertinent data. The PRN medication list was implemented on September 15, 2010. Data collection terminated as of September 14, 2010, regardless of discharge status. All data collected for this study were entered and stored in a database created by the authors. A table with set criteria to review was created for the 2010 and 2013 group to ensure standardization. The pharmacy resident reviewed all of the patient charts. The following data were collected for each patient in the 2010 group:

• Demographic data: Patient name, last 4 digits of their social security number, age
• Program information: Admitted to GEN or SAR program, admission and discharge date, duration of stay, reason for discharge
• ECS data: Date, type of visit, chief condition, medications administered during the visit, whether the visit resulted in a hospital admission, and whether the visit was avoidable
• Avoidable visit: visit in which the patient received or could have received medication(s) that are on the PRN medication list at the ECS visit to treat their illness

The same information was collected for each patient in the 2013 group in addition to the following: PRN medication data (medications administered from the PRN medication list and the number of times each medication was administered if applicable); and ECS data (along with the aforementioned data, it was noted if PRN medications were taken prior to the ECS visit).

In addition, nurse and patient satisfaction with the PRN medication list were assessed via a simple satisfaction survey. The survey was given to 120 patients admitted to the MHRRTP as well as to 32 nurses at the time of distribution. A cover letter on each survey explained the study and informed the patient that the survey was voluntary and anonymous. Satisfaction was based on 10-point scale, with 1 (lowest) and 10 (highest) in satisfaction. Additional questions were asked to identify areas of improvement (see eAppendixes A and B for patient and nurse surveys, respectively).

Statistical Analysis

Descriptive statistics were used to analyze collected data. The primary outcome was assessed for the group admitted postintervention by calculating the average number of times each medication on the PRN medication list was used per patient during their length of stay (LOS) as applicable. The administration totals for each medication on the PRN medication list during the postintervention study period were also recorded.

Secondary outcomes were assessed by comparing the recorded total number of ECS visits pre- and postimplementation. Additionally, the average number of ECS visits per admission and the number of avoidable ECS visits were recorded for each study group. The cost reduction from avoided ECS use was estimated by calculating the total cost of ECS used pre- and postimplementation. The difference between the number of avoidable ECS visits in the pre- and postintervention groups was assessed for statistical significance by using a chi-square test. The 2013 cost saving estimation was based on the average ECS visit cost in the 2013 fiscal year ($657). Of note, power for this study could not be calculated as this has not been studied prior; therefore, no precedence has been set.

Results

On completion of the data collection, 583 patients were assessed for inclusion into the study, 325 in the 2010 preimplementation group and 258 in the 2013 postimplementation group. A total of 200 patients were randomized in each group (n = 400); however, 69 (35%) and 63 (32%) were excluded from the 2010 group and 2013 group, respectively. Sample demographics are described in the Table.

PRN Medication and ECS Use

Between April 1, 2013, and September 14, 2013, 3,959 doses of PRN medications were administered to MHRRTP patients who were included in the study (Figure). Prior to accessing ECS for their problem, 22 (36%) of the 61 patients who used ECS had trialed the PRN medication(s).

When comparing the total number of ECS visits, the 2010 group had 145 visits and the 2013 group had 96 visits. The preimplementation group averaged 1.1 ECS visits per MHRRTP admission, whereas the postimplementation group averaged 0.7 ECS visits per admission. The difference in the number of avoidable ECS visits was statistically significant, with the 2010 group totaling 15 avoidable visits, while the 2013 group totaled 1 ECS visit (P = .0045).

It was estimated that 9 (9.3%) ECS visits were avoided due to the PRN medication list in 2013. Using 137 patients, who were included in the postimplementation group, it can be calculated that $5,867 was saved due to the PRN medication list, or $42.83 per patient in 2013. Using the 2013 MHRRTP census of 898 patients, the financial impact of the PRN medication list can be extrapolated to produce an estimated annual cost savings of $38,461.

Patient and Nurse Satisfaction

Of the 120 patients given the patient satisfaction questionnaire, 28 (23%) patients responded. Of the respondents, 25 (89%) stated they were aware of the PRN medication list. The median rank of satisfaction reported was 8 on a 10-point scale. Twenty-two (79%) patients felt that the PRN medication list had or may have reduced the need to go to ECS or urgent care. Twenty-three (82%) patients recommended not removing any drugs listed on the PRN medication list.

Of the 32 registered nurses and licensed practical nurses working in the MHRRTP, 7 (22%) responded to the nurse satisfaction questionnaire. Of the respondents, 6 (86%) stated they discuss the PRN medication list during admission assessments every time or most of the time. The median rank of satisfaction was 9 on a 10-point scale. Four (57%) nurses felt patients had a clear understanding of the PRN medication list, and 100% of nurses stated they had enough guidance on situations to administer the medications. Seven (100%) stated that the PRN medication list had not caused adverse events; however, 5 (71%) stated that the list had been used inappropriately.

Discussion

This retrospective case-controlled study of 400 patients revealed high use of the PRN medication list and a cost avoidance of nearly $40,000. Although this represents a small reduction of the annual ECS budget, the PRN medication list also improved patient care by providing more efficient and convenient access to medications. The most commonly used medications were acetaminophen, trazodone, and ibuprofen. In addition, the nursing and patient surveys demonstrated an overall satisfaction with the current PRN medication list. It is important to note that the number of avoidable ECS visits decreased significantly after the implementation of the PRN medication list in 2010.

Roughly 35% of patients in each group were excluded from the study. The main exclusion criteria included a < 4-week LOS, being admitted to the hospital, being female, and being admitted prior to the study period. Women veterans were treated through different programs prior to the implementation of the PRN medication list; therefore, they were excluded to decrease variability. Only patients in the GEN and SAR programs were included, because they were well established prior to and after the intervention. The other programs, which included PTSD, WOM, OEF/OIF/OND, DCHV, and I-ACT, accounted for about one-third of MHRRTP admissions. However, they were not all available or structured similarly in 2010. Including the other programs would have increased variability.

Survey Results

Although the response rates were low, the patient and nurse satisfaction surveys revealed useful information that may assist in identifying the strengths and weaknesses of the current program. More rigorous surveying needs to be conducted to make the results more generalizable. Fifty percent of patients reported using a PRN medication on a daily basis or 3 times per week. However, 28.6% stated they never used the PRN medication list, which was thought to be an overestimation due to an incomplete understanding of what medications are on the PRN medication list. This finding does not correlate with the high use demonstrated with the actual number of PRN medications used.

Two patients marked “other,” one reported using the list when they “need the medication,” and another did not mark an answer. Similarly, 57.1% of the nursing staff reported offering a PRN medication on a daily basis and discussing the list on admission every time. However, 28.6% of nursing staff stated they do not complete admission assessments or work in the medication room, most likely because they are licensed practical nurses and do not have those responsibilities. Interestingly, when asked about medications that should be removed from the PRN medication list, 1 nurse suggested removing trazodone, which was the second most used drug. Some of the medications patients suggested adding to the PRN medication list included creams for dry skin or fungal infections, calcium carbonate, and pain medications such as tramadol, aspirin, and naproxen. Nurses suggested adding aspirin, diphenhydramine, and nicotine gum. These responses will aid in enhancing the current PRN medication list by potentially increasing the types of medications offered.

Limitations

This study has several limitations that may affect its interpretation. The study was retrospective in nature and had a short study period. The data were collected from a single specialty program, which decreases the study’s generalizability, as not all VAMCs have a MHRRTP. Also, the average LOS in 2010 was longer than in 2013. This was related to the restructuring of the MHRRTP in the spring of 2013 to allow for more condensed programming. As a result, it may be reasonable to infer that there were more ECS visits prior to implementation of the PRN medication list due to the longer LOS in 2010. This confounding variable was minimized by normalizing the calculation for the number and percent of ECS visits avoided.

The patient population was limited to male veterans and the satisfaction questionnaires had low response rates. The low patient response rate may have been due to a lack of incentive, decreased health literacy, or possibly lack of time. The low nurse response rate may have been due to limited time and also lack of incentive. A larger response rate may have increased the PRN medication list use and satisfaction reported. This study looked at the change in the number of ECS visits; but, it did not investigate any changes in the number of primary care visits. Patients were able to go to their primary care appointments during their stay in the MHRRTP and may have received medications listed on the PRN medication list at these appointments, which could have been avoided. Last, the accuracy of the documentation in CPRS may be unclear and may have subjected the study to bias. Unfortunately, ECS does not use bar code medication administration, so the administration of medications has to be manually written into the ECS visit note. This method may be vulnerable to human error.

Future Directions

Future directions from this study include discussing the results with the MHRRTP staff and identifying areas of improvement to enhance the medication list. Some discussion points include the reasoning to remove trazodone and examples of inappropriate use. Furthermore, the questions asked by patients and general
suggestions made by the nursing staff identified that increased patient education of the PRN medication list should be implemented during the admission assessment process. This would improve patient understanding and awareness of the PRN medication list, because some patients did not know about the list or what medications it included. Moving forward, the results of this project may provide incentive for future implementation of PRN medication lists at other VA MHRRTPs.

Conclusion

This study confirms that the MHRRTP PRN medication list has been highly used since its implementation in 2010. The study also suggests that the nursing staff and patients are satisfied with the current process. Furthermore, these findings illustrate the PRN medication list’s success at decreasing unnecessary use of ECS and its association with avoiding cost. Further studies are needed to support the results seen in this analysis. Although these discoveries are preliminary, they may provide incentive for future implementation of PRN medication lists at other VA MHRRTPs.

Acknowledgements
Michelle Bury had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

The Mental Health Residential Rehabilitation Treatment Program (MHRRTP) is an essential part of the mental health services offered at the Clement J. Zablocki VAMC (ZVAMC) in Milwaukee, Wisconsin. Across the nation, there are about 250 MHRRTPs, which are designed to provide rehabilitation and treatment services to veterans ranging in age from 18 to 80 years, with medical conditions, mental illness, addiction, or psychosocial deficits.¹ About 900 patients were admitted to the ZVAMC MHRRTP in 2013.

Background

Prior to 2010, pharmacy administrators recognized that many MHRRTP patients were inappropriately using emergency care services (ECS) to obtain treatments for simple ailments that often required only the use of over-the-counter medications. This was likely associated with the Safe Medication Management (SMM) Policy as defined in Professional Services Memorandum VII-29.^2,3 This policy states that MHRRTP patients are not allowed to bring in any home medications—all medications are reconciled and readministered on admission in an effort to reduce diversion.

A lack of 24-hour-per-day provider availability forced patients to find treatment elsewhere. A 6-month review was completed in 2010, which identified all of the MHRRTP patients who used ECS, their chief medical condition, and the medication(s) that were administered to each patient. This review identified a total of 254 ECS visits made by MHRRTP patients during this period. Twenty percent of these visits resulted in prescriptions for over-the-counter medications. As a result, an as needed (PRN) medication list was created for patients to have medications readily available for simple ailments with nursing oversight (Box). The goal of the PRN medication list is to reduce the amount of unnecessary ECS visits, decrease unnecessary cost, and improve treatment efficiency and overall patient care.

Treatment Programs

The ZVAMC MHRRTP has 189 beds divided among 7 different 6-week treatment programs, including General Men’s Program (GEN), Substance Abuse Rehabilitation (SAR), Posttraumatic Stress Disorder (PTSD), Women’s Program (WOM), Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn (OEF/OIF/OND), Domiciliary Care for Homeless Veterans (DCHV), and Individualized Addiction Consultation Team (I-ACT).⁴

The treatment programs within the MHRRTP at the ZVAMC address goals of rehabilitation, recovery, health maintenance, improved quality of life, and community integration in addition to specific treatment of medical conditions, mental illnesses, addictive disorders, and homelessness. Various levels of care are available through the program, based on the needs of each veteran. This care generally provides methods to enhance patients’ functional status and psychosocial rehabilitation.

A SMM program is used to ensure safe and effective medication use for all patients in the MHRRTP.² As a result, the patients are admitted to the MHRRTP with inpatient status, and the medication delivery procedure varies based on the veteran’s ability to take medication independently. Veterans are assisted in developing self-care skills, which include comprehensive medication education. The goal of the SMM program is to give patients the assistance to eventually manage their medications independently.

MHRRTP Staffing

The MHRRTP must have adequate staffing in order to provide safe and effective patient care. Program staffing patterns are based on workload indicators and a bed-to-staff ratio.⁴ The MHRRTP is a multidisciplinary program; however, the only providers who can address medication issues are the 1.2 full-time employee equivalent MHRRTP psychiatrists. Unfortunately, the psychiatrists are not available for triage on nights, weekends, or holidays.

The role of the psychiatrist is to focus on the mental health needs of the MHRRTP patients, not the primary care medical concerns, which are the main reason for ECS visits. With the current model, providers are sometimes unavailable to meet the emergent needs of patients in the MHRRTP, and patients may be forced to choose between using ECS or leaving the concern unaddressed. Patients’ needs vary from mild to serious emergent needs but may not necessarily require full emergency assessments. For example, if a patient has a headache and a physician is not available to write an order for acetaminophen, the patient may need to visit the ECS to obtain a medication that otherwise would have been readily available at home. The restrictions are designed to promote medication safety, prevent medication diversion and misuse, and be in compliance with regulatory agencies (eg, The Joint Commission and the Commission on Accreditation of Rehabilitation Facilities).

ECS Use

During fiscal year 2010, pharmacy administrators discovered that many patients were using ECS to obtain medications for nonemergent conditions. Inappropriate and unnecessary use of ECS by MHRRTP patients delayed treatment, increased wait times for veterans in need of emergent care, and increased the cost of caring for simple ailments. To put this into perspective, the average cost of all conditions at the ZVAMC during the 2013 fiscal year was $657 per ECS visit, while the total cost of ECS was about $14 million.

In response to the inappropriate ECS use, the ZVAMC created a PRN medication list in 2010, which is offered to all MHRRTP patients, with the goal of reducing the number of patients inappropriately using ECS for minor ailments and providing more efficient and cost-effective patient care.² The MHRRTP PRN medication list is initially evaluated by the admitting psychiatrist or nurse practitioner and mental health clinical pharmacy specialist completing the admission orders for appropriateness based on each patient’s comorbidities, medication regimen, and past medical history. For example, if a new patient with liver dysfunction is admitted to the MHRRTP, acetaminophen would not be made available due to an increased risk of hepatotoxicity. The other PRN medications would still be available for the patient if clinically appropriate.

Once the PRN medications are ordered, the MHRRTP nurse can assess a patient’s condition and administer the medication(s) to the patient as indicated. For instance, if a patient requests ibuprofen for pain, the nurse will document an initial pain score and administer the ibuprofendose. As a result, the patient obtains more efficient and convenient care and does not need to wait for a provider to become available or use ECS. Per ZVAMC policy, the nurse has 96 hours to reassess the PRN medication effectiveness; however, this is typically done within the same shift. Since the implementation of the PRN medication list, no formal assessment has been completed.

To the authors’ knowledge, the ZVAMC is the only MHRRTP in the VHA system that incorporates a PRN medication list in the admission orders to reduce unnecessary ECS visits. After completing a thorough literature review and contacting the national VA mental health pharmacist listserve, no studies discussing the use of PRN medication lists in this setting were identified, and no sites offered information as to a similar practice in place.

Methods

A randomized, retrospective case-controlled study involving a chart review was completed for patients admitted to the MHRRTP at the ZVAMC pre- and postimplementation of the MHRRTP PRN medication list between April 2010 and August 2010 and between April 2013 and August 2013, respectively. The ZVAMC is a teaching institution. This study was approved by the ZVAMC institutional review board.

Patients were eligible for the study if they were male, aged > 18 years, and admitted during the study period for treatment in the GEN or SAR programs at the ZVAMC for at least 4 weeks. Patients were excluded if they were female, admitted to the hospital after being seen by ECS, or if they were receiving treatment in the following programs: PTSD, WOM, OEF/OIF/OND, DCHV, and I-ACT. Patients studied in 2010 served as the control group, and patients studied in 2013 were the treatment group.

Objectives

The primary objective of this study was to evaluate the use of the current PRN medication list. Secondary objectives included the evaluation of the use of ECS by patients admitted to the MHRRTP pre- and postimplementation of the PRN medication list, the potential cost reduction due to avoided ECS use, and nurse and patient satisfaction with the PRN medication list.

Data

A list of all patients admitted to the MHRRTP at the ZVAMC between April and August of 2010 and 2013 was generated using the Veterans Health Information Systems and Technology Architecture (VISTA)system. The Computerized Patient Record System (CPRS) was used to evaluate the patient for inclusion and collect pertinent data. The PRN medication list was implemented on September 15, 2010. Data collection terminated as of September 14, 2010, regardless of discharge status. All data collected for this study were entered and stored in a database created by the authors. A table with set criteria to review was created for the 2010 and 2013 group to ensure standardization. The pharmacy resident reviewed all of the patient charts. The following data were collected for each patient in the 2010 group:

• Demographic data: Patient name, last 4 digits of their social security number, age
• Program information: Admitted to GEN or SAR program, admission and discharge date, duration of stay, reason for discharge
• ECS data: Date, type of visit, chief condition, medications administered during the visit, whether the visit resulted in a hospital admission, and whether the visit was avoidable
• Avoidable visit: visit in which the patient received or could have received medication(s) that are on the PRN medication list at the ECS visit to treat their illness

The same information was collected for each patient in the 2013 group in addition to the following: PRN medication data (medications administered from the PRN medication list and the number of times each medication was administered if applicable); and ECS data (along with the aforementioned data, it was noted if PRN medications were taken prior to the ECS visit).

In addition, nurse and patient satisfaction with the PRN medication list were assessed via a simple satisfaction survey. The survey was given to 120 patients admitted to the MHRRTP as well as to 32 nurses at the time of distribution. A cover letter on each survey explained the study and informed the patient that the survey was voluntary and anonymous. Satisfaction was based on 10-point scale, with 1 (lowest) and 10 (highest) in satisfaction. Additional questions were asked to identify areas of improvement (see eAppendixes A and B for patient and nurse surveys, respectively).

Statistical Analysis

Descriptive statistics were used to analyze collected data. The primary outcome was assessed for the group admitted postintervention by calculating the average number of times each medication on the PRN medication list was used per patient during their length of stay (LOS) as applicable. The administration totals for each medication on the PRN medication list during the postintervention study period were also recorded.

Secondary outcomes were assessed by comparing the recorded total number of ECS visits pre- and postimplementation. Additionally, the average number of ECS visits per admission and the number of avoidable ECS visits were recorded for each study group. The cost reduction from avoided ECS use was estimated by calculating the total cost of ECS used pre- and postimplementation. The difference between the number of avoidable ECS visits in the pre- and postintervention groups was assessed for statistical significance by using a chi-square test. The 2013 cost saving estimation was based on the average ECS visit cost in the 2013 fiscal year ($657). Of note, power for this study could not be calculated as this has not been studied prior; therefore, no precedence has been set.

Results

On completion of the data collection, 583 patients were assessed for inclusion into the study, 325 in the 2010 preimplementation group and 258 in the 2013 postimplementation group. A total of 200 patients were randomized in each group (n = 400); however, 69 (35%) and 63 (32%) were excluded from the 2010 group and 2013 group, respectively. Sample demographics are described in the Table.

PRN Medication and ECS Use

Between April 1, 2013, and September 14, 2013, 3,959 doses of PRN medications were administered to MHRRTP patients who were included in the study (Figure). Prior to accessing ECS for their problem, 22 (36%) of the 61 patients who used ECS had trialed the PRN medication(s).

When comparing the total number of ECS visits, the 2010 group had 145 visits and the 2013 group had 96 visits. The preimplementation group averaged 1.1 ECS visits per MHRRTP admission, whereas the postimplementation group averaged 0.7 ECS visits per admission. The difference in the number of avoidable ECS visits was statistically significant, with the 2010 group totaling 15 avoidable visits, while the 2013 group totaled 1 ECS visit (P = .0045).

It was estimated that 9 (9.3%) ECS visits were avoided due to the PRN medication list in 2013. Using 137 patients, who were included in the postimplementation group, it can be calculated that $5,867 was saved due to the PRN medication list, or $42.83 per patient in 2013. Using the 2013 MHRRTP census of 898 patients, the financial impact of the PRN medication list can be extrapolated to produce an estimated annual cost savings of $38,461.

Patient and Nurse Satisfaction

Of the 120 patients given the patient satisfaction questionnaire, 28 (23%) patients responded. Of the respondents, 25 (89%) stated they were aware of the PRN medication list. The median rank of satisfaction reported was 8 on a 10-point scale. Twenty-two (79%) patients felt that the PRN medication list had or may have reduced the need to go to ECS or urgent care. Twenty-three (82%) patients recommended not removing any drugs listed on the PRN medication list.

Of the 32 registered nurses and licensed practical nurses working in the MHRRTP, 7 (22%) responded to the nurse satisfaction questionnaire. Of the respondents, 6 (86%) stated they discuss the PRN medication list during admission assessments every time or most of the time. The median rank of satisfaction was 9 on a 10-point scale. Four (57%) nurses felt patients had a clear understanding of the PRN medication list, and 100% of nurses stated they had enough guidance on situations to administer the medications. Seven (100%) stated that the PRN medication list had not caused adverse events; however, 5 (71%) stated that the list had been used inappropriately.

Discussion

This retrospective case-controlled study of 400 patients revealed high use of the PRN medication list and a cost avoidance of nearly $40,000. Although this represents a small reduction of the annual ECS budget, the PRN medication list also improved patient care by providing more efficient and convenient access to medications. The most commonly used medications were acetaminophen, trazodone, and ibuprofen. In addition, the nursing and patient surveys demonstrated an overall satisfaction with the current PRN medication list. It is important to note that the number of avoidable ECS visits decreased significantly after the implementation of the PRN medication list in 2010.

Roughly 35% of patients in each group were excluded from the study. The main exclusion criteria included a < 4-week LOS, being admitted to the hospital, being female, and being admitted prior to the study period. Women veterans were treated through different programs prior to the implementation of the PRN medication list; therefore, they were excluded to decrease variability. Only patients in the GEN and SAR programs were included, because they were well established prior to and after the intervention. The other programs, which included PTSD, WOM, OEF/OIF/OND, DCHV, and I-ACT, accounted for about one-third of MHRRTP admissions. However, they were not all available or structured similarly in 2010. Including the other programs would have increased variability.

Survey Results

Although the response rates were low, the patient and nurse satisfaction surveys revealed useful information that may assist in identifying the strengths and weaknesses of the current program. More rigorous surveying needs to be conducted to make the results more generalizable. Fifty percent of patients reported using a PRN medication on a daily basis or 3 times per week. However, 28.6% stated they never used the PRN medication list, which was thought to be an overestimation due to an incomplete understanding of what medications are on the PRN medication list. This finding does not correlate with the high use demonstrated with the actual number of PRN medications used.

Two patients marked “other,” one reported using the list when they “need the medication,” and another did not mark an answer. Similarly, 57.1% of the nursing staff reported offering a PRN medication on a daily basis and discussing the list on admission every time. However, 28.6% of nursing staff stated they do not complete admission assessments or work in the medication room, most likely because they are licensed practical nurses and do not have those responsibilities. Interestingly, when asked about medications that should be removed from the PRN medication list, 1 nurse suggested removing trazodone, which was the second most used drug. Some of the medications patients suggested adding to the PRN medication list included creams for dry skin or fungal infections, calcium carbonate, and pain medications such as tramadol, aspirin, and naproxen. Nurses suggested adding aspirin, diphenhydramine, and nicotine gum. These responses will aid in enhancing the current PRN medication list by potentially increasing the types of medications offered.

Limitations

This study has several limitations that may affect its interpretation. The study was retrospective in nature and had a short study period. The data were collected from a single specialty program, which decreases the study’s generalizability, as not all VAMCs have a MHRRTP. Also, the average LOS in 2010 was longer than in 2013. This was related to the restructuring of the MHRRTP in the spring of 2013 to allow for more condensed programming. As a result, it may be reasonable to infer that there were more ECS visits prior to implementation of the PRN medication list due to the longer LOS in 2010. This confounding variable was minimized by normalizing the calculation for the number and percent of ECS visits avoided.

The patient population was limited to male veterans and the satisfaction questionnaires had low response rates. The low patient response rate may have been due to a lack of incentive, decreased health literacy, or possibly lack of time. The low nurse response rate may have been due to limited time and also lack of incentive. A larger response rate may have increased the PRN medication list use and satisfaction reported. This study looked at the change in the number of ECS visits; but, it did not investigate any changes in the number of primary care visits. Patients were able to go to their primary care appointments during their stay in the MHRRTP and may have received medications listed on the PRN medication list at these appointments, which could have been avoided. Last, the accuracy of the documentation in CPRS may be unclear and may have subjected the study to bias. Unfortunately, ECS does not use bar code medication administration, so the administration of medications has to be manually written into the ECS visit note. This method may be vulnerable to human error.

Future Directions

Future directions from this study include discussing the results with the MHRRTP staff and identifying areas of improvement to enhance the medication list. Some discussion points include the reasoning to remove trazodone and examples of inappropriate use. Furthermore, the questions asked by patients and general
suggestions made by the nursing staff identified that increased patient education of the PRN medication list should be implemented during the admission assessment process. This would improve patient understanding and awareness of the PRN medication list, because some patients did not know about the list or what medications it included. Moving forward, the results of this project may provide incentive for future implementation of PRN medication lists at other VA MHRRTPs.

Conclusion

This study confirms that the MHRRTP PRN medication list has been highly used since its implementation in 2010. The study also suggests that the nursing staff and patients are satisfied with the current process. Furthermore, these findings illustrate the PRN medication list’s success at decreasing unnecessary use of ECS and its association with avoiding cost. Further studies are needed to support the results seen in this analysis. Although these discoveries are preliminary, they may provide incentive for future implementation of PRN medication lists at other VA MHRRTPs.

Acknowledgements
Michelle Bury had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

The Mental Health Residential Rehabilitation Treatment Program (MHRRTP) is an essential part of the mental health services offered at the Clement J. Zablocki VAMC (ZVAMC) in Milwaukee, Wisconsin. Across the nation, there are about 250 MHRRTPs, which are designed to provide rehabilitation and treatment services to veterans ranging in age from 18 to 80 years, with medical conditions, mental illness, addiction, or psychosocial deficits.¹ About 900 patients were admitted to the ZVAMC MHRRTP in 2013.

Background

Prior to 2010, pharmacy administrators recognized that many MHRRTP patients were inappropriately using emergency care services (ECS) to obtain treatments for simple ailments that often required only the use of over-the-counter medications. This was likely associated with the Safe Medication Management (SMM) Policy as defined in Professional Services Memorandum VII-29.^2,3 This policy states that MHRRTP patients are not allowed to bring in any home medications—all medications are reconciled and readministered on admission in an effort to reduce diversion.

A lack of 24-hour-per-day provider availability forced patients to find treatment elsewhere. A 6-month review was completed in 2010, which identified all of the MHRRTP patients who used ECS, their chief medical condition, and the medication(s) that were administered to each patient. This review identified a total of 254 ECS visits made by MHRRTP patients during this period. Twenty percent of these visits resulted in prescriptions for over-the-counter medications. As a result, an as needed (PRN) medication list was created for patients to have medications readily available for simple ailments with nursing oversight (Box). The goal of the PRN medication list is to reduce the amount of unnecessary ECS visits, decrease unnecessary cost, and improve treatment efficiency and overall patient care.

Treatment Programs

The ZVAMC MHRRTP has 189 beds divided among 7 different 6-week treatment programs, including General Men’s Program (GEN), Substance Abuse Rehabilitation (SAR), Posttraumatic Stress Disorder (PTSD), Women’s Program (WOM), Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn (OEF/OIF/OND), Domiciliary Care for Homeless Veterans (DCHV), and Individualized Addiction Consultation Team (I-ACT).⁴

The treatment programs within the MHRRTP at the ZVAMC address goals of rehabilitation, recovery, health maintenance, improved quality of life, and community integration in addition to specific treatment of medical conditions, mental illnesses, addictive disorders, and homelessness. Various levels of care are available through the program, based on the needs of each veteran. This care generally provides methods to enhance patients’ functional status and psychosocial rehabilitation.

A SMM program is used to ensure safe and effective medication use for all patients in the MHRRTP.² As a result, the patients are admitted to the MHRRTP with inpatient status, and the medication delivery procedure varies based on the veteran’s ability to take medication independently. Veterans are assisted in developing self-care skills, which include comprehensive medication education. The goal of the SMM program is to give patients the assistance to eventually manage their medications independently.

MHRRTP Staffing

The MHRRTP must have adequate staffing in order to provide safe and effective patient care. Program staffing patterns are based on workload indicators and a bed-to-staff ratio.⁴ The MHRRTP is a multidisciplinary program; however, the only providers who can address medication issues are the 1.2 full-time employee equivalent MHRRTP psychiatrists. Unfortunately, the psychiatrists are not available for triage on nights, weekends, or holidays.

The role of the psychiatrist is to focus on the mental health needs of the MHRRTP patients, not the primary care medical concerns, which are the main reason for ECS visits. With the current model, providers are sometimes unavailable to meet the emergent needs of patients in the MHRRTP, and patients may be forced to choose between using ECS or leaving the concern unaddressed. Patients’ needs vary from mild to serious emergent needs but may not necessarily require full emergency assessments. For example, if a patient has a headache and a physician is not available to write an order for acetaminophen, the patient may need to visit the ECS to obtain a medication that otherwise would have been readily available at home. The restrictions are designed to promote medication safety, prevent medication diversion and misuse, and be in compliance with regulatory agencies (eg, The Joint Commission and the Commission on Accreditation of Rehabilitation Facilities).

ECS Use

During fiscal year 2010, pharmacy administrators discovered that many patients were using ECS to obtain medications for nonemergent conditions. Inappropriate and unnecessary use of ECS by MHRRTP patients delayed treatment, increased wait times for veterans in need of emergent care, and increased the cost of caring for simple ailments. To put this into perspective, the average cost of all conditions at the ZVAMC during the 2013 fiscal year was $657 per ECS visit, while the total cost of ECS was about $14 million.

In response to the inappropriate ECS use, the ZVAMC created a PRN medication list in 2010, which is offered to all MHRRTP patients, with the goal of reducing the number of patients inappropriately using ECS for minor ailments and providing more efficient and cost-effective patient care.² The MHRRTP PRN medication list is initially evaluated by the admitting psychiatrist or nurse practitioner and mental health clinical pharmacy specialist completing the admission orders for appropriateness based on each patient’s comorbidities, medication regimen, and past medical history. For example, if a new patient with liver dysfunction is admitted to the MHRRTP, acetaminophen would not be made available due to an increased risk of hepatotoxicity. The other PRN medications would still be available for the patient if clinically appropriate.

Once the PRN medications are ordered, the MHRRTP nurse can assess a patient’s condition and administer the medication(s) to the patient as indicated. For instance, if a patient requests ibuprofen for pain, the nurse will document an initial pain score and administer the ibuprofendose. As a result, the patient obtains more efficient and convenient care and does not need to wait for a provider to become available or use ECS. Per ZVAMC policy, the nurse has 96 hours to reassess the PRN medication effectiveness; however, this is typically done within the same shift. Since the implementation of the PRN medication list, no formal assessment has been completed.

To the authors’ knowledge, the ZVAMC is the only MHRRTP in the VHA system that incorporates a PRN medication list in the admission orders to reduce unnecessary ECS visits. After completing a thorough literature review and contacting the national VA mental health pharmacist listserve, no studies discussing the use of PRN medication lists in this setting were identified, and no sites offered information as to a similar practice in place.

Methods

A randomized, retrospective case-controlled study involving a chart review was completed for patients admitted to the MHRRTP at the ZVAMC pre- and postimplementation of the MHRRTP PRN medication list between April 2010 and August 2010 and between April 2013 and August 2013, respectively. The ZVAMC is a teaching institution. This study was approved by the ZVAMC institutional review board.

Patients were eligible for the study if they were male, aged > 18 years, and admitted during the study period for treatment in the GEN or SAR programs at the ZVAMC for at least 4 weeks. Patients were excluded if they were female, admitted to the hospital after being seen by ECS, or if they were receiving treatment in the following programs: PTSD, WOM, OEF/OIF/OND, DCHV, and I-ACT. Patients studied in 2010 served as the control group, and patients studied in 2013 were the treatment group.

Objectives

The primary objective of this study was to evaluate the use of the current PRN medication list. Secondary objectives included the evaluation of the use of ECS by patients admitted to the MHRRTP pre- and postimplementation of the PRN medication list, the potential cost reduction due to avoided ECS use, and nurse and patient satisfaction with the PRN medication list.

Data

A list of all patients admitted to the MHRRTP at the ZVAMC between April and August of 2010 and 2013 was generated using the Veterans Health Information Systems and Technology Architecture (VISTA)system. The Computerized Patient Record System (CPRS) was used to evaluate the patient for inclusion and collect pertinent data. The PRN medication list was implemented on September 15, 2010. Data collection terminated as of September 14, 2010, regardless of discharge status. All data collected for this study were entered and stored in a database created by the authors. A table with set criteria to review was created for the 2010 and 2013 group to ensure standardization. The pharmacy resident reviewed all of the patient charts. The following data were collected for each patient in the 2010 group:

• Demographic data: Patient name, last 4 digits of their social security number, age
• Program information: Admitted to GEN or SAR program, admission and discharge date, duration of stay, reason for discharge
• ECS data: Date, type of visit, chief condition, medications administered during the visit, whether the visit resulted in a hospital admission, and whether the visit was avoidable
• Avoidable visit: visit in which the patient received or could have received medication(s) that are on the PRN medication list at the ECS visit to treat their illness

The same information was collected for each patient in the 2013 group in addition to the following: PRN medication data (medications administered from the PRN medication list and the number of times each medication was administered if applicable); and ECS data (along with the aforementioned data, it was noted if PRN medications were taken prior to the ECS visit).

In addition, nurse and patient satisfaction with the PRN medication list were assessed via a simple satisfaction survey. The survey was given to 120 patients admitted to the MHRRTP as well as to 32 nurses at the time of distribution. A cover letter on each survey explained the study and informed the patient that the survey was voluntary and anonymous. Satisfaction was based on 10-point scale, with 1 (lowest) and 10 (highest) in satisfaction. Additional questions were asked to identify areas of improvement (see eAppendixes A and B for patient and nurse surveys, respectively).

Statistical Analysis

Descriptive statistics were used to analyze collected data. The primary outcome was assessed for the group admitted postintervention by calculating the average number of times each medication on the PRN medication list was used per patient during their length of stay (LOS) as applicable. The administration totals for each medication on the PRN medication list during the postintervention study period were also recorded.

Secondary outcomes were assessed by comparing the recorded total number of ECS visits pre- and postimplementation. Additionally, the average number of ECS visits per admission and the number of avoidable ECS visits were recorded for each study group. The cost reduction from avoided ECS use was estimated by calculating the total cost of ECS used pre- and postimplementation. The difference between the number of avoidable ECS visits in the pre- and postintervention groups was assessed for statistical significance by using a chi-square test. The 2013 cost saving estimation was based on the average ECS visit cost in the 2013 fiscal year ($657). Of note, power for this study could not be calculated as this has not been studied prior; therefore, no precedence has been set.

Results

On completion of the data collection, 583 patients were assessed for inclusion into the study, 325 in the 2010 preimplementation group and 258 in the 2013 postimplementation group. A total of 200 patients were randomized in each group (n = 400); however, 69 (35%) and 63 (32%) were excluded from the 2010 group and 2013 group, respectively. Sample demographics are described in the Table.

PRN Medication and ECS Use

Between April 1, 2013, and September 14, 2013, 3,959 doses of PRN medications were administered to MHRRTP patients who were included in the study (Figure). Prior to accessing ECS for their problem, 22 (36%) of the 61 patients who used ECS had trialed the PRN medication(s).

When comparing the total number of ECS visits, the 2010 group had 145 visits and the 2013 group had 96 visits. The preimplementation group averaged 1.1 ECS visits per MHRRTP admission, whereas the postimplementation group averaged 0.7 ECS visits per admission. The difference in the number of avoidable ECS visits was statistically significant, with the 2010 group totaling 15 avoidable visits, while the 2013 group totaled 1 ECS visit (P = .0045).

It was estimated that 9 (9.3%) ECS visits were avoided due to the PRN medication list in 2013. Using 137 patients, who were included in the postimplementation group, it can be calculated that $5,867 was saved due to the PRN medication list, or $42.83 per patient in 2013. Using the 2013 MHRRTP census of 898 patients, the financial impact of the PRN medication list can be extrapolated to produce an estimated annual cost savings of $38,461.

Patient and Nurse Satisfaction

Of the 120 patients given the patient satisfaction questionnaire, 28 (23%) patients responded. Of the respondents, 25 (89%) stated they were aware of the PRN medication list. The median rank of satisfaction reported was 8 on a 10-point scale. Twenty-two (79%) patients felt that the PRN medication list had or may have reduced the need to go to ECS or urgent care. Twenty-three (82%) patients recommended not removing any drugs listed on the PRN medication list.

Of the 32 registered nurses and licensed practical nurses working in the MHRRTP, 7 (22%) responded to the nurse satisfaction questionnaire. Of the respondents, 6 (86%) stated they discuss the PRN medication list during admission assessments every time or most of the time. The median rank of satisfaction was 9 on a 10-point scale. Four (57%) nurses felt patients had a clear understanding of the PRN medication list, and 100% of nurses stated they had enough guidance on situations to administer the medications. Seven (100%) stated that the PRN medication list had not caused adverse events; however, 5 (71%) stated that the list had been used inappropriately.

Discussion

This retrospective case-controlled study of 400 patients revealed high use of the PRN medication list and a cost avoidance of nearly $40,000. Although this represents a small reduction of the annual ECS budget, the PRN medication list also improved patient care by providing more efficient and convenient access to medications. The most commonly used medications were acetaminophen, trazodone, and ibuprofen. In addition, the nursing and patient surveys demonstrated an overall satisfaction with the current PRN medication list. It is important to note that the number of avoidable ECS visits decreased significantly after the implementation of the PRN medication list in 2010.

Roughly 35% of patients in each group were excluded from the study. The main exclusion criteria included a < 4-week LOS, being admitted to the hospital, being female, and being admitted prior to the study period. Women veterans were treated through different programs prior to the implementation of the PRN medication list; therefore, they were excluded to decrease variability. Only patients in the GEN and SAR programs were included, because they were well established prior to and after the intervention. The other programs, which included PTSD, WOM, OEF/OIF/OND, DCHV, and I-ACT, accounted for about one-third of MHRRTP admissions. However, they were not all available or structured similarly in 2010. Including the other programs would have increased variability.

Survey Results

Although the response rates were low, the patient and nurse satisfaction surveys revealed useful information that may assist in identifying the strengths and weaknesses of the current program. More rigorous surveying needs to be conducted to make the results more generalizable. Fifty percent of patients reported using a PRN medication on a daily basis or 3 times per week. However, 28.6% stated they never used the PRN medication list, which was thought to be an overestimation due to an incomplete understanding of what medications are on the PRN medication list. This finding does not correlate with the high use demonstrated with the actual number of PRN medications used.

Two patients marked “other,” one reported using the list when they “need the medication,” and another did not mark an answer. Similarly, 57.1% of the nursing staff reported offering a PRN medication on a daily basis and discussing the list on admission every time. However, 28.6% of nursing staff stated they do not complete admission assessments or work in the medication room, most likely because they are licensed practical nurses and do not have those responsibilities. Interestingly, when asked about medications that should be removed from the PRN medication list, 1 nurse suggested removing trazodone, which was the second most used drug. Some of the medications patients suggested adding to the PRN medication list included creams for dry skin or fungal infections, calcium carbonate, and pain medications such as tramadol, aspirin, and naproxen. Nurses suggested adding aspirin, diphenhydramine, and nicotine gum. These responses will aid in enhancing the current PRN medication list by potentially increasing the types of medications offered.

Limitations

This study has several limitations that may affect its interpretation. The study was retrospective in nature and had a short study period. The data were collected from a single specialty program, which decreases the study’s generalizability, as not all VAMCs have a MHRRTP. Also, the average LOS in 2010 was longer than in 2013. This was related to the restructuring of the MHRRTP in the spring of 2013 to allow for more condensed programming. As a result, it may be reasonable to infer that there were more ECS visits prior to implementation of the PRN medication list due to the longer LOS in 2010. This confounding variable was minimized by normalizing the calculation for the number and percent of ECS visits avoided.

The patient population was limited to male veterans and the satisfaction questionnaires had low response rates. The low patient response rate may have been due to a lack of incentive, decreased health literacy, or possibly lack of time. The low nurse response rate may have been due to limited time and also lack of incentive. A larger response rate may have increased the PRN medication list use and satisfaction reported. This study looked at the change in the number of ECS visits; but, it did not investigate any changes in the number of primary care visits. Patients were able to go to their primary care appointments during their stay in the MHRRTP and may have received medications listed on the PRN medication list at these appointments, which could have been avoided. Last, the accuracy of the documentation in CPRS may be unclear and may have subjected the study to bias. Unfortunately, ECS does not use bar code medication administration, so the administration of medications has to be manually written into the ECS visit note. This method may be vulnerable to human error.

Future Directions

Future directions from this study include discussing the results with the MHRRTP staff and identifying areas of improvement to enhance the medication list. Some discussion points include the reasoning to remove trazodone and examples of inappropriate use. Furthermore, the questions asked by patients and general
suggestions made by the nursing staff identified that increased patient education of the PRN medication list should be implemented during the admission assessment process. This would improve patient understanding and awareness of the PRN medication list, because some patients did not know about the list or what medications it included. Moving forward, the results of this project may provide incentive for future implementation of PRN medication lists at other VA MHRRTPs.

Conclusion

This study confirms that the MHRRTP PRN medication list has been highly used since its implementation in 2010. The study also suggests that the nursing staff and patients are satisfied with the current process. Furthermore, these findings illustrate the PRN medication list’s success at decreasing unnecessary use of ECS and its association with avoiding cost. Further studies are needed to support the results seen in this analysis. Although these discoveries are preliminary, they may provide incentive for future implementation of PRN medication lists at other VA MHRRTPs.

Acknowledgements
Michelle Bury had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

Institutions conducting research involving animals have established operational frameworks, referred to as animal care and use programs (ACUPs), to ensure research animal welfare and high-quality research data and to meet ethical and regulatory requirements.^1-4 The Institutional Animal Care and Use Committee (IACUC) is a critical component of the ACUP and is responsible for the oversight and evaluation of all aspects of the ACUP.⁵ However, investigators, IACUCs, institutions, the research sponsor, and the federal government share responsibilities for ensuring research animal welfare.

Effective policies, procedures, practices, and systems in the ACUP are critical to an institution’s ability to ensure that animal research is conducted humanely and complies with applicable regulations, policies, and guidelines. To this end, considerable effort and resources have been devoted to improve the effectiveness of ACUPs, including external accreditation of ACUPs by the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC International) and implementation of science-based performance standards, postapproval monitoring, and risk assessments and mitigation of identified vulnerability.^6-9 However, the impact of these quality improvement measures remains unclear. There have been no valid, reliable, and quantifiable measures to assess the effectiveness and quality of ACUPs.      

Compliance with federal regulations is not only required, but also essential in protecting laboratory animals. However, the goal is not to ensure compliance but to prevent unnecessary harm, injury, and suffering to those research animals. Overemphasis on compliance and documentation may negatively impact the system by diverting resources away from ensuring research animal welfare. The authors propose that although research animal welfare cannot be directly measured, it is possible to assess the quality of ACUPs. High-quality ACUPs are expected to minimize risk to research animals to the extent possible while maintaining the integrity of the research.

The authors previously developed a set of quality indicators (QIs) for human research protection programs (HRPPs) at the VA, emphasizing performance outcomes built on a foundation of compliance.¹⁰ Implementation of these QIs allowed the research team to collect data to assess the quality of VA HRPPs.¹¹ It also allowed the team to answer important questions, such as whether there were significant differences in the quality of HRPPs among facilities using their own institutional review boards (IRBs) and those using affiliated university IRBs as their IRBs of record.¹² 

Background

The VA health care system (VAHCS) is the largest integrated health care system in the U.S. Currently, there are 77 VA facilities conducting research involving laboratory animals. In addition to federal regulations governing research with animals, researchers in the VAHCS must comply with requirements established by VA.^1-4  For example, in the VAHCS, the IACUC is a subcommittee of the Research and Development Committee (R&DC). Research involving animals may not be initiated until it has been approved by both the IACUC and the R&DC.^13,14 All investigators, including animal research investigators, are required to have approved scopes of practice.¹⁴ Furthermore, all VA facilities that conduct animal research are required to have their ACUPs accredited by the AAALAC International.¹³

Based on the experience gained from the VA HRPP QIs, the authors developed a set of QIs that emphasize assessing the outcome of ACUPs rather than solely on IACUC review or compliance with animal research regulations and policies. This report describes the proposed QIs for assessing the quality of VA ACUPs and presents preliminary data using some of these QIs.

Methods

The VA ACUP QIs were developed through a process that included (1) identification of a set of potential indicators by the authors; (2) review and comments on the potential indicators by individuals within and outside VA who have expertise in protecting research animal welfare, including veterinarians with board certification in laboratory animal medicine, IACUC chairs, and individuals involved in the accreditation and oversight of ACUPs; and (3) review and revision by the authors of the proposed QIs in light of the suggestions and comments received. After 6 months of deliberation, a set of 13 QIs was finalized for consideration for implementation.

Data Collection

As part of the VA ACUP quality assurance program, each VA research facility is required to conduct regulatory audits of all animal research protocols once every 3 years by qualified research compliance officers (RCOs).¹⁵ Audit tools were developed for the triennial animal protocol regulatory audits (available at http://www.va.gov/oro/rcep.asp).^11,12 Facility RCOs were then trained to use these tools to conduct audits throughout the year.

Results of the protocol regulatory audits, conducted between June 1, 2011, and May 31, 2012, were collected through a Web-based system from all 74 VA facilities conducting animal research during that period. Information collected included IACUC and R&DC initial approval of human research protocols; for-cause suspension or termination of animal research protocols; compliance with continuing review requirements; research personnel scopes of practice; and investigator animal research protection training requirements.

Because this study did not involve the use of laboratory animals, no ACUC review and approval was required.

Data Analysis

All data collected were entered into a database for analysis. When necessary, facilities were contacted to verify the accuracy and uniformity of data reported. Only descriptive statistics were obtained and presented.

Quality Indicators

As shown in the Box, a total of 13 QIs covering a broad range of areas that may have significant impact on research animal welfare were selected.

QI 1. ACUP accreditation status was chosen, because accreditation of an institutional ACUP by AAALAC International, the sole widely accepted ACUP accrediting organization, suggests that the institution establish acceptable operational frameworks to ensure research animal welfare. Because VA policy requires that all facilities conducting animal research be accredited, failure to achieve full accreditation may indicate that research animals are at an elevated risk due to a less than optimal system to protect research animals.¹³

QI 2.  IACUC and R&DC initial approval of animal research protocols was chosen because of the importance of IACUC and R&DC review and approval in ensuring the scientific merit of the research and the adequacy of research animal protection. The number and the percentage of protocols conducted without or initiated prior to IACUC and/or R&DC approval, which may put animals at risk, is a good measure of the adequacy of the institution’s ACUP.

QI 3. For-cause suspension or termination of animal research protocols was chosen, because this is a serious event. Protocols can be suspended or prematurely terminated by IACUCs due to investigators’ serious or continuing noncompliance or due to serious adverse events/injuries to the animals or research personnel. The number and percentage of protocols suspended reflect the adequacy of the IACUC oversight of the institution’s animal research program.

QI 4. Investigator sanction was chosen, because investigators and research personnel play an important role in protecting research animals. The number and percentage of investigators or technicians whose research privileges were suspended due to noncompliance reflect the adequacy of the institution’s education and training program as well as oversight of the ACUP.

QI 5. Annual review requirement was chosen because of the importance of ongoing oversight of approved animal research by the IACUC. The number and percentage of protocols lapsed in annual reviews, particularly when research activities continued during the lapse reflects the adequacy of IACUC oversight.

QI 6. Unanticipated loss of animal lives was chosen, because loss of animal lives is the most serious harm to animals that the ACUP is intended to prevent. The number and percentage of animals whose lives are unnecessarily lost due to heating, ventilation, or air-conditioning failure reflect the adequacy of the institution’s animal care infrastructure and effectiveness of the emergency response plan.

QI 7. Serious or continuing noncompliance resulting in actual harm to animals was chosen, because actual harm to animals is an important outcome measure of the adequacy of ACUP. The number and percentage of animals harmed due to investigator noncompliance or inadequate care reflect the adequacy of the institution’s veterinarian and IACUC oversight.

QI 8. Semi-annual program review and facility inspection was chosen because of the importance of semi-annual program review and facility inspection in IACUC’s oversight of the institution’s ACUP. This QI emphasizes the timely correction and remediation of both major and minor deficiencies identified during semi-annual program reviews and facility inspections. Failure to promptly address identified deficiencies in a timely manner may place research animals at significant risk.

QI 9. Scope of practice was chosen because of the importance of the investigator’s qualification in ensuring not only high-quality research data, but also adequate protection of research animals. Certain animal procedures can be safely performed only by investigators with adequate training and experience. Allowing investigators who are unqualified to perform these procedures places animals at significant risk of being harmed.

QI 10. Work- or research-related injuries was chosen because of the importance of the safety of investigators and animal caretakers in the institution’s ACUP. The importance of the institution’s occupational health and safety program in protecting investigators and animal care workers cannot be overemphasized. The number and percentage of investigators and animal care workers covered by the occupational health and safety program and work- or research-related injuries reflect the adequacy of the ACUP.

QI 11. Investigator animal care and use education/training requirements was chosen because of the important role of investigators in protecting animal welfare. The number and percentage of investigators who fail to maintain required animal care and use education/training reflect the adequacy of the institution’s IACUC oversight.

QI 12. IACUC chair and members’ animal care and use education and training requirements was chosen because of the important role of the IACUC chair and members in the institution’s ACUP. To appropriately evaluate and approve/disapprove animal research protocols, the chair and members of IACUC must maintain sufficient knowledge of federal regulations and VA policies regarding animal protections.

QI 13. Veterinarian and veterinary medical unit staff qualification was chosen because of the important role of veterinarian and veterinary medical unit staff in the day-to-day care of research animals and the specialized knowledge and qualification they need to maintain the animal research facilities. The number of veterinarians and nonveterinary animal care staff with appropriate board certifications reflects the strength of an institution’s ACUP.

Results

Recognizing the importance of assessing the quality of VA ACUPs, the authors started to collect some QI data of VA ACUPs parallel to those of VA HRPPs before the aforementioned proposed QIs for VA ACUPs were fully developed. These preliminary data are included here to demonstrate the feasibility of implementing these proposed VA ACUP QIs.

IACUC and R&DC Approvals (QI 2)

VA policies require that all animal research protocols be reviewed and approved first by the IACUC and then by the R&DC.^13,14 The IACUC is a subcommittee of the R&DC. No animal research activities in VA may be initiated before receiving both IACUC and R&DC approval.^13,14

Between June 1, 2011, and May 31, 2012, regulatory audits were conducted on 1,286 animal research protocols. Among them, 1 (0.08%) protocol was conducted and completed without the required IACUC approval, 1 (0.08%) was conducted and completed without the required R&DC approval, 1 (0.08%) was initiated prior to IACUC approval, and 2 (0.16%) were initiated prior to R&DC approval.

For-Cause Suspension or Termination (QI 3)

Among the 1,286 animal research protocols audited, 14 (1.09%) protocols were suspended or terminated for cause; 10 (0.78%) protocols were suspended or terminated due to animal safety concerns; and 4 (0.31%) protocols were suspended or terminated due to investigator-related concerns.

Lapse in Continuing Reviews (QI 5)

Federal regulations and VA policies require that IACUC conduct continuing review of all animal research protocols annually.^2,13 Of the 1,286 animal research protocols audited, 1,159 protocols required IACUC continuing reviews during the auditing period. Fifty-three protocols (4.57%) lapsed in IACUC annual reviews, and in 25 of these 53 protocols, investigators continued research activities during the lapse.

Scope of Practice (QI 9)                                                                   

VA policies require all research personnel to have an approved research scope of practice or functional statement that defines the duties that the individual is qualified and allowed to perform for research purposes.¹⁴

A total of 4,604 research personnel records were reviewed from the 1,286 animal research protocols audited. Of these, 276 (5.99%) did not have an approved research scope of practice; 1 (0.02%) had an approved research scope of practice but was working outside the approved research scope of practice.

Training Requirements (QI 11)

VA policies require that all research personnel who participate in animal research complete initial and annual training to ensure that they can competently and humanely perform their duties related to animal research.¹⁴

Among the 4,604 animal research personnel records reviewed, 186 (4.04%) did not maintain their training requirements, including 26 (0.56%) without required initial training and 160 (3.48%) with lapses in required continuing training.

Discussion

Collectively, these proposed QIs should provide useful information about the overall quality of an ACUP. This allows semiquantitative assessment of the quality and performance of VA facilities’ ACUPs over time and comparison of the performance of ACUPs across research facilities in the VAHCS. The information obtained may also help administrators identify program vulnerabilities and make management decisions regarding where improvements are most needed. Specifically, QI data will be collected from all VA research facilities’ ACUPs annually. National averages for all QIs will be calculated. Each facility will then be provided with the results of its own ACUP QI data as well as the national averages, allowing the facility to compare its QI data with the national averages and determine how its ACUP performs compared with the overall VA ACUP performance.

These QIs were designed for use in assessing the quality of ACUPs at VA research facilities annually or at least once every other year. With the recent requirement that a full-time RCO at each VA research facility conduct regulatory audits of all animal research protocols once every 3 years, it is feasible that an assessment of the VA ACUPs using these QIs could be conducted annually as demonstrated by the preliminary data for QIs 2, 3, 5, 9, and 11 reported here.^15,16 These preliminary data also showed high rates of lapses in IACUC continuing review (4.57%), lack of research personnel scopes of practice (5.99%), and noncompliance with training requirements (4.04%). These are areas that need improvements.

The size and complexity of animal research programs are different among different facilities, which can make it difficult to compare different facilities’ ACUPs using the same quality measures. In addition, VA facilities may use their own IACUCs or the affiliate university IACUCs as the IACUCs of record. However, based on the authors’ experience  using HRPP QIs to assess the quality of VA HRPPs, the collected data using ACUP QIs will help determine whether such variables as the size and complexity of a program or the kind of IACUCs used (either VA, own IACUC, or affiliate IACUC) affect the quality of VA ACUPs.^10-12

Limitations

There is no evidence proving that these QIs are the most optimal measures for evaluating the quality of a VA facility’s ACUP. It is also unknown whether these QIs correlate directly with the protection of research animals. Furthermore, a quantitative, numerical value cannot be put on each indicator to allow evaluators to rank facilities’ ACUPs.

Some QIs, such as QIs 3, 4, 7, and 8, may depend on how stringent an IACUC is. For example, it is possible that a conscientious IACUC may report more noncompliance or suspend more protocols, giving the appearance of a poor quality ACUP, whereas in fact it might be an excellent program. However, the authors want to emphasize that no single QI by itself is sufficient to assess the quality of a program. It is the combination of various QIs that provides information about the overall quality of a program. It is also through the data collected that the usefulness of any particular indicators may be determined.     

Conclusion

These proposed QIs provide a useful first step toward developing a robust and valid assessment of VA ACUPs. As these QIs are used at VA facilities, they will likely be redefined and modified. The authors hope that other institutions will find these indicators useful as they develop instruments to assess their own ACUPs.

Acknowledgement
The authors thank Dr. Kathryn Bayne, Global Director, Association for Assessment and Accreditation of Laboratory Animal Care International, for her suggestions and comments during the development of these quality indicators and critical review of the manuscript, and Dr. J. Thomas Puglisi, Chief Officer, VA Office of Research Oversight, for his support and critical review of the manuscript. 

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

Institutions conducting research involving animals have established operational frameworks, referred to as animal care and use programs (ACUPs), to ensure research animal welfare and high-quality research data and to meet ethical and regulatory requirements.^1-4 The Institutional Animal Care and Use Committee (IACUC) is a critical component of the ACUP and is responsible for the oversight and evaluation of all aspects of the ACUP.⁵ However, investigators, IACUCs, institutions, the research sponsor, and the federal government share responsibilities for ensuring research animal welfare.

Effective policies, procedures, practices, and systems in the ACUP are critical to an institution’s ability to ensure that animal research is conducted humanely and complies with applicable regulations, policies, and guidelines. To this end, considerable effort and resources have been devoted to improve the effectiveness of ACUPs, including external accreditation of ACUPs by the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC International) and implementation of science-based performance standards, postapproval monitoring, and risk assessments and mitigation of identified vulnerability.^6-9 However, the impact of these quality improvement measures remains unclear. There have been no valid, reliable, and quantifiable measures to assess the effectiveness and quality of ACUPs.      

Compliance with federal regulations is not only required, but also essential in protecting laboratory animals. However, the goal is not to ensure compliance but to prevent unnecessary harm, injury, and suffering to those research animals. Overemphasis on compliance and documentation may negatively impact the system by diverting resources away from ensuring research animal welfare. The authors propose that although research animal welfare cannot be directly measured, it is possible to assess the quality of ACUPs. High-quality ACUPs are expected to minimize risk to research animals to the extent possible while maintaining the integrity of the research.

The authors previously developed a set of quality indicators (QIs) for human research protection programs (HRPPs) at the VA, emphasizing performance outcomes built on a foundation of compliance.¹⁰ Implementation of these QIs allowed the research team to collect data to assess the quality of VA HRPPs.¹¹ It also allowed the team to answer important questions, such as whether there were significant differences in the quality of HRPPs among facilities using their own institutional review boards (IRBs) and those using affiliated university IRBs as their IRBs of record.¹² 

Background

The VA health care system (VAHCS) is the largest integrated health care system in the U.S. Currently, there are 77 VA facilities conducting research involving laboratory animals. In addition to federal regulations governing research with animals, researchers in the VAHCS must comply with requirements established by VA.^1-4  For example, in the VAHCS, the IACUC is a subcommittee of the Research and Development Committee (R&DC). Research involving animals may not be initiated until it has been approved by both the IACUC and the R&DC.^13,14 All investigators, including animal research investigators, are required to have approved scopes of practice.¹⁴ Furthermore, all VA facilities that conduct animal research are required to have their ACUPs accredited by the AAALAC International.¹³

Based on the experience gained from the VA HRPP QIs, the authors developed a set of QIs that emphasize assessing the outcome of ACUPs rather than solely on IACUC review or compliance with animal research regulations and policies. This report describes the proposed QIs for assessing the quality of VA ACUPs and presents preliminary data using some of these QIs.

Methods

The VA ACUP QIs were developed through a process that included (1) identification of a set of potential indicators by the authors; (2) review and comments on the potential indicators by individuals within and outside VA who have expertise in protecting research animal welfare, including veterinarians with board certification in laboratory animal medicine, IACUC chairs, and individuals involved in the accreditation and oversight of ACUPs; and (3) review and revision by the authors of the proposed QIs in light of the suggestions and comments received. After 6 months of deliberation, a set of 13 QIs was finalized for consideration for implementation.

Data Collection

As part of the VA ACUP quality assurance program, each VA research facility is required to conduct regulatory audits of all animal research protocols once every 3 years by qualified research compliance officers (RCOs).¹⁵ Audit tools were developed for the triennial animal protocol regulatory audits (available at http://www.va.gov/oro/rcep.asp).^11,12 Facility RCOs were then trained to use these tools to conduct audits throughout the year.

Results of the protocol regulatory audits, conducted between June 1, 2011, and May 31, 2012, were collected through a Web-based system from all 74 VA facilities conducting animal research during that period. Information collected included IACUC and R&DC initial approval of human research protocols; for-cause suspension or termination of animal research protocols; compliance with continuing review requirements; research personnel scopes of practice; and investigator animal research protection training requirements.

Because this study did not involve the use of laboratory animals, no ACUC review and approval was required.

Data Analysis

All data collected were entered into a database for analysis. When necessary, facilities were contacted to verify the accuracy and uniformity of data reported. Only descriptive statistics were obtained and presented.

Quality Indicators

As shown in the Box, a total of 13 QIs covering a broad range of areas that may have significant impact on research animal welfare were selected.

QI 1. ACUP accreditation status was chosen, because accreditation of an institutional ACUP by AAALAC International, the sole widely accepted ACUP accrediting organization, suggests that the institution establish acceptable operational frameworks to ensure research animal welfare. Because VA policy requires that all facilities conducting animal research be accredited, failure to achieve full accreditation may indicate that research animals are at an elevated risk due to a less than optimal system to protect research animals.¹³

QI 2.  IACUC and R&DC initial approval of animal research protocols was chosen because of the importance of IACUC and R&DC review and approval in ensuring the scientific merit of the research and the adequacy of research animal protection. The number and the percentage of protocols conducted without or initiated prior to IACUC and/or R&DC approval, which may put animals at risk, is a good measure of the adequacy of the institution’s ACUP.

QI 3. For-cause suspension or termination of animal research protocols was chosen, because this is a serious event. Protocols can be suspended or prematurely terminated by IACUCs due to investigators’ serious or continuing noncompliance or due to serious adverse events/injuries to the animals or research personnel. The number and percentage of protocols suspended reflect the adequacy of the IACUC oversight of the institution’s animal research program.

QI 4. Investigator sanction was chosen, because investigators and research personnel play an important role in protecting research animals. The number and percentage of investigators or technicians whose research privileges were suspended due to noncompliance reflect the adequacy of the institution’s education and training program as well as oversight of the ACUP.

QI 5. Annual review requirement was chosen because of the importance of ongoing oversight of approved animal research by the IACUC. The number and percentage of protocols lapsed in annual reviews, particularly when research activities continued during the lapse reflects the adequacy of IACUC oversight.

QI 6. Unanticipated loss of animal lives was chosen, because loss of animal lives is the most serious harm to animals that the ACUP is intended to prevent. The number and percentage of animals whose lives are unnecessarily lost due to heating, ventilation, or air-conditioning failure reflect the adequacy of the institution’s animal care infrastructure and effectiveness of the emergency response plan.

QI 7. Serious or continuing noncompliance resulting in actual harm to animals was chosen, because actual harm to animals is an important outcome measure of the adequacy of ACUP. The number and percentage of animals harmed due to investigator noncompliance or inadequate care reflect the adequacy of the institution’s veterinarian and IACUC oversight.

QI 8. Semi-annual program review and facility inspection was chosen because of the importance of semi-annual program review and facility inspection in IACUC’s oversight of the institution’s ACUP. This QI emphasizes the timely correction and remediation of both major and minor deficiencies identified during semi-annual program reviews and facility inspections. Failure to promptly address identified deficiencies in a timely manner may place research animals at significant risk.

QI 9. Scope of practice was chosen because of the importance of the investigator’s qualification in ensuring not only high-quality research data, but also adequate protection of research animals. Certain animal procedures can be safely performed only by investigators with adequate training and experience. Allowing investigators who are unqualified to perform these procedures places animals at significant risk of being harmed.

QI 10. Work- or research-related injuries was chosen because of the importance of the safety of investigators and animal caretakers in the institution’s ACUP. The importance of the institution’s occupational health and safety program in protecting investigators and animal care workers cannot be overemphasized. The number and percentage of investigators and animal care workers covered by the occupational health and safety program and work- or research-related injuries reflect the adequacy of the ACUP.

QI 11. Investigator animal care and use education/training requirements was chosen because of the important role of investigators in protecting animal welfare. The number and percentage of investigators who fail to maintain required animal care and use education/training reflect the adequacy of the institution’s IACUC oversight.

QI 12. IACUC chair and members’ animal care and use education and training requirements was chosen because of the important role of the IACUC chair and members in the institution’s ACUP. To appropriately evaluate and approve/disapprove animal research protocols, the chair and members of IACUC must maintain sufficient knowledge of federal regulations and VA policies regarding animal protections.

QI 13. Veterinarian and veterinary medical unit staff qualification was chosen because of the important role of veterinarian and veterinary medical unit staff in the day-to-day care of research animals and the specialized knowledge and qualification they need to maintain the animal research facilities. The number of veterinarians and nonveterinary animal care staff with appropriate board certifications reflects the strength of an institution’s ACUP.

Results

Recognizing the importance of assessing the quality of VA ACUPs, the authors started to collect some QI data of VA ACUPs parallel to those of VA HRPPs before the aforementioned proposed QIs for VA ACUPs were fully developed. These preliminary data are included here to demonstrate the feasibility of implementing these proposed VA ACUP QIs.

IACUC and R&DC Approvals (QI 2)

VA policies require that all animal research protocols be reviewed and approved first by the IACUC and then by the R&DC.^13,14 The IACUC is a subcommittee of the R&DC. No animal research activities in VA may be initiated before receiving both IACUC and R&DC approval.^13,14

Between June 1, 2011, and May 31, 2012, regulatory audits were conducted on 1,286 animal research protocols. Among them, 1 (0.08%) protocol was conducted and completed without the required IACUC approval, 1 (0.08%) was conducted and completed without the required R&DC approval, 1 (0.08%) was initiated prior to IACUC approval, and 2 (0.16%) were initiated prior to R&DC approval.

For-Cause Suspension or Termination (QI 3)

Among the 1,286 animal research protocols audited, 14 (1.09%) protocols were suspended or terminated for cause; 10 (0.78%) protocols were suspended or terminated due to animal safety concerns; and 4 (0.31%) protocols were suspended or terminated due to investigator-related concerns.

Lapse in Continuing Reviews (QI 5)

Federal regulations and VA policies require that IACUC conduct continuing review of all animal research protocols annually.^2,13 Of the 1,286 animal research protocols audited, 1,159 protocols required IACUC continuing reviews during the auditing period. Fifty-three protocols (4.57%) lapsed in IACUC annual reviews, and in 25 of these 53 protocols, investigators continued research activities during the lapse.

Scope of Practice (QI 9)                                                                   

VA policies require all research personnel to have an approved research scope of practice or functional statement that defines the duties that the individual is qualified and allowed to perform for research purposes.¹⁴

A total of 4,604 research personnel records were reviewed from the 1,286 animal research protocols audited. Of these, 276 (5.99%) did not have an approved research scope of practice; 1 (0.02%) had an approved research scope of practice but was working outside the approved research scope of practice.

Training Requirements (QI 11)

VA policies require that all research personnel who participate in animal research complete initial and annual training to ensure that they can competently and humanely perform their duties related to animal research.¹⁴

Among the 4,604 animal research personnel records reviewed, 186 (4.04%) did not maintain their training requirements, including 26 (0.56%) without required initial training and 160 (3.48%) with lapses in required continuing training.

Discussion

Collectively, these proposed QIs should provide useful information about the overall quality of an ACUP. This allows semiquantitative assessment of the quality and performance of VA facilities’ ACUPs over time and comparison of the performance of ACUPs across research facilities in the VAHCS. The information obtained may also help administrators identify program vulnerabilities and make management decisions regarding where improvements are most needed. Specifically, QI data will be collected from all VA research facilities’ ACUPs annually. National averages for all QIs will be calculated. Each facility will then be provided with the results of its own ACUP QI data as well as the national averages, allowing the facility to compare its QI data with the national averages and determine how its ACUP performs compared with the overall VA ACUP performance.

These QIs were designed for use in assessing the quality of ACUPs at VA research facilities annually or at least once every other year. With the recent requirement that a full-time RCO at each VA research facility conduct regulatory audits of all animal research protocols once every 3 years, it is feasible that an assessment of the VA ACUPs using these QIs could be conducted annually as demonstrated by the preliminary data for QIs 2, 3, 5, 9, and 11 reported here.^15,16 These preliminary data also showed high rates of lapses in IACUC continuing review (4.57%), lack of research personnel scopes of practice (5.99%), and noncompliance with training requirements (4.04%). These are areas that need improvements.

The size and complexity of animal research programs are different among different facilities, which can make it difficult to compare different facilities’ ACUPs using the same quality measures. In addition, VA facilities may use their own IACUCs or the affiliate university IACUCs as the IACUCs of record. However, based on the authors’ experience  using HRPP QIs to assess the quality of VA HRPPs, the collected data using ACUP QIs will help determine whether such variables as the size and complexity of a program or the kind of IACUCs used (either VA, own IACUC, or affiliate IACUC) affect the quality of VA ACUPs.^10-12

Limitations

There is no evidence proving that these QIs are the most optimal measures for evaluating the quality of a VA facility’s ACUP. It is also unknown whether these QIs correlate directly with the protection of research animals. Furthermore, a quantitative, numerical value cannot be put on each indicator to allow evaluators to rank facilities’ ACUPs.

Some QIs, such as QIs 3, 4, 7, and 8, may depend on how stringent an IACUC is. For example, it is possible that a conscientious IACUC may report more noncompliance or suspend more protocols, giving the appearance of a poor quality ACUP, whereas in fact it might be an excellent program. However, the authors want to emphasize that no single QI by itself is sufficient to assess the quality of a program. It is the combination of various QIs that provides information about the overall quality of a program. It is also through the data collected that the usefulness of any particular indicators may be determined.     

Conclusion

These proposed QIs provide a useful first step toward developing a robust and valid assessment of VA ACUPs. As these QIs are used at VA facilities, they will likely be redefined and modified. The authors hope that other institutions will find these indicators useful as they develop instruments to assess their own ACUPs.

Acknowledgement
The authors thank Dr. Kathryn Bayne, Global Director, Association for Assessment and Accreditation of Laboratory Animal Care International, for her suggestions and comments during the development of these quality indicators and critical review of the manuscript, and Dr. J. Thomas Puglisi, Chief Officer, VA Office of Research Oversight, for his support and critical review of the manuscript. 

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

Institutions conducting research involving animals have established operational frameworks, referred to as animal care and use programs (ACUPs), to ensure research animal welfare and high-quality research data and to meet ethical and regulatory requirements.^1-4 The Institutional Animal Care and Use Committee (IACUC) is a critical component of the ACUP and is responsible for the oversight and evaluation of all aspects of the ACUP.⁵ However, investigators, IACUCs, institutions, the research sponsor, and the federal government share responsibilities for ensuring research animal welfare.

Effective policies, procedures, practices, and systems in the ACUP are critical to an institution’s ability to ensure that animal research is conducted humanely and complies with applicable regulations, policies, and guidelines. To this end, considerable effort and resources have been devoted to improve the effectiveness of ACUPs, including external accreditation of ACUPs by the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC International) and implementation of science-based performance standards, postapproval monitoring, and risk assessments and mitigation of identified vulnerability.^6-9 However, the impact of these quality improvement measures remains unclear. There have been no valid, reliable, and quantifiable measures to assess the effectiveness and quality of ACUPs.      

Compliance with federal regulations is not only required, but also essential in protecting laboratory animals. However, the goal is not to ensure compliance but to prevent unnecessary harm, injury, and suffering to those research animals. Overemphasis on compliance and documentation may negatively impact the system by diverting resources away from ensuring research animal welfare. The authors propose that although research animal welfare cannot be directly measured, it is possible to assess the quality of ACUPs. High-quality ACUPs are expected to minimize risk to research animals to the extent possible while maintaining the integrity of the research.

The authors previously developed a set of quality indicators (QIs) for human research protection programs (HRPPs) at the VA, emphasizing performance outcomes built on a foundation of compliance.¹⁰ Implementation of these QIs allowed the research team to collect data to assess the quality of VA HRPPs.¹¹ It also allowed the team to answer important questions, such as whether there were significant differences in the quality of HRPPs among facilities using their own institutional review boards (IRBs) and those using affiliated university IRBs as their IRBs of record.¹² 

Background

The VA health care system (VAHCS) is the largest integrated health care system in the U.S. Currently, there are 77 VA facilities conducting research involving laboratory animals. In addition to federal regulations governing research with animals, researchers in the VAHCS must comply with requirements established by VA.^1-4  For example, in the VAHCS, the IACUC is a subcommittee of the Research and Development Committee (R&DC). Research involving animals may not be initiated until it has been approved by both the IACUC and the R&DC.^13,14 All investigators, including animal research investigators, are required to have approved scopes of practice.¹⁴ Furthermore, all VA facilities that conduct animal research are required to have their ACUPs accredited by the AAALAC International.¹³

Based on the experience gained from the VA HRPP QIs, the authors developed a set of QIs that emphasize assessing the outcome of ACUPs rather than solely on IACUC review or compliance with animal research regulations and policies. This report describes the proposed QIs for assessing the quality of VA ACUPs and presents preliminary data using some of these QIs.

Methods

The VA ACUP QIs were developed through a process that included (1) identification of a set of potential indicators by the authors; (2) review and comments on the potential indicators by individuals within and outside VA who have expertise in protecting research animal welfare, including veterinarians with board certification in laboratory animal medicine, IACUC chairs, and individuals involved in the accreditation and oversight of ACUPs; and (3) review and revision by the authors of the proposed QIs in light of the suggestions and comments received. After 6 months of deliberation, a set of 13 QIs was finalized for consideration for implementation.

Data Collection

As part of the VA ACUP quality assurance program, each VA research facility is required to conduct regulatory audits of all animal research protocols once every 3 years by qualified research compliance officers (RCOs).¹⁵ Audit tools were developed for the triennial animal protocol regulatory audits (available at http://www.va.gov/oro/rcep.asp).^11,12 Facility RCOs were then trained to use these tools to conduct audits throughout the year.

Results of the protocol regulatory audits, conducted between June 1, 2011, and May 31, 2012, were collected through a Web-based system from all 74 VA facilities conducting animal research during that period. Information collected included IACUC and R&DC initial approval of human research protocols; for-cause suspension or termination of animal research protocols; compliance with continuing review requirements; research personnel scopes of practice; and investigator animal research protection training requirements.

Because this study did not involve the use of laboratory animals, no ACUC review and approval was required.

Data Analysis

All data collected were entered into a database for analysis. When necessary, facilities were contacted to verify the accuracy and uniformity of data reported. Only descriptive statistics were obtained and presented.

Quality Indicators

As shown in the Box, a total of 13 QIs covering a broad range of areas that may have significant impact on research animal welfare were selected.

QI 1. ACUP accreditation status was chosen, because accreditation of an institutional ACUP by AAALAC International, the sole widely accepted ACUP accrediting organization, suggests that the institution establish acceptable operational frameworks to ensure research animal welfare. Because VA policy requires that all facilities conducting animal research be accredited, failure to achieve full accreditation may indicate that research animals are at an elevated risk due to a less than optimal system to protect research animals.¹³

QI 2.  IACUC and R&DC initial approval of animal research protocols was chosen because of the importance of IACUC and R&DC review and approval in ensuring the scientific merit of the research and the adequacy of research animal protection. The number and the percentage of protocols conducted without or initiated prior to IACUC and/or R&DC approval, which may put animals at risk, is a good measure of the adequacy of the institution’s ACUP.

QI 3. For-cause suspension or termination of animal research protocols was chosen, because this is a serious event. Protocols can be suspended or prematurely terminated by IACUCs due to investigators’ serious or continuing noncompliance or due to serious adverse events/injuries to the animals or research personnel. The number and percentage of protocols suspended reflect the adequacy of the IACUC oversight of the institution’s animal research program.

QI 4. Investigator sanction was chosen, because investigators and research personnel play an important role in protecting research animals. The number and percentage of investigators or technicians whose research privileges were suspended due to noncompliance reflect the adequacy of the institution’s education and training program as well as oversight of the ACUP.

QI 5. Annual review requirement was chosen because of the importance of ongoing oversight of approved animal research by the IACUC. The number and percentage of protocols lapsed in annual reviews, particularly when research activities continued during the lapse reflects the adequacy of IACUC oversight.

QI 6. Unanticipated loss of animal lives was chosen, because loss of animal lives is the most serious harm to animals that the ACUP is intended to prevent. The number and percentage of animals whose lives are unnecessarily lost due to heating, ventilation, or air-conditioning failure reflect the adequacy of the institution’s animal care infrastructure and effectiveness of the emergency response plan.

QI 7. Serious or continuing noncompliance resulting in actual harm to animals was chosen, because actual harm to animals is an important outcome measure of the adequacy of ACUP. The number and percentage of animals harmed due to investigator noncompliance or inadequate care reflect the adequacy of the institution’s veterinarian and IACUC oversight.

QI 8. Semi-annual program review and facility inspection was chosen because of the importance of semi-annual program review and facility inspection in IACUC’s oversight of the institution’s ACUP. This QI emphasizes the timely correction and remediation of both major and minor deficiencies identified during semi-annual program reviews and facility inspections. Failure to promptly address identified deficiencies in a timely manner may place research animals at significant risk.

QI 9. Scope of practice was chosen because of the importance of the investigator’s qualification in ensuring not only high-quality research data, but also adequate protection of research animals. Certain animal procedures can be safely performed only by investigators with adequate training and experience. Allowing investigators who are unqualified to perform these procedures places animals at significant risk of being harmed.

QI 10. Work- or research-related injuries was chosen because of the importance of the safety of investigators and animal caretakers in the institution’s ACUP. The importance of the institution’s occupational health and safety program in protecting investigators and animal care workers cannot be overemphasized. The number and percentage of investigators and animal care workers covered by the occupational health and safety program and work- or research-related injuries reflect the adequacy of the ACUP.

QI 11. Investigator animal care and use education/training requirements was chosen because of the important role of investigators in protecting animal welfare. The number and percentage of investigators who fail to maintain required animal care and use education/training reflect the adequacy of the institution’s IACUC oversight.

QI 12. IACUC chair and members’ animal care and use education and training requirements was chosen because of the important role of the IACUC chair and members in the institution’s ACUP. To appropriately evaluate and approve/disapprove animal research protocols, the chair and members of IACUC must maintain sufficient knowledge of federal regulations and VA policies regarding animal protections.

QI 13. Veterinarian and veterinary medical unit staff qualification was chosen because of the important role of veterinarian and veterinary medical unit staff in the day-to-day care of research animals and the specialized knowledge and qualification they need to maintain the animal research facilities. The number of veterinarians and nonveterinary animal care staff with appropriate board certifications reflects the strength of an institution’s ACUP.

Results

Recognizing the importance of assessing the quality of VA ACUPs, the authors started to collect some QI data of VA ACUPs parallel to those of VA HRPPs before the aforementioned proposed QIs for VA ACUPs were fully developed. These preliminary data are included here to demonstrate the feasibility of implementing these proposed VA ACUP QIs.

IACUC and R&DC Approvals (QI 2)

VA policies require that all animal research protocols be reviewed and approved first by the IACUC and then by the R&DC.^13,14 The IACUC is a subcommittee of the R&DC. No animal research activities in VA may be initiated before receiving both IACUC and R&DC approval.^13,14

Between June 1, 2011, and May 31, 2012, regulatory audits were conducted on 1,286 animal research protocols. Among them, 1 (0.08%) protocol was conducted and completed without the required IACUC approval, 1 (0.08%) was conducted and completed without the required R&DC approval, 1 (0.08%) was initiated prior to IACUC approval, and 2 (0.16%) were initiated prior to R&DC approval.

For-Cause Suspension or Termination (QI 3)

Among the 1,286 animal research protocols audited, 14 (1.09%) protocols were suspended or terminated for cause; 10 (0.78%) protocols were suspended or terminated due to animal safety concerns; and 4 (0.31%) protocols were suspended or terminated due to investigator-related concerns.

Lapse in Continuing Reviews (QI 5)

Federal regulations and VA policies require that IACUC conduct continuing review of all animal research protocols annually.^2,13 Of the 1,286 animal research protocols audited, 1,159 protocols required IACUC continuing reviews during the auditing period. Fifty-three protocols (4.57%) lapsed in IACUC annual reviews, and in 25 of these 53 protocols, investigators continued research activities during the lapse.

Scope of Practice (QI 9)                                                                   

VA policies require all research personnel to have an approved research scope of practice or functional statement that defines the duties that the individual is qualified and allowed to perform for research purposes.¹⁴

A total of 4,604 research personnel records were reviewed from the 1,286 animal research protocols audited. Of these, 276 (5.99%) did not have an approved research scope of practice; 1 (0.02%) had an approved research scope of practice but was working outside the approved research scope of practice.

Training Requirements (QI 11)

VA policies require that all research personnel who participate in animal research complete initial and annual training to ensure that they can competently and humanely perform their duties related to animal research.¹⁴

Among the 4,604 animal research personnel records reviewed, 186 (4.04%) did not maintain their training requirements, including 26 (0.56%) without required initial training and 160 (3.48%) with lapses in required continuing training.

Discussion

Collectively, these proposed QIs should provide useful information about the overall quality of an ACUP. This allows semiquantitative assessment of the quality and performance of VA facilities’ ACUPs over time and comparison of the performance of ACUPs across research facilities in the VAHCS. The information obtained may also help administrators identify program vulnerabilities and make management decisions regarding where improvements are most needed. Specifically, QI data will be collected from all VA research facilities’ ACUPs annually. National averages for all QIs will be calculated. Each facility will then be provided with the results of its own ACUP QI data as well as the national averages, allowing the facility to compare its QI data with the national averages and determine how its ACUP performs compared with the overall VA ACUP performance.

These QIs were designed for use in assessing the quality of ACUPs at VA research facilities annually or at least once every other year. With the recent requirement that a full-time RCO at each VA research facility conduct regulatory audits of all animal research protocols once every 3 years, it is feasible that an assessment of the VA ACUPs using these QIs could be conducted annually as demonstrated by the preliminary data for QIs 2, 3, 5, 9, and 11 reported here.^15,16 These preliminary data also showed high rates of lapses in IACUC continuing review (4.57%), lack of research personnel scopes of practice (5.99%), and noncompliance with training requirements (4.04%). These are areas that need improvements.

The size and complexity of animal research programs are different among different facilities, which can make it difficult to compare different facilities’ ACUPs using the same quality measures. In addition, VA facilities may use their own IACUCs or the affiliate university IACUCs as the IACUCs of record. However, based on the authors’ experience  using HRPP QIs to assess the quality of VA HRPPs, the collected data using ACUP QIs will help determine whether such variables as the size and complexity of a program or the kind of IACUCs used (either VA, own IACUC, or affiliate IACUC) affect the quality of VA ACUPs.^10-12

Limitations

There is no evidence proving that these QIs are the most optimal measures for evaluating the quality of a VA facility’s ACUP. It is also unknown whether these QIs correlate directly with the protection of research animals. Furthermore, a quantitative, numerical value cannot be put on each indicator to allow evaluators to rank facilities’ ACUPs.

Some QIs, such as QIs 3, 4, 7, and 8, may depend on how stringent an IACUC is. For example, it is possible that a conscientious IACUC may report more noncompliance or suspend more protocols, giving the appearance of a poor quality ACUP, whereas in fact it might be an excellent program. However, the authors want to emphasize that no single QI by itself is sufficient to assess the quality of a program. It is the combination of various QIs that provides information about the overall quality of a program. It is also through the data collected that the usefulness of any particular indicators may be determined.     

Conclusion

These proposed QIs provide a useful first step toward developing a robust and valid assessment of VA ACUPs. As these QIs are used at VA facilities, they will likely be redefined and modified. The authors hope that other institutions will find these indicators useful as they develop instruments to assess their own ACUPs.

Acknowledgement
The authors thank Dr. Kathryn Bayne, Global Director, Association for Assessment and Accreditation of Laboratory Animal Care International, for her suggestions and comments during the development of these quality indicators and critical review of the manuscript, and Dr. J. Thomas Puglisi, Chief Officer, VA Office of Research Oversight, for his support and critical review of the manuscript. 

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

The progressive symptoms of diabetic peripheral neuropathy (DPN) are some of the most frequent presentations of patients seeking care at the VHA. Patients with DPN often experience unmanageable pain in the lower extremities, loss of sensation in the feet, loss of balance, and an inability to perform daily functional activities.¹ In addition, these patients are at significant risk for lower extremity ulceration and amputation.² The symptoms and consequences of DPN are strongly linked to chronic use of pain medications as well as increased fall risk and injury.³ The high health care usage of veterans with these complex issues makes DPN a significant burden for the patient, the VHA, and society as a whole.

At the William Jennings Bryan Dorn VA Medical Center (WJBDVAMC) in Columbia, South Carolina, 10,763 veterans were identified to be at risk for limb loss in 2014 due to loss of protective sensation and 5,667 veterans diagnosed with DPN were treated in 2014.⁴ Although WJBDVAMC offers multiple clinics and programs to address the complex issues of diabetes and DPN, veterans oftentimes continue to experience uncontrolled pain, loss of protective sensation, and a decline in function even after diagnosis.

One area of improvement the authors identified in the WJBDVAMC Physical Medicine and Rehabilitation Services Department was the need for an effective, nonpharmacologic treatment for patients who experience DPN. As a result, the authors designed a pilot research study to determine whether or not a combined physical therapy intervention of monochromatic near-infrared energy (MIRE) treatments and a standardized balance exercise program would help improve the protective sensation, reduce fall risk, and decrease the adverse impact of pain on daily function. The study was approved by the institutional review board (IRB) and had no outside source of funding.

Background

Current treatments for DPN are primarily pharmacologic and are viewed as only moderately effective, limited by significant adverse effects (AEs) and drug interactions.⁵ Patients in the VHA at risk for amputation in low-, moderate-, and high-risk groups total 541,475 and 363,468 have a history of neuropathy. They are considered at risk due to multiple, documented factors, including weakness, callus, foot deformity, loss of protective sensation, and/or history of amputation.⁴ Neuropathy can affect tissues throughout the body, including organs, sensory neurons, cardiovascular status, the autonomic system, and the gastrointestinal tract as it progresses.

Individuals who develop DPN often experience severe, uncontrolled pain in the lower extremities, insensate feet, and decreased proprioceptive skills. The functional status of individuals with DPN often declines insidiously while mortality rate increases.⁶ Increased levels of neuropathic pain often lead to decreased activity levels, which, in turn, contribute to decreased endurance, poorly managed glycemic indexes, decreased strength, and decreased independence.

Additional DPN complications, such as decreased sensation and muscle atrophy in the lower extremities, often lead to foot deformity and increased areas of pressure during weight bearing postures. These areas of increased pressure may develop unknowingly into ulceration. If a patient’s wound becomes chronic and nonhealing, it can also lead to amputation. In such cases, early mortality may result.^6,7 The cascading effects of neuropathic pain and decreased sensation place a patient with diabetes at risk for falls. Injuries from falls are widely known to be a leading cause of hospitalization and mortality in the elderly.⁸

Physical therapy may be prescribed for DPN and its resulting sequelae. Several studies present conflicting results regarding the benefits of therapeutic exercise in the treatment of DPN. Akbari and colleagues showed that balance exercises can increase stability in patients with DPN; whereas, a study by Kruse and colleagues noted a training program consisting of lower-extremity exercises, balance training, and walking resulted in minimal improvement of participants’ balance and leg strength over a 12-month period.^9,10 Recent studies have shown that weight bearing does not increase ulceration in patients with diabetes and DPN. This is contrary to previous assumptions that patients with diabetes and DPN need to avoid weight-bearing activities.^11,12

Transcutaneous electrical nerve stimulation (TENS), a modality often used in physical therapy, has been studied in the treatment of DPN with conflicting results. Gossrau and colleagues found that pain reduction with micro-TENS applied peripherally is not superior to a placebo.¹³ However, a case study by Somers and Somers indicated that TENS applied to the lumbar area seemed to reduce pain and insomnia associated with diabetic neuropathy.¹⁴

Several recent research studies suggest that MIRE, another available modality, may be effective in treating symptoms of DPN. Monochromatic infrared energy therapy is a noninvasive, drug-free, FDA-approved medical device that emits monochromatic near-infrared light to improve local circulation and decrease pain. A large study of 2,239 patients with DPN reported an increase in foot sensation and decreased neuropathic pain levels when treated with MIRE.¹⁵

Leonard and colleagues found that the MIRE treatments resulted in a significant increase in sensation in individuals with baseline sensation of 6.65 Semmes-Weinstein Monofilament (SWM) after 6 and 12 active treatments as well as a decrease in neuropathic symptoms as measured by the Michigan Neuropathy Screening Instrument.¹⁶ Prendergast and colleagues noted improved electrophysical changes in both large and small myelinated nerve fibers of patients with DPN following 10 MIRE treatments.¹⁷ When studying 49 patients with DPN, Kochman and colleagues found 100% of participants had improved sensation after 12 MIRE treatments when tested with monofilaments.¹⁸

An additional benefit of MIRE treatment is that it can be safely performed at home once the patient is educated on proper use and application. Home DPN treatment has the potential to decrease the burden this population places on health care systems by reducing provider visits, medication, hospitalization secondary to pain, ulceration, fall injuries, and amputations.

Methods

This was a prospective, case series pilot study designed to measure changes in patient pain levels using the visual analog scale (VAS) and Pain Outcomes Questionnaire-VA (POQ-VA), degree of protective sensation loss as measured by SWM, and fall risk as denoted by Tinetti scores from entry to 6 months. Informed consent was obtained prior to treatment, and 33 patients referred by primary care providers and specialty clinics met the criteria and enrolled in the study. Twenty-one patients completed the entire 6-month study. The nonparametric Friedman test with a Dunn’s multiple comparison (DMC) post hoc test was used to analyze the data from the initial, 4-week, 3-month, and 6-month follow-up visits.

Setting and Participants

The study was performed in the Outpatient Physical Therapy Department at WJBDVAMC. Veterans with DPN who met the inclusion/exclusion criteria were enrolled. Inclusion criteria specified that the participant must be referred by a qualified health care provider for the treatment of DPN, be able to read and write in English, have consistent transportation to and from the study location, and be able to apply MIRE therapy as directed at home.

Exclusion criteria were subjects for whom MIRE or exercise were contraindicated. Subjects were excluded if they had medical conditions that suggested a possible decline in health status in the next 6 months. Such conditions included a current regimen of chemotherapy, radiation therapy, or dialysis; recent lower extremity amputation without prosthesis; documented active alcohol and/or drug misuse; advanced chronic obstructive pulmonary disease as defined as dyspnea at rest at least once per day; unstable angina; hemiplegia or other lower extremity paralysis; and a history of central nervous system or peripheral nervous system demyelinating disorders. Additional exclusion criteria included hospitalization in the past 60 days, use of any apparatus for continuous or patient-controlled analgesia; history of chronic low back pain with documented radiculopathy; and any change in pertinent medications in the past 60 days, including pain medications, insulin, metformin, and anti-inflammatories.

Interventions

Subjects participated in a combined physical therapy approach using MIRE and a standardized balance program. Patients received treatment in the outpatient clinic 3 times each week for 4 weeks. The treatment then continued at the same frequency at home until the scheduled 6-month follow-up visit. Clinic and home treatments included application of MIRE to bilateral lower extremities and feet for 30 minutes each as well as performance of a therapeutic exercise program for balance.

In the clinic, 2 pads from the MIRE device (Anodyne Therapy, LLC, Tampa, FL) were placed along the medial and lateral aspect of each lower leg, and an additional 2 pads were placed in a T formation on the plantar surface of each foot, per the manufacturer’s recommendations. The T formation consisted of the first pad placed horizontally across the metatarsal heads and the second placed vertically down the length of the foot. Each pad was protected by plastic wrap to ensure proper hygiene and secured. The intensity of clinic treatments was set at 7 bars, which minimized the risk of burns. Home treatments were similar to those in the clinic, except that each leg had to be treated individually instead of simultaneously and home MIRE units are preset and only function at an intensity that is equivalent to around 7 bars on the clinical unit.

The standardized balance program consisted of a progression of the following exercises: ankle alphabet/ankle range of motion, standing lateral weight shifts, bilateral heel raises, bilateral toe raises, unilateral heel raises, unilateral toe raises, partial wall squats, and single leg stance. Each participant performed these exercises 3 times per week in the clinic and then 3 times per week at home following the 12th visit.

Outcomes and Follow-up

The POQ-VA, a subjective quality of life (QOL) measure for veterans, as well as VAS, SWM testing, and the Tinetti Gait and Balance Assessment scores were used to measure outcomes. Data were collected for each of these measures during the initial and 12th clinic visits and at the 3-month and 6-month follow-up visits. The POQ-VA and VAS scores were self-reported and filled out by each participant at the initial, 12th, 3-month, and 6-month visits. The POQ-VA score has proven to be reliable and valid for the assessment of noncancer, chronic pain in veterans.¹⁹ The VAS scores were measured using a scale of 0 to 10 cm.

The SWM was standardized, and 7 sites were tested on each foot during the initial, 12th, 3-month, and 6-month visits: plantar surface of the distal great toe, the distal 3rd toe, the distal 5th toe, the 1st metatarsal head, the 3rd metatarsal head, the 5th metatarsal head, and the mid-plantar arch. At each site, the SWM was applied with just enough force to initiate a bending force and held for 1.5 seconds. Each site was tested 3 times. Participants had to detect the monofilament at least twice for the monofilament value to be recorded. Monofilament testing began with 6.65 SWM and decreased to 5.07, 4.56, 4.32, and lower until the patient was no longer able to detect sensation.

The Tinetti Gait and Balance Assessments was performed on each participant at the initial, 12th, 3-month, and 6-month visits. Tinetti balance, gait, and total scores were recorded at each interval.

Results

Thirty-three patients, referred by primary care providers and specialty clinics, met the inclusion criteria and enrolled in the study. Twenty-one patients (20 men and 1 woman) completed the entire 6-month study. Causes for withdrawal included travel difficulties (5), did not show up for follow-up visits (4), lumbar radiculopathy (1), perceived minimal/no benefit (1), and unrelated death (1). No AEs were reported.

The Friedman test with DMC post hoc test was performed on the POQ-VA total score and subscale scores. The POQ-VA subscale scores were divided into the following domains: pain, activities of daily living (ADL),  fear, negative affect, mobility, and  vitality. The POQ-VA domains were analyzed to compare data from the initial, 12th, 3-month, and 6-month visits. The POQ-VA total score significantly decreased from the initial to the 12th visit (P < .01), from the initial to the 3-month (P < .01), and from the initial to the 6-month visit (P < .05). However, there was no significant change from the 12th visit to the 3-month follow-up, 12th visit to the 6-month follow-up, or the 3-month to 6-month follow-up.

The POQ-VA pain score decreased significantly from the initial to the 12th visit (P < .05) and from the initial to the 6-month visit (P < .05). However, there was no significant interval change from the initial to the 3-month, the 12th to 3-month, 12th to 6-month, or 3-month to 6-month visit (Figure 1). The POQ-VA vitality scores and POQ-VA fear scores did not yield significant changes. The POQ-VA negative affect scores showed significant improvement only between the initial and the 3-month visit (P < .05) (Figure 2). The POQ-VA ADL scores showed significant improvement in the initial vs 3-month score (P < .05). The POQ-VA mobility scores were significantly improved for the initial vs 12th visit (P < .01), initial vs 3-month visit (P < .01), and the initial vs 6-month visit (P < .001) (Figure 1).

Analysis of VAS scores revealed a significant decrease at the 6-month time frame compared with the initial score for the left foot (P < .05). Further VAS analysis revealed no significant difference between the initial and 6-month right foot VAS score. When both feet were compared together, there was no significant difference in VAS ratings between any 2 points in time.

Analysis of Tinetti Total Score, Tinetti Balance Score, and Tinetti Gait Score revealed a significant difference between the initial vs 3-month visit for all 3 scores (P < .001, P < .001, and P < .05, respectively). In addition, Tinetti Total (P < .001) and Tinetti Balance (P < .01) scores were significantly improved from initial to the final 6-month visit. There were no significant findings between interim scores of the initial and 12th visits, the 12th and 3-month visits, or the 3-month and 6-month scores (Figure 2).

Analysis of SWM testing indicated a significant decrease in the total number of insensate sites (> 5.07) when both feet were grouped together between the initial and 3-month visits (P < .05) as well as the initial and 6-month (P < .01) visits. When the left and right feet were compared independently of each other, there was a significant decrease in the number of insensate sites between the initial and 6-month visits (P < .01 for both) (Figure 3).

Discussion

This study investigated whether or not a multimodal physical therapy approach would reduce several of the debilitating symptoms of DPN experienced by many veterans at WJBDVAMC. The results support the idea that a combined treatment protocol of MIRE and a standardized exercise program can lead to decreased POQ-VA pain levels, improved balance, and improved protective sensation in veterans with DPN. Alleviation of these DPN complications may ultimately decrease an individual’s risk of injury and improve overall QOL.

Because the POQ-VA is a reliable, valid self-reported measure for veterans, it was chosen to quantify the impact of pain. Overall, veterans who participated in this study perceived decreased pain interference in multiple areas of their lives. The most significant findings were in overall QOL, household and community mobility, and pain ratings. This suggests that the combined treatment protocol will help veterans maintain an active lifestyle despite poorly controlled diabetes and neuropathic pain.

Along with decreased pain interference with QOL, participants demonstrated a decrease in fall risk as quantified by the Tinetti Gait and Balance Assessment. The SWM testing showed improved protective sensation as early as 3 months and continued through the 6-month visit. As protective sensation improves and fall risk decreases, the risk of injury is lessened, fear of falling is decreased, and individuals are less likely to self-impose limitations on daily activity levels, which improves QOL. In addition, decreased fall risk and improved protective sensation can reduce the financial burden on both the patient and the health care system. Many individuals are hospitalized secondary to fall injury, nonhealing wounds, resulting infections, and/or secondary complications from prolonged immobility. This treatment protocol demonstrates how a standardized physical therapy protocol, including MIRE and balance exercises, can be used preventively to reduce both the personal and financial impact of DPN.

It is interesting to note that some POQ-VA and Tinetti subscores were significantly improved at 3 months but not at 6 months. The significance achieved at 3 months may be due to the time required (ie, > 12 visits) to make significant physiological changes. The lack of significance at 6 months may be due to the natural tendency of participants to less consistently perform the home exercise program and MIRE protocol when unsupervised in the home. Differences in the VAS and POQ-VA pain score ratings were noted in the data. The POQ-VA pain rating scale indicated significant improvement in pain levels over the course of the study. However, when asked about pain using the 10-cm VAS, patients reported no significant improvements. This may be because veterans are more familiar with the numerical pain rating scale and are rarely asked to use the 10-cm VAS. It may also be because the POQ-VA pain rating asks for an average pain level over the previous week, whereas the 10-cm VAS asks for pain level at a discrete point in time.

Historically, physical therapy has had little to offer individuals with DPN. As a result of this study, however, a standardized treatment program for DPN has been implemented at the WJBDVAMC Physical Therapy Clinic. Referred patients are seen in the clinic on a trial basis. If positive results are documented during the clinic treatments, a home MIRE unit and exercise program are provided. The patients are expected to continue performing home treatments of MIRE and exercise 3 times a week after discharge.

Strengths and Limitations

Strengths of the study include a stringent IRB review, control of medication changes during the study through alerts to all VA providers, and a standardized MIRE and exercise protocol. An additional strength is the long duration of the study, which included supervised and unsupervised interventions that simulate real-life scenarios.

Limitations of the study include a small sample size, case-controlled design rather than a randomized, double-blinded study, which can contribute to selection bias, inability to differentiate between the benefits of physical therapy alone vs physical therapy and MIRE treatments, and retention of participants due to travel difficulties across a wide catchment area.

This pilot study should be expanded to a multicenter, randomized, double-blinded study to clarify the most beneficial treatments for individuals with diabetic neuropathy. Examining the number of documented falls pre- and postintervention may also be helpful to determine actual effects on an individual’s fall risk.

Conclusion

The use of a multimodal physical therapy approach seems to be effective in reducing the impact of neuropathic pain, the risk of amputation, and the risk of falls in individuals who have pursued all standard medical options but still experience the long-term effects of DPN. By adhering to a standardized treatment protocol of MIRE and therapeutic exercise, it seems that the benefits of this intervention can be maintained over time. This offers new, nonconventional treatment options in the field of physical therapy for veterans whose QOL is negatively impacted by the devastating effects of diabetic neuropathy.  

Acknowledgements
Clinical support was provided by David Metzelfeld, DPT, and Cam Lendrim, PTA of William Jennings Bryan Dorn VA Medical Center. Paul Bartels, PhD, of Warren Wilson College provided data analysis support. Anodyne Therapy, LLC, provided the MIRE unit used in the clinic.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

The progressive symptoms of diabetic peripheral neuropathy (DPN) are some of the most frequent presentations of patients seeking care at the VHA. Patients with DPN often experience unmanageable pain in the lower extremities, loss of sensation in the feet, loss of balance, and an inability to perform daily functional activities.¹ In addition, these patients are at significant risk for lower extremity ulceration and amputation.² The symptoms and consequences of DPN are strongly linked to chronic use of pain medications as well as increased fall risk and injury.³ The high health care usage of veterans with these complex issues makes DPN a significant burden for the patient, the VHA, and society as a whole.

At the William Jennings Bryan Dorn VA Medical Center (WJBDVAMC) in Columbia, South Carolina, 10,763 veterans were identified to be at risk for limb loss in 2014 due to loss of protective sensation and 5,667 veterans diagnosed with DPN were treated in 2014.⁴ Although WJBDVAMC offers multiple clinics and programs to address the complex issues of diabetes and DPN, veterans oftentimes continue to experience uncontrolled pain, loss of protective sensation, and a decline in function even after diagnosis.

One area of improvement the authors identified in the WJBDVAMC Physical Medicine and Rehabilitation Services Department was the need for an effective, nonpharmacologic treatment for patients who experience DPN. As a result, the authors designed a pilot research study to determine whether or not a combined physical therapy intervention of monochromatic near-infrared energy (MIRE) treatments and a standardized balance exercise program would help improve the protective sensation, reduce fall risk, and decrease the adverse impact of pain on daily function. The study was approved by the institutional review board (IRB) and had no outside source of funding.

Background

Current treatments for DPN are primarily pharmacologic and are viewed as only moderately effective, limited by significant adverse effects (AEs) and drug interactions.⁵ Patients in the VHA at risk for amputation in low-, moderate-, and high-risk groups total 541,475 and 363,468 have a history of neuropathy. They are considered at risk due to multiple, documented factors, including weakness, callus, foot deformity, loss of protective sensation, and/or history of amputation.⁴ Neuropathy can affect tissues throughout the body, including organs, sensory neurons, cardiovascular status, the autonomic system, and the gastrointestinal tract as it progresses.

Individuals who develop DPN often experience severe, uncontrolled pain in the lower extremities, insensate feet, and decreased proprioceptive skills. The functional status of individuals with DPN often declines insidiously while mortality rate increases.⁶ Increased levels of neuropathic pain often lead to decreased activity levels, which, in turn, contribute to decreased endurance, poorly managed glycemic indexes, decreased strength, and decreased independence.

Additional DPN complications, such as decreased sensation and muscle atrophy in the lower extremities, often lead to foot deformity and increased areas of pressure during weight bearing postures. These areas of increased pressure may develop unknowingly into ulceration. If a patient’s wound becomes chronic and nonhealing, it can also lead to amputation. In such cases, early mortality may result.^6,7 The cascading effects of neuropathic pain and decreased sensation place a patient with diabetes at risk for falls. Injuries from falls are widely known to be a leading cause of hospitalization and mortality in the elderly.⁸

Physical therapy may be prescribed for DPN and its resulting sequelae. Several studies present conflicting results regarding the benefits of therapeutic exercise in the treatment of DPN. Akbari and colleagues showed that balance exercises can increase stability in patients with DPN; whereas, a study by Kruse and colleagues noted a training program consisting of lower-extremity exercises, balance training, and walking resulted in minimal improvement of participants’ balance and leg strength over a 12-month period.^9,10 Recent studies have shown that weight bearing does not increase ulceration in patients with diabetes and DPN. This is contrary to previous assumptions that patients with diabetes and DPN need to avoid weight-bearing activities.^11,12

Transcutaneous electrical nerve stimulation (TENS), a modality often used in physical therapy, has been studied in the treatment of DPN with conflicting results. Gossrau and colleagues found that pain reduction with micro-TENS applied peripherally is not superior to a placebo.¹³ However, a case study by Somers and Somers indicated that TENS applied to the lumbar area seemed to reduce pain and insomnia associated with diabetic neuropathy.¹⁴

Several recent research studies suggest that MIRE, another available modality, may be effective in treating symptoms of DPN. Monochromatic infrared energy therapy is a noninvasive, drug-free, FDA-approved medical device that emits monochromatic near-infrared light to improve local circulation and decrease pain. A large study of 2,239 patients with DPN reported an increase in foot sensation and decreased neuropathic pain levels when treated with MIRE.¹⁵

Leonard and colleagues found that the MIRE treatments resulted in a significant increase in sensation in individuals with baseline sensation of 6.65 Semmes-Weinstein Monofilament (SWM) after 6 and 12 active treatments as well as a decrease in neuropathic symptoms as measured by the Michigan Neuropathy Screening Instrument.¹⁶ Prendergast and colleagues noted improved electrophysical changes in both large and small myelinated nerve fibers of patients with DPN following 10 MIRE treatments.¹⁷ When studying 49 patients with DPN, Kochman and colleagues found 100% of participants had improved sensation after 12 MIRE treatments when tested with monofilaments.¹⁸

An additional benefit of MIRE treatment is that it can be safely performed at home once the patient is educated on proper use and application. Home DPN treatment has the potential to decrease the burden this population places on health care systems by reducing provider visits, medication, hospitalization secondary to pain, ulceration, fall injuries, and amputations.

Methods

This was a prospective, case series pilot study designed to measure changes in patient pain levels using the visual analog scale (VAS) and Pain Outcomes Questionnaire-VA (POQ-VA), degree of protective sensation loss as measured by SWM, and fall risk as denoted by Tinetti scores from entry to 6 months. Informed consent was obtained prior to treatment, and 33 patients referred by primary care providers and specialty clinics met the criteria and enrolled in the study. Twenty-one patients completed the entire 6-month study. The nonparametric Friedman test with a Dunn’s multiple comparison (DMC) post hoc test was used to analyze the data from the initial, 4-week, 3-month, and 6-month follow-up visits.

Setting and Participants

The study was performed in the Outpatient Physical Therapy Department at WJBDVAMC. Veterans with DPN who met the inclusion/exclusion criteria were enrolled. Inclusion criteria specified that the participant must be referred by a qualified health care provider for the treatment of DPN, be able to read and write in English, have consistent transportation to and from the study location, and be able to apply MIRE therapy as directed at home.

Exclusion criteria were subjects for whom MIRE or exercise were contraindicated. Subjects were excluded if they had medical conditions that suggested a possible decline in health status in the next 6 months. Such conditions included a current regimen of chemotherapy, radiation therapy, or dialysis; recent lower extremity amputation without prosthesis; documented active alcohol and/or drug misuse; advanced chronic obstructive pulmonary disease as defined as dyspnea at rest at least once per day; unstable angina; hemiplegia or other lower extremity paralysis; and a history of central nervous system or peripheral nervous system demyelinating disorders. Additional exclusion criteria included hospitalization in the past 60 days, use of any apparatus for continuous or patient-controlled analgesia; history of chronic low back pain with documented radiculopathy; and any change in pertinent medications in the past 60 days, including pain medications, insulin, metformin, and anti-inflammatories.

Interventions

Subjects participated in a combined physical therapy approach using MIRE and a standardized balance program. Patients received treatment in the outpatient clinic 3 times each week for 4 weeks. The treatment then continued at the same frequency at home until the scheduled 6-month follow-up visit. Clinic and home treatments included application of MIRE to bilateral lower extremities and feet for 30 minutes each as well as performance of a therapeutic exercise program for balance.

In the clinic, 2 pads from the MIRE device (Anodyne Therapy, LLC, Tampa, FL) were placed along the medial and lateral aspect of each lower leg, and an additional 2 pads were placed in a T formation on the plantar surface of each foot, per the manufacturer’s recommendations. The T formation consisted of the first pad placed horizontally across the metatarsal heads and the second placed vertically down the length of the foot. Each pad was protected by plastic wrap to ensure proper hygiene and secured. The intensity of clinic treatments was set at 7 bars, which minimized the risk of burns. Home treatments were similar to those in the clinic, except that each leg had to be treated individually instead of simultaneously and home MIRE units are preset and only function at an intensity that is equivalent to around 7 bars on the clinical unit.

The standardized balance program consisted of a progression of the following exercises: ankle alphabet/ankle range of motion, standing lateral weight shifts, bilateral heel raises, bilateral toe raises, unilateral heel raises, unilateral toe raises, partial wall squats, and single leg stance. Each participant performed these exercises 3 times per week in the clinic and then 3 times per week at home following the 12th visit.

Outcomes and Follow-up

The POQ-VA, a subjective quality of life (QOL) measure for veterans, as well as VAS, SWM testing, and the Tinetti Gait and Balance Assessment scores were used to measure outcomes. Data were collected for each of these measures during the initial and 12th clinic visits and at the 3-month and 6-month follow-up visits. The POQ-VA and VAS scores were self-reported and filled out by each participant at the initial, 12th, 3-month, and 6-month visits. The POQ-VA score has proven to be reliable and valid for the assessment of noncancer, chronic pain in veterans.¹⁹ The VAS scores were measured using a scale of 0 to 10 cm.

The SWM was standardized, and 7 sites were tested on each foot during the initial, 12th, 3-month, and 6-month visits: plantar surface of the distal great toe, the distal 3rd toe, the distal 5th toe, the 1st metatarsal head, the 3rd metatarsal head, the 5th metatarsal head, and the mid-plantar arch. At each site, the SWM was applied with just enough force to initiate a bending force and held for 1.5 seconds. Each site was tested 3 times. Participants had to detect the monofilament at least twice for the monofilament value to be recorded. Monofilament testing began with 6.65 SWM and decreased to 5.07, 4.56, 4.32, and lower until the patient was no longer able to detect sensation.

The Tinetti Gait and Balance Assessments was performed on each participant at the initial, 12th, 3-month, and 6-month visits. Tinetti balance, gait, and total scores were recorded at each interval.

Results

Thirty-three patients, referred by primary care providers and specialty clinics, met the inclusion criteria and enrolled in the study. Twenty-one patients (20 men and 1 woman) completed the entire 6-month study. Causes for withdrawal included travel difficulties (5), did not show up for follow-up visits (4), lumbar radiculopathy (1), perceived minimal/no benefit (1), and unrelated death (1). No AEs were reported.

The Friedman test with DMC post hoc test was performed on the POQ-VA total score and subscale scores. The POQ-VA subscale scores were divided into the following domains: pain, activities of daily living (ADL),  fear, negative affect, mobility, and  vitality. The POQ-VA domains were analyzed to compare data from the initial, 12th, 3-month, and 6-month visits. The POQ-VA total score significantly decreased from the initial to the 12th visit (P < .01), from the initial to the 3-month (P < .01), and from the initial to the 6-month visit (P < .05). However, there was no significant change from the 12th visit to the 3-month follow-up, 12th visit to the 6-month follow-up, or the 3-month to 6-month follow-up.

The POQ-VA pain score decreased significantly from the initial to the 12th visit (P < .05) and from the initial to the 6-month visit (P < .05). However, there was no significant interval change from the initial to the 3-month, the 12th to 3-month, 12th to 6-month, or 3-month to 6-month visit (Figure 1). The POQ-VA vitality scores and POQ-VA fear scores did not yield significant changes. The POQ-VA negative affect scores showed significant improvement only between the initial and the 3-month visit (P < .05) (Figure 2). The POQ-VA ADL scores showed significant improvement in the initial vs 3-month score (P < .05). The POQ-VA mobility scores were significantly improved for the initial vs 12th visit (P < .01), initial vs 3-month visit (P < .01), and the initial vs 6-month visit (P < .001) (Figure 1).

Analysis of VAS scores revealed a significant decrease at the 6-month time frame compared with the initial score for the left foot (P < .05). Further VAS analysis revealed no significant difference between the initial and 6-month right foot VAS score. When both feet were compared together, there was no significant difference in VAS ratings between any 2 points in time.

Analysis of Tinetti Total Score, Tinetti Balance Score, and Tinetti Gait Score revealed a significant difference between the initial vs 3-month visit for all 3 scores (P < .001, P < .001, and P < .05, respectively). In addition, Tinetti Total (P < .001) and Tinetti Balance (P < .01) scores were significantly improved from initial to the final 6-month visit. There were no significant findings between interim scores of the initial and 12th visits, the 12th and 3-month visits, or the 3-month and 6-month scores (Figure 2).

Analysis of SWM testing indicated a significant decrease in the total number of insensate sites (> 5.07) when both feet were grouped together between the initial and 3-month visits (P < .05) as well as the initial and 6-month (P < .01) visits. When the left and right feet were compared independently of each other, there was a significant decrease in the number of insensate sites between the initial and 6-month visits (P < .01 for both) (Figure 3).

Discussion

This study investigated whether or not a multimodal physical therapy approach would reduce several of the debilitating symptoms of DPN experienced by many veterans at WJBDVAMC. The results support the idea that a combined treatment protocol of MIRE and a standardized exercise program can lead to decreased POQ-VA pain levels, improved balance, and improved protective sensation in veterans with DPN. Alleviation of these DPN complications may ultimately decrease an individual’s risk of injury and improve overall QOL.

Because the POQ-VA is a reliable, valid self-reported measure for veterans, it was chosen to quantify the impact of pain. Overall, veterans who participated in this study perceived decreased pain interference in multiple areas of their lives. The most significant findings were in overall QOL, household and community mobility, and pain ratings. This suggests that the combined treatment protocol will help veterans maintain an active lifestyle despite poorly controlled diabetes and neuropathic pain.

Along with decreased pain interference with QOL, participants demonstrated a decrease in fall risk as quantified by the Tinetti Gait and Balance Assessment. The SWM testing showed improved protective sensation as early as 3 months and continued through the 6-month visit. As protective sensation improves and fall risk decreases, the risk of injury is lessened, fear of falling is decreased, and individuals are less likely to self-impose limitations on daily activity levels, which improves QOL. In addition, decreased fall risk and improved protective sensation can reduce the financial burden on both the patient and the health care system. Many individuals are hospitalized secondary to fall injury, nonhealing wounds, resulting infections, and/or secondary complications from prolonged immobility. This treatment protocol demonstrates how a standardized physical therapy protocol, including MIRE and balance exercises, can be used preventively to reduce both the personal and financial impact of DPN.

It is interesting to note that some POQ-VA and Tinetti subscores were significantly improved at 3 months but not at 6 months. The significance achieved at 3 months may be due to the time required (ie, > 12 visits) to make significant physiological changes. The lack of significance at 6 months may be due to the natural tendency of participants to less consistently perform the home exercise program and MIRE protocol when unsupervised in the home. Differences in the VAS and POQ-VA pain score ratings were noted in the data. The POQ-VA pain rating scale indicated significant improvement in pain levels over the course of the study. However, when asked about pain using the 10-cm VAS, patients reported no significant improvements. This may be because veterans are more familiar with the numerical pain rating scale and are rarely asked to use the 10-cm VAS. It may also be because the POQ-VA pain rating asks for an average pain level over the previous week, whereas the 10-cm VAS asks for pain level at a discrete point in time.

Historically, physical therapy has had little to offer individuals with DPN. As a result of this study, however, a standardized treatment program for DPN has been implemented at the WJBDVAMC Physical Therapy Clinic. Referred patients are seen in the clinic on a trial basis. If positive results are documented during the clinic treatments, a home MIRE unit and exercise program are provided. The patients are expected to continue performing home treatments of MIRE and exercise 3 times a week after discharge.

Strengths and Limitations

Strengths of the study include a stringent IRB review, control of medication changes during the study through alerts to all VA providers, and a standardized MIRE and exercise protocol. An additional strength is the long duration of the study, which included supervised and unsupervised interventions that simulate real-life scenarios.

Limitations of the study include a small sample size, case-controlled design rather than a randomized, double-blinded study, which can contribute to selection bias, inability to differentiate between the benefits of physical therapy alone vs physical therapy and MIRE treatments, and retention of participants due to travel difficulties across a wide catchment area.

This pilot study should be expanded to a multicenter, randomized, double-blinded study to clarify the most beneficial treatments for individuals with diabetic neuropathy. Examining the number of documented falls pre- and postintervention may also be helpful to determine actual effects on an individual’s fall risk.

Conclusion

The use of a multimodal physical therapy approach seems to be effective in reducing the impact of neuropathic pain, the risk of amputation, and the risk of falls in individuals who have pursued all standard medical options but still experience the long-term effects of DPN. By adhering to a standardized treatment protocol of MIRE and therapeutic exercise, it seems that the benefits of this intervention can be maintained over time. This offers new, nonconventional treatment options in the field of physical therapy for veterans whose QOL is negatively impacted by the devastating effects of diabetic neuropathy.  

Acknowledgements
Clinical support was provided by David Metzelfeld, DPT, and Cam Lendrim, PTA of William Jennings Bryan Dorn VA Medical Center. Paul Bartels, PhD, of Warren Wilson College provided data analysis support. Anodyne Therapy, LLC, provided the MIRE unit used in the clinic.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

The progressive symptoms of diabetic peripheral neuropathy (DPN) are some of the most frequent presentations of patients seeking care at the VHA. Patients with DPN often experience unmanageable pain in the lower extremities, loss of sensation in the feet, loss of balance, and an inability to perform daily functional activities.¹ In addition, these patients are at significant risk for lower extremity ulceration and amputation.² The symptoms and consequences of DPN are strongly linked to chronic use of pain medications as well as increased fall risk and injury.³ The high health care usage of veterans with these complex issues makes DPN a significant burden for the patient, the VHA, and society as a whole.

At the William Jennings Bryan Dorn VA Medical Center (WJBDVAMC) in Columbia, South Carolina, 10,763 veterans were identified to be at risk for limb loss in 2014 due to loss of protective sensation and 5,667 veterans diagnosed with DPN were treated in 2014.⁴ Although WJBDVAMC offers multiple clinics and programs to address the complex issues of diabetes and DPN, veterans oftentimes continue to experience uncontrolled pain, loss of protective sensation, and a decline in function even after diagnosis.

One area of improvement the authors identified in the WJBDVAMC Physical Medicine and Rehabilitation Services Department was the need for an effective, nonpharmacologic treatment for patients who experience DPN. As a result, the authors designed a pilot research study to determine whether or not a combined physical therapy intervention of monochromatic near-infrared energy (MIRE) treatments and a standardized balance exercise program would help improve the protective sensation, reduce fall risk, and decrease the adverse impact of pain on daily function. The study was approved by the institutional review board (IRB) and had no outside source of funding.

Background

Current treatments for DPN are primarily pharmacologic and are viewed as only moderately effective, limited by significant adverse effects (AEs) and drug interactions.⁵ Patients in the VHA at risk for amputation in low-, moderate-, and high-risk groups total 541,475 and 363,468 have a history of neuropathy. They are considered at risk due to multiple, documented factors, including weakness, callus, foot deformity, loss of protective sensation, and/or history of amputation.⁴ Neuropathy can affect tissues throughout the body, including organs, sensory neurons, cardiovascular status, the autonomic system, and the gastrointestinal tract as it progresses.

Individuals who develop DPN often experience severe, uncontrolled pain in the lower extremities, insensate feet, and decreased proprioceptive skills. The functional status of individuals with DPN often declines insidiously while mortality rate increases.⁶ Increased levels of neuropathic pain often lead to decreased activity levels, which, in turn, contribute to decreased endurance, poorly managed glycemic indexes, decreased strength, and decreased independence.

Additional DPN complications, such as decreased sensation and muscle atrophy in the lower extremities, often lead to foot deformity and increased areas of pressure during weight bearing postures. These areas of increased pressure may develop unknowingly into ulceration. If a patient’s wound becomes chronic and nonhealing, it can also lead to amputation. In such cases, early mortality may result.^6,7 The cascading effects of neuropathic pain and decreased sensation place a patient with diabetes at risk for falls. Injuries from falls are widely known to be a leading cause of hospitalization and mortality in the elderly.⁸

Physical therapy may be prescribed for DPN and its resulting sequelae. Several studies present conflicting results regarding the benefits of therapeutic exercise in the treatment of DPN. Akbari and colleagues showed that balance exercises can increase stability in patients with DPN; whereas, a study by Kruse and colleagues noted a training program consisting of lower-extremity exercises, balance training, and walking resulted in minimal improvement of participants’ balance and leg strength over a 12-month period.^9,10 Recent studies have shown that weight bearing does not increase ulceration in patients with diabetes and DPN. This is contrary to previous assumptions that patients with diabetes and DPN need to avoid weight-bearing activities.^11,12

Transcutaneous electrical nerve stimulation (TENS), a modality often used in physical therapy, has been studied in the treatment of DPN with conflicting results. Gossrau and colleagues found that pain reduction with micro-TENS applied peripherally is not superior to a placebo.¹³ However, a case study by Somers and Somers indicated that TENS applied to the lumbar area seemed to reduce pain and insomnia associated with diabetic neuropathy.¹⁴

Several recent research studies suggest that MIRE, another available modality, may be effective in treating symptoms of DPN. Monochromatic infrared energy therapy is a noninvasive, drug-free, FDA-approved medical device that emits monochromatic near-infrared light to improve local circulation and decrease pain. A large study of 2,239 patients with DPN reported an increase in foot sensation and decreased neuropathic pain levels when treated with MIRE.¹⁵

Leonard and colleagues found that the MIRE treatments resulted in a significant increase in sensation in individuals with baseline sensation of 6.65 Semmes-Weinstein Monofilament (SWM) after 6 and 12 active treatments as well as a decrease in neuropathic symptoms as measured by the Michigan Neuropathy Screening Instrument.¹⁶ Prendergast and colleagues noted improved electrophysical changes in both large and small myelinated nerve fibers of patients with DPN following 10 MIRE treatments.¹⁷ When studying 49 patients with DPN, Kochman and colleagues found 100% of participants had improved sensation after 12 MIRE treatments when tested with monofilaments.¹⁸

An additional benefit of MIRE treatment is that it can be safely performed at home once the patient is educated on proper use and application. Home DPN treatment has the potential to decrease the burden this population places on health care systems by reducing provider visits, medication, hospitalization secondary to pain, ulceration, fall injuries, and amputations.

Methods

This was a prospective, case series pilot study designed to measure changes in patient pain levels using the visual analog scale (VAS) and Pain Outcomes Questionnaire-VA (POQ-VA), degree of protective sensation loss as measured by SWM, and fall risk as denoted by Tinetti scores from entry to 6 months. Informed consent was obtained prior to treatment, and 33 patients referred by primary care providers and specialty clinics met the criteria and enrolled in the study. Twenty-one patients completed the entire 6-month study. The nonparametric Friedman test with a Dunn’s multiple comparison (DMC) post hoc test was used to analyze the data from the initial, 4-week, 3-month, and 6-month follow-up visits.

Setting and Participants

The study was performed in the Outpatient Physical Therapy Department at WJBDVAMC. Veterans with DPN who met the inclusion/exclusion criteria were enrolled. Inclusion criteria specified that the participant must be referred by a qualified health care provider for the treatment of DPN, be able to read and write in English, have consistent transportation to and from the study location, and be able to apply MIRE therapy as directed at home.

Exclusion criteria were subjects for whom MIRE or exercise were contraindicated. Subjects were excluded if they had medical conditions that suggested a possible decline in health status in the next 6 months. Such conditions included a current regimen of chemotherapy, radiation therapy, or dialysis; recent lower extremity amputation without prosthesis; documented active alcohol and/or drug misuse; advanced chronic obstructive pulmonary disease as defined as dyspnea at rest at least once per day; unstable angina; hemiplegia or other lower extremity paralysis; and a history of central nervous system or peripheral nervous system demyelinating disorders. Additional exclusion criteria included hospitalization in the past 60 days, use of any apparatus for continuous or patient-controlled analgesia; history of chronic low back pain with documented radiculopathy; and any change in pertinent medications in the past 60 days, including pain medications, insulin, metformin, and anti-inflammatories.

Interventions

Subjects participated in a combined physical therapy approach using MIRE and a standardized balance program. Patients received treatment in the outpatient clinic 3 times each week for 4 weeks. The treatment then continued at the same frequency at home until the scheduled 6-month follow-up visit. Clinic and home treatments included application of MIRE to bilateral lower extremities and feet for 30 minutes each as well as performance of a therapeutic exercise program for balance.

In the clinic, 2 pads from the MIRE device (Anodyne Therapy, LLC, Tampa, FL) were placed along the medial and lateral aspect of each lower leg, and an additional 2 pads were placed in a T formation on the plantar surface of each foot, per the manufacturer’s recommendations. The T formation consisted of the first pad placed horizontally across the metatarsal heads and the second placed vertically down the length of the foot. Each pad was protected by plastic wrap to ensure proper hygiene and secured. The intensity of clinic treatments was set at 7 bars, which minimized the risk of burns. Home treatments were similar to those in the clinic, except that each leg had to be treated individually instead of simultaneously and home MIRE units are preset and only function at an intensity that is equivalent to around 7 bars on the clinical unit.

The standardized balance program consisted of a progression of the following exercises: ankle alphabet/ankle range of motion, standing lateral weight shifts, bilateral heel raises, bilateral toe raises, unilateral heel raises, unilateral toe raises, partial wall squats, and single leg stance. Each participant performed these exercises 3 times per week in the clinic and then 3 times per week at home following the 12th visit.

Outcomes and Follow-up

The POQ-VA, a subjective quality of life (QOL) measure for veterans, as well as VAS, SWM testing, and the Tinetti Gait and Balance Assessment scores were used to measure outcomes. Data were collected for each of these measures during the initial and 12th clinic visits and at the 3-month and 6-month follow-up visits. The POQ-VA and VAS scores were self-reported and filled out by each participant at the initial, 12th, 3-month, and 6-month visits. The POQ-VA score has proven to be reliable and valid for the assessment of noncancer, chronic pain in veterans.¹⁹ The VAS scores were measured using a scale of 0 to 10 cm.

The SWM was standardized, and 7 sites were tested on each foot during the initial, 12th, 3-month, and 6-month visits: plantar surface of the distal great toe, the distal 3rd toe, the distal 5th toe, the 1st metatarsal head, the 3rd metatarsal head, the 5th metatarsal head, and the mid-plantar arch. At each site, the SWM was applied with just enough force to initiate a bending force and held for 1.5 seconds. Each site was tested 3 times. Participants had to detect the monofilament at least twice for the monofilament value to be recorded. Monofilament testing began with 6.65 SWM and decreased to 5.07, 4.56, 4.32, and lower until the patient was no longer able to detect sensation.

The Tinetti Gait and Balance Assessments was performed on each participant at the initial, 12th, 3-month, and 6-month visits. Tinetti balance, gait, and total scores were recorded at each interval.

Results

Thirty-three patients, referred by primary care providers and specialty clinics, met the inclusion criteria and enrolled in the study. Twenty-one patients (20 men and 1 woman) completed the entire 6-month study. Causes for withdrawal included travel difficulties (5), did not show up for follow-up visits (4), lumbar radiculopathy (1), perceived minimal/no benefit (1), and unrelated death (1). No AEs were reported.

The Friedman test with DMC post hoc test was performed on the POQ-VA total score and subscale scores. The POQ-VA subscale scores were divided into the following domains: pain, activities of daily living (ADL),  fear, negative affect, mobility, and  vitality. The POQ-VA domains were analyzed to compare data from the initial, 12th, 3-month, and 6-month visits. The POQ-VA total score significantly decreased from the initial to the 12th visit (P < .01), from the initial to the 3-month (P < .01), and from the initial to the 6-month visit (P < .05). However, there was no significant change from the 12th visit to the 3-month follow-up, 12th visit to the 6-month follow-up, or the 3-month to 6-month follow-up.

The POQ-VA pain score decreased significantly from the initial to the 12th visit (P < .05) and from the initial to the 6-month visit (P < .05). However, there was no significant interval change from the initial to the 3-month, the 12th to 3-month, 12th to 6-month, or 3-month to 6-month visit (Figure 1). The POQ-VA vitality scores and POQ-VA fear scores did not yield significant changes. The POQ-VA negative affect scores showed significant improvement only between the initial and the 3-month visit (P < .05) (Figure 2). The POQ-VA ADL scores showed significant improvement in the initial vs 3-month score (P < .05). The POQ-VA mobility scores were significantly improved for the initial vs 12th visit (P < .01), initial vs 3-month visit (P < .01), and the initial vs 6-month visit (P < .001) (Figure 1).

Analysis of VAS scores revealed a significant decrease at the 6-month time frame compared with the initial score for the left foot (P < .05). Further VAS analysis revealed no significant difference between the initial and 6-month right foot VAS score. When both feet were compared together, there was no significant difference in VAS ratings between any 2 points in time.

Analysis of Tinetti Total Score, Tinetti Balance Score, and Tinetti Gait Score revealed a significant difference between the initial vs 3-month visit for all 3 scores (P < .001, P < .001, and P < .05, respectively). In addition, Tinetti Total (P < .001) and Tinetti Balance (P < .01) scores were significantly improved from initial to the final 6-month visit. There were no significant findings between interim scores of the initial and 12th visits, the 12th and 3-month visits, or the 3-month and 6-month scores (Figure 2).

Analysis of SWM testing indicated a significant decrease in the total number of insensate sites (> 5.07) when both feet were grouped together between the initial and 3-month visits (P < .05) as well as the initial and 6-month (P < .01) visits. When the left and right feet were compared independently of each other, there was a significant decrease in the number of insensate sites between the initial and 6-month visits (P < .01 for both) (Figure 3).

Discussion

This study investigated whether or not a multimodal physical therapy approach would reduce several of the debilitating symptoms of DPN experienced by many veterans at WJBDVAMC. The results support the idea that a combined treatment protocol of MIRE and a standardized exercise program can lead to decreased POQ-VA pain levels, improved balance, and improved protective sensation in veterans with DPN. Alleviation of these DPN complications may ultimately decrease an individual’s risk of injury and improve overall QOL.

Because the POQ-VA is a reliable, valid self-reported measure for veterans, it was chosen to quantify the impact of pain. Overall, veterans who participated in this study perceived decreased pain interference in multiple areas of their lives. The most significant findings were in overall QOL, household and community mobility, and pain ratings. This suggests that the combined treatment protocol will help veterans maintain an active lifestyle despite poorly controlled diabetes and neuropathic pain.

Along with decreased pain interference with QOL, participants demonstrated a decrease in fall risk as quantified by the Tinetti Gait and Balance Assessment. The SWM testing showed improved protective sensation as early as 3 months and continued through the 6-month visit. As protective sensation improves and fall risk decreases, the risk of injury is lessened, fear of falling is decreased, and individuals are less likely to self-impose limitations on daily activity levels, which improves QOL. In addition, decreased fall risk and improved protective sensation can reduce the financial burden on both the patient and the health care system. Many individuals are hospitalized secondary to fall injury, nonhealing wounds, resulting infections, and/or secondary complications from prolonged immobility. This treatment protocol demonstrates how a standardized physical therapy protocol, including MIRE and balance exercises, can be used preventively to reduce both the personal and financial impact of DPN.

It is interesting to note that some POQ-VA and Tinetti subscores were significantly improved at 3 months but not at 6 months. The significance achieved at 3 months may be due to the time required (ie, > 12 visits) to make significant physiological changes. The lack of significance at 6 months may be due to the natural tendency of participants to less consistently perform the home exercise program and MIRE protocol when unsupervised in the home. Differences in the VAS and POQ-VA pain score ratings were noted in the data. The POQ-VA pain rating scale indicated significant improvement in pain levels over the course of the study. However, when asked about pain using the 10-cm VAS, patients reported no significant improvements. This may be because veterans are more familiar with the numerical pain rating scale and are rarely asked to use the 10-cm VAS. It may also be because the POQ-VA pain rating asks for an average pain level over the previous week, whereas the 10-cm VAS asks for pain level at a discrete point in time.

Historically, physical therapy has had little to offer individuals with DPN. As a result of this study, however, a standardized treatment program for DPN has been implemented at the WJBDVAMC Physical Therapy Clinic. Referred patients are seen in the clinic on a trial basis. If positive results are documented during the clinic treatments, a home MIRE unit and exercise program are provided. The patients are expected to continue performing home treatments of MIRE and exercise 3 times a week after discharge.

Strengths and Limitations

Strengths of the study include a stringent IRB review, control of medication changes during the study through alerts to all VA providers, and a standardized MIRE and exercise protocol. An additional strength is the long duration of the study, which included supervised and unsupervised interventions that simulate real-life scenarios.

Limitations of the study include a small sample size, case-controlled design rather than a randomized, double-blinded study, which can contribute to selection bias, inability to differentiate between the benefits of physical therapy alone vs physical therapy and MIRE treatments, and retention of participants due to travel difficulties across a wide catchment area.

This pilot study should be expanded to a multicenter, randomized, double-blinded study to clarify the most beneficial treatments for individuals with diabetic neuropathy. Examining the number of documented falls pre- and postintervention may also be helpful to determine actual effects on an individual’s fall risk.

Conclusion

The use of a multimodal physical therapy approach seems to be effective in reducing the impact of neuropathic pain, the risk of amputation, and the risk of falls in individuals who have pursued all standard medical options but still experience the long-term effects of DPN. By adhering to a standardized treatment protocol of MIRE and therapeutic exercise, it seems that the benefits of this intervention can be maintained over time. This offers new, nonconventional treatment options in the field of physical therapy for veterans whose QOL is negatively impacted by the devastating effects of diabetic neuropathy.  

Acknowledgements
Clinical support was provided by David Metzelfeld, DPT, and Cam Lendrim, PTA of William Jennings Bryan Dorn VA Medical Center. Paul Bartels, PhD, of Warren Wilson College provided data analysis support. Anodyne Therapy, LLC, provided the MIRE unit used in the clinic.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.