Federal Practitioner

In 2019, diabetes mellitus (DM) was the seventh leading cause of death in the United States, and currently, about 11% of the American population has a DM diagnosis.¹ Most have a diagnosis of type 2 diabetes (T2DM), which has a strong genetic predisposition, and the risk of developing T2DM increases with age, obesity, and lack of physical activity.^1,2 Nearly one-quarter of veterans have a diagnosis of DM, and DM is the leading cause of comorbidities, such as blindness, end-stage renal disease, and amputation for patients receiving care from the Veterans Health Administration (VHA).² The elevated incidence of DM in the veteran population is attributed to a variety of factors, including exposure to herbicides, such as Agent Orange, advanced age, increased risk of obesity, and limited access to high-quality food.³

After diagnosis, both the American Diabetes Association (ADA) and the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) emphasize the appropriate use of lifestyle management and pharmacologic therapy for DM care. The use of pharmacologic agents (oral medications, insulin, or noninsulin injectables) is often determined by efficacy, cost, potential adverse effects (AEs), and patient factors and comorbidities.^4,5

The initial recommendation for pharmacologic treatment for T2DM differs slightly between expert guidelines. The ADA and AACE/ACE recommend any of the following as initial monotherapy, listed in order to represent a hierarchy of usage: metformin, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), sodium-glucose cotransporter 2 (SGLT-2) inhibitors, or dipeptidyl peptidase-4 (DPP-4) inhibitors, with the first 3 agents carrying the strongest recommendations.^4,5 For patients with established atherosclerotic cardiovascular disease (CVD), chronic kidney disease, or heart failure, it is recommended to start a long-acting GLP-1 RA or SGLT-2 inhibitor. For patients with T2DM and hemoglobin A_1c (HbA_1c) between 7.5% and 9.0% at diagnosis, the AACE/ACE recommend initiation of dual therapy using metformin alongside another first-line agent and recommend the addition of another antidiabetic agent if glycemic goals are not met after regular follow-up. AACE/ACE recommend the consideration of insulin therapy in symptomatic patients with HbA_1c > 9.0%.⁵ In contrast, the ADA recommends metformin as first-line therapy for all patients with T2DM and recommends dual therapy using metformin and another preferred agent (selection based on comorbidities) when HbA_1c is 1.5% to 2% above target. The ADA recommends the consideration of insulin with HbA_1c > 10% or with evidence of ongoing catabolism or symptoms of hyperglycemia.⁴ There are several reasons why insulin may be initiated prior to GLP-1 RAs, including profound hyperglycemia at time of diagnosis or implementation of insulin agents prior to commercial availability of GLP-1 RA.

GLP-1 RAs are analogs of the hormone incretin, which increases glucose-dependent insulin secretion, decreases postprandial glucagon secretion, increases satiety, and slows gastric emptying.^6,7 When used in combination with noninsulin agents, GLP-1 RAs have demonstrated HbA_1c reductions of 0.5% to 1.5%.⁸ The use of GLP-1 RAs with basal insulin also has been studied extensively.^6,8-10 When the combination of GLP-1 RAs and basal insulin was compared with basal/bolus insulin regimens, the use of the GLP-1 RAs resulted in lower HbA_1c levels and lower incidence of hypoglycemia.^6,9 Data have demonstrated the complementary mechanisms of using basal insulin and GLP 1 RAs in decreasing HbA_1c levels, insulin requirements, and weight compared with using basal insulin monotherapy and basal/bolus combinations.^6,9-13 Moreover, 3 GLP-1 RA medications currently on the market (liraglutide, dulaglutide, and semaglutide) have displayed cardiovascular and renal benefits, further supporting the use of these medications.^2,5

Despite these benefits, GLP-1 RAs may have bothersome AEs and are associated with a high cost.⁶ In addition, some studies have found that as the length of therapy increases, the positive effects of these agents may diminish.^9,11 In one study, which looked at the impact of the addition of exenatide to patients taking basal or basal/bolus insulin regimens, mean changes in weight were −2.4 kg at 0 to 6 months, −4.3 kg at 6 to 12 months, −6.2 kg at 12 to 18 months, and −5.5 kg at 18 to 27 months. After 18 months, an increase in weight was observed, but the increase remained lower than baseline.¹¹ Another study, conducted over 12 months, found no significant decrease in weight or total daily dose (TDD) of insulin when exenatide or liraglutide were added to various insulin regimens (basal or basal/bolus).¹³ To date, minimal published data exist regarding the addition of newer GLP-1 RAs and the long-term use of these agents beyond 12 months in patients taking basal/bolus insulin regimens. The primary goal of this study was to evaluate the effect of adding GLP-1 RAs to basal/bolus insulin regimens over a 24-month period.

Methods

This study was a retrospective, electronic health record review of all patients on basal and bolus insulin regimens who received additional therapy with a GLP-1 RA at Veteran Health Indiana in Indianapolis from September 1, 2015, to June 30, 2019. Patients meeting inclusion criteria served as their own control. The primary outcome was change in HbA_1c at 3, 6, 12, 18, and 24 months after initiation of the GLP-1 RA. Secondary outcomes included change in weight and TDD of insulin at 3, 6, 12, 18, and 24 months after the initiation of the GLP-1 RAs and incidence of patient-reported or laboratory-confirmed hypoglycemia and other AEs.

Patients were included if they were aged ≥ 18 years with a diagnosis of T2DM, had concomitant prescriptions for both a basal insulin (glargine, detemir, or NPH) and a bolus insulin (aspart, lispro, or regular) before receiving add-on therapy with a GLP-1 RA (exenatide, liraglutide, albiglutide, lixisenatide, dulaglutide, or semaglutide) from September 1, 2015, to June 30, 2019, and had baseline and subsequent Hb A_1c measurements available in the electronic health record. Patients were excluded if they had a diagnosis of T1DM, were followed by an outside clinician for DM care, or if the GLP-1 RA was discontinued before subsequent HbA_1c measurement. The study protocol was approved by the Research and Development Office of Veteran Health Indiana, and the project was deemed exempt from review by the Indiana University Institutional Review Board due to the retrospective nature of the study.

Data analysis was performed using Excel. Change from baseline for each interval was computed, and 1 sample t tests (2-tailed) compared change from baseline to no change. Due to the disparity in the number of patients with data available at each of the time intervals, a mean plot was presented for each group of patients within each interval, allowing mean changes in individual groups to be observed over time.

Results

One hundred twenty-three subjects met inclusion criteria; 16 patients were excluded due to GLP-1 RA discontinuation before follow-up measurement of HbA_1c; 14 were excluded due to patients being managed by a clinician outside of the facility; 1 patient was excluded for lack of documentation regarding baseline and subsequent insulin doses. Ninety-two patient charts were reviewed. Participants had a mean age of 64 years, 95% were male, and 89% were White. Mean baseline Hb A_1c was 9.2%, mean body mass index was 38.9, and the mean TDD of insulin was 184 units. Mean duration of DM was 10 years, and mean use of basal/bolus insulin regimen was 6.1 years. Most participants (91%) used an insulin regimen containing insulin glargine and insulin aspart; the remaining participants used insulin detemir and insulin aspart. Semaglutide and liraglutide were the most commonly used GLP-1 RAs (44% and 39%, respectively) (Table 1).

Since some patients switched between GLP-1 RAs throughout the study and there was variation in timing of laboratory and clinic follow-up, a different number of patient charts were available for review at each period (Table 2). Glycemic control was significantly improved at all time points when compared with baseline, but over time the benefit declined. The mean change in HbA_1c was −1.1% (95% CI, −1.3 to −0.8; P < .001) at 3 months; −1.0% (95% CI, −1.3 to −0.7; P < .001) at 6 months; −0.9% (95% CI, −1.3 to −0.6; P < .001) at 12 months; −0.9% (95% CI −1.4 to −0.3; P = .002) at 18 months; and −0.7% (95% CI, −1.4 to 0.1; P = .07) at 24 months (Figure 1). Mean weight decreased from baseline −2.7 kg (95% CI, −3.7 to −1.6; P < .001); −4.4 kg (95% CI −5.7 to −3.2; P < .001) at 6 months; −3.9 kg (95% CI −6.0 to −1.9; P < .001) at 12 months; −4.7 kg (95% CI −6.7 to −2.6; P < .001) at 18 months; and −2.8 kg (95% CI, −5.9 to 0.3; P = .07) at 24 months (Figure 2). Mean TDD decreased at 3 months −12 units (95% CI, −19 to −5; P < .001); −18 units (95% CI, −27 to −9; P < .001) at 6 months; −14 units (95% CI, −24 to −5; P = .004) at 12 months; −9 units (95% CI, −21 to 3; P = .15) at 18 months; and −18 units (95% CI, −43 to 5 units; P = .12) at 24 months (Figure 3). The most common AEs were hypoglycemia (30%), diarrhea (11%), nausea (4%), and abdominal pain (3%).

Discussion

Adding a GLP-1 RA to basal/bolus insulin regimens was associated with a statistically significant decrease in HbA_1c at each time point through 18 months. The greatest improvement in glycemic control from baseline was seen at 3 months, with improvements in HbA_1c diminishing at each subsequent period. The study also demonstrated a significant decrease in weight at each time point through 18 months. The greatest decrease in weight was observed at both 6 and 12 months. Statistically significant decreases in TDD were observed at 3, 6, and 12 months. Insulin changes after 12 months were not found to be statistically significant.

Few studies have previously evaluated the use of GLP-1 RAs in patients with T2DM who are already taking basal/bolus insulin regimens. Gyorffy and colleagues reported significant improvements in glycemic control at 3 and 6 months in a sample of 54 patients taking basal/bolus insulin when liraglutide or exenatide was added, although statistical significance was not found at the final 12-month time point.¹³ That study also found a significant decrease in weight at 6 months; however there was not a significant reduction in weight at both 3 and 12 months of GLP-1 RA therapy. There was not a significant decrease in TDD at any of the collected time points. Nonetheless, Gyorffy and colleagues concluded that reduction in TDD leveled off after 12 months, which is consistent with this study’s findings. The small size of the study may have limited the ability to detect statistical significance; however, this study was conducted in a population that was racially diverse and included a higher proportion of women, though average age was similar.¹³

Yoon and colleagues reported weight loss through 18 months, then saw weight increase, though weights did remain lover than baseline. The study also showed no significant change in TDD of insulin after 12 months of concomitant exenatide and insulin therapy.¹¹ Although these results mirror the outcomes observed in this study, Yoon and colleagues did not differentiate results between basal and basal/bolus insulin groups.¹¹ Seino and colleagues observed no significant change in weight after 36 weeks of GLP-1 RA therapy in Japanese patients when used with basal and basal/bolus insulin regimens. Despite the consideration that the population in the study was not overweight (mean body mass index was 25.6), the results of these studies support the idea that effects of GLP-1 RAs on weight and TDD may diminish over time.¹⁴

Within the VHA, GLP-1 RAs are nonformulary medications. Patients must meet certain criteria in order to be approved for these agents, which may include diagnosis of CVD, renal disease, or failure to reach glycemic control with the use of oral agents or insulin. Therefore, participants of this study represent a particular subset of VHA patients, many of whom may have been selected for consideration due to long-standing or uncontrolled T2DM and failure of previous therapies. The baseline demographics support this idea, given poor glycemic control at baseline and high insulin requirements. Once approved for GLP-1 RA therapy, semaglutide is currently the preferred agent within the VHA, with other agents being available for select considerations. It should be noted that albiglutide, which was the primary agent selected for some of the patients included in this study, was removed from the market in 2017 for economic considerations.¹⁵ In the case for these patients, a conversion to a formulary-preferred GLP-1 RA was made.

Most of the patients included in this study (70%) were maintained on metformin from baseline throughout the study period. Fifty-seven percent of patients were taking TDD of insulin > 150 units. Considering the significant cost of concentrated insulins, the addition of GLP-1 RAs to standard insulin may prove to be beneficial from a cost standpoint. Additional research in this area may be warranted to establish more data regarding this potential benefit of GLP-1 RAs as add-on therapy.

Limitations and Strengths

Limitations of this study include a small patient population and a gradual reduction in available data as time periods progressed, making even smaller sample sizes for subsequent time periods. A majority of participants were older males of White race. This could have limited the determination of statistical significance and applicability of the results to other patient populations. Another potential limitation was the retrospective nature of the study design, which may have limited reporting of hypoglycemia and other AEs based on the documentation of the clinician.

Strengths included the length of study duration and the diversity of GLP-1 RAs used by participants, as the impact of many of these agents has not yet been assessed in the literature. In addition, the retrospective nature of the study allows for a more realistic representation of patient adherence, education, and motivation, which are likely different from those of patients included in prospective clinical trials.

There are no clear guidelines dictating the optimal duration of concomitant GLP-1 RA and insulin therapy; however, our study suggests that there may be continued benefits past short-term use. Also our study suggests that patients with T2DM treated with basal/bolus insulin regimens may glean additional benefit from adding GLP-1 RAs; however, further randomized, controlled studies are warranted, particularly in poorly controlled patients requiring even more aggressive treatment regimens, such as concentrated insulins.

Conclusions

In our study, adding GLP-1 RA to basal/bolus insulin was associated with a significant decrease in HbA_1c from baseline through 18 months. An overall decrease in weight and TDD of insulin was observed through 24 months, but the change in weight was not significant past 18 months, and the change in insulin requirement was not significant past 12 months. Hypoglycemia was observed in almost one-third of patients, and gastrointestinal symptoms were the most common AE observed as a result adding GLP-1 RAs. More studies are needed to better evaluate the durability and cost benefit of GLP-1 RAs, especially in patients with high insulin requirements.

Acknowledgments

This material is the result of work supported with resources and facilities at Veteran Health Indiana in Indianapolis. Study data were collected and managed using REDCap electronic data capture tools hosted at Veteran Health Indiana. The authors also acknowledge George Eckert for his assistance with data analysis.

In 2019, diabetes mellitus (DM) was the seventh leading cause of death in the United States, and currently, about 11% of the American population has a DM diagnosis.¹ Most have a diagnosis of type 2 diabetes (T2DM), which has a strong genetic predisposition, and the risk of developing T2DM increases with age, obesity, and lack of physical activity.^1,2 Nearly one-quarter of veterans have a diagnosis of DM, and DM is the leading cause of comorbidities, such as blindness, end-stage renal disease, and amputation for patients receiving care from the Veterans Health Administration (VHA).² The elevated incidence of DM in the veteran population is attributed to a variety of factors, including exposure to herbicides, such as Agent Orange, advanced age, increased risk of obesity, and limited access to high-quality food.³

After diagnosis, both the American Diabetes Association (ADA) and the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) emphasize the appropriate use of lifestyle management and pharmacologic therapy for DM care. The use of pharmacologic agents (oral medications, insulin, or noninsulin injectables) is often determined by efficacy, cost, potential adverse effects (AEs), and patient factors and comorbidities.^4,5

The initial recommendation for pharmacologic treatment for T2DM differs slightly between expert guidelines. The ADA and AACE/ACE recommend any of the following as initial monotherapy, listed in order to represent a hierarchy of usage: metformin, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), sodium-glucose cotransporter 2 (SGLT-2) inhibitors, or dipeptidyl peptidase-4 (DPP-4) inhibitors, with the first 3 agents carrying the strongest recommendations.^4,5 For patients with established atherosclerotic cardiovascular disease (CVD), chronic kidney disease, or heart failure, it is recommended to start a long-acting GLP-1 RA or SGLT-2 inhibitor. For patients with T2DM and hemoglobin A_1c (HbA_1c) between 7.5% and 9.0% at diagnosis, the AACE/ACE recommend initiation of dual therapy using metformin alongside another first-line agent and recommend the addition of another antidiabetic agent if glycemic goals are not met after regular follow-up. AACE/ACE recommend the consideration of insulin therapy in symptomatic patients with HbA_1c > 9.0%.⁵ In contrast, the ADA recommends metformin as first-line therapy for all patients with T2DM and recommends dual therapy using metformin and another preferred agent (selection based on comorbidities) when HbA_1c is 1.5% to 2% above target. The ADA recommends the consideration of insulin with HbA_1c > 10% or with evidence of ongoing catabolism or symptoms of hyperglycemia.⁴ There are several reasons why insulin may be initiated prior to GLP-1 RAs, including profound hyperglycemia at time of diagnosis or implementation of insulin agents prior to commercial availability of GLP-1 RA.

GLP-1 RAs are analogs of the hormone incretin, which increases glucose-dependent insulin secretion, decreases postprandial glucagon secretion, increases satiety, and slows gastric emptying.^6,7 When used in combination with noninsulin agents, GLP-1 RAs have demonstrated HbA_1c reductions of 0.5% to 1.5%.⁸ The use of GLP-1 RAs with basal insulin also has been studied extensively.^6,8-10 When the combination of GLP-1 RAs and basal insulin was compared with basal/bolus insulin regimens, the use of the GLP-1 RAs resulted in lower HbA_1c levels and lower incidence of hypoglycemia.^6,9 Data have demonstrated the complementary mechanisms of using basal insulin and GLP 1 RAs in decreasing HbA_1c levels, insulin requirements, and weight compared with using basal insulin monotherapy and basal/bolus combinations.^6,9-13 Moreover, 3 GLP-1 RA medications currently on the market (liraglutide, dulaglutide, and semaglutide) have displayed cardiovascular and renal benefits, further supporting the use of these medications.^2,5

Despite these benefits, GLP-1 RAs may have bothersome AEs and are associated with a high cost.⁶ In addition, some studies have found that as the length of therapy increases, the positive effects of these agents may diminish.^9,11 In one study, which looked at the impact of the addition of exenatide to patients taking basal or basal/bolus insulin regimens, mean changes in weight were −2.4 kg at 0 to 6 months, −4.3 kg at 6 to 12 months, −6.2 kg at 12 to 18 months, and −5.5 kg at 18 to 27 months. After 18 months, an increase in weight was observed, but the increase remained lower than baseline.¹¹ Another study, conducted over 12 months, found no significant decrease in weight or total daily dose (TDD) of insulin when exenatide or liraglutide were added to various insulin regimens (basal or basal/bolus).¹³ To date, minimal published data exist regarding the addition of newer GLP-1 RAs and the long-term use of these agents beyond 12 months in patients taking basal/bolus insulin regimens. The primary goal of this study was to evaluate the effect of adding GLP-1 RAs to basal/bolus insulin regimens over a 24-month period.

Methods

This study was a retrospective, electronic health record review of all patients on basal and bolus insulin regimens who received additional therapy with a GLP-1 RA at Veteran Health Indiana in Indianapolis from September 1, 2015, to June 30, 2019. Patients meeting inclusion criteria served as their own control. The primary outcome was change in HbA_1c at 3, 6, 12, 18, and 24 months after initiation of the GLP-1 RA. Secondary outcomes included change in weight and TDD of insulin at 3, 6, 12, 18, and 24 months after the initiation of the GLP-1 RAs and incidence of patient-reported or laboratory-confirmed hypoglycemia and other AEs.

Patients were included if they were aged ≥ 18 years with a diagnosis of T2DM, had concomitant prescriptions for both a basal insulin (glargine, detemir, or NPH) and a bolus insulin (aspart, lispro, or regular) before receiving add-on therapy with a GLP-1 RA (exenatide, liraglutide, albiglutide, lixisenatide, dulaglutide, or semaglutide) from September 1, 2015, to June 30, 2019, and had baseline and subsequent Hb A_1c measurements available in the electronic health record. Patients were excluded if they had a diagnosis of T1DM, were followed by an outside clinician for DM care, or if the GLP-1 RA was discontinued before subsequent HbA_1c measurement. The study protocol was approved by the Research and Development Office of Veteran Health Indiana, and the project was deemed exempt from review by the Indiana University Institutional Review Board due to the retrospective nature of the study.

Data analysis was performed using Excel. Change from baseline for each interval was computed, and 1 sample t tests (2-tailed) compared change from baseline to no change. Due to the disparity in the number of patients with data available at each of the time intervals, a mean plot was presented for each group of patients within each interval, allowing mean changes in individual groups to be observed over time.

Results

One hundred twenty-three subjects met inclusion criteria; 16 patients were excluded due to GLP-1 RA discontinuation before follow-up measurement of HbA_1c; 14 were excluded due to patients being managed by a clinician outside of the facility; 1 patient was excluded for lack of documentation regarding baseline and subsequent insulin doses. Ninety-two patient charts were reviewed. Participants had a mean age of 64 years, 95% were male, and 89% were White. Mean baseline Hb A_1c was 9.2%, mean body mass index was 38.9, and the mean TDD of insulin was 184 units. Mean duration of DM was 10 years, and mean use of basal/bolus insulin regimen was 6.1 years. Most participants (91%) used an insulin regimen containing insulin glargine and insulin aspart; the remaining participants used insulin detemir and insulin aspart. Semaglutide and liraglutide were the most commonly used GLP-1 RAs (44% and 39%, respectively) (Table 1).

Since some patients switched between GLP-1 RAs throughout the study and there was variation in timing of laboratory and clinic follow-up, a different number of patient charts were available for review at each period (Table 2). Glycemic control was significantly improved at all time points when compared with baseline, but over time the benefit declined. The mean change in HbA_1c was −1.1% (95% CI, −1.3 to −0.8; P < .001) at 3 months; −1.0% (95% CI, −1.3 to −0.7; P < .001) at 6 months; −0.9% (95% CI, −1.3 to −0.6; P < .001) at 12 months; −0.9% (95% CI −1.4 to −0.3; P = .002) at 18 months; and −0.7% (95% CI, −1.4 to 0.1; P = .07) at 24 months (Figure 1). Mean weight decreased from baseline −2.7 kg (95% CI, −3.7 to −1.6; P < .001); −4.4 kg (95% CI −5.7 to −3.2; P < .001) at 6 months; −3.9 kg (95% CI −6.0 to −1.9; P < .001) at 12 months; −4.7 kg (95% CI −6.7 to −2.6; P < .001) at 18 months; and −2.8 kg (95% CI, −5.9 to 0.3; P = .07) at 24 months (Figure 2). Mean TDD decreased at 3 months −12 units (95% CI, −19 to −5; P < .001); −18 units (95% CI, −27 to −9; P < .001) at 6 months; −14 units (95% CI, −24 to −5; P = .004) at 12 months; −9 units (95% CI, −21 to 3; P = .15) at 18 months; and −18 units (95% CI, −43 to 5 units; P = .12) at 24 months (Figure 3). The most common AEs were hypoglycemia (30%), diarrhea (11%), nausea (4%), and abdominal pain (3%).

Discussion

Adding a GLP-1 RA to basal/bolus insulin regimens was associated with a statistically significant decrease in HbA_1c at each time point through 18 months. The greatest improvement in glycemic control from baseline was seen at 3 months, with improvements in HbA_1c diminishing at each subsequent period. The study also demonstrated a significant decrease in weight at each time point through 18 months. The greatest decrease in weight was observed at both 6 and 12 months. Statistically significant decreases in TDD were observed at 3, 6, and 12 months. Insulin changes after 12 months were not found to be statistically significant.

Few studies have previously evaluated the use of GLP-1 RAs in patients with T2DM who are already taking basal/bolus insulin regimens. Gyorffy and colleagues reported significant improvements in glycemic control at 3 and 6 months in a sample of 54 patients taking basal/bolus insulin when liraglutide or exenatide was added, although statistical significance was not found at the final 12-month time point.¹³ That study also found a significant decrease in weight at 6 months; however there was not a significant reduction in weight at both 3 and 12 months of GLP-1 RA therapy. There was not a significant decrease in TDD at any of the collected time points. Nonetheless, Gyorffy and colleagues concluded that reduction in TDD leveled off after 12 months, which is consistent with this study’s findings. The small size of the study may have limited the ability to detect statistical significance; however, this study was conducted in a population that was racially diverse and included a higher proportion of women, though average age was similar.¹³

Yoon and colleagues reported weight loss through 18 months, then saw weight increase, though weights did remain lover than baseline. The study also showed no significant change in TDD of insulin after 12 months of concomitant exenatide and insulin therapy.¹¹ Although these results mirror the outcomes observed in this study, Yoon and colleagues did not differentiate results between basal and basal/bolus insulin groups.¹¹ Seino and colleagues observed no significant change in weight after 36 weeks of GLP-1 RA therapy in Japanese patients when used with basal and basal/bolus insulin regimens. Despite the consideration that the population in the study was not overweight (mean body mass index was 25.6), the results of these studies support the idea that effects of GLP-1 RAs on weight and TDD may diminish over time.¹⁴

Within the VHA, GLP-1 RAs are nonformulary medications. Patients must meet certain criteria in order to be approved for these agents, which may include diagnosis of CVD, renal disease, or failure to reach glycemic control with the use of oral agents or insulin. Therefore, participants of this study represent a particular subset of VHA patients, many of whom may have been selected for consideration due to long-standing or uncontrolled T2DM and failure of previous therapies. The baseline demographics support this idea, given poor glycemic control at baseline and high insulin requirements. Once approved for GLP-1 RA therapy, semaglutide is currently the preferred agent within the VHA, with other agents being available for select considerations. It should be noted that albiglutide, which was the primary agent selected for some of the patients included in this study, was removed from the market in 2017 for economic considerations.¹⁵ In the case for these patients, a conversion to a formulary-preferred GLP-1 RA was made.

Most of the patients included in this study (70%) were maintained on metformin from baseline throughout the study period. Fifty-seven percent of patients were taking TDD of insulin > 150 units. Considering the significant cost of concentrated insulins, the addition of GLP-1 RAs to standard insulin may prove to be beneficial from a cost standpoint. Additional research in this area may be warranted to establish more data regarding this potential benefit of GLP-1 RAs as add-on therapy.

Limitations and Strengths

Limitations of this study include a small patient population and a gradual reduction in available data as time periods progressed, making even smaller sample sizes for subsequent time periods. A majority of participants were older males of White race. This could have limited the determination of statistical significance and applicability of the results to other patient populations. Another potential limitation was the retrospective nature of the study design, which may have limited reporting of hypoglycemia and other AEs based on the documentation of the clinician.

Strengths included the length of study duration and the diversity of GLP-1 RAs used by participants, as the impact of many of these agents has not yet been assessed in the literature. In addition, the retrospective nature of the study allows for a more realistic representation of patient adherence, education, and motivation, which are likely different from those of patients included in prospective clinical trials.

There are no clear guidelines dictating the optimal duration of concomitant GLP-1 RA and insulin therapy; however, our study suggests that there may be continued benefits past short-term use. Also our study suggests that patients with T2DM treated with basal/bolus insulin regimens may glean additional benefit from adding GLP-1 RAs; however, further randomized, controlled studies are warranted, particularly in poorly controlled patients requiring even more aggressive treatment regimens, such as concentrated insulins.

Conclusions

In our study, adding GLP-1 RA to basal/bolus insulin was associated with a significant decrease in HbA_1c from baseline through 18 months. An overall decrease in weight and TDD of insulin was observed through 24 months, but the change in weight was not significant past 18 months, and the change in insulin requirement was not significant past 12 months. Hypoglycemia was observed in almost one-third of patients, and gastrointestinal symptoms were the most common AE observed as a result adding GLP-1 RAs. More studies are needed to better evaluate the durability and cost benefit of GLP-1 RAs, especially in patients with high insulin requirements.

Acknowledgments

This material is the result of work supported with resources and facilities at Veteran Health Indiana in Indianapolis. Study data were collected and managed using REDCap electronic data capture tools hosted at Veteran Health Indiana. The authors also acknowledge George Eckert for his assistance with data analysis.

In 2019, diabetes mellitus (DM) was the seventh leading cause of death in the United States, and currently, about 11% of the American population has a DM diagnosis.¹ Most have a diagnosis of type 2 diabetes (T2DM), which has a strong genetic predisposition, and the risk of developing T2DM increases with age, obesity, and lack of physical activity.^1,2 Nearly one-quarter of veterans have a diagnosis of DM, and DM is the leading cause of comorbidities, such as blindness, end-stage renal disease, and amputation for patients receiving care from the Veterans Health Administration (VHA).² The elevated incidence of DM in the veteran population is attributed to a variety of factors, including exposure to herbicides, such as Agent Orange, advanced age, increased risk of obesity, and limited access to high-quality food.³

After diagnosis, both the American Diabetes Association (ADA) and the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) emphasize the appropriate use of lifestyle management and pharmacologic therapy for DM care. The use of pharmacologic agents (oral medications, insulin, or noninsulin injectables) is often determined by efficacy, cost, potential adverse effects (AEs), and patient factors and comorbidities.^4,5

The initial recommendation for pharmacologic treatment for T2DM differs slightly between expert guidelines. The ADA and AACE/ACE recommend any of the following as initial monotherapy, listed in order to represent a hierarchy of usage: metformin, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), sodium-glucose cotransporter 2 (SGLT-2) inhibitors, or dipeptidyl peptidase-4 (DPP-4) inhibitors, with the first 3 agents carrying the strongest recommendations.^4,5 For patients with established atherosclerotic cardiovascular disease (CVD), chronic kidney disease, or heart failure, it is recommended to start a long-acting GLP-1 RA or SGLT-2 inhibitor. For patients with T2DM and hemoglobin A_1c (HbA_1c) between 7.5% and 9.0% at diagnosis, the AACE/ACE recommend initiation of dual therapy using metformin alongside another first-line agent and recommend the addition of another antidiabetic agent if glycemic goals are not met after regular follow-up. AACE/ACE recommend the consideration of insulin therapy in symptomatic patients with HbA_1c > 9.0%.⁵ In contrast, the ADA recommends metformin as first-line therapy for all patients with T2DM and recommends dual therapy using metformin and another preferred agent (selection based on comorbidities) when HbA_1c is 1.5% to 2% above target. The ADA recommends the consideration of insulin with HbA_1c > 10% or with evidence of ongoing catabolism or symptoms of hyperglycemia.⁴ There are several reasons why insulin may be initiated prior to GLP-1 RAs, including profound hyperglycemia at time of diagnosis or implementation of insulin agents prior to commercial availability of GLP-1 RA.

GLP-1 RAs are analogs of the hormone incretin, which increases glucose-dependent insulin secretion, decreases postprandial glucagon secretion, increases satiety, and slows gastric emptying.^6,7 When used in combination with noninsulin agents, GLP-1 RAs have demonstrated HbA_1c reductions of 0.5% to 1.5%.⁸ The use of GLP-1 RAs with basal insulin also has been studied extensively.^6,8-10 When the combination of GLP-1 RAs and basal insulin was compared with basal/bolus insulin regimens, the use of the GLP-1 RAs resulted in lower HbA_1c levels and lower incidence of hypoglycemia.^6,9 Data have demonstrated the complementary mechanisms of using basal insulin and GLP 1 RAs in decreasing HbA_1c levels, insulin requirements, and weight compared with using basal insulin monotherapy and basal/bolus combinations.^6,9-13 Moreover, 3 GLP-1 RA medications currently on the market (liraglutide, dulaglutide, and semaglutide) have displayed cardiovascular and renal benefits, further supporting the use of these medications.^2,5

Despite these benefits, GLP-1 RAs may have bothersome AEs and are associated with a high cost.⁶ In addition, some studies have found that as the length of therapy increases, the positive effects of these agents may diminish.^9,11 In one study, which looked at the impact of the addition of exenatide to patients taking basal or basal/bolus insulin regimens, mean changes in weight were −2.4 kg at 0 to 6 months, −4.3 kg at 6 to 12 months, −6.2 kg at 12 to 18 months, and −5.5 kg at 18 to 27 months. After 18 months, an increase in weight was observed, but the increase remained lower than baseline.¹¹ Another study, conducted over 12 months, found no significant decrease in weight or total daily dose (TDD) of insulin when exenatide or liraglutide were added to various insulin regimens (basal or basal/bolus).¹³ To date, minimal published data exist regarding the addition of newer GLP-1 RAs and the long-term use of these agents beyond 12 months in patients taking basal/bolus insulin regimens. The primary goal of this study was to evaluate the effect of adding GLP-1 RAs to basal/bolus insulin regimens over a 24-month period.

Methods

This study was a retrospective, electronic health record review of all patients on basal and bolus insulin regimens who received additional therapy with a GLP-1 RA at Veteran Health Indiana in Indianapolis from September 1, 2015, to June 30, 2019. Patients meeting inclusion criteria served as their own control. The primary outcome was change in HbA_1c at 3, 6, 12, 18, and 24 months after initiation of the GLP-1 RA. Secondary outcomes included change in weight and TDD of insulin at 3, 6, 12, 18, and 24 months after the initiation of the GLP-1 RAs and incidence of patient-reported or laboratory-confirmed hypoglycemia and other AEs.

Patients were included if they were aged ≥ 18 years with a diagnosis of T2DM, had concomitant prescriptions for both a basal insulin (glargine, detemir, or NPH) and a bolus insulin (aspart, lispro, or regular) before receiving add-on therapy with a GLP-1 RA (exenatide, liraglutide, albiglutide, lixisenatide, dulaglutide, or semaglutide) from September 1, 2015, to June 30, 2019, and had baseline and subsequent Hb A_1c measurements available in the electronic health record. Patients were excluded if they had a diagnosis of T1DM, were followed by an outside clinician for DM care, or if the GLP-1 RA was discontinued before subsequent HbA_1c measurement. The study protocol was approved by the Research and Development Office of Veteran Health Indiana, and the project was deemed exempt from review by the Indiana University Institutional Review Board due to the retrospective nature of the study.

Data analysis was performed using Excel. Change from baseline for each interval was computed, and 1 sample t tests (2-tailed) compared change from baseline to no change. Due to the disparity in the number of patients with data available at each of the time intervals, a mean plot was presented for each group of patients within each interval, allowing mean changes in individual groups to be observed over time.

Results

One hundred twenty-three subjects met inclusion criteria; 16 patients were excluded due to GLP-1 RA discontinuation before follow-up measurement of HbA_1c; 14 were excluded due to patients being managed by a clinician outside of the facility; 1 patient was excluded for lack of documentation regarding baseline and subsequent insulin doses. Ninety-two patient charts were reviewed. Participants had a mean age of 64 years, 95% were male, and 89% were White. Mean baseline Hb A_1c was 9.2%, mean body mass index was 38.9, and the mean TDD of insulin was 184 units. Mean duration of DM was 10 years, and mean use of basal/bolus insulin regimen was 6.1 years. Most participants (91%) used an insulin regimen containing insulin glargine and insulin aspart; the remaining participants used insulin detemir and insulin aspart. Semaglutide and liraglutide were the most commonly used GLP-1 RAs (44% and 39%, respectively) (Table 1).

Since some patients switched between GLP-1 RAs throughout the study and there was variation in timing of laboratory and clinic follow-up, a different number of patient charts were available for review at each period (Table 2). Glycemic control was significantly improved at all time points when compared with baseline, but over time the benefit declined. The mean change in HbA_1c was −1.1% (95% CI, −1.3 to −0.8; P < .001) at 3 months; −1.0% (95% CI, −1.3 to −0.7; P < .001) at 6 months; −0.9% (95% CI, −1.3 to −0.6; P < .001) at 12 months; −0.9% (95% CI −1.4 to −0.3; P = .002) at 18 months; and −0.7% (95% CI, −1.4 to 0.1; P = .07) at 24 months (Figure 1). Mean weight decreased from baseline −2.7 kg (95% CI, −3.7 to −1.6; P < .001); −4.4 kg (95% CI −5.7 to −3.2; P < .001) at 6 months; −3.9 kg (95% CI −6.0 to −1.9; P < .001) at 12 months; −4.7 kg (95% CI −6.7 to −2.6; P < .001) at 18 months; and −2.8 kg (95% CI, −5.9 to 0.3; P = .07) at 24 months (Figure 2). Mean TDD decreased at 3 months −12 units (95% CI, −19 to −5; P < .001); −18 units (95% CI, −27 to −9; P < .001) at 6 months; −14 units (95% CI, −24 to −5; P = .004) at 12 months; −9 units (95% CI, −21 to 3; P = .15) at 18 months; and −18 units (95% CI, −43 to 5 units; P = .12) at 24 months (Figure 3). The most common AEs were hypoglycemia (30%), diarrhea (11%), nausea (4%), and abdominal pain (3%).

Discussion

Adding a GLP-1 RA to basal/bolus insulin regimens was associated with a statistically significant decrease in HbA_1c at each time point through 18 months. The greatest improvement in glycemic control from baseline was seen at 3 months, with improvements in HbA_1c diminishing at each subsequent period. The study also demonstrated a significant decrease in weight at each time point through 18 months. The greatest decrease in weight was observed at both 6 and 12 months. Statistically significant decreases in TDD were observed at 3, 6, and 12 months. Insulin changes after 12 months were not found to be statistically significant.

Few studies have previously evaluated the use of GLP-1 RAs in patients with T2DM who are already taking basal/bolus insulin regimens. Gyorffy and colleagues reported significant improvements in glycemic control at 3 and 6 months in a sample of 54 patients taking basal/bolus insulin when liraglutide or exenatide was added, although statistical significance was not found at the final 12-month time point.¹³ That study also found a significant decrease in weight at 6 months; however there was not a significant reduction in weight at both 3 and 12 months of GLP-1 RA therapy. There was not a significant decrease in TDD at any of the collected time points. Nonetheless, Gyorffy and colleagues concluded that reduction in TDD leveled off after 12 months, which is consistent with this study’s findings. The small size of the study may have limited the ability to detect statistical significance; however, this study was conducted in a population that was racially diverse and included a higher proportion of women, though average age was similar.¹³

Yoon and colleagues reported weight loss through 18 months, then saw weight increase, though weights did remain lover than baseline. The study also showed no significant change in TDD of insulin after 12 months of concomitant exenatide and insulin therapy.¹¹ Although these results mirror the outcomes observed in this study, Yoon and colleagues did not differentiate results between basal and basal/bolus insulin groups.¹¹ Seino and colleagues observed no significant change in weight after 36 weeks of GLP-1 RA therapy in Japanese patients when used with basal and basal/bolus insulin regimens. Despite the consideration that the population in the study was not overweight (mean body mass index was 25.6), the results of these studies support the idea that effects of GLP-1 RAs on weight and TDD may diminish over time.¹⁴

Within the VHA, GLP-1 RAs are nonformulary medications. Patients must meet certain criteria in order to be approved for these agents, which may include diagnosis of CVD, renal disease, or failure to reach glycemic control with the use of oral agents or insulin. Therefore, participants of this study represent a particular subset of VHA patients, many of whom may have been selected for consideration due to long-standing or uncontrolled T2DM and failure of previous therapies. The baseline demographics support this idea, given poor glycemic control at baseline and high insulin requirements. Once approved for GLP-1 RA therapy, semaglutide is currently the preferred agent within the VHA, with other agents being available for select considerations. It should be noted that albiglutide, which was the primary agent selected for some of the patients included in this study, was removed from the market in 2017 for economic considerations.¹⁵ In the case for these patients, a conversion to a formulary-preferred GLP-1 RA was made.

Most of the patients included in this study (70%) were maintained on metformin from baseline throughout the study period. Fifty-seven percent of patients were taking TDD of insulin > 150 units. Considering the significant cost of concentrated insulins, the addition of GLP-1 RAs to standard insulin may prove to be beneficial from a cost standpoint. Additional research in this area may be warranted to establish more data regarding this potential benefit of GLP-1 RAs as add-on therapy.

Limitations and Strengths

Limitations of this study include a small patient population and a gradual reduction in available data as time periods progressed, making even smaller sample sizes for subsequent time periods. A majority of participants were older males of White race. This could have limited the determination of statistical significance and applicability of the results to other patient populations. Another potential limitation was the retrospective nature of the study design, which may have limited reporting of hypoglycemia and other AEs based on the documentation of the clinician.

Strengths included the length of study duration and the diversity of GLP-1 RAs used by participants, as the impact of many of these agents has not yet been assessed in the literature. In addition, the retrospective nature of the study allows for a more realistic representation of patient adherence, education, and motivation, which are likely different from those of patients included in prospective clinical trials.

There are no clear guidelines dictating the optimal duration of concomitant GLP-1 RA and insulin therapy; however, our study suggests that there may be continued benefits past short-term use. Also our study suggests that patients with T2DM treated with basal/bolus insulin regimens may glean additional benefit from adding GLP-1 RAs; however, further randomized, controlled studies are warranted, particularly in poorly controlled patients requiring even more aggressive treatment regimens, such as concentrated insulins.

Conclusions

In our study, adding GLP-1 RA to basal/bolus insulin was associated with a significant decrease in HbA_1c from baseline through 18 months. An overall decrease in weight and TDD of insulin was observed through 24 months, but the change in weight was not significant past 18 months, and the change in insulin requirement was not significant past 12 months. Hypoglycemia was observed in almost one-third of patients, and gastrointestinal symptoms were the most common AE observed as a result adding GLP-1 RAs. More studies are needed to better evaluate the durability and cost benefit of GLP-1 RAs, especially in patients with high insulin requirements.

Acknowledgments

This material is the result of work supported with resources and facilities at Veteran Health Indiana in Indianapolis. Study data were collected and managed using REDCap electronic data capture tools hosted at Veteran Health Indiana. The authors also acknowledge George Eckert for his assistance with data analysis.

From our first days as medical students, we are told that politics and religion are topics to be avoided with patients, but I disagree. Knowing more about our patients allows us to deliver better care. I propose that we consider adding politics and religion to our list of risk factors.

Politics and religion: New risk factors

The importance of politics and religion in the health of patients was clearly demonstrated during the COVID-19 pandemic. Lives were needlessly lost because of stands taken based on religious beliefs or a political ideology. Families, friends, and the community at large were impacted.

Over my years of practice, I have found that while these are difficult topics to address, they should not be avoided. Studies have shown that open acknowledgement of religious beliefs can affect both clinical outcomes and well-being. Religion and spirituality are as much a part of our patient’s lives as the physical parameters that we measure. To neglect these significant aspects is to miss the very essence of the individual.

I made it a practice to ask patients about their religious beliefs, the extent to which religion shaped their life, and whether they were part of a church community. Knowing this allowed me to separate deep personal belief from stances based on personal freedom, misinformation, conspiracies, and politics.

I found that information about political leanings flowed naturally in discussions with patients as we trusted and respected each other over time. If I approached politics objectively and nonjudgmentally, it generally led to meaningful conversation. This helped me to understand the patient as an individual and informed my diagnosis and treatment plan.
 

Politics as stress

For example, on more than one occasion, a patient with atrial fibrillation presented with persistent elevated blood pressure and pulse rate despite adherence to the medical regimen that I had prescribed. After a few minutes of discussion, it was clear that excessive attention to political commentary on TV and social media raised their anxiety and anger level, putting them at greater risk for adverse outcomes. I advised that they refocus their leisure activities rather than change or increase medication.

It is disappointing to see how one of the great scientific advances of our lifetime, vaccination science, has been tarnished because of political or religious ideology and to see the extent to which these beliefs influenced COVID-19 vaccination compliance. As health care providers, we must promote information based on the scientific method. If patients challenge us and point out that recommendations based on science seem to change over time, we must explain that science evolves on the basis of new information objectively gathered. We need to find out what information the patient has gotten from the Internet, TV, or conspiracy theories and counter this with scientific facts. If we do not discuss religion and politics with our patients along with other risk factors, we may compromise our ability to give them the best advice and treatment.

Our patients have a right to their own spiritual and political ideology. If it differs dramatically from our own, this should not influence our commitment to care for them. But we have an obligation to challenge unfounded beliefs about medicine and counter with scientific facts. There are times when individual freedoms must be secondary to public health. Ultimately, it is up to the patient to choose, but they should not be given a “free pass” on the basis of religion or politics. If I know something is true and I would do it myself or recommend it for my family, I have an obligation to provide this recommendation to my patients.

Religious preference is included in medical records. It is not appropriate to add political preference, but the patient benefits if a long-term caregiver knows this information.

During the pandemic, for the first time in my 40+ years of practice, some patients questioned my recommendations and placed equal or greater weight on religion, politics, or conspiracy theories. This continues to be a very real struggle.

Knowing and understanding our patients as individuals is critical to providing optimum care and that means tackling these formally taboo topics. If having a potentially uncomfortable conversation with patients allows us to save one life, it is worth it.
 

Dr. Francis is a cardiologist at Inova Heart and Vascular Institute, McLean, Va. He disclosed no relevant conflict of interest. A version of this article first appeared on Medscape.com.

From our first days as medical students, we are told that politics and religion are topics to be avoided with patients, but I disagree. Knowing more about our patients allows us to deliver better care. I propose that we consider adding politics and religion to our list of risk factors.

Politics and religion: New risk factors

The importance of politics and religion in the health of patients was clearly demonstrated during the COVID-19 pandemic. Lives were needlessly lost because of stands taken based on religious beliefs or a political ideology. Families, friends, and the community at large were impacted.

Over my years of practice, I have found that while these are difficult topics to address, they should not be avoided. Studies have shown that open acknowledgement of religious beliefs can affect both clinical outcomes and well-being. Religion and spirituality are as much a part of our patient’s lives as the physical parameters that we measure. To neglect these significant aspects is to miss the very essence of the individual.

I made it a practice to ask patients about their religious beliefs, the extent to which religion shaped their life, and whether they were part of a church community. Knowing this allowed me to separate deep personal belief from stances based on personal freedom, misinformation, conspiracies, and politics.

I found that information about political leanings flowed naturally in discussions with patients as we trusted and respected each other over time. If I approached politics objectively and nonjudgmentally, it generally led to meaningful conversation. This helped me to understand the patient as an individual and informed my diagnosis and treatment plan.
 

Politics as stress

For example, on more than one occasion, a patient with atrial fibrillation presented with persistent elevated blood pressure and pulse rate despite adherence to the medical regimen that I had prescribed. After a few minutes of discussion, it was clear that excessive attention to political commentary on TV and social media raised their anxiety and anger level, putting them at greater risk for adverse outcomes. I advised that they refocus their leisure activities rather than change or increase medication.

It is disappointing to see how one of the great scientific advances of our lifetime, vaccination science, has been tarnished because of political or religious ideology and to see the extent to which these beliefs influenced COVID-19 vaccination compliance. As health care providers, we must promote information based on the scientific method. If patients challenge us and point out that recommendations based on science seem to change over time, we must explain that science evolves on the basis of new information objectively gathered. We need to find out what information the patient has gotten from the Internet, TV, or conspiracy theories and counter this with scientific facts. If we do not discuss religion and politics with our patients along with other risk factors, we may compromise our ability to give them the best advice and treatment.

Our patients have a right to their own spiritual and political ideology. If it differs dramatically from our own, this should not influence our commitment to care for them. But we have an obligation to challenge unfounded beliefs about medicine and counter with scientific facts. There are times when individual freedoms must be secondary to public health. Ultimately, it is up to the patient to choose, but they should not be given a “free pass” on the basis of religion or politics. If I know something is true and I would do it myself or recommend it for my family, I have an obligation to provide this recommendation to my patients.

Religious preference is included in medical records. It is not appropriate to add political preference, but the patient benefits if a long-term caregiver knows this information.

During the pandemic, for the first time in my 40+ years of practice, some patients questioned my recommendations and placed equal or greater weight on religion, politics, or conspiracy theories. This continues to be a very real struggle.

Knowing and understanding our patients as individuals is critical to providing optimum care and that means tackling these formally taboo topics. If having a potentially uncomfortable conversation with patients allows us to save one life, it is worth it.
 

Dr. Francis is a cardiologist at Inova Heart and Vascular Institute, McLean, Va. He disclosed no relevant conflict of interest. A version of this article first appeared on Medscape.com.

From our first days as medical students, we are told that politics and religion are topics to be avoided with patients, but I disagree. Knowing more about our patients allows us to deliver better care. I propose that we consider adding politics and religion to our list of risk factors.

Politics and religion: New risk factors

The importance of politics and religion in the health of patients was clearly demonstrated during the COVID-19 pandemic. Lives were needlessly lost because of stands taken based on religious beliefs or a political ideology. Families, friends, and the community at large were impacted.

Over my years of practice, I have found that while these are difficult topics to address, they should not be avoided. Studies have shown that open acknowledgement of religious beliefs can affect both clinical outcomes and well-being. Religion and spirituality are as much a part of our patient’s lives as the physical parameters that we measure. To neglect these significant aspects is to miss the very essence of the individual.

I made it a practice to ask patients about their religious beliefs, the extent to which religion shaped their life, and whether they were part of a church community. Knowing this allowed me to separate deep personal belief from stances based on personal freedom, misinformation, conspiracies, and politics.

I found that information about political leanings flowed naturally in discussions with patients as we trusted and respected each other over time. If I approached politics objectively and nonjudgmentally, it generally led to meaningful conversation. This helped me to understand the patient as an individual and informed my diagnosis and treatment plan.
 

Politics as stress

For example, on more than one occasion, a patient with atrial fibrillation presented with persistent elevated blood pressure and pulse rate despite adherence to the medical regimen that I had prescribed. After a few minutes of discussion, it was clear that excessive attention to political commentary on TV and social media raised their anxiety and anger level, putting them at greater risk for adverse outcomes. I advised that they refocus their leisure activities rather than change or increase medication.

It is disappointing to see how one of the great scientific advances of our lifetime, vaccination science, has been tarnished because of political or religious ideology and to see the extent to which these beliefs influenced COVID-19 vaccination compliance. As health care providers, we must promote information based on the scientific method. If patients challenge us and point out that recommendations based on science seem to change over time, we must explain that science evolves on the basis of new information objectively gathered. We need to find out what information the patient has gotten from the Internet, TV, or conspiracy theories and counter this with scientific facts. If we do not discuss religion and politics with our patients along with other risk factors, we may compromise our ability to give them the best advice and treatment.

Our patients have a right to their own spiritual and political ideology. If it differs dramatically from our own, this should not influence our commitment to care for them. But we have an obligation to challenge unfounded beliefs about medicine and counter with scientific facts. There are times when individual freedoms must be secondary to public health. Ultimately, it is up to the patient to choose, but they should not be given a “free pass” on the basis of religion or politics. If I know something is true and I would do it myself or recommend it for my family, I have an obligation to provide this recommendation to my patients.

Religious preference is included in medical records. It is not appropriate to add political preference, but the patient benefits if a long-term caregiver knows this information.

During the pandemic, for the first time in my 40+ years of practice, some patients questioned my recommendations and placed equal or greater weight on religion, politics, or conspiracy theories. This continues to be a very real struggle.

Knowing and understanding our patients as individuals is critical to providing optimum care and that means tackling these formally taboo topics. If having a potentially uncomfortable conversation with patients allows us to save one life, it is worth it.
 

Dr. Francis is a cardiologist at Inova Heart and Vascular Institute, McLean, Va. He disclosed no relevant conflict of interest. A version of this article first appeared on Medscape.com.

Americans are not rushing to receive the updated COVID-19 booster vaccine.

The newest booster became available to the public around Labor Day weekend, and about 4.4 million people have gotten it as of Sept. 21, according to Centers for Disease Control and Prevention data. That figure represents about 1.5% of the people eligible to receive the booster, NBC News reported.

The White House has said the total is probably closer to 5 million people. The CDC totals don’t yet include Texas and Idaho, which use an aggregate vaccination record reporting method for the Pfizer vaccine.

Scott Roberts, MD, a Yale Medicine infectious disease specialist in New Haven, Conn., told NBC News the low numbers are “demoralizing.”

“I would expect a much higher proportion of Americans to have gotten the booster by this point,” he said. “The fact that this booster came out days before Biden said the pandemic is over is a huge mixed message. Now it’s going to be that much harder to convince those at risk who are on the fence to get a booster.”

White House COVID-19 coordinator Ashish Jha, MD, says he thinks demand will pick up in the coming weeks.

“We’ve been thinking and talking about this as an annual vaccine like the flu vaccine. Flu vaccine season picks up in late September and early October. We’re just getting our education campaign going. So we expect to see, despite the fact that this was a strong start, we actually expect this to ramp up stronger,” Dr. Jha said.

The new booster is the third one authorized by the federal government and was redesigned to protect against the currently circulating subvariants BA.4 and BA.5 of the Omicron strain. People who have received a primary vaccine series or a booster at least 2 months before can receive it.

The new Pfizer booster is available for people 12 and up and the Moderna version for people 18 and up. The vaccines can be mixed and matched.

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

Americans are not rushing to receive the updated COVID-19 booster vaccine.

The newest booster became available to the public around Labor Day weekend, and about 4.4 million people have gotten it as of Sept. 21, according to Centers for Disease Control and Prevention data. That figure represents about 1.5% of the people eligible to receive the booster, NBC News reported.

The White House has said the total is probably closer to 5 million people. The CDC totals don’t yet include Texas and Idaho, which use an aggregate vaccination record reporting method for the Pfizer vaccine.

Scott Roberts, MD, a Yale Medicine infectious disease specialist in New Haven, Conn., told NBC News the low numbers are “demoralizing.”

“I would expect a much higher proportion of Americans to have gotten the booster by this point,” he said. “The fact that this booster came out days before Biden said the pandemic is over is a huge mixed message. Now it’s going to be that much harder to convince those at risk who are on the fence to get a booster.”

White House COVID-19 coordinator Ashish Jha, MD, says he thinks demand will pick up in the coming weeks.

“We’ve been thinking and talking about this as an annual vaccine like the flu vaccine. Flu vaccine season picks up in late September and early October. We’re just getting our education campaign going. So we expect to see, despite the fact that this was a strong start, we actually expect this to ramp up stronger,” Dr. Jha said.

The new booster is the third one authorized by the federal government and was redesigned to protect against the currently circulating subvariants BA.4 and BA.5 of the Omicron strain. People who have received a primary vaccine series or a booster at least 2 months before can receive it.

The new Pfizer booster is available for people 12 and up and the Moderna version for people 18 and up. The vaccines can be mixed and matched.

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

Americans are not rushing to receive the updated COVID-19 booster vaccine.

The newest booster became available to the public around Labor Day weekend, and about 4.4 million people have gotten it as of Sept. 21, according to Centers for Disease Control and Prevention data. That figure represents about 1.5% of the people eligible to receive the booster, NBC News reported.

The White House has said the total is probably closer to 5 million people. The CDC totals don’t yet include Texas and Idaho, which use an aggregate vaccination record reporting method for the Pfizer vaccine.

Scott Roberts, MD, a Yale Medicine infectious disease specialist in New Haven, Conn., told NBC News the low numbers are “demoralizing.”

“I would expect a much higher proportion of Americans to have gotten the booster by this point,” he said. “The fact that this booster came out days before Biden said the pandemic is over is a huge mixed message. Now it’s going to be that much harder to convince those at risk who are on the fence to get a booster.”

White House COVID-19 coordinator Ashish Jha, MD, says he thinks demand will pick up in the coming weeks.

“We’ve been thinking and talking about this as an annual vaccine like the flu vaccine. Flu vaccine season picks up in late September and early October. We’re just getting our education campaign going. So we expect to see, despite the fact that this was a strong start, we actually expect this to ramp up stronger,” Dr. Jha said.

The new booster is the third one authorized by the federal government and was redesigned to protect against the currently circulating subvariants BA.4 and BA.5 of the Omicron strain. People who have received a primary vaccine series or a booster at least 2 months before can receive it.

The new Pfizer booster is available for people 12 and up and the Moderna version for people 18 and up. The vaccines can be mixed and matched.

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

Shift workers who confine their eating to the daytime may experience fewer mood symptoms compared to those who eat both day and night, new research suggests.

Investigators at Brigham and Women’s Hospital, Boston, created a simulated nightwork schedule for 19 individuals in a laboratory setting. Participants then engaged in two different meal timing models – daytime-only meals (DMI), and meals taken during both daytime and nighttime (DNMC).

Depression- and anxiety-like mood levels increased by 26% and 16%, respectively, among the daytime and nighttime eaters, but there was no such increase in daytime-only eaters.

“Our findings provide evidence for the timing of food intake as a novel strategy to potentially minimize mood vulnerability in individuals experiencing circadian misalignment, such as people engaged in shift work, experiencing jet lag, or suffering from circadian rhythm disorders,” co–corresponding author Frank A.J.L. Scheer, PhD, director of the medical chronobiology program, Brigham and Women’s Hospital, Boston, said in a news release.

The study was published online in the Proceedings of the National Academy of Sciences.
 

Misaligned circadian clock

“Shift workers often experience a misalignment between their central circadian clock in the brain and daily behaviors, such as sleep/wake and fasting/eating cycles,” senior author Sarah Chellappa, MD, PhD, currently the Alexander Von Humboldt Experienced Fellow in the department of nuclear medicine, University of Cologne (Germany). Dr. Chellappa was a postdoctoral fellow at Brigham and Women’s Hospital when the study was conducted.

“They also have a 25%-40% higher risk of depression and anxiety,” she continued. “Since meal timing is important for physical health and diet is important for mood, we sought to find out whether meal timing can benefit mental health as well.”

Given that impaired glycemic control is a “risk factor for mood disruption,” the researchers tested the prediction that daytime eating “would prevent mood vulnerability, despite simulated night work.”

To investigate the question, they conducted a parallel-design, randomized clinical trial that included a 14-day circadian laboratory protocol with 19 healthy adults (12 men, 7 women; mean age, 26.5 ± 4.1 years) who underwent a forced desynchrony (FD) in dim light for 4 “days,” each of which consisted of 28 hours. Each 28-hour “day” resulted in an additional 4-hour misalignment between the central circadian clock and external behavioral/environmental cycles.

By the fourth day, the participants were misaligned by 12 hours, compared to baseline (that is, the first day). They were then randomly assigned to two groups.

The DNMC group – the control group – had a “typical 28-hour FD protocol,” with behavioral and environmental cycles (sleep/wake, rest/activity, supine/upright posture, dark during scheduled sleep/dim light during wakefulness) scheduled on a 28-hour cycle. Thus, they took their meals during both “daytime” and “nighttime,” which is the typical way that night workers eat.

The DMI group underwent a modified 28-hour FD protocol, with all cycles scheduled on a 28-hour basis, except for the fasting/eating cycle, which was scheduled on a 24-hour basis, resulting in meals consumed only during the “daytime.”

Depression- and anxiety-like mood (which “correspond to an amalgam of mood states typically observed in depression and anxiety) were assessed every hour during the 4 FD days, using computerized visual analogue scales.
 

Nutritional psychiatry

Participants in the DNMC group experienced an increase from baseline in depression- and anxiety-like mood levels of 26.2% (95% confidence interval, 21-31.5; P = .001; P value using false discovery rate, .01; effect-size r, 0.78) and 16.1% (95% CI, 8.5-23.6; P = .005; PFDR, .001; effect-size r, 0.47), respectively.

By contrast, a similar increase did not take place in the DMI group for either depression- or anxiety-like mood levels (95% CI, –5.7% to 7.4%, P not significant and 95% CI, –3.1% to 9.9%, P not significant, respectively).

The researchers tested “whether increase mood vulnerability during simulated night work was associated with the degree of internal circadian misalignment” — defined as “change in the phase difference between the acrophase of circadian glucose rhythms and the bathyphase of circadian body temperature rhythms.”

They found that a larger degree of internal circadian misalignment was “robustly associated” with more depression-like (r, 0.77; P = .001) and anxiety-like (r, 0.67; P = .002) mood levels during simulated night work.

The findings imply that meal timing had “moderate to large effects in depression-like and anxiety-like mood levels during night work, and that such effects were associated with the degree of internal circadian misalignment,” the authors wrote.

The laboratory protocol of both groups was identical except for the timing of meals. The authors noted that the “relevance of diet on sleep, circadian rhythms, and mental health is receiving growing awareness with the emergence of a new field, nutritional psychiatry.”

People who experience depression “often report poor-quality diets with high carbohydrate intake,” and there is evidence that adherence to the Mediterranean diet is associated “with lower odds of depression, anxiety, and psychological distress.”

They cautioned that although these emerging studies suggest an association between dietary factors and mental health, “experimental studies in individuals with depression and/or anxiety/anxiety-related disorders are required to determine causality and direction of effects.”

They described meal timing as “an emerging aspect of nutrition, with increasing research interest because of its influence on physical health.” However, they noted, “the causal role of the timing of food intake on mental health remains to be tested.”
 

Novel findings

Commenting for this article, Kathleen Merikangas, PhD, distinguished investigator and chief, genetic epidemiology research branch, intramural research program, National Institute of Mental Health, Bethesda, Md., described the research as important with novel findings.

The research “employs the elegant, carefully controlled laboratory procedures that have unraveled the influence of light and other environmental cues on sleep and circadian rhythms over the past 2 decades,” said Dr. Merikangas, who was not involved with the study.

“One of the most significant contributions of this work is its demonstration of the importance of investigating circadian rhythms of multiple systems rather than solely focusing on sleep, eating, or emotional states that have often been studied in isolation,” she pointed out.

“Growing evidence from basic research highlights the interdependence of multiple human systems that should be built into interventions that tend to focus on one or two domains.”

She recommended that this work be replicated “in more diverse samples ... in both controlled and naturalistic settings...to test both the generalizability and mechanism of these intriguing findings.”

The study was funded by the National Institutes of Health. Individual investigators were funded by the Alexander Von Humboldt Foundation and the American Diabetes Association. Dr. Chellappa disclosed no relevant financial relationships. Dr. Merikangas disclosed no relevant financial relationships.

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

Shift workers who confine their eating to the daytime may experience fewer mood symptoms compared to those who eat both day and night, new research suggests.

Investigators at Brigham and Women’s Hospital, Boston, created a simulated nightwork schedule for 19 individuals in a laboratory setting. Participants then engaged in two different meal timing models – daytime-only meals (DMI), and meals taken during both daytime and nighttime (DNMC).

Depression- and anxiety-like mood levels increased by 26% and 16%, respectively, among the daytime and nighttime eaters, but there was no such increase in daytime-only eaters.

“Our findings provide evidence for the timing of food intake as a novel strategy to potentially minimize mood vulnerability in individuals experiencing circadian misalignment, such as people engaged in shift work, experiencing jet lag, or suffering from circadian rhythm disorders,” co–corresponding author Frank A.J.L. Scheer, PhD, director of the medical chronobiology program, Brigham and Women’s Hospital, Boston, said in a news release.

The study was published online in the Proceedings of the National Academy of Sciences.
 

Misaligned circadian clock

“Shift workers often experience a misalignment between their central circadian clock in the brain and daily behaviors, such as sleep/wake and fasting/eating cycles,” senior author Sarah Chellappa, MD, PhD, currently the Alexander Von Humboldt Experienced Fellow in the department of nuclear medicine, University of Cologne (Germany). Dr. Chellappa was a postdoctoral fellow at Brigham and Women’s Hospital when the study was conducted.

“They also have a 25%-40% higher risk of depression and anxiety,” she continued. “Since meal timing is important for physical health and diet is important for mood, we sought to find out whether meal timing can benefit mental health as well.”

Given that impaired glycemic control is a “risk factor for mood disruption,” the researchers tested the prediction that daytime eating “would prevent mood vulnerability, despite simulated night work.”

To investigate the question, they conducted a parallel-design, randomized clinical trial that included a 14-day circadian laboratory protocol with 19 healthy adults (12 men, 7 women; mean age, 26.5 ± 4.1 years) who underwent a forced desynchrony (FD) in dim light for 4 “days,” each of which consisted of 28 hours. Each 28-hour “day” resulted in an additional 4-hour misalignment between the central circadian clock and external behavioral/environmental cycles.

By the fourth day, the participants were misaligned by 12 hours, compared to baseline (that is, the first day). They were then randomly assigned to two groups.

The DNMC group – the control group – had a “typical 28-hour FD protocol,” with behavioral and environmental cycles (sleep/wake, rest/activity, supine/upright posture, dark during scheduled sleep/dim light during wakefulness) scheduled on a 28-hour cycle. Thus, they took their meals during both “daytime” and “nighttime,” which is the typical way that night workers eat.

The DMI group underwent a modified 28-hour FD protocol, with all cycles scheduled on a 28-hour basis, except for the fasting/eating cycle, which was scheduled on a 24-hour basis, resulting in meals consumed only during the “daytime.”

Depression- and anxiety-like mood (which “correspond to an amalgam of mood states typically observed in depression and anxiety) were assessed every hour during the 4 FD days, using computerized visual analogue scales.
 

Nutritional psychiatry

Participants in the DNMC group experienced an increase from baseline in depression- and anxiety-like mood levels of 26.2% (95% confidence interval, 21-31.5; P = .001; P value using false discovery rate, .01; effect-size r, 0.78) and 16.1% (95% CI, 8.5-23.6; P = .005; PFDR, .001; effect-size r, 0.47), respectively.

By contrast, a similar increase did not take place in the DMI group for either depression- or anxiety-like mood levels (95% CI, –5.7% to 7.4%, P not significant and 95% CI, –3.1% to 9.9%, P not significant, respectively).

The researchers tested “whether increase mood vulnerability during simulated night work was associated with the degree of internal circadian misalignment” — defined as “change in the phase difference between the acrophase of circadian glucose rhythms and the bathyphase of circadian body temperature rhythms.”

They found that a larger degree of internal circadian misalignment was “robustly associated” with more depression-like (r, 0.77; P = .001) and anxiety-like (r, 0.67; P = .002) mood levels during simulated night work.

The findings imply that meal timing had “moderate to large effects in depression-like and anxiety-like mood levels during night work, and that such effects were associated with the degree of internal circadian misalignment,” the authors wrote.

The laboratory protocol of both groups was identical except for the timing of meals. The authors noted that the “relevance of diet on sleep, circadian rhythms, and mental health is receiving growing awareness with the emergence of a new field, nutritional psychiatry.”

People who experience depression “often report poor-quality diets with high carbohydrate intake,” and there is evidence that adherence to the Mediterranean diet is associated “with lower odds of depression, anxiety, and psychological distress.”

They cautioned that although these emerging studies suggest an association between dietary factors and mental health, “experimental studies in individuals with depression and/or anxiety/anxiety-related disorders are required to determine causality and direction of effects.”

They described meal timing as “an emerging aspect of nutrition, with increasing research interest because of its influence on physical health.” However, they noted, “the causal role of the timing of food intake on mental health remains to be tested.”
 

Novel findings

Commenting for this article, Kathleen Merikangas, PhD, distinguished investigator and chief, genetic epidemiology research branch, intramural research program, National Institute of Mental Health, Bethesda, Md., described the research as important with novel findings.

The research “employs the elegant, carefully controlled laboratory procedures that have unraveled the influence of light and other environmental cues on sleep and circadian rhythms over the past 2 decades,” said Dr. Merikangas, who was not involved with the study.

“One of the most significant contributions of this work is its demonstration of the importance of investigating circadian rhythms of multiple systems rather than solely focusing on sleep, eating, or emotional states that have often been studied in isolation,” she pointed out.

“Growing evidence from basic research highlights the interdependence of multiple human systems that should be built into interventions that tend to focus on one or two domains.”

She recommended that this work be replicated “in more diverse samples ... in both controlled and naturalistic settings...to test both the generalizability and mechanism of these intriguing findings.”

The study was funded by the National Institutes of Health. Individual investigators were funded by the Alexander Von Humboldt Foundation and the American Diabetes Association. Dr. Chellappa disclosed no relevant financial relationships. Dr. Merikangas disclosed no relevant financial relationships.

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

Shift workers who confine their eating to the daytime may experience fewer mood symptoms compared to those who eat both day and night, new research suggests.

Investigators at Brigham and Women’s Hospital, Boston, created a simulated nightwork schedule for 19 individuals in a laboratory setting. Participants then engaged in two different meal timing models – daytime-only meals (DMI), and meals taken during both daytime and nighttime (DNMC).

Depression- and anxiety-like mood levels increased by 26% and 16%, respectively, among the daytime and nighttime eaters, but there was no such increase in daytime-only eaters.

“Our findings provide evidence for the timing of food intake as a novel strategy to potentially minimize mood vulnerability in individuals experiencing circadian misalignment, such as people engaged in shift work, experiencing jet lag, or suffering from circadian rhythm disorders,” co–corresponding author Frank A.J.L. Scheer, PhD, director of the medical chronobiology program, Brigham and Women’s Hospital, Boston, said in a news release.

The study was published online in the Proceedings of the National Academy of Sciences.
 

Misaligned circadian clock

“Shift workers often experience a misalignment between their central circadian clock in the brain and daily behaviors, such as sleep/wake and fasting/eating cycles,” senior author Sarah Chellappa, MD, PhD, currently the Alexander Von Humboldt Experienced Fellow in the department of nuclear medicine, University of Cologne (Germany). Dr. Chellappa was a postdoctoral fellow at Brigham and Women’s Hospital when the study was conducted.

“They also have a 25%-40% higher risk of depression and anxiety,” she continued. “Since meal timing is important for physical health and diet is important for mood, we sought to find out whether meal timing can benefit mental health as well.”

Given that impaired glycemic control is a “risk factor for mood disruption,” the researchers tested the prediction that daytime eating “would prevent mood vulnerability, despite simulated night work.”

To investigate the question, they conducted a parallel-design, randomized clinical trial that included a 14-day circadian laboratory protocol with 19 healthy adults (12 men, 7 women; mean age, 26.5 ± 4.1 years) who underwent a forced desynchrony (FD) in dim light for 4 “days,” each of which consisted of 28 hours. Each 28-hour “day” resulted in an additional 4-hour misalignment between the central circadian clock and external behavioral/environmental cycles.

By the fourth day, the participants were misaligned by 12 hours, compared to baseline (that is, the first day). They were then randomly assigned to two groups.

The DNMC group – the control group – had a “typical 28-hour FD protocol,” with behavioral and environmental cycles (sleep/wake, rest/activity, supine/upright posture, dark during scheduled sleep/dim light during wakefulness) scheduled on a 28-hour cycle. Thus, they took their meals during both “daytime” and “nighttime,” which is the typical way that night workers eat.

The DMI group underwent a modified 28-hour FD protocol, with all cycles scheduled on a 28-hour basis, except for the fasting/eating cycle, which was scheduled on a 24-hour basis, resulting in meals consumed only during the “daytime.”

Depression- and anxiety-like mood (which “correspond to an amalgam of mood states typically observed in depression and anxiety) were assessed every hour during the 4 FD days, using computerized visual analogue scales.
 

Nutritional psychiatry

Participants in the DNMC group experienced an increase from baseline in depression- and anxiety-like mood levels of 26.2% (95% confidence interval, 21-31.5; P = .001; P value using false discovery rate, .01; effect-size r, 0.78) and 16.1% (95% CI, 8.5-23.6; P = .005; PFDR, .001; effect-size r, 0.47), respectively.

By contrast, a similar increase did not take place in the DMI group for either depression- or anxiety-like mood levels (95% CI, –5.7% to 7.4%, P not significant and 95% CI, –3.1% to 9.9%, P not significant, respectively).

The researchers tested “whether increase mood vulnerability during simulated night work was associated with the degree of internal circadian misalignment” — defined as “change in the phase difference between the acrophase of circadian glucose rhythms and the bathyphase of circadian body temperature rhythms.”

They found that a larger degree of internal circadian misalignment was “robustly associated” with more depression-like (r, 0.77; P = .001) and anxiety-like (r, 0.67; P = .002) mood levels during simulated night work.

The findings imply that meal timing had “moderate to large effects in depression-like and anxiety-like mood levels during night work, and that such effects were associated with the degree of internal circadian misalignment,” the authors wrote.

The laboratory protocol of both groups was identical except for the timing of meals. The authors noted that the “relevance of diet on sleep, circadian rhythms, and mental health is receiving growing awareness with the emergence of a new field, nutritional psychiatry.”

People who experience depression “often report poor-quality diets with high carbohydrate intake,” and there is evidence that adherence to the Mediterranean diet is associated “with lower odds of depression, anxiety, and psychological distress.”

They cautioned that although these emerging studies suggest an association between dietary factors and mental health, “experimental studies in individuals with depression and/or anxiety/anxiety-related disorders are required to determine causality and direction of effects.”

They described meal timing as “an emerging aspect of nutrition, with increasing research interest because of its influence on physical health.” However, they noted, “the causal role of the timing of food intake on mental health remains to be tested.”
 

Novel findings

Commenting for this article, Kathleen Merikangas, PhD, distinguished investigator and chief, genetic epidemiology research branch, intramural research program, National Institute of Mental Health, Bethesda, Md., described the research as important with novel findings.

The research “employs the elegant, carefully controlled laboratory procedures that have unraveled the influence of light and other environmental cues on sleep and circadian rhythms over the past 2 decades,” said Dr. Merikangas, who was not involved with the study.

“One of the most significant contributions of this work is its demonstration of the importance of investigating circadian rhythms of multiple systems rather than solely focusing on sleep, eating, or emotional states that have often been studied in isolation,” she pointed out.

“Growing evidence from basic research highlights the interdependence of multiple human systems that should be built into interventions that tend to focus on one or two domains.”

She recommended that this work be replicated “in more diverse samples ... in both controlled and naturalistic settings...to test both the generalizability and mechanism of these intriguing findings.”

The study was funded by the National Institutes of Health. Individual investigators were funded by the Alexander Von Humboldt Foundation and the American Diabetes Association. Dr. Chellappa disclosed no relevant financial relationships. Dr. Merikangas disclosed no relevant financial relationships.

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

For some parents, resuming sexual intimacy after having a baby is a top priority. For others, not so much – and late-night feedings and diaper changes may not be the only hang-ups.

Dyspareunia – pain during sex – occurs in a substantial number of women after childbirth, and recent research sheds light on how psychological and biomedical factors relate to this condition.

Mode of delivery, for instance, may have less of an effect on sexual well-being than some people suspect.

Despite a perception that cesarean delivery might affect sexual function less than vaginal delivery does, how mothers delivered did not affect how often they had sex postpartum or the amount of enjoyment they got from it, according to research published in BJOG.

Eleven years after delivery, however, cesarean delivery was associated with a 74% increased likelihood of pain in the vagina during sex, compared with vaginal delivery, the researchers found (odds ratio, 1.74; 95% confidence interval, 1.46-2.08).

The results suggest that cesarean delivery “may not help protect against sexual dysfunction, as previously thought,” Flo Martin, a PhD student in epidemiology at the University of Bristol, United Kingdom, and lead author of the study, said in a news release.

For their study, Ms. Martin and her colleagues analyzed data from more than 10,300 participants in the Avon Longitudinal Study of Parents and Children, which recruited women in the United Kingdom who were pregnant in 1991 and 1992.

The researchers had data about pain during sex at 11 years. They had data about sexual enjoyment and frequency at 33  months, 5 years, 12 years, and 18 years after delivery.

If women experienced pain during sex years after cesarean delivery, uterine scarring might have been a cause, Ms. Martin and colleagues suggested. Alternatively, women with dyspareunia before delivery may be more likely to have cesarean surgery, which also could explain the association.

Other studies have likewise found that different modes of delivery generally lead to similar outcomes of sexual well-being after birth.

“Several of my own longitudinal studies have shown limited associations between mode of delivery and various aspects of sexual well-being, including sexual satisfaction, sexual function, and sexual desire,” said Natalie O. Rosen, PhD, director of the Couples and Sexual Health Laboratory at Dalhousie University, Halifax, N.S.

Nevertheless, other published studies have yielded conflicting results, so the question warrants further study, she said.
 

Pain catastrophizing

One study by Dr. Rosen’s group, published in Obstetrics & Gynecology, tracked sexual pain in 582 people from mid-pregnancy to 2 years postpartum.

About 21% of participants experienced moderate pain during sex, as determined by an average pain score greater than 4 on scale of 0-10 points. The rest were classified as having “minimal dyspareunia.”

Pain tended to peak at 3 months postpartum and then steadily decrease in both the moderate and minimal pain groups.

Mode of delivery did not affect the odds that a participant would have moderate dyspareunia. Neither did breastfeeding or prior chronic pain.

“But we did find one key thing to look out for: Those who reported a lot of negative thoughts and feelings about pain, something called pain catastrophizing, were more likely to experience moderate persistent pain during sex,” the researchers said in a video about their findings.

Pain catastrophizing 3 months after delivery was associated with significantly increased odds of following a moderate pain trajectory (odds ratio, 1.09; 95% confidence interval, 1.04-1.15).
 

Let’s talk about #postbabyhankypanky

Caring for a newborn while maintaining a romantic relationship can be challenging, and “there is a lack of evidence-based research aimed at helping couples prevent and navigate changes to their sexual well-being postpartum,” Dr. Rosen said.

During the 2-year study, a growing number of participants reported having sex less often over time. The percentage of women who had engaged in sexual activity in the past 4 weeks was 99% at baseline (20-24 weeks of gestation), 83.5% at 32 weeks of gestation, 73.9% at 3 months postpartum, and 69.6% at 2 years postpartum.

“One crucial way that couples sustain their connection is through their sexuality,” Dr. Rosen said. “Unfortunately, most new parents experience significant disruptions to their sexual function,” such as lower sexual desire or more pain during intercourse.

Dr. Rosen’s group has created a series of videos related to this topic dubbed #postbabyhankypanky to facilitate communication about sex postpartum. She encourages women with dyspareunia to talk with a health care provider because treatments such as cognitive-behavioral therapy, pelvic floor physical therapy, and topical medications can help manage pain.
 

‘Reassuring’ data

Veronica Gillispie-Bell, MD, MAS, director of quality for women’s services at the Ochsner Health System, New Orleans, said that she sees patients with postpartum sexual pain frequently.

Patients typically are instructed to have pelvic rest from delivery until 6 weeks after.

At the 6-week appointment, she tells patients to make sure that they are using lots of lubrication, because vaginal dryness related to hormonal changes during pregnancy and breastfeeding can make sex more painful, regardless of mode of delivery.

For many patients, she also recommends pelvic floor physical therapy.

As the medical director for the Louisiana Perinatal Quality Collaborative – a network of care providers, public health officials, and advocates that aims to improve outcomes for birthing persons, families, and newborns – Dr. Gillispie-Bell also is focused on reducing the rate of cesarean deliveries in the state. The BJOG study showing an increased risk for dyspareunia after a cesarean surgery serves as a reminder that there may be “long-term effects of having a C-section that may not be as obvious,” she said.

“C-sections are life-saving procedures, but they are not without risk,” Dr. Gillispie-Bell said.

Leila Frodsham, MBChB, a spokesperson for the Royal College of Obstetricians and Gynaecologists, told Medscape UK that it was “reassuring” to see “no difference in sexual enjoyment or sexual frequency at any time point postpartum between women who gave birth via cesarean section and those who delivered vaginally.”

“Women should be supported to make informed decisions about how they plan to give birth, and it is vital that health care professionals respect their preferences,” Dr. Frodsham added.

Clinicians should also remain aware that sexual pain is also common during periods of subfertility, perimenopause, and initiation of sexual activity.

Combinations of biological, psychological, and social factors can influence pain during sex, and there is an interpersonal element to keep in mind as well, Dr. Rosen noted.

“Pain during sex is typically elicited in the context of a partnered relationship,” Dr. Rosen said. “This means that this is an inherently interpersonal issue – let’s not forget about the partner who is both impacted by and can impact the pain through their own responses.”

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

For some parents, resuming sexual intimacy after having a baby is a top priority. For others, not so much – and late-night feedings and diaper changes may not be the only hang-ups.

Dyspareunia – pain during sex – occurs in a substantial number of women after childbirth, and recent research sheds light on how psychological and biomedical factors relate to this condition.

Mode of delivery, for instance, may have less of an effect on sexual well-being than some people suspect.

Despite a perception that cesarean delivery might affect sexual function less than vaginal delivery does, how mothers delivered did not affect how often they had sex postpartum or the amount of enjoyment they got from it, according to research published in BJOG.

Eleven years after delivery, however, cesarean delivery was associated with a 74% increased likelihood of pain in the vagina during sex, compared with vaginal delivery, the researchers found (odds ratio, 1.74; 95% confidence interval, 1.46-2.08).

The results suggest that cesarean delivery “may not help protect against sexual dysfunction, as previously thought,” Flo Martin, a PhD student in epidemiology at the University of Bristol, United Kingdom, and lead author of the study, said in a news release.

For their study, Ms. Martin and her colleagues analyzed data from more than 10,300 participants in the Avon Longitudinal Study of Parents and Children, which recruited women in the United Kingdom who were pregnant in 1991 and 1992.

The researchers had data about pain during sex at 11 years. They had data about sexual enjoyment and frequency at 33  months, 5 years, 12 years, and 18 years after delivery.

If women experienced pain during sex years after cesarean delivery, uterine scarring might have been a cause, Ms. Martin and colleagues suggested. Alternatively, women with dyspareunia before delivery may be more likely to have cesarean surgery, which also could explain the association.

Other studies have likewise found that different modes of delivery generally lead to similar outcomes of sexual well-being after birth.

“Several of my own longitudinal studies have shown limited associations between mode of delivery and various aspects of sexual well-being, including sexual satisfaction, sexual function, and sexual desire,” said Natalie O. Rosen, PhD, director of the Couples and Sexual Health Laboratory at Dalhousie University, Halifax, N.S.

Nevertheless, other published studies have yielded conflicting results, so the question warrants further study, she said.
 

Pain catastrophizing

One study by Dr. Rosen’s group, published in Obstetrics & Gynecology, tracked sexual pain in 582 people from mid-pregnancy to 2 years postpartum.

About 21% of participants experienced moderate pain during sex, as determined by an average pain score greater than 4 on scale of 0-10 points. The rest were classified as having “minimal dyspareunia.”

Pain tended to peak at 3 months postpartum and then steadily decrease in both the moderate and minimal pain groups.

Mode of delivery did not affect the odds that a participant would have moderate dyspareunia. Neither did breastfeeding or prior chronic pain.

“But we did find one key thing to look out for: Those who reported a lot of negative thoughts and feelings about pain, something called pain catastrophizing, were more likely to experience moderate persistent pain during sex,” the researchers said in a video about their findings.

Pain catastrophizing 3 months after delivery was associated with significantly increased odds of following a moderate pain trajectory (odds ratio, 1.09; 95% confidence interval, 1.04-1.15).
 

Let’s talk about #postbabyhankypanky

Caring for a newborn while maintaining a romantic relationship can be challenging, and “there is a lack of evidence-based research aimed at helping couples prevent and navigate changes to their sexual well-being postpartum,” Dr. Rosen said.

During the 2-year study, a growing number of participants reported having sex less often over time. The percentage of women who had engaged in sexual activity in the past 4 weeks was 99% at baseline (20-24 weeks of gestation), 83.5% at 32 weeks of gestation, 73.9% at 3 months postpartum, and 69.6% at 2 years postpartum.

“One crucial way that couples sustain their connection is through their sexuality,” Dr. Rosen said. “Unfortunately, most new parents experience significant disruptions to their sexual function,” such as lower sexual desire or more pain during intercourse.

Dr. Rosen’s group has created a series of videos related to this topic dubbed #postbabyhankypanky to facilitate communication about sex postpartum. She encourages women with dyspareunia to talk with a health care provider because treatments such as cognitive-behavioral therapy, pelvic floor physical therapy, and topical medications can help manage pain.
 

‘Reassuring’ data

Veronica Gillispie-Bell, MD, MAS, director of quality for women’s services at the Ochsner Health System, New Orleans, said that she sees patients with postpartum sexual pain frequently.

Patients typically are instructed to have pelvic rest from delivery until 6 weeks after.

At the 6-week appointment, she tells patients to make sure that they are using lots of lubrication, because vaginal dryness related to hormonal changes during pregnancy and breastfeeding can make sex more painful, regardless of mode of delivery.

For many patients, she also recommends pelvic floor physical therapy.

As the medical director for the Louisiana Perinatal Quality Collaborative – a network of care providers, public health officials, and advocates that aims to improve outcomes for birthing persons, families, and newborns – Dr. Gillispie-Bell also is focused on reducing the rate of cesarean deliveries in the state. The BJOG study showing an increased risk for dyspareunia after a cesarean surgery serves as a reminder that there may be “long-term effects of having a C-section that may not be as obvious,” she said.

“C-sections are life-saving procedures, but they are not without risk,” Dr. Gillispie-Bell said.

Leila Frodsham, MBChB, a spokesperson for the Royal College of Obstetricians and Gynaecologists, told Medscape UK that it was “reassuring” to see “no difference in sexual enjoyment or sexual frequency at any time point postpartum between women who gave birth via cesarean section and those who delivered vaginally.”

“Women should be supported to make informed decisions about how they plan to give birth, and it is vital that health care professionals respect their preferences,” Dr. Frodsham added.

Clinicians should also remain aware that sexual pain is also common during periods of subfertility, perimenopause, and initiation of sexual activity.

Combinations of biological, psychological, and social factors can influence pain during sex, and there is an interpersonal element to keep in mind as well, Dr. Rosen noted.

“Pain during sex is typically elicited in the context of a partnered relationship,” Dr. Rosen said. “This means that this is an inherently interpersonal issue – let’s not forget about the partner who is both impacted by and can impact the pain through their own responses.”

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

For some parents, resuming sexual intimacy after having a baby is a top priority. For others, not so much – and late-night feedings and diaper changes may not be the only hang-ups.

Dyspareunia – pain during sex – occurs in a substantial number of women after childbirth, and recent research sheds light on how psychological and biomedical factors relate to this condition.

Mode of delivery, for instance, may have less of an effect on sexual well-being than some people suspect.

Despite a perception that cesarean delivery might affect sexual function less than vaginal delivery does, how mothers delivered did not affect how often they had sex postpartum or the amount of enjoyment they got from it, according to research published in BJOG.

Eleven years after delivery, however, cesarean delivery was associated with a 74% increased likelihood of pain in the vagina during sex, compared with vaginal delivery, the researchers found (odds ratio, 1.74; 95% confidence interval, 1.46-2.08).

The results suggest that cesarean delivery “may not help protect against sexual dysfunction, as previously thought,” Flo Martin, a PhD student in epidemiology at the University of Bristol, United Kingdom, and lead author of the study, said in a news release.

For their study, Ms. Martin and her colleagues analyzed data from more than 10,300 participants in the Avon Longitudinal Study of Parents and Children, which recruited women in the United Kingdom who were pregnant in 1991 and 1992.

The researchers had data about pain during sex at 11 years. They had data about sexual enjoyment and frequency at 33  months, 5 years, 12 years, and 18 years after delivery.

If women experienced pain during sex years after cesarean delivery, uterine scarring might have been a cause, Ms. Martin and colleagues suggested. Alternatively, women with dyspareunia before delivery may be more likely to have cesarean surgery, which also could explain the association.

Other studies have likewise found that different modes of delivery generally lead to similar outcomes of sexual well-being after birth.

“Several of my own longitudinal studies have shown limited associations between mode of delivery and various aspects of sexual well-being, including sexual satisfaction, sexual function, and sexual desire,” said Natalie O. Rosen, PhD, director of the Couples and Sexual Health Laboratory at Dalhousie University, Halifax, N.S.

Nevertheless, other published studies have yielded conflicting results, so the question warrants further study, she said.
 

Pain catastrophizing

One study by Dr. Rosen’s group, published in Obstetrics & Gynecology, tracked sexual pain in 582 people from mid-pregnancy to 2 years postpartum.

About 21% of participants experienced moderate pain during sex, as determined by an average pain score greater than 4 on scale of 0-10 points. The rest were classified as having “minimal dyspareunia.”

Pain tended to peak at 3 months postpartum and then steadily decrease in both the moderate and minimal pain groups.

Mode of delivery did not affect the odds that a participant would have moderate dyspareunia. Neither did breastfeeding or prior chronic pain.

“But we did find one key thing to look out for: Those who reported a lot of negative thoughts and feelings about pain, something called pain catastrophizing, were more likely to experience moderate persistent pain during sex,” the researchers said in a video about their findings.

Pain catastrophizing 3 months after delivery was associated with significantly increased odds of following a moderate pain trajectory (odds ratio, 1.09; 95% confidence interval, 1.04-1.15).
 

Let’s talk about #postbabyhankypanky

Caring for a newborn while maintaining a romantic relationship can be challenging, and “there is a lack of evidence-based research aimed at helping couples prevent and navigate changes to their sexual well-being postpartum,” Dr. Rosen said.

During the 2-year study, a growing number of participants reported having sex less often over time. The percentage of women who had engaged in sexual activity in the past 4 weeks was 99% at baseline (20-24 weeks of gestation), 83.5% at 32 weeks of gestation, 73.9% at 3 months postpartum, and 69.6% at 2 years postpartum.

“One crucial way that couples sustain their connection is through their sexuality,” Dr. Rosen said. “Unfortunately, most new parents experience significant disruptions to their sexual function,” such as lower sexual desire or more pain during intercourse.

Dr. Rosen’s group has created a series of videos related to this topic dubbed #postbabyhankypanky to facilitate communication about sex postpartum. She encourages women with dyspareunia to talk with a health care provider because treatments such as cognitive-behavioral therapy, pelvic floor physical therapy, and topical medications can help manage pain.
 

‘Reassuring’ data

Veronica Gillispie-Bell, MD, MAS, director of quality for women’s services at the Ochsner Health System, New Orleans, said that she sees patients with postpartum sexual pain frequently.

Patients typically are instructed to have pelvic rest from delivery until 6 weeks after.

At the 6-week appointment, she tells patients to make sure that they are using lots of lubrication, because vaginal dryness related to hormonal changes during pregnancy and breastfeeding can make sex more painful, regardless of mode of delivery.

For many patients, she also recommends pelvic floor physical therapy.

As the medical director for the Louisiana Perinatal Quality Collaborative – a network of care providers, public health officials, and advocates that aims to improve outcomes for birthing persons, families, and newborns – Dr. Gillispie-Bell also is focused on reducing the rate of cesarean deliveries in the state. The BJOG study showing an increased risk for dyspareunia after a cesarean surgery serves as a reminder that there may be “long-term effects of having a C-section that may not be as obvious,” she said.

“C-sections are life-saving procedures, but they are not without risk,” Dr. Gillispie-Bell said.

Leila Frodsham, MBChB, a spokesperson for the Royal College of Obstetricians and Gynaecologists, told Medscape UK that it was “reassuring” to see “no difference in sexual enjoyment or sexual frequency at any time point postpartum between women who gave birth via cesarean section and those who delivered vaginally.”

“Women should be supported to make informed decisions about how they plan to give birth, and it is vital that health care professionals respect their preferences,” Dr. Frodsham added.

Clinicians should also remain aware that sexual pain is also common during periods of subfertility, perimenopause, and initiation of sexual activity.

Combinations of biological, psychological, and social factors can influence pain during sex, and there is an interpersonal element to keep in mind as well, Dr. Rosen noted.

“Pain during sex is typically elicited in the context of a partnered relationship,” Dr. Rosen said. “This means that this is an inherently interpersonal issue – let’s not forget about the partner who is both impacted by and can impact the pain through their own responses.”

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

Cancer cachexia is a syndrome of weight loss that frequently occurs during cancer treatment. Consequences can include skeletal muscle loss, fatigue, functional impairment, worse quality of life, and worse survival. On the other hand, weight gain during cancer treatment has been tied to better survival.

A new study shows that, among patients with non–small cell lung cancer (NSCLC), weight gain over the course of treatment with standard of care chemotherapy was associated with improved survival in both men and women. Few studies have examined the relationship between weight gain and outcomes by sex.

“The finding that weight gain occurred in subsets of males and females is a new observation. The fact that weight gain occurs in cancer patients during anticancer treatment could confound results of clinical [trials] evaluating novel anticachexia treatments. Simultaneously studying longitudinal body weights and serum and cellular biomarkers in cancer patients might provide insights into mechanisms involved in cachexia. Increased understanding of mechanisms driving cachexia could lead to new therapeutic strategies,” said study coauthor Philip Bonomi, MD, who is an oncologist at Rush Medical College, Chicago.

“This data, although it appears to be very basic, is critically important, especially as we consider our novel interventions in the treatment of cancer cachexia,” said Eric Roeland, MD, during his presentation of the study at the annual meeting of European Society for Medical Oncology. Dr. Roeland is a medical oncologist at Oregon Health & Science University, Portland.

Dr. Roeland is also the lead author of cancer cachexia guidelines published by the American Society of Clinical Oncology in 2020. The guidelines suggest that dietary counseling can be offered to patients, but warns against routine use of enteral feeding tubes and parenteral nutrition. Although no specific drug can be recommended for cancer cachexia, progesterone analogs and corticosteroids used over the short term (weeks) can be used on a trial base to improve appetite and weight gain. While not approved in the United States, anamorelin was approved in 2020 in Japan for cancer cachexia in NSCLC, gastric cancer, pancreatic cancer, and colorectal cancer.

The new study should raise awareness of the importance of adverse effects of cancer treatments, said Karin Jordan, MD, University Hospital Heidelberg (Germany). She served as a discussant following the presentation. “As a medical oncologist, we focus a bit too much on the benefits of antineoplastic therapy, both on cure and on the survival benefit. But what is also very, very important to do is a balanced oncology treatment to focus on the risks of oncology therapies,” she said.

The study is limited by its retrospective nature and potential for bias. “The hypothesis that weight gain leads to improved survival is not really proven as it likewise may be the other way around,” Dr. Jordan said.

However, in oncology research, a phenomenon called the “obesity paradox” is increasingly catching the interest of investigators. Observational studies have shown that overweight patients with certain cancers (specifically, colorectal, endometrial and lung cancer). actually have improved overall survival as compared with normal-weight patients.
 

Details from the new study

The researchers pooled data 1,030 patients who participated in three phase 3 clinical trials conducted between 2005 and 2011. The patients all received platinum-based chemotherapy as part of control arms. 304 were female and 726 were male. The median age was 62. 16.7% were Asian, the mean body mass index was 24.6 kg/m², 88.5% had stage 4 disease, 36.9% had adenocarcinoma, and 86.3% were current or former smokers.

Males and females had similar magnitudes and rate of weight gain over the course of treatment. Any weight gain was associated with improved overall survival in both males (12.7 vs. 8.0 months; hazard ratio, 0.60; P < .001) and females (16.2 vs. 10.1 months; HR, 0.65; P = .0028). Patients who had a weight gain of 2.5% of body weight or more saw an improvement in overall survival in both males (14.0 vs. 8.2 months; HR, 0.57; P < .001) and females (16.7 vs. 11.3 months; HR, 0.61; P = .0041).

Patients with a weight gain of 5% or more was associated with improved survival in males (13.6 vs. 8.9 months; HR, 0.62; P = .0001), but there was no statistically significant association in females (16.7 vs. 12.6 months; HR, 0.69; P = .1107).

Regardless of weight-gain status, males had lower survival rates than females. All of the associations were independent of smoking status.

The study was funded by Pfizer. Dr. Bonomi has received honoraria from Pfizer and Helsinn for participation in scientific advisory boards. Dr. Jordan has consulted for Amgen, Hexal, Riemser, Helsinn, Voluntis, Pfizer, and BD Solution. She has received research funding from Deutsche Krebshilfe. She has received honoraria from MSD, Merck, Amgen, Hexal, Riemser, Helsinn, Voluntis, Pfizer, Pomme-med, PharmaMar, arttemoi, OnkoUpdate, Stemline, and Roche.

Cancer cachexia is a syndrome of weight loss that frequently occurs during cancer treatment. Consequences can include skeletal muscle loss, fatigue, functional impairment, worse quality of life, and worse survival. On the other hand, weight gain during cancer treatment has been tied to better survival.

A new study shows that, among patients with non–small cell lung cancer (NSCLC), weight gain over the course of treatment with standard of care chemotherapy was associated with improved survival in both men and women. Few studies have examined the relationship between weight gain and outcomes by sex.

“The finding that weight gain occurred in subsets of males and females is a new observation. The fact that weight gain occurs in cancer patients during anticancer treatment could confound results of clinical [trials] evaluating novel anticachexia treatments. Simultaneously studying longitudinal body weights and serum and cellular biomarkers in cancer patients might provide insights into mechanisms involved in cachexia. Increased understanding of mechanisms driving cachexia could lead to new therapeutic strategies,” said study coauthor Philip Bonomi, MD, who is an oncologist at Rush Medical College, Chicago.

“This data, although it appears to be very basic, is critically important, especially as we consider our novel interventions in the treatment of cancer cachexia,” said Eric Roeland, MD, during his presentation of the study at the annual meeting of European Society for Medical Oncology. Dr. Roeland is a medical oncologist at Oregon Health & Science University, Portland.

Dr. Roeland is also the lead author of cancer cachexia guidelines published by the American Society of Clinical Oncology in 2020. The guidelines suggest that dietary counseling can be offered to patients, but warns against routine use of enteral feeding tubes and parenteral nutrition. Although no specific drug can be recommended for cancer cachexia, progesterone analogs and corticosteroids used over the short term (weeks) can be used on a trial base to improve appetite and weight gain. While not approved in the United States, anamorelin was approved in 2020 in Japan for cancer cachexia in NSCLC, gastric cancer, pancreatic cancer, and colorectal cancer.

The new study should raise awareness of the importance of adverse effects of cancer treatments, said Karin Jordan, MD, University Hospital Heidelberg (Germany). She served as a discussant following the presentation. “As a medical oncologist, we focus a bit too much on the benefits of antineoplastic therapy, both on cure and on the survival benefit. But what is also very, very important to do is a balanced oncology treatment to focus on the risks of oncology therapies,” she said.

The study is limited by its retrospective nature and potential for bias. “The hypothesis that weight gain leads to improved survival is not really proven as it likewise may be the other way around,” Dr. Jordan said.

However, in oncology research, a phenomenon called the “obesity paradox” is increasingly catching the interest of investigators. Observational studies have shown that overweight patients with certain cancers (specifically, colorectal, endometrial and lung cancer). actually have improved overall survival as compared with normal-weight patients.
 

Details from the new study

The researchers pooled data 1,030 patients who participated in three phase 3 clinical trials conducted between 2005 and 2011. The patients all received platinum-based chemotherapy as part of control arms. 304 were female and 726 were male. The median age was 62. 16.7% were Asian, the mean body mass index was 24.6 kg/m², 88.5% had stage 4 disease, 36.9% had adenocarcinoma, and 86.3% were current or former smokers.

Males and females had similar magnitudes and rate of weight gain over the course of treatment. Any weight gain was associated with improved overall survival in both males (12.7 vs. 8.0 months; hazard ratio, 0.60; P < .001) and females (16.2 vs. 10.1 months; HR, 0.65; P = .0028). Patients who had a weight gain of 2.5% of body weight or more saw an improvement in overall survival in both males (14.0 vs. 8.2 months; HR, 0.57; P < .001) and females (16.7 vs. 11.3 months; HR, 0.61; P = .0041).

Patients with a weight gain of 5% or more was associated with improved survival in males (13.6 vs. 8.9 months; HR, 0.62; P = .0001), but there was no statistically significant association in females (16.7 vs. 12.6 months; HR, 0.69; P = .1107).

Regardless of weight-gain status, males had lower survival rates than females. All of the associations were independent of smoking status.

The study was funded by Pfizer. Dr. Bonomi has received honoraria from Pfizer and Helsinn for participation in scientific advisory boards. Dr. Jordan has consulted for Amgen, Hexal, Riemser, Helsinn, Voluntis, Pfizer, and BD Solution. She has received research funding from Deutsche Krebshilfe. She has received honoraria from MSD, Merck, Amgen, Hexal, Riemser, Helsinn, Voluntis, Pfizer, Pomme-med, PharmaMar, arttemoi, OnkoUpdate, Stemline, and Roche.

Cancer cachexia is a syndrome of weight loss that frequently occurs during cancer treatment. Consequences can include skeletal muscle loss, fatigue, functional impairment, worse quality of life, and worse survival. On the other hand, weight gain during cancer treatment has been tied to better survival.

A new study shows that, among patients with non–small cell lung cancer (NSCLC), weight gain over the course of treatment with standard of care chemotherapy was associated with improved survival in both men and women. Few studies have examined the relationship between weight gain and outcomes by sex.

“The finding that weight gain occurred in subsets of males and females is a new observation. The fact that weight gain occurs in cancer patients during anticancer treatment could confound results of clinical [trials] evaluating novel anticachexia treatments. Simultaneously studying longitudinal body weights and serum and cellular biomarkers in cancer patients might provide insights into mechanisms involved in cachexia. Increased understanding of mechanisms driving cachexia could lead to new therapeutic strategies,” said study coauthor Philip Bonomi, MD, who is an oncologist at Rush Medical College, Chicago.

“This data, although it appears to be very basic, is critically important, especially as we consider our novel interventions in the treatment of cancer cachexia,” said Eric Roeland, MD, during his presentation of the study at the annual meeting of European Society for Medical Oncology. Dr. Roeland is a medical oncologist at Oregon Health & Science University, Portland.

Dr. Roeland is also the lead author of cancer cachexia guidelines published by the American Society of Clinical Oncology in 2020. The guidelines suggest that dietary counseling can be offered to patients, but warns against routine use of enteral feeding tubes and parenteral nutrition. Although no specific drug can be recommended for cancer cachexia, progesterone analogs and corticosteroids used over the short term (weeks) can be used on a trial base to improve appetite and weight gain. While not approved in the United States, anamorelin was approved in 2020 in Japan for cancer cachexia in NSCLC, gastric cancer, pancreatic cancer, and colorectal cancer.

The new study should raise awareness of the importance of adverse effects of cancer treatments, said Karin Jordan, MD, University Hospital Heidelberg (Germany). She served as a discussant following the presentation. “As a medical oncologist, we focus a bit too much on the benefits of antineoplastic therapy, both on cure and on the survival benefit. But what is also very, very important to do is a balanced oncology treatment to focus on the risks of oncology therapies,” she said.

The study is limited by its retrospective nature and potential for bias. “The hypothesis that weight gain leads to improved survival is not really proven as it likewise may be the other way around,” Dr. Jordan said.

However, in oncology research, a phenomenon called the “obesity paradox” is increasingly catching the interest of investigators. Observational studies have shown that overweight patients with certain cancers (specifically, colorectal, endometrial and lung cancer). actually have improved overall survival as compared with normal-weight patients.
 

Details from the new study

The researchers pooled data 1,030 patients who participated in three phase 3 clinical trials conducted between 2005 and 2011. The patients all received platinum-based chemotherapy as part of control arms. 304 were female and 726 were male. The median age was 62. 16.7% were Asian, the mean body mass index was 24.6 kg/m², 88.5% had stage 4 disease, 36.9% had adenocarcinoma, and 86.3% were current or former smokers.

Males and females had similar magnitudes and rate of weight gain over the course of treatment. Any weight gain was associated with improved overall survival in both males (12.7 vs. 8.0 months; hazard ratio, 0.60; P < .001) and females (16.2 vs. 10.1 months; HR, 0.65; P = .0028). Patients who had a weight gain of 2.5% of body weight or more saw an improvement in overall survival in both males (14.0 vs. 8.2 months; HR, 0.57; P < .001) and females (16.7 vs. 11.3 months; HR, 0.61; P = .0041).

Patients with a weight gain of 5% or more was associated with improved survival in males (13.6 vs. 8.9 months; HR, 0.62; P = .0001), but there was no statistically significant association in females (16.7 vs. 12.6 months; HR, 0.69; P = .1107).

Regardless of weight-gain status, males had lower survival rates than females. All of the associations were independent of smoking status.

The study was funded by Pfizer. Dr. Bonomi has received honoraria from Pfizer and Helsinn for participation in scientific advisory boards. Dr. Jordan has consulted for Amgen, Hexal, Riemser, Helsinn, Voluntis, Pfizer, and BD Solution. She has received research funding from Deutsche Krebshilfe. She has received honoraria from MSD, Merck, Amgen, Hexal, Riemser, Helsinn, Voluntis, Pfizer, Pomme-med, PharmaMar, arttemoi, OnkoUpdate, Stemline, and Roche.

Kashyap Patel, MD, followed an unconventional path to becoming a nationally known oncologist. A former news photographer in his native India, Dr. Patel has practiced medicine on three continents.

In 2020, he published a book aimed at cancer specialists and their patients on how to die “with hope and dignity,” titled “Between Life and Death” (Penguin Random House India).

When Dr. Patel, the CEO of Carolina Blood and Cancer Care Associates in Rock Hill, S.C., became president of the Washington-based Community Oncology Alliance 2 years ago, he stepped into a leadership role in community oncology. As an advocate for health care payment reform on Capitol Hill, the South Carolina legislature, and within his own practice, Dr. Patel has long worked to eliminate disparities in U.S. cancer care.

This news organization spoke with Dr. Patel about his unusual career path.
 

Question: Your father had a great influence on you. Can you tell us more about him?

Answer: My dad was a hermit and a saint. He lost his dad when he was 4 years old and moved to the big city with his cousins. When he was 9 or so, he got a message saying that his mum was very ill. So, he and his cousin raised some money, got a doctor and one of those old, rugged jeeps, and they started driving to the village, but rains had destroyed the road. So, without penicillin, his mum died of pneumonia.

He felt that roads and doctor access were the two big factors that could have saved her life. He eventually became the Superintending Engineer for four districts in Gujarat State, building roads connecting every village, but he never gave up his simplistic, minimalist life.

When I was in elementary school, every other weekend my dad would literally dump me at the Mahatma Gandhi Ashram and come back in 2 hours. So, I’m looking at Gandhi’s cabinets, his pictures, reading about his life. So, my formative years were born in that.
 

Q: I read that you were intending to become an engineer and join the space race. How did your father nudge you toward medicine?

A: When I was 9 years old, my favorite movie hero died of cancer. To comfort me, my father inserted the idea into my brain: When you grow up, you can become a doctor to cure cancer. So, when I finished high school, I was 24th in the state and had an option to go to the space school in India. On the day when I was going for the interview, I could see tears in my father’s eyes, and he said, You know what, boy? I thought you’re going to become a doctor and cure cancer. So, to honor him, I went to med school instead.

Courtesty Dr. Kashyap Patel

Q: I understand that your father also triggered your interest in photography?

A: I started photographing Kutchi tribal people in 1977, after I bought a camera from a famous architect [Hasmukh Patel], while traveling with my dad. And then my dad bought me a motorcycle, so I started riding myself. From the time I entered med school in 1978 until I finished my residency in 1987, I made several trips following Kutchi migrant families and livestock. They leave their homeland in Kutch [district] during summer in search of grass and water to keep their livestock alive and walk across the state from the desert of Kutch all the way to central Gujarat until monsoon begins. Then they return, only to resume the journey next year. I would catch them along their journey, would talk to them, drink tea and eat millet crepes with them.

Courtesy Dr. Kashyap Patel

In 1984, between Dr. Patel’s medical school and residency, the Lions Club in his hometown, Ahmedabad, India, sponsored him and three buddies to document people and wildlife in Gujarat state. Traveling by motorcycle, the four friends stayed for free with local families by knocking on doors and explaining that they were medical students. Dr. Patel’s photographs were exhibited by the Lions Club of Ahmedabad and at India’s top art institution, the Lalit Kala gallery.

In the 3rd year of his internal-medicine residency in Bombay (now Mumbai), Dr. Patel approached a national newspaper, The Indian Express, for work. He was immediately sent on assignment to cover a cholera epidemic and filed his story and photographs the following day. He worked as a photojournalist and subeditor for a year.
 

Courtesy Dr. Kashyap Patel

Q: Among all your thousands of pictures, do you have a favorite?

A: There were two photos of Kutchi people that touched me. There was one photo of a lady. All of her worldly belongings were in the picture and a smile on her face showed that we don’t need so many things to be happy. The second photo is of an elderly lady shifting her water pan on her head to a younger family member. And a little girl looks up with a look of curiosity: Will I be doing this when I grow up? We seek so much materialistic happiness. But when you look at the curiosity, smiles, and happiness [in these photos], you realize we could have a lot of happiness in minimalism, as well.

Q: After you finished your residency in Ahmedabad, how did you get started in oncology?

A: In 1986, Ahmedabad City and Gujarat State did not have structured training programs in oncology, so I went to Bombay [Mumbai], where Dr. B.C. Mehta, a true legend and pioneer in India, had started hematology-oncology training. I was a post-doc research fellow with him for a little over a year but when I started seeing patients, I had to answer to myself, Am I doing everything I can to help these people? I saw that the U.K. had one of the best training programs in hem malignancy, so I started applying. Then something happened that was almost like a miracle.

In April 1992, Dr. Patel was working at the Institute of Kidney Diseases in Ahmedabad. One afternoon, just as the clinic was closing for siesta, a family brought in a young girl. She had drug-induced thrombocytopenia and needed an immediate transfusion. The father offered to sell his wedding ring to pay Dr. Patel if he would supervise the treatment and stay by the girl’s side. Dr. Patel told the man to keep his ring, then he remained in the office with the child. At 4 p.m., the office phone rang. It was Dr. H.K. Parikh, an eminent British physician who was wintering in India and needed to make a medical appointment for his wife. On a normal day, Dr. Patel would have missed the call.

“This is how I got to meet Dr. Parikh, out of the blue,” said Dr. Patel. “His wife came to the office for 6 weeks and after 6 weeks, he said, You’re a smart guy; you should come to England. That was in April. I sent a resume and all the usual paperwork. On July 16, 1992, at 2 in the morning, I got a call from the U.K. saying, Your job is confirmed. I’m going to fax your appointment through the Royal College of Physicians, and you’re coming to Manchester to work with us. I’d been sponsored by the Overseas Doctors Training Program.

“So, it turns out that if I’d declined to see that patient and declined to stay in my clinic that afternoon, if I’d declined to see this doctor’s wife, I would never have been in the U.K. And that opened up the doors for me. I like that story because I’ve found that standing up for people who do not have a voice, who do not have hope, always leads to what is destined for me.”
 

Q: After working as a registrar in the United Kingdom 4 years, you found yourself in the United States and, once again, had to train as an internist. What was new about U.S. oncology?

A: I took 3 years to get recertified in Jamaica Hospital in Queens, then became a fellow in hematology-oncology at the Thomas Jefferson in Philadelphia. My U.K. training was all based on hematological malignancy. In the United States, I shifted into solid tumors.

Q: You have a long history of advocating for affordable oncology at the community, state, and federal level, and you recently launched a disparities initiative in your center called NOLA (No One Left Alone). What was the trigger for NOLA?

A: In the spring of 2020, when we started seeing the COVID surge and the difference in mortality rate between the multiple races, at the same time I saw the AACR [American Association for Cancer Research] 2020 disparity report showing that 34% of cancer deaths are preventable – one in three – if we took care of disparities. The same year, the Community Oncology Alliance asked me to become the president. So, I felt that there is something herding me, leading me, to this position. Eighty percent of cancer patients are treated in community clinics like ours. It put the onus on me to do something.

I learned from Gandhi that I cannot depend on government, I cannot depend on the policy, I have to act myself.

I said, I would not worry about making money, I would rather lose funding on this. So, we started. I read 400+ papers; I spent over 1,000 hours reading about disparities. And I realized that it’s not complicated. There are five pillars to eliminate disparity: access to care for financial reasons, access to biomarker testing or precision medicine, access to social determinants of health, access to cancer screening, and trials. If we focus on these five, we can at least bring that number from 34% to 20%, if not lower.

So, we put that plan in place. I dedicated three employees whose only role is to ensure that not a single patient has to take financial burden from my practice. And we showed it’s doable.

This has now become my mission for the last quarter of my life.
 

In 2020, Dr. Patel published a book on dying well titled “Between Life and Death.” It’s framed as a series of his conversations with a former patient, Harry Falls. Harry wanted to understand death better, so Dr. Patel narrated five patient stories, drawing the threads together to help Harry face the inevitable. Dr. Patel now uses a similar approach to train clinicians on having meaningful end-of-life conversations with patients.

Courtesy Dr. Kashyap Patel

Q: Why did you feel the need to write a book about dying?

A: The more I’ve witnessed, the more I’m convinced that there are things that we don’t know about this process, which needs to be explored much more. However, I do feel that there’s a power within all of us to steer the process of leaving this world.

Before I sat down with Harry, I loved to counsel patients, but I didn’t have any structural ideas. It was Harry himself who told me that I now had a simple way to explain dying to a much larger audience.
 

Q: What is your secret for fitting everything into your life?

A: I’ll tell you, it’s very simple. If I put my soul, heart, mind, actions, and language on the one plane and don’t let my brain and conditioning influence my choices, then I live in the moment. Whenever I let my conditioned mind take all the decisions, those are crooked, because you know, we’re selfish creatures – we can use what we call the convenient lie to hide inconvenient truth. And I try not to do that. I mean, it’s been a journey. It didn’t come overnight. I learned. And I feel that over all these years, the only thing that rewarded me, that opened the door of where I am today, was pure, selfless process, whether it’s the act of talking, speaking, or doing.

Kashyap Patel, MD, followed an unconventional path to becoming a nationally known oncologist. A former news photographer in his native India, Dr. Patel has practiced medicine on three continents.

In 2020, he published a book aimed at cancer specialists and their patients on how to die “with hope and dignity,” titled “Between Life and Death” (Penguin Random House India).

When Dr. Patel, the CEO of Carolina Blood and Cancer Care Associates in Rock Hill, S.C., became president of the Washington-based Community Oncology Alliance 2 years ago, he stepped into a leadership role in community oncology. As an advocate for health care payment reform on Capitol Hill, the South Carolina legislature, and within his own practice, Dr. Patel has long worked to eliminate disparities in U.S. cancer care.

This news organization spoke with Dr. Patel about his unusual career path.
 

Question: Your father had a great influence on you. Can you tell us more about him?

Answer: My dad was a hermit and a saint. He lost his dad when he was 4 years old and moved to the big city with his cousins. When he was 9 or so, he got a message saying that his mum was very ill. So, he and his cousin raised some money, got a doctor and one of those old, rugged jeeps, and they started driving to the village, but rains had destroyed the road. So, without penicillin, his mum died of pneumonia.

He felt that roads and doctor access were the two big factors that could have saved her life. He eventually became the Superintending Engineer for four districts in Gujarat State, building roads connecting every village, but he never gave up his simplistic, minimalist life.

When I was in elementary school, every other weekend my dad would literally dump me at the Mahatma Gandhi Ashram and come back in 2 hours. So, I’m looking at Gandhi’s cabinets, his pictures, reading about his life. So, my formative years were born in that.
 

Q: I read that you were intending to become an engineer and join the space race. How did your father nudge you toward medicine?

A: When I was 9 years old, my favorite movie hero died of cancer. To comfort me, my father inserted the idea into my brain: When you grow up, you can become a doctor to cure cancer. So, when I finished high school, I was 24th in the state and had an option to go to the space school in India. On the day when I was going for the interview, I could see tears in my father’s eyes, and he said, You know what, boy? I thought you’re going to become a doctor and cure cancer. So, to honor him, I went to med school instead.

Courtesty Dr. Kashyap Patel

Q: I understand that your father also triggered your interest in photography?

A: I started photographing Kutchi tribal people in 1977, after I bought a camera from a famous architect [Hasmukh Patel], while traveling with my dad. And then my dad bought me a motorcycle, so I started riding myself. From the time I entered med school in 1978 until I finished my residency in 1987, I made several trips following Kutchi migrant families and livestock. They leave their homeland in Kutch [district] during summer in search of grass and water to keep their livestock alive and walk across the state from the desert of Kutch all the way to central Gujarat until monsoon begins. Then they return, only to resume the journey next year. I would catch them along their journey, would talk to them, drink tea and eat millet crepes with them.

Courtesy Dr. Kashyap Patel

In 1984, between Dr. Patel’s medical school and residency, the Lions Club in his hometown, Ahmedabad, India, sponsored him and three buddies to document people and wildlife in Gujarat state. Traveling by motorcycle, the four friends stayed for free with local families by knocking on doors and explaining that they were medical students. Dr. Patel’s photographs were exhibited by the Lions Club of Ahmedabad and at India’s top art institution, the Lalit Kala gallery.

In the 3rd year of his internal-medicine residency in Bombay (now Mumbai), Dr. Patel approached a national newspaper, The Indian Express, for work. He was immediately sent on assignment to cover a cholera epidemic and filed his story and photographs the following day. He worked as a photojournalist and subeditor for a year.
 

Courtesy Dr. Kashyap Patel

Q: Among all your thousands of pictures, do you have a favorite?

A: There were two photos of Kutchi people that touched me. There was one photo of a lady. All of her worldly belongings were in the picture and a smile on her face showed that we don’t need so many things to be happy. The second photo is of an elderly lady shifting her water pan on her head to a younger family member. And a little girl looks up with a look of curiosity: Will I be doing this when I grow up? We seek so much materialistic happiness. But when you look at the curiosity, smiles, and happiness [in these photos], you realize we could have a lot of happiness in minimalism, as well.

Q: After you finished your residency in Ahmedabad, how did you get started in oncology?

A: In 1986, Ahmedabad City and Gujarat State did not have structured training programs in oncology, so I went to Bombay [Mumbai], where Dr. B.C. Mehta, a true legend and pioneer in India, had started hematology-oncology training. I was a post-doc research fellow with him for a little over a year but when I started seeing patients, I had to answer to myself, Am I doing everything I can to help these people? I saw that the U.K. had one of the best training programs in hem malignancy, so I started applying. Then something happened that was almost like a miracle.

In April 1992, Dr. Patel was working at the Institute of Kidney Diseases in Ahmedabad. One afternoon, just as the clinic was closing for siesta, a family brought in a young girl. She had drug-induced thrombocytopenia and needed an immediate transfusion. The father offered to sell his wedding ring to pay Dr. Patel if he would supervise the treatment and stay by the girl’s side. Dr. Patel told the man to keep his ring, then he remained in the office with the child. At 4 p.m., the office phone rang. It was Dr. H.K. Parikh, an eminent British physician who was wintering in India and needed to make a medical appointment for his wife. On a normal day, Dr. Patel would have missed the call.

“This is how I got to meet Dr. Parikh, out of the blue,” said Dr. Patel. “His wife came to the office for 6 weeks and after 6 weeks, he said, You’re a smart guy; you should come to England. That was in April. I sent a resume and all the usual paperwork. On July 16, 1992, at 2 in the morning, I got a call from the U.K. saying, Your job is confirmed. I’m going to fax your appointment through the Royal College of Physicians, and you’re coming to Manchester to work with us. I’d been sponsored by the Overseas Doctors Training Program.

“So, it turns out that if I’d declined to see that patient and declined to stay in my clinic that afternoon, if I’d declined to see this doctor’s wife, I would never have been in the U.K. And that opened up the doors for me. I like that story because I’ve found that standing up for people who do not have a voice, who do not have hope, always leads to what is destined for me.”
 

Q: After working as a registrar in the United Kingdom 4 years, you found yourself in the United States and, once again, had to train as an internist. What was new about U.S. oncology?

A: I took 3 years to get recertified in Jamaica Hospital in Queens, then became a fellow in hematology-oncology at the Thomas Jefferson in Philadelphia. My U.K. training was all based on hematological malignancy. In the United States, I shifted into solid tumors.

Q: You have a long history of advocating for affordable oncology at the community, state, and federal level, and you recently launched a disparities initiative in your center called NOLA (No One Left Alone). What was the trigger for NOLA?

A: In the spring of 2020, when we started seeing the COVID surge and the difference in mortality rate between the multiple races, at the same time I saw the AACR [American Association for Cancer Research] 2020 disparity report showing that 34% of cancer deaths are preventable – one in three – if we took care of disparities. The same year, the Community Oncology Alliance asked me to become the president. So, I felt that there is something herding me, leading me, to this position. Eighty percent of cancer patients are treated in community clinics like ours. It put the onus on me to do something.

I learned from Gandhi that I cannot depend on government, I cannot depend on the policy, I have to act myself.

I said, I would not worry about making money, I would rather lose funding on this. So, we started. I read 400+ papers; I spent over 1,000 hours reading about disparities. And I realized that it’s not complicated. There are five pillars to eliminate disparity: access to care for financial reasons, access to biomarker testing or precision medicine, access to social determinants of health, access to cancer screening, and trials. If we focus on these five, we can at least bring that number from 34% to 20%, if not lower.

So, we put that plan in place. I dedicated three employees whose only role is to ensure that not a single patient has to take financial burden from my practice. And we showed it’s doable.

This has now become my mission for the last quarter of my life.
 

In 2020, Dr. Patel published a book on dying well titled “Between Life and Death.” It’s framed as a series of his conversations with a former patient, Harry Falls. Harry wanted to understand death better, so Dr. Patel narrated five patient stories, drawing the threads together to help Harry face the inevitable. Dr. Patel now uses a similar approach to train clinicians on having meaningful end-of-life conversations with patients.

Courtesy Dr. Kashyap Patel

Q: Why did you feel the need to write a book about dying?

A: The more I’ve witnessed, the more I’m convinced that there are things that we don’t know about this process, which needs to be explored much more. However, I do feel that there’s a power within all of us to steer the process of leaving this world.

Before I sat down with Harry, I loved to counsel patients, but I didn’t have any structural ideas. It was Harry himself who told me that I now had a simple way to explain dying to a much larger audience.
 

Q: What is your secret for fitting everything into your life?

A: I’ll tell you, it’s very simple. If I put my soul, heart, mind, actions, and language on the one plane and don’t let my brain and conditioning influence my choices, then I live in the moment. Whenever I let my conditioned mind take all the decisions, those are crooked, because you know, we’re selfish creatures – we can use what we call the convenient lie to hide inconvenient truth. And I try not to do that. I mean, it’s been a journey. It didn’t come overnight. I learned. And I feel that over all these years, the only thing that rewarded me, that opened the door of where I am today, was pure, selfless process, whether it’s the act of talking, speaking, or doing.

Kashyap Patel, MD, followed an unconventional path to becoming a nationally known oncologist. A former news photographer in his native India, Dr. Patel has practiced medicine on three continents.

In 2020, he published a book aimed at cancer specialists and their patients on how to die “with hope and dignity,” titled “Between Life and Death” (Penguin Random House India).

When Dr. Patel, the CEO of Carolina Blood and Cancer Care Associates in Rock Hill, S.C., became president of the Washington-based Community Oncology Alliance 2 years ago, he stepped into a leadership role in community oncology. As an advocate for health care payment reform on Capitol Hill, the South Carolina legislature, and within his own practice, Dr. Patel has long worked to eliminate disparities in U.S. cancer care.

This news organization spoke with Dr. Patel about his unusual career path.
 

Question: Your father had a great influence on you. Can you tell us more about him?

Answer: My dad was a hermit and a saint. He lost his dad when he was 4 years old and moved to the big city with his cousins. When he was 9 or so, he got a message saying that his mum was very ill. So, he and his cousin raised some money, got a doctor and one of those old, rugged jeeps, and they started driving to the village, but rains had destroyed the road. So, without penicillin, his mum died of pneumonia.

He felt that roads and doctor access were the two big factors that could have saved her life. He eventually became the Superintending Engineer for four districts in Gujarat State, building roads connecting every village, but he never gave up his simplistic, minimalist life.

When I was in elementary school, every other weekend my dad would literally dump me at the Mahatma Gandhi Ashram and come back in 2 hours. So, I’m looking at Gandhi’s cabinets, his pictures, reading about his life. So, my formative years were born in that.
 

Q: I read that you were intending to become an engineer and join the space race. How did your father nudge you toward medicine?

A: When I was 9 years old, my favorite movie hero died of cancer. To comfort me, my father inserted the idea into my brain: When you grow up, you can become a doctor to cure cancer. So, when I finished high school, I was 24th in the state and had an option to go to the space school in India. On the day when I was going for the interview, I could see tears in my father’s eyes, and he said, You know what, boy? I thought you’re going to become a doctor and cure cancer. So, to honor him, I went to med school instead.

Courtesty Dr. Kashyap Patel

Q: I understand that your father also triggered your interest in photography?

A: I started photographing Kutchi tribal people in 1977, after I bought a camera from a famous architect [Hasmukh Patel], while traveling with my dad. And then my dad bought me a motorcycle, so I started riding myself. From the time I entered med school in 1978 until I finished my residency in 1987, I made several trips following Kutchi migrant families and livestock. They leave their homeland in Kutch [district] during summer in search of grass and water to keep their livestock alive and walk across the state from the desert of Kutch all the way to central Gujarat until monsoon begins. Then they return, only to resume the journey next year. I would catch them along their journey, would talk to them, drink tea and eat millet crepes with them.

Courtesy Dr. Kashyap Patel

In 1984, between Dr. Patel’s medical school and residency, the Lions Club in his hometown, Ahmedabad, India, sponsored him and three buddies to document people and wildlife in Gujarat state. Traveling by motorcycle, the four friends stayed for free with local families by knocking on doors and explaining that they were medical students. Dr. Patel’s photographs were exhibited by the Lions Club of Ahmedabad and at India’s top art institution, the Lalit Kala gallery.

In the 3rd year of his internal-medicine residency in Bombay (now Mumbai), Dr. Patel approached a national newspaper, The Indian Express, for work. He was immediately sent on assignment to cover a cholera epidemic and filed his story and photographs the following day. He worked as a photojournalist and subeditor for a year.
 

Courtesy Dr. Kashyap Patel

Q: Among all your thousands of pictures, do you have a favorite?

A: There were two photos of Kutchi people that touched me. There was one photo of a lady. All of her worldly belongings were in the picture and a smile on her face showed that we don’t need so many things to be happy. The second photo is of an elderly lady shifting her water pan on her head to a younger family member. And a little girl looks up with a look of curiosity: Will I be doing this when I grow up? We seek so much materialistic happiness. But when you look at the curiosity, smiles, and happiness [in these photos], you realize we could have a lot of happiness in minimalism, as well.

Q: After you finished your residency in Ahmedabad, how did you get started in oncology?

A: In 1986, Ahmedabad City and Gujarat State did not have structured training programs in oncology, so I went to Bombay [Mumbai], where Dr. B.C. Mehta, a true legend and pioneer in India, had started hematology-oncology training. I was a post-doc research fellow with him for a little over a year but when I started seeing patients, I had to answer to myself, Am I doing everything I can to help these people? I saw that the U.K. had one of the best training programs in hem malignancy, so I started applying. Then something happened that was almost like a miracle.

In April 1992, Dr. Patel was working at the Institute of Kidney Diseases in Ahmedabad. One afternoon, just as the clinic was closing for siesta, a family brought in a young girl. She had drug-induced thrombocytopenia and needed an immediate transfusion. The father offered to sell his wedding ring to pay Dr. Patel if he would supervise the treatment and stay by the girl’s side. Dr. Patel told the man to keep his ring, then he remained in the office with the child. At 4 p.m., the office phone rang. It was Dr. H.K. Parikh, an eminent British physician who was wintering in India and needed to make a medical appointment for his wife. On a normal day, Dr. Patel would have missed the call.

“This is how I got to meet Dr. Parikh, out of the blue,” said Dr. Patel. “His wife came to the office for 6 weeks and after 6 weeks, he said, You’re a smart guy; you should come to England. That was in April. I sent a resume and all the usual paperwork. On July 16, 1992, at 2 in the morning, I got a call from the U.K. saying, Your job is confirmed. I’m going to fax your appointment through the Royal College of Physicians, and you’re coming to Manchester to work with us. I’d been sponsored by the Overseas Doctors Training Program.

“So, it turns out that if I’d declined to see that patient and declined to stay in my clinic that afternoon, if I’d declined to see this doctor’s wife, I would never have been in the U.K. And that opened up the doors for me. I like that story because I’ve found that standing up for people who do not have a voice, who do not have hope, always leads to what is destined for me.”
 

Q: After working as a registrar in the United Kingdom 4 years, you found yourself in the United States and, once again, had to train as an internist. What was new about U.S. oncology?

A: I took 3 years to get recertified in Jamaica Hospital in Queens, then became a fellow in hematology-oncology at the Thomas Jefferson in Philadelphia. My U.K. training was all based on hematological malignancy. In the United States, I shifted into solid tumors.

Q: You have a long history of advocating for affordable oncology at the community, state, and federal level, and you recently launched a disparities initiative in your center called NOLA (No One Left Alone). What was the trigger for NOLA?

A: In the spring of 2020, when we started seeing the COVID surge and the difference in mortality rate between the multiple races, at the same time I saw the AACR [American Association for Cancer Research] 2020 disparity report showing that 34% of cancer deaths are preventable – one in three – if we took care of disparities. The same year, the Community Oncology Alliance asked me to become the president. So, I felt that there is something herding me, leading me, to this position. Eighty percent of cancer patients are treated in community clinics like ours. It put the onus on me to do something.

I learned from Gandhi that I cannot depend on government, I cannot depend on the policy, I have to act myself.

I said, I would not worry about making money, I would rather lose funding on this. So, we started. I read 400+ papers; I spent over 1,000 hours reading about disparities. And I realized that it’s not complicated. There are five pillars to eliminate disparity: access to care for financial reasons, access to biomarker testing or precision medicine, access to social determinants of health, access to cancer screening, and trials. If we focus on these five, we can at least bring that number from 34% to 20%, if not lower.

So, we put that plan in place. I dedicated three employees whose only role is to ensure that not a single patient has to take financial burden from my practice. And we showed it’s doable.

This has now become my mission for the last quarter of my life.
 

In 2020, Dr. Patel published a book on dying well titled “Between Life and Death.” It’s framed as a series of his conversations with a former patient, Harry Falls. Harry wanted to understand death better, so Dr. Patel narrated five patient stories, drawing the threads together to help Harry face the inevitable. Dr. Patel now uses a similar approach to train clinicians on having meaningful end-of-life conversations with patients.

Courtesy Dr. Kashyap Patel

Q: Why did you feel the need to write a book about dying?

A: The more I’ve witnessed, the more I’m convinced that there are things that we don’t know about this process, which needs to be explored much more. However, I do feel that there’s a power within all of us to steer the process of leaving this world.

Before I sat down with Harry, I loved to counsel patients, but I didn’t have any structural ideas. It was Harry himself who told me that I now had a simple way to explain dying to a much larger audience.
 

Q: What is your secret for fitting everything into your life?

A: I’ll tell you, it’s very simple. If I put my soul, heart, mind, actions, and language on the one plane and don’t let my brain and conditioning influence my choices, then I live in the moment. Whenever I let my conditioned mind take all the decisions, those are crooked, because you know, we’re selfish creatures – we can use what we call the convenient lie to hide inconvenient truth. And I try not to do that. I mean, it’s been a journey. It didn’t come overnight. I learned. And I feel that over all these years, the only thing that rewarded me, that opened the door of where I am today, was pure, selfless process, whether it’s the act of talking, speaking, or doing.

A statement by the Society for Healthcare Epidemiology of America, published online in Infection Control & Hospital Epidemiology, offers health care providers guidelines on how to prevent inappropriate antibiotic use in future pandemics and to avoid some of the negative scenarios that have been seen with COVID-19.

According to the U.S. Centers of Disease Control and Prevention, the COVID-19 pandemic brought an alarming increase in antimicrobial resistance in hospitals, with infections and deaths caused by resistant bacteria and fungi going up by 15%. For some pathogens, such as the Carbapenem-resistant Acinetobacter, that number is now as high as 78%.

The culprit might be the widespread antibiotic overprescription during the current pandemic. A 2022 meta-analysis revealed that in high-income countries, 58% of patients with COVID-19 were given antibiotics, whereas in lower- and middle-income countries, 89% of patients were put on such drugs. Some hospitals in Europe and the United States reported similarly elevated numbers, sometimes approaching 100%.

“We’ve lost control,” Natasha Pettit, PharmD, pharmacy director at University of Chicago Medicine, told this news organization. Dr. Pettit was not involved in the SHEA study. “Even if CDC didn’t come out with that data, I can tell you right now more of my time is spent trying to figure out how to manage these multi-drug–resistant infections, and we are running out of options for these patients,”

“Dealing with uncertainty, exhaustion, [and] critical illness in often young, otherwise healthy patients meant doctors wanted to do something for their patients,” said Tamar Barlam, MD, an infectious diseases expert at the Boston Medical Center who led the development of the SHEA white paper, in an interview.

That something often was a prescription for antibiotics, even without a clear indication that they were actually needed. A British study revealed that in times of pandemic uncertainty, clinicians often reached for antibiotics “just in case” and referred to conservative prescribing as “bravery.”

Studies have shown, however, that bacterial co-infections in COVID-19 are rare. A 2020 meta-analysis of 24 studies concluded that only 3.5% of patients had a bacterial co-infection on presentation, and 14.3% had a secondary infection. Similar patterns had previously been observed in other viral outbreaks. Research on MERS-CoV, for example, documented only 1% of patients with a bacterial co-infection on admission. During the 2009 H1N1 influenza pandemic, that number was 12% of non–ICU hospitalized patients.

Yet, according to Dr. Pettit, even when such data became available, it didn’t necessarily change prescribing patterns. “Information was coming at us so quickly, I think the providers didn’t have a moment to see the data, to understand what it meant for their prescribing. Having external guidance earlier on would have been hugely helpful,” she told this news organization.

That’s where the newly published SHEA statement comes in: It outlines recommendations on when to prescribe antibiotics during a respiratory viral pandemic, what tests to order, and when to de-escalate or discontinue the treatment. These recommendations include, for instance, advice to not trust inflammatory markers as reliable indicators of bacterial or fungal infection and to not use procalcitonin routinely to aid in the decision to initiate antibiotics.

According to Dr. Barlam, one of the crucial lessons here is that if clinicians see patients with symptoms that are consistent with the current pandemic, they should trust their own impressions and avoid reaching for antimicrobials “just in case.”

Another important lesson is that antibiotic stewardship programs have a huge role to play during pandemics. They should not only monitor prescribing but also compile new information on bacterial co-infections as it gets released and make sure it reaches the clinicians in a clear form.

Evidence suggests that such programs and guidelines do work to limit unnecessary antibiotic use. In one medical center in Chicago, for example, before recommendations on when to initiate and discontinue antimicrobials were released, over 74% of COVID-19 patients received antibiotics. After guidelines were put in place, the use of such drugs fell to 42%.

Dr. Pettit believes, however, that it’s important not to leave each medical center to its own devices. “Hindsight is always twenty-twenty,” she said, “but I think it would be great that, if we start hearing about a pathogen that might lead to another pandemic, we should have a mechanism in place to call together an expert body to get guidance for how antimicrobial stewardship programs should get involved.”

One of the authors of the SHEA statement, Susan Seo, reports an investigator-initiated Merck grant on cost-effectiveness of letermovir in hematopoietic stem cell transplant patients. Another author, Graeme Forrest, reports a clinical study grant from Regeneron for inpatient monoclonals against SARS-CoV-2. All other authors report no conflicts of interest. The study was independently supported.

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

A statement by the Society for Healthcare Epidemiology of America, published online in Infection Control & Hospital Epidemiology, offers health care providers guidelines on how to prevent inappropriate antibiotic use in future pandemics and to avoid some of the negative scenarios that have been seen with COVID-19.

According to the U.S. Centers of Disease Control and Prevention, the COVID-19 pandemic brought an alarming increase in antimicrobial resistance in hospitals, with infections and deaths caused by resistant bacteria and fungi going up by 15%. For some pathogens, such as the Carbapenem-resistant Acinetobacter, that number is now as high as 78%.

The culprit might be the widespread antibiotic overprescription during the current pandemic. A 2022 meta-analysis revealed that in high-income countries, 58% of patients with COVID-19 were given antibiotics, whereas in lower- and middle-income countries, 89% of patients were put on such drugs. Some hospitals in Europe and the United States reported similarly elevated numbers, sometimes approaching 100%.

“We’ve lost control,” Natasha Pettit, PharmD, pharmacy director at University of Chicago Medicine, told this news organization. Dr. Pettit was not involved in the SHEA study. “Even if CDC didn’t come out with that data, I can tell you right now more of my time is spent trying to figure out how to manage these multi-drug–resistant infections, and we are running out of options for these patients,”

“Dealing with uncertainty, exhaustion, [and] critical illness in often young, otherwise healthy patients meant doctors wanted to do something for their patients,” said Tamar Barlam, MD, an infectious diseases expert at the Boston Medical Center who led the development of the SHEA white paper, in an interview.

That something often was a prescription for antibiotics, even without a clear indication that they were actually needed. A British study revealed that in times of pandemic uncertainty, clinicians often reached for antibiotics “just in case” and referred to conservative prescribing as “bravery.”

Studies have shown, however, that bacterial co-infections in COVID-19 are rare. A 2020 meta-analysis of 24 studies concluded that only 3.5% of patients had a bacterial co-infection on presentation, and 14.3% had a secondary infection. Similar patterns had previously been observed in other viral outbreaks. Research on MERS-CoV, for example, documented only 1% of patients with a bacterial co-infection on admission. During the 2009 H1N1 influenza pandemic, that number was 12% of non–ICU hospitalized patients.

Yet, according to Dr. Pettit, even when such data became available, it didn’t necessarily change prescribing patterns. “Information was coming at us so quickly, I think the providers didn’t have a moment to see the data, to understand what it meant for their prescribing. Having external guidance earlier on would have been hugely helpful,” she told this news organization.

That’s where the newly published SHEA statement comes in: It outlines recommendations on when to prescribe antibiotics during a respiratory viral pandemic, what tests to order, and when to de-escalate or discontinue the treatment. These recommendations include, for instance, advice to not trust inflammatory markers as reliable indicators of bacterial or fungal infection and to not use procalcitonin routinely to aid in the decision to initiate antibiotics.

According to Dr. Barlam, one of the crucial lessons here is that if clinicians see patients with symptoms that are consistent with the current pandemic, they should trust their own impressions and avoid reaching for antimicrobials “just in case.”

Another important lesson is that antibiotic stewardship programs have a huge role to play during pandemics. They should not only monitor prescribing but also compile new information on bacterial co-infections as it gets released and make sure it reaches the clinicians in a clear form.

Evidence suggests that such programs and guidelines do work to limit unnecessary antibiotic use. In one medical center in Chicago, for example, before recommendations on when to initiate and discontinue antimicrobials were released, over 74% of COVID-19 patients received antibiotics. After guidelines were put in place, the use of such drugs fell to 42%.

Dr. Pettit believes, however, that it’s important not to leave each medical center to its own devices. “Hindsight is always twenty-twenty,” she said, “but I think it would be great that, if we start hearing about a pathogen that might lead to another pandemic, we should have a mechanism in place to call together an expert body to get guidance for how antimicrobial stewardship programs should get involved.”

One of the authors of the SHEA statement, Susan Seo, reports an investigator-initiated Merck grant on cost-effectiveness of letermovir in hematopoietic stem cell transplant patients. Another author, Graeme Forrest, reports a clinical study grant from Regeneron for inpatient monoclonals against SARS-CoV-2. All other authors report no conflicts of interest. The study was independently supported.