With several new biologic (b) disease-modifying antirheumatic drugs (DMARD) and targeted synthetic (ts) DMARD now available for the treatment of rheumatoid arthritis (RA), information regarding their comparative effectiveness would be of interest. Relatively few head-to-head trials have been published, however. Though "real-world" studies have been published to provide some information about comparative effectiveness, Deakin and colleagues used a target trial emulation framework to apply clinical trial methods to real-world data. Using the Australian OPAL registry of bDMARD/tsDMARD-naive patients, they developed a randomized controlled trial protocol of tofacitinib vs adalimumab using an intention-to-treat analysis. Under this framework, there was small reduction of disease activity with tofacitinib vs adalimumab at 3 months and no difference at 9 months. While this framework is conceptually interesting, it may be more meaningful used in side-by-side comparison to a real-world analysis of the same data to evaluate pitfalls and biases in both; otherwise, its utility as a stand-alone analysis of observational data is not fully clear.

Østergaard and colleagues also performed a head-to-head study of several different therapies to address the question of optimal treatment strategies for patients with early RA. Patients with moderate to severe disease activity were randomly assigned to treatment with methotrexate combined with (1) oral glucocorticoid or sulfasalazine, hydroxychloroquine, and intra-articular steroid injections, (2) certolizumab, (3) abatacept, or (4) tocilizumab. Disease activity and radiographic changes were evaluated at 48 weeks. In this study of over 800 patients, treatment with abatacept or certolizumab was associated with improved Clinical Disease Activity Index (CDAI) remission rates compared with the active conventional therapy (group 1), but tocilizumab was not. The overall differences between bDMARD treatment groups were small and thus may not reflect significant differences in effectiveness. Instead, this study challenges the notion of initiating conventional synthetic DMARD (csDMARD) therapy in patients with early RA and stepping up to bDMARD, as initial bDMARD therapy may be of benefit in patients with more active early RA.

Alongside the question of the effectiveness of bMARD and tsDMARD in real-world settings, the appropriate role for long-term low-dose prednisone in the treatment of RA remains unknown. A recent study by Güler-Yüksel and colleagues examined the effects of 5 mg prednisolone daily in addition to standard therapy in patients over 65 years of age with active RA. Due to the potential complications of weight gain and glucose intolerance with long-term glucocorticoids, in addition to low-bone-density issues, their use has generally not been viewed favorably. In this multicenter trial, 449 patients were randomly assigned to receive prednisolone vs placebo in addition to their usual medications over 2 years. Notably, patients in the prednisolone group had an average of 0.9 kg weight gain compared with placebo with 0.4 kg weight loss over 2 years. By the end of 2 years, 29% of patients in the prednisolone group had a weight gain of > 2 kg compared with 18% of patients in the placebo group. Only 57 patients in all underwent body composition analysis, and, interestingly, those in the prednisolone group had small increases in lean body mass compared with fat mass, though these patients were not necessarily representative. The authors suggest, though the study does not prove, that low-dose prednisolone can be protective against sarcopenia, which is associated with older age and "rheumatoid cachexia." The study also did not examine the interaction of glucocorticoid use with diet and exercise. While it is reassuring that patients in this study did not experience major weight gain, it does not appear to be a generalizable finding at this point.

With several new biologic (b) disease-modifying antirheumatic drugs (DMARD) and targeted synthetic (ts) DMARD now available for the treatment of rheumatoid arthritis (RA), information regarding their comparative effectiveness would be of interest. Relatively few head-to-head trials have been published, however. Though "real-world" studies have been published to provide some information about comparative effectiveness, Deakin and colleagues used a target trial emulation framework to apply clinical trial methods to real-world data. Using the Australian OPAL registry of bDMARD/tsDMARD-naive patients, they developed a randomized controlled trial protocol of tofacitinib vs adalimumab using an intention-to-treat analysis. Under this framework, there was small reduction of disease activity with tofacitinib vs adalimumab at 3 months and no difference at 9 months. While this framework is conceptually interesting, it may be more meaningful used in side-by-side comparison to a real-world analysis of the same data to evaluate pitfalls and biases in both; otherwise, its utility as a stand-alone analysis of observational data is not fully clear.

Østergaard and colleagues also performed a head-to-head study of several different therapies to address the question of optimal treatment strategies for patients with early RA. Patients with moderate to severe disease activity were randomly assigned to treatment with methotrexate combined with (1) oral glucocorticoid or sulfasalazine, hydroxychloroquine, and intra-articular steroid injections, (2) certolizumab, (3) abatacept, or (4) tocilizumab. Disease activity and radiographic changes were evaluated at 48 weeks. In this study of over 800 patients, treatment with abatacept or certolizumab was associated with improved Clinical Disease Activity Index (CDAI) remission rates compared with the active conventional therapy (group 1), but tocilizumab was not. The overall differences between bDMARD treatment groups were small and thus may not reflect significant differences in effectiveness. Instead, this study challenges the notion of initiating conventional synthetic DMARD (csDMARD) therapy in patients with early RA and stepping up to bDMARD, as initial bDMARD therapy may be of benefit in patients with more active early RA.

Alongside the question of the effectiveness of bMARD and tsDMARD in real-world settings, the appropriate role for long-term low-dose prednisone in the treatment of RA remains unknown. A recent study by Güler-Yüksel and colleagues examined the effects of 5 mg prednisolone daily in addition to standard therapy in patients over 65 years of age with active RA. Due to the potential complications of weight gain and glucose intolerance with long-term glucocorticoids, in addition to low-bone-density issues, their use has generally not been viewed favorably. In this multicenter trial, 449 patients were randomly assigned to receive prednisolone vs placebo in addition to their usual medications over 2 years. Notably, patients in the prednisolone group had an average of 0.9 kg weight gain compared with placebo with 0.4 kg weight loss over 2 years. By the end of 2 years, 29% of patients in the prednisolone group had a weight gain of > 2 kg compared with 18% of patients in the placebo group. Only 57 patients in all underwent body composition analysis, and, interestingly, those in the prednisolone group had small increases in lean body mass compared with fat mass, though these patients were not necessarily representative. The authors suggest, though the study does not prove, that low-dose prednisolone can be protective against sarcopenia, which is associated with older age and "rheumatoid cachexia." The study also did not examine the interaction of glucocorticoid use with diet and exercise. While it is reassuring that patients in this study did not experience major weight gain, it does not appear to be a generalizable finding at this point.

With several new biologic (b) disease-modifying antirheumatic drugs (DMARD) and targeted synthetic (ts) DMARD now available for the treatment of rheumatoid arthritis (RA), information regarding their comparative effectiveness would be of interest. Relatively few head-to-head trials have been published, however. Though "real-world" studies have been published to provide some information about comparative effectiveness, Deakin and colleagues used a target trial emulation framework to apply clinical trial methods to real-world data. Using the Australian OPAL registry of bDMARD/tsDMARD-naive patients, they developed a randomized controlled trial protocol of tofacitinib vs adalimumab using an intention-to-treat analysis. Under this framework, there was small reduction of disease activity with tofacitinib vs adalimumab at 3 months and no difference at 9 months. While this framework is conceptually interesting, it may be more meaningful used in side-by-side comparison to a real-world analysis of the same data to evaluate pitfalls and biases in both; otherwise, its utility as a stand-alone analysis of observational data is not fully clear.

Østergaard and colleagues also performed a head-to-head study of several different therapies to address the question of optimal treatment strategies for patients with early RA. Patients with moderate to severe disease activity were randomly assigned to treatment with methotrexate combined with (1) oral glucocorticoid or sulfasalazine, hydroxychloroquine, and intra-articular steroid injections, (2) certolizumab, (3) abatacept, or (4) tocilizumab. Disease activity and radiographic changes were evaluated at 48 weeks. In this study of over 800 patients, treatment with abatacept or certolizumab was associated with improved Clinical Disease Activity Index (CDAI) remission rates compared with the active conventional therapy (group 1), but tocilizumab was not. The overall differences between bDMARD treatment groups were small and thus may not reflect significant differences in effectiveness. Instead, this study challenges the notion of initiating conventional synthetic DMARD (csDMARD) therapy in patients with early RA and stepping up to bDMARD, as initial bDMARD therapy may be of benefit in patients with more active early RA.

Alongside the question of the effectiveness of bMARD and tsDMARD in real-world settings, the appropriate role for long-term low-dose prednisone in the treatment of RA remains unknown. A recent study by Güler-Yüksel and colleagues examined the effects of 5 mg prednisolone daily in addition to standard therapy in patients over 65 years of age with active RA. Due to the potential complications of weight gain and glucose intolerance with long-term glucocorticoids, in addition to low-bone-density issues, their use has generally not been viewed favorably. In this multicenter trial, 449 patients were randomly assigned to receive prednisolone vs placebo in addition to their usual medications over 2 years. Notably, patients in the prednisolone group had an average of 0.9 kg weight gain compared with placebo with 0.4 kg weight loss over 2 years. By the end of 2 years, 29% of patients in the prednisolone group had a weight gain of > 2 kg compared with 18% of patients in the placebo group. Only 57 patients in all underwent body composition analysis, and, interestingly, those in the prednisolone group had small increases in lean body mass compared with fat mass, though these patients were not necessarily representative. The authors suggest, though the study does not prove, that low-dose prednisolone can be protective against sarcopenia, which is associated with older age and "rheumatoid cachexia." The study also did not examine the interaction of glucocorticoid use with diet and exercise. While it is reassuring that patients in this study did not experience major weight gain, it does not appear to be a generalizable finding at this point.

SAN DIEGO – Bariatric surgery produced sustained, long-term glucose control and weight loss for at least 7 years, and for up to 12 years, in some U.S. patients with type 2 diabetes and a baseline body mass index (BMI) of at least 27 kg/m², according to new study results.

The findings are from ARMMS-T2D, a prospective, controlled trial with the largest cohort and longest follow-up of bariatric surgery reported to date. The results reinforce the potential role of surgery “as an option to improve diabetes-related outcomes, including people with a BMI of less than 35 kg/m²,” said Anita P. Courcoulas, MD, at the recent annual scientific sessions of the American Diabetes Association.

People who underwent bariatric surgery (gastric band, sleeve gastrectomy, or Roux-en-Y gastric bypass) had an average 1.6–percentage point drop in hemoglobin A1c from baseline 7 years after surgery and an average 1.4–percentage point reduction from baseline after 12 years. Average decreases from baseline were 0.2 and 0.3 percentage points at these time points, respectively, among controls who underwent lifestyle and medical interventions only. Between-group differences were significant at both the 7-year (primary endpoint) and 12-year time points in the intention-to-treat analysis, reported Dr. Courcoulas, a professor of surgery at the University of Pittsburgh.

Average weight loss from baseline to 7 and 12 years was 19.9% and 19.3%, respectively, in the surgery group and 8.3% and 10.8%, respectively, among controls, which was significantly different between groups at both time points (a secondary endpoint).

Dr. Courcoulas highlighted that the 10.8% average weight loss after 12 years among controls included crossovers, with 25% of patients progressing from their initial intervention of lifestyle and medical management to undergoing bariatric surgery during follow-up. Among the controls who never underwent surgery (per-protocol analysis), the 12-year average weight loss from baseline was 7.3%.
 

High-dose incretin-hormone therapy missing

A major limitation of ARMMS-T2D (Alliance of Randomized Trials of Medicine vs. Metabolic Surgery in Type 2 Diabetes) is that it prospectively followed a combined cohort from four independently run controlled U.S. trials that all began more than a decade ago, before the contemporary era of medical weight loss management that’s been revolutionized by incretin-hormone receptor agonists such as semaglutide (Ozempic/Wegovy, Novo Nordisk) and tirzepatide (Mounjaro, Lilly).

New randomized, controlled trials “are needed” that compare metabolic bariatric surgery with medical and lifestyle management that includes “high-dose incretin-hormone therapy,” commented Robert H. Eckel, MD, designated discussant for ARMMS-T2D at the session.

The results also showed notable rates of two adverse events associated with bariatric surgery: a 14% incidence of bone fractures, compared with a rate of 5% among controls, and a 12% incidence of anemia after surgery, compared with a rate of 3% among controls.

The control group also had a significantly higher 3% incidence of new need for hemodialysis, compared with no incident dialysis cases among the surgery patients.

“The fracture difference [after bariatric surgery] needs more careful follow-up,” commented Dr. Eckel, an endocrinologist and emeritus professor at the University of Colorado at Denver, Aurora.

ARMMS-T2D included data from 262 people with overweight or obesity and type 2 diabetes randomized in any of four U.S. studies that compared the outcomes of 166 patients who underwent bariatric surgery with 96 patients who served as controls and had lifestyle and medical interventions for weight loss and glycemic control. Seven-year follow-up included 82 (85%) of the initial 96 control patients and 136 (82%) of the initial 166 surgery patients. After 12 years, 31 of the controls (32%) and 83 surgery patients (50%) remained for the A1c analysis.
 

A quartet of studies joined together

The ARMMS-T2D prospective analysis resulted from an early partnership by the organizers of the four independent randomized studies that compared bariatric surgery with lifestyle and medical intervention in people with type 2 diabetes and overweight or obesity: STAMPEDE, which included 150 people at the Cleveland Clinic starting in 2007; SLIMM-T2D, which included 88 people at Brigham and Women’s Hospital and the Joslin Diabetes Center in Boston starting in 2010; TRIABETES, which included 69 people at the University of Pittsburgh starting in 2009; and CROSSROADS, which included 43 people at the University of Washington, Seattle, starting in 2011.

Further secondary findings from the ARMMS-T2D analyses showed that 38% of the surgery patients and 17% of controls had an A1c < 6.5% after 7 years.

At 7 years, type 2 diabetes remission, defined as those with an A1c < 6.5% who were not taking any antidiabetes medications, was reached in 18% of surgery patients and 6% of controls. At 12 years, 13% of the surgery patients and none of the controls met this metric, Dr. Courcoulas said.

The duration of diabetes a person had before undergoing bariatric surgery “may be an important factor” as to whether patients undergo remission, suggested Dr. Eckel. He noted that longer duration type 2 diabetes usually results in increased glucose intolerance and makes remission less likely

Roux-en-Y gastric bypass appeared to have the best rates of patients achieving both lower A1c levels and more weight loss, followed by sleeve gastrectomy and gastric banding, which had the worst performance. But Dr. Courcoulas cautioned that the study was underpowered to reliably compare individual surgical procedures.

In terms of those with an A1c < 7.0%, surgery patients maintained a steady prevalence rate of about 55% during the first 5 years of follow-up, roughly twice the rate of controls, at 28% during all years of follow-up starting at year 5.

About 37% of enrolled patients had a BMI < 35 kg/m², and the A1c-lowering benefit and weight loss in this subgroup were consistent with the overall findings, which supports consideration of bariatric surgery for people with type 2 diabetes and a BMI < 35 kg/m², Dr. Courcoulas said.

She also highlighted that bariatric surgery was linked with significant reductions in triglyceride levels and increased high-density lipoprotein cholesterol levels, compared with controls. However, 22% of surgery patients experienced abdominal pain, compared with 10% of controls, and 7% experienced dysphagia, compared with no cases among the controls.

ARMMS-T2D received no commercial funding. Dr. Courcoulas had no disclosures. Dr. Eckel has been a consultant to numerous companies but said he had no relevant disclosures.

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

SAN DIEGO – Bariatric surgery produced sustained, long-term glucose control and weight loss for at least 7 years, and for up to 12 years, in some U.S. patients with type 2 diabetes and a baseline body mass index (BMI) of at least 27 kg/m², according to new study results.

The findings are from ARMMS-T2D, a prospective, controlled trial with the largest cohort and longest follow-up of bariatric surgery reported to date. The results reinforce the potential role of surgery “as an option to improve diabetes-related outcomes, including people with a BMI of less than 35 kg/m²,” said Anita P. Courcoulas, MD, at the recent annual scientific sessions of the American Diabetes Association.

People who underwent bariatric surgery (gastric band, sleeve gastrectomy, or Roux-en-Y gastric bypass) had an average 1.6–percentage point drop in hemoglobin A1c from baseline 7 years after surgery and an average 1.4–percentage point reduction from baseline after 12 years. Average decreases from baseline were 0.2 and 0.3 percentage points at these time points, respectively, among controls who underwent lifestyle and medical interventions only. Between-group differences were significant at both the 7-year (primary endpoint) and 12-year time points in the intention-to-treat analysis, reported Dr. Courcoulas, a professor of surgery at the University of Pittsburgh.

Average weight loss from baseline to 7 and 12 years was 19.9% and 19.3%, respectively, in the surgery group and 8.3% and 10.8%, respectively, among controls, which was significantly different between groups at both time points (a secondary endpoint).

Dr. Courcoulas highlighted that the 10.8% average weight loss after 12 years among controls included crossovers, with 25% of patients progressing from their initial intervention of lifestyle and medical management to undergoing bariatric surgery during follow-up. Among the controls who never underwent surgery (per-protocol analysis), the 12-year average weight loss from baseline was 7.3%.
 

High-dose incretin-hormone therapy missing

A major limitation of ARMMS-T2D (Alliance of Randomized Trials of Medicine vs. Metabolic Surgery in Type 2 Diabetes) is that it prospectively followed a combined cohort from four independently run controlled U.S. trials that all began more than a decade ago, before the contemporary era of medical weight loss management that’s been revolutionized by incretin-hormone receptor agonists such as semaglutide (Ozempic/Wegovy, Novo Nordisk) and tirzepatide (Mounjaro, Lilly).

New randomized, controlled trials “are needed” that compare metabolic bariatric surgery with medical and lifestyle management that includes “high-dose incretin-hormone therapy,” commented Robert H. Eckel, MD, designated discussant for ARMMS-T2D at the session.

The results also showed notable rates of two adverse events associated with bariatric surgery: a 14% incidence of bone fractures, compared with a rate of 5% among controls, and a 12% incidence of anemia after surgery, compared with a rate of 3% among controls.

The control group also had a significantly higher 3% incidence of new need for hemodialysis, compared with no incident dialysis cases among the surgery patients.

“The fracture difference [after bariatric surgery] needs more careful follow-up,” commented Dr. Eckel, an endocrinologist and emeritus professor at the University of Colorado at Denver, Aurora.

ARMMS-T2D included data from 262 people with overweight or obesity and type 2 diabetes randomized in any of four U.S. studies that compared the outcomes of 166 patients who underwent bariatric surgery with 96 patients who served as controls and had lifestyle and medical interventions for weight loss and glycemic control. Seven-year follow-up included 82 (85%) of the initial 96 control patients and 136 (82%) of the initial 166 surgery patients. After 12 years, 31 of the controls (32%) and 83 surgery patients (50%) remained for the A1c analysis.
 

A quartet of studies joined together

The ARMMS-T2D prospective analysis resulted from an early partnership by the organizers of the four independent randomized studies that compared bariatric surgery with lifestyle and medical intervention in people with type 2 diabetes and overweight or obesity: STAMPEDE, which included 150 people at the Cleveland Clinic starting in 2007; SLIMM-T2D, which included 88 people at Brigham and Women’s Hospital and the Joslin Diabetes Center in Boston starting in 2010; TRIABETES, which included 69 people at the University of Pittsburgh starting in 2009; and CROSSROADS, which included 43 people at the University of Washington, Seattle, starting in 2011.

Further secondary findings from the ARMMS-T2D analyses showed that 38% of the surgery patients and 17% of controls had an A1c < 6.5% after 7 years.

At 7 years, type 2 diabetes remission, defined as those with an A1c < 6.5% who were not taking any antidiabetes medications, was reached in 18% of surgery patients and 6% of controls. At 12 years, 13% of the surgery patients and none of the controls met this metric, Dr. Courcoulas said.

The duration of diabetes a person had before undergoing bariatric surgery “may be an important factor” as to whether patients undergo remission, suggested Dr. Eckel. He noted that longer duration type 2 diabetes usually results in increased glucose intolerance and makes remission less likely

Roux-en-Y gastric bypass appeared to have the best rates of patients achieving both lower A1c levels and more weight loss, followed by sleeve gastrectomy and gastric banding, which had the worst performance. But Dr. Courcoulas cautioned that the study was underpowered to reliably compare individual surgical procedures.

In terms of those with an A1c < 7.0%, surgery patients maintained a steady prevalence rate of about 55% during the first 5 years of follow-up, roughly twice the rate of controls, at 28% during all years of follow-up starting at year 5.

About 37% of enrolled patients had a BMI < 35 kg/m², and the A1c-lowering benefit and weight loss in this subgroup were consistent with the overall findings, which supports consideration of bariatric surgery for people with type 2 diabetes and a BMI < 35 kg/m², Dr. Courcoulas said.

She also highlighted that bariatric surgery was linked with significant reductions in triglyceride levels and increased high-density lipoprotein cholesterol levels, compared with controls. However, 22% of surgery patients experienced abdominal pain, compared with 10% of controls, and 7% experienced dysphagia, compared with no cases among the controls.

ARMMS-T2D received no commercial funding. Dr. Courcoulas had no disclosures. Dr. Eckel has been a consultant to numerous companies but said he had no relevant disclosures.

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

SAN DIEGO – Bariatric surgery produced sustained, long-term glucose control and weight loss for at least 7 years, and for up to 12 years, in some U.S. patients with type 2 diabetes and a baseline body mass index (BMI) of at least 27 kg/m², according to new study results.

The findings are from ARMMS-T2D, a prospective, controlled trial with the largest cohort and longest follow-up of bariatric surgery reported to date. The results reinforce the potential role of surgery “as an option to improve diabetes-related outcomes, including people with a BMI of less than 35 kg/m²,” said Anita P. Courcoulas, MD, at the recent annual scientific sessions of the American Diabetes Association.

People who underwent bariatric surgery (gastric band, sleeve gastrectomy, or Roux-en-Y gastric bypass) had an average 1.6–percentage point drop in hemoglobin A1c from baseline 7 years after surgery and an average 1.4–percentage point reduction from baseline after 12 years. Average decreases from baseline were 0.2 and 0.3 percentage points at these time points, respectively, among controls who underwent lifestyle and medical interventions only. Between-group differences were significant at both the 7-year (primary endpoint) and 12-year time points in the intention-to-treat analysis, reported Dr. Courcoulas, a professor of surgery at the University of Pittsburgh.

Average weight loss from baseline to 7 and 12 years was 19.9% and 19.3%, respectively, in the surgery group and 8.3% and 10.8%, respectively, among controls, which was significantly different between groups at both time points (a secondary endpoint).

Dr. Courcoulas highlighted that the 10.8% average weight loss after 12 years among controls included crossovers, with 25% of patients progressing from their initial intervention of lifestyle and medical management to undergoing bariatric surgery during follow-up. Among the controls who never underwent surgery (per-protocol analysis), the 12-year average weight loss from baseline was 7.3%.
 

High-dose incretin-hormone therapy missing

A major limitation of ARMMS-T2D (Alliance of Randomized Trials of Medicine vs. Metabolic Surgery in Type 2 Diabetes) is that it prospectively followed a combined cohort from four independently run controlled U.S. trials that all began more than a decade ago, before the contemporary era of medical weight loss management that’s been revolutionized by incretin-hormone receptor agonists such as semaglutide (Ozempic/Wegovy, Novo Nordisk) and tirzepatide (Mounjaro, Lilly).

New randomized, controlled trials “are needed” that compare metabolic bariatric surgery with medical and lifestyle management that includes “high-dose incretin-hormone therapy,” commented Robert H. Eckel, MD, designated discussant for ARMMS-T2D at the session.

The results also showed notable rates of two adverse events associated with bariatric surgery: a 14% incidence of bone fractures, compared with a rate of 5% among controls, and a 12% incidence of anemia after surgery, compared with a rate of 3% among controls.

The control group also had a significantly higher 3% incidence of new need for hemodialysis, compared with no incident dialysis cases among the surgery patients.

“The fracture difference [after bariatric surgery] needs more careful follow-up,” commented Dr. Eckel, an endocrinologist and emeritus professor at the University of Colorado at Denver, Aurora.

ARMMS-T2D included data from 262 people with overweight or obesity and type 2 diabetes randomized in any of four U.S. studies that compared the outcomes of 166 patients who underwent bariatric surgery with 96 patients who served as controls and had lifestyle and medical interventions for weight loss and glycemic control. Seven-year follow-up included 82 (85%) of the initial 96 control patients and 136 (82%) of the initial 166 surgery patients. After 12 years, 31 of the controls (32%) and 83 surgery patients (50%) remained for the A1c analysis.
 

A quartet of studies joined together

The ARMMS-T2D prospective analysis resulted from an early partnership by the organizers of the four independent randomized studies that compared bariatric surgery with lifestyle and medical intervention in people with type 2 diabetes and overweight or obesity: STAMPEDE, which included 150 people at the Cleveland Clinic starting in 2007; SLIMM-T2D, which included 88 people at Brigham and Women’s Hospital and the Joslin Diabetes Center in Boston starting in 2010; TRIABETES, which included 69 people at the University of Pittsburgh starting in 2009; and CROSSROADS, which included 43 people at the University of Washington, Seattle, starting in 2011.

Further secondary findings from the ARMMS-T2D analyses showed that 38% of the surgery patients and 17% of controls had an A1c < 6.5% after 7 years.

At 7 years, type 2 diabetes remission, defined as those with an A1c < 6.5% who were not taking any antidiabetes medications, was reached in 18% of surgery patients and 6% of controls. At 12 years, 13% of the surgery patients and none of the controls met this metric, Dr. Courcoulas said.

The duration of diabetes a person had before undergoing bariatric surgery “may be an important factor” as to whether patients undergo remission, suggested Dr. Eckel. He noted that longer duration type 2 diabetes usually results in increased glucose intolerance and makes remission less likely

Roux-en-Y gastric bypass appeared to have the best rates of patients achieving both lower A1c levels and more weight loss, followed by sleeve gastrectomy and gastric banding, which had the worst performance. But Dr. Courcoulas cautioned that the study was underpowered to reliably compare individual surgical procedures.

In terms of those with an A1c < 7.0%, surgery patients maintained a steady prevalence rate of about 55% during the first 5 years of follow-up, roughly twice the rate of controls, at 28% during all years of follow-up starting at year 5.

About 37% of enrolled patients had a BMI < 35 kg/m², and the A1c-lowering benefit and weight loss in this subgroup were consistent with the overall findings, which supports consideration of bariatric surgery for people with type 2 diabetes and a BMI < 35 kg/m², Dr. Courcoulas said.

She also highlighted that bariatric surgery was linked with significant reductions in triglyceride levels and increased high-density lipoprotein cholesterol levels, compared with controls. However, 22% of surgery patients experienced abdominal pain, compared with 10% of controls, and 7% experienced dysphagia, compared with no cases among the controls.

ARMMS-T2D received no commercial funding. Dr. Courcoulas had no disclosures. Dr. Eckel has been a consultant to numerous companies but said he had no relevant disclosures.

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

A new model can predict which patients are more likely to experience side effects from long-term methotrexate (MTX) use, research suggests. Patients with a lower risk profile may benefit from less frequent testing, the authors hypothesize.

Most recommendations advise that patients initiating MTX therapy should get blood testing every 2-4 weeks to monitor for full blood count, liver function, urea electrolytes, and creatinine. After 6 months taking MTX, monitoring can be tapered to every 3 months. But Abhishek Abhishek, MD, PhD, professor of rheumatology and honorary consultant rheumatologist at Nottingham (England) University Hospitals NHS Trust and colleagues argue that abnormal results after the initial 6 months of treatment are “infrequent,” and patients may benefit from fewer tests throughout the year.

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“Unnecessary blood tests waste patients’ time and health care resources, including the time of general practitioners and phlebotomists,” Dr. Abhishek and associates write. “It would be beneficial to predict the risk of clinically significant abnormal blood test results during long-term methotrexate treatment to inform the frequency of testing for individuals.”
 

Stratifying risk

In the study, published in the BMJ, researchers used the UK’s Clinical Practice Research Datalink (CPRD) to identify the electronic medical records of over 37,000 adult patients with an immune-mediated inflammatory disease who were prescribed MTX during 2007-2019. All included patients were prescribed MTX for at least 6 months. The main outcome was discontinuation of methotrexate because of abnormal blood test results. Around 62% of patients had rheumatoid arthritis and 22% had psoriasis or psoriatic arthritis.

Using these anonymized data, the group developed a risk stratification model using 11 clinical predictors. “The factors that went in the model are simple things that most patients can self-report or doctors can get from their patient’s medical records,” Dr. Abhishek told this news organization, including methotrexate dose, age, sex, and comorbidities. Dr. Abhishek emphasized that the model should be used only in patients who have continued taking MTX for at least 6 months and have already undergone more frequent initial testing.

The strongest individual predictors were diabetes (hazard ratio, 1.25), chronic kidney disease stage 3 (HR, 2.01), and previous cytopenia or raised liver enzyme levels during the first 6 months of MTX therapy (HR, 2.97). However, Dr. Abhishek emphasized that the individual factors were less important, noting that the model sums the risks to predict outcomes more accurately. Most patients (68.4%) were sorted into the low-risk cohort, with a less than 10% estimated risk of discontinuing MTX over the next 5 years. About one-fifth (20.9%) were categorized as moderate risk (10%-20% estimated risk over 5 years), and 10.7% were high risk, with a greater than 20% estimated risk of discontinuing the drug over 5 years.

The authors argue that low-risk patients could receive less frequent testing – perhaps every 6 months or annually, while moderate-risk patients would continue to be tested every 3 months. High-risk patients could potentially be tested with even greater frequently.
 

More research needed

The research involved “incredibly sophisticated statistical analysis,” said Daniel E. Furst, MD, professor emeritus of medicine at the University of California, Los Angeles, who was not involved with the study. However, the data do not yet support altering blood testing frequency based on this model.

“The hypothesis that not all patients have to be examined so frequently is a very reasonable hypothesis,” Dr. Furst said in an interview, and additional research is needed to corroborate it. The model also needs to be validated in patient populations outside of the United Kingdom, he added.

Dr. Abhishek agreed that validating the model in other patient populations is an important next step. “When we develop a tool [using] a one-nation data set, we want other researchers to then validate it in other countries’ data sets to make sure there is nothing odd about patients in the U.K. that makes the tool work well here but not in [the] U.S., Europe, or Asia, for example,” he said. Doing so should be relatively easy, he said, as the model is publicly available, and the information required is routinely collected during clinic visits.

To understand if less frequent testing might be appropriate for some patients, researchers would need to look at data registries like the Brigham and Women’s Hospital Rheumatoid Arthritis Sequential Study (BRASS) registry or CorEvitas registries “where the testing is done in a very regular way over the long haul,” Dr. Furst said. Analyzing these datasets, researchers could determine the testing intervals that would be most efficient for low- and high-risk patients.
 

A word of caution

While less frequent testing for long-term MTX therapy could likely have benefits, there is still some risk involved, cautioned Prabha Ranganathan, MD, professor of medicine at Washington University in St. Louis.

“Although most methotrexate toxicity occurs within the first 6 months of starting treatment, rare idiosyncratic toxicity can occur that does not correlate with the dose, duration, or method of how methotrexate is administered,” she wrote in an accompanying editorial. “Most rheumatologists can identify a handful of patients who receive methotrexate in their practice who develop sudden leukopenia or thrombocytopenia or transaminitis that is severe enough to warrant drug discontinuation.” While tools like this prediction model can be useful, clinicians need to consider each patient individually and use shared decision-making when monitoring for MTX toxicity, she advised.

“As in most of areas of medicine, the one-size-fits-all approach does not work for methotrexate users,” she noted.

This study was funded by the U.K. National Institute for Health and Care Research and Health Technology Assessment. Dr. Abhishek has received institutional research grants from AstraZeneca and Oxford Immunotech and personal fees from UpToDate, Springer, Cadila Pharmaceuticals, NGM Bio, Limbic, and Inflazome. Dr. Furst and Dr. Ranganathan report no relevant financial relationships.

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

A new model can predict which patients are more likely to experience side effects from long-term methotrexate (MTX) use, research suggests. Patients with a lower risk profile may benefit from less frequent testing, the authors hypothesize.

Most recommendations advise that patients initiating MTX therapy should get blood testing every 2-4 weeks to monitor for full blood count, liver function, urea electrolytes, and creatinine. After 6 months taking MTX, monitoring can be tapered to every 3 months. But Abhishek Abhishek, MD, PhD, professor of rheumatology and honorary consultant rheumatologist at Nottingham (England) University Hospitals NHS Trust and colleagues argue that abnormal results after the initial 6 months of treatment are “infrequent,” and patients may benefit from fewer tests throughout the year.

ftwitty/E+/Getty Images

“Unnecessary blood tests waste patients’ time and health care resources, including the time of general practitioners and phlebotomists,” Dr. Abhishek and associates write. “It would be beneficial to predict the risk of clinically significant abnormal blood test results during long-term methotrexate treatment to inform the frequency of testing for individuals.”
 

Stratifying risk

In the study, published in the BMJ, researchers used the UK’s Clinical Practice Research Datalink (CPRD) to identify the electronic medical records of over 37,000 adult patients with an immune-mediated inflammatory disease who were prescribed MTX during 2007-2019. All included patients were prescribed MTX for at least 6 months. The main outcome was discontinuation of methotrexate because of abnormal blood test results. Around 62% of patients had rheumatoid arthritis and 22% had psoriasis or psoriatic arthritis.

Using these anonymized data, the group developed a risk stratification model using 11 clinical predictors. “The factors that went in the model are simple things that most patients can self-report or doctors can get from their patient’s medical records,” Dr. Abhishek told this news organization, including methotrexate dose, age, sex, and comorbidities. Dr. Abhishek emphasized that the model should be used only in patients who have continued taking MTX for at least 6 months and have already undergone more frequent initial testing.

The strongest individual predictors were diabetes (hazard ratio, 1.25), chronic kidney disease stage 3 (HR, 2.01), and previous cytopenia or raised liver enzyme levels during the first 6 months of MTX therapy (HR, 2.97). However, Dr. Abhishek emphasized that the individual factors were less important, noting that the model sums the risks to predict outcomes more accurately. Most patients (68.4%) were sorted into the low-risk cohort, with a less than 10% estimated risk of discontinuing MTX over the next 5 years. About one-fifth (20.9%) were categorized as moderate risk (10%-20% estimated risk over 5 years), and 10.7% were high risk, with a greater than 20% estimated risk of discontinuing the drug over 5 years.

The authors argue that low-risk patients could receive less frequent testing – perhaps every 6 months or annually, while moderate-risk patients would continue to be tested every 3 months. High-risk patients could potentially be tested with even greater frequently.
 

More research needed

The research involved “incredibly sophisticated statistical analysis,” said Daniel E. Furst, MD, professor emeritus of medicine at the University of California, Los Angeles, who was not involved with the study. However, the data do not yet support altering blood testing frequency based on this model.

“The hypothesis that not all patients have to be examined so frequently is a very reasonable hypothesis,” Dr. Furst said in an interview, and additional research is needed to corroborate it. The model also needs to be validated in patient populations outside of the United Kingdom, he added.

Dr. Abhishek agreed that validating the model in other patient populations is an important next step. “When we develop a tool [using] a one-nation data set, we want other researchers to then validate it in other countries’ data sets to make sure there is nothing odd about patients in the U.K. that makes the tool work well here but not in [the] U.S., Europe, or Asia, for example,” he said. Doing so should be relatively easy, he said, as the model is publicly available, and the information required is routinely collected during clinic visits.

To understand if less frequent testing might be appropriate for some patients, researchers would need to look at data registries like the Brigham and Women’s Hospital Rheumatoid Arthritis Sequential Study (BRASS) registry or CorEvitas registries “where the testing is done in a very regular way over the long haul,” Dr. Furst said. Analyzing these datasets, researchers could determine the testing intervals that would be most efficient for low- and high-risk patients.
 

A word of caution

While less frequent testing for long-term MTX therapy could likely have benefits, there is still some risk involved, cautioned Prabha Ranganathan, MD, professor of medicine at Washington University in St. Louis.

“Although most methotrexate toxicity occurs within the first 6 months of starting treatment, rare idiosyncratic toxicity can occur that does not correlate with the dose, duration, or method of how methotrexate is administered,” she wrote in an accompanying editorial. “Most rheumatologists can identify a handful of patients who receive methotrexate in their practice who develop sudden leukopenia or thrombocytopenia or transaminitis that is severe enough to warrant drug discontinuation.” While tools like this prediction model can be useful, clinicians need to consider each patient individually and use shared decision-making when monitoring for MTX toxicity, she advised.

“As in most of areas of medicine, the one-size-fits-all approach does not work for methotrexate users,” she noted.

This study was funded by the U.K. National Institute for Health and Care Research and Health Technology Assessment. Dr. Abhishek has received institutional research grants from AstraZeneca and Oxford Immunotech and personal fees from UpToDate, Springer, Cadila Pharmaceuticals, NGM Bio, Limbic, and Inflazome. Dr. Furst and Dr. Ranganathan report no relevant financial relationships.

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

A new model can predict which patients are more likely to experience side effects from long-term methotrexate (MTX) use, research suggests. Patients with a lower risk profile may benefit from less frequent testing, the authors hypothesize.

Most recommendations advise that patients initiating MTX therapy should get blood testing every 2-4 weeks to monitor for full blood count, liver function, urea electrolytes, and creatinine. After 6 months taking MTX, monitoring can be tapered to every 3 months. But Abhishek Abhishek, MD, PhD, professor of rheumatology and honorary consultant rheumatologist at Nottingham (England) University Hospitals NHS Trust and colleagues argue that abnormal results after the initial 6 months of treatment are “infrequent,” and patients may benefit from fewer tests throughout the year.

ftwitty/E+/Getty Images

“Unnecessary blood tests waste patients’ time and health care resources, including the time of general practitioners and phlebotomists,” Dr. Abhishek and associates write. “It would be beneficial to predict the risk of clinically significant abnormal blood test results during long-term methotrexate treatment to inform the frequency of testing for individuals.”
 

Stratifying risk

In the study, published in the BMJ, researchers used the UK’s Clinical Practice Research Datalink (CPRD) to identify the electronic medical records of over 37,000 adult patients with an immune-mediated inflammatory disease who were prescribed MTX during 2007-2019. All included patients were prescribed MTX for at least 6 months. The main outcome was discontinuation of methotrexate because of abnormal blood test results. Around 62% of patients had rheumatoid arthritis and 22% had psoriasis or psoriatic arthritis.

Using these anonymized data, the group developed a risk stratification model using 11 clinical predictors. “The factors that went in the model are simple things that most patients can self-report or doctors can get from their patient’s medical records,” Dr. Abhishek told this news organization, including methotrexate dose, age, sex, and comorbidities. Dr. Abhishek emphasized that the model should be used only in patients who have continued taking MTX for at least 6 months and have already undergone more frequent initial testing.

The strongest individual predictors were diabetes (hazard ratio, 1.25), chronic kidney disease stage 3 (HR, 2.01), and previous cytopenia or raised liver enzyme levels during the first 6 months of MTX therapy (HR, 2.97). However, Dr. Abhishek emphasized that the individual factors were less important, noting that the model sums the risks to predict outcomes more accurately. Most patients (68.4%) were sorted into the low-risk cohort, with a less than 10% estimated risk of discontinuing MTX over the next 5 years. About one-fifth (20.9%) were categorized as moderate risk (10%-20% estimated risk over 5 years), and 10.7% were high risk, with a greater than 20% estimated risk of discontinuing the drug over 5 years.

The authors argue that low-risk patients could receive less frequent testing – perhaps every 6 months or annually, while moderate-risk patients would continue to be tested every 3 months. High-risk patients could potentially be tested with even greater frequently.
 

More research needed

The research involved “incredibly sophisticated statistical analysis,” said Daniel E. Furst, MD, professor emeritus of medicine at the University of California, Los Angeles, who was not involved with the study. However, the data do not yet support altering blood testing frequency based on this model.

“The hypothesis that not all patients have to be examined so frequently is a very reasonable hypothesis,” Dr. Furst said in an interview, and additional research is needed to corroborate it. The model also needs to be validated in patient populations outside of the United Kingdom, he added.

Dr. Abhishek agreed that validating the model in other patient populations is an important next step. “When we develop a tool [using] a one-nation data set, we want other researchers to then validate it in other countries’ data sets to make sure there is nothing odd about patients in the U.K. that makes the tool work well here but not in [the] U.S., Europe, or Asia, for example,” he said. Doing so should be relatively easy, he said, as the model is publicly available, and the information required is routinely collected during clinic visits.

To understand if less frequent testing might be appropriate for some patients, researchers would need to look at data registries like the Brigham and Women’s Hospital Rheumatoid Arthritis Sequential Study (BRASS) registry or CorEvitas registries “where the testing is done in a very regular way over the long haul,” Dr. Furst said. Analyzing these datasets, researchers could determine the testing intervals that would be most efficient for low- and high-risk patients.
 

A word of caution

While less frequent testing for long-term MTX therapy could likely have benefits, there is still some risk involved, cautioned Prabha Ranganathan, MD, professor of medicine at Washington University in St. Louis.

“Although most methotrexate toxicity occurs within the first 6 months of starting treatment, rare idiosyncratic toxicity can occur that does not correlate with the dose, duration, or method of how methotrexate is administered,” she wrote in an accompanying editorial. “Most rheumatologists can identify a handful of patients who receive methotrexate in their practice who develop sudden leukopenia or thrombocytopenia or transaminitis that is severe enough to warrant drug discontinuation.” While tools like this prediction model can be useful, clinicians need to consider each patient individually and use shared decision-making when monitoring for MTX toxicity, she advised.

“As in most of areas of medicine, the one-size-fits-all approach does not work for methotrexate users,” she noted.

This study was funded by the U.K. National Institute for Health and Care Research and Health Technology Assessment. Dr. Abhishek has received institutional research grants from AstraZeneca and Oxford Immunotech and personal fees from UpToDate, Springer, Cadila Pharmaceuticals, NGM Bio, Limbic, and Inflazome. Dr. Furst and Dr. Ranganathan report no relevant financial relationships.

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

Children’s intelligence quotient scores are not significantly different in the first months after concussion, compared with before concussion, data suggest.

In a multicenter study of almost 900 children with concussion or orthopedic injury, differences between groups in full-scale IQ (Cohen’s d = 0.13) and matrix reasoning scores (d = 0.16) were small.

“We draw the inference that IQ scores are unchanged, in the sense that they’re not different from [those of] kids with other types of injuries that don’t involve the brain,” said study author Keith Owen Yeates, PhD, Ronald and Irene Ward Chair in Pediatric Brain Injury and a professor of psychology at the University of Calgary (Alta.).

The study was published in Pediatrics.
 

A representative sample

The investigators analyzed data from two prospective cohort studies of children who were treated for concussion or mild orthopedic injury at two hospitals in the United States and five in Canada. Participants were aged 8-17 years and were recruited within 24 hours of the index event. Patients in the United States completed IQ and performance validity testing at 3-18 days after injury. Patients in Canada did so at 3 months after injury. The study used the short-form IQ test. The investigators included 866 children in their analysis.

Using linear modeling, Bayesian analysis, and multigroup factor analysis, the researchers found “very small group differences” in full-scale IQ scores between the two groups. Mean IQ was 104.95 for the concussion group and 106.08 for the orthopedic-injury group. Matrix reasoning scores were 52.28 and 53.81 for the concussion and orthopedic-injury groups, respectively.

Vocabulary scores did not differ between the two groups (53.25 for the concussion group and 53.27 for the orthopedic-injury group).

The study population is “pretty representative” from a demographic perspective, although it was predominantly White, said Dr. Yeates. “On the other hand, we did look at socioeconomic status, and that didn’t seem to alter the findings at all.”

The sample size is one of the study’s strengths, said Dr. Yeates. “Having 866 kids is far larger, I think, than just about any other study out there.” Drawing from seven children’s hospitals in North America is another strength. “Previous studies, in addition to having smaller samples, were from a single site and often recruited from a clinic population, not a representative group for a general population of kids with concussion.”

The findings must be interpreted precisely, however. “We don’t have actual preinjury data, so the more precise way of describing the findings is to say they’re not different from kids who are very similar to them demographically, have the same risk factors for injuries, and had a similar experience of a traumatic injury,” said Dr. Yeates. “The IQ scores for both groups are smack dab in the average range.”

Overall, the results are encouraging. “There’s been a lot of bad news in the media and in the science about concussion that worries patients, so it’s nice to be able to provide a little bit of balance,” said Dr. Yeates. “The message I give parents is that most kids recover within 2-4 weeks, and we’re much better now at predicting who’s going to [recover] and who isn’t, and that helps, too, so that we can focus our intervention on kids who are most at risk.”

Some children will have persisting symptoms, but evidence-based treatments are lacking. “I think that’ll be a really important direction for the future,” said Dr. Yeates.
 

Graduated return

Commenting on the findings, Michael Esser, MD, a pediatric neurologist at Alberta Children’s Hospital, Calgary, and an associate professor in pediatrics at the University of Calgary, said that they can help allay parents’ concerns about concussions. “It can also be of help for clinicians who want to have evidence to reassure families and promote a graduated return to activities. In particular, the study would support the philosophy of a graduated return to school or work, after a brief period of rest, following concussion.” Dr. Esser did not participate in the study.

The research is also noteworthy because it acknowledges that the differences in the design and methodology used in prior studies may explain the apparent disagreement over how concussion may influence cognitive function.

“This is an important message,” said Dr. Esser. “Families struggle with determining the merit of a lot of information due to the myriad of social media comments about concussion and the risk for cognitive impairment. Therefore, it is important that conclusions with a significant implication are evaluated with a variety of approaches.”

The study received funding from the National Institutes of Health and the Canadian Institutes for Health Research. Dr. Yeates disclosed relationships with the American Psychological Association, Guilford Press, and Cambridge University Press. He has received grant funding from the Canadian Institutes of Health Research, the National Institutes of Health, Brain Canada Foundation, and the National Football League Scientific Advisory Board. He also has relationships with the National Institute for Child Health and Human Development, National Institute of Neurologic Disorders and Stroke, National Pediatric Rehabilitation Resource Center, Center for Pediatric Rehabilitation, and Virginia Tech University. Dr. Esser had no relevant relationships to disclose.

A version of this article appeared on Medscape.com.

Children’s intelligence quotient scores are not significantly different in the first months after concussion, compared with before concussion, data suggest.

In a multicenter study of almost 900 children with concussion or orthopedic injury, differences between groups in full-scale IQ (Cohen’s d = 0.13) and matrix reasoning scores (d = 0.16) were small.

“We draw the inference that IQ scores are unchanged, in the sense that they’re not different from [those of] kids with other types of injuries that don’t involve the brain,” said study author Keith Owen Yeates, PhD, Ronald and Irene Ward Chair in Pediatric Brain Injury and a professor of psychology at the University of Calgary (Alta.).

The study was published in Pediatrics.
 

A representative sample

The investigators analyzed data from two prospective cohort studies of children who were treated for concussion or mild orthopedic injury at two hospitals in the United States and five in Canada. Participants were aged 8-17 years and were recruited within 24 hours of the index event. Patients in the United States completed IQ and performance validity testing at 3-18 days after injury. Patients in Canada did so at 3 months after injury. The study used the short-form IQ test. The investigators included 866 children in their analysis.

Using linear modeling, Bayesian analysis, and multigroup factor analysis, the researchers found “very small group differences” in full-scale IQ scores between the two groups. Mean IQ was 104.95 for the concussion group and 106.08 for the orthopedic-injury group. Matrix reasoning scores were 52.28 and 53.81 for the concussion and orthopedic-injury groups, respectively.

Vocabulary scores did not differ between the two groups (53.25 for the concussion group and 53.27 for the orthopedic-injury group).

The study population is “pretty representative” from a demographic perspective, although it was predominantly White, said Dr. Yeates. “On the other hand, we did look at socioeconomic status, and that didn’t seem to alter the findings at all.”

The sample size is one of the study’s strengths, said Dr. Yeates. “Having 866 kids is far larger, I think, than just about any other study out there.” Drawing from seven children’s hospitals in North America is another strength. “Previous studies, in addition to having smaller samples, were from a single site and often recruited from a clinic population, not a representative group for a general population of kids with concussion.”

The findings must be interpreted precisely, however. “We don’t have actual preinjury data, so the more precise way of describing the findings is to say they’re not different from kids who are very similar to them demographically, have the same risk factors for injuries, and had a similar experience of a traumatic injury,” said Dr. Yeates. “The IQ scores for both groups are smack dab in the average range.”

Overall, the results are encouraging. “There’s been a lot of bad news in the media and in the science about concussion that worries patients, so it’s nice to be able to provide a little bit of balance,” said Dr. Yeates. “The message I give parents is that most kids recover within 2-4 weeks, and we’re much better now at predicting who’s going to [recover] and who isn’t, and that helps, too, so that we can focus our intervention on kids who are most at risk.”

Some children will have persisting symptoms, but evidence-based treatments are lacking. “I think that’ll be a really important direction for the future,” said Dr. Yeates.
 

Graduated return

Commenting on the findings, Michael Esser, MD, a pediatric neurologist at Alberta Children’s Hospital, Calgary, and an associate professor in pediatrics at the University of Calgary, said that they can help allay parents’ concerns about concussions. “It can also be of help for clinicians who want to have evidence to reassure families and promote a graduated return to activities. In particular, the study would support the philosophy of a graduated return to school or work, after a brief period of rest, following concussion.” Dr. Esser did not participate in the study.

The research is also noteworthy because it acknowledges that the differences in the design and methodology used in prior studies may explain the apparent disagreement over how concussion may influence cognitive function.

“This is an important message,” said Dr. Esser. “Families struggle with determining the merit of a lot of information due to the myriad of social media comments about concussion and the risk for cognitive impairment. Therefore, it is important that conclusions with a significant implication are evaluated with a variety of approaches.”

The study received funding from the National Institutes of Health and the Canadian Institutes for Health Research. Dr. Yeates disclosed relationships with the American Psychological Association, Guilford Press, and Cambridge University Press. He has received grant funding from the Canadian Institutes of Health Research, the National Institutes of Health, Brain Canada Foundation, and the National Football League Scientific Advisory Board. He also has relationships with the National Institute for Child Health and Human Development, National Institute of Neurologic Disorders and Stroke, National Pediatric Rehabilitation Resource Center, Center for Pediatric Rehabilitation, and Virginia Tech University. Dr. Esser had no relevant relationships to disclose.

A version of this article appeared on Medscape.com.

Children’s intelligence quotient scores are not significantly different in the first months after concussion, compared with before concussion, data suggest.

In a multicenter study of almost 900 children with concussion or orthopedic injury, differences between groups in full-scale IQ (Cohen’s d = 0.13) and matrix reasoning scores (d = 0.16) were small.

“We draw the inference that IQ scores are unchanged, in the sense that they’re not different from [those of] kids with other types of injuries that don’t involve the brain,” said study author Keith Owen Yeates, PhD, Ronald and Irene Ward Chair in Pediatric Brain Injury and a professor of psychology at the University of Calgary (Alta.).

The study was published in Pediatrics.
 

A representative sample

The investigators analyzed data from two prospective cohort studies of children who were treated for concussion or mild orthopedic injury at two hospitals in the United States and five in Canada. Participants were aged 8-17 years and were recruited within 24 hours of the index event. Patients in the United States completed IQ and performance validity testing at 3-18 days after injury. Patients in Canada did so at 3 months after injury. The study used the short-form IQ test. The investigators included 866 children in their analysis.

Using linear modeling, Bayesian analysis, and multigroup factor analysis, the researchers found “very small group differences” in full-scale IQ scores between the two groups. Mean IQ was 104.95 for the concussion group and 106.08 for the orthopedic-injury group. Matrix reasoning scores were 52.28 and 53.81 for the concussion and orthopedic-injury groups, respectively.

Vocabulary scores did not differ between the two groups (53.25 for the concussion group and 53.27 for the orthopedic-injury group).

The study population is “pretty representative” from a demographic perspective, although it was predominantly White, said Dr. Yeates. “On the other hand, we did look at socioeconomic status, and that didn’t seem to alter the findings at all.”

The sample size is one of the study’s strengths, said Dr. Yeates. “Having 866 kids is far larger, I think, than just about any other study out there.” Drawing from seven children’s hospitals in North America is another strength. “Previous studies, in addition to having smaller samples, were from a single site and often recruited from a clinic population, not a representative group for a general population of kids with concussion.”

The findings must be interpreted precisely, however. “We don’t have actual preinjury data, so the more precise way of describing the findings is to say they’re not different from kids who are very similar to them demographically, have the same risk factors for injuries, and had a similar experience of a traumatic injury,” said Dr. Yeates. “The IQ scores for both groups are smack dab in the average range.”

Overall, the results are encouraging. “There’s been a lot of bad news in the media and in the science about concussion that worries patients, so it’s nice to be able to provide a little bit of balance,” said Dr. Yeates. “The message I give parents is that most kids recover within 2-4 weeks, and we’re much better now at predicting who’s going to [recover] and who isn’t, and that helps, too, so that we can focus our intervention on kids who are most at risk.”

Some children will have persisting symptoms, but evidence-based treatments are lacking. “I think that’ll be a really important direction for the future,” said Dr. Yeates.
 

Graduated return

Commenting on the findings, Michael Esser, MD, a pediatric neurologist at Alberta Children’s Hospital, Calgary, and an associate professor in pediatrics at the University of Calgary, said that they can help allay parents’ concerns about concussions. “It can also be of help for clinicians who want to have evidence to reassure families and promote a graduated return to activities. In particular, the study would support the philosophy of a graduated return to school or work, after a brief period of rest, following concussion.” Dr. Esser did not participate in the study.

The research is also noteworthy because it acknowledges that the differences in the design and methodology used in prior studies may explain the apparent disagreement over how concussion may influence cognitive function.

“This is an important message,” said Dr. Esser. “Families struggle with determining the merit of a lot of information due to the myriad of social media comments about concussion and the risk for cognitive impairment. Therefore, it is important that conclusions with a significant implication are evaluated with a variety of approaches.”

The study received funding from the National Institutes of Health and the Canadian Institutes for Health Research. Dr. Yeates disclosed relationships with the American Psychological Association, Guilford Press, and Cambridge University Press. He has received grant funding from the Canadian Institutes of Health Research, the National Institutes of Health, Brain Canada Foundation, and the National Football League Scientific Advisory Board. He also has relationships with the National Institute for Child Health and Human Development, National Institute of Neurologic Disorders and Stroke, National Pediatric Rehabilitation Resource Center, Center for Pediatric Rehabilitation, and Virginia Tech University. Dr. Esser had no relevant relationships to disclose.

A version of this article appeared on Medscape.com.

In 2017, Sanofi Genzyme launched a phase 2 clinical trial of a drug designed to target a specific genetic mutation in some patients with Parkinson’s disease. Researchers hoped the drug would slow or even stop disease progression.

Like many before it, the trial yielded disappointing results and the company shut it down in 2021. It was the latest in a string of unsuccessful clinical trials testing disease-modifying Parkinson’s disease drugs.

Although it failed, the Sanofi Genzyme study was different: It was the first to enroll patients with Parkinson’s disease who had a specific genotype and marked the earliest days of precision medicine and gene-specific drug development for the disease.

Once thought to play only a small role in a small number of patients with Parkinson’s disease, a growing body of work has prompted researchers and drug developers to take a longer look at how genetics influence Parkinson’s disease risk and progression.

“We’re about to enter this era of precision medicine for Parkinson’s disease, which makes genetic testing important,” said James Beck, PhD, senior vice president and chief scientific officer for the Parkinson’s Foundation.

“A number of companies have clinical trials or are in preparation for clinical trials to test some specific therapies that would depend upon people having a specific genetic mutation,” he said.

Today, at least four clinical trials of drugs that target specific Parkinson’s disease-related gene variants on LRRK2 and GBA are under way, and more are in the pipeline. Whether these drugs will be effective at modifying the course of the disease remains to be seen. First, the trials must enroll enough patients. And therein lies the challenge: Genetic testing isn’t part of routine Parkinson’s disease care and isn’t covered by most insurance policies. Most patients don’t know their genotype.

It’s a significant roadblock to the future of a precision medicine approach that is based on a patient’s individual genotype, which some experts argue offers the best shot at slowing disease progression.

“To enroll in clinical trials for precision drugs people with Parkinson’s disease have to be aware of their genetic status,” said Roy N. Alcalay, MD, chief of the movement disorders division at Tel Aviv Medical Center in Israel and part-time associate professor at Columbia University in New York. “How can a person with Parkinson’s and a LRRK2 mutation join a precision medicine trial for LRRK2 if she does not know she is a LRRK2 carrier?”
 

Free genetic testing

Previous studies have shown that some genetic variants increase the risk for Parkinson’s disease after exposure to environmental factors such as pesticides. Research has also shown that a patient’s genotype can predict survival time and that certain medications may prove more effective at slowing disease progression in patients with specific genotypes. All of this points to a significant role for genetics in a disorder that is rapidly increasing.

This makes expanding patient access to genetic testing even more important, Dr. Alcalay said, noting that it’s equally important that patients are informed of their genotype, something that doesn’t usually happen in blinded clinical trials.

To that end, Dr. Alcalay hopes a national genetics study he is leading will address access and need-to-know issues. PD GENEration, a project launched in 2019 by the Parkinson’s Foundation, offers patients free genetic testing for seven clinically relevant Parkinson’s disease-related genes.

Testing is done at home or in a nearby clinic and the results are shared with patients during a free genetic counseling session and with site investigators. Patient samples are stored in a genetic data bank that is open to researchers around the world.

“We surveyed clinical trialists in the Parkinson’s disease field prior to initiation of PD GENEration and estimated that over 90% of people with Parkinson’s disease prior to the effort were not aware of their genetic status,” Dr. Alcalay said.

“I think precision medicine in Parkinson’s disease will not happen without PD GENEration or similar efforts.”
 

‘Overwhelming’ patient interest

Participants in the study are screened for variants in seven genes known to be involved in Parkinson’s disease risk: GBA, LRRK2, PRKN, PINK1, SNCA, PARK7, and VPS35.

In less than 3 years, the study has already produced what is thought to be the largest genetic data bank of sequenced sets of Parkinson’s disease-risk genes made accessible to patients. Since the end of 2020, the first year of patient enrollment, the number of participants has increased from 676 to 10,515 and the number of participating clinical sites rose from 12 to 101.

The foundation has spent nearly $20 million on the project so far and plans to spend another $10 million to reach a goal of 15,000 patients. The study, which is funded by private donors, is so successful that the foundation has had to scale back enrollment.

“When we were at a peak, we had over 700 participants enrolling each month,” Dr. Beck said. Beginning in April, the program capped new sign-ups to 200 patients per month and created a waiting list for future enrollment. The waiting list is hundreds of patients long.

“The participants’ response to enroll in PD GENEration demonstrates there is an overwhelming interest by people with Parkinson’s disease to learn more about their genetic risk factors,” Dr. Alcalay said.
 

A research driver

Nearly 60% of participants enrolled so far are male and close to 80% are White. The average age is 69 years and 44% were diagnosed in the past 5 years. Close to 75% had never participated in a clinical trial.

Nearly 13% have tested positive for mutations on at least one of the seven target genes. Previous studies had suggested genetics were involved in only about 10% of cases.

The majority of those with positive results had early-onset Parkinson’s disease, high-risk ancestry, or a first-degree relative with the disease. However, 9% of people who tested positive weren’t in any of those categories.

Genetic information collected by the project is shared with the Global Parkinson’s Genetics Program (GP2), a resource program of the Aligning Science Across Parkinson’s initiative that is focused on the disease’s genetic architecture. Researchers around the world have access to GP2 data to study known gene variants and identify new ones.

PD GENEration participants can choose to be notified if they are carriers of gene variants discovered in the future.

“All DNA samples shared by participants are undergoing research-grade testing,” Dr. Beck said. “Not only do we want to be able to inform people with Parkinson’s disease about their genetic status, but we also want to be able to use this precious resource to further drive research into the genetics of Parkinson’s disease.”
 

Early success

Patient recruitment has long been one of the biggest challenges to any clinical trial’s success. Research suggests that 90% of all clinical trials fail to reach recruitment milestones in their allotted time frame and two-thirds of multicenter trials fold because too few patients sign up. Data from the Parkinson’s Foundation show that only about 1% of all patients with Parkinson’s disease participate in clinical trials.

Increasing those numbers is the primary goal of PD GENEration, Dr. Beck said. And there’s evidence it’s already paying off.

Earlier this year, one of the program’s participating clinical sites, Intermountain Health, in Salt Lake City, Utah, joined a phase 2 clinical trial of an experimental drug that targets a mutation on the GBA1 gene.

“One of the reasons we were able to participate was when we got the call about joining, we were able to say that we had patients with that specific gene mutation, and we could only say that because the patients had been genotyped through PD GENEration,” said Kathleen E. McKee, MD, director of movement disorders, associate medical director of neurosciences research, and PD GENEration principal investigator at Intermountain Health.

Since 2021, Dr. McKee has enrolled hundreds of patients in the foundation’s gene study and hopes to enroll even more. Few patients turn down the opportunity to participate, she added. Knowing their genotype has proven empowering for her patients, most of whom could not afford genetic testing on their own.

“Previously I would tell patients this is not going to change your immediate management,” Dr. McKee said. “Now I tell my patients that these trials are out there, it may actually change how I treat you and what I recommend.”
 

A version of this article appeared on Medscape.com.

In 2017, Sanofi Genzyme launched a phase 2 clinical trial of a drug designed to target a specific genetic mutation in some patients with Parkinson’s disease. Researchers hoped the drug would slow or even stop disease progression.

Like many before it, the trial yielded disappointing results and the company shut it down in 2021. It was the latest in a string of unsuccessful clinical trials testing disease-modifying Parkinson’s disease drugs.

Although it failed, the Sanofi Genzyme study was different: It was the first to enroll patients with Parkinson’s disease who had a specific genotype and marked the earliest days of precision medicine and gene-specific drug development for the disease.

Once thought to play only a small role in a small number of patients with Parkinson’s disease, a growing body of work has prompted researchers and drug developers to take a longer look at how genetics influence Parkinson’s disease risk and progression.

“We’re about to enter this era of precision medicine for Parkinson’s disease, which makes genetic testing important,” said James Beck, PhD, senior vice president and chief scientific officer for the Parkinson’s Foundation.

“A number of companies have clinical trials or are in preparation for clinical trials to test some specific therapies that would depend upon people having a specific genetic mutation,” he said.

Today, at least four clinical trials of drugs that target specific Parkinson’s disease-related gene variants on LRRK2 and GBA are under way, and more are in the pipeline. Whether these drugs will be effective at modifying the course of the disease remains to be seen. First, the trials must enroll enough patients. And therein lies the challenge: Genetic testing isn’t part of routine Parkinson’s disease care and isn’t covered by most insurance policies. Most patients don’t know their genotype.

It’s a significant roadblock to the future of a precision medicine approach that is based on a patient’s individual genotype, which some experts argue offers the best shot at slowing disease progression.

“To enroll in clinical trials for precision drugs people with Parkinson’s disease have to be aware of their genetic status,” said Roy N. Alcalay, MD, chief of the movement disorders division at Tel Aviv Medical Center in Israel and part-time associate professor at Columbia University in New York. “How can a person with Parkinson’s and a LRRK2 mutation join a precision medicine trial for LRRK2 if she does not know she is a LRRK2 carrier?”
 

Free genetic testing

Previous studies have shown that some genetic variants increase the risk for Parkinson’s disease after exposure to environmental factors such as pesticides. Research has also shown that a patient’s genotype can predict survival time and that certain medications may prove more effective at slowing disease progression in patients with specific genotypes. All of this points to a significant role for genetics in a disorder that is rapidly increasing.

This makes expanding patient access to genetic testing even more important, Dr. Alcalay said, noting that it’s equally important that patients are informed of their genotype, something that doesn’t usually happen in blinded clinical trials.

To that end, Dr. Alcalay hopes a national genetics study he is leading will address access and need-to-know issues. PD GENEration, a project launched in 2019 by the Parkinson’s Foundation, offers patients free genetic testing for seven clinically relevant Parkinson’s disease-related genes.

Testing is done at home or in a nearby clinic and the results are shared with patients during a free genetic counseling session and with site investigators. Patient samples are stored in a genetic data bank that is open to researchers around the world.

“We surveyed clinical trialists in the Parkinson’s disease field prior to initiation of PD GENEration and estimated that over 90% of people with Parkinson’s disease prior to the effort were not aware of their genetic status,” Dr. Alcalay said.

“I think precision medicine in Parkinson’s disease will not happen without PD GENEration or similar efforts.”
 

‘Overwhelming’ patient interest

Participants in the study are screened for variants in seven genes known to be involved in Parkinson’s disease risk: GBA, LRRK2, PRKN, PINK1, SNCA, PARK7, and VPS35.

In less than 3 years, the study has already produced what is thought to be the largest genetic data bank of sequenced sets of Parkinson’s disease-risk genes made accessible to patients. Since the end of 2020, the first year of patient enrollment, the number of participants has increased from 676 to 10,515 and the number of participating clinical sites rose from 12 to 101.

The foundation has spent nearly $20 million on the project so far and plans to spend another $10 million to reach a goal of 15,000 patients. The study, which is funded by private donors, is so successful that the foundation has had to scale back enrollment.

“When we were at a peak, we had over 700 participants enrolling each month,” Dr. Beck said. Beginning in April, the program capped new sign-ups to 200 patients per month and created a waiting list for future enrollment. The waiting list is hundreds of patients long.

“The participants’ response to enroll in PD GENEration demonstrates there is an overwhelming interest by people with Parkinson’s disease to learn more about their genetic risk factors,” Dr. Alcalay said.
 

A research driver

Nearly 60% of participants enrolled so far are male and close to 80% are White. The average age is 69 years and 44% were diagnosed in the past 5 years. Close to 75% had never participated in a clinical trial.

Nearly 13% have tested positive for mutations on at least one of the seven target genes. Previous studies had suggested genetics were involved in only about 10% of cases.

The majority of those with positive results had early-onset Parkinson’s disease, high-risk ancestry, or a first-degree relative with the disease. However, 9% of people who tested positive weren’t in any of those categories.

Genetic information collected by the project is shared with the Global Parkinson’s Genetics Program (GP2), a resource program of the Aligning Science Across Parkinson’s initiative that is focused on the disease’s genetic architecture. Researchers around the world have access to GP2 data to study known gene variants and identify new ones.

PD GENEration participants can choose to be notified if they are carriers of gene variants discovered in the future.

“All DNA samples shared by participants are undergoing research-grade testing,” Dr. Beck said. “Not only do we want to be able to inform people with Parkinson’s disease about their genetic status, but we also want to be able to use this precious resource to further drive research into the genetics of Parkinson’s disease.”
 

Early success

Patient recruitment has long been one of the biggest challenges to any clinical trial’s success. Research suggests that 90% of all clinical trials fail to reach recruitment milestones in their allotted time frame and two-thirds of multicenter trials fold because too few patients sign up. Data from the Parkinson’s Foundation show that only about 1% of all patients with Parkinson’s disease participate in clinical trials.

Increasing those numbers is the primary goal of PD GENEration, Dr. Beck said. And there’s evidence it’s already paying off.

Earlier this year, one of the program’s participating clinical sites, Intermountain Health, in Salt Lake City, Utah, joined a phase 2 clinical trial of an experimental drug that targets a mutation on the GBA1 gene.

“One of the reasons we were able to participate was when we got the call about joining, we were able to say that we had patients with that specific gene mutation, and we could only say that because the patients had been genotyped through PD GENEration,” said Kathleen E. McKee, MD, director of movement disorders, associate medical director of neurosciences research, and PD GENEration principal investigator at Intermountain Health.

Since 2021, Dr. McKee has enrolled hundreds of patients in the foundation’s gene study and hopes to enroll even more. Few patients turn down the opportunity to participate, she added. Knowing their genotype has proven empowering for her patients, most of whom could not afford genetic testing on their own.

“Previously I would tell patients this is not going to change your immediate management,” Dr. McKee said. “Now I tell my patients that these trials are out there, it may actually change how I treat you and what I recommend.”
 

A version of this article appeared on Medscape.com.

In 2017, Sanofi Genzyme launched a phase 2 clinical trial of a drug designed to target a specific genetic mutation in some patients with Parkinson’s disease. Researchers hoped the drug would slow or even stop disease progression.

Like many before it, the trial yielded disappointing results and the company shut it down in 2021. It was the latest in a string of unsuccessful clinical trials testing disease-modifying Parkinson’s disease drugs.

Although it failed, the Sanofi Genzyme study was different: It was the first to enroll patients with Parkinson’s disease who had a specific genotype and marked the earliest days of precision medicine and gene-specific drug development for the disease.

Once thought to play only a small role in a small number of patients with Parkinson’s disease, a growing body of work has prompted researchers and drug developers to take a longer look at how genetics influence Parkinson’s disease risk and progression.

“We’re about to enter this era of precision medicine for Parkinson’s disease, which makes genetic testing important,” said James Beck, PhD, senior vice president and chief scientific officer for the Parkinson’s Foundation.

“A number of companies have clinical trials or are in preparation for clinical trials to test some specific therapies that would depend upon people having a specific genetic mutation,” he said.

Today, at least four clinical trials of drugs that target specific Parkinson’s disease-related gene variants on LRRK2 and GBA are under way, and more are in the pipeline. Whether these drugs will be effective at modifying the course of the disease remains to be seen. First, the trials must enroll enough patients. And therein lies the challenge: Genetic testing isn’t part of routine Parkinson’s disease care and isn’t covered by most insurance policies. Most patients don’t know their genotype.

It’s a significant roadblock to the future of a precision medicine approach that is based on a patient’s individual genotype, which some experts argue offers the best shot at slowing disease progression.

“To enroll in clinical trials for precision drugs people with Parkinson’s disease have to be aware of their genetic status,” said Roy N. Alcalay, MD, chief of the movement disorders division at Tel Aviv Medical Center in Israel and part-time associate professor at Columbia University in New York. “How can a person with Parkinson’s and a LRRK2 mutation join a precision medicine trial for LRRK2 if she does not know she is a LRRK2 carrier?”
 

Free genetic testing

Previous studies have shown that some genetic variants increase the risk for Parkinson’s disease after exposure to environmental factors such as pesticides. Research has also shown that a patient’s genotype can predict survival time and that certain medications may prove more effective at slowing disease progression in patients with specific genotypes. All of this points to a significant role for genetics in a disorder that is rapidly increasing.

This makes expanding patient access to genetic testing even more important, Dr. Alcalay said, noting that it’s equally important that patients are informed of their genotype, something that doesn’t usually happen in blinded clinical trials.

To that end, Dr. Alcalay hopes a national genetics study he is leading will address access and need-to-know issues. PD GENEration, a project launched in 2019 by the Parkinson’s Foundation, offers patients free genetic testing for seven clinically relevant Parkinson’s disease-related genes.

Testing is done at home or in a nearby clinic and the results are shared with patients during a free genetic counseling session and with site investigators. Patient samples are stored in a genetic data bank that is open to researchers around the world.

“We surveyed clinical trialists in the Parkinson’s disease field prior to initiation of PD GENEration and estimated that over 90% of people with Parkinson’s disease prior to the effort were not aware of their genetic status,” Dr. Alcalay said.

“I think precision medicine in Parkinson’s disease will not happen without PD GENEration or similar efforts.”
 

‘Overwhelming’ patient interest

Participants in the study are screened for variants in seven genes known to be involved in Parkinson’s disease risk: GBA, LRRK2, PRKN, PINK1, SNCA, PARK7, and VPS35.

In less than 3 years, the study has already produced what is thought to be the largest genetic data bank of sequenced sets of Parkinson’s disease-risk genes made accessible to patients. Since the end of 2020, the first year of patient enrollment, the number of participants has increased from 676 to 10,515 and the number of participating clinical sites rose from 12 to 101.

The foundation has spent nearly $20 million on the project so far and plans to spend another $10 million to reach a goal of 15,000 patients. The study, which is funded by private donors, is so successful that the foundation has had to scale back enrollment.

“When we were at a peak, we had over 700 participants enrolling each month,” Dr. Beck said. Beginning in April, the program capped new sign-ups to 200 patients per month and created a waiting list for future enrollment. The waiting list is hundreds of patients long.

“The participants’ response to enroll in PD GENEration demonstrates there is an overwhelming interest by people with Parkinson’s disease to learn more about their genetic risk factors,” Dr. Alcalay said.
 

A research driver

Nearly 60% of participants enrolled so far are male and close to 80% are White. The average age is 69 years and 44% were diagnosed in the past 5 years. Close to 75% had never participated in a clinical trial.

Nearly 13% have tested positive for mutations on at least one of the seven target genes. Previous studies had suggested genetics were involved in only about 10% of cases.

The majority of those with positive results had early-onset Parkinson’s disease, high-risk ancestry, or a first-degree relative with the disease. However, 9% of people who tested positive weren’t in any of those categories.

Genetic information collected by the project is shared with the Global Parkinson’s Genetics Program (GP2), a resource program of the Aligning Science Across Parkinson’s initiative that is focused on the disease’s genetic architecture. Researchers around the world have access to GP2 data to study known gene variants and identify new ones.

PD GENEration participants can choose to be notified if they are carriers of gene variants discovered in the future.

“All DNA samples shared by participants are undergoing research-grade testing,” Dr. Beck said. “Not only do we want to be able to inform people with Parkinson’s disease about their genetic status, but we also want to be able to use this precious resource to further drive research into the genetics of Parkinson’s disease.”
 

Early success

Patient recruitment has long been one of the biggest challenges to any clinical trial’s success. Research suggests that 90% of all clinical trials fail to reach recruitment milestones in their allotted time frame and two-thirds of multicenter trials fold because too few patients sign up. Data from the Parkinson’s Foundation show that only about 1% of all patients with Parkinson’s disease participate in clinical trials.

Increasing those numbers is the primary goal of PD GENEration, Dr. Beck said. And there’s evidence it’s already paying off.

Earlier this year, one of the program’s participating clinical sites, Intermountain Health, in Salt Lake City, Utah, joined a phase 2 clinical trial of an experimental drug that targets a mutation on the GBA1 gene.

“One of the reasons we were able to participate was when we got the call about joining, we were able to say that we had patients with that specific gene mutation, and we could only say that because the patients had been genotyped through PD GENEration,” said Kathleen E. McKee, MD, director of movement disorders, associate medical director of neurosciences research, and PD GENEration principal investigator at Intermountain Health.

Since 2021, Dr. McKee has enrolled hundreds of patients in the foundation’s gene study and hopes to enroll even more. Few patients turn down the opportunity to participate, she added. Knowing their genotype has proven empowering for her patients, most of whom could not afford genetic testing on their own.

“Previously I would tell patients this is not going to change your immediate management,” Dr. McKee said. “Now I tell my patients that these trials are out there, it may actually change how I treat you and what I recommend.”
 

A version of this article appeared on Medscape.com.

Continuous glucose monitors (CGMs) may help curb the severity of hypoglycemia after weight loss operations and even other gastrointestinal procedures, according to recent findings from a small study published in Diabetes, Obesity, and Metabolism.

Hypoglycemia is a chronic and persistent complication common in patients following bariatric surgery, affecting as many as 30% of people who undergo a sleeve gastrectomy or Roux-en-Y gastric bypass.

The symptoms of hypoglycemia, including lightheadedness, heart palpitations, difficulty concentrating, and confusion, can mimic anxiety disorders, arrhythmia, and dumping syndrome.

If a postoperative patient experiences these symptoms within a few hours following a meal or exercising, “primary care doctors should consider the possibility that hypoglycemia may be a contributor,” said Mary-Elizabeth Patti, MD, director of the Hypoglycemia Clinic at the Joslin Diabetes Center in Boston and senior author of the new study. 

“In fact, hypoglycemia is a possible diagnosis even among those who underwent [operations other than bariatric, including] fundoplication or other upper gastrointestinal or esophageal surgeries,” she said. 

To understand how CGM could benefit patients, Dr. Patti and colleagues recruited 22 participants who had undergone bariatric surgery more than 8 years prior and had postbariatric hypoglycemia. Their mean age was 51 years, 90% were women, 82% were diagnosed with level 3 hypoglycemia, and none had type 1 or 2 diabetes. 

All participants experienced neuronal dysfunction with symptoms like fatigue, concentration difficulties, and confusion. More than 90% had received medical nutrition therapy for postbariatric hypoglycemia in the past.

CGM data were collected in the 22 individuals in two sequential phases: masked (no access to sensor glucose or alarms) and unmasked (access to sensor glucose and alarms for low or rapidly declining sensor glucose). Twelve participants wore a CGM (Dexcom G4 device) for a total of 28 days, whereas 10 wore a CGM (the Dexcom G6 device) for a total of 20 days.

The team observed that the percentage of time when the participants’ blood glucose was below 70 mg/dL – the definition of hypoglycemia – was significantly lower during the unmasked phase. 

Though CGM devices are not sensitive enough to serve as a diagnostic tool for hypoglycemia, “the alarms on CGM devices can provide some much-needed awareness,” Dr. Patti said. “After a detailed diagnosis, CGM devices can be a helpful tool to assess dietary patterns and make modifications that could reduce the severity of postbariatric hypoglycemia.”

If a patient frequently experiences hypoglycemia, they may not sense when their glucose levels drop, also known as hypoglycemia unawareness, according to Dr. Patti. Studies have found that postbariatric hypoglycemia remains underdiagnosed because most patients are asymptomatic. 

“The use of CGM devices may improve safety in postbariatric hypoglycemia, particularly for patients with hypoglycemia unawareness,” the researchers conclude.
 

Next steps 

Patients are more vulnerable to hypoglycemia after a sleeve gastrectomy or gastric bypass surgery because these procedures involve removing the pylorus. This valve plays a crucial role in only allowing small portions of food to enter the intestine and prevents sudden spikes in blood glucose.

Without the pylorus, large amounts of food directly enter the intestine and soon result in large amounts of glucose getting absorbed, according to Sriram Machineni, MD, an associate professor of medicine at Albert Einstein College of Medicine, New York, who was not affiliated with the study.

“The pancreas then goes into overdrive and produces a lot of insulin, which continues reducing sugar levels,” Dr. Machineni said. “That is what causes hypoglycemia.”

Dr. Patti and associates are next working on research using CGM-derived data to investigate how different types of meals, physical activities, and other factors could influence glucose metabolism patterns in patients with hypoglycemia.

The study was funded by Dexcom, a manufacturer of continuous glucose monitoring systems. Dr. Patti reported receiving grant funding from the Diabetes Research Center.

A version of this article appeared on Medscape.com.

Continuous glucose monitors (CGMs) may help curb the severity of hypoglycemia after weight loss operations and even other gastrointestinal procedures, according to recent findings from a small study published in Diabetes, Obesity, and Metabolism.

Hypoglycemia is a chronic and persistent complication common in patients following bariatric surgery, affecting as many as 30% of people who undergo a sleeve gastrectomy or Roux-en-Y gastric bypass.

The symptoms of hypoglycemia, including lightheadedness, heart palpitations, difficulty concentrating, and confusion, can mimic anxiety disorders, arrhythmia, and dumping syndrome.

If a postoperative patient experiences these symptoms within a few hours following a meal or exercising, “primary care doctors should consider the possibility that hypoglycemia may be a contributor,” said Mary-Elizabeth Patti, MD, director of the Hypoglycemia Clinic at the Joslin Diabetes Center in Boston and senior author of the new study. 

“In fact, hypoglycemia is a possible diagnosis even among those who underwent [operations other than bariatric, including] fundoplication or other upper gastrointestinal or esophageal surgeries,” she said. 

To understand how CGM could benefit patients, Dr. Patti and colleagues recruited 22 participants who had undergone bariatric surgery more than 8 years prior and had postbariatric hypoglycemia. Their mean age was 51 years, 90% were women, 82% were diagnosed with level 3 hypoglycemia, and none had type 1 or 2 diabetes. 

All participants experienced neuronal dysfunction with symptoms like fatigue, concentration difficulties, and confusion. More than 90% had received medical nutrition therapy for postbariatric hypoglycemia in the past.

CGM data were collected in the 22 individuals in two sequential phases: masked (no access to sensor glucose or alarms) and unmasked (access to sensor glucose and alarms for low or rapidly declining sensor glucose). Twelve participants wore a CGM (Dexcom G4 device) for a total of 28 days, whereas 10 wore a CGM (the Dexcom G6 device) for a total of 20 days.

The team observed that the percentage of time when the participants’ blood glucose was below 70 mg/dL – the definition of hypoglycemia – was significantly lower during the unmasked phase. 

Though CGM devices are not sensitive enough to serve as a diagnostic tool for hypoglycemia, “the alarms on CGM devices can provide some much-needed awareness,” Dr. Patti said. “After a detailed diagnosis, CGM devices can be a helpful tool to assess dietary patterns and make modifications that could reduce the severity of postbariatric hypoglycemia.”

If a patient frequently experiences hypoglycemia, they may not sense when their glucose levels drop, also known as hypoglycemia unawareness, according to Dr. Patti. Studies have found that postbariatric hypoglycemia remains underdiagnosed because most patients are asymptomatic. 

“The use of CGM devices may improve safety in postbariatric hypoglycemia, particularly for patients with hypoglycemia unawareness,” the researchers conclude.
 

Next steps 

Patients are more vulnerable to hypoglycemia after a sleeve gastrectomy or gastric bypass surgery because these procedures involve removing the pylorus. This valve plays a crucial role in only allowing small portions of food to enter the intestine and prevents sudden spikes in blood glucose.

Without the pylorus, large amounts of food directly enter the intestine and soon result in large amounts of glucose getting absorbed, according to Sriram Machineni, MD, an associate professor of medicine at Albert Einstein College of Medicine, New York, who was not affiliated with the study.

“The pancreas then goes into overdrive and produces a lot of insulin, which continues reducing sugar levels,” Dr. Machineni said. “That is what causes hypoglycemia.”

Dr. Patti and associates are next working on research using CGM-derived data to investigate how different types of meals, physical activities, and other factors could influence glucose metabolism patterns in patients with hypoglycemia.

The study was funded by Dexcom, a manufacturer of continuous glucose monitoring systems. Dr. Patti reported receiving grant funding from the Diabetes Research Center.

A version of this article appeared on Medscape.com.

Continuous glucose monitors (CGMs) may help curb the severity of hypoglycemia after weight loss operations and even other gastrointestinal procedures, according to recent findings from a small study published in Diabetes, Obesity, and Metabolism.

Hypoglycemia is a chronic and persistent complication common in patients following bariatric surgery, affecting as many as 30% of people who undergo a sleeve gastrectomy or Roux-en-Y gastric bypass.

The symptoms of hypoglycemia, including lightheadedness, heart palpitations, difficulty concentrating, and confusion, can mimic anxiety disorders, arrhythmia, and dumping syndrome.

If a postoperative patient experiences these symptoms within a few hours following a meal or exercising, “primary care doctors should consider the possibility that hypoglycemia may be a contributor,” said Mary-Elizabeth Patti, MD, director of the Hypoglycemia Clinic at the Joslin Diabetes Center in Boston and senior author of the new study. 

“In fact, hypoglycemia is a possible diagnosis even among those who underwent [operations other than bariatric, including] fundoplication or other upper gastrointestinal or esophageal surgeries,” she said. 

To understand how CGM could benefit patients, Dr. Patti and colleagues recruited 22 participants who had undergone bariatric surgery more than 8 years prior and had postbariatric hypoglycemia. Their mean age was 51 years, 90% were women, 82% were diagnosed with level 3 hypoglycemia, and none had type 1 or 2 diabetes. 

All participants experienced neuronal dysfunction with symptoms like fatigue, concentration difficulties, and confusion. More than 90% had received medical nutrition therapy for postbariatric hypoglycemia in the past.

CGM data were collected in the 22 individuals in two sequential phases: masked (no access to sensor glucose or alarms) and unmasked (access to sensor glucose and alarms for low or rapidly declining sensor glucose). Twelve participants wore a CGM (Dexcom G4 device) for a total of 28 days, whereas 10 wore a CGM (the Dexcom G6 device) for a total of 20 days.

The team observed that the percentage of time when the participants’ blood glucose was below 70 mg/dL – the definition of hypoglycemia – was significantly lower during the unmasked phase. 

Though CGM devices are not sensitive enough to serve as a diagnostic tool for hypoglycemia, “the alarms on CGM devices can provide some much-needed awareness,” Dr. Patti said. “After a detailed diagnosis, CGM devices can be a helpful tool to assess dietary patterns and make modifications that could reduce the severity of postbariatric hypoglycemia.”

If a patient frequently experiences hypoglycemia, they may not sense when their glucose levels drop, also known as hypoglycemia unawareness, according to Dr. Patti. Studies have found that postbariatric hypoglycemia remains underdiagnosed because most patients are asymptomatic. 

“The use of CGM devices may improve safety in postbariatric hypoglycemia, particularly for patients with hypoglycemia unawareness,” the researchers conclude.
 

Next steps 

Patients are more vulnerable to hypoglycemia after a sleeve gastrectomy or gastric bypass surgery because these procedures involve removing the pylorus. This valve plays a crucial role in only allowing small portions of food to enter the intestine and prevents sudden spikes in blood glucose.

Without the pylorus, large amounts of food directly enter the intestine and soon result in large amounts of glucose getting absorbed, according to Sriram Machineni, MD, an associate professor of medicine at Albert Einstein College of Medicine, New York, who was not affiliated with the study.

“The pancreas then goes into overdrive and produces a lot of insulin, which continues reducing sugar levels,” Dr. Machineni said. “That is what causes hypoglycemia.”

Dr. Patti and associates are next working on research using CGM-derived data to investigate how different types of meals, physical activities, and other factors could influence glucose metabolism patterns in patients with hypoglycemia.

The study was funded by Dexcom, a manufacturer of continuous glucose monitoring systems. Dr. Patti reported receiving grant funding from the Diabetes Research Center.

A version of this article appeared on Medscape.com.

A new discovery of differences between the eyes of people with and without diabetes could point to new approaches for treating diabetic keratopathy, as well as other diabetes-related wound healing problems.

Vision loss caused by diabetes arises primarily from retinopathy, but up to 70% of people with diabetes also experience corneal problems, including keratopathy and neuropathy. Diabetic keratopathy involves impairments in epithelial wound healing, barrier function, and tear production, along with epithelial erosions and keratitis. As a result, the cornea may heal more slowly and less completely following an injury or procedures such as cataract surgery or laser therapy for diabetic retinopathy.

The abnormal wound healing is caused by impaired limbal epithelial stem cells, and the new research, published online in Diabetologia, involved isolation of those cells from 30 donor eyes of humans with and 23 without diabetes. Significant differences were found in DNA methylation between the cells of those two groups. Specifically, the WNT5A gene was hypermethylated at the promotor region in the diabetic cells and its protein markedly repressed.

However, treatment with various approaches, including exogenous WNT5A methylation inhibitors and a nanoconjugate that inhibits WNT5A suppression, improved corneal epithelial wound healing as well as expression of the limbic epithelial stem cells.

“Overall, [the] Wnt-5a [protein] is a new corneal epithelial wound healing stimulator that can be targeted to improve wound healing and stem cells in the diabetic cornea,” wrote Ruchi Shah, PhD, of the Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, and colleagues.

The finding represents more cellular changes than researchers had previously been aware of, study senior author Alexander Ljubimov, PhD, DSc, director of the eye program at the Institute, said in a statement.

“The discovery does not affect gene sequence but entails specific DNA modifications altering gene expression – what are known as epigenetic alterations,” he said.

In the experiments, treatment of the impaired diabetic limbal epithelial cells with the exogenous Wnt-5a accelerated wound healing by 1.4-fold (P < .05), compared with untreated cells and reduced healing time in diabetic organ-ultured corneas by 37% (P < .05).

Treatment with the DNA methylation inhibitor zebularine also increased levels of Wnt-5a in the diabetic limbic epithelial cells by 37% (P < .01), dose-dependently stimulated wound healing by 60% at 24 hours (P < .01), and improved wound healing by 30% in diabetic organ-cultured corneas.

The finding of Wnt-5a as a new diabetic corneal marker regulating wound healing and stem cell function may have implications for other diabetes complications involving impaired wound healing, including diabetic foot ulcers, as they share similar neurovascular, sensory, and immunological compromise with diabetic eye disease, Dr. Shah and colleagues wrote.

“Novel therapies to reverse both types of epigenetic silencing could benefit corneal function and may also prove to be beneficial in other wound healing–related diabetic complications,” they wrote.

The investigators are now working on combination therapies that target both mRNA and DNA methylation in hopes of obtaining even better wound healing.

“Our goal is to develop topical, sustained-release drugs for corneal wound healing,” said Dr. Ljubimov. “Drugs that are [Food and Drug Administration] approved and could be easily applied may be one of the most promising approaches for effective future therapies.”

This work was funded by the National Institutes of Health and the Cedars-Sinai Board of Governors Regenerative Medicine Institute. The authors reported no further disclosures.

A version of this article appeared on Medscape.com.

A new discovery of differences between the eyes of people with and without diabetes could point to new approaches for treating diabetic keratopathy, as well as other diabetes-related wound healing problems.

Vision loss caused by diabetes arises primarily from retinopathy, but up to 70% of people with diabetes also experience corneal problems, including keratopathy and neuropathy. Diabetic keratopathy involves impairments in epithelial wound healing, barrier function, and tear production, along with epithelial erosions and keratitis. As a result, the cornea may heal more slowly and less completely following an injury or procedures such as cataract surgery or laser therapy for diabetic retinopathy.

The abnormal wound healing is caused by impaired limbal epithelial stem cells, and the new research, published online in Diabetologia, involved isolation of those cells from 30 donor eyes of humans with and 23 without diabetes. Significant differences were found in DNA methylation between the cells of those two groups. Specifically, the WNT5A gene was hypermethylated at the promotor region in the diabetic cells and its protein markedly repressed.

However, treatment with various approaches, including exogenous WNT5A methylation inhibitors and a nanoconjugate that inhibits WNT5A suppression, improved corneal epithelial wound healing as well as expression of the limbic epithelial stem cells.

“Overall, [the] Wnt-5a [protein] is a new corneal epithelial wound healing stimulator that can be targeted to improve wound healing and stem cells in the diabetic cornea,” wrote Ruchi Shah, PhD, of the Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, and colleagues.

The finding represents more cellular changes than researchers had previously been aware of, study senior author Alexander Ljubimov, PhD, DSc, director of the eye program at the Institute, said in a statement.

“The discovery does not affect gene sequence but entails specific DNA modifications altering gene expression – what are known as epigenetic alterations,” he said.

In the experiments, treatment of the impaired diabetic limbal epithelial cells with the exogenous Wnt-5a accelerated wound healing by 1.4-fold (P < .05), compared with untreated cells and reduced healing time in diabetic organ-ultured corneas by 37% (P < .05).

Treatment with the DNA methylation inhibitor zebularine also increased levels of Wnt-5a in the diabetic limbic epithelial cells by 37% (P < .01), dose-dependently stimulated wound healing by 60% at 24 hours (P < .01), and improved wound healing by 30% in diabetic organ-cultured corneas.

The finding of Wnt-5a as a new diabetic corneal marker regulating wound healing and stem cell function may have implications for other diabetes complications involving impaired wound healing, including diabetic foot ulcers, as they share similar neurovascular, sensory, and immunological compromise with diabetic eye disease, Dr. Shah and colleagues wrote.

“Novel therapies to reverse both types of epigenetic silencing could benefit corneal function and may also prove to be beneficial in other wound healing–related diabetic complications,” they wrote.

The investigators are now working on combination therapies that target both mRNA and DNA methylation in hopes of obtaining even better wound healing.

“Our goal is to develop topical, sustained-release drugs for corneal wound healing,” said Dr. Ljubimov. “Drugs that are [Food and Drug Administration] approved and could be easily applied may be one of the most promising approaches for effective future therapies.”

This work was funded by the National Institutes of Health and the Cedars-Sinai Board of Governors Regenerative Medicine Institute. The authors reported no further disclosures.

A version of this article appeared on Medscape.com.

A new discovery of differences between the eyes of people with and without diabetes could point to new approaches for treating diabetic keratopathy, as well as other diabetes-related wound healing problems.

Vision loss caused by diabetes arises primarily from retinopathy, but up to 70% of people with diabetes also experience corneal problems, including keratopathy and neuropathy. Diabetic keratopathy involves impairments in epithelial wound healing, barrier function, and tear production, along with epithelial erosions and keratitis. As a result, the cornea may heal more slowly and less completely following an injury or procedures such as cataract surgery or laser therapy for diabetic retinopathy.

The abnormal wound healing is caused by impaired limbal epithelial stem cells, and the new research, published online in Diabetologia, involved isolation of those cells from 30 donor eyes of humans with and 23 without diabetes. Significant differences were found in DNA methylation between the cells of those two groups. Specifically, the WNT5A gene was hypermethylated at the promotor region in the diabetic cells and its protein markedly repressed.

However, treatment with various approaches, including exogenous WNT5A methylation inhibitors and a nanoconjugate that inhibits WNT5A suppression, improved corneal epithelial wound healing as well as expression of the limbic epithelial stem cells.

“Overall, [the] Wnt-5a [protein] is a new corneal epithelial wound healing stimulator that can be targeted to improve wound healing and stem cells in the diabetic cornea,” wrote Ruchi Shah, PhD, of the Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, and colleagues.

The finding represents more cellular changes than researchers had previously been aware of, study senior author Alexander Ljubimov, PhD, DSc, director of the eye program at the Institute, said in a statement.

“The discovery does not affect gene sequence but entails specific DNA modifications altering gene expression – what are known as epigenetic alterations,” he said.

In the experiments, treatment of the impaired diabetic limbal epithelial cells with the exogenous Wnt-5a accelerated wound healing by 1.4-fold (P < .05), compared with untreated cells and reduced healing time in diabetic organ-ultured corneas by 37% (P < .05).

Treatment with the DNA methylation inhibitor zebularine also increased levels of Wnt-5a in the diabetic limbic epithelial cells by 37% (P < .01), dose-dependently stimulated wound healing by 60% at 24 hours (P < .01), and improved wound healing by 30% in diabetic organ-cultured corneas.

The finding of Wnt-5a as a new diabetic corneal marker regulating wound healing and stem cell function may have implications for other diabetes complications involving impaired wound healing, including diabetic foot ulcers, as they share similar neurovascular, sensory, and immunological compromise with diabetic eye disease, Dr. Shah and colleagues wrote.

“Novel therapies to reverse both types of epigenetic silencing could benefit corneal function and may also prove to be beneficial in other wound healing–related diabetic complications,” they wrote.

The investigators are now working on combination therapies that target both mRNA and DNA methylation in hopes of obtaining even better wound healing.

“Our goal is to develop topical, sustained-release drugs for corneal wound healing,” said Dr. Ljubimov. “Drugs that are [Food and Drug Administration] approved and could be easily applied may be one of the most promising approaches for effective future therapies.”

This work was funded by the National Institutes of Health and the Cedars-Sinai Board of Governors Regenerative Medicine Institute. The authors reported no further disclosures.

A version of this article appeared on Medscape.com.

A defined exercise program significantly improved cardiometabolic health and body composition in children with overweight and obesity, but no effect was seen on mental health, based on data from 92 children.

Childhood obesity is associated with negative health outcomes including type 2 diabetes, cardiovascular disease, and mental health disorders, and exercise is considered essential to treatment, wrote Jairo H. Migueles, PhD, of the University of Granada, Spain, and colleagues. However, the effect on children with obesity and overweight of an exercise program on physical and mental health, including within-individual changes, has not been well studied, they said.

In a study published in JAMA Network Open, the researchers reviewed data from 36 girls and 56 boys with overweight or obesity who were randomized to a 20-week exercise program with aerobic and resistance elements, or waitlisted to serve as controls. The participants ranged in age from 8 to 11 years with a mean age of 10 years. The data were collected between Nov. 1, 2014, and June 30, 2016, as part of a parallel-group randomized clinical trial. The exercise program consisted of three to five 90-minute exercise sessions per week for 20 weeks, and the control children continued their usual routines.

The main cardiometabolic outcomes measured in the study were divided into three categories: body composition, physical fitness, and traditional risk factors (waist circumference, blood lipid levels, glucose levels, insulin levels, and blood pressure).

A cardiometabolic risk score was defined by z score. The researchers also added cardiorespiratory fitness (CRF) to the cardiometabolic risk score. Mental health was assessed using composite standardized scores for psychological well-being and poor mental health.

After 20 weeks, cardiometabolic risk scores decreased by approximately 0.38 standard deviations in the exercise group compared with the control group. In addition, specific measures of cardiometabolic health improved significantly from baseline in the exercise group compared with control children for low-density lipoprotein (change of –7.00 mg/dL), body mass index (–5.9 kg/m²), fat mass index (−0.67), and visceral adipose tissue (31.44 g).

Cardiorespiratory fitness improved by 2.75 laps in the exercise group compared with control children. In addition, significantly more children in the exercise group showed meaningful changes (defined as individual changes of at least 0.2 SDs) compared with control children in measures of fat mass index (37 vs. 17, P < .001) and CRF performance (30 vs. 17, P = .03).

However, no significant effects appeared on mental health outcomes in exercisers, the researchers noted.

The reduction in cardiometabolic score was attributable mainly to improvements in cardiovascular fitness, blood lipid levels, and total and visceral adiposity, the researchers wrote in their discussion. The lack of changes in mental health measures may be a result of the healthy mental state of the children at the study outset, they said. “The null effect on mental health outcomes needs to be further investigated, including, among other things, whether the instruments are sensitive enough to detect changes and whether there is a ceiling effect in young children who might be mentally healthy overall,” they wrote.

The findings were limited by several factors, including the relatively small sample size and lack of blinding for some evaluators. However, the results show the potential of exercise programs to affect meaningful change and improve cardiometabolic health in overweight and obese children, although more research is needed to explore the effects of larger-scale and longer-lasting public health interventions combining exercise and other health behaviors such as diet, the researchers concluded.
 

Bottom line: Exercise works

The increasing rates of overweight and obesity in children in the United States have “significant downstream consequences that include increased risk of metabolic disease, including diabetes and hypertension, as well as increased rates of anxiety and depression,” Neil Skolnik, MD, professor of family and community medicine at the Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, said in an interview.

Therefore, the effect of interventions such as exercise training on outcomes is important, he said. 

The current study findings are “what you would hope for and expect – improvement in cardiometabolic parameters and fitness,” said Dr. Skolnik. “It was encouraging to see the effect of this relatively short duration of intervention has a clear positive effect on weight, BMI, and cardiometabolic parameters,” he said. “The real benefit, of course, comes from sustaining these habits over a long period of time.”

The lack of improvement in mental health is not surprising given the small study population “who did not have a high rate of mental health problems to begin with,” Dr. Skolnik added.

Barriers to promoting exercise programs for obese and overweight children in primary care are many, Dr. Skolnik said, including “having the motivation and funding to create programs like this so they are readily available to youth.”

However, the key message from the current study is simple and straightforward, according to Dr. Skolnik. “Exercise works! It works to improve fitness, cardiometabolic parameters, and weight control,” he said.

“There is always room for more research,” Dr. Skolnik added. The questions now are not about whether exercise benefits health; they are about figuring out how to implement the known benefits of exercise into daily living for all children, athletes and nonathletes alike, he said. “We need to find nonjudgmental ways to encourage exercise as a part of routine daily healthy living, up there with brushing teeth every day,” he emphasized.

The study was supported by grants from the Spanish Ministry of Economy and Competitiveness and El Fondo Europeo de Desarrollo Regional (FEDER) and by the MCIN (Ministerio de Ciencia e Innovación) / AEI (Agencia Estatal de Investigación. The researchers and Dr. Skolnik had no financial conflicts to disclose. Dr. Skolnik serves on the editorial advisory board of Family Practice News.

A defined exercise program significantly improved cardiometabolic health and body composition in children with overweight and obesity, but no effect was seen on mental health, based on data from 92 children.

Childhood obesity is associated with negative health outcomes including type 2 diabetes, cardiovascular disease, and mental health disorders, and exercise is considered essential to treatment, wrote Jairo H. Migueles, PhD, of the University of Granada, Spain, and colleagues. However, the effect on children with obesity and overweight of an exercise program on physical and mental health, including within-individual changes, has not been well studied, they said.

In a study published in JAMA Network Open, the researchers reviewed data from 36 girls and 56 boys with overweight or obesity who were randomized to a 20-week exercise program with aerobic and resistance elements, or waitlisted to serve as controls. The participants ranged in age from 8 to 11 years with a mean age of 10 years. The data were collected between Nov. 1, 2014, and June 30, 2016, as part of a parallel-group randomized clinical trial. The exercise program consisted of three to five 90-minute exercise sessions per week for 20 weeks, and the control children continued their usual routines.

The main cardiometabolic outcomes measured in the study were divided into three categories: body composition, physical fitness, and traditional risk factors (waist circumference, blood lipid levels, glucose levels, insulin levels, and blood pressure).

A cardiometabolic risk score was defined by z score. The researchers also added cardiorespiratory fitness (CRF) to the cardiometabolic risk score. Mental health was assessed using composite standardized scores for psychological well-being and poor mental health.

After 20 weeks, cardiometabolic risk scores decreased by approximately 0.38 standard deviations in the exercise group compared with the control group. In addition, specific measures of cardiometabolic health improved significantly from baseline in the exercise group compared with control children for low-density lipoprotein (change of –7.00 mg/dL), body mass index (–5.9 kg/m²), fat mass index (−0.67), and visceral adipose tissue (31.44 g).

Cardiorespiratory fitness improved by 2.75 laps in the exercise group compared with control children. In addition, significantly more children in the exercise group showed meaningful changes (defined as individual changes of at least 0.2 SDs) compared with control children in measures of fat mass index (37 vs. 17, P < .001) and CRF performance (30 vs. 17, P = .03).

However, no significant effects appeared on mental health outcomes in exercisers, the researchers noted.

The reduction in cardiometabolic score was attributable mainly to improvements in cardiovascular fitness, blood lipid levels, and total and visceral adiposity, the researchers wrote in their discussion. The lack of changes in mental health measures may be a result of the healthy mental state of the children at the study outset, they said. “The null effect on mental health outcomes needs to be further investigated, including, among other things, whether the instruments are sensitive enough to detect changes and whether there is a ceiling effect in young children who might be mentally healthy overall,” they wrote.

The findings were limited by several factors, including the relatively small sample size and lack of blinding for some evaluators. However, the results show the potential of exercise programs to affect meaningful change and improve cardiometabolic health in overweight and obese children, although more research is needed to explore the effects of larger-scale and longer-lasting public health interventions combining exercise and other health behaviors such as diet, the researchers concluded.
 

Bottom line: Exercise works

The increasing rates of overweight and obesity in children in the United States have “significant downstream consequences that include increased risk of metabolic disease, including diabetes and hypertension, as well as increased rates of anxiety and depression,” Neil Skolnik, MD, professor of family and community medicine at the Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, said in an interview.

Therefore, the effect of interventions such as exercise training on outcomes is important, he said. 

The current study findings are “what you would hope for and expect – improvement in cardiometabolic parameters and fitness,” said Dr. Skolnik. “It was encouraging to see the effect of this relatively short duration of intervention has a clear positive effect on weight, BMI, and cardiometabolic parameters,” he said. “The real benefit, of course, comes from sustaining these habits over a long period of time.”

The lack of improvement in mental health is not surprising given the small study population “who did not have a high rate of mental health problems to begin with,” Dr. Skolnik added.

Barriers to promoting exercise programs for obese and overweight children in primary care are many, Dr. Skolnik said, including “having the motivation and funding to create programs like this so they are readily available to youth.”

However, the key message from the current study is simple and straightforward, according to Dr. Skolnik. “Exercise works! It works to improve fitness, cardiometabolic parameters, and weight control,” he said.

“There is always room for more research,” Dr. Skolnik added. The questions now are not about whether exercise benefits health; they are about figuring out how to implement the known benefits of exercise into daily living for all children, athletes and nonathletes alike, he said. “We need to find nonjudgmental ways to encourage exercise as a part of routine daily healthy living, up there with brushing teeth every day,” he emphasized.

The study was supported by grants from the Spanish Ministry of Economy and Competitiveness and El Fondo Europeo de Desarrollo Regional (FEDER) and by the MCIN (Ministerio de Ciencia e Innovación) / AEI (Agencia Estatal de Investigación. The researchers and Dr. Skolnik had no financial conflicts to disclose. Dr. Skolnik serves on the editorial advisory board of Family Practice News.

A defined exercise program significantly improved cardiometabolic health and body composition in children with overweight and obesity, but no effect was seen on mental health, based on data from 92 children.

Childhood obesity is associated with negative health outcomes including type 2 diabetes, cardiovascular disease, and mental health disorders, and exercise is considered essential to treatment, wrote Jairo H. Migueles, PhD, of the University of Granada, Spain, and colleagues. However, the effect on children with obesity and overweight of an exercise program on physical and mental health, including within-individual changes, has not been well studied, they said.

In a study published in JAMA Network Open, the researchers reviewed data from 36 girls and 56 boys with overweight or obesity who were randomized to a 20-week exercise program with aerobic and resistance elements, or waitlisted to serve as controls. The participants ranged in age from 8 to 11 years with a mean age of 10 years. The data were collected between Nov. 1, 2014, and June 30, 2016, as part of a parallel-group randomized clinical trial. The exercise program consisted of three to five 90-minute exercise sessions per week for 20 weeks, and the control children continued their usual routines.

The main cardiometabolic outcomes measured in the study were divided into three categories: body composition, physical fitness, and traditional risk factors (waist circumference, blood lipid levels, glucose levels, insulin levels, and blood pressure).

A cardiometabolic risk score was defined by z score. The researchers also added cardiorespiratory fitness (CRF) to the cardiometabolic risk score. Mental health was assessed using composite standardized scores for psychological well-being and poor mental health.

After 20 weeks, cardiometabolic risk scores decreased by approximately 0.38 standard deviations in the exercise group compared with the control group. In addition, specific measures of cardiometabolic health improved significantly from baseline in the exercise group compared with control children for low-density lipoprotein (change of –7.00 mg/dL), body mass index (–5.9 kg/m²), fat mass index (−0.67), and visceral adipose tissue (31.44 g).

Cardiorespiratory fitness improved by 2.75 laps in the exercise group compared with control children. In addition, significantly more children in the exercise group showed meaningful changes (defined as individual changes of at least 0.2 SDs) compared with control children in measures of fat mass index (37 vs. 17, P < .001) and CRF performance (30 vs. 17, P = .03).

However, no significant effects appeared on mental health outcomes in exercisers, the researchers noted.

The reduction in cardiometabolic score was attributable mainly to improvements in cardiovascular fitness, blood lipid levels, and total and visceral adiposity, the researchers wrote in their discussion. The lack of changes in mental health measures may be a result of the healthy mental state of the children at the study outset, they said. “The null effect on mental health outcomes needs to be further investigated, including, among other things, whether the instruments are sensitive enough to detect changes and whether there is a ceiling effect in young children who might be mentally healthy overall,” they wrote.

The findings were limited by several factors, including the relatively small sample size and lack of blinding for some evaluators. However, the results show the potential of exercise programs to affect meaningful change and improve cardiometabolic health in overweight and obese children, although more research is needed to explore the effects of larger-scale and longer-lasting public health interventions combining exercise and other health behaviors such as diet, the researchers concluded.
 

Bottom line: Exercise works

The increasing rates of overweight and obesity in children in the United States have “significant downstream consequences that include increased risk of metabolic disease, including diabetes and hypertension, as well as increased rates of anxiety and depression,” Neil Skolnik, MD, professor of family and community medicine at the Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, said in an interview.

Therefore, the effect of interventions such as exercise training on outcomes is important, he said. 

The current study findings are “what you would hope for and expect – improvement in cardiometabolic parameters and fitness,” said Dr. Skolnik. “It was encouraging to see the effect of this relatively short duration of intervention has a clear positive effect on weight, BMI, and cardiometabolic parameters,” he said. “The real benefit, of course, comes from sustaining these habits over a long period of time.”

The lack of improvement in mental health is not surprising given the small study population “who did not have a high rate of mental health problems to begin with,” Dr. Skolnik added.

Barriers to promoting exercise programs for obese and overweight children in primary care are many, Dr. Skolnik said, including “having the motivation and funding to create programs like this so they are readily available to youth.”

However, the key message from the current study is simple and straightforward, according to Dr. Skolnik. “Exercise works! It works to improve fitness, cardiometabolic parameters, and weight control,” he said.

“There is always room for more research,” Dr. Skolnik added. The questions now are not about whether exercise benefits health; they are about figuring out how to implement the known benefits of exercise into daily living for all children, athletes and nonathletes alike, he said. “We need to find nonjudgmental ways to encourage exercise as a part of routine daily healthy living, up there with brushing teeth every day,” he emphasized.

The study was supported by grants from the Spanish Ministry of Economy and Competitiveness and El Fondo Europeo de Desarrollo Regional (FEDER) and by the MCIN (Ministerio de Ciencia e Innovación) / AEI (Agencia Estatal de Investigación. The researchers and Dr. Skolnik had no financial conflicts to disclose. Dr. Skolnik serves on the editorial advisory board of Family Practice News.

This past June, during the search for the Titan submersible, and since then, we’ve had a not-entirely-unexpected development: Sick humor.

There was a lot of it. The Subway owner who got reprimanded for putting “Our subs don’t implode” on his sign was minor league compared with other things circulating on the Internet. One example that was sent to me showed the late Stockton Rush, OceanGate’s co-owner, as the new spokesman for Cap’n Crunch.

Of course, this is nothing new. People have made jokes about awful situations since to the dawn of civilization.

Why do we do this?

Humor is a remarkably human trait. There’s evidence other mammals have it, but not to the extent we do. We’ve created a multitude of forms that vary between cultures. But there isn’t a civilization or culture on Earth that doesn’t have humor.

Why we developed it I’ll leave to others, though I assume a key part is that it strengthens bonds between people, helping them stick together in the groups that keep society moving forward.

Sick humor is part of this, though having grown up watching Monty Python and reading National Lampoon magazine I’m certainly guilty of enjoying it. To this day I think “Eating Raoul” is one of the greatest comedies ever.

It’s also pretty common in medicine. I’ve been involved in plenty of hospital situations that were quite unfunny, yet there are always jokes about it flying as we work.

I assume it’s a defense mechanism. Helping us cope with a bad situation as we do our best to deal with it. Using humor to put a block between the obvious realization that someday this could happen to us. To help psychologically shield us from something tragic.

Years ago I was trying to describe the plot of “Eating Raoul” and said “if you read about this sort of crime spree in a newspaper you’d be horrified. But the way it’s handled in the movie it’s hysterical.” Perhaps that’s as close to understanding sick humor as I’ll ever get. It makes the unfunny funny.

Perhaps the better phrase is the more generic “it’s human nature.” We seek relief in humor, even (maybe especially) in bad situations of our own and others.

Whether or not it’s funny depends on the person. There were plenty of people horrified by the Subway sign, enough that the owner had to change it. But there were also those who admitted they found it tasteless, but still got a laugh out of it. I’m sure the families of those lost on the Titan were justifiably upset, but the closer you get to a personal tragedy the more serious it is.

There’s a fine line, as National Lampoon put it, between funny and sick. But it’s also part of who we are.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

This past June, during the search for the Titan submersible, and since then, we’ve had a not-entirely-unexpected development: Sick humor.

There was a lot of it. The Subway owner who got reprimanded for putting “Our subs don’t implode” on his sign was minor league compared with other things circulating on the Internet. One example that was sent to me showed the late Stockton Rush, OceanGate’s co-owner, as the new spokesman for Cap’n Crunch.

Of course, this is nothing new. People have made jokes about awful situations since to the dawn of civilization.

Why do we do this?

Humor is a remarkably human trait. There’s evidence other mammals have it, but not to the extent we do. We’ve created a multitude of forms that vary between cultures. But there isn’t a civilization or culture on Earth that doesn’t have humor.

Why we developed it I’ll leave to others, though I assume a key part is that it strengthens bonds between people, helping them stick together in the groups that keep society moving forward.

Sick humor is part of this, though having grown up watching Monty Python and reading National Lampoon magazine I’m certainly guilty of enjoying it. To this day I think “Eating Raoul” is one of the greatest comedies ever.

It’s also pretty common in medicine. I’ve been involved in plenty of hospital situations that were quite unfunny, yet there are always jokes about it flying as we work.

I assume it’s a defense mechanism. Helping us cope with a bad situation as we do our best to deal with it. Using humor to put a block between the obvious realization that someday this could happen to us. To help psychologically shield us from something tragic.

Years ago I was trying to describe the plot of “Eating Raoul” and said “if you read about this sort of crime spree in a newspaper you’d be horrified. But the way it’s handled in the movie it’s hysterical.” Perhaps that’s as close to understanding sick humor as I’ll ever get. It makes the unfunny funny.

Perhaps the better phrase is the more generic “it’s human nature.” We seek relief in humor, even (maybe especially) in bad situations of our own and others.

Whether or not it’s funny depends on the person. There were plenty of people horrified by the Subway sign, enough that the owner had to change it. But there were also those who admitted they found it tasteless, but still got a laugh out of it. I’m sure the families of those lost on the Titan were justifiably upset, but the closer you get to a personal tragedy the more serious it is.

There’s a fine line, as National Lampoon put it, between funny and sick. But it’s also part of who we are.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

This past June, during the search for the Titan submersible, and since then, we’ve had a not-entirely-unexpected development: Sick humor.

There was a lot of it. The Subway owner who got reprimanded for putting “Our subs don’t implode” on his sign was minor league compared with other things circulating on the Internet. One example that was sent to me showed the late Stockton Rush, OceanGate’s co-owner, as the new spokesman for Cap’n Crunch.

Of course, this is nothing new. People have made jokes about awful situations since to the dawn of civilization.

Why do we do this?

Humor is a remarkably human trait. There’s evidence other mammals have it, but not to the extent we do. We’ve created a multitude of forms that vary between cultures. But there isn’t a civilization or culture on Earth that doesn’t have humor.

Why we developed it I’ll leave to others, though I assume a key part is that it strengthens bonds between people, helping them stick together in the groups that keep society moving forward.

Sick humor is part of this, though having grown up watching Monty Python and reading National Lampoon magazine I’m certainly guilty of enjoying it. To this day I think “Eating Raoul” is one of the greatest comedies ever.

It’s also pretty common in medicine. I’ve been involved in plenty of hospital situations that were quite unfunny, yet there are always jokes about it flying as we work.

I assume it’s a defense mechanism. Helping us cope with a bad situation as we do our best to deal with it. Using humor to put a block between the obvious realization that someday this could happen to us. To help psychologically shield us from something tragic.

Years ago I was trying to describe the plot of “Eating Raoul” and said “if you read about this sort of crime spree in a newspaper you’d be horrified. But the way it’s handled in the movie it’s hysterical.” Perhaps that’s as close to understanding sick humor as I’ll ever get. It makes the unfunny funny.

Perhaps the better phrase is the more generic “it’s human nature.” We seek relief in humor, even (maybe especially) in bad situations of our own and others.

Whether or not it’s funny depends on the person. There were plenty of people horrified by the Subway sign, enough that the owner had to change it. But there were also those who admitted they found it tasteless, but still got a laugh out of it. I’m sure the families of those lost on the Titan were justifiably upset, but the closer you get to a personal tragedy the more serious it is.

There’s a fine line, as National Lampoon put it, between funny and sick. But it’s also part of who we are.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Abiomed is recalling all Impella left-sided blood pumps in the United States over a potential safety issue when used in patients with a transcatheter aortic valve replacement (TAVR) stent – something that is not adequately addressed in the pumps’ current instructions for use (IFU).

This recall represents a “voluntary correction, not a product removal.” Impella heart pumps do not need to be returned, the U.S. Food and Drug Administration says.

Instead, the company will update the pump’s IFU to include guidance to clinicians on how to manage use of Impella in patients with TAVR.

Clinicians may continue to use the Impella devices, with the additional instructions for patients with TAVR in mind, the FDA says.

As explained in the recall notice, there is a potential risk that the Impella motor housing may come into contact with the distal stent of a TAVR, which may damage or destroy the motor’s impeller blades.

“The damaged Impella system may have reduced blood flow or pump stop, which may delay therapy or fail to provide enough support to the patient. This could be life threatening in people who require high levels of support. There is also a risk that pieces of the broken blades could enter the patient’s bloodstream,” the notice warns.

The recall covers 7895 devices distributed from May 1, 2021, to the present, including the following devices:

• Impella 5.0 Blood Pump, product number 005062
• Impella CP Blood Pump, product number 0048-0032
• Impella 2.5 Blood Pump, product number 005042
• Impella CP with SmartAssist Blood Pump, product numbers 0048-0024, 0048-0045, and 1000080
• Impella LD Blood Pump, product number 005082
• Impella 5.5 with SmartAssist Blood Pump, product numbers 0550-0008 and 1000100.

Abiomed reports 30 complaints, 26 injuries, and 4 deaths related to this issue, which has garnered a class I recall from the FDA, the most serious type.

In an urgent device correction letter sent to health care professionals in June, Abiomed says, “For a patient with TAVR who needs hemodynamic support, clinicians should factor this risk into the risk benefit analysis and are cautioned to position the Impella system carefully as directed in this notification.

“The risk of interaction is increased for oversized or under expanded frames with the distal ends not flush with the aortic wall, resulting in the distal stent structures oriented in such a way as to potentially enter the outflow window and allow contact of the end of the stent with the spinning impeller,” the letter states.

Clinicians are advised to avoid repositioning while the device is spinning and to turn the device to P0 during repositioning or any movement that could bring the outlet windows into proximity with the valve stent structures.

If low flow is observed in a patient implanted with a TAVR while on Impella heart pump support, clinicians should consider damage of the impeller and replace the Impella pump as soon as possible, the company says.

Questions about this recall can be addressed to Shashi Thoutam at 734-262-6255 and/or local clinical field staff.

Health care professionals can report adverse reactions or quality problems they experience using these devices to the FDA’s MedWatch program.

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

Abiomed is recalling all Impella left-sided blood pumps in the United States over a potential safety issue when used in patients with a transcatheter aortic valve replacement (TAVR) stent – something that is not adequately addressed in the pumps’ current instructions for use (IFU).

This recall represents a “voluntary correction, not a product removal.” Impella heart pumps do not need to be returned, the U.S. Food and Drug Administration says.

Instead, the company will update the pump’s IFU to include guidance to clinicians on how to manage use of Impella in patients with TAVR.

Clinicians may continue to use the Impella devices, with the additional instructions for patients with TAVR in mind, the FDA says.

As explained in the recall notice, there is a potential risk that the Impella motor housing may come into contact with the distal stent of a TAVR, which may damage or destroy the motor’s impeller blades.

“The damaged Impella system may have reduced blood flow or pump stop, which may delay therapy or fail to provide enough support to the patient. This could be life threatening in people who require high levels of support. There is also a risk that pieces of the broken blades could enter the patient’s bloodstream,” the notice warns.

The recall covers 7895 devices distributed from May 1, 2021, to the present, including the following devices:

• Impella 5.0 Blood Pump, product number 005062
• Impella CP Blood Pump, product number 0048-0032
• Impella 2.5 Blood Pump, product number 005042
• Impella CP with SmartAssist Blood Pump, product numbers 0048-0024, 0048-0045, and 1000080
• Impella LD Blood Pump, product number 005082
• Impella 5.5 with SmartAssist Blood Pump, product numbers 0550-0008 and 1000100.

Abiomed reports 30 complaints, 26 injuries, and 4 deaths related to this issue, which has garnered a class I recall from the FDA, the most serious type.

In an urgent device correction letter sent to health care professionals in June, Abiomed says, “For a patient with TAVR who needs hemodynamic support, clinicians should factor this risk into the risk benefit analysis and are cautioned to position the Impella system carefully as directed in this notification.

“The risk of interaction is increased for oversized or under expanded frames with the distal ends not flush with the aortic wall, resulting in the distal stent structures oriented in such a way as to potentially enter the outflow window and allow contact of the end of the stent with the spinning impeller,” the letter states.

Clinicians are advised to avoid repositioning while the device is spinning and to turn the device to P0 during repositioning or any movement that could bring the outlet windows into proximity with the valve stent structures.

If low flow is observed in a patient implanted with a TAVR while on Impella heart pump support, clinicians should consider damage of the impeller and replace the Impella pump as soon as possible, the company says.

Questions about this recall can be addressed to Shashi Thoutam at 734-262-6255 and/or local clinical field staff.

Health care professionals can report adverse reactions or quality problems they experience using these devices to the FDA’s MedWatch program.

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

Abiomed is recalling all Impella left-sided blood pumps in the United States over a potential safety issue when used in patients with a transcatheter aortic valve replacement (TAVR) stent – something that is not adequately addressed in the pumps’ current instructions for use (IFU).

This recall represents a “voluntary correction, not a product removal.” Impella heart pumps do not need to be returned, the U.S. Food and Drug Administration says.

Instead, the company will update the pump’s IFU to include guidance to clinicians on how to manage use of Impella in patients with TAVR.

Clinicians may continue to use the Impella devices, with the additional instructions for patients with TAVR in mind, the FDA says.

As explained in the recall notice, there is a potential risk that the Impella motor housing may come into contact with the distal stent of a TAVR, which may damage or destroy the motor’s impeller blades.

“The damaged Impella system may have reduced blood flow or pump stop, which may delay therapy or fail to provide enough support to the patient. This could be life threatening in people who require high levels of support. There is also a risk that pieces of the broken blades could enter the patient’s bloodstream,” the notice warns.

The recall covers 7895 devices distributed from May 1, 2021, to the present, including the following devices:

• Impella 5.0 Blood Pump, product number 005062
• Impella CP Blood Pump, product number 0048-0032
• Impella 2.5 Blood Pump, product number 005042
• Impella CP with SmartAssist Blood Pump, product numbers 0048-0024, 0048-0045, and 1000080
• Impella LD Blood Pump, product number 005082
• Impella 5.5 with SmartAssist Blood Pump, product numbers 0550-0008 and 1000100.

Abiomed reports 30 complaints, 26 injuries, and 4 deaths related to this issue, which has garnered a class I recall from the FDA, the most serious type.

In an urgent device correction letter sent to health care professionals in June, Abiomed says, “For a patient with TAVR who needs hemodynamic support, clinicians should factor this risk into the risk benefit analysis and are cautioned to position the Impella system carefully as directed in this notification.

“The risk of interaction is increased for oversized or under expanded frames with the distal ends not flush with the aortic wall, resulting in the distal stent structures oriented in such a way as to potentially enter the outflow window and allow contact of the end of the stent with the spinning impeller,” the letter states.

Clinicians are advised to avoid repositioning while the device is spinning and to turn the device to P0 during repositioning or any movement that could bring the outlet windows into proximity with the valve stent structures.

If low flow is observed in a patient implanted with a TAVR while on Impella heart pump support, clinicians should consider damage of the impeller and replace the Impella pump as soon as possible, the company says.

Questions about this recall can be addressed to Shashi Thoutam at 734-262-6255 and/or local clinical field staff.

Health care professionals can report adverse reactions or quality problems they experience using these devices to the FDA’s MedWatch program.

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