Federal Practitioner

An examination of coffee consumption habits of almost 400,000 people suggests that those habits are largely driven by a person’s cardiovascular health.

©Elena Moiseeva/fotolia.com

Data from a large population database showed that people with essential hypertension, angina, or cardiac arrhythmias drank less coffee than people who had none of these conditions. When they did drink coffee, it tended to be decaffeinated.

The investigators, led by Elina Hyppönen, PhD, director of the Australian Centre for Precision Health at the University of South Australia, Adelaide, say that this predilection for avoiding coffee, which is known to produce jitteriness and heart palpitations, is based on genetics.

“If your body is telling you not to drink that extra cup of coffee, there’s likely a reason why,” Dr. Hyppönen said in an interview.

The study was published online in the American Journal of Clinical Nutrition.

“People drink coffee as a pick-me-up when they’re feeling tired, or because it tastes good, or simply because it’s part of their daily routine, but what we don’t recognize is that people subconsciously self-regulate safe levels of caffeine based on how high their blood pressure is, and this is likely a result of a protective genetic mechanism, [meaning] that someone who drinks a lot of coffee is likely more genetically tolerant of caffeine, as compared to someone who drinks very little,” Dr. Hyppönen said.

“In addition, we’ve known from past research that when people feel unwell, they tend to drink less coffee. This type of phenomenon, where disease drives behavior, is called reverse causality,” Dr. Hyppönen said.

For this analysis, she and her team used information on 390,435 individuals of European ancestry from the UK Biobank, a large epidemiologic database. Habitual coffee consumption was self-reported, and systolic and diastolic blood pressure and heart rate were measured at baseline. Cardiovascular symptoms at baseline were gleaned from hospital diagnoses, primary care records, and/or self report, the authors note.

To look at the relationship of systolic BP, diastolic BP, and heart rate with coffee consumption, they used a strategy called Mendelian randomization, which allows genetic information such as variants reflecting higher blood pressures and heart rate to be used to provide evidence for a causal association.

Results showed that participants with essential hypertension, angina, or arrhythmia were “all more likely to drink less caffeinated coffee and to be nonhabitual or decaffeinated coffee drinkers compared with those who did not report related symptoms,” the authors write.

Those with higher systolic and diastolic BP based on their genetics tended to drink less caffeinated coffee at baseline, “with consistent genetic evidence to support a causal explanation across all methods,” they noted.

They also found that those people who have a higher resting heart rate due to their genes were more likely to choose decaffeinated coffee.

“These results have two major implications,” Dr. Hyppönen said. “Firstly, they show that our bodies can regulate behavior in ways that we may not realize, and that if something does not feel good to us, there is a likely to be a reason why.”

“Second, our results show that our health status in part regulates the amount of coffee we drink. This is important, because when disease drives behavior, it can lead to misleading health associations in observational studies, and indeed, create a false impression for health benefits if the group of people who do not drink coffee also includes more people who are unwell,” she said.

For now, doctors can tell their patients that this study provides an explanation as to why research on the health effects of habitual coffee consumption has been conflicting, Dr. Hyppönen said.

“Our study also highlights the uncertainty that underlies the claimed health benefits of coffee, but at the same time, it gives a positive message about the ability of our body to regulate our level of coffee consumption in a way that helps us avoid adverse effects.”

“The most common symptoms of excessive coffee consumption are palpitations and rapid heartbeat, also known as tachycardia,” Nieca Goldberg, MD, medical director of the NYU Women’s Heart Program at NYU Langone Health, said in an interview.

“This study was designed to see if cardiac symptoms affect coffee consumption, and it showed that people with hypertension, angina, history of arrhythmias, and poor health tend to be decaffeinated coffee drinkers or no coffee drinkers,” Dr. Goldberg said.

“People naturally alter their coffee intake base on their blood pressure and symptoms of palpitations and/or rapid heart rate,” she said.

The results also suggest that, “we cannot infer health benefit or harm based on the available coffee studies,” Dr. Goldberg added.

The study was funded by the National Health and Medical Research Council, Australia. Dr. Hyppönen and Dr. Goldberg have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

An examination of coffee consumption habits of almost 400,000 people suggests that those habits are largely driven by a person’s cardiovascular health.

©Elena Moiseeva/fotolia.com

Data from a large population database showed that people with essential hypertension, angina, or cardiac arrhythmias drank less coffee than people who had none of these conditions. When they did drink coffee, it tended to be decaffeinated.

The investigators, led by Elina Hyppönen, PhD, director of the Australian Centre for Precision Health at the University of South Australia, Adelaide, say that this predilection for avoiding coffee, which is known to produce jitteriness and heart palpitations, is based on genetics.

“If your body is telling you not to drink that extra cup of coffee, there’s likely a reason why,” Dr. Hyppönen said in an interview.

The study was published online in the American Journal of Clinical Nutrition.

“People drink coffee as a pick-me-up when they’re feeling tired, or because it tastes good, or simply because it’s part of their daily routine, but what we don’t recognize is that people subconsciously self-regulate safe levels of caffeine based on how high their blood pressure is, and this is likely a result of a protective genetic mechanism, [meaning] that someone who drinks a lot of coffee is likely more genetically tolerant of caffeine, as compared to someone who drinks very little,” Dr. Hyppönen said.

“In addition, we’ve known from past research that when people feel unwell, they tend to drink less coffee. This type of phenomenon, where disease drives behavior, is called reverse causality,” Dr. Hyppönen said.

For this analysis, she and her team used information on 390,435 individuals of European ancestry from the UK Biobank, a large epidemiologic database. Habitual coffee consumption was self-reported, and systolic and diastolic blood pressure and heart rate were measured at baseline. Cardiovascular symptoms at baseline were gleaned from hospital diagnoses, primary care records, and/or self report, the authors note.

To look at the relationship of systolic BP, diastolic BP, and heart rate with coffee consumption, they used a strategy called Mendelian randomization, which allows genetic information such as variants reflecting higher blood pressures and heart rate to be used to provide evidence for a causal association.

Results showed that participants with essential hypertension, angina, or arrhythmia were “all more likely to drink less caffeinated coffee and to be nonhabitual or decaffeinated coffee drinkers compared with those who did not report related symptoms,” the authors write.

Those with higher systolic and diastolic BP based on their genetics tended to drink less caffeinated coffee at baseline, “with consistent genetic evidence to support a causal explanation across all methods,” they noted.

They also found that those people who have a higher resting heart rate due to their genes were more likely to choose decaffeinated coffee.

“These results have two major implications,” Dr. Hyppönen said. “Firstly, they show that our bodies can regulate behavior in ways that we may not realize, and that if something does not feel good to us, there is a likely to be a reason why.”

“Second, our results show that our health status in part regulates the amount of coffee we drink. This is important, because when disease drives behavior, it can lead to misleading health associations in observational studies, and indeed, create a false impression for health benefits if the group of people who do not drink coffee also includes more people who are unwell,” she said.

For now, doctors can tell their patients that this study provides an explanation as to why research on the health effects of habitual coffee consumption has been conflicting, Dr. Hyppönen said.

“Our study also highlights the uncertainty that underlies the claimed health benefits of coffee, but at the same time, it gives a positive message about the ability of our body to regulate our level of coffee consumption in a way that helps us avoid adverse effects.”

“The most common symptoms of excessive coffee consumption are palpitations and rapid heartbeat, also known as tachycardia,” Nieca Goldberg, MD, medical director of the NYU Women’s Heart Program at NYU Langone Health, said in an interview.

“This study was designed to see if cardiac symptoms affect coffee consumption, and it showed that people with hypertension, angina, history of arrhythmias, and poor health tend to be decaffeinated coffee drinkers or no coffee drinkers,” Dr. Goldberg said.

“People naturally alter their coffee intake base on their blood pressure and symptoms of palpitations and/or rapid heart rate,” she said.

The results also suggest that, “we cannot infer health benefit or harm based on the available coffee studies,” Dr. Goldberg added.

The study was funded by the National Health and Medical Research Council, Australia. Dr. Hyppönen and Dr. Goldberg have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

An examination of coffee consumption habits of almost 400,000 people suggests that those habits are largely driven by a person’s cardiovascular health.

©Elena Moiseeva/fotolia.com

Data from a large population database showed that people with essential hypertension, angina, or cardiac arrhythmias drank less coffee than people who had none of these conditions. When they did drink coffee, it tended to be decaffeinated.

The investigators, led by Elina Hyppönen, PhD, director of the Australian Centre for Precision Health at the University of South Australia, Adelaide, say that this predilection for avoiding coffee, which is known to produce jitteriness and heart palpitations, is based on genetics.

“If your body is telling you not to drink that extra cup of coffee, there’s likely a reason why,” Dr. Hyppönen said in an interview.

The study was published online in the American Journal of Clinical Nutrition.

“People drink coffee as a pick-me-up when they’re feeling tired, or because it tastes good, or simply because it’s part of their daily routine, but what we don’t recognize is that people subconsciously self-regulate safe levels of caffeine based on how high their blood pressure is, and this is likely a result of a protective genetic mechanism, [meaning] that someone who drinks a lot of coffee is likely more genetically tolerant of caffeine, as compared to someone who drinks very little,” Dr. Hyppönen said.

“In addition, we’ve known from past research that when people feel unwell, they tend to drink less coffee. This type of phenomenon, where disease drives behavior, is called reverse causality,” Dr. Hyppönen said.

For this analysis, she and her team used information on 390,435 individuals of European ancestry from the UK Biobank, a large epidemiologic database. Habitual coffee consumption was self-reported, and systolic and diastolic blood pressure and heart rate were measured at baseline. Cardiovascular symptoms at baseline were gleaned from hospital diagnoses, primary care records, and/or self report, the authors note.

To look at the relationship of systolic BP, diastolic BP, and heart rate with coffee consumption, they used a strategy called Mendelian randomization, which allows genetic information such as variants reflecting higher blood pressures and heart rate to be used to provide evidence for a causal association.

Results showed that participants with essential hypertension, angina, or arrhythmia were “all more likely to drink less caffeinated coffee and to be nonhabitual or decaffeinated coffee drinkers compared with those who did not report related symptoms,” the authors write.

Those with higher systolic and diastolic BP based on their genetics tended to drink less caffeinated coffee at baseline, “with consistent genetic evidence to support a causal explanation across all methods,” they noted.

They also found that those people who have a higher resting heart rate due to their genes were more likely to choose decaffeinated coffee.

“These results have two major implications,” Dr. Hyppönen said. “Firstly, they show that our bodies can regulate behavior in ways that we may not realize, and that if something does not feel good to us, there is a likely to be a reason why.”

“Second, our results show that our health status in part regulates the amount of coffee we drink. This is important, because when disease drives behavior, it can lead to misleading health associations in observational studies, and indeed, create a false impression for health benefits if the group of people who do not drink coffee also includes more people who are unwell,” she said.

For now, doctors can tell their patients that this study provides an explanation as to why research on the health effects of habitual coffee consumption has been conflicting, Dr. Hyppönen said.

“Our study also highlights the uncertainty that underlies the claimed health benefits of coffee, but at the same time, it gives a positive message about the ability of our body to regulate our level of coffee consumption in a way that helps us avoid adverse effects.”

“The most common symptoms of excessive coffee consumption are palpitations and rapid heartbeat, also known as tachycardia,” Nieca Goldberg, MD, medical director of the NYU Women’s Heart Program at NYU Langone Health, said in an interview.

“This study was designed to see if cardiac symptoms affect coffee consumption, and it showed that people with hypertension, angina, history of arrhythmias, and poor health tend to be decaffeinated coffee drinkers or no coffee drinkers,” Dr. Goldberg said.

“People naturally alter their coffee intake base on their blood pressure and symptoms of palpitations and/or rapid heart rate,” she said.

The results also suggest that, “we cannot infer health benefit or harm based on the available coffee studies,” Dr. Goldberg added.

The study was funded by the National Health and Medical Research Council, Australia. Dr. Hyppönen and Dr. Goldberg have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Among patients with locally advanced resectable esophageal or junctional cancer, the overall survival benefit conferred by preoperative chemoradiotherapy persists for at least 10 years, according to long-term results of the Chemoradiotherapy for Esophageal Cancer Followed by Surgery Study (CROSS). As a result of earlier publication of CROSS data, chemoradiotherapy followed by surgery has become one of the standards of care for patients with locally advanced resectable esophageal cancer, stated lead author Ben M. Eyck, MD, of Erasmus University Medical Center, Rotterdam, the Netherlands, and colleagues in the Journal of Clinical Oncology.

In the multicenter, randomized trial, initiated in 2004, 178 patients randomized to chemoradiotherapy with subsequent surgery and 188 patients randomized to surgery alone were followed with overall survival as the primary, and cause-specific survival and risks of locoregional and distant relapse as the secondary endpoints. Chemoradiotherapy consisted of 5 weekly cycles of carboplatin (area under the curve of 2 mg/mL/min) and paclitaxel (50 mg/m² body surface area on days 1, 8, 15, 22, and 29) with concurrent radiotherapy (41.4 Gy in 23 fractions, 5 days per week. Mean age was 60 years (around 78% male), with squamous cell carcinoma (23%) and adenocarcinoma (75%) as the predominant histologies.

The first analysis showed low short-term toxicity and 2-year survival increased from 50% for patients receiving surgery alone to 67% for neoadjuvant chemoradiotherapy plus surgery. Five-year follow-up data were consistent with initial reporting. Long-term benefits and harms of this regimen remain unclear, according to the researchers. Neoadjuvant chemoradiotherapy’s side effects could lead to long-term death from other causes than esophageal cancer, and may not be preventing but rather merely postponing cancer-related death. The aim of the current analysis was to determine whether the observed benefits persisted beyond 5 years.

As of Dec. 31, 2018, 117/178 patients in the chemoradiotherapy-surgery arm and 144/188 in the surgery arm had died. Median follow-up for surviving patients was 147 months. Patients in the chemoradiotherapy surgery arm had better overall survival than patients in the surgery arm (hazard ratio, 0.70; 95% confidence interval, 0.55-0.89; P = .004), with a 10-year overall survival of 38% (95% CI, 31-45) and 25% (95% CI, 19-32), respectively. No significant subgroup differences were observed for overall survival. Also, there was no evidence of a time-dependent effect of neoadjuvant chemoradiotherapy on overall survival. The major effect of neoadjuvant chemoradiotherapy, landmark analyses showed, was in the first 5 years of follow-up, with the effect on overall survival stabilized thereafter, with a hazard ratio approaching 1.00.
 

Cause-specific mortality

Eighty-four of 178 patients in the chemoradiotherapy-surgery arm died of esophageal cancer, with 32 dying of other causes. In the surgery arm, 121/188 died of esophageal cancer and 22 of other causes. The hazard ratio for esophageal cancer death in the chemoradiotherapy-surgery arm was 0.60 (95% CI, 0.46 to 0.80), with 10-year absolute risks of 47% (95% CI, 40-54) and 64% (95% CI,57-71), respectively, in the two arms. Death from other causes was comparable, with 10-year absolute risks of 15% (95% CI, 10-21) and 11% (95% CI, 7-16), respectively, for chemoradiotherapy-surgery versus surgery alone.

Locoregional relapse

Locoregional relapse rates were 8% (15/178) and 18% (33/188) in the chemoradiotherapy-surgery and surgery arms, respectively (HR, 0.39; 95% CI, 0.21-0.72). Eighty-seven percent of those developed within 3 years of follow-up in the chemoradiotherapy arm, with the median relapse-free interval at 3.9 months. In the surgery arm, 28 of 33 relapses (85%) developed within 3 years and the median relapse-free interval was 7.1 months. Beyond 6 years, there were no further relapses in either arm.

While synchronous distant plus locoregional relapse developed in 23 of 178 patients (13%) in the chemoradiotherapy-surgery arm and in 42 of 188 patients (22%) in the surgery arm (HR, 0.43; 95% CI, 0.26-0.72), isolated distant relapse developed at similar rates (around 27.5%) in both groups. Risk of distant relapse (with or without locoregional relapse) was lower in the chemoradiotherapy-surgery arm (HR, 0.61; 95%CI, 0.45-0.84). The median relapse-free interval was 15.1 months (interquartile range, 9.3-27.6) in the chemoradiotherapy-surgery arm and 9.0 months (IQR, 5.3-19.7) in the surgery arm.
 

Safety and health-related quality of life

The combination of paclitaxel and carboplatin with concurrent 41.4 Gy radiotherapy before surgery seems safe in the long term and does not significantly increase the risk of toxicity-related death, the researchers stated. Within the CROSS trial, short-term and long-term health-related quality of life after neoadjuvant chemoradiotherapy plus surgery for surviving patients was comparable to that after surgery alone.

Long-term persistent overall survival benefit

Ten-year CROSS results show that “for locally advanced resectable cancer of the esophagus or esophagogastric junction, preoperative chemoradiotherapy induces a long-term persistent improvement in overall survival.” Also, neoadjuvant chemoradiotherapy does not lead to an increased risk of death from other causes, and the survival benefit of long-term survivors is not compromised, compared with surgery alone. Furthermore, neoadjuvant chemoradiotherapy plus surgery according to CROSS can still be regarded as a standard of care, the researchers added.

Dr. Eyck and colleagues are currently performing the phase II TNT-OES-1 trial. It combines FLOT (fluorouracil, leucovorin, oxaliplatin and docetaxel) chemotherapy followed by CROSS chemoradiotherapy in patients with advanced esophageal and junctional adenocarcinoma. If this regimen appears to be safe in advanced cancer, they plan to perform a phase III trial with this regimen in locally advanced cancer. In addition, they are currently evaluating the implementation of adjuvant nivolumab in clinical practice for patients with pathologically residual disease after CROSS + surgery, based on the recently published CheckMate 577 trial .

“If possible, we prefer adding better systemic therapy to chemoradiotherapy rather than replacing chemoradiotherapy with systemic therapy alone,” Dr. Eyck said in an interview. “The reason for this is that we would like to allow patients with a complete response to neoadjuvant therapy to undergo active surveillance instead of surgery in the near future. … Since the pathologically complete response rate after regimens containing radiotherapy is substantially higher, we still prefer the addition of radiotherapy.”

The study was funded by the Dutch Cancer Foundation (KWF Kankerbestrijding). Dr. Eyck reported no disclosures. Several of the coauthors reported consulting and advisory roles with a variety of pharmaceutical companies.

Among patients with locally advanced resectable esophageal or junctional cancer, the overall survival benefit conferred by preoperative chemoradiotherapy persists for at least 10 years, according to long-term results of the Chemoradiotherapy for Esophageal Cancer Followed by Surgery Study (CROSS). As a result of earlier publication of CROSS data, chemoradiotherapy followed by surgery has become one of the standards of care for patients with locally advanced resectable esophageal cancer, stated lead author Ben M. Eyck, MD, of Erasmus University Medical Center, Rotterdam, the Netherlands, and colleagues in the Journal of Clinical Oncology.

In the multicenter, randomized trial, initiated in 2004, 178 patients randomized to chemoradiotherapy with subsequent surgery and 188 patients randomized to surgery alone were followed with overall survival as the primary, and cause-specific survival and risks of locoregional and distant relapse as the secondary endpoints. Chemoradiotherapy consisted of 5 weekly cycles of carboplatin (area under the curve of 2 mg/mL/min) and paclitaxel (50 mg/m² body surface area on days 1, 8, 15, 22, and 29) with concurrent radiotherapy (41.4 Gy in 23 fractions, 5 days per week. Mean age was 60 years (around 78% male), with squamous cell carcinoma (23%) and adenocarcinoma (75%) as the predominant histologies.

The first analysis showed low short-term toxicity and 2-year survival increased from 50% for patients receiving surgery alone to 67% for neoadjuvant chemoradiotherapy plus surgery. Five-year follow-up data were consistent with initial reporting. Long-term benefits and harms of this regimen remain unclear, according to the researchers. Neoadjuvant chemoradiotherapy’s side effects could lead to long-term death from other causes than esophageal cancer, and may not be preventing but rather merely postponing cancer-related death. The aim of the current analysis was to determine whether the observed benefits persisted beyond 5 years.

As of Dec. 31, 2018, 117/178 patients in the chemoradiotherapy-surgery arm and 144/188 in the surgery arm had died. Median follow-up for surviving patients was 147 months. Patients in the chemoradiotherapy surgery arm had better overall survival than patients in the surgery arm (hazard ratio, 0.70; 95% confidence interval, 0.55-0.89; P = .004), with a 10-year overall survival of 38% (95% CI, 31-45) and 25% (95% CI, 19-32), respectively. No significant subgroup differences were observed for overall survival. Also, there was no evidence of a time-dependent effect of neoadjuvant chemoradiotherapy on overall survival. The major effect of neoadjuvant chemoradiotherapy, landmark analyses showed, was in the first 5 years of follow-up, with the effect on overall survival stabilized thereafter, with a hazard ratio approaching 1.00.
 

Cause-specific mortality

Eighty-four of 178 patients in the chemoradiotherapy-surgery arm died of esophageal cancer, with 32 dying of other causes. In the surgery arm, 121/188 died of esophageal cancer and 22 of other causes. The hazard ratio for esophageal cancer death in the chemoradiotherapy-surgery arm was 0.60 (95% CI, 0.46 to 0.80), with 10-year absolute risks of 47% (95% CI, 40-54) and 64% (95% CI,57-71), respectively, in the two arms. Death from other causes was comparable, with 10-year absolute risks of 15% (95% CI, 10-21) and 11% (95% CI, 7-16), respectively, for chemoradiotherapy-surgery versus surgery alone.

Locoregional relapse

Locoregional relapse rates were 8% (15/178) and 18% (33/188) in the chemoradiotherapy-surgery and surgery arms, respectively (HR, 0.39; 95% CI, 0.21-0.72). Eighty-seven percent of those developed within 3 years of follow-up in the chemoradiotherapy arm, with the median relapse-free interval at 3.9 months. In the surgery arm, 28 of 33 relapses (85%) developed within 3 years and the median relapse-free interval was 7.1 months. Beyond 6 years, there were no further relapses in either arm.

While synchronous distant plus locoregional relapse developed in 23 of 178 patients (13%) in the chemoradiotherapy-surgery arm and in 42 of 188 patients (22%) in the surgery arm (HR, 0.43; 95% CI, 0.26-0.72), isolated distant relapse developed at similar rates (around 27.5%) in both groups. Risk of distant relapse (with or without locoregional relapse) was lower in the chemoradiotherapy-surgery arm (HR, 0.61; 95%CI, 0.45-0.84). The median relapse-free interval was 15.1 months (interquartile range, 9.3-27.6) in the chemoradiotherapy-surgery arm and 9.0 months (IQR, 5.3-19.7) in the surgery arm.
 

Safety and health-related quality of life

The combination of paclitaxel and carboplatin with concurrent 41.4 Gy radiotherapy before surgery seems safe in the long term and does not significantly increase the risk of toxicity-related death, the researchers stated. Within the CROSS trial, short-term and long-term health-related quality of life after neoadjuvant chemoradiotherapy plus surgery for surviving patients was comparable to that after surgery alone.

Long-term persistent overall survival benefit

Ten-year CROSS results show that “for locally advanced resectable cancer of the esophagus or esophagogastric junction, preoperative chemoradiotherapy induces a long-term persistent improvement in overall survival.” Also, neoadjuvant chemoradiotherapy does not lead to an increased risk of death from other causes, and the survival benefit of long-term survivors is not compromised, compared with surgery alone. Furthermore, neoadjuvant chemoradiotherapy plus surgery according to CROSS can still be regarded as a standard of care, the researchers added.

Dr. Eyck and colleagues are currently performing the phase II TNT-OES-1 trial. It combines FLOT (fluorouracil, leucovorin, oxaliplatin and docetaxel) chemotherapy followed by CROSS chemoradiotherapy in patients with advanced esophageal and junctional adenocarcinoma. If this regimen appears to be safe in advanced cancer, they plan to perform a phase III trial with this regimen in locally advanced cancer. In addition, they are currently evaluating the implementation of adjuvant nivolumab in clinical practice for patients with pathologically residual disease after CROSS + surgery, based on the recently published CheckMate 577 trial .

“If possible, we prefer adding better systemic therapy to chemoradiotherapy rather than replacing chemoradiotherapy with systemic therapy alone,” Dr. Eyck said in an interview. “The reason for this is that we would like to allow patients with a complete response to neoadjuvant therapy to undergo active surveillance instead of surgery in the near future. … Since the pathologically complete response rate after regimens containing radiotherapy is substantially higher, we still prefer the addition of radiotherapy.”

The study was funded by the Dutch Cancer Foundation (KWF Kankerbestrijding). Dr. Eyck reported no disclosures. Several of the coauthors reported consulting and advisory roles with a variety of pharmaceutical companies.

Among patients with locally advanced resectable esophageal or junctional cancer, the overall survival benefit conferred by preoperative chemoradiotherapy persists for at least 10 years, according to long-term results of the Chemoradiotherapy for Esophageal Cancer Followed by Surgery Study (CROSS). As a result of earlier publication of CROSS data, chemoradiotherapy followed by surgery has become one of the standards of care for patients with locally advanced resectable esophageal cancer, stated lead author Ben M. Eyck, MD, of Erasmus University Medical Center, Rotterdam, the Netherlands, and colleagues in the Journal of Clinical Oncology.

In the multicenter, randomized trial, initiated in 2004, 178 patients randomized to chemoradiotherapy with subsequent surgery and 188 patients randomized to surgery alone were followed with overall survival as the primary, and cause-specific survival and risks of locoregional and distant relapse as the secondary endpoints. Chemoradiotherapy consisted of 5 weekly cycles of carboplatin (area under the curve of 2 mg/mL/min) and paclitaxel (50 mg/m² body surface area on days 1, 8, 15, 22, and 29) with concurrent radiotherapy (41.4 Gy in 23 fractions, 5 days per week. Mean age was 60 years (around 78% male), with squamous cell carcinoma (23%) and adenocarcinoma (75%) as the predominant histologies.

The first analysis showed low short-term toxicity and 2-year survival increased from 50% for patients receiving surgery alone to 67% for neoadjuvant chemoradiotherapy plus surgery. Five-year follow-up data were consistent with initial reporting. Long-term benefits and harms of this regimen remain unclear, according to the researchers. Neoadjuvant chemoradiotherapy’s side effects could lead to long-term death from other causes than esophageal cancer, and may not be preventing but rather merely postponing cancer-related death. The aim of the current analysis was to determine whether the observed benefits persisted beyond 5 years.

As of Dec. 31, 2018, 117/178 patients in the chemoradiotherapy-surgery arm and 144/188 in the surgery arm had died. Median follow-up for surviving patients was 147 months. Patients in the chemoradiotherapy surgery arm had better overall survival than patients in the surgery arm (hazard ratio, 0.70; 95% confidence interval, 0.55-0.89; P = .004), with a 10-year overall survival of 38% (95% CI, 31-45) and 25% (95% CI, 19-32), respectively. No significant subgroup differences were observed for overall survival. Also, there was no evidence of a time-dependent effect of neoadjuvant chemoradiotherapy on overall survival. The major effect of neoadjuvant chemoradiotherapy, landmark analyses showed, was in the first 5 years of follow-up, with the effect on overall survival stabilized thereafter, with a hazard ratio approaching 1.00.
 

Cause-specific mortality

Eighty-four of 178 patients in the chemoradiotherapy-surgery arm died of esophageal cancer, with 32 dying of other causes. In the surgery arm, 121/188 died of esophageal cancer and 22 of other causes. The hazard ratio for esophageal cancer death in the chemoradiotherapy-surgery arm was 0.60 (95% CI, 0.46 to 0.80), with 10-year absolute risks of 47% (95% CI, 40-54) and 64% (95% CI,57-71), respectively, in the two arms. Death from other causes was comparable, with 10-year absolute risks of 15% (95% CI, 10-21) and 11% (95% CI, 7-16), respectively, for chemoradiotherapy-surgery versus surgery alone.

Locoregional relapse

Locoregional relapse rates were 8% (15/178) and 18% (33/188) in the chemoradiotherapy-surgery and surgery arms, respectively (HR, 0.39; 95% CI, 0.21-0.72). Eighty-seven percent of those developed within 3 years of follow-up in the chemoradiotherapy arm, with the median relapse-free interval at 3.9 months. In the surgery arm, 28 of 33 relapses (85%) developed within 3 years and the median relapse-free interval was 7.1 months. Beyond 6 years, there were no further relapses in either arm.

While synchronous distant plus locoregional relapse developed in 23 of 178 patients (13%) in the chemoradiotherapy-surgery arm and in 42 of 188 patients (22%) in the surgery arm (HR, 0.43; 95% CI, 0.26-0.72), isolated distant relapse developed at similar rates (around 27.5%) in both groups. Risk of distant relapse (with or without locoregional relapse) was lower in the chemoradiotherapy-surgery arm (HR, 0.61; 95%CI, 0.45-0.84). The median relapse-free interval was 15.1 months (interquartile range, 9.3-27.6) in the chemoradiotherapy-surgery arm and 9.0 months (IQR, 5.3-19.7) in the surgery arm.
 

Safety and health-related quality of life

The combination of paclitaxel and carboplatin with concurrent 41.4 Gy radiotherapy before surgery seems safe in the long term and does not significantly increase the risk of toxicity-related death, the researchers stated. Within the CROSS trial, short-term and long-term health-related quality of life after neoadjuvant chemoradiotherapy plus surgery for surviving patients was comparable to that after surgery alone.

Long-term persistent overall survival benefit

Ten-year CROSS results show that “for locally advanced resectable cancer of the esophagus or esophagogastric junction, preoperative chemoradiotherapy induces a long-term persistent improvement in overall survival.” Also, neoadjuvant chemoradiotherapy does not lead to an increased risk of death from other causes, and the survival benefit of long-term survivors is not compromised, compared with surgery alone. Furthermore, neoadjuvant chemoradiotherapy plus surgery according to CROSS can still be regarded as a standard of care, the researchers added.

Dr. Eyck and colleagues are currently performing the phase II TNT-OES-1 trial. It combines FLOT (fluorouracil, leucovorin, oxaliplatin and docetaxel) chemotherapy followed by CROSS chemoradiotherapy in patients with advanced esophageal and junctional adenocarcinoma. If this regimen appears to be safe in advanced cancer, they plan to perform a phase III trial with this regimen in locally advanced cancer. In addition, they are currently evaluating the implementation of adjuvant nivolumab in clinical practice for patients with pathologically residual disease after CROSS + surgery, based on the recently published CheckMate 577 trial .

“If possible, we prefer adding better systemic therapy to chemoradiotherapy rather than replacing chemoradiotherapy with systemic therapy alone,” Dr. Eyck said in an interview. “The reason for this is that we would like to allow patients with a complete response to neoadjuvant therapy to undergo active surveillance instead of surgery in the near future. … Since the pathologically complete response rate after regimens containing radiotherapy is substantially higher, we still prefer the addition of radiotherapy.”

The study was funded by the Dutch Cancer Foundation (KWF Kankerbestrijding). Dr. Eyck reported no disclosures. Several of the coauthors reported consulting and advisory roles with a variety of pharmaceutical companies.

Six months after mild SARS-CoV-2 infection in a representative health care workforce, no long-term cardiovascular sequelae were detected, compared with a matched SARS-CoV-2 seronegative group.

“Mild COVID-19 left no measurable cardiovascular impact on LV structure, function, scar burden, aortic stiffness, or serum biomarkers,” the researchers reported in an article published online May 8 in JACC: Cardiovascular Imaging.

“We provide societal reassurance and support for the position that screening in asymptomatic individuals following mild disease is not indicated,” first author George Joy, MBBS, University College London, said in presenting the results at EuroCMR, the annual CMR congress of the European Association of Cardiovascular Imaging (EACVI).

Briefing comoderator Leyla Elif Sade, MD, University of Baskent, Ankara, Turkey, said, “This is the hot topic of our time because of obvious reasons and I think [this] study is quite important to avoid unnecessary further testing, surveillance testing, and to avoid a significant burden of health care costs.”
 

‘Alarming’ early data

Early cardiac magnetic resonance (CMR) studies in patients recovered from mild COVID-19 were “alarming,” Dr. Joy said.

As previously reported, one study showed cardiac abnormalities after mild COVID-19 in up to 78% of patients, with evidence of ongoing myocardial inflammation in 60%. The CMR findings correlated with elevations in troponin T by high-sensitivity assay (hs-TnT).

To investigate further, Dr. Joy and colleagues did a nested case-control study within the COVIDsortium, a prospective study of 731 health care workers from three London hospitals who underwent weekly symptom, polymerase chain reaction, and serology assessment over 4 months during the first wave of the pandemic.

A total of 157 (21.5%) participants seroconverted during the study period.

Six months after infection, 74 seropositive (median age, 39; 62% women) and 75 age-, sex-, and ethnicity-matched seronegative controls underwent cardiovascular phenotyping (comprehensive phantom-calibrated CMR and blood biomarkers). The analysis was blinded, using objective artificial intelligence analytics when available.

The results showed no statistically significant differences between seropositive and seronegative participants in cardiac structure (left ventricular volumes, mass, atrial area), function (ejection fraction, global longitudinal shortening, aortic distensibility), tissue characterization (T1, T2, extracellular volume fraction mapping, late gadolinium enhancement) or biomarkers (troponin, N-terminal pro–B-type natriuretic peptide).

Cardiovascular abnormalities were no more common in seropositive than seronegative otherwise healthy health care workers 6 months post mild SARS-CoV-2 infection. Measured abnormalities were “evenly distributed between both groups,” Dr. Joy said.

Therefore, it’s “important to reassure patients with mild SARS-CoV-2 infection regarding its cardiovascular effects,” Dr. Joy and colleagues concluded.
 

Limitations and caveats

They caution, however, that the study provides insight only into the short- to medium-term sequelae of patients aged 18-69 with mild COVID-19 who did not require hospitalization and had low numbers of comorbidities.

The study does not address the cardiovascular effects after severe COVID-19 infection requiring hospitalization or in those with multiple comorbid conditions, they noted. It also does not prove that apparently mild SARS-CoV-2 never causes chronic myocarditis.

“The study design would not distinguish between people who had sustained completely healed myocarditis and pericarditis and those in whom the heart had never been affected,” the researchers noted.

They pointed to a recent cross-sectional study of athletes 1-month post mild COVID-19 that found significant pericardial involvement (late enhancement and/or pericardial effusion), although no baseline pre-COVID-19 imaging was performed. In the current study at 6 months post infection the pericardium was normal.

The coauthors of a linked editorial say this study provides “welcome, reassuring information that in healthy individuals who experience mild infection with COVID-19, persisting evidence of cardiovascular complications is very uncommon. The results do not support cardiovascular screening in individuals with mild or asymptomatic infection with COVID-19.”  

Colin Berry, PhD, and Kenneth Mangion, PhD, both from University of Glasgow, cautioned that the population is restricted to health care workers; therefore, the findings may not necessarily be generalized to a community population .

“Healthcare workers do not reflect the population of individuals most clinically affected by COVID-19 illness. The severity of acute COVID-19 infection is greatest in older individuals and those with preexisting health problems. Healthcare workers are not representative of the wider, unselected, at-risk, community population,” they pointed out.

Cardiovascular risk factors and concomitant health problems (heart and respiratory disease) may be more common in the community than in health care workers, and prior studies have highlighted their potential impact for disease pathogenesis in COVID-19.

Dr. Berry and Dr. Mangion also noted that women made up nearly two-thirds of the seropositive group. This may reflect a selection bias or may naturally reflect the fact that proportionately more women are asymptomatic or have milder forms of illness, whereas severe SARS-CoV-2 infection requiring hospitalization affects men to a greater degree.

COVIDsortium funding was donated by individuals, charitable trusts, and corporations including Goldman Sachs, Citadel and Citadel Securities, The Guy Foundation, GW Pharmaceuticals, Kusuma Trust, and Jagclif Charitable Trust, and enabled by Barts Charity with support from UCLH Charity. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Six months after mild SARS-CoV-2 infection in a representative health care workforce, no long-term cardiovascular sequelae were detected, compared with a matched SARS-CoV-2 seronegative group.

“Mild COVID-19 left no measurable cardiovascular impact on LV structure, function, scar burden, aortic stiffness, or serum biomarkers,” the researchers reported in an article published online May 8 in JACC: Cardiovascular Imaging.

“We provide societal reassurance and support for the position that screening in asymptomatic individuals following mild disease is not indicated,” first author George Joy, MBBS, University College London, said in presenting the results at EuroCMR, the annual CMR congress of the European Association of Cardiovascular Imaging (EACVI).

Briefing comoderator Leyla Elif Sade, MD, University of Baskent, Ankara, Turkey, said, “This is the hot topic of our time because of obvious reasons and I think [this] study is quite important to avoid unnecessary further testing, surveillance testing, and to avoid a significant burden of health care costs.”
 

‘Alarming’ early data

Early cardiac magnetic resonance (CMR) studies in patients recovered from mild COVID-19 were “alarming,” Dr. Joy said.

As previously reported, one study showed cardiac abnormalities after mild COVID-19 in up to 78% of patients, with evidence of ongoing myocardial inflammation in 60%. The CMR findings correlated with elevations in troponin T by high-sensitivity assay (hs-TnT).

To investigate further, Dr. Joy and colleagues did a nested case-control study within the COVIDsortium, a prospective study of 731 health care workers from three London hospitals who underwent weekly symptom, polymerase chain reaction, and serology assessment over 4 months during the first wave of the pandemic.

A total of 157 (21.5%) participants seroconverted during the study period.

Six months after infection, 74 seropositive (median age, 39; 62% women) and 75 age-, sex-, and ethnicity-matched seronegative controls underwent cardiovascular phenotyping (comprehensive phantom-calibrated CMR and blood biomarkers). The analysis was blinded, using objective artificial intelligence analytics when available.

The results showed no statistically significant differences between seropositive and seronegative participants in cardiac structure (left ventricular volumes, mass, atrial area), function (ejection fraction, global longitudinal shortening, aortic distensibility), tissue characterization (T1, T2, extracellular volume fraction mapping, late gadolinium enhancement) or biomarkers (troponin, N-terminal pro–B-type natriuretic peptide).

Cardiovascular abnormalities were no more common in seropositive than seronegative otherwise healthy health care workers 6 months post mild SARS-CoV-2 infection. Measured abnormalities were “evenly distributed between both groups,” Dr. Joy said.

Therefore, it’s “important to reassure patients with mild SARS-CoV-2 infection regarding its cardiovascular effects,” Dr. Joy and colleagues concluded.
 

Limitations and caveats

They caution, however, that the study provides insight only into the short- to medium-term sequelae of patients aged 18-69 with mild COVID-19 who did not require hospitalization and had low numbers of comorbidities.

The study does not address the cardiovascular effects after severe COVID-19 infection requiring hospitalization or in those with multiple comorbid conditions, they noted. It also does not prove that apparently mild SARS-CoV-2 never causes chronic myocarditis.

“The study design would not distinguish between people who had sustained completely healed myocarditis and pericarditis and those in whom the heart had never been affected,” the researchers noted.

They pointed to a recent cross-sectional study of athletes 1-month post mild COVID-19 that found significant pericardial involvement (late enhancement and/or pericardial effusion), although no baseline pre-COVID-19 imaging was performed. In the current study at 6 months post infection the pericardium was normal.

The coauthors of a linked editorial say this study provides “welcome, reassuring information that in healthy individuals who experience mild infection with COVID-19, persisting evidence of cardiovascular complications is very uncommon. The results do not support cardiovascular screening in individuals with mild or asymptomatic infection with COVID-19.”  

Colin Berry, PhD, and Kenneth Mangion, PhD, both from University of Glasgow, cautioned that the population is restricted to health care workers; therefore, the findings may not necessarily be generalized to a community population .

“Healthcare workers do not reflect the population of individuals most clinically affected by COVID-19 illness. The severity of acute COVID-19 infection is greatest in older individuals and those with preexisting health problems. Healthcare workers are not representative of the wider, unselected, at-risk, community population,” they pointed out.

Cardiovascular risk factors and concomitant health problems (heart and respiratory disease) may be more common in the community than in health care workers, and prior studies have highlighted their potential impact for disease pathogenesis in COVID-19.

Dr. Berry and Dr. Mangion also noted that women made up nearly two-thirds of the seropositive group. This may reflect a selection bias or may naturally reflect the fact that proportionately more women are asymptomatic or have milder forms of illness, whereas severe SARS-CoV-2 infection requiring hospitalization affects men to a greater degree.

COVIDsortium funding was donated by individuals, charitable trusts, and corporations including Goldman Sachs, Citadel and Citadel Securities, The Guy Foundation, GW Pharmaceuticals, Kusuma Trust, and Jagclif Charitable Trust, and enabled by Barts Charity with support from UCLH Charity. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Six months after mild SARS-CoV-2 infection in a representative health care workforce, no long-term cardiovascular sequelae were detected, compared with a matched SARS-CoV-2 seronegative group.

“Mild COVID-19 left no measurable cardiovascular impact on LV structure, function, scar burden, aortic stiffness, or serum biomarkers,” the researchers reported in an article published online May 8 in JACC: Cardiovascular Imaging.

“We provide societal reassurance and support for the position that screening in asymptomatic individuals following mild disease is not indicated,” first author George Joy, MBBS, University College London, said in presenting the results at EuroCMR, the annual CMR congress of the European Association of Cardiovascular Imaging (EACVI).

Briefing comoderator Leyla Elif Sade, MD, University of Baskent, Ankara, Turkey, said, “This is the hot topic of our time because of obvious reasons and I think [this] study is quite important to avoid unnecessary further testing, surveillance testing, and to avoid a significant burden of health care costs.”
 

‘Alarming’ early data

Early cardiac magnetic resonance (CMR) studies in patients recovered from mild COVID-19 were “alarming,” Dr. Joy said.

As previously reported, one study showed cardiac abnormalities after mild COVID-19 in up to 78% of patients, with evidence of ongoing myocardial inflammation in 60%. The CMR findings correlated with elevations in troponin T by high-sensitivity assay (hs-TnT).

To investigate further, Dr. Joy and colleagues did a nested case-control study within the COVIDsortium, a prospective study of 731 health care workers from three London hospitals who underwent weekly symptom, polymerase chain reaction, and serology assessment over 4 months during the first wave of the pandemic.

A total of 157 (21.5%) participants seroconverted during the study period.

Six months after infection, 74 seropositive (median age, 39; 62% women) and 75 age-, sex-, and ethnicity-matched seronegative controls underwent cardiovascular phenotyping (comprehensive phantom-calibrated CMR and blood biomarkers). The analysis was blinded, using objective artificial intelligence analytics when available.

The results showed no statistically significant differences between seropositive and seronegative participants in cardiac structure (left ventricular volumes, mass, atrial area), function (ejection fraction, global longitudinal shortening, aortic distensibility), tissue characterization (T1, T2, extracellular volume fraction mapping, late gadolinium enhancement) or biomarkers (troponin, N-terminal pro–B-type natriuretic peptide).

Cardiovascular abnormalities were no more common in seropositive than seronegative otherwise healthy health care workers 6 months post mild SARS-CoV-2 infection. Measured abnormalities were “evenly distributed between both groups,” Dr. Joy said.

Therefore, it’s “important to reassure patients with mild SARS-CoV-2 infection regarding its cardiovascular effects,” Dr. Joy and colleagues concluded.
 

Limitations and caveats

They caution, however, that the study provides insight only into the short- to medium-term sequelae of patients aged 18-69 with mild COVID-19 who did not require hospitalization and had low numbers of comorbidities.

The study does not address the cardiovascular effects after severe COVID-19 infection requiring hospitalization or in those with multiple comorbid conditions, they noted. It also does not prove that apparently mild SARS-CoV-2 never causes chronic myocarditis.

“The study design would not distinguish between people who had sustained completely healed myocarditis and pericarditis and those in whom the heart had never been affected,” the researchers noted.

They pointed to a recent cross-sectional study of athletes 1-month post mild COVID-19 that found significant pericardial involvement (late enhancement and/or pericardial effusion), although no baseline pre-COVID-19 imaging was performed. In the current study at 6 months post infection the pericardium was normal.

The coauthors of a linked editorial say this study provides “welcome, reassuring information that in healthy individuals who experience mild infection with COVID-19, persisting evidence of cardiovascular complications is very uncommon. The results do not support cardiovascular screening in individuals with mild or asymptomatic infection with COVID-19.”  

Colin Berry, PhD, and Kenneth Mangion, PhD, both from University of Glasgow, cautioned that the population is restricted to health care workers; therefore, the findings may not necessarily be generalized to a community population .

“Healthcare workers do not reflect the population of individuals most clinically affected by COVID-19 illness. The severity of acute COVID-19 infection is greatest in older individuals and those with preexisting health problems. Healthcare workers are not representative of the wider, unselected, at-risk, community population,” they pointed out.

Cardiovascular risk factors and concomitant health problems (heart and respiratory disease) may be more common in the community than in health care workers, and prior studies have highlighted their potential impact for disease pathogenesis in COVID-19.

Dr. Berry and Dr. Mangion also noted that women made up nearly two-thirds of the seropositive group. This may reflect a selection bias or may naturally reflect the fact that proportionately more women are asymptomatic or have milder forms of illness, whereas severe SARS-CoV-2 infection requiring hospitalization affects men to a greater degree.

COVIDsortium funding was donated by individuals, charitable trusts, and corporations including Goldman Sachs, Citadel and Citadel Securities, The Guy Foundation, GW Pharmaceuticals, Kusuma Trust, and Jagclif Charitable Trust, and enabled by Barts Charity with support from UCLH Charity. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The American Heart Association, the American College of Cardiology, and the Obesity Society define overweight as a body mass index (BMI) of 25 to 29.9 and obesity as a BMI ≥ 30. Morbid obesity is defined as a BMI ≥ 35 or 40.^2,3 Based on these BMI cutoffs, the Endocrine Society recommends diet and lifestyle as the foundation of weight management and pharmacotherapy for those with a BMI ≥ 30 without comorbidities. In patients with a BMI ≥ 27, weight management medications may be considered if a patient has comorbid hypertension, T2DM, dyslipidemia, metabolic syndrome, obstructive sleep apnea, or nonalcoholic fatty liver disease. Patients with BMI > 40 are eligible for weight loss surgery.⁴

Lifestyle and dietary interventions are the foundation of current weight management guidelines from the Endocrine Society.⁴ At a minimum, guidelines recommended enrolling motivated patients in a high-intensity lifestyle intervention class of at least 14 sessions in the first 6 months to reach a goal weight loss of 5 to 10% from baseline and to maintain a reduction of 3 to 5% from baseline.³ Medications are recommended as an adjunct to lifestyle and dietary changes. Most weight management medications work in the brain to stimulate satiety signaling, which helps motivated patients adhere to their dietary interventions, assist those who have been unsuccessful in earlier weight loss attempts, and help maintain weight.^3,4

Guidelines recommend 7 weight management medications, including orlistat (both prescription strength and over-the-counter), liraglutide, phentermine, phentermine/topiramate, lorcaserin, and naltrexone/bupropion. Using medications to assist with weight loss increases likelihood that patients will achieve 5 to 10% weight loss from baseline.^5,6 Studies looking at long-term effects of these medications on weight loss have found improvements in blood pressure (BP), biomarkers for cardiovascular disease, and T2DM-related comorbidities.^3,5,7

Positive effects on comorbidities have been found to be related to drug class and mechanism of action (MOA); those that also are approved for T2DM have demonstrated the most favorable cardiovascular effects.⁷ Other medications that work as stimulants or as modulators of serotonin pathways are associated with increased risks, prompting the US Food and Drug Administration (FDA) to remove some medications from the market.^7,8 In January 2020, lorcaserin was taken off the market because of increased risk of cancer found in postmarketing surveillance.⁹ The benefit of weight loss must be weighed against the risk of medication use.

Monthly follow-up is recommended with weight management medications in the beginning to assess safety and efficacy; medications should be discontinued if weight loss is inadequate in the first 3 months.^1,3,4 Limited studies have assessed the long-term use of weight management medications in a real-world setting. Medications are prescribed for weight management at Veteran Health Indiana (VHI) in outpatient clinics, including primary care, endocrinology, and gastrointestinal (GI) specialties. However, prescribing practices, outcomes, and adherence to guideline recommendations have not been studied. Data from this study will be used to better understand how VHI can serve its veterans through diet, lifestyle, and pharmacologic interventions.

Methods

We conducted a single-center, retrospective chart review for patients started on weight management medications at VHI. A patient list was generated based on prescription fills from June 1, 2017 to June 30, 2019. All data were obtained using the Computerized Patient Record System and patients were not contacted. This study was approved by the Indiana University Health Institutional Review Board and the VHI Research and Development Committee.

At the time of study, orlistat, liraglutide, phentermine/topiramate, lorcaserin, and naltrexone/bupropion were available at VHI for patients who met the criteria. All patients must have been enrolled in dietary and lifestyle management to be approved for these medications. The US Department of Veterans Affairs (VA) MOVE! weight management program, designed by the VA National Center for Health Promotion and Disease Promotion, is available at VA sites throughout the country. After MOVE! orientation, patients can participate in group or individual 12-week programs that include weigh ins, goal-setting strategies, meal planning, and habit modification support. If patients are unable to meet in person, phone and other telehealth opportunities are available.

Patients were included in the study if they received a prescription of any 1 of the 5 available medications during the enrollment period. Patients were excluded if they received a prescription from or were treated by a civilian health care provider, if they never used the medication, or if their weight loss was attributed to a cancer diagnosis. These criteria produced 86 patients of whom 96 unique weight loss prescriptions were generated. Data were collected for each instance of medication use so that some patients were included multiple times. In this case, data collection for the failed medication ended when failure was documented, and new data points began when new medication was prescribed; all data collected were per medication, not per patient. This method was used to account for medication failure and provide accurate weight loss results based on medication choice within this institution.

The primary outcomes included total weight loss and weight loss as a percentage of baseline weight at 3, 6, 12, and > 12 months of therapy. Secondary outcomes included weight loss of 5% from baseline, rate of successful weight maintenance after initial weight loss of 5% from baseline, adverse drug reaction (ADR) monitoring, and use of weight management medications across clinics at VHI.

Demographic data included race, age, sex, baseline weight, BMI, and comorbid medical conditions. Comorbidities were collected based on the most recent primary care clinical note before initiating medication. Medication data collected included medications used to manage comorbidities. Data related to weight management medication included prescribing clinic, reason for medication discontinuation, or bariatric surgery intervention if applicable.

Efficacy outcome data included weight and BMI across therapy duration. Safety outcomes data included heart rate, BP, and ADRs that resulted in medication discontinuation as documented in the electronic health record (EHR).

Results

A total of 86 patients were identified based on prescription fills, which produced 99 unique instances of medication use. Of the 99 identified, 3 met exclusion criteria and were not included in the final analysis. Among included veterans, 16 were female and 80 were male (Table 1). Most of those included identified as White race (86%), male (83%), and mean age 53 years. At baseline, mean weight was 130 kg and mean BMI 41.

Comorbidities and Medication Use

Hypertension (66%), hyperlipidemia (64%), and psychiatric diagnoses (50%) were most common comorbid conditions. Substance use (23%) and T2DM (40%) were the most common comorbidities influencing medication choice. Substance use evaluation included amphetamines and cocaine for this analysis.

Phentermine/topiramate is the preferred first-line agent unless patients have contraindications for use, in which case naltrexone/bupropion is recommended, based on guidelines for weight management medications within the VHI system. However, for patients with comorbid T2DM, liraglutide is preferred because of its beneficial effects for both weight loss and blood glucose control.² Most patients at VHI were started on liraglutide (44%) or phentermine/topiramate (42%), which was in line with recommendations. Our sample included ≥ 1 prescription for each medication available at our facility, although the number of patients on each medication was not equal. Of note, the one patient taking lorcaserin at the time of study discontinued therapy in response to recent FDA guidance.⁹

Medications for comorbid conditions could contribute to weight gain. Of the patient sample, β blockers (n = 24) and anticonvulsants, including gabapentin and pregabalin (n = 22) were the most common Other medications that could have contributed to weight gain included sulfonylureas (n = 5), antipsychotics (n = 4), tricyclic antidepressants (n = 2), and hormone replacement therapies (n = 2).

Primary Outcomes

The mean weight of participants dropped from 129.9 to 114.2 kg over the 12 months of weight management medication therapy for a absolute difference of 15.8 kg (Figure 1 and eTable 1 available at doi:10.12788/fp.0117). Weight loss was recorded at 3, 6, 12, and > 12 months of weight management therapy. At each time point, weight loss was statistically significant (P < .001) compared with baseline (Table 2), even though not every patient had weight loss records at each time point.

When classified by medication choice, mean change in weight was orlistat −25.9 kg (n = 5); lorcaserin −22.5 kg (n = 1); liraglutide −10.3 kg (n = 43); phentermine/topiramate −5.0 kg (n = 42); and naltrexone/ bupropion +2.1 kg (n = 5) over the duration of the study (eTable 2 available at doi:10.12788/fp.0117). Patients receiving orlistat and liraglutide had increasing weight loss across the duration of treatment compared with those on lorcaserin who had initial weight gain before weight loss. Phentermine/topiramate showed initial weight loss that tapered off, and naltrexone/bupropion demonstrated initial weight loss with eventual weight gain at study end point.

Secondary Outcomes

More than one-half of the patients analyzed lost 5 to 10% from baseline while taking weight management medication. Fifty-six (59%) patients lost 5% at any point while on therapy (Table 3). Among those patients, 31 (32%) lost ≥ 10% from baseline. When looking at success related to guideline recommendations, 32 (38%) patients lost 5% from baseline in the first 3 months of medication therapy.

Among patients who lost at least 5% from baseline, we performed further analysis to assess weight maintenance of 3 to 5% from baseline for 12 months. In the 12 months after initial weight loss, the number of patients who were able to maintain their weight loss steadily declined (Figure 2). In the end, 17 (30%) of patients who achieved 5 to 10% weight loss at baseline were able to maintain weight loss. Only 18% of study patients were able to achieve guideline-directed weight loss and maintain that weight for 12 months.

Discussion

This study evaluated the use and outcomes of weight management medication among veterans at VHI. The study aimed to better understand the efficacy and safety of these medications while exposing potential weaknesses in care and to promote avenues to improve weight loss and maintenance.

Clinical trials for weight management medications reported weight loss of 8 to 10 kg over 56 weeks: 21 to 63% of patients losing at least 5% from baseline weight.^10-14 The findings from our study found a higher average weight loss (−15.8 kg) than that reported in trials and a consistent percentage of patients (58.3%) who achieved at least 5% weight loss. It is promising to see that when used in a noncontrolled setting, these medications were able to produce weight loss consistent with results seen in large, controlled trials.

Pi-Sunyer and colleagues found continued weight loss after the initial 5% weight loss to an eventual 10% weight loss in many patients.¹⁰ Additionally, Smith and colleagues found that nearly 68% of their participants who took lorcaserin were able to maintain 3 to 5% weight loss over 12 months.¹³ Sjöström and colleagues acknowledged that many patients taking orlistat for an extended period began to gain weight, although at one-half the rate than that seen in the placebo group.¹² This study found that fewer patients were able to maintain their weight loss over 12 months, with only 30% of patients maintaining 3 to 5% weight loss from baseline. This difference in weight maintenance likely was because of the uncontrolled nature of this study. Once patients reach their initial weight loss goal, even the most motivated patients will have trouble maintaining that weight.⁴ Despite the challenges associated with maintaining weight loss, the quality of life benefits patients gained and potential reductions in health care spending support using resources to improve these outcomes.^2,14,15

Pi-Sunyer and colleagues reported high incidences of nausea (40%), vomiting (16%), diarrhea (21%), and constipation (20%) with liraglutide.¹⁰ Sjöström and colleagues reported 7% of patients experienced GI upset with orlistat.¹² Comparatively, only 17% of our patients reported AEs that required discontinuation, including GI upset. One patient in our study discontinued naltrexone/bupropion because of a significant change in mental status and suicide attempt. Clinical trials did not report a greater risk of depression or suicidality compared with placebo; however, there is a warning on the labeling of naltrexone/bupropion for increased suicidality with the use of antidepressant agents.^16,17 The neurologic AE that required discontinuation of phentermine/topiramate at our institution is unique based on published information.^11,18

The data from this study reinforced the observation that weight maintenance is the most challenging aspect of weight loss. Although our data showed clinically meaningful weight loss from baseline, many patients regained their weight, and some exceeded their baseline weight. Beyond providing these medications, this evidence suggests the need for close, continued follow-up through patients’ weight loss journey.

Limitations

Because this is a retrospective chart review, data collection was influenced by and limited to information that had been recorded in the EHR. AEs that resulted in medication discontinuation were assessed from the patient’s chart, which might not be correct if providers did not update the records. Follow-up was not always scheduled at regular intervals after medication initiation, resulting in varying sample numbers at each time point, potentially interfering with true weight loss averages. Although not included in this analysis, it might be beneficial to evaluate adherence to recommendations for follow-up with laboratory and weight monitoring to better capture where future monitoring can be improved. Second, there was an unbalanced number of patients taking each medication. Specifically, we saw a change in weight with orlistat that exceeded what is consistently seen in larger, more controlled trials. Although this is an effect of the real world, small sample sizes cannot be generalized to the larger population and might result in data reflecting that of an outlier. Last, there is a lack of generalizability because of the veteran population demographic, which is more male and lacks ethnic diversity. This study also was carried out at a single, educational tertiary medical center, which might not apply to all populations.

Conclusions

Despite the limitations discussed, this study shows that the use of weight management medications in a general veteran population produces initial weight loss consistent with previous studies. However, there is room for continued improvement in follow-up strategies to promote greater weight maintenance after initial weight loss. Considering the high health care costs, personal burden, and potential long-term complications associated with obesity, efforts to promote development of programs that support weight management and maintenance are imperative.

Acknowledgment
This material is the result of work supported with resources and the use of facilities at Veteran Health Indiana.

The American Heart Association, the American College of Cardiology, and the Obesity Society define overweight as a body mass index (BMI) of 25 to 29.9 and obesity as a BMI ≥ 30. Morbid obesity is defined as a BMI ≥ 35 or 40.^2,3 Based on these BMI cutoffs, the Endocrine Society recommends diet and lifestyle as the foundation of weight management and pharmacotherapy for those with a BMI ≥ 30 without comorbidities. In patients with a BMI ≥ 27, weight management medications may be considered if a patient has comorbid hypertension, T2DM, dyslipidemia, metabolic syndrome, obstructive sleep apnea, or nonalcoholic fatty liver disease. Patients with BMI > 40 are eligible for weight loss surgery.⁴

Lifestyle and dietary interventions are the foundation of current weight management guidelines from the Endocrine Society.⁴ At a minimum, guidelines recommended enrolling motivated patients in a high-intensity lifestyle intervention class of at least 14 sessions in the first 6 months to reach a goal weight loss of 5 to 10% from baseline and to maintain a reduction of 3 to 5% from baseline.³ Medications are recommended as an adjunct to lifestyle and dietary changes. Most weight management medications work in the brain to stimulate satiety signaling, which helps motivated patients adhere to their dietary interventions, assist those who have been unsuccessful in earlier weight loss attempts, and help maintain weight.^3,4

Guidelines recommend 7 weight management medications, including orlistat (both prescription strength and over-the-counter), liraglutide, phentermine, phentermine/topiramate, lorcaserin, and naltrexone/bupropion. Using medications to assist with weight loss increases likelihood that patients will achieve 5 to 10% weight loss from baseline.^5,6 Studies looking at long-term effects of these medications on weight loss have found improvements in blood pressure (BP), biomarkers for cardiovascular disease, and T2DM-related comorbidities.^3,5,7

Positive effects on comorbidities have been found to be related to drug class and mechanism of action (MOA); those that also are approved for T2DM have demonstrated the most favorable cardiovascular effects.⁷ Other medications that work as stimulants or as modulators of serotonin pathways are associated with increased risks, prompting the US Food and Drug Administration (FDA) to remove some medications from the market.^7,8 In January 2020, lorcaserin was taken off the market because of increased risk of cancer found in postmarketing surveillance.⁹ The benefit of weight loss must be weighed against the risk of medication use.

Monthly follow-up is recommended with weight management medications in the beginning to assess safety and efficacy; medications should be discontinued if weight loss is inadequate in the first 3 months.^1,3,4 Limited studies have assessed the long-term use of weight management medications in a real-world setting. Medications are prescribed for weight management at Veteran Health Indiana (VHI) in outpatient clinics, including primary care, endocrinology, and gastrointestinal (GI) specialties. However, prescribing practices, outcomes, and adherence to guideline recommendations have not been studied. Data from this study will be used to better understand how VHI can serve its veterans through diet, lifestyle, and pharmacologic interventions.

Methods

We conducted a single-center, retrospective chart review for patients started on weight management medications at VHI. A patient list was generated based on prescription fills from June 1, 2017 to June 30, 2019. All data were obtained using the Computerized Patient Record System and patients were not contacted. This study was approved by the Indiana University Health Institutional Review Board and the VHI Research and Development Committee.

At the time of study, orlistat, liraglutide, phentermine/topiramate, lorcaserin, and naltrexone/bupropion were available at VHI for patients who met the criteria. All patients must have been enrolled in dietary and lifestyle management to be approved for these medications. The US Department of Veterans Affairs (VA) MOVE! weight management program, designed by the VA National Center for Health Promotion and Disease Promotion, is available at VA sites throughout the country. After MOVE! orientation, patients can participate in group or individual 12-week programs that include weigh ins, goal-setting strategies, meal planning, and habit modification support. If patients are unable to meet in person, phone and other telehealth opportunities are available.

Patients were included in the study if they received a prescription of any 1 of the 5 available medications during the enrollment period. Patients were excluded if they received a prescription from or were treated by a civilian health care provider, if they never used the medication, or if their weight loss was attributed to a cancer diagnosis. These criteria produced 86 patients of whom 96 unique weight loss prescriptions were generated. Data were collected for each instance of medication use so that some patients were included multiple times. In this case, data collection for the failed medication ended when failure was documented, and new data points began when new medication was prescribed; all data collected were per medication, not per patient. This method was used to account for medication failure and provide accurate weight loss results based on medication choice within this institution.

The primary outcomes included total weight loss and weight loss as a percentage of baseline weight at 3, 6, 12, and > 12 months of therapy. Secondary outcomes included weight loss of 5% from baseline, rate of successful weight maintenance after initial weight loss of 5% from baseline, adverse drug reaction (ADR) monitoring, and use of weight management medications across clinics at VHI.

Demographic data included race, age, sex, baseline weight, BMI, and comorbid medical conditions. Comorbidities were collected based on the most recent primary care clinical note before initiating medication. Medication data collected included medications used to manage comorbidities. Data related to weight management medication included prescribing clinic, reason for medication discontinuation, or bariatric surgery intervention if applicable.

Efficacy outcome data included weight and BMI across therapy duration. Safety outcomes data included heart rate, BP, and ADRs that resulted in medication discontinuation as documented in the electronic health record (EHR).

Results

A total of 86 patients were identified based on prescription fills, which produced 99 unique instances of medication use. Of the 99 identified, 3 met exclusion criteria and were not included in the final analysis. Among included veterans, 16 were female and 80 were male (Table 1). Most of those included identified as White race (86%), male (83%), and mean age 53 years. At baseline, mean weight was 130 kg and mean BMI 41.

Comorbidities and Medication Use

Hypertension (66%), hyperlipidemia (64%), and psychiatric diagnoses (50%) were most common comorbid conditions. Substance use (23%) and T2DM (40%) were the most common comorbidities influencing medication choice. Substance use evaluation included amphetamines and cocaine for this analysis.

Phentermine/topiramate is the preferred first-line agent unless patients have contraindications for use, in which case naltrexone/bupropion is recommended, based on guidelines for weight management medications within the VHI system. However, for patients with comorbid T2DM, liraglutide is preferred because of its beneficial effects for both weight loss and blood glucose control.² Most patients at VHI were started on liraglutide (44%) or phentermine/topiramate (42%), which was in line with recommendations. Our sample included ≥ 1 prescription for each medication available at our facility, although the number of patients on each medication was not equal. Of note, the one patient taking lorcaserin at the time of study discontinued therapy in response to recent FDA guidance.⁹

Medications for comorbid conditions could contribute to weight gain. Of the patient sample, β blockers (n = 24) and anticonvulsants, including gabapentin and pregabalin (n = 22) were the most common Other medications that could have contributed to weight gain included sulfonylureas (n = 5), antipsychotics (n = 4), tricyclic antidepressants (n = 2), and hormone replacement therapies (n = 2).

Primary Outcomes

The mean weight of participants dropped from 129.9 to 114.2 kg over the 12 months of weight management medication therapy for a absolute difference of 15.8 kg (Figure 1 and eTable 1 available at doi:10.12788/fp.0117). Weight loss was recorded at 3, 6, 12, and > 12 months of weight management therapy. At each time point, weight loss was statistically significant (P < .001) compared with baseline (Table 2), even though not every patient had weight loss records at each time point.

When classified by medication choice, mean change in weight was orlistat −25.9 kg (n = 5); lorcaserin −22.5 kg (n = 1); liraglutide −10.3 kg (n = 43); phentermine/topiramate −5.0 kg (n = 42); and naltrexone/ bupropion +2.1 kg (n = 5) over the duration of the study (eTable 2 available at doi:10.12788/fp.0117). Patients receiving orlistat and liraglutide had increasing weight loss across the duration of treatment compared with those on lorcaserin who had initial weight gain before weight loss. Phentermine/topiramate showed initial weight loss that tapered off, and naltrexone/bupropion demonstrated initial weight loss with eventual weight gain at study end point.

Secondary Outcomes

More than one-half of the patients analyzed lost 5 to 10% from baseline while taking weight management medication. Fifty-six (59%) patients lost 5% at any point while on therapy (Table 3). Among those patients, 31 (32%) lost ≥ 10% from baseline. When looking at success related to guideline recommendations, 32 (38%) patients lost 5% from baseline in the first 3 months of medication therapy.

Among patients who lost at least 5% from baseline, we performed further analysis to assess weight maintenance of 3 to 5% from baseline for 12 months. In the 12 months after initial weight loss, the number of patients who were able to maintain their weight loss steadily declined (Figure 2). In the end, 17 (30%) of patients who achieved 5 to 10% weight loss at baseline were able to maintain weight loss. Only 18% of study patients were able to achieve guideline-directed weight loss and maintain that weight for 12 months.

Discussion

This study evaluated the use and outcomes of weight management medication among veterans at VHI. The study aimed to better understand the efficacy and safety of these medications while exposing potential weaknesses in care and to promote avenues to improve weight loss and maintenance.

Clinical trials for weight management medications reported weight loss of 8 to 10 kg over 56 weeks: 21 to 63% of patients losing at least 5% from baseline weight.^10-14 The findings from our study found a higher average weight loss (−15.8 kg) than that reported in trials and a consistent percentage of patients (58.3%) who achieved at least 5% weight loss. It is promising to see that when used in a noncontrolled setting, these medications were able to produce weight loss consistent with results seen in large, controlled trials.

Pi-Sunyer and colleagues found continued weight loss after the initial 5% weight loss to an eventual 10% weight loss in many patients.¹⁰ Additionally, Smith and colleagues found that nearly 68% of their participants who took lorcaserin were able to maintain 3 to 5% weight loss over 12 months.¹³ Sjöström and colleagues acknowledged that many patients taking orlistat for an extended period began to gain weight, although at one-half the rate than that seen in the placebo group.¹² This study found that fewer patients were able to maintain their weight loss over 12 months, with only 30% of patients maintaining 3 to 5% weight loss from baseline. This difference in weight maintenance likely was because of the uncontrolled nature of this study. Once patients reach their initial weight loss goal, even the most motivated patients will have trouble maintaining that weight.⁴ Despite the challenges associated with maintaining weight loss, the quality of life benefits patients gained and potential reductions in health care spending support using resources to improve these outcomes.^2,14,15

Pi-Sunyer and colleagues reported high incidences of nausea (40%), vomiting (16%), diarrhea (21%), and constipation (20%) with liraglutide.¹⁰ Sjöström and colleagues reported 7% of patients experienced GI upset with orlistat.¹² Comparatively, only 17% of our patients reported AEs that required discontinuation, including GI upset. One patient in our study discontinued naltrexone/bupropion because of a significant change in mental status and suicide attempt. Clinical trials did not report a greater risk of depression or suicidality compared with placebo; however, there is a warning on the labeling of naltrexone/bupropion for increased suicidality with the use of antidepressant agents.^16,17 The neurologic AE that required discontinuation of phentermine/topiramate at our institution is unique based on published information.^11,18

The data from this study reinforced the observation that weight maintenance is the most challenging aspect of weight loss. Although our data showed clinically meaningful weight loss from baseline, many patients regained their weight, and some exceeded their baseline weight. Beyond providing these medications, this evidence suggests the need for close, continued follow-up through patients’ weight loss journey.

Limitations

Because this is a retrospective chart review, data collection was influenced by and limited to information that had been recorded in the EHR. AEs that resulted in medication discontinuation were assessed from the patient’s chart, which might not be correct if providers did not update the records. Follow-up was not always scheduled at regular intervals after medication initiation, resulting in varying sample numbers at each time point, potentially interfering with true weight loss averages. Although not included in this analysis, it might be beneficial to evaluate adherence to recommendations for follow-up with laboratory and weight monitoring to better capture where future monitoring can be improved. Second, there was an unbalanced number of patients taking each medication. Specifically, we saw a change in weight with orlistat that exceeded what is consistently seen in larger, more controlled trials. Although this is an effect of the real world, small sample sizes cannot be generalized to the larger population and might result in data reflecting that of an outlier. Last, there is a lack of generalizability because of the veteran population demographic, which is more male and lacks ethnic diversity. This study also was carried out at a single, educational tertiary medical center, which might not apply to all populations.

Conclusions

Despite the limitations discussed, this study shows that the use of weight management medications in a general veteran population produces initial weight loss consistent with previous studies. However, there is room for continued improvement in follow-up strategies to promote greater weight maintenance after initial weight loss. Considering the high health care costs, personal burden, and potential long-term complications associated with obesity, efforts to promote development of programs that support weight management and maintenance are imperative.

Acknowledgment
This material is the result of work supported with resources and the use of facilities at Veteran Health Indiana.

The American Heart Association, the American College of Cardiology, and the Obesity Society define overweight as a body mass index (BMI) of 25 to 29.9 and obesity as a BMI ≥ 30. Morbid obesity is defined as a BMI ≥ 35 or 40.^2,3 Based on these BMI cutoffs, the Endocrine Society recommends diet and lifestyle as the foundation of weight management and pharmacotherapy for those with a BMI ≥ 30 without comorbidities. In patients with a BMI ≥ 27, weight management medications may be considered if a patient has comorbid hypertension, T2DM, dyslipidemia, metabolic syndrome, obstructive sleep apnea, or nonalcoholic fatty liver disease. Patients with BMI > 40 are eligible for weight loss surgery.⁴

Lifestyle and dietary interventions are the foundation of current weight management guidelines from the Endocrine Society.⁴ At a minimum, guidelines recommended enrolling motivated patients in a high-intensity lifestyle intervention class of at least 14 sessions in the first 6 months to reach a goal weight loss of 5 to 10% from baseline and to maintain a reduction of 3 to 5% from baseline.³ Medications are recommended as an adjunct to lifestyle and dietary changes. Most weight management medications work in the brain to stimulate satiety signaling, which helps motivated patients adhere to their dietary interventions, assist those who have been unsuccessful in earlier weight loss attempts, and help maintain weight.^3,4

Guidelines recommend 7 weight management medications, including orlistat (both prescription strength and over-the-counter), liraglutide, phentermine, phentermine/topiramate, lorcaserin, and naltrexone/bupropion. Using medications to assist with weight loss increases likelihood that patients will achieve 5 to 10% weight loss from baseline.^5,6 Studies looking at long-term effects of these medications on weight loss have found improvements in blood pressure (BP), biomarkers for cardiovascular disease, and T2DM-related comorbidities.^3,5,7

Positive effects on comorbidities have been found to be related to drug class and mechanism of action (MOA); those that also are approved for T2DM have demonstrated the most favorable cardiovascular effects.⁷ Other medications that work as stimulants or as modulators of serotonin pathways are associated with increased risks, prompting the US Food and Drug Administration (FDA) to remove some medications from the market.^7,8 In January 2020, lorcaserin was taken off the market because of increased risk of cancer found in postmarketing surveillance.⁹ The benefit of weight loss must be weighed against the risk of medication use.

Monthly follow-up is recommended with weight management medications in the beginning to assess safety and efficacy; medications should be discontinued if weight loss is inadequate in the first 3 months.^1,3,4 Limited studies have assessed the long-term use of weight management medications in a real-world setting. Medications are prescribed for weight management at Veteran Health Indiana (VHI) in outpatient clinics, including primary care, endocrinology, and gastrointestinal (GI) specialties. However, prescribing practices, outcomes, and adherence to guideline recommendations have not been studied. Data from this study will be used to better understand how VHI can serve its veterans through diet, lifestyle, and pharmacologic interventions.

Methods

We conducted a single-center, retrospective chart review for patients started on weight management medications at VHI. A patient list was generated based on prescription fills from June 1, 2017 to June 30, 2019. All data were obtained using the Computerized Patient Record System and patients were not contacted. This study was approved by the Indiana University Health Institutional Review Board and the VHI Research and Development Committee.

At the time of study, orlistat, liraglutide, phentermine/topiramate, lorcaserin, and naltrexone/bupropion were available at VHI for patients who met the criteria. All patients must have been enrolled in dietary and lifestyle management to be approved for these medications. The US Department of Veterans Affairs (VA) MOVE! weight management program, designed by the VA National Center for Health Promotion and Disease Promotion, is available at VA sites throughout the country. After MOVE! orientation, patients can participate in group or individual 12-week programs that include weigh ins, goal-setting strategies, meal planning, and habit modification support. If patients are unable to meet in person, phone and other telehealth opportunities are available.

Patients were included in the study if they received a prescription of any 1 of the 5 available medications during the enrollment period. Patients were excluded if they received a prescription from or were treated by a civilian health care provider, if they never used the medication, or if their weight loss was attributed to a cancer diagnosis. These criteria produced 86 patients of whom 96 unique weight loss prescriptions were generated. Data were collected for each instance of medication use so that some patients were included multiple times. In this case, data collection for the failed medication ended when failure was documented, and new data points began when new medication was prescribed; all data collected were per medication, not per patient. This method was used to account for medication failure and provide accurate weight loss results based on medication choice within this institution.

The primary outcomes included total weight loss and weight loss as a percentage of baseline weight at 3, 6, 12, and > 12 months of therapy. Secondary outcomes included weight loss of 5% from baseline, rate of successful weight maintenance after initial weight loss of 5% from baseline, adverse drug reaction (ADR) monitoring, and use of weight management medications across clinics at VHI.

Demographic data included race, age, sex, baseline weight, BMI, and comorbid medical conditions. Comorbidities were collected based on the most recent primary care clinical note before initiating medication. Medication data collected included medications used to manage comorbidities. Data related to weight management medication included prescribing clinic, reason for medication discontinuation, or bariatric surgery intervention if applicable.

Efficacy outcome data included weight and BMI across therapy duration. Safety outcomes data included heart rate, BP, and ADRs that resulted in medication discontinuation as documented in the electronic health record (EHR).

Results

A total of 86 patients were identified based on prescription fills, which produced 99 unique instances of medication use. Of the 99 identified, 3 met exclusion criteria and were not included in the final analysis. Among included veterans, 16 were female and 80 were male (Table 1). Most of those included identified as White race (86%), male (83%), and mean age 53 years. At baseline, mean weight was 130 kg and mean BMI 41.

Comorbidities and Medication Use

Hypertension (66%), hyperlipidemia (64%), and psychiatric diagnoses (50%) were most common comorbid conditions. Substance use (23%) and T2DM (40%) were the most common comorbidities influencing medication choice. Substance use evaluation included amphetamines and cocaine for this analysis.

Phentermine/topiramate is the preferred first-line agent unless patients have contraindications for use, in which case naltrexone/bupropion is recommended, based on guidelines for weight management medications within the VHI system. However, for patients with comorbid T2DM, liraglutide is preferred because of its beneficial effects for both weight loss and blood glucose control.² Most patients at VHI were started on liraglutide (44%) or phentermine/topiramate (42%), which was in line with recommendations. Our sample included ≥ 1 prescription for each medication available at our facility, although the number of patients on each medication was not equal. Of note, the one patient taking lorcaserin at the time of study discontinued therapy in response to recent FDA guidance.⁹

Medications for comorbid conditions could contribute to weight gain. Of the patient sample, β blockers (n = 24) and anticonvulsants, including gabapentin and pregabalin (n = 22) were the most common Other medications that could have contributed to weight gain included sulfonylureas (n = 5), antipsychotics (n = 4), tricyclic antidepressants (n = 2), and hormone replacement therapies (n = 2).

Primary Outcomes

The mean weight of participants dropped from 129.9 to 114.2 kg over the 12 months of weight management medication therapy for a absolute difference of 15.8 kg (Figure 1 and eTable 1 available at doi:10.12788/fp.0117). Weight loss was recorded at 3, 6, 12, and > 12 months of weight management therapy. At each time point, weight loss was statistically significant (P < .001) compared with baseline (Table 2), even though not every patient had weight loss records at each time point.

When classified by medication choice, mean change in weight was orlistat −25.9 kg (n = 5); lorcaserin −22.5 kg (n = 1); liraglutide −10.3 kg (n = 43); phentermine/topiramate −5.0 kg (n = 42); and naltrexone/ bupropion +2.1 kg (n = 5) over the duration of the study (eTable 2 available at doi:10.12788/fp.0117). Patients receiving orlistat and liraglutide had increasing weight loss across the duration of treatment compared with those on lorcaserin who had initial weight gain before weight loss. Phentermine/topiramate showed initial weight loss that tapered off, and naltrexone/bupropion demonstrated initial weight loss with eventual weight gain at study end point.

Secondary Outcomes

More than one-half of the patients analyzed lost 5 to 10% from baseline while taking weight management medication. Fifty-six (59%) patients lost 5% at any point while on therapy (Table 3). Among those patients, 31 (32%) lost ≥ 10% from baseline. When looking at success related to guideline recommendations, 32 (38%) patients lost 5% from baseline in the first 3 months of medication therapy.

Among patients who lost at least 5% from baseline, we performed further analysis to assess weight maintenance of 3 to 5% from baseline for 12 months. In the 12 months after initial weight loss, the number of patients who were able to maintain their weight loss steadily declined (Figure 2). In the end, 17 (30%) of patients who achieved 5 to 10% weight loss at baseline were able to maintain weight loss. Only 18% of study patients were able to achieve guideline-directed weight loss and maintain that weight for 12 months.

Discussion

This study evaluated the use and outcomes of weight management medication among veterans at VHI. The study aimed to better understand the efficacy and safety of these medications while exposing potential weaknesses in care and to promote avenues to improve weight loss and maintenance.

Clinical trials for weight management medications reported weight loss of 8 to 10 kg over 56 weeks: 21 to 63% of patients losing at least 5% from baseline weight.^10-14 The findings from our study found a higher average weight loss (−15.8 kg) than that reported in trials and a consistent percentage of patients (58.3%) who achieved at least 5% weight loss. It is promising to see that when used in a noncontrolled setting, these medications were able to produce weight loss consistent with results seen in large, controlled trials.

Pi-Sunyer and colleagues found continued weight loss after the initial 5% weight loss to an eventual 10% weight loss in many patients.¹⁰ Additionally, Smith and colleagues found that nearly 68% of their participants who took lorcaserin were able to maintain 3 to 5% weight loss over 12 months.¹³ Sjöström and colleagues acknowledged that many patients taking orlistat for an extended period began to gain weight, although at one-half the rate than that seen in the placebo group.¹² This study found that fewer patients were able to maintain their weight loss over 12 months, with only 30% of patients maintaining 3 to 5% weight loss from baseline. This difference in weight maintenance likely was because of the uncontrolled nature of this study. Once patients reach their initial weight loss goal, even the most motivated patients will have trouble maintaining that weight.⁴ Despite the challenges associated with maintaining weight loss, the quality of life benefits patients gained and potential reductions in health care spending support using resources to improve these outcomes.^2,14,15

Pi-Sunyer and colleagues reported high incidences of nausea (40%), vomiting (16%), diarrhea (21%), and constipation (20%) with liraglutide.¹⁰ Sjöström and colleagues reported 7% of patients experienced GI upset with orlistat.¹² Comparatively, only 17% of our patients reported AEs that required discontinuation, including GI upset. One patient in our study discontinued naltrexone/bupropion because of a significant change in mental status and suicide attempt. Clinical trials did not report a greater risk of depression or suicidality compared with placebo; however, there is a warning on the labeling of naltrexone/bupropion for increased suicidality with the use of antidepressant agents.^16,17 The neurologic AE that required discontinuation of phentermine/topiramate at our institution is unique based on published information.^11,18

The data from this study reinforced the observation that weight maintenance is the most challenging aspect of weight loss. Although our data showed clinically meaningful weight loss from baseline, many patients regained their weight, and some exceeded their baseline weight. Beyond providing these medications, this evidence suggests the need for close, continued follow-up through patients’ weight loss journey.

Limitations

Because this is a retrospective chart review, data collection was influenced by and limited to information that had been recorded in the EHR. AEs that resulted in medication discontinuation were assessed from the patient’s chart, which might not be correct if providers did not update the records. Follow-up was not always scheduled at regular intervals after medication initiation, resulting in varying sample numbers at each time point, potentially interfering with true weight loss averages. Although not included in this analysis, it might be beneficial to evaluate adherence to recommendations for follow-up with laboratory and weight monitoring to better capture where future monitoring can be improved. Second, there was an unbalanced number of patients taking each medication. Specifically, we saw a change in weight with orlistat that exceeded what is consistently seen in larger, more controlled trials. Although this is an effect of the real world, small sample sizes cannot be generalized to the larger population and might result in data reflecting that of an outlier. Last, there is a lack of generalizability because of the veteran population demographic, which is more male and lacks ethnic diversity. This study also was carried out at a single, educational tertiary medical center, which might not apply to all populations.

Conclusions

Despite the limitations discussed, this study shows that the use of weight management medications in a general veteran population produces initial weight loss consistent with previous studies. However, there is room for continued improvement in follow-up strategies to promote greater weight maintenance after initial weight loss. Considering the high health care costs, personal burden, and potential long-term complications associated with obesity, efforts to promote development of programs that support weight management and maintenance are imperative.

Acknowledgment
This material is the result of work supported with resources and the use of facilities at Veteran Health Indiana.

Vocational rehabilitation (VR) interventions are offered through Compensated Work Therapy (CWT) as part of clinical care in the Veterans Health Administration (VHA) to improve employment and quality of life outcomes for veterans with life-altering disabilities.^1–5 CWT vocational services range from assessment, vocational counseling, and treatment plan development to job placement, coaching, and follow-along support.¹ However, many veterans receive care in community-based clinics that are not staffed with a VR specialist (VRS) to provide these services.^6–8 Telehealth may increase patient access to VR, especially for rural veterans and those with travel barriers, but it is not known whether veterans and VRS would find this to be a satisfactory service delivery method.^8,9 This paper examines veteran and VRS provider perspectives on VR provided by telehealth (VRtele) as part of a VHA clinical demonstration project. To our knowledge, this is the first report of using real-time, clinic-based VRtele.

Methods

The Rural Veterans Supported Employment Telerehabilitation Initiative (RVSETI) was conducted as a field-initiated demonstration project at 2 US Department of Veterans Affairs (VA) medical centers (VAMCs) in Florida between 2014 and 2016: James A. Haley Veterans’ Hospital & Clinics (Tampa) and Malcom Randall VAMC (Gainesville). This retrospective evaluation of its first year did not require institutional review board approval as it was determined to be a quality improvement project by the local research service.

The patient population for the project was veterans with disabilities who were referred by clinical consults to the CWT service, a recovery-oriented vocational program. During the project years, veterans were offered the option of receiving VR services, such as supported employment, community-based employment services, or vocational assistance, through VRtele rather than traditional face-to-face meetings. The specific interventions delivered included patient orientation, interview assessment, treatment plan development, referral activities, vocational counseling, assessment of workplace for accommodation needs, vocational case management, and other employment supports. VR staff participating in the project included 2 VR supervisors, 1 supported employment mentor trainer, and 5 VRSs.

Each clinic was set up for VRtele, and codes were added to the electronic health record (EHR) to ensure proper documentation. Participating VRSs completed teleconferencing training, including a skills assessment using the equipment for real-time, high-quality video streaming over an encrypted network to provide services in a patient’s home or other remote locations. VRS staff provided veterans with instructions on using a VA-provided tablet or their own device and assisted them with establishing connectivity with the network. Video equipment included speakers, camera, and headphones connected to the desktop computer or laptop of the VRS. A patient’s first VRtelesession was conducted in person at the VAMC to assure veterans were able to use the technology and to identify and resolve any problems.

Demographic data, primary diagnosis, VR usage data, and zip codes of participating veterans were extracted from the EHR. Veterans completed a 2-part satisfaction survey administered 90 days after enrollment and at discharge. Part 1 was composed of 15 items, most with a 5-point Likert scale (higher ratings indicated greater satisfaction), on various aspects of the VRtele experience, such as audio and video quality and wait times.¹⁰ Part 2 addressed VR services and the VRS and consisted of 8 Likert scale items with the option to add a comment for each and 2 open-ended items that asked the participant to list what they liked best and least about VRtele.

Semistructured, in-person 30- to 60-minute interviews were conducted with VRSs at the initiation of VRteleand audio-recorded with permission. An interview guide consisting of 14 questions was used to obtain data on caseload, VRtele set up, use of teleconferencing equipment, and veteran access to VR services.

After ≥ 2 months of VRtele use, researchers observed a session with each participant to obtain qualitative data from all participants on their VRtele experience. Using an observation form with open notes, data were collected on the use of the videoconferencing technology, the quality of the VRtele session, and reactions of veterans and their VRS. Following the observation session, both the VRS and the participating veteran were interviewed separately using a 9-question interview form to obtain data on the use of the technology in general and for VR. Interviews were audio-recorded with the permission of the VRS and veteran and transcribed for analysis.

Analyses

Descriptive statistics were used for EHR data and satisfaction surveys. For qualitative analysis, each transcript was read in full by 2 researchers to get an overview of the data, and a rapid analysis approach was used to identify central themes focused on how technology was used and the experiences of the participants.^11,12 Relevant text for each topic was tabulated, and a summary table was created that highlighted overlapping ideas discussed by the interviewees as well as differences.

Results

Of the 22 veterans who participated in the project, 11 completed satisfaction surveys and 4 participated in qualitative interviews. The rural and nonrural groups did not differ demographically or by diagnosis, which was predominantly mental health related. Only 1 veteran in each group owned a tablet; the majority of both groups required VA-issued devices: 80% (n = 8) rural and 91.7% (n = 11) nonrural. The number of VRtele sessions for the groups also was similar, 53 for rural and 60 for nonrural, as was the mean (SD) number of sessions per veteran: 5.3 (SD, 3.2) rural and 5.0 (SD, 2.5) urban. Overall, 63 miles per session were saved, mostly for rural veterans, and the number of mean (SD) miles saved per veteran was greater for rural than nonrural veterans: 379.2 (243.0) and 256.1 (275.9), respectively. One veteran who moved to a different state during the program continued VRtele at the new location. In a qualitative sampling of 5 VRtele sessions, all the VRSs used office desktop computers.

Level of satisfaction with aspects of VRtele related to the technology rated was consistently > 4 on the Likert scale. The lowest mean (SD) ratings were 4.2 (1.0) for audio quality and 4.4 (0.5) for video quality, and the highest rating was given for equipment operation explanation and privacy was respected, 4.9 (0.3) for both. All questions related to satisfaction with services were also rated high: The mean (SD) lowest ratings were 4.3 (1.0) given to both vocational needs 4.3 (1.0) and tasks effectively helped achieve goals 4.3 (0.7). The highest mean (SD) ratings were 4.6 (0.5) given to VR program service explained and 4.7 (0.5) for appointment timeliness.

Qualitative Results

At first, some VRSs thought the teleconferencing system might be difficult or awkward to use, but they found it easier to set up than expected and seamless to use. VRS staff reported being surprised at how well it worked despite some issues that occurred with loading the software. Once loaded, however, the connection worked well, one VRS noting that following step-by-step instructions solved the problem. Some VRSs indicated they did not invite all the veterans on their caseload to participate in VRtele due to concerns with the patient’s familiarity with technology, but one VRS stated, “I haven’t had anybody that failed to do a [session] that I couldn’t get them up and running within a few minutes.”

When working in the community, VRSs reported using laptops for VRtele but found that these devices were unreliable due to lack of internet access and were slow to start; several VRSs thought tablets would have been more helpful. Some veterans reported technical glitches, lack of comfort with technology, or a problem with sound due to a tablet’s protective case blocking the speakers. To solve the sound issue, a veteran used headphones. This veteran also explained that the log-on process required a new password every time, so he would keep a pen and paper ready to write it down. Because signing in and setting up takes a little time, this veteran and his VRS agreed to start connecting 5 minutes before their meeting time to allow for that set- up time.

Initially, some VRSs expressed concern that transitioning to VRtele would affect the quality of interactions with the veterans. However, VRSs also identified strengths of VRtele, including flexibility, saved time, and increased interaction. One VRS discussed a veteran’s adaptation by saying, “I think he feels even more involved in his plan [and] enjoys the increased interaction.” Veterans reported enjoying using tablets and identified the main strength of VRtele as being able to talk face-to-face with the VRS. Echoing the VRSs, veterans reported teleconferencing saved time by avoiding travel and enabled spontaneous meetings. One of the veterans summed up the benefits of using VRtele: “I’d rather just connect. It’s going to take us 40 to 50 minutes [to meet in person] when we can just connect right here and it takes 15 to 20. We don’t have to go through the driving.… So this right here, doing it ahead of time and having the appointment, it’s a lot easier.”

In their interviews, VRSs talked about enjoying VRtele. A VRS explained: “It makes it a lot easier. It makes me feel less guilty. This way [veterans] don’t have to use their gas money, use their time. I know [the veteran] had something else he needed to do today.” Thus, both veterans and VRSs were satisfied with their VRtele experiences.

Discussion

This first report on the perspective of providers and veterans using VRtele suggests that it is a viable option for service delivery and that is highly satisfactory for serving veterans with disabilities, many of whom live in rural areas or have travel barriers. These findings are consistent with data on telerehabilitation for veterans with cognitive, physical, and mental disabilities.^13-22 Further, the data support the notion of using VRtele to facilitate long-term VR follow-up for persons with disabilities, as illustrated by successful continuation of vocational services after a veteran moved out of state.²³

Similar to other reports, our experience highlighted 2 factors that affect successful VRtele: (1) Troubleshooting technology barriers for both VR providers and clients; and (2) supportive leadership to facilitate implementation.^24-26These areas have been improved with recent telehealth VHA initiatives and upgrades. After the conclusion of this project evaluation, the program was expanded, and local facilities may now receive mentored support to implement similar programs.²⁷ This ongoing telerehabilitation program uses the recently upgraded VHA telehealth platform that enables encrypted sessions to be provided to any mobile or online device, and veterans simply click on a link to connect rather than waiting for a session-specific password.²⁸ By using virtual medical rooms accessed by cameras on tablets, smartphones, or computers, veterans and VR providers now have an easier time scheduling and attending online appointments.²⁹ Improved access to VRtele is important as VHA began providing the majority of appointments via video telemedicine in Spring of 2020 due to the COVID-19 pandemic. The accelerated use of telehealth due to the COVID crisis makes these findings highly relevant to the current practice environment.

Changes to technology and increased usage of VA Video Connect may indicate that the barriers identified from the earlier process described here have been diminished or eliminated. More evaluation is needed to assess whether system upgrades have increased ease of use and access for veterans with disabilities.

Conclusions

Encouragingly, this clinical demonstration project showed that both providers and clients recognize the benefits of VRtele. Patient satisfaction and decreased travel costs were clear advantages to using VRtele for this small group of veterans who had barriers to care due to travel or disability barriers. As this program evaluation was limited by a small sample, absence of a comparison group, and lack of outcome data (eg, employment rates, hours, wages, retention), future research is needed on implementation and outcomes of VRtele.

Acknowledgments
The authors thank Lynn Dirk, MAMC, for substantial editorial assistance. This material was based on work supported by Rural Veterans Supported Employment TeleRehabilitation Initiative (RVSETI), funded by the VA Office of Rural Health (Project # N08-FY14Q3-S2-P01222) and by support of the VA Health Services Research and Development Service. This work was presented in part at the 114th Annual Meeting of the American Anthropological Association at Denver, Colorado, November 21, 2015; a field-based Health Services Research and Development Service meeting, US Department of Veterans Affairs at Washington, DC, September 12, 2016; and the 2016 Annual Conference of the American Congress for Rehabilitation Medicine at Chicago, Illinois, October-November 2016.

Vocational rehabilitation (VR) interventions are offered through Compensated Work Therapy (CWT) as part of clinical care in the Veterans Health Administration (VHA) to improve employment and quality of life outcomes for veterans with life-altering disabilities.^1–5 CWT vocational services range from assessment, vocational counseling, and treatment plan development to job placement, coaching, and follow-along support.¹ However, many veterans receive care in community-based clinics that are not staffed with a VR specialist (VRS) to provide these services.^6–8 Telehealth may increase patient access to VR, especially for rural veterans and those with travel barriers, but it is not known whether veterans and VRS would find this to be a satisfactory service delivery method.^8,9 This paper examines veteran and VRS provider perspectives on VR provided by telehealth (VRtele) as part of a VHA clinical demonstration project. To our knowledge, this is the first report of using real-time, clinic-based VRtele.

Methods

The Rural Veterans Supported Employment Telerehabilitation Initiative (RVSETI) was conducted as a field-initiated demonstration project at 2 US Department of Veterans Affairs (VA) medical centers (VAMCs) in Florida between 2014 and 2016: James A. Haley Veterans’ Hospital & Clinics (Tampa) and Malcom Randall VAMC (Gainesville). This retrospective evaluation of its first year did not require institutional review board approval as it was determined to be a quality improvement project by the local research service.

The patient population for the project was veterans with disabilities who were referred by clinical consults to the CWT service, a recovery-oriented vocational program. During the project years, veterans were offered the option of receiving VR services, such as supported employment, community-based employment services, or vocational assistance, through VRtele rather than traditional face-to-face meetings. The specific interventions delivered included patient orientation, interview assessment, treatment plan development, referral activities, vocational counseling, assessment of workplace for accommodation needs, vocational case management, and other employment supports. VR staff participating in the project included 2 VR supervisors, 1 supported employment mentor trainer, and 5 VRSs.

Each clinic was set up for VRtele, and codes were added to the electronic health record (EHR) to ensure proper documentation. Participating VRSs completed teleconferencing training, including a skills assessment using the equipment for real-time, high-quality video streaming over an encrypted network to provide services in a patient’s home or other remote locations. VRS staff provided veterans with instructions on using a VA-provided tablet or their own device and assisted them with establishing connectivity with the network. Video equipment included speakers, camera, and headphones connected to the desktop computer or laptop of the VRS. A patient’s first VRtelesession was conducted in person at the VAMC to assure veterans were able to use the technology and to identify and resolve any problems.

Demographic data, primary diagnosis, VR usage data, and zip codes of participating veterans were extracted from the EHR. Veterans completed a 2-part satisfaction survey administered 90 days after enrollment and at discharge. Part 1 was composed of 15 items, most with a 5-point Likert scale (higher ratings indicated greater satisfaction), on various aspects of the VRtele experience, such as audio and video quality and wait times.¹⁰ Part 2 addressed VR services and the VRS and consisted of 8 Likert scale items with the option to add a comment for each and 2 open-ended items that asked the participant to list what they liked best and least about VRtele.

Semistructured, in-person 30- to 60-minute interviews were conducted with VRSs at the initiation of VRteleand audio-recorded with permission. An interview guide consisting of 14 questions was used to obtain data on caseload, VRtele set up, use of teleconferencing equipment, and veteran access to VR services.

After ≥ 2 months of VRtele use, researchers observed a session with each participant to obtain qualitative data from all participants on their VRtele experience. Using an observation form with open notes, data were collected on the use of the videoconferencing technology, the quality of the VRtele session, and reactions of veterans and their VRS. Following the observation session, both the VRS and the participating veteran were interviewed separately using a 9-question interview form to obtain data on the use of the technology in general and for VR. Interviews were audio-recorded with the permission of the VRS and veteran and transcribed for analysis.

Analyses

Descriptive statistics were used for EHR data and satisfaction surveys. For qualitative analysis, each transcript was read in full by 2 researchers to get an overview of the data, and a rapid analysis approach was used to identify central themes focused on how technology was used and the experiences of the participants.^11,12 Relevant text for each topic was tabulated, and a summary table was created that highlighted overlapping ideas discussed by the interviewees as well as differences.

Results

Of the 22 veterans who participated in the project, 11 completed satisfaction surveys and 4 participated in qualitative interviews. The rural and nonrural groups did not differ demographically or by diagnosis, which was predominantly mental health related. Only 1 veteran in each group owned a tablet; the majority of both groups required VA-issued devices: 80% (n = 8) rural and 91.7% (n = 11) nonrural. The number of VRtele sessions for the groups also was similar, 53 for rural and 60 for nonrural, as was the mean (SD) number of sessions per veteran: 5.3 (SD, 3.2) rural and 5.0 (SD, 2.5) urban. Overall, 63 miles per session were saved, mostly for rural veterans, and the number of mean (SD) miles saved per veteran was greater for rural than nonrural veterans: 379.2 (243.0) and 256.1 (275.9), respectively. One veteran who moved to a different state during the program continued VRtele at the new location. In a qualitative sampling of 5 VRtele sessions, all the VRSs used office desktop computers.

Level of satisfaction with aspects of VRtele related to the technology rated was consistently > 4 on the Likert scale. The lowest mean (SD) ratings were 4.2 (1.0) for audio quality and 4.4 (0.5) for video quality, and the highest rating was given for equipment operation explanation and privacy was respected, 4.9 (0.3) for both. All questions related to satisfaction with services were also rated high: The mean (SD) lowest ratings were 4.3 (1.0) given to both vocational needs 4.3 (1.0) and tasks effectively helped achieve goals 4.3 (0.7). The highest mean (SD) ratings were 4.6 (0.5) given to VR program service explained and 4.7 (0.5) for appointment timeliness.

Qualitative Results

At first, some VRSs thought the teleconferencing system might be difficult or awkward to use, but they found it easier to set up than expected and seamless to use. VRS staff reported being surprised at how well it worked despite some issues that occurred with loading the software. Once loaded, however, the connection worked well, one VRS noting that following step-by-step instructions solved the problem. Some VRSs indicated they did not invite all the veterans on their caseload to participate in VRtele due to concerns with the patient’s familiarity with technology, but one VRS stated, “I haven’t had anybody that failed to do a [session] that I couldn’t get them up and running within a few minutes.”

When working in the community, VRSs reported using laptops for VRtele but found that these devices were unreliable due to lack of internet access and were slow to start; several VRSs thought tablets would have been more helpful. Some veterans reported technical glitches, lack of comfort with technology, or a problem with sound due to a tablet’s protective case blocking the speakers. To solve the sound issue, a veteran used headphones. This veteran also explained that the log-on process required a new password every time, so he would keep a pen and paper ready to write it down. Because signing in and setting up takes a little time, this veteran and his VRS agreed to start connecting 5 minutes before their meeting time to allow for that set- up time.

Initially, some VRSs expressed concern that transitioning to VRtele would affect the quality of interactions with the veterans. However, VRSs also identified strengths of VRtele, including flexibility, saved time, and increased interaction. One VRS discussed a veteran’s adaptation by saying, “I think he feels even more involved in his plan [and] enjoys the increased interaction.” Veterans reported enjoying using tablets and identified the main strength of VRtele as being able to talk face-to-face with the VRS. Echoing the VRSs, veterans reported teleconferencing saved time by avoiding travel and enabled spontaneous meetings. One of the veterans summed up the benefits of using VRtele: “I’d rather just connect. It’s going to take us 40 to 50 minutes [to meet in person] when we can just connect right here and it takes 15 to 20. We don’t have to go through the driving.… So this right here, doing it ahead of time and having the appointment, it’s a lot easier.”

In their interviews, VRSs talked about enjoying VRtele. A VRS explained: “It makes it a lot easier. It makes me feel less guilty. This way [veterans] don’t have to use their gas money, use their time. I know [the veteran] had something else he needed to do today.” Thus, both veterans and VRSs were satisfied with their VRtele experiences.

Discussion

This first report on the perspective of providers and veterans using VRtele suggests that it is a viable option for service delivery and that is highly satisfactory for serving veterans with disabilities, many of whom live in rural areas or have travel barriers. These findings are consistent with data on telerehabilitation for veterans with cognitive, physical, and mental disabilities.^13-22 Further, the data support the notion of using VRtele to facilitate long-term VR follow-up for persons with disabilities, as illustrated by successful continuation of vocational services after a veteran moved out of state.²³

Similar to other reports, our experience highlighted 2 factors that affect successful VRtele: (1) Troubleshooting technology barriers for both VR providers and clients; and (2) supportive leadership to facilitate implementation.^24-26These areas have been improved with recent telehealth VHA initiatives and upgrades. After the conclusion of this project evaluation, the program was expanded, and local facilities may now receive mentored support to implement similar programs.²⁷ This ongoing telerehabilitation program uses the recently upgraded VHA telehealth platform that enables encrypted sessions to be provided to any mobile or online device, and veterans simply click on a link to connect rather than waiting for a session-specific password.²⁸ By using virtual medical rooms accessed by cameras on tablets, smartphones, or computers, veterans and VR providers now have an easier time scheduling and attending online appointments.²⁹ Improved access to VRtele is important as VHA began providing the majority of appointments via video telemedicine in Spring of 2020 due to the COVID-19 pandemic. The accelerated use of telehealth due to the COVID crisis makes these findings highly relevant to the current practice environment.

Changes to technology and increased usage of VA Video Connect may indicate that the barriers identified from the earlier process described here have been diminished or eliminated. More evaluation is needed to assess whether system upgrades have increased ease of use and access for veterans with disabilities.

Conclusions

Encouragingly, this clinical demonstration project showed that both providers and clients recognize the benefits of VRtele. Patient satisfaction and decreased travel costs were clear advantages to using VRtele for this small group of veterans who had barriers to care due to travel or disability barriers. As this program evaluation was limited by a small sample, absence of a comparison group, and lack of outcome data (eg, employment rates, hours, wages, retention), future research is needed on implementation and outcomes of VRtele.

Acknowledgments
The authors thank Lynn Dirk, MAMC, for substantial editorial assistance. This material was based on work supported by Rural Veterans Supported Employment TeleRehabilitation Initiative (RVSETI), funded by the VA Office of Rural Health (Project # N08-FY14Q3-S2-P01222) and by support of the VA Health Services Research and Development Service. This work was presented in part at the 114th Annual Meeting of the American Anthropological Association at Denver, Colorado, November 21, 2015; a field-based Health Services Research and Development Service meeting, US Department of Veterans Affairs at Washington, DC, September 12, 2016; and the 2016 Annual Conference of the American Congress for Rehabilitation Medicine at Chicago, Illinois, October-November 2016.

Vocational rehabilitation (VR) interventions are offered through Compensated Work Therapy (CWT) as part of clinical care in the Veterans Health Administration (VHA) to improve employment and quality of life outcomes for veterans with life-altering disabilities.^1–5 CWT vocational services range from assessment, vocational counseling, and treatment plan development to job placement, coaching, and follow-along support.¹ However, many veterans receive care in community-based clinics that are not staffed with a VR specialist (VRS) to provide these services.^6–8 Telehealth may increase patient access to VR, especially for rural veterans and those with travel barriers, but it is not known whether veterans and VRS would find this to be a satisfactory service delivery method.^8,9 This paper examines veteran and VRS provider perspectives on VR provided by telehealth (VRtele) as part of a VHA clinical demonstration project. To our knowledge, this is the first report of using real-time, clinic-based VRtele.

Methods

The Rural Veterans Supported Employment Telerehabilitation Initiative (RVSETI) was conducted as a field-initiated demonstration project at 2 US Department of Veterans Affairs (VA) medical centers (VAMCs) in Florida between 2014 and 2016: James A. Haley Veterans’ Hospital & Clinics (Tampa) and Malcom Randall VAMC (Gainesville). This retrospective evaluation of its first year did not require institutional review board approval as it was determined to be a quality improvement project by the local research service.

The patient population for the project was veterans with disabilities who were referred by clinical consults to the CWT service, a recovery-oriented vocational program. During the project years, veterans were offered the option of receiving VR services, such as supported employment, community-based employment services, or vocational assistance, through VRtele rather than traditional face-to-face meetings. The specific interventions delivered included patient orientation, interview assessment, treatment plan development, referral activities, vocational counseling, assessment of workplace for accommodation needs, vocational case management, and other employment supports. VR staff participating in the project included 2 VR supervisors, 1 supported employment mentor trainer, and 5 VRSs.

Each clinic was set up for VRtele, and codes were added to the electronic health record (EHR) to ensure proper documentation. Participating VRSs completed teleconferencing training, including a skills assessment using the equipment for real-time, high-quality video streaming over an encrypted network to provide services in a patient’s home or other remote locations. VRS staff provided veterans with instructions on using a VA-provided tablet or their own device and assisted them with establishing connectivity with the network. Video equipment included speakers, camera, and headphones connected to the desktop computer or laptop of the VRS. A patient’s first VRtelesession was conducted in person at the VAMC to assure veterans were able to use the technology and to identify and resolve any problems.

Demographic data, primary diagnosis, VR usage data, and zip codes of participating veterans were extracted from the EHR. Veterans completed a 2-part satisfaction survey administered 90 days after enrollment and at discharge. Part 1 was composed of 15 items, most with a 5-point Likert scale (higher ratings indicated greater satisfaction), on various aspects of the VRtele experience, such as audio and video quality and wait times.¹⁰ Part 2 addressed VR services and the VRS and consisted of 8 Likert scale items with the option to add a comment for each and 2 open-ended items that asked the participant to list what they liked best and least about VRtele.

Semistructured, in-person 30- to 60-minute interviews were conducted with VRSs at the initiation of VRteleand audio-recorded with permission. An interview guide consisting of 14 questions was used to obtain data on caseload, VRtele set up, use of teleconferencing equipment, and veteran access to VR services.

After ≥ 2 months of VRtele use, researchers observed a session with each participant to obtain qualitative data from all participants on their VRtele experience. Using an observation form with open notes, data were collected on the use of the videoconferencing technology, the quality of the VRtele session, and reactions of veterans and their VRS. Following the observation session, both the VRS and the participating veteran were interviewed separately using a 9-question interview form to obtain data on the use of the technology in general and for VR. Interviews were audio-recorded with the permission of the VRS and veteran and transcribed for analysis.

Analyses

Descriptive statistics were used for EHR data and satisfaction surveys. For qualitative analysis, each transcript was read in full by 2 researchers to get an overview of the data, and a rapid analysis approach was used to identify central themes focused on how technology was used and the experiences of the participants.^11,12 Relevant text for each topic was tabulated, and a summary table was created that highlighted overlapping ideas discussed by the interviewees as well as differences.

Results

Of the 22 veterans who participated in the project, 11 completed satisfaction surveys and 4 participated in qualitative interviews. The rural and nonrural groups did not differ demographically or by diagnosis, which was predominantly mental health related. Only 1 veteran in each group owned a tablet; the majority of both groups required VA-issued devices: 80% (n = 8) rural and 91.7% (n = 11) nonrural. The number of VRtele sessions for the groups also was similar, 53 for rural and 60 for nonrural, as was the mean (SD) number of sessions per veteran: 5.3 (SD, 3.2) rural and 5.0 (SD, 2.5) urban. Overall, 63 miles per session were saved, mostly for rural veterans, and the number of mean (SD) miles saved per veteran was greater for rural than nonrural veterans: 379.2 (243.0) and 256.1 (275.9), respectively. One veteran who moved to a different state during the program continued VRtele at the new location. In a qualitative sampling of 5 VRtele sessions, all the VRSs used office desktop computers.

Level of satisfaction with aspects of VRtele related to the technology rated was consistently > 4 on the Likert scale. The lowest mean (SD) ratings were 4.2 (1.0) for audio quality and 4.4 (0.5) for video quality, and the highest rating was given for equipment operation explanation and privacy was respected, 4.9 (0.3) for both. All questions related to satisfaction with services were also rated high: The mean (SD) lowest ratings were 4.3 (1.0) given to both vocational needs 4.3 (1.0) and tasks effectively helped achieve goals 4.3 (0.7). The highest mean (SD) ratings were 4.6 (0.5) given to VR program service explained and 4.7 (0.5) for appointment timeliness.

Qualitative Results

At first, some VRSs thought the teleconferencing system might be difficult or awkward to use, but they found it easier to set up than expected and seamless to use. VRS staff reported being surprised at how well it worked despite some issues that occurred with loading the software. Once loaded, however, the connection worked well, one VRS noting that following step-by-step instructions solved the problem. Some VRSs indicated they did not invite all the veterans on their caseload to participate in VRtele due to concerns with the patient’s familiarity with technology, but one VRS stated, “I haven’t had anybody that failed to do a [session] that I couldn’t get them up and running within a few minutes.”

When working in the community, VRSs reported using laptops for VRtele but found that these devices were unreliable due to lack of internet access and were slow to start; several VRSs thought tablets would have been more helpful. Some veterans reported technical glitches, lack of comfort with technology, or a problem with sound due to a tablet’s protective case blocking the speakers. To solve the sound issue, a veteran used headphones. This veteran also explained that the log-on process required a new password every time, so he would keep a pen and paper ready to write it down. Because signing in and setting up takes a little time, this veteran and his VRS agreed to start connecting 5 minutes before their meeting time to allow for that set- up time.

Initially, some VRSs expressed concern that transitioning to VRtele would affect the quality of interactions with the veterans. However, VRSs also identified strengths of VRtele, including flexibility, saved time, and increased interaction. One VRS discussed a veteran’s adaptation by saying, “I think he feels even more involved in his plan [and] enjoys the increased interaction.” Veterans reported enjoying using tablets and identified the main strength of VRtele as being able to talk face-to-face with the VRS. Echoing the VRSs, veterans reported teleconferencing saved time by avoiding travel and enabled spontaneous meetings. One of the veterans summed up the benefits of using VRtele: “I’d rather just connect. It’s going to take us 40 to 50 minutes [to meet in person] when we can just connect right here and it takes 15 to 20. We don’t have to go through the driving.… So this right here, doing it ahead of time and having the appointment, it’s a lot easier.”

In their interviews, VRSs talked about enjoying VRtele. A VRS explained: “It makes it a lot easier. It makes me feel less guilty. This way [veterans] don’t have to use their gas money, use their time. I know [the veteran] had something else he needed to do today.” Thus, both veterans and VRSs were satisfied with their VRtele experiences.

Discussion

This first report on the perspective of providers and veterans using VRtele suggests that it is a viable option for service delivery and that is highly satisfactory for serving veterans with disabilities, many of whom live in rural areas or have travel barriers. These findings are consistent with data on telerehabilitation for veterans with cognitive, physical, and mental disabilities.^13-22 Further, the data support the notion of using VRtele to facilitate long-term VR follow-up for persons with disabilities, as illustrated by successful continuation of vocational services after a veteran moved out of state.²³

Similar to other reports, our experience highlighted 2 factors that affect successful VRtele: (1) Troubleshooting technology barriers for both VR providers and clients; and (2) supportive leadership to facilitate implementation.^24-26These areas have been improved with recent telehealth VHA initiatives and upgrades. After the conclusion of this project evaluation, the program was expanded, and local facilities may now receive mentored support to implement similar programs.²⁷ This ongoing telerehabilitation program uses the recently upgraded VHA telehealth platform that enables encrypted sessions to be provided to any mobile or online device, and veterans simply click on a link to connect rather than waiting for a session-specific password.²⁸ By using virtual medical rooms accessed by cameras on tablets, smartphones, or computers, veterans and VR providers now have an easier time scheduling and attending online appointments.²⁹ Improved access to VRtele is important as VHA began providing the majority of appointments via video telemedicine in Spring of 2020 due to the COVID-19 pandemic. The accelerated use of telehealth due to the COVID crisis makes these findings highly relevant to the current practice environment.

Changes to technology and increased usage of VA Video Connect may indicate that the barriers identified from the earlier process described here have been diminished or eliminated. More evaluation is needed to assess whether system upgrades have increased ease of use and access for veterans with disabilities.

Conclusions

Encouragingly, this clinical demonstration project showed that both providers and clients recognize the benefits of VRtele. Patient satisfaction and decreased travel costs were clear advantages to using VRtele for this small group of veterans who had barriers to care due to travel or disability barriers. As this program evaluation was limited by a small sample, absence of a comparison group, and lack of outcome data (eg, employment rates, hours, wages, retention), future research is needed on implementation and outcomes of VRtele.

Acknowledgments
The authors thank Lynn Dirk, MAMC, for substantial editorial assistance. This material was based on work supported by Rural Veterans Supported Employment TeleRehabilitation Initiative (RVSETI), funded by the VA Office of Rural Health (Project # N08-FY14Q3-S2-P01222) and by support of the VA Health Services Research and Development Service. This work was presented in part at the 114th Annual Meeting of the American Anthropological Association at Denver, Colorado, November 21, 2015; a field-based Health Services Research and Development Service meeting, US Department of Veterans Affairs at Washington, DC, September 12, 2016; and the 2016 Annual Conference of the American Congress for Rehabilitation Medicine at Chicago, Illinois, October-November 2016.

In the late 1980s and early 1990s, an emphasis on better pain management led health care professionals (HCPs) to increase prescribing of opioids to better manage patient’s pain. In 1991, 76 million prescriptions were written for opioids in the United States, and by 2011, the number had nearly tripled to 219 million.¹ Overdose rates increased as well, nearly tripling from 1999 to 2014.² Of the 52,404 US deaths from drug overdoses in the in 2015, 63% involved an opioid.²

Opioid Safety Initiative

In response to the growing opioid epidemic, the US Department of Veterans Affairs (VA) created the Opioid Safety Initiative in 2014.³ This comprehensive, multifaceted initiative was designed to improve the care and safety of veterans managed with opioid therapy and promote rational opioid prescribing and monitoring. In 2016 the Centers for Disease Control and Prevention (CDC) issued guidelines for opioid prescriptions, and the following year the VA and the US Department of Defense (DoD) updated the VA/DoD Clinical Practice Guidelines for Opioid Therapy for Chronic Pain (VA/DoD guidelines).^4,5 After the release of these guidelines, the use of opioid tapers expanded. However, due to public outcry of forced opioid tapering in 2019, the US Food and Drug Administration updated its opioid labeling requirements to provide clearer guidance on opioid tapers for tolerant patients.^6,7

As a result, HCPs began to develop various strategies to balance the safety and efficacy of opioid use in patients with chronic pain. The West Palm Beach VA Medical Center (WPBVAMC) in Florida has a Pain Clinic that includes 2 pain management clinical pharmacy specialists (CPSs) with specialized training in pain management, who are uniquely qualified to assess and evaluate medication therapy in complex pain patient cases. These CPSs were involved in the face-to-face management of patients requiring specialized pain care and participated in a pain pharmacy electronic consult (eConsult) service to document pain management consultative recommendations for patients appropriate for management at the primary care level. This formalized process increased specialty pain care access for veterans whose pain was managed by primary care providers (PCPs).

The pain pharmacy eConsult service was initiated at the WPBVAMC in June 2013 to assist PCPs in the management of outpatients with chronic pain. The eConsult service includes evaluation of a patient’s electronic health records (EHRs) by CPSs. The eConsult service also provided PCPs with the option to engage a pharmacist who could provide recommendations for opioid dosing conversion, opioid tapering, pain pharmacotherapy, or drug screen interpretation, without the necessity for an additional patient visit.

Subsequent to the release of the 2016 CDC (and later the 2017 VA/DoD) guidelines recommending reducing morphine equivalent daily dose (MEDD) levels, the WPBVAMC had a large increase in pain eConsult requests for opioid tapering and opioid pharmacotherapy. A 3.4-fold increase in requests occurred in March, April, and May vs the following 9 months, and a nearly 4-fold increase in requests for opioid tapers during the same period. However, the impact of the completed eConsults was unclear. Therefore, the primary objective of this study was to assess the effect of CPS services for opioid tapering and opioid pharmacotherapy by quantifying the number of recommendations accepted/implemented by PCPs. The secondary objectives included evaluating harms associated with the recommendations (eg, increase in visits to the emergency department [ED], hospitalizations, suicide attempts, or PCP visits) and provider satisfaction.

Methods

A retrospective chart review was completed to assess data of patients from the WPBVAMC and its associated community-based outpatient clinics (CBOCs). The project was approved by the WPBVAMC Scientific Advisory Committee as part of the facility’s performance improvement efforts.

Included patients had a pain pharmacy eConsult placed between April 1, 2016 and March 31, 2017. EHRs were reviewed and only eConsults for opioid pharmacotherapy recommendation or opioid tapers were evaluated. eConsults were excluded if the request was discontinued, completed by a HCP other than the pain CPS, or placed for an opioid dose conversion, nonopioid pharmacotherapy, or drug screen interpretation.

Data for analyses were entered into Microsoft Excel 2016 and were securely saved and accessible to relevant researchers. Patient protected health information used during patient care remained confidential.

Demographic data were collected, including age, gender, race, pertinent medical comorbidities (eg, diabetes mellitus, sleep apnea), and mental health comorbidities. Pain scores were collected at baseline and 6-months postconsult. Pain medications used by patients were noted at baseline and 6 months postconsult, including concomitant opioid and benzodiazepine use, MEDD, and other pain medication. The duration of time needed by pain CPS to complete each eConsult and total time from eConsult entered to HCP implementation of the initial recommendation was collected. The number of actionable recommendations (eg, changes in drug therapy, urine drug screens [UDSs], and referrals to other services also were recorded and reviewed 6 months postconsult to determine the number and percentage of recommendations implemented by the HCP. The EHR was examined to determine adverse events (AEs) (eg, any documentation of suicide attempt, calls to the Veterans Crisis Line, or death 6 month postconsult). Collected data also included new eConsults, the reason for opioid tapering either by HCP or patient, and assessment of economic harms (count of the number of visits to ED, hospitalizations, or unscheduled PCP visits with uncontrolled pain as chief reason within 6 months postconsult). Last, PCPs were sent a survey to assess their satisfaction with the pain eConsult service.

Results

Of 517 eConsults received from April 1, 2016 to March 31, 2017, 285 (55.1%) met inclusion criteria (Figure). Using a random number generator, 100 eConsults were further reviewed for outcomes of interest.

In this cohort, the mean age was 61 years, 87% were male, and 80% were White individuals. Most patients (83%) had ≥ 1 mental health comorbidity, and 53% had ≥ 2, with depressive symptoms, tobacco use, and/or posttraumatic stress disorder the most common diagnoses (Table 1). Eighty-seven percent of eConsults were for opioid tapers and the remaining 13% were for opioid pharmacotherapy.

The median pain score at time of consult was 6 on a 10-point scale, with no change at 6 months postconsult. However, 41% of patients overall had a median 3.3-point drop in pain score, 17% had no change in pain score, and 42% had a median 2.6-point increase in pain score.

Electronic Consults

Table 2 describes the reasons eConsults were requested. The most common reason was to taper the dose to be in compliance with the CDC 2016 guideline recommendation of MEDD < 90 mg, which was later increased to 100 mg by the VA/DoD guideline.

On average, eConsults were completed within a mean of 11.5 days of the PCP request, including nights and weekends. The CPS spent a mean 66.8 minutes to complete each eConsult. Once the eConsult was completed, PCPs took a mean of 9 days to initiate the primary recommendation. This 9-day average does not include 11 eConsults with no accepted recommendations and 11 eConsults for which the PCP implemented the primary recommendation before the CPS completed the consult, most likely due to a phone call or direct contact with the CPS at the time the eConsult was ordered.

A mean 3.5 actionable recommendations were made by the CPS and a mean 1.6 recommendations were implemented within 6 months by the PCP. At least 1 recommendation was accepted/implemented for 89% of patients, with a mean 55% recommendations that were accepted/implemented. Eleven percent of the eConsult final recommendations were not accepted by PCPs and clear documentation of the reasons were not provided.

In the 6 months postconsult, 11 patients (7 men and 4 women) experienced 32 AEs (Table 3). Eight patients had 15 ED visits, with 3 of the visits resulting in hospitalizations, 8 patients had 9 unscheduled PCP visits, 1 patient reported suicidal ideation and 2 patients made a total of 4 calls to the Veterans Crisis Line. There were also 2 deaths; however, both were due to end-stage disease (cirrhosis and amyotrophic lateral sclerosis) and not believed to be related to eConsult recommendations.

Eight patients had a history of substance use disorders (SUDs) and 8 had a history of a mood disorder or psychosis. One patient had both SUD and a mood/psychosis-related mental health disorder, including a reported suicidal attempt/ideation at an ED visit and a subsequent hospitalization. A similar number of AEs occurred in patients with decreases in MEDD of 0 to 24% compared with those that received more aggressive tapers of 75 to 100% (Table 4).

Primary Care Providers

Nine patients were reconsulted, with only 1 secondary to the PCP not implementing recommendations from the initial consult. No factors were found that correlated with likelihood of a patient being reconsulted.

Surveys on PCP satisfaction with the eConsult service were completed by 29 of the 55 PCPs. PCP feedback was generally positive with nearly 90% of PCPs planning to use the service in the future as well as recommending use to other providers.

Discussion

Most (89%) PCPs accepted at least 1 recommendation from the completed eConsult, and MEDDs decreased by 60%, likely reducing the patient’s risk of overdose or other AEs from opioids. There also was a slight reduction in patient’s mean pain scores; however, 41% had a decrease and 42% had an increase in pain scores. There was no clear relationship when pain scores were compared with MEDDs, likely giving credence to the idea that pain scores are largely subjective and an unreliable surrogate marker for assessing effectiveness of analgesic regimens.

Eleven patients experienced AEs, including 1 patient for whom the recommendations were not implemented by the PCP. Eight of the 11 had multiple AEs. One interesting finding was that 7 of the 11 patients with an AE tested positive for unexpected substances on routine UDS or were arrested for driving while intoxicated (DWI). However, only 3 of the 7 had an active SUD diagnosis. With 25% of the AEs coming from patients with a history of SUD, it is important that any history of SUD be documented in the EHR. Maintaining this documentation can be especially difficult if patients switch VA medical centers or receive services outside the VA. Thorough and accurate history and chart review should ideally be completed before prescribing opioids.

Guidelines

While the PCPs were following VA/DoD and CDC recommendations for opioid tapering to < 100 or 90 mg MEDD, respectively, there is weak evidence in these guidelines to support specific MEDD cutoffs. The CDC guidelines even state, “a single dosage threshold for safe opioid use could not be identified.”⁵ One of the largest issues when using MEDD as a cutoff is the lack of agreement on its calculation. In 2014, Nuckols and colleagues al conducted a study to compare the existing guidelines on the use of opioids for chronic pain. While 13 guidelines were considered eligible, most recommendations were supported only by observational data or expert recommendations, and there was no consensus on what constitutes a “morphine equivalent.”⁸ Currently there is no universally accepted opioid-conversion method, resulting in a substantial problem when calculating a MEDD.⁹ A survey of 8 online opioid dose conversion tools found a -55% to +242% variation.¹⁰ As Fudin and colleagues concluded in response to the large variations found in these various analyses, the studies “unequivocally disqualify the validity of embracing MEDD to assess risk in any meaningful statistical way.”¹¹ Pharmacogenetics, drug tolerance, drug-drug interactions, body surface area, and organ function are patient- specific factors that are not taken into consideration when relying solely on a MEDD calculation. Tapering to lowest functional dose rather than a specific number or cutoff may be a more effective way to treat patients, and providers should use the guidelines as recommendations and not a hardline mandate.

At 6 months, 6 patients were receiving no pain medications from the VA, and 24 of the patients were tapered from their opiate to discontinuation. It is unclear whether patients are no longer taking opioids or switched their care to non-VA providers to receive medications, including opioids, privately. This is difficult to verify, though a prescription drug monitoring program (PDMP) could be used to assess patient adherence. As many of the patients that were tapered due to identification of aberrant behaviors, lack of continuity of care across health care systems may result in future patient harm.

The results of this analysis highlight the importance of checking PDMP databases and routine UDSs when prescribing opioids—there can be serious safety concerns if patients are taking other prescribed or illicit medications. However, care must be taken; there were 2 instances of patients’ chronic opioid prescriptions discontinued by their VA provider after a review of the PDMP showed they had received non-VA opioids. In both cases, the quantity and doses received were small (counts of ≤ 12) and were received more than 6 months prior to the check of the PDMP. While this constitutes a breach of the Informed Consent for long-term opioid use, if there are no other concerning behaviors, it may be more prudent to review the informed consent with the patient and discuss why the behavior is a breach to ensure that patients and PCPs continue to work as a team to manage chronic pain.

Limitations

The study population was one limitation of this project. While data suggest that chronic pain affects women more than men, this study’s population was only 13% female. Thirty percent of the women in this study had an AE compared with only 8% of the men. Additional limitations included use of problem list for comorbidities, as lists may be inaccurate or outdated, and limiting the monitoring of AE to only 6 months. As some tapers were not initiated immediately and some taper schedules can last several months to years; therefor, outcomes may have been higher if patients were followed longer. Many of the patients with AEs had increased ED visits or unscheduled primary care visits as the tapers went on and their pain worsened, but the visits were outside the 6-month time frame for data collection. An additional weakness of this review included assessing a pain score, but not functional status, which may be a better predictor of the effectiveness of a patient’s pain management regimen. This assessment is needed in future studies for more reliable data. Finally, PCP survey results also should be viewed with caution. The current survey had only 29 respondents, and the 2014 survey had only 10 respondents and did not include CBOC providers.

Conclusion

A pain eConsult service managed by CPSs specializing in pain management can assist patients and PCPs with opioid therapy recommendations in a safe and timely manner, reducing risk of overdose secondary to high dose opioid therapy and with limited harm to patients.

In the late 1980s and early 1990s, an emphasis on better pain management led health care professionals (HCPs) to increase prescribing of opioids to better manage patient’s pain. In 1991, 76 million prescriptions were written for opioids in the United States, and by 2011, the number had nearly tripled to 219 million.¹ Overdose rates increased as well, nearly tripling from 1999 to 2014.² Of the 52,404 US deaths from drug overdoses in the in 2015, 63% involved an opioid.²

Opioid Safety Initiative

In response to the growing opioid epidemic, the US Department of Veterans Affairs (VA) created the Opioid Safety Initiative in 2014.³ This comprehensive, multifaceted initiative was designed to improve the care and safety of veterans managed with opioid therapy and promote rational opioid prescribing and monitoring. In 2016 the Centers for Disease Control and Prevention (CDC) issued guidelines for opioid prescriptions, and the following year the VA and the US Department of Defense (DoD) updated the VA/DoD Clinical Practice Guidelines for Opioid Therapy for Chronic Pain (VA/DoD guidelines).^4,5 After the release of these guidelines, the use of opioid tapers expanded. However, due to public outcry of forced opioid tapering in 2019, the US Food and Drug Administration updated its opioid labeling requirements to provide clearer guidance on opioid tapers for tolerant patients.^6,7

As a result, HCPs began to develop various strategies to balance the safety and efficacy of opioid use in patients with chronic pain. The West Palm Beach VA Medical Center (WPBVAMC) in Florida has a Pain Clinic that includes 2 pain management clinical pharmacy specialists (CPSs) with specialized training in pain management, who are uniquely qualified to assess and evaluate medication therapy in complex pain patient cases. These CPSs were involved in the face-to-face management of patients requiring specialized pain care and participated in a pain pharmacy electronic consult (eConsult) service to document pain management consultative recommendations for patients appropriate for management at the primary care level. This formalized process increased specialty pain care access for veterans whose pain was managed by primary care providers (PCPs).

The pain pharmacy eConsult service was initiated at the WPBVAMC in June 2013 to assist PCPs in the management of outpatients with chronic pain. The eConsult service includes evaluation of a patient’s electronic health records (EHRs) by CPSs. The eConsult service also provided PCPs with the option to engage a pharmacist who could provide recommendations for opioid dosing conversion, opioid tapering, pain pharmacotherapy, or drug screen interpretation, without the necessity for an additional patient visit.

Subsequent to the release of the 2016 CDC (and later the 2017 VA/DoD) guidelines recommending reducing morphine equivalent daily dose (MEDD) levels, the WPBVAMC had a large increase in pain eConsult requests for opioid tapering and opioid pharmacotherapy. A 3.4-fold increase in requests occurred in March, April, and May vs the following 9 months, and a nearly 4-fold increase in requests for opioid tapers during the same period. However, the impact of the completed eConsults was unclear. Therefore, the primary objective of this study was to assess the effect of CPS services for opioid tapering and opioid pharmacotherapy by quantifying the number of recommendations accepted/implemented by PCPs. The secondary objectives included evaluating harms associated with the recommendations (eg, increase in visits to the emergency department [ED], hospitalizations, suicide attempts, or PCP visits) and provider satisfaction.

Methods

A retrospective chart review was completed to assess data of patients from the WPBVAMC and its associated community-based outpatient clinics (CBOCs). The project was approved by the WPBVAMC Scientific Advisory Committee as part of the facility’s performance improvement efforts.

Included patients had a pain pharmacy eConsult placed between April 1, 2016 and March 31, 2017. EHRs were reviewed and only eConsults for opioid pharmacotherapy recommendation or opioid tapers were evaluated. eConsults were excluded if the request was discontinued, completed by a HCP other than the pain CPS, or placed for an opioid dose conversion, nonopioid pharmacotherapy, or drug screen interpretation.

Data for analyses were entered into Microsoft Excel 2016 and were securely saved and accessible to relevant researchers. Patient protected health information used during patient care remained confidential.

Demographic data were collected, including age, gender, race, pertinent medical comorbidities (eg, diabetes mellitus, sleep apnea), and mental health comorbidities. Pain scores were collected at baseline and 6-months postconsult. Pain medications used by patients were noted at baseline and 6 months postconsult, including concomitant opioid and benzodiazepine use, MEDD, and other pain medication. The duration of time needed by pain CPS to complete each eConsult and total time from eConsult entered to HCP implementation of the initial recommendation was collected. The number of actionable recommendations (eg, changes in drug therapy, urine drug screens [UDSs], and referrals to other services also were recorded and reviewed 6 months postconsult to determine the number and percentage of recommendations implemented by the HCP. The EHR was examined to determine adverse events (AEs) (eg, any documentation of suicide attempt, calls to the Veterans Crisis Line, or death 6 month postconsult). Collected data also included new eConsults, the reason for opioid tapering either by HCP or patient, and assessment of economic harms (count of the number of visits to ED, hospitalizations, or unscheduled PCP visits with uncontrolled pain as chief reason within 6 months postconsult). Last, PCPs were sent a survey to assess their satisfaction with the pain eConsult service.

Results

Of 517 eConsults received from April 1, 2016 to March 31, 2017, 285 (55.1%) met inclusion criteria (Figure). Using a random number generator, 100 eConsults were further reviewed for outcomes of interest.

In this cohort, the mean age was 61 years, 87% were male, and 80% were White individuals. Most patients (83%) had ≥ 1 mental health comorbidity, and 53% had ≥ 2, with depressive symptoms, tobacco use, and/or posttraumatic stress disorder the most common diagnoses (Table 1). Eighty-seven percent of eConsults were for opioid tapers and the remaining 13% were for opioid pharmacotherapy.

The median pain score at time of consult was 6 on a 10-point scale, with no change at 6 months postconsult. However, 41% of patients overall had a median 3.3-point drop in pain score, 17% had no change in pain score, and 42% had a median 2.6-point increase in pain score.

Electronic Consults

Table 2 describes the reasons eConsults were requested. The most common reason was to taper the dose to be in compliance with the CDC 2016 guideline recommendation of MEDD < 90 mg, which was later increased to 100 mg by the VA/DoD guideline.

On average, eConsults were completed within a mean of 11.5 days of the PCP request, including nights and weekends. The CPS spent a mean 66.8 minutes to complete each eConsult. Once the eConsult was completed, PCPs took a mean of 9 days to initiate the primary recommendation. This 9-day average does not include 11 eConsults with no accepted recommendations and 11 eConsults for which the PCP implemented the primary recommendation before the CPS completed the consult, most likely due to a phone call or direct contact with the CPS at the time the eConsult was ordered.

A mean 3.5 actionable recommendations were made by the CPS and a mean 1.6 recommendations were implemented within 6 months by the PCP. At least 1 recommendation was accepted/implemented for 89% of patients, with a mean 55% recommendations that were accepted/implemented. Eleven percent of the eConsult final recommendations were not accepted by PCPs and clear documentation of the reasons were not provided.

In the 6 months postconsult, 11 patients (7 men and 4 women) experienced 32 AEs (Table 3). Eight patients had 15 ED visits, with 3 of the visits resulting in hospitalizations, 8 patients had 9 unscheduled PCP visits, 1 patient reported suicidal ideation and 2 patients made a total of 4 calls to the Veterans Crisis Line. There were also 2 deaths; however, both were due to end-stage disease (cirrhosis and amyotrophic lateral sclerosis) and not believed to be related to eConsult recommendations.

Eight patients had a history of substance use disorders (SUDs) and 8 had a history of a mood disorder or psychosis. One patient had both SUD and a mood/psychosis-related mental health disorder, including a reported suicidal attempt/ideation at an ED visit and a subsequent hospitalization. A similar number of AEs occurred in patients with decreases in MEDD of 0 to 24% compared with those that received more aggressive tapers of 75 to 100% (Table 4).

Primary Care Providers

Nine patients were reconsulted, with only 1 secondary to the PCP not implementing recommendations from the initial consult. No factors were found that correlated with likelihood of a patient being reconsulted.

Surveys on PCP satisfaction with the eConsult service were completed by 29 of the 55 PCPs. PCP feedback was generally positive with nearly 90% of PCPs planning to use the service in the future as well as recommending use to other providers.

Discussion

Most (89%) PCPs accepted at least 1 recommendation from the completed eConsult, and MEDDs decreased by 60%, likely reducing the patient’s risk of overdose or other AEs from opioids. There also was a slight reduction in patient’s mean pain scores; however, 41% had a decrease and 42% had an increase in pain scores. There was no clear relationship when pain scores were compared with MEDDs, likely giving credence to the idea that pain scores are largely subjective and an unreliable surrogate marker for assessing effectiveness of analgesic regimens.

Eleven patients experienced AEs, including 1 patient for whom the recommendations were not implemented by the PCP. Eight of the 11 had multiple AEs. One interesting finding was that 7 of the 11 patients with an AE tested positive for unexpected substances on routine UDS or were arrested for driving while intoxicated (DWI). However, only 3 of the 7 had an active SUD diagnosis. With 25% of the AEs coming from patients with a history of SUD, it is important that any history of SUD be documented in the EHR. Maintaining this documentation can be especially difficult if patients switch VA medical centers or receive services outside the VA. Thorough and accurate history and chart review should ideally be completed before prescribing opioids.

Guidelines

While the PCPs were following VA/DoD and CDC recommendations for opioid tapering to < 100 or 90 mg MEDD, respectively, there is weak evidence in these guidelines to support specific MEDD cutoffs. The CDC guidelines even state, “a single dosage threshold for safe opioid use could not be identified.”⁵ One of the largest issues when using MEDD as a cutoff is the lack of agreement on its calculation. In 2014, Nuckols and colleagues al conducted a study to compare the existing guidelines on the use of opioids for chronic pain. While 13 guidelines were considered eligible, most recommendations were supported only by observational data or expert recommendations, and there was no consensus on what constitutes a “morphine equivalent.”⁸ Currently there is no universally accepted opioid-conversion method, resulting in a substantial problem when calculating a MEDD.⁹ A survey of 8 online opioid dose conversion tools found a -55% to +242% variation.¹⁰ As Fudin and colleagues concluded in response to the large variations found in these various analyses, the studies “unequivocally disqualify the validity of embracing MEDD to assess risk in any meaningful statistical way.”¹¹ Pharmacogenetics, drug tolerance, drug-drug interactions, body surface area, and organ function are patient- specific factors that are not taken into consideration when relying solely on a MEDD calculation. Tapering to lowest functional dose rather than a specific number or cutoff may be a more effective way to treat patients, and providers should use the guidelines as recommendations and not a hardline mandate.

At 6 months, 6 patients were receiving no pain medications from the VA, and 24 of the patients were tapered from their opiate to discontinuation. It is unclear whether patients are no longer taking opioids or switched their care to non-VA providers to receive medications, including opioids, privately. This is difficult to verify, though a prescription drug monitoring program (PDMP) could be used to assess patient adherence. As many of the patients that were tapered due to identification of aberrant behaviors, lack of continuity of care across health care systems may result in future patient harm.

The results of this analysis highlight the importance of checking PDMP databases and routine UDSs when prescribing opioids—there can be serious safety concerns if patients are taking other prescribed or illicit medications. However, care must be taken; there were 2 instances of patients’ chronic opioid prescriptions discontinued by their VA provider after a review of the PDMP showed they had received non-VA opioids. In both cases, the quantity and doses received were small (counts of ≤ 12) and were received more than 6 months prior to the check of the PDMP. While this constitutes a breach of the Informed Consent for long-term opioid use, if there are no other concerning behaviors, it may be more prudent to review the informed consent with the patient and discuss why the behavior is a breach to ensure that patients and PCPs continue to work as a team to manage chronic pain.

Limitations

The study population was one limitation of this project. While data suggest that chronic pain affects women more than men, this study’s population was only 13% female. Thirty percent of the women in this study had an AE compared with only 8% of the men. Additional limitations included use of problem list for comorbidities, as lists may be inaccurate or outdated, and limiting the monitoring of AE to only 6 months. As some tapers were not initiated immediately and some taper schedules can last several months to years; therefor, outcomes may have been higher if patients were followed longer. Many of the patients with AEs had increased ED visits or unscheduled primary care visits as the tapers went on and their pain worsened, but the visits were outside the 6-month time frame for data collection. An additional weakness of this review included assessing a pain score, but not functional status, which may be a better predictor of the effectiveness of a patient’s pain management regimen. This assessment is needed in future studies for more reliable data. Finally, PCP survey results also should be viewed with caution. The current survey had only 29 respondents, and the 2014 survey had only 10 respondents and did not include CBOC providers.

Conclusion

A pain eConsult service managed by CPSs specializing in pain management can assist patients and PCPs with opioid therapy recommendations in a safe and timely manner, reducing risk of overdose secondary to high dose opioid therapy and with limited harm to patients.

In the late 1980s and early 1990s, an emphasis on better pain management led health care professionals (HCPs) to increase prescribing of opioids to better manage patient’s pain. In 1991, 76 million prescriptions were written for opioids in the United States, and by 2011, the number had nearly tripled to 219 million.¹ Overdose rates increased as well, nearly tripling from 1999 to 2014.² Of the 52,404 US deaths from drug overdoses in the in 2015, 63% involved an opioid.²

Opioid Safety Initiative

In response to the growing opioid epidemic, the US Department of Veterans Affairs (VA) created the Opioid Safety Initiative in 2014.³ This comprehensive, multifaceted initiative was designed to improve the care and safety of veterans managed with opioid therapy and promote rational opioid prescribing and monitoring. In 2016 the Centers for Disease Control and Prevention (CDC) issued guidelines for opioid prescriptions, and the following year the VA and the US Department of Defense (DoD) updated the VA/DoD Clinical Practice Guidelines for Opioid Therapy for Chronic Pain (VA/DoD guidelines).^4,5 After the release of these guidelines, the use of opioid tapers expanded. However, due to public outcry of forced opioid tapering in 2019, the US Food and Drug Administration updated its opioid labeling requirements to provide clearer guidance on opioid tapers for tolerant patients.^6,7

As a result, HCPs began to develop various strategies to balance the safety and efficacy of opioid use in patients with chronic pain. The West Palm Beach VA Medical Center (WPBVAMC) in Florida has a Pain Clinic that includes 2 pain management clinical pharmacy specialists (CPSs) with specialized training in pain management, who are uniquely qualified to assess and evaluate medication therapy in complex pain patient cases. These CPSs were involved in the face-to-face management of patients requiring specialized pain care and participated in a pain pharmacy electronic consult (eConsult) service to document pain management consultative recommendations for patients appropriate for management at the primary care level. This formalized process increased specialty pain care access for veterans whose pain was managed by primary care providers (PCPs).

The pain pharmacy eConsult service was initiated at the WPBVAMC in June 2013 to assist PCPs in the management of outpatients with chronic pain. The eConsult service includes evaluation of a patient’s electronic health records (EHRs) by CPSs. The eConsult service also provided PCPs with the option to engage a pharmacist who could provide recommendations for opioid dosing conversion, opioid tapering, pain pharmacotherapy, or drug screen interpretation, without the necessity for an additional patient visit.

Subsequent to the release of the 2016 CDC (and later the 2017 VA/DoD) guidelines recommending reducing morphine equivalent daily dose (MEDD) levels, the WPBVAMC had a large increase in pain eConsult requests for opioid tapering and opioid pharmacotherapy. A 3.4-fold increase in requests occurred in March, April, and May vs the following 9 months, and a nearly 4-fold increase in requests for opioid tapers during the same period. However, the impact of the completed eConsults was unclear. Therefore, the primary objective of this study was to assess the effect of CPS services for opioid tapering and opioid pharmacotherapy by quantifying the number of recommendations accepted/implemented by PCPs. The secondary objectives included evaluating harms associated with the recommendations (eg, increase in visits to the emergency department [ED], hospitalizations, suicide attempts, or PCP visits) and provider satisfaction.

Methods

A retrospective chart review was completed to assess data of patients from the WPBVAMC and its associated community-based outpatient clinics (CBOCs). The project was approved by the WPBVAMC Scientific Advisory Committee as part of the facility’s performance improvement efforts.

Included patients had a pain pharmacy eConsult placed between April 1, 2016 and March 31, 2017. EHRs were reviewed and only eConsults for opioid pharmacotherapy recommendation or opioid tapers were evaluated. eConsults were excluded if the request was discontinued, completed by a HCP other than the pain CPS, or placed for an opioid dose conversion, nonopioid pharmacotherapy, or drug screen interpretation.

Data for analyses were entered into Microsoft Excel 2016 and were securely saved and accessible to relevant researchers. Patient protected health information used during patient care remained confidential.

Demographic data were collected, including age, gender, race, pertinent medical comorbidities (eg, diabetes mellitus, sleep apnea), and mental health comorbidities. Pain scores were collected at baseline and 6-months postconsult. Pain medications used by patients were noted at baseline and 6 months postconsult, including concomitant opioid and benzodiazepine use, MEDD, and other pain medication. The duration of time needed by pain CPS to complete each eConsult and total time from eConsult entered to HCP implementation of the initial recommendation was collected. The number of actionable recommendations (eg, changes in drug therapy, urine drug screens [UDSs], and referrals to other services also were recorded and reviewed 6 months postconsult to determine the number and percentage of recommendations implemented by the HCP. The EHR was examined to determine adverse events (AEs) (eg, any documentation of suicide attempt, calls to the Veterans Crisis Line, or death 6 month postconsult). Collected data also included new eConsults, the reason for opioid tapering either by HCP or patient, and assessment of economic harms (count of the number of visits to ED, hospitalizations, or unscheduled PCP visits with uncontrolled pain as chief reason within 6 months postconsult). Last, PCPs were sent a survey to assess their satisfaction with the pain eConsult service.

Results

Of 517 eConsults received from April 1, 2016 to March 31, 2017, 285 (55.1%) met inclusion criteria (Figure). Using a random number generator, 100 eConsults were further reviewed for outcomes of interest.

In this cohort, the mean age was 61 years, 87% were male, and 80% were White individuals. Most patients (83%) had ≥ 1 mental health comorbidity, and 53% had ≥ 2, with depressive symptoms, tobacco use, and/or posttraumatic stress disorder the most common diagnoses (Table 1). Eighty-seven percent of eConsults were for opioid tapers and the remaining 13% were for opioid pharmacotherapy.

The median pain score at time of consult was 6 on a 10-point scale, with no change at 6 months postconsult. However, 41% of patients overall had a median 3.3-point drop in pain score, 17% had no change in pain score, and 42% had a median 2.6-point increase in pain score.

Electronic Consults

Table 2 describes the reasons eConsults were requested. The most common reason was to taper the dose to be in compliance with the CDC 2016 guideline recommendation of MEDD < 90 mg, which was later increased to 100 mg by the VA/DoD guideline.