The metabolic benefits achieved with weight loss for patients with type 2 diabetes appear to be similar whether achieved via diet or gastric bypass surgery, according to new research.

The findings, from a small study of 22 people with type 2 diabetes and obesity, were published online August 19 in the New England Journal of Medicine. The study was conducted by Mihoko Yoshino, MD, PhD, of Washington University, St. Louis, and colleagues.

Among 11 patients in each group who experienced comparable degrees of weight loss (about 18%), there were very similar benefits in multiorgan insulin sensitivity, beta-cell function, 24-hour plasma glucose and insulin profiles, and body composition.

“The results from our study underscore the profound effect that marked weight loss can have on metabolic function in people with diabetes,” Dr. Yoshino and colleagues wrote.

“The similar findings in participants in the two groups challenge the current belief that upper gastrointestinal bypass has clinically meaningful effects on key metabolic factors involved in glucose homeostasis and the pathogenesis of diabetes that are independent of weight loss,” they added.

However, they acknowledged, “the difficulty in achieving successful long-term weight loss with lifestyle therapy often renders gastric bypass surgery far more effective than diet therapy for most patients with obesity and type 2 diabetes.”

“This study confirms the pathogenic nature of obesity in driving insulin resistance and, ultimately, type 2 diabetes; furthermore, it delivers a straightforward and important message for both clinicians and patients – reducing adipose tissue volume, by whatever means, will improve blood glucose control in persons with type 2 diabetes,” stated the authors of an accompanying editorial.

Asked to comment, Matthew M. Hutter, MD, president of the American Society for Metabolic and Bariatric Surgery and professor of surgery at Harvard Medical School and Massachusetts General Hospital, both in Boston, said in an interview that the study was “very elegant” and “well designed.”

However, he pointed out, “the reality is diet alone has been shown over and over that it’s not sustainable. For a very small few it is, but for the vast majority, that’s not the case.”

Dr. Hutter also noted that the research was conducted in a laboratory setting and that the diet group was given prepackaged food. Therefore, the study “doesn’t look at how effective [dieting] is in the real world.”

Bariatric surgery, on the other hand, “is very effective for treating type 2 diabetes. It’s a good long-term solution.”
 

No significant differences in multiple parameters

The nonrandomized prospective cohort study began with 33 adults with obesity and type 2 diabetes, of whom 18 received weekly diet education sessions and prepackaged food, and 15 underwent Roux-en-Y gastric bypass procedures. Seven in the diet group and four in the surgery group were withdrawn from the study because of a failure to achieve the target of 16%-18% loss of body weight.

Of those remaining in the study, mean weight loss at around 4 months was 17.8% of body weight for the 11 in the diet group and 18.7% for the 11 in the surgery group. For the diet group, the mean age was 54 years and the mean duration of diabetes was 9.1 years; for the surgery group, the mean age was 49 years and the mean duration of diabetes 9.6 years.

A three-stage hyperinsulinemic euglycemic pancreatic clamp was used to control both portal and systemic plasma insulin concentrations to provide a reliable assessment of hepatic, muscle, and adipose tissue insulin sensitivity across a physiological range of plasma insulin concentrations. In both treatment groups, similar improvements were seen in hepatic, adipose tissue, and skeletal muscle insulin sensitivity

Both groups experienced a similar drop in the use of diabetes medications. Four individuals in the diet group and two in the surgery group achieved hemoglobin A1c levels below 6.0% without any medications.

After ingestion of identical mixed meals, 4-hour areas under the curve (AUC) for plasma glucose and insulin were lower after weight loss than before for both groups, although the decrease in glucose was greater in the diet group. Postprandial glucose peaks were greater in the surgery group as well, owing to an increase in the rate of glucose delivery into the circulation.

Weight loss was associated with decreased total AUC for glucose, free fatty acids, insulin, and insulin secretion to similar degrees in both groups. However, there were differences in several factors that have been attributed to the effects of bariatric surgery independently of weight loss. These include a greater decrease in 24-hour plasma branched-chain amino acid and C3 and C5 acylcarnitine concentrations after weight loss in the surgery group than in the diet group.

Plasma bile acid levels after weight loss dropped from baseline in the diet group but rose in the surgery group. Although microbiome changes occurred in both groups, they were more pronounced with weight loss following surgery.
 

Study limitations: Small, not randomized, long diabetes duration

The authors acknowledged some of the study’s limitations, including the fact that it wasn’t randomized and there was a large number of dropouts, although they say that the method used to assess the primary outcome can detect small differences even in a few patients.

The editorialists – endocrinologist Clifford J. Rosen, MD, director of the Center for Clinical and Translational Research at Maine Medical Center Research Institute, Scarborough, and pediatric nephrologist and deputy editor for the New England Journal of Medicine Julie R. Ingelfinger, MD, of Massachusetts General Hospital, Boston – pointed out that today more sleeve gastrectomies are performed than Roux-en-Y bypass procedures.

However, Dr. Hutter said that gastric bypass procedures are still being performed, that both procedures are effective and safe, and that for patients with diabetes the bypass tends to be somewhat more effective than sleeve gastrectomy.

He also qualified: “What phase you’re in is critical. Here, the 18% [weight loss] is still early in the track for bariatric surgery. They could still be losing weight after that. The diet groups could have been in the plateau or regain phase. Those [numbers] could look very different with time.”

In addition, he noted that the relatively long average duration of diabetes in the study participants makes the success of bariatric surgery less likely.

“The pancreas burns out, and the tissues become less insulin sensitive. I would have wanted to stratify the patients into early versus later disease, but you would need a larger sample size to do that,” he said.

Dr. Hutter noted: “I thought the study was very interesting. It just amazes me that 60 years after the gastric bypass procedure was invented, we’re still trying to figure out how it works.”

Dr. Hutter is a consultant for Vicarious Surgical and has received honoraria from Ethicon, Medtronic, and Olympus.

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

The AGA Practice guide on Obesity and Weight management, Education and Resources (POWER) white paper provides physicians with a comprehensive, multi-disciplinary process to guide and personalize innovative obesity care for safe and effective weight management. Learn more at www.gastro.org/obesity. 

The metabolic benefits achieved with weight loss for patients with type 2 diabetes appear to be similar whether achieved via diet or gastric bypass surgery, according to new research.

The findings, from a small study of 22 people with type 2 diabetes and obesity, were published online August 19 in the New England Journal of Medicine. The study was conducted by Mihoko Yoshino, MD, PhD, of Washington University, St. Louis, and colleagues.

Among 11 patients in each group who experienced comparable degrees of weight loss (about 18%), there were very similar benefits in multiorgan insulin sensitivity, beta-cell function, 24-hour plasma glucose and insulin profiles, and body composition.

“The results from our study underscore the profound effect that marked weight loss can have on metabolic function in people with diabetes,” Dr. Yoshino and colleagues wrote.

“The similar findings in participants in the two groups challenge the current belief that upper gastrointestinal bypass has clinically meaningful effects on key metabolic factors involved in glucose homeostasis and the pathogenesis of diabetes that are independent of weight loss,” they added.

However, they acknowledged, “the difficulty in achieving successful long-term weight loss with lifestyle therapy often renders gastric bypass surgery far more effective than diet therapy for most patients with obesity and type 2 diabetes.”

“This study confirms the pathogenic nature of obesity in driving insulin resistance and, ultimately, type 2 diabetes; furthermore, it delivers a straightforward and important message for both clinicians and patients – reducing adipose tissue volume, by whatever means, will improve blood glucose control in persons with type 2 diabetes,” stated the authors of an accompanying editorial.

Asked to comment, Matthew M. Hutter, MD, president of the American Society for Metabolic and Bariatric Surgery and professor of surgery at Harvard Medical School and Massachusetts General Hospital, both in Boston, said in an interview that the study was “very elegant” and “well designed.”

However, he pointed out, “the reality is diet alone has been shown over and over that it’s not sustainable. For a very small few it is, but for the vast majority, that’s not the case.”

Dr. Hutter also noted that the research was conducted in a laboratory setting and that the diet group was given prepackaged food. Therefore, the study “doesn’t look at how effective [dieting] is in the real world.”

Bariatric surgery, on the other hand, “is very effective for treating type 2 diabetes. It’s a good long-term solution.”
 

No significant differences in multiple parameters

The nonrandomized prospective cohort study began with 33 adults with obesity and type 2 diabetes, of whom 18 received weekly diet education sessions and prepackaged food, and 15 underwent Roux-en-Y gastric bypass procedures. Seven in the diet group and four in the surgery group were withdrawn from the study because of a failure to achieve the target of 16%-18% loss of body weight.

Of those remaining in the study, mean weight loss at around 4 months was 17.8% of body weight for the 11 in the diet group and 18.7% for the 11 in the surgery group. For the diet group, the mean age was 54 years and the mean duration of diabetes was 9.1 years; for the surgery group, the mean age was 49 years and the mean duration of diabetes 9.6 years.

A three-stage hyperinsulinemic euglycemic pancreatic clamp was used to control both portal and systemic plasma insulin concentrations to provide a reliable assessment of hepatic, muscle, and adipose tissue insulin sensitivity across a physiological range of plasma insulin concentrations. In both treatment groups, similar improvements were seen in hepatic, adipose tissue, and skeletal muscle insulin sensitivity

Both groups experienced a similar drop in the use of diabetes medications. Four individuals in the diet group and two in the surgery group achieved hemoglobin A1c levels below 6.0% without any medications.

After ingestion of identical mixed meals, 4-hour areas under the curve (AUC) for plasma glucose and insulin were lower after weight loss than before for both groups, although the decrease in glucose was greater in the diet group. Postprandial glucose peaks were greater in the surgery group as well, owing to an increase in the rate of glucose delivery into the circulation.

Weight loss was associated with decreased total AUC for glucose, free fatty acids, insulin, and insulin secretion to similar degrees in both groups. However, there were differences in several factors that have been attributed to the effects of bariatric surgery independently of weight loss. These include a greater decrease in 24-hour plasma branched-chain amino acid and C3 and C5 acylcarnitine concentrations after weight loss in the surgery group than in the diet group.

Plasma bile acid levels after weight loss dropped from baseline in the diet group but rose in the surgery group. Although microbiome changes occurred in both groups, they were more pronounced with weight loss following surgery.
 

Study limitations: Small, not randomized, long diabetes duration

The authors acknowledged some of the study’s limitations, including the fact that it wasn’t randomized and there was a large number of dropouts, although they say that the method used to assess the primary outcome can detect small differences even in a few patients.

The editorialists – endocrinologist Clifford J. Rosen, MD, director of the Center for Clinical and Translational Research at Maine Medical Center Research Institute, Scarborough, and pediatric nephrologist and deputy editor for the New England Journal of Medicine Julie R. Ingelfinger, MD, of Massachusetts General Hospital, Boston – pointed out that today more sleeve gastrectomies are performed than Roux-en-Y bypass procedures.

However, Dr. Hutter said that gastric bypass procedures are still being performed, that both procedures are effective and safe, and that for patients with diabetes the bypass tends to be somewhat more effective than sleeve gastrectomy.

He also qualified: “What phase you’re in is critical. Here, the 18% [weight loss] is still early in the track for bariatric surgery. They could still be losing weight after that. The diet groups could have been in the plateau or regain phase. Those [numbers] could look very different with time.”

In addition, he noted that the relatively long average duration of diabetes in the study participants makes the success of bariatric surgery less likely.

“The pancreas burns out, and the tissues become less insulin sensitive. I would have wanted to stratify the patients into early versus later disease, but you would need a larger sample size to do that,” he said.

Dr. Hutter noted: “I thought the study was very interesting. It just amazes me that 60 years after the gastric bypass procedure was invented, we’re still trying to figure out how it works.”

Dr. Hutter is a consultant for Vicarious Surgical and has received honoraria from Ethicon, Medtronic, and Olympus.

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

The AGA Practice guide on Obesity and Weight management, Education and Resources (POWER) white paper provides physicians with a comprehensive, multi-disciplinary process to guide and personalize innovative obesity care for safe and effective weight management. Learn more at www.gastro.org/obesity. 

The metabolic benefits achieved with weight loss for patients with type 2 diabetes appear to be similar whether achieved via diet or gastric bypass surgery, according to new research.

The findings, from a small study of 22 people with type 2 diabetes and obesity, were published online August 19 in the New England Journal of Medicine. The study was conducted by Mihoko Yoshino, MD, PhD, of Washington University, St. Louis, and colleagues.

Among 11 patients in each group who experienced comparable degrees of weight loss (about 18%), there were very similar benefits in multiorgan insulin sensitivity, beta-cell function, 24-hour plasma glucose and insulin profiles, and body composition.

“The results from our study underscore the profound effect that marked weight loss can have on metabolic function in people with diabetes,” Dr. Yoshino and colleagues wrote.

“The similar findings in participants in the two groups challenge the current belief that upper gastrointestinal bypass has clinically meaningful effects on key metabolic factors involved in glucose homeostasis and the pathogenesis of diabetes that are independent of weight loss,” they added.

However, they acknowledged, “the difficulty in achieving successful long-term weight loss with lifestyle therapy often renders gastric bypass surgery far more effective than diet therapy for most patients with obesity and type 2 diabetes.”

“This study confirms the pathogenic nature of obesity in driving insulin resistance and, ultimately, type 2 diabetes; furthermore, it delivers a straightforward and important message for both clinicians and patients – reducing adipose tissue volume, by whatever means, will improve blood glucose control in persons with type 2 diabetes,” stated the authors of an accompanying editorial.

Asked to comment, Matthew M. Hutter, MD, president of the American Society for Metabolic and Bariatric Surgery and professor of surgery at Harvard Medical School and Massachusetts General Hospital, both in Boston, said in an interview that the study was “very elegant” and “well designed.”

However, he pointed out, “the reality is diet alone has been shown over and over that it’s not sustainable. For a very small few it is, but for the vast majority, that’s not the case.”

Dr. Hutter also noted that the research was conducted in a laboratory setting and that the diet group was given prepackaged food. Therefore, the study “doesn’t look at how effective [dieting] is in the real world.”

Bariatric surgery, on the other hand, “is very effective for treating type 2 diabetes. It’s a good long-term solution.”
 

No significant differences in multiple parameters

The nonrandomized prospective cohort study began with 33 adults with obesity and type 2 diabetes, of whom 18 received weekly diet education sessions and prepackaged food, and 15 underwent Roux-en-Y gastric bypass procedures. Seven in the diet group and four in the surgery group were withdrawn from the study because of a failure to achieve the target of 16%-18% loss of body weight.

Of those remaining in the study, mean weight loss at around 4 months was 17.8% of body weight for the 11 in the diet group and 18.7% for the 11 in the surgery group. For the diet group, the mean age was 54 years and the mean duration of diabetes was 9.1 years; for the surgery group, the mean age was 49 years and the mean duration of diabetes 9.6 years.

A three-stage hyperinsulinemic euglycemic pancreatic clamp was used to control both portal and systemic plasma insulin concentrations to provide a reliable assessment of hepatic, muscle, and adipose tissue insulin sensitivity across a physiological range of plasma insulin concentrations. In both treatment groups, similar improvements were seen in hepatic, adipose tissue, and skeletal muscle insulin sensitivity

Both groups experienced a similar drop in the use of diabetes medications. Four individuals in the diet group and two in the surgery group achieved hemoglobin A1c levels below 6.0% without any medications.

After ingestion of identical mixed meals, 4-hour areas under the curve (AUC) for plasma glucose and insulin were lower after weight loss than before for both groups, although the decrease in glucose was greater in the diet group. Postprandial glucose peaks were greater in the surgery group as well, owing to an increase in the rate of glucose delivery into the circulation.

Weight loss was associated with decreased total AUC for glucose, free fatty acids, insulin, and insulin secretion to similar degrees in both groups. However, there were differences in several factors that have been attributed to the effects of bariatric surgery independently of weight loss. These include a greater decrease in 24-hour plasma branched-chain amino acid and C3 and C5 acylcarnitine concentrations after weight loss in the surgery group than in the diet group.

Plasma bile acid levels after weight loss dropped from baseline in the diet group but rose in the surgery group. Although microbiome changes occurred in both groups, they were more pronounced with weight loss following surgery.
 

Study limitations: Small, not randomized, long diabetes duration

The authors acknowledged some of the study’s limitations, including the fact that it wasn’t randomized and there was a large number of dropouts, although they say that the method used to assess the primary outcome can detect small differences even in a few patients.

The editorialists – endocrinologist Clifford J. Rosen, MD, director of the Center for Clinical and Translational Research at Maine Medical Center Research Institute, Scarborough, and pediatric nephrologist and deputy editor for the New England Journal of Medicine Julie R. Ingelfinger, MD, of Massachusetts General Hospital, Boston – pointed out that today more sleeve gastrectomies are performed than Roux-en-Y bypass procedures.

However, Dr. Hutter said that gastric bypass procedures are still being performed, that both procedures are effective and safe, and that for patients with diabetes the bypass tends to be somewhat more effective than sleeve gastrectomy.

He also qualified: “What phase you’re in is critical. Here, the 18% [weight loss] is still early in the track for bariatric surgery. They could still be losing weight after that. The diet groups could have been in the plateau or regain phase. Those [numbers] could look very different with time.”

In addition, he noted that the relatively long average duration of diabetes in the study participants makes the success of bariatric surgery less likely.

“The pancreas burns out, and the tissues become less insulin sensitive. I would have wanted to stratify the patients into early versus later disease, but you would need a larger sample size to do that,” he said.

Dr. Hutter noted: “I thought the study was very interesting. It just amazes me that 60 years after the gastric bypass procedure was invented, we’re still trying to figure out how it works.”

Dr. Hutter is a consultant for Vicarious Surgical and has received honoraria from Ethicon, Medtronic, and Olympus.

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

The AGA Practice guide on Obesity and Weight management, Education and Resources (POWER) white paper provides physicians with a comprehensive, multi-disciplinary process to guide and personalize innovative obesity care for safe and effective weight management. Learn more at www.gastro.org/obesity. 

Among hospitalized COVID-19 patients, the use of famotidine was significantly associated with a reduction in death and either death or intubation. It also demonstrated lower levels of serum markers for severe disease.

The findings come from an observational study of 83 hospitalized patients that was published in the American Journal of Gastroenterology.

“The mechanism of exactly how famotidine works has yet to be proven,” lead study author Jeffrey F. Mather, MS, said in an interview. “There’s thought that it works directly on the virus, and there is thought that it works through inactivating certain proteases that are required for the virus infection, but I think the most interesting [hypothesis] is by Malone et al. “They’re looking at the blocking of the histamine-2 receptor causing a decrease in the amount of histamine. It’s all speculative, but it will be interesting if that gets worked out.”

In a study that largely mimicked that of an earlier, larger published observational study on the topic (doi: 10.1053/j.gastro.2020.05.053), Mr. Mather and colleagues retrospectively evaluated 878 patients who tested positive for SARS-CoV-2 and who required admission to Hartford (Conn.) Hospital between Feb. 24, 2020, and May 14, 2020. Patients were classified as receiving famotidine if they were treated with either oral or intravenous drug within 1 week of COVID-19 screening and/or hospital admission. Primary outcomes of interest were in-hospital death as recorded in the discharge of the patients, requirement for mechanical ventilation, and the composite of death or requirement for ventilation. Secondary outcomes of interest were several serum markers of disease activity including white blood cell count, lymphocyte count, and eosinophil count.

Famotidine was administered orally in 83% of the patients and intravenously in the remaining 17%. Mr. Mather, director of data management in the division of research management at Hartford Hospital, and his colleagues reported that 83 of the 878 patients studied (9.5%) received famotidine. Compared with patients not treated with famotidine, those who received the drug were slightly younger (a mean of 64 vs. 68 years, respectively; P = .021); otherwise, there were no differences between the two groups in baseline demographics or in preexisting comorbidities.

The use of famotidine was associated with a decreased risk of in-hospital mortality (odds ratio, 0.37; P = .021) as well as combined death or intubation (OR, 0.47; P = .040). The outcomes were similar when the researchers performed propensity score matching to adjust for age differences between groups.

In addition, the use of famotidine was associated with lower levels of serum markers for severe disease including lower median peak C-reactive protein levels (9.4 vs. 12.7 mg/dL; P =. 002), lower median procalcitonin levels (0.16 vs. 0.30 ng/mL; P = .004), and a nonsignificant trend to lower median mean ferritin levels (797.5 vs. 964 ng/mL; P = .076).

Logistic regression analysis revealed that use of famotidine was an independent predictor of both lower mortality and combined death/intubation. In addition, predictors of both adverse outcomes included older age, a body mass index of greater than 30 kg/m², chronic kidney disease, the national early warning score, and a higher neutrophil-lymphocyte ratio.

“This is an important stepping stone, but until we have a randomized, controlled trial, we really can’t speak about causation; we can only speak about association, and that’s okay,” Brennan Spiegel, MD, MSHS, director of health services research at Cedars-Sinai, Los Angeles, who was not affiliated with the study, said in an interview. “There’s nothing wrong with association because finding associations can raise important hypotheses that can then be tested in prospective randomized trials, for example.”

In July 2020, Dr. Spiegel and his colleagues published a separate paper looking at proton pump inhibitors and the risk of COVID-19. “In that study we did look at H₂ blockers, and we did find that they were slightly associated with a reduction in COVID-19,” he said. “It was a small effect, but it was a benefit. When we see consistency among studies, it’s a signal in the noise we can try and follow and see if there is something more to it.”

Mr. Mather acknowledged certain limitations of the study, including the fact that patients who did and did not receive famotidine were propensity-matched for age. “The risk factors that others have shown for adverse events are equivalent in the groups, but anytime you do a retrospective study like this there is the potential for underlying factors that may play a role in the outcomes that you’re not considering,” Mr. Mather said. “That’s why the gold standard is the randomized trial, to wash those effects out. There’s only an association here, and it supports the need for a randomized trial.”

Famotidine is currently being tested in a double-blind randomized clinical trial in combination with either hydroxychloroquine or remdesivir (NCT 04370262).

“It’s fascinating because famotidine is a safe medicine,” added Dr. Spiegel, who is also co–editor in chief of the American Journal of Gastroenterology. “There are very few side effects; it’s something we’ve been using for decades.”

Mr. Mather and his colleagues reported having no financial disclosures. Dr. Spiegel disclosed that he has served on advisory boards for Allergan, Alnylam Pharmaceuticals, Arena Pharmaceuticals, Ironwood Pharmaceuticals, Salix Pharmaceuticals, Synergy Pharmaceuticals, and Takeda Pharmaceuticals.

dbrunk@mdedge.com

SOURCE: Mather J et al. 2020 Aug 14. Am J Gastroenterol.

Among hospitalized COVID-19 patients, the use of famotidine was significantly associated with a reduction in death and either death or intubation. It also demonstrated lower levels of serum markers for severe disease.

The findings come from an observational study of 83 hospitalized patients that was published in the American Journal of Gastroenterology.

“The mechanism of exactly how famotidine works has yet to be proven,” lead study author Jeffrey F. Mather, MS, said in an interview. “There’s thought that it works directly on the virus, and there is thought that it works through inactivating certain proteases that are required for the virus infection, but I think the most interesting [hypothesis] is by Malone et al. “They’re looking at the blocking of the histamine-2 receptor causing a decrease in the amount of histamine. It’s all speculative, but it will be interesting if that gets worked out.”

In a study that largely mimicked that of an earlier, larger published observational study on the topic (doi: 10.1053/j.gastro.2020.05.053), Mr. Mather and colleagues retrospectively evaluated 878 patients who tested positive for SARS-CoV-2 and who required admission to Hartford (Conn.) Hospital between Feb. 24, 2020, and May 14, 2020. Patients were classified as receiving famotidine if they were treated with either oral or intravenous drug within 1 week of COVID-19 screening and/or hospital admission. Primary outcomes of interest were in-hospital death as recorded in the discharge of the patients, requirement for mechanical ventilation, and the composite of death or requirement for ventilation. Secondary outcomes of interest were several serum markers of disease activity including white blood cell count, lymphocyte count, and eosinophil count.

Famotidine was administered orally in 83% of the patients and intravenously in the remaining 17%. Mr. Mather, director of data management in the division of research management at Hartford Hospital, and his colleagues reported that 83 of the 878 patients studied (9.5%) received famotidine. Compared with patients not treated with famotidine, those who received the drug were slightly younger (a mean of 64 vs. 68 years, respectively; P = .021); otherwise, there were no differences between the two groups in baseline demographics or in preexisting comorbidities.

The use of famotidine was associated with a decreased risk of in-hospital mortality (odds ratio, 0.37; P = .021) as well as combined death or intubation (OR, 0.47; P = .040). The outcomes were similar when the researchers performed propensity score matching to adjust for age differences between groups.

In addition, the use of famotidine was associated with lower levels of serum markers for severe disease including lower median peak C-reactive protein levels (9.4 vs. 12.7 mg/dL; P =. 002), lower median procalcitonin levels (0.16 vs. 0.30 ng/mL; P = .004), and a nonsignificant trend to lower median mean ferritin levels (797.5 vs. 964 ng/mL; P = .076).

Logistic regression analysis revealed that use of famotidine was an independent predictor of both lower mortality and combined death/intubation. In addition, predictors of both adverse outcomes included older age, a body mass index of greater than 30 kg/m², chronic kidney disease, the national early warning score, and a higher neutrophil-lymphocyte ratio.

“This is an important stepping stone, but until we have a randomized, controlled trial, we really can’t speak about causation; we can only speak about association, and that’s okay,” Brennan Spiegel, MD, MSHS, director of health services research at Cedars-Sinai, Los Angeles, who was not affiliated with the study, said in an interview. “There’s nothing wrong with association because finding associations can raise important hypotheses that can then be tested in prospective randomized trials, for example.”

In July 2020, Dr. Spiegel and his colleagues published a separate paper looking at proton pump inhibitors and the risk of COVID-19. “In that study we did look at H₂ blockers, and we did find that they were slightly associated with a reduction in COVID-19,” he said. “It was a small effect, but it was a benefit. When we see consistency among studies, it’s a signal in the noise we can try and follow and see if there is something more to it.”

Mr. Mather acknowledged certain limitations of the study, including the fact that patients who did and did not receive famotidine were propensity-matched for age. “The risk factors that others have shown for adverse events are equivalent in the groups, but anytime you do a retrospective study like this there is the potential for underlying factors that may play a role in the outcomes that you’re not considering,” Mr. Mather said. “That’s why the gold standard is the randomized trial, to wash those effects out. There’s only an association here, and it supports the need for a randomized trial.”

Famotidine is currently being tested in a double-blind randomized clinical trial in combination with either hydroxychloroquine or remdesivir (NCT 04370262).

“It’s fascinating because famotidine is a safe medicine,” added Dr. Spiegel, who is also co–editor in chief of the American Journal of Gastroenterology. “There are very few side effects; it’s something we’ve been using for decades.”

Mr. Mather and his colleagues reported having no financial disclosures. Dr. Spiegel disclosed that he has served on advisory boards for Allergan, Alnylam Pharmaceuticals, Arena Pharmaceuticals, Ironwood Pharmaceuticals, Salix Pharmaceuticals, Synergy Pharmaceuticals, and Takeda Pharmaceuticals.

dbrunk@mdedge.com

SOURCE: Mather J et al. 2020 Aug 14. Am J Gastroenterol.

Among hospitalized COVID-19 patients, the use of famotidine was significantly associated with a reduction in death and either death or intubation. It also demonstrated lower levels of serum markers for severe disease.

The findings come from an observational study of 83 hospitalized patients that was published in the American Journal of Gastroenterology.

“The mechanism of exactly how famotidine works has yet to be proven,” lead study author Jeffrey F. Mather, MS, said in an interview. “There’s thought that it works directly on the virus, and there is thought that it works through inactivating certain proteases that are required for the virus infection, but I think the most interesting [hypothesis] is by Malone et al. “They’re looking at the blocking of the histamine-2 receptor causing a decrease in the amount of histamine. It’s all speculative, but it will be interesting if that gets worked out.”

In a study that largely mimicked that of an earlier, larger published observational study on the topic (doi: 10.1053/j.gastro.2020.05.053), Mr. Mather and colleagues retrospectively evaluated 878 patients who tested positive for SARS-CoV-2 and who required admission to Hartford (Conn.) Hospital between Feb. 24, 2020, and May 14, 2020. Patients were classified as receiving famotidine if they were treated with either oral or intravenous drug within 1 week of COVID-19 screening and/or hospital admission. Primary outcomes of interest were in-hospital death as recorded in the discharge of the patients, requirement for mechanical ventilation, and the composite of death or requirement for ventilation. Secondary outcomes of interest were several serum markers of disease activity including white blood cell count, lymphocyte count, and eosinophil count.

Famotidine was administered orally in 83% of the patients and intravenously in the remaining 17%. Mr. Mather, director of data management in the division of research management at Hartford Hospital, and his colleagues reported that 83 of the 878 patients studied (9.5%) received famotidine. Compared with patients not treated with famotidine, those who received the drug were slightly younger (a mean of 64 vs. 68 years, respectively; P = .021); otherwise, there were no differences between the two groups in baseline demographics or in preexisting comorbidities.

The use of famotidine was associated with a decreased risk of in-hospital mortality (odds ratio, 0.37; P = .021) as well as combined death or intubation (OR, 0.47; P = .040). The outcomes were similar when the researchers performed propensity score matching to adjust for age differences between groups.

In addition, the use of famotidine was associated with lower levels of serum markers for severe disease including lower median peak C-reactive protein levels (9.4 vs. 12.7 mg/dL; P =. 002), lower median procalcitonin levels (0.16 vs. 0.30 ng/mL; P = .004), and a nonsignificant trend to lower median mean ferritin levels (797.5 vs. 964 ng/mL; P = .076).

Logistic regression analysis revealed that use of famotidine was an independent predictor of both lower mortality and combined death/intubation. In addition, predictors of both adverse outcomes included older age, a body mass index of greater than 30 kg/m², chronic kidney disease, the national early warning score, and a higher neutrophil-lymphocyte ratio.

“This is an important stepping stone, but until we have a randomized, controlled trial, we really can’t speak about causation; we can only speak about association, and that’s okay,” Brennan Spiegel, MD, MSHS, director of health services research at Cedars-Sinai, Los Angeles, who was not affiliated with the study, said in an interview. “There’s nothing wrong with association because finding associations can raise important hypotheses that can then be tested in prospective randomized trials, for example.”

In July 2020, Dr. Spiegel and his colleagues published a separate paper looking at proton pump inhibitors and the risk of COVID-19. “In that study we did look at H₂ blockers, and we did find that they were slightly associated with a reduction in COVID-19,” he said. “It was a small effect, but it was a benefit. When we see consistency among studies, it’s a signal in the noise we can try and follow and see if there is something more to it.”

Mr. Mather acknowledged certain limitations of the study, including the fact that patients who did and did not receive famotidine were propensity-matched for age. “The risk factors that others have shown for adverse events are equivalent in the groups, but anytime you do a retrospective study like this there is the potential for underlying factors that may play a role in the outcomes that you’re not considering,” Mr. Mather said. “That’s why the gold standard is the randomized trial, to wash those effects out. There’s only an association here, and it supports the need for a randomized trial.”

Famotidine is currently being tested in a double-blind randomized clinical trial in combination with either hydroxychloroquine or remdesivir (NCT 04370262).

“It’s fascinating because famotidine is a safe medicine,” added Dr. Spiegel, who is also co–editor in chief of the American Journal of Gastroenterology. “There are very few side effects; it’s something we’ve been using for decades.”

Mr. Mather and his colleagues reported having no financial disclosures. Dr. Spiegel disclosed that he has served on advisory boards for Allergan, Alnylam Pharmaceuticals, Arena Pharmaceuticals, Ironwood Pharmaceuticals, Salix Pharmaceuticals, Synergy Pharmaceuticals, and Takeda Pharmaceuticals.

dbrunk@mdedge.com

SOURCE: Mather J et al. 2020 Aug 14. Am J Gastroenterol.

Parents, teachers, children, and adolescents are facing stress and anxiety as K-12 school districts across the country debate whether to return to in-person instruction amid the COVID-19 pandemic. As we approach the opening of schools, the stress and anxiety seem to be heightening.

alexsokolov/Thinkstock

According to Education Week, which is tracking the reopening plans of public schools across the United States, 21 of the 25 largest school districts are opting to implement remote learning only as their model. I would like to see all of those districts adopt that model until we understand more about this illness, and can prevent and treat it.

Yes, it’s true – I am a psychiatrist – not an infectious disease specialist. And I realize that the American Academy of Pediatrics and the Centers for Disease Control and Prevention have taken nuanced positions on this issue. Their positions make it clear that it is within a child’s best interests – from an educational and social point of view – to attend school in person. Not only is the classroom experience important, but so is the socialization and the exercise. However, when I look at the science on children who have been exposed to the coronavirus, I worry.

For example, a study by Lael M. Yonker, MD, and associates on pediatric SARS-CoV-2 found that the children in days 0-2 of illness have far higher viral loads than adults who have been hospitalized for severe disease. “This study reveals that children may be a potential source of contagion in the SARS-CoV-2 pandemic in spite of milder disease or lack of symptoms, and immune dysregulation is implicated in severe post-infectious [multisystem inflammatory syndrome in children],” Dr. Yonker and associates wrote, referring to the illness associated with COVID-19 in children. Their study was published recently in the Journal of Pediatrics (2020 Aug 19. doi: 10.1016/j.jpeds.2020.08.037).

In my state, where positivity rates are fairly low, Gov. Andrew Cuomo admitted in an interview recently that sending children to school in New York City is a “tricky proposition.” At this point, New York City public schools are scheduled to open in mid-September using a hybrid mixture of in-person and remote learning.

And look at what happened several weeks ago in Israel, where schools reopened after the virus was beaten back. At one high school in Jerusalem, just days after the reopening, the virus spread so prolifically to students, teachers, and relatives that the schools had to be closed again. Other countries should not follow Israel’s example, Eli Weizmann, who chairs the team advising Israel’s National Security Council on the pandemic, reportedly told the New York Times. “It was a major failure.”

But I must be honest: I was worried about children returning to school before I heard about the study by Dr. Yonker and associates, Gov. Cuomo’s comments, and what happened in Israel. So far, here in the Northeast, particularly in New York, New Jersey, and Connecticut, we have managed to get COVID-19 under control. Perhaps, in this part of the country, opening classroom education might be feasible – with close monitoring and proper precautions.

But COVID-19 has taken the lives of hundreds of thousands of Americans – more than 176,000 as of this writing. A new model from the University of Washington’s Institute for Health Metrics and Evaluation projects that COVID-19 could lead to more than 300,000 U.S. deaths by Dec. 1. Thankfully, the number of COVID-19–positive children who have died has been low. But they could still pass on the virus to adults.

To get a better understanding of COVID-19, I spoke with Sheryl L. Wulkan, MD, an internist and expert in personal protective equipment (PPE) who has consulted for numerous health care agencies about these issues. Dr. Wulkan said that, in some areas with low infection rates, school openings might be appropriate. However, she said, without proper testing and contact tracing, we are at a loss of controlling the spread.
 

What we should tell patients, family, and friends

From a psychiatric point of view, how should we advise our patients, family, and friends about sending their children back to school? Is on-site learning better than remote learning? It is. Do our children need the socialization that a school brings? Yes, they do.

Socialization and relating to peers are, indeed, important, but today’s children socialize in many ways beyond attending school – and they have peer friendships and interactions with electronic devices at their disposal.

Can remote learning cause social isolation – an isolation so profound that school is necessary not only for learning but the psyche as well? A meta-analysis of 80 studies that looked at the impact of social isolation and loneliness on adolescents and children who were previously healthy found that the young people “are probably more likely to experience high rates of depression and probably anxiety during and after enforced isolation ends. This may increase as enforced isolation continues,” wrote Maria Elizabeth Loades, PhD, and associates (J Am Acad Child Adolesc Psychiatry. 2020 Jun 3. S0890-8567[20]30337-3).

I am concerned about young people who experience anxiety and depression, and agree with Dr. Loades that we mental health professionals need to be ready to intervene early and provide preventive support. To do this, we should encourage parents to keep us informed about how their children are doing.

So my advice is that, in the absence of a vaccine and an effective treatment like we have for influenza – such as Tamiflu – and effective testing, such the saliva-based test developed by Yale University researchers, if I had school-aged children, I would continue to keep them home from school. Ultimately, however, parents must look at the science and make their decisions based on that. My children are adults with their own children, and only they can make informed decisions about which options are best for their families.

Interestingly, Sanjay Gupta, MD, the neurosurgeon who works as chief medical correspondent of CNN, recently discussed the thought process he and his wife used to determine whether their daughters would return to the classroom. After weighing many factors, including the viral spread in Fulton County, Ga., where they live, the Guptas decided that, at this time, the risks of allowing the girls to return to the classroom outweigh the benefits. “This was not an easy decision, but one that we believe best respects the science, decreases the risk of further spread, and follows the task force criteria,” wrote Dr. Gupta, who is affiliated with Emory University in Atlanta. “After 2 weeks, we will reassess.”

I understand that parents worry about the social and psychological costs of remote learning. And I can only imagine the difficulty of those who must balance homeschooling with working. And frankly, remote learning is not an option for all students. For those less fortunate, substantial governmental aid is important to assist these people and to keep them safe and on their feet until this pandemic is done. Also, those who were under the care of a psychiatrist should continue to receive care during the pandemic. We must be prepared to step in with interventions that can address the suffering that is inevitable, such as the use of targeted cognitive-behavioral therapy.

Public TV as an educational tool

Families with Internet access and those without it could benefit from using public television as a tool.

I would advise educators and the entertainment industry to harness the wonder of TV to develop curricula that can be used to educate children. As we know, Sesame Street proved to be an effective early childhood intervention, particularly for boys (Am Econ J: Applied Economics. 2019;11[1]:318-50). I would like to see programming that goes beyond Sesame Street. Learning from watching this kind of programming would be no substitute for engaging with teachers in real, live classrooms, however.

Children and adolescents will be changed by learning remotely. They will miss their friends, teachers, and other staff members, but their lives will not be ruined. Mental health professionals should be prepared to intervene to address depression, anxiety, and other sequelae and problematic behaviors that could result from social isolation. Schools, businesses, and the economy will again flourish after we get the virus behind us but controlling and eliminating this pandemic need to come first. Let’s keep our children home – to the extent that we can – until we move beyond this pandemic.
 

Dr. London has been a practicing psychiatrist for 4 decades and a newspaper columnist for almost as long. He has a private practice in New York and is author of “Find Freedom Fast: Short-Term Therapy That Works” (New York: Kettlehole Publishing, 2019). Dr. London has no conflicts of interest.

Parents, teachers, children, and adolescents are facing stress and anxiety as K-12 school districts across the country debate whether to return to in-person instruction amid the COVID-19 pandemic. As we approach the opening of schools, the stress and anxiety seem to be heightening.

alexsokolov/Thinkstock

According to Education Week, which is tracking the reopening plans of public schools across the United States, 21 of the 25 largest school districts are opting to implement remote learning only as their model. I would like to see all of those districts adopt that model until we understand more about this illness, and can prevent and treat it.

Yes, it’s true – I am a psychiatrist – not an infectious disease specialist. And I realize that the American Academy of Pediatrics and the Centers for Disease Control and Prevention have taken nuanced positions on this issue. Their positions make it clear that it is within a child’s best interests – from an educational and social point of view – to attend school in person. Not only is the classroom experience important, but so is the socialization and the exercise. However, when I look at the science on children who have been exposed to the coronavirus, I worry.

For example, a study by Lael M. Yonker, MD, and associates on pediatric SARS-CoV-2 found that the children in days 0-2 of illness have far higher viral loads than adults who have been hospitalized for severe disease. “This study reveals that children may be a potential source of contagion in the SARS-CoV-2 pandemic in spite of milder disease or lack of symptoms, and immune dysregulation is implicated in severe post-infectious [multisystem inflammatory syndrome in children],” Dr. Yonker and associates wrote, referring to the illness associated with COVID-19 in children. Their study was published recently in the Journal of Pediatrics (2020 Aug 19. doi: 10.1016/j.jpeds.2020.08.037).

In my state, where positivity rates are fairly low, Gov. Andrew Cuomo admitted in an interview recently that sending children to school in New York City is a “tricky proposition.” At this point, New York City public schools are scheduled to open in mid-September using a hybrid mixture of in-person and remote learning.

And look at what happened several weeks ago in Israel, where schools reopened after the virus was beaten back. At one high school in Jerusalem, just days after the reopening, the virus spread so prolifically to students, teachers, and relatives that the schools had to be closed again. Other countries should not follow Israel’s example, Eli Weizmann, who chairs the team advising Israel’s National Security Council on the pandemic, reportedly told the New York Times. “It was a major failure.”

But I must be honest: I was worried about children returning to school before I heard about the study by Dr. Yonker and associates, Gov. Cuomo’s comments, and what happened in Israel. So far, here in the Northeast, particularly in New York, New Jersey, and Connecticut, we have managed to get COVID-19 under control. Perhaps, in this part of the country, opening classroom education might be feasible – with close monitoring and proper precautions.

But COVID-19 has taken the lives of hundreds of thousands of Americans – more than 176,000 as of this writing. A new model from the University of Washington’s Institute for Health Metrics and Evaluation projects that COVID-19 could lead to more than 300,000 U.S. deaths by Dec. 1. Thankfully, the number of COVID-19–positive children who have died has been low. But they could still pass on the virus to adults.

To get a better understanding of COVID-19, I spoke with Sheryl L. Wulkan, MD, an internist and expert in personal protective equipment (PPE) who has consulted for numerous health care agencies about these issues. Dr. Wulkan said that, in some areas with low infection rates, school openings might be appropriate. However, she said, without proper testing and contact tracing, we are at a loss of controlling the spread.
 

What we should tell patients, family, and friends

From a psychiatric point of view, how should we advise our patients, family, and friends about sending their children back to school? Is on-site learning better than remote learning? It is. Do our children need the socialization that a school brings? Yes, they do.

Socialization and relating to peers are, indeed, important, but today’s children socialize in many ways beyond attending school – and they have peer friendships and interactions with electronic devices at their disposal.

Can remote learning cause social isolation – an isolation so profound that school is necessary not only for learning but the psyche as well? A meta-analysis of 80 studies that looked at the impact of social isolation and loneliness on adolescents and children who were previously healthy found that the young people “are probably more likely to experience high rates of depression and probably anxiety during and after enforced isolation ends. This may increase as enforced isolation continues,” wrote Maria Elizabeth Loades, PhD, and associates (J Am Acad Child Adolesc Psychiatry. 2020 Jun 3. S0890-8567[20]30337-3).

I am concerned about young people who experience anxiety and depression, and agree with Dr. Loades that we mental health professionals need to be ready to intervene early and provide preventive support. To do this, we should encourage parents to keep us informed about how their children are doing.

So my advice is that, in the absence of a vaccine and an effective treatment like we have for influenza – such as Tamiflu – and effective testing, such the saliva-based test developed by Yale University researchers, if I had school-aged children, I would continue to keep them home from school. Ultimately, however, parents must look at the science and make their decisions based on that. My children are adults with their own children, and only they can make informed decisions about which options are best for their families.

Interestingly, Sanjay Gupta, MD, the neurosurgeon who works as chief medical correspondent of CNN, recently discussed the thought process he and his wife used to determine whether their daughters would return to the classroom. After weighing many factors, including the viral spread in Fulton County, Ga., where they live, the Guptas decided that, at this time, the risks of allowing the girls to return to the classroom outweigh the benefits. “This was not an easy decision, but one that we believe best respects the science, decreases the risk of further spread, and follows the task force criteria,” wrote Dr. Gupta, who is affiliated with Emory University in Atlanta. “After 2 weeks, we will reassess.”

I understand that parents worry about the social and psychological costs of remote learning. And I can only imagine the difficulty of those who must balance homeschooling with working. And frankly, remote learning is not an option for all students. For those less fortunate, substantial governmental aid is important to assist these people and to keep them safe and on their feet until this pandemic is done. Also, those who were under the care of a psychiatrist should continue to receive care during the pandemic. We must be prepared to step in with interventions that can address the suffering that is inevitable, such as the use of targeted cognitive-behavioral therapy.

Public TV as an educational tool

Families with Internet access and those without it could benefit from using public television as a tool.

I would advise educators and the entertainment industry to harness the wonder of TV to develop curricula that can be used to educate children. As we know, Sesame Street proved to be an effective early childhood intervention, particularly for boys (Am Econ J: Applied Economics. 2019;11[1]:318-50). I would like to see programming that goes beyond Sesame Street. Learning from watching this kind of programming would be no substitute for engaging with teachers in real, live classrooms, however.

Children and adolescents will be changed by learning remotely. They will miss their friends, teachers, and other staff members, but their lives will not be ruined. Mental health professionals should be prepared to intervene to address depression, anxiety, and other sequelae and problematic behaviors that could result from social isolation. Schools, businesses, and the economy will again flourish after we get the virus behind us but controlling and eliminating this pandemic need to come first. Let’s keep our children home – to the extent that we can – until we move beyond this pandemic.
 

Dr. London has been a practicing psychiatrist for 4 decades and a newspaper columnist for almost as long. He has a private practice in New York and is author of “Find Freedom Fast: Short-Term Therapy That Works” (New York: Kettlehole Publishing, 2019). Dr. London has no conflicts of interest.

Parents, teachers, children, and adolescents are facing stress and anxiety as K-12 school districts across the country debate whether to return to in-person instruction amid the COVID-19 pandemic. As we approach the opening of schools, the stress and anxiety seem to be heightening.

alexsokolov/Thinkstock

According to Education Week, which is tracking the reopening plans of public schools across the United States, 21 of the 25 largest school districts are opting to implement remote learning only as their model. I would like to see all of those districts adopt that model until we understand more about this illness, and can prevent and treat it.

Yes, it’s true – I am a psychiatrist – not an infectious disease specialist. And I realize that the American Academy of Pediatrics and the Centers for Disease Control and Prevention have taken nuanced positions on this issue. Their positions make it clear that it is within a child’s best interests – from an educational and social point of view – to attend school in person. Not only is the classroom experience important, but so is the socialization and the exercise. However, when I look at the science on children who have been exposed to the coronavirus, I worry.

For example, a study by Lael M. Yonker, MD, and associates on pediatric SARS-CoV-2 found that the children in days 0-2 of illness have far higher viral loads than adults who have been hospitalized for severe disease. “This study reveals that children may be a potential source of contagion in the SARS-CoV-2 pandemic in spite of milder disease or lack of symptoms, and immune dysregulation is implicated in severe post-infectious [multisystem inflammatory syndrome in children],” Dr. Yonker and associates wrote, referring to the illness associated with COVID-19 in children. Their study was published recently in the Journal of Pediatrics (2020 Aug 19. doi: 10.1016/j.jpeds.2020.08.037).

In my state, where positivity rates are fairly low, Gov. Andrew Cuomo admitted in an interview recently that sending children to school in New York City is a “tricky proposition.” At this point, New York City public schools are scheduled to open in mid-September using a hybrid mixture of in-person and remote learning.

And look at what happened several weeks ago in Israel, where schools reopened after the virus was beaten back. At one high school in Jerusalem, just days after the reopening, the virus spread so prolifically to students, teachers, and relatives that the schools had to be closed again. Other countries should not follow Israel’s example, Eli Weizmann, who chairs the team advising Israel’s National Security Council on the pandemic, reportedly told the New York Times. “It was a major failure.”

But I must be honest: I was worried about children returning to school before I heard about the study by Dr. Yonker and associates, Gov. Cuomo’s comments, and what happened in Israel. So far, here in the Northeast, particularly in New York, New Jersey, and Connecticut, we have managed to get COVID-19 under control. Perhaps, in this part of the country, opening classroom education might be feasible – with close monitoring and proper precautions.

But COVID-19 has taken the lives of hundreds of thousands of Americans – more than 176,000 as of this writing. A new model from the University of Washington’s Institute for Health Metrics and Evaluation projects that COVID-19 could lead to more than 300,000 U.S. deaths by Dec. 1. Thankfully, the number of COVID-19–positive children who have died has been low. But they could still pass on the virus to adults.

To get a better understanding of COVID-19, I spoke with Sheryl L. Wulkan, MD, an internist and expert in personal protective equipment (PPE) who has consulted for numerous health care agencies about these issues. Dr. Wulkan said that, in some areas with low infection rates, school openings might be appropriate. However, she said, without proper testing and contact tracing, we are at a loss of controlling the spread.
 

What we should tell patients, family, and friends

From a psychiatric point of view, how should we advise our patients, family, and friends about sending their children back to school? Is on-site learning better than remote learning? It is. Do our children need the socialization that a school brings? Yes, they do.

Socialization and relating to peers are, indeed, important, but today’s children socialize in many ways beyond attending school – and they have peer friendships and interactions with electronic devices at their disposal.

Can remote learning cause social isolation – an isolation so profound that school is necessary not only for learning but the psyche as well? A meta-analysis of 80 studies that looked at the impact of social isolation and loneliness on adolescents and children who were previously healthy found that the young people “are probably more likely to experience high rates of depression and probably anxiety during and after enforced isolation ends. This may increase as enforced isolation continues,” wrote Maria Elizabeth Loades, PhD, and associates (J Am Acad Child Adolesc Psychiatry. 2020 Jun 3. S0890-8567[20]30337-3).

I am concerned about young people who experience anxiety and depression, and agree with Dr. Loades that we mental health professionals need to be ready to intervene early and provide preventive support. To do this, we should encourage parents to keep us informed about how their children are doing.

So my advice is that, in the absence of a vaccine and an effective treatment like we have for influenza – such as Tamiflu – and effective testing, such the saliva-based test developed by Yale University researchers, if I had school-aged children, I would continue to keep them home from school. Ultimately, however, parents must look at the science and make their decisions based on that. My children are adults with their own children, and only they can make informed decisions about which options are best for their families.

Interestingly, Sanjay Gupta, MD, the neurosurgeon who works as chief medical correspondent of CNN, recently discussed the thought process he and his wife used to determine whether their daughters would return to the classroom. After weighing many factors, including the viral spread in Fulton County, Ga., where they live, the Guptas decided that, at this time, the risks of allowing the girls to return to the classroom outweigh the benefits. “This was not an easy decision, but one that we believe best respects the science, decreases the risk of further spread, and follows the task force criteria,” wrote Dr. Gupta, who is affiliated with Emory University in Atlanta. “After 2 weeks, we will reassess.”

I understand that parents worry about the social and psychological costs of remote learning. And I can only imagine the difficulty of those who must balance homeschooling with working. And frankly, remote learning is not an option for all students. For those less fortunate, substantial governmental aid is important to assist these people and to keep them safe and on their feet until this pandemic is done. Also, those who were under the care of a psychiatrist should continue to receive care during the pandemic. We must be prepared to step in with interventions that can address the suffering that is inevitable, such as the use of targeted cognitive-behavioral therapy.

Public TV as an educational tool

Families with Internet access and those without it could benefit from using public television as a tool.

I would advise educators and the entertainment industry to harness the wonder of TV to develop curricula that can be used to educate children. As we know, Sesame Street proved to be an effective early childhood intervention, particularly for boys (Am Econ J: Applied Economics. 2019;11[1]:318-50). I would like to see programming that goes beyond Sesame Street. Learning from watching this kind of programming would be no substitute for engaging with teachers in real, live classrooms, however.

Children and adolescents will be changed by learning remotely. They will miss their friends, teachers, and other staff members, but their lives will not be ruined. Mental health professionals should be prepared to intervene to address depression, anxiety, and other sequelae and problematic behaviors that could result from social isolation. Schools, businesses, and the economy will again flourish after we get the virus behind us but controlling and eliminating this pandemic need to come first. Let’s keep our children home – to the extent that we can – until we move beyond this pandemic.
 

Dr. London has been a practicing psychiatrist for 4 decades and a newspaper columnist for almost as long. He has a private practice in New York and is author of “Find Freedom Fast: Short-Term Therapy That Works” (New York: Kettlehole Publishing, 2019). Dr. London has no conflicts of interest.

“My other doctor has an office blog. You should have one, too. They’re really helpful.”

I hear that line a fair amount.

No, thank you.

I legitimately did try to have an office blog 7-8 years ago. I figured it might bring in a few more patients, answer FAQs from others, and give me something to do. So I did some reading, created an account on Blogger, and started one. I think my first post was on multiple sclerosis. Nothing really specific, more just generic “living with MS” tips.

I wrote another the next week, then a third post about 2 months later. Roughly 6 months after starting I gave up and quietly deleted the account.

I have no idea how some doctors have time for that sort of thing. They must have more free time than I do. Maybe they pay someone to write the posts for them. But it didn’t take me long to realize I didn’t have the time, or personal interest, to make it worthwhile. Besides, generic medical blogs spouting common sense (“Eat more vegetables! Exercise!”) are a dime a dozen. To put anything more specific in this day and age runs the risk of litigation.

I like writing, as evidenced by this column. But the time and effort that a regular office blog demanded was beyond what I could put into it, and the nature of the writing needed was more milquetoast than I enjoyed doing.

Time is, perhaps, the most precious commodity we have. Writing a nondescript office blog, as I learned, definitely wasn’t my cup of tea. I’m pretty sure an office Twitter account would be the same, and I have no interest in opening that door.

If another doctor wants to invest time in a blog, that’s fine. I hope it is something worthwhile and that they enjoy it. If a patient thinks that makes them a better doctor, they can.

But not me. If I’m going to devote time to my work, I’ll do it in the best way I know, and the one I still enjoy: seeing and treating patients.

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

“My other doctor has an office blog. You should have one, too. They’re really helpful.”

I hear that line a fair amount.

No, thank you.

I legitimately did try to have an office blog 7-8 years ago. I figured it might bring in a few more patients, answer FAQs from others, and give me something to do. So I did some reading, created an account on Blogger, and started one. I think my first post was on multiple sclerosis. Nothing really specific, more just generic “living with MS” tips.

I wrote another the next week, then a third post about 2 months later. Roughly 6 months after starting I gave up and quietly deleted the account.

I have no idea how some doctors have time for that sort of thing. They must have more free time than I do. Maybe they pay someone to write the posts for them. But it didn’t take me long to realize I didn’t have the time, or personal interest, to make it worthwhile. Besides, generic medical blogs spouting common sense (“Eat more vegetables! Exercise!”) are a dime a dozen. To put anything more specific in this day and age runs the risk of litigation.

I like writing, as evidenced by this column. But the time and effort that a regular office blog demanded was beyond what I could put into it, and the nature of the writing needed was more milquetoast than I enjoyed doing.

Time is, perhaps, the most precious commodity we have. Writing a nondescript office blog, as I learned, definitely wasn’t my cup of tea. I’m pretty sure an office Twitter account would be the same, and I have no interest in opening that door.

If another doctor wants to invest time in a blog, that’s fine. I hope it is something worthwhile and that they enjoy it. If a patient thinks that makes them a better doctor, they can.

But not me. If I’m going to devote time to my work, I’ll do it in the best way I know, and the one I still enjoy: seeing and treating patients.

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

“My other doctor has an office blog. You should have one, too. They’re really helpful.”

I hear that line a fair amount.

No, thank you.

I legitimately did try to have an office blog 7-8 years ago. I figured it might bring in a few more patients, answer FAQs from others, and give me something to do. So I did some reading, created an account on Blogger, and started one. I think my first post was on multiple sclerosis. Nothing really specific, more just generic “living with MS” tips.

I wrote another the next week, then a third post about 2 months later. Roughly 6 months after starting I gave up and quietly deleted the account.

I have no idea how some doctors have time for that sort of thing. They must have more free time than I do. Maybe they pay someone to write the posts for them. But it didn’t take me long to realize I didn’t have the time, or personal interest, to make it worthwhile. Besides, generic medical blogs spouting common sense (“Eat more vegetables! Exercise!”) are a dime a dozen. To put anything more specific in this day and age runs the risk of litigation.

I like writing, as evidenced by this column. But the time and effort that a regular office blog demanded was beyond what I could put into it, and the nature of the writing needed was more milquetoast than I enjoyed doing.

Time is, perhaps, the most precious commodity we have. Writing a nondescript office blog, as I learned, definitely wasn’t my cup of tea. I’m pretty sure an office Twitter account would be the same, and I have no interest in opening that door.

If another doctor wants to invest time in a blog, that’s fine. I hope it is something worthwhile and that they enjoy it. If a patient thinks that makes them a better doctor, they can.

But not me. If I’m going to devote time to my work, I’ll do it in the best way I know, and the one I still enjoy: seeing and treating patients.

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

Alzheimer’s disease may have a causal effect on sleep patterns, but disturbed sleep does not appear to cause Alzheimer’s disease, new research suggests.

The causal association between disturbed sleep and Alzheimer’s disease that has been observed in previous studies may have resulted from reverse causation, the researchers noted. The current Mendelian randomization analysis also failed to find a causal relationship between Alzheimer’s disease and major depressive disorder. Future studies should examine the genetic heterogeneity of depression syndromes to test for causal relationships between subtypes of depression with distinct causes and Alzheimer’s disease.

Mendelian randomization compares individuals who have different genetic profiles for a given exposure. “Given that genetic variants are inherited at random, these two groups are comparable, and any differences are not likely to be due to other associated factors,” such as confounding bias, said corresponding author Abbas Dehghan, PhD, reader in cardiometabolic disease epidemiology at Imperial College London. “Moreover, given that genetic information is constant over the lifetime, the chances for reverse causation are small.”

The findings were published online August 19 in Neurology.

Causal questions

Many patients with late-life neurodegenerative disorders such as Alzheimer’s disease have comorbid depression, but whether these two disorders have a causal relationship or common risk factors has been unclear, the investigators noted. Abnormal sleep patterns are symptoms of both depression and Alzheimer’s disease. Abnormal sleep is also associated with cognitive decline and anxiety.

The researchers hypothesized that sleep causally affects major depressive disorder and Alzheimer’s disease but that there is no causal relationship between major depressive disorder and Alzheimer’s disease. They conducted a bidirectional, two-sample Mendelian randomization study to test these hypotheses.

The investigators conducted genomewide association studies (GWASs) using data from the prospective, population-based U.K. Biobank. Sleep phenotypes were measured by self-report or accelerometer. Genetic associations were derived from 403,195 patients for chronotype, 237,627 patients for insomnia, 446,118 people for sleep duration, and 85,670 people for accelerometer-derived phenotypes.

Two binary variables from sleep duration were derived: short sleep (duration of less than 7 hours) and long sleep (duration of 9 or more hours). A sleep episode was defined as a period of at least 5 minutes with a change on the dorsal-ventral axis of less than 5 degrees. The durations of all sleep episodes were added to calculate total sleep duration.

Major depressive disorder was diagnosed clinically in accordance with DSM-IV criteria. Genetic associations were derived from 9,240 case patients and 9,519 control participants. Alzheimer’s disease was diagnosed on the basis of physician examination or autopsy results. Genetic associations were obtained from a meta-analysis of GWAS on participants of European ancestry in the International Genomics of Alzheimer’s Project, which included 21,982 case patients and 41,944 control participants.

More risk factor research needed

Results showed no causal relationships between sleep-related phenotypes and major depressive disorder in either direction. Causal relationships between major depressive disorder and Alzheimer’s disease were found in both directions, but neither was statistically significant.

A genetically higher risk for Alzheimer’s disease was associated with being a “morning person,” being at decreased risk for insomnia, having shorter sleep duration on self-report and accelerometer, having decreased likelihood of reporting long sleep, having an earlier timing of the least active 5 hours, and having a smaller number of sleep episodes. However, no analysis supported a causal effect of sleep-related phenotypes on risk for Alzheimer’s disease.

Because APOE4 can influence disease processes that may contribute to Alzheimer’s disease risk, the investigators also conducted a sensitivity analysis that excluded APOE single-nucleotide polymorphisms. In this analysis, the causal associations of Alzheimer’s disease with self-reported and accelerometer-based sleep duration were not significant. The sensitivity analysis did support the other causal associations between Alzheimer’s disease and sleep phenotypes, however.

The causal associations between major depressive disorder and Alzheimer’s disease observed in other studies may have been the result of confounding, and the participants may have had other associated characteristics that put them at risk for the disease, said Dr. Dehghan. Furthermore, the previous studies considered various sleep phenotypes together, whereas in the current study, the investigators examined them separately.

The results suggest that preclinical and clinical Alzheimer’s disease may affect sleep phenotypes differently. Sleep management thus could be an important approach to improving quality of life for patients with Alzheimer’s disease, the researchers wrote.

“Our study indicates that depression and sleep disorders are not likely to be a causal factor for Alzheimer’s disease,” Dr. Dehghan said. “We need to search for other risk factors for the prevention of Alzheimer’s disease.”

Several strengths, lacks details

Walter A. Kukull, PhD, professor of epidemiology and director of the National Alzheimer’s Coordinating Center at the University of Washington, Seattle, noted that the investigators appear to have implemented their chosen methods of causal association analysis well. “They attempted to examine the direction of the causal arrow for risk factors … and that is a step usually not well examined in other studies.”

He added that the collection of objective measures, such as of sleep, is another strength of the study.

However, “the common weakness of the basic GWAS sample is that clinical symptomatology determined Alzheimer’s disease diagnosis. Thus, asymptomatic or very mildly symptomatic persons with Alzheimer’s disease pathology in their brains were likely included among normal controls,” said Dr. Kukull, who was not involved with the research.

Because of an apparent lack of biomarker data, patients who had been diagnosed with Alzheimer’s disease may in fact have had a different form of dementia. Given the nature of their data, the investigators could have done little to compensate for these possibilities, Dr. Kukull added. In addition, the article lacks details that would improve the interpretation of the results.

“Timing is everything with regard to potential associations between risk factor and outcome,” Dr. Kukull said. “With the exceptions of genes, it would be nice to know more about the timing of risk factors’ onset and Alzheimer’s disease onset.”

Still, the results indicate potential areas of future study, he noted. “Primarily, further research must address the question of pathological onset of disease and misclassification of diagnosis in both cases and controls due to lack of biomarker-confirmed diagnosis. Then research can also struggle with the timing of potential risk factors with respect to disease.”

The study was funded by the U.K. Dementia Research Institute. Dr. Dehghan and Dr. Kukull reported no relevant financial relationships.

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

Alzheimer’s disease may have a causal effect on sleep patterns, but disturbed sleep does not appear to cause Alzheimer’s disease, new research suggests.

The causal association between disturbed sleep and Alzheimer’s disease that has been observed in previous studies may have resulted from reverse causation, the researchers noted. The current Mendelian randomization analysis also failed to find a causal relationship between Alzheimer’s disease and major depressive disorder. Future studies should examine the genetic heterogeneity of depression syndromes to test for causal relationships between subtypes of depression with distinct causes and Alzheimer’s disease.

Mendelian randomization compares individuals who have different genetic profiles for a given exposure. “Given that genetic variants are inherited at random, these two groups are comparable, and any differences are not likely to be due to other associated factors,” such as confounding bias, said corresponding author Abbas Dehghan, PhD, reader in cardiometabolic disease epidemiology at Imperial College London. “Moreover, given that genetic information is constant over the lifetime, the chances for reverse causation are small.”

The findings were published online August 19 in Neurology.

Causal questions

Many patients with late-life neurodegenerative disorders such as Alzheimer’s disease have comorbid depression, but whether these two disorders have a causal relationship or common risk factors has been unclear, the investigators noted. Abnormal sleep patterns are symptoms of both depression and Alzheimer’s disease. Abnormal sleep is also associated with cognitive decline and anxiety.

The researchers hypothesized that sleep causally affects major depressive disorder and Alzheimer’s disease but that there is no causal relationship between major depressive disorder and Alzheimer’s disease. They conducted a bidirectional, two-sample Mendelian randomization study to test these hypotheses.

The investigators conducted genomewide association studies (GWASs) using data from the prospective, population-based U.K. Biobank. Sleep phenotypes were measured by self-report or accelerometer. Genetic associations were derived from 403,195 patients for chronotype, 237,627 patients for insomnia, 446,118 people for sleep duration, and 85,670 people for accelerometer-derived phenotypes.

Two binary variables from sleep duration were derived: short sleep (duration of less than 7 hours) and long sleep (duration of 9 or more hours). A sleep episode was defined as a period of at least 5 minutes with a change on the dorsal-ventral axis of less than 5 degrees. The durations of all sleep episodes were added to calculate total sleep duration.

Major depressive disorder was diagnosed clinically in accordance with DSM-IV criteria. Genetic associations were derived from 9,240 case patients and 9,519 control participants. Alzheimer’s disease was diagnosed on the basis of physician examination or autopsy results. Genetic associations were obtained from a meta-analysis of GWAS on participants of European ancestry in the International Genomics of Alzheimer’s Project, which included 21,982 case patients and 41,944 control participants.

More risk factor research needed

Results showed no causal relationships between sleep-related phenotypes and major depressive disorder in either direction. Causal relationships between major depressive disorder and Alzheimer’s disease were found in both directions, but neither was statistically significant.

A genetically higher risk for Alzheimer’s disease was associated with being a “morning person,” being at decreased risk for insomnia, having shorter sleep duration on self-report and accelerometer, having decreased likelihood of reporting long sleep, having an earlier timing of the least active 5 hours, and having a smaller number of sleep episodes. However, no analysis supported a causal effect of sleep-related phenotypes on risk for Alzheimer’s disease.

Because APOE4 can influence disease processes that may contribute to Alzheimer’s disease risk, the investigators also conducted a sensitivity analysis that excluded APOE single-nucleotide polymorphisms. In this analysis, the causal associations of Alzheimer’s disease with self-reported and accelerometer-based sleep duration were not significant. The sensitivity analysis did support the other causal associations between Alzheimer’s disease and sleep phenotypes, however.

The causal associations between major depressive disorder and Alzheimer’s disease observed in other studies may have been the result of confounding, and the participants may have had other associated characteristics that put them at risk for the disease, said Dr. Dehghan. Furthermore, the previous studies considered various sleep phenotypes together, whereas in the current study, the investigators examined them separately.

The results suggest that preclinical and clinical Alzheimer’s disease may affect sleep phenotypes differently. Sleep management thus could be an important approach to improving quality of life for patients with Alzheimer’s disease, the researchers wrote.

“Our study indicates that depression and sleep disorders are not likely to be a causal factor for Alzheimer’s disease,” Dr. Dehghan said. “We need to search for other risk factors for the prevention of Alzheimer’s disease.”

Several strengths, lacks details

Walter A. Kukull, PhD, professor of epidemiology and director of the National Alzheimer’s Coordinating Center at the University of Washington, Seattle, noted that the investigators appear to have implemented their chosen methods of causal association analysis well. “They attempted to examine the direction of the causal arrow for risk factors … and that is a step usually not well examined in other studies.”

He added that the collection of objective measures, such as of sleep, is another strength of the study.

However, “the common weakness of the basic GWAS sample is that clinical symptomatology determined Alzheimer’s disease diagnosis. Thus, asymptomatic or very mildly symptomatic persons with Alzheimer’s disease pathology in their brains were likely included among normal controls,” said Dr. Kukull, who was not involved with the research.

Because of an apparent lack of biomarker data, patients who had been diagnosed with Alzheimer’s disease may in fact have had a different form of dementia. Given the nature of their data, the investigators could have done little to compensate for these possibilities, Dr. Kukull added. In addition, the article lacks details that would improve the interpretation of the results.

“Timing is everything with regard to potential associations between risk factor and outcome,” Dr. Kukull said. “With the exceptions of genes, it would be nice to know more about the timing of risk factors’ onset and Alzheimer’s disease onset.”

Still, the results indicate potential areas of future study, he noted. “Primarily, further research must address the question of pathological onset of disease and misclassification of diagnosis in both cases and controls due to lack of biomarker-confirmed diagnosis. Then research can also struggle with the timing of potential risk factors with respect to disease.”

The study was funded by the U.K. Dementia Research Institute. Dr. Dehghan and Dr. Kukull reported no relevant financial relationships.

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

Alzheimer’s disease may have a causal effect on sleep patterns, but disturbed sleep does not appear to cause Alzheimer’s disease, new research suggests.

The causal association between disturbed sleep and Alzheimer’s disease that has been observed in previous studies may have resulted from reverse causation, the researchers noted. The current Mendelian randomization analysis also failed to find a causal relationship between Alzheimer’s disease and major depressive disorder. Future studies should examine the genetic heterogeneity of depression syndromes to test for causal relationships between subtypes of depression with distinct causes and Alzheimer’s disease.

Mendelian randomization compares individuals who have different genetic profiles for a given exposure. “Given that genetic variants are inherited at random, these two groups are comparable, and any differences are not likely to be due to other associated factors,” such as confounding bias, said corresponding author Abbas Dehghan, PhD, reader in cardiometabolic disease epidemiology at Imperial College London. “Moreover, given that genetic information is constant over the lifetime, the chances for reverse causation are small.”

The findings were published online August 19 in Neurology.

Causal questions

Many patients with late-life neurodegenerative disorders such as Alzheimer’s disease have comorbid depression, but whether these two disorders have a causal relationship or common risk factors has been unclear, the investigators noted. Abnormal sleep patterns are symptoms of both depression and Alzheimer’s disease. Abnormal sleep is also associated with cognitive decline and anxiety.

The researchers hypothesized that sleep causally affects major depressive disorder and Alzheimer’s disease but that there is no causal relationship between major depressive disorder and Alzheimer’s disease. They conducted a bidirectional, two-sample Mendelian randomization study to test these hypotheses.

The investigators conducted genomewide association studies (GWASs) using data from the prospective, population-based U.K. Biobank. Sleep phenotypes were measured by self-report or accelerometer. Genetic associations were derived from 403,195 patients for chronotype, 237,627 patients for insomnia, 446,118 people for sleep duration, and 85,670 people for accelerometer-derived phenotypes.

Two binary variables from sleep duration were derived: short sleep (duration of less than 7 hours) and long sleep (duration of 9 or more hours). A sleep episode was defined as a period of at least 5 minutes with a change on the dorsal-ventral axis of less than 5 degrees. The durations of all sleep episodes were added to calculate total sleep duration.

Major depressive disorder was diagnosed clinically in accordance with DSM-IV criteria. Genetic associations were derived from 9,240 case patients and 9,519 control participants. Alzheimer’s disease was diagnosed on the basis of physician examination or autopsy results. Genetic associations were obtained from a meta-analysis of GWAS on participants of European ancestry in the International Genomics of Alzheimer’s Project, which included 21,982 case patients and 41,944 control participants.

More risk factor research needed

Results showed no causal relationships between sleep-related phenotypes and major depressive disorder in either direction. Causal relationships between major depressive disorder and Alzheimer’s disease were found in both directions, but neither was statistically significant.

A genetically higher risk for Alzheimer’s disease was associated with being a “morning person,” being at decreased risk for insomnia, having shorter sleep duration on self-report and accelerometer, having decreased likelihood of reporting long sleep, having an earlier timing of the least active 5 hours, and having a smaller number of sleep episodes. However, no analysis supported a causal effect of sleep-related phenotypes on risk for Alzheimer’s disease.

Because APOE4 can influence disease processes that may contribute to Alzheimer’s disease risk, the investigators also conducted a sensitivity analysis that excluded APOE single-nucleotide polymorphisms. In this analysis, the causal associations of Alzheimer’s disease with self-reported and accelerometer-based sleep duration were not significant. The sensitivity analysis did support the other causal associations between Alzheimer’s disease and sleep phenotypes, however.

The causal associations between major depressive disorder and Alzheimer’s disease observed in other studies may have been the result of confounding, and the participants may have had other associated characteristics that put them at risk for the disease, said Dr. Dehghan. Furthermore, the previous studies considered various sleep phenotypes together, whereas in the current study, the investigators examined them separately.

The results suggest that preclinical and clinical Alzheimer’s disease may affect sleep phenotypes differently. Sleep management thus could be an important approach to improving quality of life for patients with Alzheimer’s disease, the researchers wrote.

“Our study indicates that depression and sleep disorders are not likely to be a causal factor for Alzheimer’s disease,” Dr. Dehghan said. “We need to search for other risk factors for the prevention of Alzheimer’s disease.”

Several strengths, lacks details

Walter A. Kukull, PhD, professor of epidemiology and director of the National Alzheimer’s Coordinating Center at the University of Washington, Seattle, noted that the investigators appear to have implemented their chosen methods of causal association analysis well. “They attempted to examine the direction of the causal arrow for risk factors … and that is a step usually not well examined in other studies.”

He added that the collection of objective measures, such as of sleep, is another strength of the study.

However, “the common weakness of the basic GWAS sample is that clinical symptomatology determined Alzheimer’s disease diagnosis. Thus, asymptomatic or very mildly symptomatic persons with Alzheimer’s disease pathology in their brains were likely included among normal controls,” said Dr. Kukull, who was not involved with the research.

Because of an apparent lack of biomarker data, patients who had been diagnosed with Alzheimer’s disease may in fact have had a different form of dementia. Given the nature of their data, the investigators could have done little to compensate for these possibilities, Dr. Kukull added. In addition, the article lacks details that would improve the interpretation of the results.

“Timing is everything with regard to potential associations between risk factor and outcome,” Dr. Kukull said. “With the exceptions of genes, it would be nice to know more about the timing of risk factors’ onset and Alzheimer’s disease onset.”

Still, the results indicate potential areas of future study, he noted. “Primarily, further research must address the question of pathological onset of disease and misclassification of diagnosis in both cases and controls due to lack of biomarker-confirmed diagnosis. Then research can also struggle with the timing of potential risk factors with respect to disease.”

The study was funded by the U.K. Dementia Research Institute. Dr. Dehghan and Dr. Kukull reported no relevant financial relationships.

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

The United Kingdom’s National Obesity Forum has apparently decided that returning to school this fall in the middle of a pandemic isn’t stressful enough for kids, and is recommending that its National Child Measurement Programme be expanded to have 4- to 5-year-old and 10- to 11-year-old children weighed when they return to the classroom – and then weighed again in the spring – in a bid to tackle COVID-19–related gains.

It’s difficult to conceive a single plausible mechanism by which this recommendation could be helpful. Given that weight is, by a substantial margin, the No. 1 reported cause of schoolyard bullying, it’s certainly unlikely that children with obesity don’t already know that they have it. It’s also unlikely that they don’t know that obesity confers risks to health, given the near constant drumbeats of concern percussed by the media and public health authorities, and the fact that watching people with obesity be blamed, shamed, and berated for their condition has in the past 2 decades become a regularly repeated prime-time reality show spectacle.

It’s also unlikely, especially in younger grades, to be something within a child’s direct control.

What about the parents? Well, given that they dress their children and that changes in weight affect clothing sizes and fit, they’re already aware if their kids are gaining weight. And like their children, they have been exposed to constant public health alarms around obesity.

Many parents will have seen their time and resources, both real and mental, become significantly impaired during the time of COVID-19, which in turn understandably challenges change. Simply put, permanent intentional behavior change in the name of health requires tremendous privilege and is elusive for many people even during easier times. For non–evidence-based proof of this assertion, simply reflect on all of your own best-laid intentions and plans that might have been good for your health (fitness, relationships, CME, etc.) that you let slide despite probably having far more privilege than the average person.

Then, of course, there is the hugely inconvenient truth that we have yet to see the development of a parent- or child-based educational intervention or directive for weight gain that has shown itself to be beneficial on a population level.
 

Can something else be done instead?

At this point, we can only speculate about the potential risks associated with school room weigh-ins because randomized controlled trials, thankfully, have not been conducted to explore this area. But I can certainly tell you that I have met many adult patients in my office who traced their lifetime of yo-yo dieting – along with a history of teenage eating disorders, at times – to their well-intentioned physician, school nurse, gym teacher, or parent using a scale to measure their weights. And in doing so, they were teaching that scales measure health, happiness, success, self-worth, and effort.

If governments are concerned about weight gain in children, they need to look to initiatives that will help all children and parents. Weighing them will not somehow inspire parents or kids to discover an as-yet unknown effective childhood obesity treatment. Changes that would be helpful may include:

• Banning food advertisements to children.
• Reforming school cafeteria meals and then ensuring that school meals are made available to children during COVID-19–related school shutdowns.
• Bringing back home economics classes to teach children how to cook (and perhaps doing the same for parents during school off-hours or in community centers).
• Enacting sugar-sweetened beverage taxes and using revenues to fund aforementioned reforms and programs, along with others, which might include the subsidization of fresh produce.
• Reforming front-of-package health claims for foods with questionable nutritional quality.

Given that there is literally no age category in any country on the planet that hasn’t seen rising weights, this is clearly not a disease reflecting a pandemic loss of willpower. Rather, this is a disease of the world’s changing food environments and culture, and until we address both through systemic changes, schemes such as the one being proposed by the UK National Obesity Forum are far more likely to do harm than good.

Yoni Freedhoff is associate professor of family medicine at the University of Ottawa and medical director of the Bariatric Medical Institute, a nonsurgical weight management center. He is one of Canada’s most outspoken obesity experts and the author of “The Diet Fix: Why Diets Fail and How to Make Yours Work.” A version of this article originally appeared on Medscape.com.

The United Kingdom’s National Obesity Forum has apparently decided that returning to school this fall in the middle of a pandemic isn’t stressful enough for kids, and is recommending that its National Child Measurement Programme be expanded to have 4- to 5-year-old and 10- to 11-year-old children weighed when they return to the classroom – and then weighed again in the spring – in a bid to tackle COVID-19–related gains.

It’s difficult to conceive a single plausible mechanism by which this recommendation could be helpful. Given that weight is, by a substantial margin, the No. 1 reported cause of schoolyard bullying, it’s certainly unlikely that children with obesity don’t already know that they have it. It’s also unlikely that they don’t know that obesity confers risks to health, given the near constant drumbeats of concern percussed by the media and public health authorities, and the fact that watching people with obesity be blamed, shamed, and berated for their condition has in the past 2 decades become a regularly repeated prime-time reality show spectacle.

It’s also unlikely, especially in younger grades, to be something within a child’s direct control.

What about the parents? Well, given that they dress their children and that changes in weight affect clothing sizes and fit, they’re already aware if their kids are gaining weight. And like their children, they have been exposed to constant public health alarms around obesity.

Many parents will have seen their time and resources, both real and mental, become significantly impaired during the time of COVID-19, which in turn understandably challenges change. Simply put, permanent intentional behavior change in the name of health requires tremendous privilege and is elusive for many people even during easier times. For non–evidence-based proof of this assertion, simply reflect on all of your own best-laid intentions and plans that might have been good for your health (fitness, relationships, CME, etc.) that you let slide despite probably having far more privilege than the average person.

Then, of course, there is the hugely inconvenient truth that we have yet to see the development of a parent- or child-based educational intervention or directive for weight gain that has shown itself to be beneficial on a population level.
 

Can something else be done instead?

At this point, we can only speculate about the potential risks associated with school room weigh-ins because randomized controlled trials, thankfully, have not been conducted to explore this area. But I can certainly tell you that I have met many adult patients in my office who traced their lifetime of yo-yo dieting – along with a history of teenage eating disorders, at times – to their well-intentioned physician, school nurse, gym teacher, or parent using a scale to measure their weights. And in doing so, they were teaching that scales measure health, happiness, success, self-worth, and effort.

If governments are concerned about weight gain in children, they need to look to initiatives that will help all children and parents. Weighing them will not somehow inspire parents or kids to discover an as-yet unknown effective childhood obesity treatment. Changes that would be helpful may include:

• Banning food advertisements to children.
• Reforming school cafeteria meals and then ensuring that school meals are made available to children during COVID-19–related school shutdowns.
• Bringing back home economics classes to teach children how to cook (and perhaps doing the same for parents during school off-hours or in community centers).
• Enacting sugar-sweetened beverage taxes and using revenues to fund aforementioned reforms and programs, along with others, which might include the subsidization of fresh produce.
• Reforming front-of-package health claims for foods with questionable nutritional quality.

Given that there is literally no age category in any country on the planet that hasn’t seen rising weights, this is clearly not a disease reflecting a pandemic loss of willpower. Rather, this is a disease of the world’s changing food environments and culture, and until we address both through systemic changes, schemes such as the one being proposed by the UK National Obesity Forum are far more likely to do harm than good.

Yoni Freedhoff is associate professor of family medicine at the University of Ottawa and medical director of the Bariatric Medical Institute, a nonsurgical weight management center. He is one of Canada’s most outspoken obesity experts and the author of “The Diet Fix: Why Diets Fail and How to Make Yours Work.” A version of this article originally appeared on Medscape.com.

The United Kingdom’s National Obesity Forum has apparently decided that returning to school this fall in the middle of a pandemic isn’t stressful enough for kids, and is recommending that its National Child Measurement Programme be expanded to have 4- to 5-year-old and 10- to 11-year-old children weighed when they return to the classroom – and then weighed again in the spring – in a bid to tackle COVID-19–related gains.

It’s difficult to conceive a single plausible mechanism by which this recommendation could be helpful. Given that weight is, by a substantial margin, the No. 1 reported cause of schoolyard bullying, it’s certainly unlikely that children with obesity don’t already know that they have it. It’s also unlikely that they don’t know that obesity confers risks to health, given the near constant drumbeats of concern percussed by the media and public health authorities, and the fact that watching people with obesity be blamed, shamed, and berated for their condition has in the past 2 decades become a regularly repeated prime-time reality show spectacle.

It’s also unlikely, especially in younger grades, to be something within a child’s direct control.

What about the parents? Well, given that they dress their children and that changes in weight affect clothing sizes and fit, they’re already aware if their kids are gaining weight. And like their children, they have been exposed to constant public health alarms around obesity.

Many parents will have seen their time and resources, both real and mental, become significantly impaired during the time of COVID-19, which in turn understandably challenges change. Simply put, permanent intentional behavior change in the name of health requires tremendous privilege and is elusive for many people even during easier times. For non–evidence-based proof of this assertion, simply reflect on all of your own best-laid intentions and plans that might have been good for your health (fitness, relationships, CME, etc.) that you let slide despite probably having far more privilege than the average person.

Then, of course, there is the hugely inconvenient truth that we have yet to see the development of a parent- or child-based educational intervention or directive for weight gain that has shown itself to be beneficial on a population level.
 

Can something else be done instead?

At this point, we can only speculate about the potential risks associated with school room weigh-ins because randomized controlled trials, thankfully, have not been conducted to explore this area. But I can certainly tell you that I have met many adult patients in my office who traced their lifetime of yo-yo dieting – along with a history of teenage eating disorders, at times – to their well-intentioned physician, school nurse, gym teacher, or parent using a scale to measure their weights. And in doing so, they were teaching that scales measure health, happiness, success, self-worth, and effort.

If governments are concerned about weight gain in children, they need to look to initiatives that will help all children and parents. Weighing them will not somehow inspire parents or kids to discover an as-yet unknown effective childhood obesity treatment. Changes that would be helpful may include:

• Banning food advertisements to children.
• Reforming school cafeteria meals and then ensuring that school meals are made available to children during COVID-19–related school shutdowns.
• Bringing back home economics classes to teach children how to cook (and perhaps doing the same for parents during school off-hours or in community centers).
• Enacting sugar-sweetened beverage taxes and using revenues to fund aforementioned reforms and programs, along with others, which might include the subsidization of fresh produce.
• Reforming front-of-package health claims for foods with questionable nutritional quality.

Given that there is literally no age category in any country on the planet that hasn’t seen rising weights, this is clearly not a disease reflecting a pandemic loss of willpower. Rather, this is a disease of the world’s changing food environments and culture, and until we address both through systemic changes, schemes such as the one being proposed by the UK National Obesity Forum are far more likely to do harm than good.

Yoni Freedhoff is associate professor of family medicine at the University of Ottawa and medical director of the Bariatric Medical Institute, a nonsurgical weight management center. He is one of Canada’s most outspoken obesity experts and the author of “The Diet Fix: Why Diets Fail and How to Make Yours Work.” A version of this article originally appeared on Medscape.com.

The US Food and Drug Administration has approved phase one clinical trials for a synthetic cannabinoid drug designed to treat acute respiratory distress syndrome (ARDS), a life-threatening lung condition which may occur in severe cases of the novel coronavirus, Forbes reported.

ARDS can be triggered by over-creation of cytokines, proteins which tell the body to produce more inflammation, Forbes said.

The drug going to clinical trials, ARDS-003, would “dampen the cytokine release” and prevent development of ARDS, Tetra Bio-Pharma company CEO and chief regulatory officer Guy Chamberland, MD, said in a news release.

Consequences of ARDS include scarring of the lungs and organ injury caused by the decrease in blood to the tissue, the release said.

“The FDA repeatedly stated that they want clinical trials for COVID-19 to begin as soon as possible, as long as they meet regulatory requirements,” the news release said. “The medical community is in urgent need of drugs that can reduce the strength and duration of the severe inflammation. It is anticipated that this type of new drug would favorably impact health care and possibly reduce the negative health outcomes post infection.”

ARDS-003 works by binding to CB2 receptors, one of two main receptors in the endocannabinoid system which modulate inflammation and cytokine activity, Forbes said. CB2 receptors don’t bring on a psychoactive high.

Phase one clinical trials would begin enrolling participants in December to determine if the drug is safe, Chamberland said, according to Forbes.

If phase one is successful, phase two would test the drug on a larger group in the second quarter of 2021 to assess safety and tolerability for people who have COVID-19. 

If phase two is successful, the company may seek emergency authorization through the FDA, Chamberland said.  Phase three would start at the end of 2021.

Tetra Bio-Pharma says it has already contracted with Dalton Pharma Services to manufacture the active pharmaceutical ingredient (API), HU-308, and the finished drug product ARDS-003.
 

This article first appeared on Medscape.com.

The US Food and Drug Administration has approved phase one clinical trials for a synthetic cannabinoid drug designed to treat acute respiratory distress syndrome (ARDS), a life-threatening lung condition which may occur in severe cases of the novel coronavirus, Forbes reported.

ARDS can be triggered by over-creation of cytokines, proteins which tell the body to produce more inflammation, Forbes said.

The drug going to clinical trials, ARDS-003, would “dampen the cytokine release” and prevent development of ARDS, Tetra Bio-Pharma company CEO and chief regulatory officer Guy Chamberland, MD, said in a news release.

Consequences of ARDS include scarring of the lungs and organ injury caused by the decrease in blood to the tissue, the release said.

“The FDA repeatedly stated that they want clinical trials for COVID-19 to begin as soon as possible, as long as they meet regulatory requirements,” the news release said. “The medical community is in urgent need of drugs that can reduce the strength and duration of the severe inflammation. It is anticipated that this type of new drug would favorably impact health care and possibly reduce the negative health outcomes post infection.”

ARDS-003 works by binding to CB2 receptors, one of two main receptors in the endocannabinoid system which modulate inflammation and cytokine activity, Forbes said. CB2 receptors don’t bring on a psychoactive high.

Phase one clinical trials would begin enrolling participants in December to determine if the drug is safe, Chamberland said, according to Forbes.

If phase one is successful, phase two would test the drug on a larger group in the second quarter of 2021 to assess safety and tolerability for people who have COVID-19. 

If phase two is successful, the company may seek emergency authorization through the FDA, Chamberland said.  Phase three would start at the end of 2021.

Tetra Bio-Pharma says it has already contracted with Dalton Pharma Services to manufacture the active pharmaceutical ingredient (API), HU-308, and the finished drug product ARDS-003.
 

This article first appeared on Medscape.com.

The US Food and Drug Administration has approved phase one clinical trials for a synthetic cannabinoid drug designed to treat acute respiratory distress syndrome (ARDS), a life-threatening lung condition which may occur in severe cases of the novel coronavirus, Forbes reported.

ARDS can be triggered by over-creation of cytokines, proteins which tell the body to produce more inflammation, Forbes said.

The drug going to clinical trials, ARDS-003, would “dampen the cytokine release” and prevent development of ARDS, Tetra Bio-Pharma company CEO and chief regulatory officer Guy Chamberland, MD, said in a news release.

Consequences of ARDS include scarring of the lungs and organ injury caused by the decrease in blood to the tissue, the release said.

“The FDA repeatedly stated that they want clinical trials for COVID-19 to begin as soon as possible, as long as they meet regulatory requirements,” the news release said. “The medical community is in urgent need of drugs that can reduce the strength and duration of the severe inflammation. It is anticipated that this type of new drug would favorably impact health care and possibly reduce the negative health outcomes post infection.”

ARDS-003 works by binding to CB2 receptors, one of two main receptors in the endocannabinoid system which modulate inflammation and cytokine activity, Forbes said. CB2 receptors don’t bring on a psychoactive high.

Phase one clinical trials would begin enrolling participants in December to determine if the drug is safe, Chamberland said, according to Forbes.

If phase one is successful, phase two would test the drug on a larger group in the second quarter of 2021 to assess safety and tolerability for people who have COVID-19. 

If phase two is successful, the company may seek emergency authorization through the FDA, Chamberland said.  Phase three would start at the end of 2021.

Tetra Bio-Pharma says it has already contracted with Dalton Pharma Services to manufacture the active pharmaceutical ingredient (API), HU-308, and the finished drug product ARDS-003.
 

This article first appeared on Medscape.com.

Researchers in Hong Kong say they’ve confirmed that a person can be infected with COVID-19 twice.

There have been sporadic accounts on social media sites of people who say they’ve gotten COVID-19 twice. But scientists have been skeptical about that possibility, saying there’s no evidence it happens.

The new proof comes from a 33-year-old man in Hong Kong who first caught COVID-19 in March. He was tested for the coronavirus after he developed a cough, sore throat, fever, and a headache for 3 days. He stayed in the hospital until he twice tested negative for the virus in mid-April.

On Aug. 15, the man returned to Hong Kong from a recent trip to Spain and the United Kingdom, areas that have recently seen a resurgence of COVID-19 cases. At the airport, he was screened for COVID-19 with a test that checks saliva for the virus. He tested positive, but this time, had no symptoms. He was taken to the hospital for monitoring. His viral load – the amount of virus he had in his body – went down over time, suggesting that his immune system was taking care of the intrusion on its own.

The special thing about his case is that each time he was hospitalized, doctors sequenced the genome of the virus that infected him. It was slightly different from one infection to the next, suggesting that the virus had mutated – or changed – in the 4 months between his infections. It also proves that it’s possible for this coronavirus to infect the same person twice.

Experts with the World Health Organization responded to the case at a news briefing.

“What we are learning about infection is that people do develop an immune response. What is not completely clear yet is how strong that immune response is and for how long that immune response lasts,” said Maria Van Kerkhove, PhD, an infectious disease epidemiologist with the World Health Organization in Geneva, Switzerland.

A study on the man’s case is being prepared for publication in the journal Clinical Infectious Diseases. Experts say the finding shouldn’t cause alarm, but it does have important implications for the development of herd immunity and efforts to come up with vaccines and treatments.

“This appears to be pretty clear-cut evidence of reinfection because of sequencing and isolation of two different viruses,” said Gregory Poland, MD, an expert on vaccine development and immunology at the Mayo Clinic in Rochester, Minn. “The big unknown is how often is this happening,” he said. More studies are needed to learn whether this was a rare case or something that is happening often.
 

Past experience guides present

Until we know more, Dr. Poland said, the possibility of getting COVID-19 twice shouldn’t make anyone worry.

This also happens with other kinds of coronaviruses – the ones that cause common colds. Those coronaviruses change slightly each year as they circle the globe, which allows them to keep spreading and causing their more run-of-the-mill kind of misery.

It also happens with seasonal flu. It is the reason people have to get vaccinated against the flu year after year, and why the flu vaccine has to change slightly each year in an effort to keep up with the ever-evolving influenza virus.

“We’ve been making flu vaccines for 80 years, and there are clinical trials happening as we speak to find new and better influenza vaccines,” Dr. Poland said.

There has been other evidence the virus that causes COVID-19 can change this way, too. Researchers at Howard Hughes Medical Center, at Rockefeller University in New York, recently used a key piece of the SARS-CoV-2 virus – the genetic instructions for its spike protein – to repeatedly infect human cells. Scientists watched as each new generation of the virus went on to infect a new batch of cells. Over time, as it copied itself, some of the copies changed their genes to allow them to survive after scientists attacked them with neutralizing antibodies. Those antibodies are among the main weapons used by the immune system to recognize and disable a virus.

Though that study is still a preprint, which means it hasn’t yet been reviewed by outside experts, the authors wrote that their findings suggest the virus can change in ways that help it evade our immune system. If true, they wrote in mid-July, it means reinfection is possible, especially in people who have a weak immune response to the virus the first time they encounter it.
 

Good news

That seems to be true in the case of the man from Hong Kong. When doctors tested his blood to look for antibodies to the virus, they didn’t find any. That could mean that he either had a weak immune response to the virus the first time around, or that the antibodies he made during his first infection diminished over time. But during his second infection, he quickly developed more antibodies, suggesting that the second infection acted a little bit like a booster to fire up his immune system. That’s probably the reason he didn’t have any symptoms the second time, too.

That’s good news, Dr. Poland said. It means our bodies can get better at fighting off the COVID-19 virus and that catching it once means the second time might not be so bad.

But the fact that the virus can change quickly this way does have some impact on the effort to come up with a vaccine that works well.

“I think a potential implication of this is that we will have to give booster doses. The question is how frequently,” Dr. Poland said. That will depend on how fast the virus is changing, and how often reinfection is happening in the real world.

“I’m a little surprised at 4½ months,” Dr. Poland said, referencing the time between the Hong Kong man’s infections. “I’m not surprised by, you know, I got infected last winter and I got infected again this winter,” he said.

It also suggests that immune-based therapies such as convalescent plasma and monoclonal antibodies may be of limited help over time, since the virus might be changing in ways that help it outsmart those treatments.

Convalescent plasma is essentially a concentrated dose of antibodies from people who have recovered from a COVID-19 infection. As the virus changes, the antibodies in that plasma may not work as well for future infections.

Drug companies have learned to harness the power of monoclonal antibodies as powerful treatments against cancer and other diseases. Monoclonal antibodies, which are mass-produced in a lab, mimic the body’s natural defenses against a pathogen. Just like the virus can become resistant to natural immunity, it can change in ways that help it outsmart lab-created treatments. Some drug companies that are developing monoclonal antibodies to fight COVID-19 have already prepared for that possibility by making antibody cocktails that are designed to disable the virus by locking onto it in different places, which may help prevent it from developing resistance to those therapies.

“We have a lot to learn,” Dr. Poland said. “Now that the proof of principle has been established, and I would say it has with this man, and with our knowledge of seasonal coronaviruses, we need to look more aggressively to define how often this occurs.”

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

Researchers in Hong Kong say they’ve confirmed that a person can be infected with COVID-19 twice.

There have been sporadic accounts on social media sites of people who say they’ve gotten COVID-19 twice. But scientists have been skeptical about that possibility, saying there’s no evidence it happens.

The new proof comes from a 33-year-old man in Hong Kong who first caught COVID-19 in March. He was tested for the coronavirus after he developed a cough, sore throat, fever, and a headache for 3 days. He stayed in the hospital until he twice tested negative for the virus in mid-April.

On Aug. 15, the man returned to Hong Kong from a recent trip to Spain and the United Kingdom, areas that have recently seen a resurgence of COVID-19 cases. At the airport, he was screened for COVID-19 with a test that checks saliva for the virus. He tested positive, but this time, had no symptoms. He was taken to the hospital for monitoring. His viral load – the amount of virus he had in his body – went down over time, suggesting that his immune system was taking care of the intrusion on its own.

The special thing about his case is that each time he was hospitalized, doctors sequenced the genome of the virus that infected him. It was slightly different from one infection to the next, suggesting that the virus had mutated – or changed – in the 4 months between his infections. It also proves that it’s possible for this coronavirus to infect the same person twice.

Experts with the World Health Organization responded to the case at a news briefing.

“What we are learning about infection is that people do develop an immune response. What is not completely clear yet is how strong that immune response is and for how long that immune response lasts,” said Maria Van Kerkhove, PhD, an infectious disease epidemiologist with the World Health Organization in Geneva, Switzerland.

A study on the man’s case is being prepared for publication in the journal Clinical Infectious Diseases. Experts say the finding shouldn’t cause alarm, but it does have important implications for the development of herd immunity and efforts to come up with vaccines and treatments.

“This appears to be pretty clear-cut evidence of reinfection because of sequencing and isolation of two different viruses,” said Gregory Poland, MD, an expert on vaccine development and immunology at the Mayo Clinic in Rochester, Minn. “The big unknown is how often is this happening,” he said. More studies are needed to learn whether this was a rare case or something that is happening often.
 

Past experience guides present

Until we know more, Dr. Poland said, the possibility of getting COVID-19 twice shouldn’t make anyone worry.

This also happens with other kinds of coronaviruses – the ones that cause common colds. Those coronaviruses change slightly each year as they circle the globe, which allows them to keep spreading and causing their more run-of-the-mill kind of misery.

It also happens with seasonal flu. It is the reason people have to get vaccinated against the flu year after year, and why the flu vaccine has to change slightly each year in an effort to keep up with the ever-evolving influenza virus.

“We’ve been making flu vaccines for 80 years, and there are clinical trials happening as we speak to find new and better influenza vaccines,” Dr. Poland said.

There has been other evidence the virus that causes COVID-19 can change this way, too. Researchers at Howard Hughes Medical Center, at Rockefeller University in New York, recently used a key piece of the SARS-CoV-2 virus – the genetic instructions for its spike protein – to repeatedly infect human cells. Scientists watched as each new generation of the virus went on to infect a new batch of cells. Over time, as it copied itself, some of the copies changed their genes to allow them to survive after scientists attacked them with neutralizing antibodies. Those antibodies are among the main weapons used by the immune system to recognize and disable a virus.

Though that study is still a preprint, which means it hasn’t yet been reviewed by outside experts, the authors wrote that their findings suggest the virus can change in ways that help it evade our immune system. If true, they wrote in mid-July, it means reinfection is possible, especially in people who have a weak immune response to the virus the first time they encounter it.
 

Good news

That seems to be true in the case of the man from Hong Kong. When doctors tested his blood to look for antibodies to the virus, they didn’t find any. That could mean that he either had a weak immune response to the virus the first time around, or that the antibodies he made during his first infection diminished over time. But during his second infection, he quickly developed more antibodies, suggesting that the second infection acted a little bit like a booster to fire up his immune system. That’s probably the reason he didn’t have any symptoms the second time, too.

That’s good news, Dr. Poland said. It means our bodies can get better at fighting off the COVID-19 virus and that catching it once means the second time might not be so bad.

But the fact that the virus can change quickly this way does have some impact on the effort to come up with a vaccine that works well.

“I think a potential implication of this is that we will have to give booster doses. The question is how frequently,” Dr. Poland said. That will depend on how fast the virus is changing, and how often reinfection is happening in the real world.

“I’m a little surprised at 4½ months,” Dr. Poland said, referencing the time between the Hong Kong man’s infections. “I’m not surprised by, you know, I got infected last winter and I got infected again this winter,” he said.

It also suggests that immune-based therapies such as convalescent plasma and monoclonal antibodies may be of limited help over time, since the virus might be changing in ways that help it outsmart those treatments.

Convalescent plasma is essentially a concentrated dose of antibodies from people who have recovered from a COVID-19 infection. As the virus changes, the antibodies in that plasma may not work as well for future infections.

Drug companies have learned to harness the power of monoclonal antibodies as powerful treatments against cancer and other diseases. Monoclonal antibodies, which are mass-produced in a lab, mimic the body’s natural defenses against a pathogen. Just like the virus can become resistant to natural immunity, it can change in ways that help it outsmart lab-created treatments. Some drug companies that are developing monoclonal antibodies to fight COVID-19 have already prepared for that possibility by making antibody cocktails that are designed to disable the virus by locking onto it in different places, which may help prevent it from developing resistance to those therapies.

“We have a lot to learn,” Dr. Poland said. “Now that the proof of principle has been established, and I would say it has with this man, and with our knowledge of seasonal coronaviruses, we need to look more aggressively to define how often this occurs.”

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

Researchers in Hong Kong say they’ve confirmed that a person can be infected with COVID-19 twice.

There have been sporadic accounts on social media sites of people who say they’ve gotten COVID-19 twice. But scientists have been skeptical about that possibility, saying there’s no evidence it happens.

The new proof comes from a 33-year-old man in Hong Kong who first caught COVID-19 in March. He was tested for the coronavirus after he developed a cough, sore throat, fever, and a headache for 3 days. He stayed in the hospital until he twice tested negative for the virus in mid-April.

On Aug. 15, the man returned to Hong Kong from a recent trip to Spain and the United Kingdom, areas that have recently seen a resurgence of COVID-19 cases. At the airport, he was screened for COVID-19 with a test that checks saliva for the virus. He tested positive, but this time, had no symptoms. He was taken to the hospital for monitoring. His viral load – the amount of virus he had in his body – went down over time, suggesting that his immune system was taking care of the intrusion on its own.

The special thing about his case is that each time he was hospitalized, doctors sequenced the genome of the virus that infected him. It was slightly different from one infection to the next, suggesting that the virus had mutated – or changed – in the 4 months between his infections. It also proves that it’s possible for this coronavirus to infect the same person twice.

Experts with the World Health Organization responded to the case at a news briefing.

“What we are learning about infection is that people do develop an immune response. What is not completely clear yet is how strong that immune response is and for how long that immune response lasts,” said Maria Van Kerkhove, PhD, an infectious disease epidemiologist with the World Health Organization in Geneva, Switzerland.

A study on the man’s case is being prepared for publication in the journal Clinical Infectious Diseases. Experts say the finding shouldn’t cause alarm, but it does have important implications for the development of herd immunity and efforts to come up with vaccines and treatments.

“This appears to be pretty clear-cut evidence of reinfection because of sequencing and isolation of two different viruses,” said Gregory Poland, MD, an expert on vaccine development and immunology at the Mayo Clinic in Rochester, Minn. “The big unknown is how often is this happening,” he said. More studies are needed to learn whether this was a rare case or something that is happening often.
 

Past experience guides present

Until we know more, Dr. Poland said, the possibility of getting COVID-19 twice shouldn’t make anyone worry.

This also happens with other kinds of coronaviruses – the ones that cause common colds. Those coronaviruses change slightly each year as they circle the globe, which allows them to keep spreading and causing their more run-of-the-mill kind of misery.

It also happens with seasonal flu. It is the reason people have to get vaccinated against the flu year after year, and why the flu vaccine has to change slightly each year in an effort to keep up with the ever-evolving influenza virus.

“We’ve been making flu vaccines for 80 years, and there are clinical trials happening as we speak to find new and better influenza vaccines,” Dr. Poland said.

There has been other evidence the virus that causes COVID-19 can change this way, too. Researchers at Howard Hughes Medical Center, at Rockefeller University in New York, recently used a key piece of the SARS-CoV-2 virus – the genetic instructions for its spike protein – to repeatedly infect human cells. Scientists watched as each new generation of the virus went on to infect a new batch of cells. Over time, as it copied itself, some of the copies changed their genes to allow them to survive after scientists attacked them with neutralizing antibodies. Those antibodies are among the main weapons used by the immune system to recognize and disable a virus.

Though that study is still a preprint, which means it hasn’t yet been reviewed by outside experts, the authors wrote that their findings suggest the virus can change in ways that help it evade our immune system. If true, they wrote in mid-July, it means reinfection is possible, especially in people who have a weak immune response to the virus the first time they encounter it.
 

Good news

That seems to be true in the case of the man from Hong Kong. When doctors tested his blood to look for antibodies to the virus, they didn’t find any. That could mean that he either had a weak immune response to the virus the first time around, or that the antibodies he made during his first infection diminished over time. But during his second infection, he quickly developed more antibodies, suggesting that the second infection acted a little bit like a booster to fire up his immune system. That’s probably the reason he didn’t have any symptoms the second time, too.

That’s good news, Dr. Poland said. It means our bodies can get better at fighting off the COVID-19 virus and that catching it once means the second time might not be so bad.

But the fact that the virus can change quickly this way does have some impact on the effort to come up with a vaccine that works well.

“I think a potential implication of this is that we will have to give booster doses. The question is how frequently,” Dr. Poland said. That will depend on how fast the virus is changing, and how often reinfection is happening in the real world.

“I’m a little surprised at 4½ months,” Dr. Poland said, referencing the time between the Hong Kong man’s infections. “I’m not surprised by, you know, I got infected last winter and I got infected again this winter,” he said.

It also suggests that immune-based therapies such as convalescent plasma and monoclonal antibodies may be of limited help over time, since the virus might be changing in ways that help it outsmart those treatments.

Convalescent plasma is essentially a concentrated dose of antibodies from people who have recovered from a COVID-19 infection. As the virus changes, the antibodies in that plasma may not work as well for future infections.

Drug companies have learned to harness the power of monoclonal antibodies as powerful treatments against cancer and other diseases. Monoclonal antibodies, which are mass-produced in a lab, mimic the body’s natural defenses against a pathogen. Just like the virus can become resistant to natural immunity, it can change in ways that help it outsmart lab-created treatments. Some drug companies that are developing monoclonal antibodies to fight COVID-19 have already prepared for that possibility by making antibody cocktails that are designed to disable the virus by locking onto it in different places, which may help prevent it from developing resistance to those therapies.

“We have a lot to learn,” Dr. Poland said. “Now that the proof of principle has been established, and I would say it has with this man, and with our knowledge of seasonal coronaviruses, we need to look more aggressively to define how often this occurs.”

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

The persistence of long-term symptoms in some individuals with COVID-19 illness has opened up a new line of research into the mechanisms underlying myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and other chronic postviral illnesses.

Some patients who had COVID-19 continue to have symptoms weeks to months later, even after they no longer test positive for the virus. In two recent reports – one published in JAMA in July and another published in Morbidity and Mortality Weekly Report in August – chronic fatigue was listed as the top symptom among individuals still feeling unwell beyond 2 weeks after COVID-19 onset.

Although some of the reported persistent symptoms appear specific to SARS-CoV-2 – such as cough, chest pain, and dyspnea – others overlap with the diagnostic criteria for ME/CFS, which is defined by substantial, profound fatigue for at least 6 months, postexertional malaise, unrefreshing sleep, and one or both of orthostatic intolerance and/or cognitive impairment. Although the etiology of ME/CFS is unclear, the condition commonly arises following a viral illness.

At the virtual meeting of the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis August 21, the opening session was devoted to research documenting the extent to which COVID-19 survivors subsequently meet ME/CFS criteria, and to exploring underlying mechanisms.

“It offers a lot of opportunities for us to study potentially early ME/CFS and how it develops, but in addition, a lot of the research that has been done on ME/CFS may also provide answers for COVID-19,” IACFS/ME vice president Lily Chu, MD, said in an interview.
 

A hint from the SARS outbreak

This isn’t the first time researchers have seen a possible link between a coronavirus and ME/CFS, Harvey Moldofsky, MD, told attendees. To illustrate that point, Dr. Moldofsky, of the department of psychiatry (emeritus) at the University of Toronto, reviewed data from a previously published case-controlled study, which included 22 health care workers who had been infected in 2003 with SARS-CoV-1 and continued to report chronic fatigue, musculoskeletal pain, and disturbed and unrefreshing sleep with EEG-documented sleep disturbances 1-3 years following the illness. None had been able to return to work by 1 year.

“We’re looking at similar symptoms now” among survivors of COVID-19, Dr. Moldofsky said. “[T]he key issue is that we have no idea of its prevalence. … We need epidemiologic studies.”
 

Distinguishing ME/CFS from other post–COVID-19 symptoms

Not everyone who has persistent symptoms after COVID-19 will develop ME/CFS, and distinguishing between cases may be important.

Clinically, Dr. Chu said, one way to assess whether a patient with persistent COVID-19 symptoms might be progressing to ME/CFS is to ask him or her specifically about the level of fatigue following physical exertion and the timing of any fatigue. With ME/CFS, postexertional malaise often involves a dramatic exacerbation of symptoms such as fatigue, pain, and cognitive impairment a day or 2 after exertion rather than immediately following it. In contrast, shortness of breath during exertion isn’t typical of ME/CFS.

Objective measures of ME/CFS include low natural killer cell function (the test can be ordered from commercial labs but requires rapid transport of the blood sample), and autonomic dysfunction assessed by a tilt-table test.

While there is currently no cure for ME/CFS, diagnosing it allows for the patient to be taught “pacing” in which the person conserves his or her energy by balancing activity with rest. “That type of behavioral technique is valuable for everyone who suffers from a chronic disease with fatigue. It can help them be more functional,” Dr. Chu said.

If a patient appears to be exhibiting signs of ME/CFS, “don’t wait until they hit the 6-month mark to start helping them manage their symptoms,” she said. “Teaching pacing to COVID-19 patients who have a lot of fatigue isn’t going to harm them. As they get better they’re going to just naturally do more. But if they do have ME/CFS, [pacing] stresses their system less, since the data seem to be pointing to deficiencies in producing energy.”
 

Will COVID-19 unleash a new wave of ME/CFS patients?

Much of the session at the virtual meeting was devoted to ongoing studies. For example, Leonard Jason, PhD, of the Center for Community Research at DePaul University, Chicago, described a prospective study launched in 2014 that looked at risk factors for developing ME/CFS in college students who contracted infectious mononucleosis as a result of Epstein-Barr virus. Now, his team is also following students from the same cohort who develop COVID-19.

Because the study included collection of baseline biological samples, the results could help reveal predisposing factors associated with long-term illness from either virus.

Another project, funded by the Open Medicine Foundation, will follow patients who are discharged from the ICU following severe COVID-19 illness. Blood, urine, and cerebrospinal fluid will be collected from those with persistent symptoms at 6 months, along with questionnaire data. At 18-24 months, those who continue to report symptoms will undergo more intensive evaluation using genomics, metabolomics, and proteomics.

“We’re taking advantage of this horrible situation, hoping to understand how a serious viral infection might lead to ME/CFS,” said lead investigator Ronald Tompkins, MD, ScD, chief medical officer at the Open Medicine Foundation and a faculty member at Harvard Medical School, Boston. The results, he said, “might give us insight into potential drug targets or biomarkers useful for prevention and treatment strategies.”

Meanwhile, Sadie Whittaker, PhD, head of the Solve ME/CFS initiative, described her organization’s new plan to use their registry to prospectively track the impact of COVID-19 on people with ME/CFS. 

She noted that they’ve also teamed up with “long-COVID” communities including Body Politic. “Our goal is to form a coalition to study together or at least harmonize data … and understand what’s going on through the power of bigger sample sizes,” Dr. Whittaker said.

None of the speakers disclosed relevant financial relationships.

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

The persistence of long-term symptoms in some individuals with COVID-19 illness has opened up a new line of research into the mechanisms underlying myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and other chronic postviral illnesses.

Some patients who had COVID-19 continue to have symptoms weeks to months later, even after they no longer test positive for the virus. In two recent reports – one published in JAMA in July and another published in Morbidity and Mortality Weekly Report in August – chronic fatigue was listed as the top symptom among individuals still feeling unwell beyond 2 weeks after COVID-19 onset.

Although some of the reported persistent symptoms appear specific to SARS-CoV-2 – such as cough, chest pain, and dyspnea – others overlap with the diagnostic criteria for ME/CFS, which is defined by substantial, profound fatigue for at least 6 months, postexertional malaise, unrefreshing sleep, and one or both of orthostatic intolerance and/or cognitive impairment. Although the etiology of ME/CFS is unclear, the condition commonly arises following a viral illness.

At the virtual meeting of the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis August 21, the opening session was devoted to research documenting the extent to which COVID-19 survivors subsequently meet ME/CFS criteria, and to exploring underlying mechanisms.

“It offers a lot of opportunities for us to study potentially early ME/CFS and how it develops, but in addition, a lot of the research that has been done on ME/CFS may also provide answers for COVID-19,” IACFS/ME vice president Lily Chu, MD, said in an interview.
 

A hint from the SARS outbreak

This isn’t the first time researchers have seen a possible link between a coronavirus and ME/CFS, Harvey Moldofsky, MD, told attendees. To illustrate that point, Dr. Moldofsky, of the department of psychiatry (emeritus) at the University of Toronto, reviewed data from a previously published case-controlled study, which included 22 health care workers who had been infected in 2003 with SARS-CoV-1 and continued to report chronic fatigue, musculoskeletal pain, and disturbed and unrefreshing sleep with EEG-documented sleep disturbances 1-3 years following the illness. None had been able to return to work by 1 year.

“We’re looking at similar symptoms now” among survivors of COVID-19, Dr. Moldofsky said. “[T]he key issue is that we have no idea of its prevalence. … We need epidemiologic studies.”
 

Distinguishing ME/CFS from other post–COVID-19 symptoms

Not everyone who has persistent symptoms after COVID-19 will develop ME/CFS, and distinguishing between cases may be important.

Clinically, Dr. Chu said, one way to assess whether a patient with persistent COVID-19 symptoms might be progressing to ME/CFS is to ask him or her specifically about the level of fatigue following physical exertion and the timing of any fatigue. With ME/CFS, postexertional malaise often involves a dramatic exacerbation of symptoms such as fatigue, pain, and cognitive impairment a day or 2 after exertion rather than immediately following it. In contrast, shortness of breath during exertion isn’t typical of ME/CFS.

Objective measures of ME/CFS include low natural killer cell function (the test can be ordered from commercial labs but requires rapid transport of the blood sample), and autonomic dysfunction assessed by a tilt-table test.

While there is currently no cure for ME/CFS, diagnosing it allows for the patient to be taught “pacing” in which the person conserves his or her energy by balancing activity with rest. “That type of behavioral technique is valuable for everyone who suffers from a chronic disease with fatigue. It can help them be more functional,” Dr. Chu said.

If a patient appears to be exhibiting signs of ME/CFS, “don’t wait until they hit the 6-month mark to start helping them manage their symptoms,” she said. “Teaching pacing to COVID-19 patients who have a lot of fatigue isn’t going to harm them. As they get better they’re going to just naturally do more. But if they do have ME/CFS, [pacing] stresses their system less, since the data seem to be pointing to deficiencies in producing energy.”
 

Will COVID-19 unleash a new wave of ME/CFS patients?

Much of the session at the virtual meeting was devoted to ongoing studies. For example, Leonard Jason, PhD, of the Center for Community Research at DePaul University, Chicago, described a prospective study launched in 2014 that looked at risk factors for developing ME/CFS in college students who contracted infectious mononucleosis as a result of Epstein-Barr virus. Now, his team is also following students from the same cohort who develop COVID-19.

Because the study included collection of baseline biological samples, the results could help reveal predisposing factors associated with long-term illness from either virus.

Another project, funded by the Open Medicine Foundation, will follow patients who are discharged from the ICU following severe COVID-19 illness. Blood, urine, and cerebrospinal fluid will be collected from those with persistent symptoms at 6 months, along with questionnaire data. At 18-24 months, those who continue to report symptoms will undergo more intensive evaluation using genomics, metabolomics, and proteomics.

“We’re taking advantage of this horrible situation, hoping to understand how a serious viral infection might lead to ME/CFS,” said lead investigator Ronald Tompkins, MD, ScD, chief medical officer at the Open Medicine Foundation and a faculty member at Harvard Medical School, Boston. The results, he said, “might give us insight into potential drug targets or biomarkers useful for prevention and treatment strategies.”

Meanwhile, Sadie Whittaker, PhD, head of the Solve ME/CFS initiative, described her organization’s new plan to use their registry to prospectively track the impact of COVID-19 on people with ME/CFS. 

She noted that they’ve also teamed up with “long-COVID” communities including Body Politic. “Our goal is to form a coalition to study together or at least harmonize data … and understand what’s going on through the power of bigger sample sizes,” Dr. Whittaker said.

None of the speakers disclosed relevant financial relationships.

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

The persistence of long-term symptoms in some individuals with COVID-19 illness has opened up a new line of research into the mechanisms underlying myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and other chronic postviral illnesses.

Some patients who had COVID-19 continue to have symptoms weeks to months later, even after they no longer test positive for the virus. In two recent reports – one published in JAMA in July and another published in Morbidity and Mortality Weekly Report in August – chronic fatigue was listed as the top symptom among individuals still feeling unwell beyond 2 weeks after COVID-19 onset.

Although some of the reported persistent symptoms appear specific to SARS-CoV-2 – such as cough, chest pain, and dyspnea – others overlap with the diagnostic criteria for ME/CFS, which is defined by substantial, profound fatigue for at least 6 months, postexertional malaise, unrefreshing sleep, and one or both of orthostatic intolerance and/or cognitive impairment. Although the etiology of ME/CFS is unclear, the condition commonly arises following a viral illness.

At the virtual meeting of the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis August 21, the opening session was devoted to research documenting the extent to which COVID-19 survivors subsequently meet ME/CFS criteria, and to exploring underlying mechanisms.

“It offers a lot of opportunities for us to study potentially early ME/CFS and how it develops, but in addition, a lot of the research that has been done on ME/CFS may also provide answers for COVID-19,” IACFS/ME vice president Lily Chu, MD, said in an interview.
 

A hint from the SARS outbreak

This isn’t the first time researchers have seen a possible link between a coronavirus and ME/CFS, Harvey Moldofsky, MD, told attendees. To illustrate that point, Dr. Moldofsky, of the department of psychiatry (emeritus) at the University of Toronto, reviewed data from a previously published case-controlled study, which included 22 health care workers who had been infected in 2003 with SARS-CoV-1 and continued to report chronic fatigue, musculoskeletal pain, and disturbed and unrefreshing sleep with EEG-documented sleep disturbances 1-3 years following the illness. None had been able to return to work by 1 year.

“We’re looking at similar symptoms now” among survivors of COVID-19, Dr. Moldofsky said. “[T]he key issue is that we have no idea of its prevalence. … We need epidemiologic studies.”
 

Distinguishing ME/CFS from other post–COVID-19 symptoms

Not everyone who has persistent symptoms after COVID-19 will develop ME/CFS, and distinguishing between cases may be important.

Clinically, Dr. Chu said, one way to assess whether a patient with persistent COVID-19 symptoms might be progressing to ME/CFS is to ask him or her specifically about the level of fatigue following physical exertion and the timing of any fatigue. With ME/CFS, postexertional malaise often involves a dramatic exacerbation of symptoms such as fatigue, pain, and cognitive impairment a day or 2 after exertion rather than immediately following it. In contrast, shortness of breath during exertion isn’t typical of ME/CFS.

Objective measures of ME/CFS include low natural killer cell function (the test can be ordered from commercial labs but requires rapid transport of the blood sample), and autonomic dysfunction assessed by a tilt-table test.

While there is currently no cure for ME/CFS, diagnosing it allows for the patient to be taught “pacing” in which the person conserves his or her energy by balancing activity with rest. “That type of behavioral technique is valuable for everyone who suffers from a chronic disease with fatigue. It can help them be more functional,” Dr. Chu said.

If a patient appears to be exhibiting signs of ME/CFS, “don’t wait until they hit the 6-month mark to start helping them manage their symptoms,” she said. “Teaching pacing to COVID-19 patients who have a lot of fatigue isn’t going to harm them. As they get better they’re going to just naturally do more. But if they do have ME/CFS, [pacing] stresses their system less, since the data seem to be pointing to deficiencies in producing energy.”
 

Will COVID-19 unleash a new wave of ME/CFS patients?

Much of the session at the virtual meeting was devoted to ongoing studies. For example, Leonard Jason, PhD, of the Center for Community Research at DePaul University, Chicago, described a prospective study launched in 2014 that looked at risk factors for developing ME/CFS in college students who contracted infectious mononucleosis as a result of Epstein-Barr virus. Now, his team is also following students from the same cohort who develop COVID-19.

Because the study included collection of baseline biological samples, the results could help reveal predisposing factors associated with long-term illness from either virus.

Another project, funded by the Open Medicine Foundation, will follow patients who are discharged from the ICU following severe COVID-19 illness. Blood, urine, and cerebrospinal fluid will be collected from those with persistent symptoms at 6 months, along with questionnaire data. At 18-24 months, those who continue to report symptoms will undergo more intensive evaluation using genomics, metabolomics, and proteomics.

“We’re taking advantage of this horrible situation, hoping to understand how a serious viral infection might lead to ME/CFS,” said lead investigator Ronald Tompkins, MD, ScD, chief medical officer at the Open Medicine Foundation and a faculty member at Harvard Medical School, Boston. The results, he said, “might give us insight into potential drug targets or biomarkers useful for prevention and treatment strategies.”

Meanwhile, Sadie Whittaker, PhD, head of the Solve ME/CFS initiative, described her organization’s new plan to use their registry to prospectively track the impact of COVID-19 on people with ME/CFS. 

She noted that they’ve also teamed up with “long-COVID” communities including Body Politic. “Our goal is to form a coalition to study together or at least harmonize data … and understand what’s going on through the power of bigger sample sizes,” Dr. Whittaker said.

None of the speakers disclosed relevant financial relationships.

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

Use of tumor necrosis factor (TNF) inhibitors in patients with autoimmune diseases may increase risk for inflammatory central nervous system (CNS) outcomes, new research suggests

The nested case-control study included more than 200 participants with diseases such as rheumatoid arthritis, psoriasis, and Crohn’s disease. Results showed that exposure to TNF inhibitors was significantly associated with increased risk for demyelinating CNS events, such as multiple sclerosis, and nondemyelinating events, such as meningitis and encephalitis.

Interestingly, disease-specific secondary analyses showed that the strongest association for inflammatory events was in patients with rheumatoid arthritis.

Lead author Amy Kunchok, MD, of Mayo Clinic, Rochester, Minn., noted that “these are highly effective therapies for patients” and that these CNS events are likely uncommon.

“Our study has observed an association, but this does not imply causality. Therefore, we are not cautioning against using these therapies in appropriate patients,” Dr. Kunchok said in an interview.

“Rather, we recommend that clinicians assessing patients with both inflammatory demyelinating and nondemyelinating CNS events consider a detailed evaluation of the medication history, particularly in patients with coexistent autoimmune diseases who may have a current or past history of biological therapies,” she said.

The findings were published in JAMA Neurology.
 

Poorly understood

TNF inhibitors “are common therapies for certain autoimmune diseases,” the investigators noted.

Previously, a link between exposure to these inhibitors and inflammatory CNS events “has been postulated but is poorly understood,” they wrote.

In the current study, they examined records for 106 patients who were treated at Mayo clinics in Minnesota, Arizona, or Florida from January 2003 through February 2019. All participants had been diagnosed with an autoimmune disease that the Food and Drug Administration has listed as an indication for TNF inhibitor use. This included rheumatoid arthritis (n = 48), ankylosing spondylitis (n = 4), psoriasis and psoriatic arthritis (n = 21), Crohn’s disease (n = 27), and ulcerative colitis (n = 6). Their records also showed diagnostic codes for the inflammatory demyelinating CNS events of relapsing-remitting or primary progressive MS, clinically isolated syndrome, radiologically isolated syndrome, neuromyelitis optica spectrum disorder, and transverse myelitis or for the inflammatory nondemyelinating CNS events of meningitis, meningoencephalitis, encephalitis, neurosarcoidosis, and CNS vasculitis.  The investigators also included 106 age-, sex-, and autoimmune disease–matched participants 1:1 to act as the control group.

In the total study population, 64% were women and the median age at disease onset was 52 years. In addition, 60% of the patient group and 40% of the control group were exposed to TNF inhibitors.
 

Novel finding?

Results showed that TNF inhibitor exposure was significantly linked to increased risk for developing any inflammatory CNS event (adjusted odds ratio, 3.01; 95% CI, 1.55-5.82; P = .001). When the outcomes were stratified by class of inflammatory event, these results were similar. The aOR was 3.09 (95% CI, 1.19-8.04; P = .02) for inflammatory demyelinating CNS events and was 2.97 (95% CI, 1.15-7.65; P = .02) for inflammatory nondemyelinating events.

Dr. Kunchok noted that the association between the inhibitors and nondemyelinating events was “a novel finding from this study.”

In secondary analyses, patients with rheumatoid arthritis and exposure to TNF inhibitors had the strongest association with any inflammatory CNS event (aOR, 4.82; 95% CI, 1.62-14.36; P = .005).

A pooled cohort comprising only the participants with the other autoimmune diseases did not show a significant association between exposure to TNF inhibitors and development of CNS events (P = .09).

“Because of the lack of power, further stratification by individual autoimmune diseases was not analyzed,” the investigators reported.

Although the overall findings showed that exposure to TNF inhibitors was linked to increased risk for inflammatory events, whether this association “represents de novo or exacerbated inflammatory pathways requires further research,” the authors wrote.

Dr. Kunchok added that more research, especially population-based studies, is also needed to examine the incidence of these inflammatory CNS events in patients exposed to TNF-alpha inhibitors.
 

Adds to the literature

In an accompanying editorial, Jeffrey M. Gelfand, MD, department of neurology at the University of California, San Francisco, and Jinoos Yazdany, MD, Zuckerberg San Francisco General Hospital at UCSF, noted that although the study adds to the literature, the magnitude of the risk found “remains unclear.”

“Randomized clinical trials are not suited to the study of rare adverse events,” Dr. Gelfand and Dr. Yazdany wrote. They agree with Dr. Kunchok that “next steps should include population-based observational studies that control for disease severity.”

Still, the current study provides additional evidence of rare adverse events in patients receiving TNF inhibitors, they noted. So how should prescribers proceed?

“As with all treatments, the risk-benefit ratio for the individual patient’s situation must be weighed and appropriate counseling must be given to facilitate shared decision-making discussions,” wrote the editorialists.

“Given what is known about the risk of harm, avoiding TNF inhibitors is advisable in patients with known MS,” they wrote.

In addition, neurologic consultation can be helpful for clarifying diagnoses and providing advice on monitoring strategies for TNF inhibitor treatment in those with possible MS or other demyelinating conditions, noted the editorialists.

“In patients who develop new concerning neurological symptoms while receiving TNF inhibitor treatment, timely evaluation is indicated, including consideration of neuroinflammatory, infectious, and neurological diagnoses that may be unrelated to treatment,” they added.

“Broader awareness of risks that studies such as this one by Kunchok et al provide can ... encourage timelier recognition of potential TNF inhibitor–associated neuroinflammatory events and may improve outcomes for patients,” Dr. Gelfand and Dr. Yazdany concluded.

The study was funded by a grant from the National Center for Advancing Translational Sciences. Dr. Kunchok reports having received research funding from Biogen outside this study. A full list of disclosures for the other study authors is in the original article. Dr. Gelfand reports having received g rants for a clinical trial from Genentech and consulting fees from Biogen, Alexion, Theranica, Impel Neuropharma, Advanced Clinical, Biohaven, and Satsuma. Dr. Yazdany reports having received grants from Pfizer and consulting fees from AstraZeneca and Eli Lilly outside the submitted work.
 

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

Use of tumor necrosis factor (TNF) inhibitors in patients with autoimmune diseases may increase risk for inflammatory central nervous system (CNS) outcomes, new research suggests

The nested case-control study included more than 200 participants with diseases such as rheumatoid arthritis, psoriasis, and Crohn’s disease. Results showed that exposure to TNF inhibitors was significantly associated with increased risk for demyelinating CNS events, such as multiple sclerosis, and nondemyelinating events, such as meningitis and encephalitis.

Interestingly, disease-specific secondary analyses showed that the strongest association for inflammatory events was in patients with rheumatoid arthritis.

Lead author Amy Kunchok, MD, of Mayo Clinic, Rochester, Minn., noted that “these are highly effective therapies for patients” and that these CNS events are likely uncommon.

“Our study has observed an association, but this does not imply causality. Therefore, we are not cautioning against using these therapies in appropriate patients,” Dr. Kunchok said in an interview.

“Rather, we recommend that clinicians assessing patients with both inflammatory demyelinating and nondemyelinating CNS events consider a detailed evaluation of the medication history, particularly in patients with coexistent autoimmune diseases who may have a current or past history of biological therapies,” she said.

The findings were published in JAMA Neurology.
 

Poorly understood

TNF inhibitors “are common therapies for certain autoimmune diseases,” the investigators noted.

Previously, a link between exposure to these inhibitors and inflammatory CNS events “has been postulated but is poorly understood,” they wrote.

In the current study, they examined records for 106 patients who were treated at Mayo clinics in Minnesota, Arizona, or Florida from January 2003 through February 2019. All participants had been diagnosed with an autoimmune disease that the Food and Drug Administration has listed as an indication for TNF inhibitor use. This included rheumatoid arthritis (n = 48), ankylosing spondylitis (n = 4), psoriasis and psoriatic arthritis (n = 21), Crohn’s disease (n = 27), and ulcerative colitis (n = 6). Their records also showed diagnostic codes for the inflammatory demyelinating CNS events of relapsing-remitting or primary progressive MS, clinically isolated syndrome, radiologically isolated syndrome, neuromyelitis optica spectrum disorder, and transverse myelitis or for the inflammatory nondemyelinating CNS events of meningitis, meningoencephalitis, encephalitis, neurosarcoidosis, and CNS vasculitis.  The investigators also included 106 age-, sex-, and autoimmune disease–matched participants 1:1 to act as the control group.

In the total study population, 64% were women and the median age at disease onset was 52 years. In addition, 60% of the patient group and 40% of the control group were exposed to TNF inhibitors.
 

Novel finding?

Results showed that TNF inhibitor exposure was significantly linked to increased risk for developing any inflammatory CNS event (adjusted odds ratio, 3.01; 95% CI, 1.55-5.82; P = .001). When the outcomes were stratified by class of inflammatory event, these results were similar. The aOR was 3.09 (95% CI, 1.19-8.04; P = .02) for inflammatory demyelinating CNS events and was 2.97 (95% CI, 1.15-7.65; P = .02) for inflammatory nondemyelinating events.

Dr. Kunchok noted that the association between the inhibitors and nondemyelinating events was “a novel finding from this study.”

In secondary analyses, patients with rheumatoid arthritis and exposure to TNF inhibitors had the strongest association with any inflammatory CNS event (aOR, 4.82; 95% CI, 1.62-14.36; P = .005).

A pooled cohort comprising only the participants with the other autoimmune diseases did not show a significant association between exposure to TNF inhibitors and development of CNS events (P = .09).

“Because of the lack of power, further stratification by individual autoimmune diseases was not analyzed,” the investigators reported.

Although the overall findings showed that exposure to TNF inhibitors was linked to increased risk for inflammatory events, whether this association “represents de novo or exacerbated inflammatory pathways requires further research,” the authors wrote.

Dr. Kunchok added that more research, especially population-based studies, is also needed to examine the incidence of these inflammatory CNS events in patients exposed to TNF-alpha inhibitors.
 

Adds to the literature

In an accompanying editorial, Jeffrey M. Gelfand, MD, department of neurology at the University of California, San Francisco, and Jinoos Yazdany, MD, Zuckerberg San Francisco General Hospital at UCSF, noted that although the study adds to the literature, the magnitude of the risk found “remains unclear.”

“Randomized clinical trials are not suited to the study of rare adverse events,” Dr. Gelfand and Dr. Yazdany wrote. They agree with Dr. Kunchok that “next steps should include population-based observational studies that control for disease severity.”

Still, the current study provides additional evidence of rare adverse events in patients receiving TNF inhibitors, they noted. So how should prescribers proceed?

“As with all treatments, the risk-benefit ratio for the individual patient’s situation must be weighed and appropriate counseling must be given to facilitate shared decision-making discussions,” wrote the editorialists.

“Given what is known about the risk of harm, avoiding TNF inhibitors is advisable in patients with known MS,” they wrote.

In addition, neurologic consultation can be helpful for clarifying diagnoses and providing advice on monitoring strategies for TNF inhibitor treatment in those with possible MS or other demyelinating conditions, noted the editorialists.

“In patients who develop new concerning neurological symptoms while receiving TNF inhibitor treatment, timely evaluation is indicated, including consideration of neuroinflammatory, infectious, and neurological diagnoses that may be unrelated to treatment,” they added.

“Broader awareness of risks that studies such as this one by Kunchok et al provide can ... encourage timelier recognition of potential TNF inhibitor–associated neuroinflammatory events and may improve outcomes for patients,” Dr. Gelfand and Dr. Yazdany concluded.

The study was funded by a grant from the National Center for Advancing Translational Sciences. Dr. Kunchok reports having received research funding from Biogen outside this study. A full list of disclosures for the other study authors is in the original article. Dr. Gelfand reports having received g rants for a clinical trial from Genentech and consulting fees from Biogen, Alexion, Theranica, Impel Neuropharma, Advanced Clinical, Biohaven, and Satsuma. Dr. Yazdany reports having received grants from Pfizer and consulting fees from AstraZeneca and Eli Lilly outside the submitted work.
 

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

Use of tumor necrosis factor (TNF) inhibitors in patients with autoimmune diseases may increase risk for inflammatory central nervous system (CNS) outcomes, new research suggests

The nested case-control study included more than 200 participants with diseases such as rheumatoid arthritis, psoriasis, and Crohn’s disease. Results showed that exposure to TNF inhibitors was significantly associated with increased risk for demyelinating CNS events, such as multiple sclerosis, and nondemyelinating events, such as meningitis and encephalitis.

Interestingly, disease-specific secondary analyses showed that the strongest association for inflammatory events was in patients with rheumatoid arthritis.

Lead author Amy Kunchok, MD, of Mayo Clinic, Rochester, Minn., noted that “these are highly effective therapies for patients” and that these CNS events are likely uncommon.

“Our study has observed an association, but this does not imply causality. Therefore, we are not cautioning against using these therapies in appropriate patients,” Dr. Kunchok said in an interview.

“Rather, we recommend that clinicians assessing patients with both inflammatory demyelinating and nondemyelinating CNS events consider a detailed evaluation of the medication history, particularly in patients with coexistent autoimmune diseases who may have a current or past history of biological therapies,” she said.

The findings were published in JAMA Neurology.
 

Poorly understood

TNF inhibitors “are common therapies for certain autoimmune diseases,” the investigators noted.

Previously, a link between exposure to these inhibitors and inflammatory CNS events “has been postulated but is poorly understood,” they wrote.

In the current study, they examined records for 106 patients who were treated at Mayo clinics in Minnesota, Arizona, or Florida from January 2003 through February 2019. All participants had been diagnosed with an autoimmune disease that the Food and Drug Administration has listed as an indication for TNF inhibitor use. This included rheumatoid arthritis (n = 48), ankylosing spondylitis (n = 4), psoriasis and psoriatic arthritis (n = 21), Crohn’s disease (n = 27), and ulcerative colitis (n = 6). Their records also showed diagnostic codes for the inflammatory demyelinating CNS events of relapsing-remitting or primary progressive MS, clinically isolated syndrome, radiologically isolated syndrome, neuromyelitis optica spectrum disorder, and transverse myelitis or for the inflammatory nondemyelinating CNS events of meningitis, meningoencephalitis, encephalitis, neurosarcoidosis, and CNS vasculitis.  The investigators also included 106 age-, sex-, and autoimmune disease–matched participants 1:1 to act as the control group.

In the total study population, 64% were women and the median age at disease onset was 52 years. In addition, 60% of the patient group and 40% of the control group were exposed to TNF inhibitors.
 

Novel finding?

Results showed that TNF inhibitor exposure was significantly linked to increased risk for developing any inflammatory CNS event (adjusted odds ratio, 3.01; 95% CI, 1.55-5.82; P = .001). When the outcomes were stratified by class of inflammatory event, these results were similar. The aOR was 3.09 (95% CI, 1.19-8.04; P = .02) for inflammatory demyelinating CNS events and was 2.97 (95% CI, 1.15-7.65; P = .02) for inflammatory nondemyelinating events.

Dr. Kunchok noted that the association between the inhibitors and nondemyelinating events was “a novel finding from this study.”

In secondary analyses, patients with rheumatoid arthritis and exposure to TNF inhibitors had the strongest association with any inflammatory CNS event (aOR, 4.82; 95% CI, 1.62-14.36; P = .005).

A pooled cohort comprising only the participants with the other autoimmune diseases did not show a significant association between exposure to TNF inhibitors and development of CNS events (P = .09).

“Because of the lack of power, further stratification by individual autoimmune diseases was not analyzed,” the investigators reported.

Although the overall findings showed that exposure to TNF inhibitors was linked to increased risk for inflammatory events, whether this association “represents de novo or exacerbated inflammatory pathways requires further research,” the authors wrote.

Dr. Kunchok added that more research, especially population-based studies, is also needed to examine the incidence of these inflammatory CNS events in patients exposed to TNF-alpha inhibitors.
 

Adds to the literature

In an accompanying editorial, Jeffrey M. Gelfand, MD, department of neurology at the University of California, San Francisco, and Jinoos Yazdany, MD, Zuckerberg San Francisco General Hospital at UCSF, noted that although the study adds to the literature, the magnitude of the risk found “remains unclear.”

“Randomized clinical trials are not suited to the study of rare adverse events,” Dr. Gelfand and Dr. Yazdany wrote. They agree with Dr. Kunchok that “next steps should include population-based observational studies that control for disease severity.”

Still, the current study provides additional evidence of rare adverse events in patients receiving TNF inhibitors, they noted. So how should prescribers proceed?

“As with all treatments, the risk-benefit ratio for the individual patient’s situation must be weighed and appropriate counseling must be given to facilitate shared decision-making discussions,” wrote the editorialists.

“Given what is known about the risk of harm, avoiding TNF inhibitors is advisable in patients with known MS,” they wrote.

In addition, neurologic consultation can be helpful for clarifying diagnoses and providing advice on monitoring strategies for TNF inhibitor treatment in those with possible MS or other demyelinating conditions, noted the editorialists.

“In patients who develop new concerning neurological symptoms while receiving TNF inhibitor treatment, timely evaluation is indicated, including consideration of neuroinflammatory, infectious, and neurological diagnoses that may be unrelated to treatment,” they added.

“Broader awareness of risks that studies such as this one by Kunchok et al provide can ... encourage timelier recognition of potential TNF inhibitor–associated neuroinflammatory events and may improve outcomes for patients,” Dr. Gelfand and Dr. Yazdany concluded.

The study was funded by a grant from the National Center for Advancing Translational Sciences. Dr. Kunchok reports having received research funding from Biogen outside this study. A full list of disclosures for the other study authors is in the original article. Dr. Gelfand reports having received g rants for a clinical trial from Genentech and consulting fees from Biogen, Alexion, Theranica, Impel Neuropharma, Advanced Clinical, Biohaven, and Satsuma. Dr. Yazdany reports having received grants from Pfizer and consulting fees from AstraZeneca and Eli Lilly outside the submitted work.
 

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