TOPLINE:

For patients receiving renally cleared cancer medications, therapeutic drug levels are higher and adverse events were more frequent for those whose cystatin C–based estimated glomerular filtration rate (eGFR) was more than 30% lower than their serum creatinine–based eGFR, a recent study suggests.

METHODOLOGY:

• The cohort study included 1,869 adult patients with cancer who had simultaneous serum creatinine–based eGFR (eGFRcr) and cystatin C–based eGFR (eGFRcys) measured. 
• The primary exposure was eGFR discordance, defined as an eGFRcys > 30% lower than the eGFRcr.
• The primary outcome was risk of medication-related adverse events associated with vancomycin, trimethoprim-sulfamethoxazole, baclofen, or digoxin.

TAKEAWAYS:

•  
• Roughly 29% of patients (n = 543) had eGFRcys more than 30% lower than their eGFRcr.These patients were more likely to experience medication-related adverse events, including supratherapeutic vancomycin levels (24% vs. 9% of patients), trimethoprim-sulfamethoxazole–related hyperkalemia (22% vs. 12%), baclofen toxic effect (26% vs. 0%), and high digoxin levels (29% vs. 0%).
• Even after adjusting for age, sex, race and ethnicity, baseline comorbidities, laboratory studies, and medication use, patients with an eGFRcys more than 30% lower than the eGFRcr had a significantly increased risk of 30-day mortality (adjusted hazard ratio, 1.98).
• These patients were more likely to experience medication-related adverse events, including supratherapeutic vancomycin levels (24% vs. 9% of patients), trimethoprim-sulfamethoxazole–related hyperkalemia (22% vs. 12%), baclofen toxic effect (26% vs. 0%), and high digoxin levels (29% vs. 0%).
  
  Even after adjusting for age, sex, race and ethnicity, baseline comorbidities, laboratory studies, and medication use, patients with an eGFRcys more than 30% lower than the eGFRcr had a significantly increased risk of 30-day mortality (adjusted hazard ratio, 1.98).

IN PRACTICE:

“We found a considerably higher rate of supratherapeutic drug levels and [adverse events] associated with select renally cleared medications and increased risk of death in patients with an eGFRcys that was more than 30% lower than the eGFRcr, compared with patients with a concordant eGFR or those whose eGFRcys was more than 30% higher than the eGFRcr,” the authors reported.

SOURCE:

This study, led by Paul Hanna, MD, with Massachusetts General Hospital, Boston, was published online in JAMA Network Open. 

LIMITATIONS:

The study likely overestimated the rate of eGFR discordance and used a one-time assessment of serum creatinine and cystatin C, which may not reflect a steady state at the time of measurement.

DISCLOSURES:

The authors report no relevant financial relationships. The study reported no specific funding.

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

TOPLINE:

For patients receiving renally cleared cancer medications, therapeutic drug levels are higher and adverse events were more frequent for those whose cystatin C–based estimated glomerular filtration rate (eGFR) was more than 30% lower than their serum creatinine–based eGFR, a recent study suggests.

METHODOLOGY:

• The cohort study included 1,869 adult patients with cancer who had simultaneous serum creatinine–based eGFR (eGFRcr) and cystatin C–based eGFR (eGFRcys) measured. 
• The primary exposure was eGFR discordance, defined as an eGFRcys > 30% lower than the eGFRcr.
• The primary outcome was risk of medication-related adverse events associated with vancomycin, trimethoprim-sulfamethoxazole, baclofen, or digoxin.

TAKEAWAYS:

•  
• Roughly 29% of patients (n = 543) had eGFRcys more than 30% lower than their eGFRcr.These patients were more likely to experience medication-related adverse events, including supratherapeutic vancomycin levels (24% vs. 9% of patients), trimethoprim-sulfamethoxazole–related hyperkalemia (22% vs. 12%), baclofen toxic effect (26% vs. 0%), and high digoxin levels (29% vs. 0%).
• Even after adjusting for age, sex, race and ethnicity, baseline comorbidities, laboratory studies, and medication use, patients with an eGFRcys more than 30% lower than the eGFRcr had a significantly increased risk of 30-day mortality (adjusted hazard ratio, 1.98).
• These patients were more likely to experience medication-related adverse events, including supratherapeutic vancomycin levels (24% vs. 9% of patients), trimethoprim-sulfamethoxazole–related hyperkalemia (22% vs. 12%), baclofen toxic effect (26% vs. 0%), and high digoxin levels (29% vs. 0%).
  
  Even after adjusting for age, sex, race and ethnicity, baseline comorbidities, laboratory studies, and medication use, patients with an eGFRcys more than 30% lower than the eGFRcr had a significantly increased risk of 30-day mortality (adjusted hazard ratio, 1.98).

IN PRACTICE:

“We found a considerably higher rate of supratherapeutic drug levels and [adverse events] associated with select renally cleared medications and increased risk of death in patients with an eGFRcys that was more than 30% lower than the eGFRcr, compared with patients with a concordant eGFR or those whose eGFRcys was more than 30% higher than the eGFRcr,” the authors reported.

SOURCE:

This study, led by Paul Hanna, MD, with Massachusetts General Hospital, Boston, was published online in JAMA Network Open. 

LIMITATIONS:

The study likely overestimated the rate of eGFR discordance and used a one-time assessment of serum creatinine and cystatin C, which may not reflect a steady state at the time of measurement.

DISCLOSURES:

The authors report no relevant financial relationships. The study reported no specific funding.

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

TOPLINE:

For patients receiving renally cleared cancer medications, therapeutic drug levels are higher and adverse events were more frequent for those whose cystatin C–based estimated glomerular filtration rate (eGFR) was more than 30% lower than their serum creatinine–based eGFR, a recent study suggests.

METHODOLOGY:

• The cohort study included 1,869 adult patients with cancer who had simultaneous serum creatinine–based eGFR (eGFRcr) and cystatin C–based eGFR (eGFRcys) measured. 
• The primary exposure was eGFR discordance, defined as an eGFRcys > 30% lower than the eGFRcr.
• The primary outcome was risk of medication-related adverse events associated with vancomycin, trimethoprim-sulfamethoxazole, baclofen, or digoxin.

TAKEAWAYS:

•  
• Roughly 29% of patients (n = 543) had eGFRcys more than 30% lower than their eGFRcr.These patients were more likely to experience medication-related adverse events, including supratherapeutic vancomycin levels (24% vs. 9% of patients), trimethoprim-sulfamethoxazole–related hyperkalemia (22% vs. 12%), baclofen toxic effect (26% vs. 0%), and high digoxin levels (29% vs. 0%).
• Even after adjusting for age, sex, race and ethnicity, baseline comorbidities, laboratory studies, and medication use, patients with an eGFRcys more than 30% lower than the eGFRcr had a significantly increased risk of 30-day mortality (adjusted hazard ratio, 1.98).
• These patients were more likely to experience medication-related adverse events, including supratherapeutic vancomycin levels (24% vs. 9% of patients), trimethoprim-sulfamethoxazole–related hyperkalemia (22% vs. 12%), baclofen toxic effect (26% vs. 0%), and high digoxin levels (29% vs. 0%).
  
  Even after adjusting for age, sex, race and ethnicity, baseline comorbidities, laboratory studies, and medication use, patients with an eGFRcys more than 30% lower than the eGFRcr had a significantly increased risk of 30-day mortality (adjusted hazard ratio, 1.98).

IN PRACTICE:

“We found a considerably higher rate of supratherapeutic drug levels and [adverse events] associated with select renally cleared medications and increased risk of death in patients with an eGFRcys that was more than 30% lower than the eGFRcr, compared with patients with a concordant eGFR or those whose eGFRcys was more than 30% higher than the eGFRcr,” the authors reported.

SOURCE:

This study, led by Paul Hanna, MD, with Massachusetts General Hospital, Boston, was published online in JAMA Network Open. 

LIMITATIONS:

The study likely overestimated the rate of eGFR discordance and used a one-time assessment of serum creatinine and cystatin C, which may not reflect a steady state at the time of measurement.

DISCLOSURES:

The authors report no relevant financial relationships. The study reported no specific funding.

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

Indigenous children or children with new abnormal auscultatory findings were significantly more likely than children in other categories to respond to oral antibiotics for exacerbations related to bronchiectasis, based on data from more than 200 individuals in New Zealand.

Children and adolescents with bronchiectasis are often treated with antibiotics for respiratory exacerbations, but the effects of antibiotics can vary among individuals, and phenotypic features associated with greater symptom resolution have not been identified, wrote Vikas Goyal, PhD, of the Centre for Children’s Health Research, Brisbane, Australia, and colleagues.

Previous studies have suggested that nearly half of exacerbations in children and adolescents resolve spontaneously after 14 days, and more data are needed to identify which patients are mostly likely to benefit from antibiotics, they noted.

In a study published in the journal Chest, the researchers reviewed secondary data from 217 children and adolescents aged 1-18 years with bronchiectasis enrolled in a pair of randomized, controlled trials comparing oral antibiotics with placebo (known as BEST-1 and BEST-2). The median age of the participants was 6.6 years, 52% were boys, and 41% were Indigenous (defined as Australian First Nations, New Zealand Maori, or Pacific Islander). All participants in the analysis received at least 14 days of oral antibiotics for treatment of nonhospitalized respiratory exacerbations.

Overall, 130 children had resolution of symptoms by day 14, and 87 were nonresponders.

In a multivariate analysis, children who were Indigenous or who had new abnormal auscultatory findings were significantly more likely to respond than children in other categories (odds ratios, 3.59 and 3.85, respectively).

Patients with multiple bronchiectatic lobes at the time of diagnosis and those with higher cough scores at the start of treatment were significantly less likely to respond to antibiotics than patients without these features (OR, 0.66 and 0.55, respectively).

The researchers conducted a further analysis to examine the association between Indigenous ethnicity and treatment response. They found no differences in the other response variables of number of affected lobes at diagnosis and cough scores at the start of treatment between Indigenous and non-Indigenous children.

Given the strong response to antibiotics among Indigenous children, the researchers also conducted a mediation analysis. “Respiratory bacterial pathogens were mediated by Indigenous ethnicity and associated with being an antibiotic ‘responder,’ ” they wrote. For new abnormal chest auscultatory findings, both direct and indirect effects on day 14 response to oral antibiotics were mediated by Indigenous ethnicity. However, neither cough scores at the start of treatment nor the number of affected lobes at diagnosis showed a mediation effect from Indigenous ethnicity.

Among the nonresponders, 59 of 87 resolved symptoms with continuing oral antibiotics over the next 2-4 weeks, and 21 improved without antibiotics.

Additionally, the detection of a respiratory virus at the start of an exacerbation was not associated with antibiotic failure at 14 days, the researchers noted.

The findings were limited by several factors including the use of data from randomized trials that were not designed to address the question in the current study, the researchers noted. Other limitations included incomplete clinical data and lack of data on inflammatory indices, potential antibiotic-resistant pathogens in nonresponders, and the follow-up period of only 14 days, they said.

However, the results suggest a role for patient and exacerbation phenotypes in management of bronchiectasis in clinical practice and promoting antimicrobial stewardship, the researchers wrote. “Although there is benefit in treating exacerbations early to avoid treatment failure and subsequent intravenous antibiotics, future research also needs to identify exacerbations that can be managed without antibiotics,” they concluded.

The BEST-1 and BEST-2 studies were supported by the Australian National Health and Medical Research Council and the NHMRC Centre for Research Excellence in Lung Health of Aboriginal and Torres Strait Islander Children. Dr. Goyal had no financial conflicts to disclose.
 

Indigenous children or children with new abnormal auscultatory findings were significantly more likely than children in other categories to respond to oral antibiotics for exacerbations related to bronchiectasis, based on data from more than 200 individuals in New Zealand.

Children and adolescents with bronchiectasis are often treated with antibiotics for respiratory exacerbations, but the effects of antibiotics can vary among individuals, and phenotypic features associated with greater symptom resolution have not been identified, wrote Vikas Goyal, PhD, of the Centre for Children’s Health Research, Brisbane, Australia, and colleagues.

Previous studies have suggested that nearly half of exacerbations in children and adolescents resolve spontaneously after 14 days, and more data are needed to identify which patients are mostly likely to benefit from antibiotics, they noted.

In a study published in the journal Chest, the researchers reviewed secondary data from 217 children and adolescents aged 1-18 years with bronchiectasis enrolled in a pair of randomized, controlled trials comparing oral antibiotics with placebo (known as BEST-1 and BEST-2). The median age of the participants was 6.6 years, 52% were boys, and 41% were Indigenous (defined as Australian First Nations, New Zealand Maori, or Pacific Islander). All participants in the analysis received at least 14 days of oral antibiotics for treatment of nonhospitalized respiratory exacerbations.

Overall, 130 children had resolution of symptoms by day 14, and 87 were nonresponders.

In a multivariate analysis, children who were Indigenous or who had new abnormal auscultatory findings were significantly more likely to respond than children in other categories (odds ratios, 3.59 and 3.85, respectively).

Patients with multiple bronchiectatic lobes at the time of diagnosis and those with higher cough scores at the start of treatment were significantly less likely to respond to antibiotics than patients without these features (OR, 0.66 and 0.55, respectively).

The researchers conducted a further analysis to examine the association between Indigenous ethnicity and treatment response. They found no differences in the other response variables of number of affected lobes at diagnosis and cough scores at the start of treatment between Indigenous and non-Indigenous children.

Given the strong response to antibiotics among Indigenous children, the researchers also conducted a mediation analysis. “Respiratory bacterial pathogens were mediated by Indigenous ethnicity and associated with being an antibiotic ‘responder,’ ” they wrote. For new abnormal chest auscultatory findings, both direct and indirect effects on day 14 response to oral antibiotics were mediated by Indigenous ethnicity. However, neither cough scores at the start of treatment nor the number of affected lobes at diagnosis showed a mediation effect from Indigenous ethnicity.

Among the nonresponders, 59 of 87 resolved symptoms with continuing oral antibiotics over the next 2-4 weeks, and 21 improved without antibiotics.

Additionally, the detection of a respiratory virus at the start of an exacerbation was not associated with antibiotic failure at 14 days, the researchers noted.

The findings were limited by several factors including the use of data from randomized trials that were not designed to address the question in the current study, the researchers noted. Other limitations included incomplete clinical data and lack of data on inflammatory indices, potential antibiotic-resistant pathogens in nonresponders, and the follow-up period of only 14 days, they said.

However, the results suggest a role for patient and exacerbation phenotypes in management of bronchiectasis in clinical practice and promoting antimicrobial stewardship, the researchers wrote. “Although there is benefit in treating exacerbations early to avoid treatment failure and subsequent intravenous antibiotics, future research also needs to identify exacerbations that can be managed without antibiotics,” they concluded.

The BEST-1 and BEST-2 studies were supported by the Australian National Health and Medical Research Council and the NHMRC Centre for Research Excellence in Lung Health of Aboriginal and Torres Strait Islander Children. Dr. Goyal had no financial conflicts to disclose.
 

Indigenous children or children with new abnormal auscultatory findings were significantly more likely than children in other categories to respond to oral antibiotics for exacerbations related to bronchiectasis, based on data from more than 200 individuals in New Zealand.

Children and adolescents with bronchiectasis are often treated with antibiotics for respiratory exacerbations, but the effects of antibiotics can vary among individuals, and phenotypic features associated with greater symptom resolution have not been identified, wrote Vikas Goyal, PhD, of the Centre for Children’s Health Research, Brisbane, Australia, and colleagues.

Previous studies have suggested that nearly half of exacerbations in children and adolescents resolve spontaneously after 14 days, and more data are needed to identify which patients are mostly likely to benefit from antibiotics, they noted.

In a study published in the journal Chest, the researchers reviewed secondary data from 217 children and adolescents aged 1-18 years with bronchiectasis enrolled in a pair of randomized, controlled trials comparing oral antibiotics with placebo (known as BEST-1 and BEST-2). The median age of the participants was 6.6 years, 52% were boys, and 41% were Indigenous (defined as Australian First Nations, New Zealand Maori, or Pacific Islander). All participants in the analysis received at least 14 days of oral antibiotics for treatment of nonhospitalized respiratory exacerbations.

Overall, 130 children had resolution of symptoms by day 14, and 87 were nonresponders.

In a multivariate analysis, children who were Indigenous or who had new abnormal auscultatory findings were significantly more likely to respond than children in other categories (odds ratios, 3.59 and 3.85, respectively).

Patients with multiple bronchiectatic lobes at the time of diagnosis and those with higher cough scores at the start of treatment were significantly less likely to respond to antibiotics than patients without these features (OR, 0.66 and 0.55, respectively).

The researchers conducted a further analysis to examine the association between Indigenous ethnicity and treatment response. They found no differences in the other response variables of number of affected lobes at diagnosis and cough scores at the start of treatment between Indigenous and non-Indigenous children.

Given the strong response to antibiotics among Indigenous children, the researchers also conducted a mediation analysis. “Respiratory bacterial pathogens were mediated by Indigenous ethnicity and associated with being an antibiotic ‘responder,’ ” they wrote. For new abnormal chest auscultatory findings, both direct and indirect effects on day 14 response to oral antibiotics were mediated by Indigenous ethnicity. However, neither cough scores at the start of treatment nor the number of affected lobes at diagnosis showed a mediation effect from Indigenous ethnicity.

Among the nonresponders, 59 of 87 resolved symptoms with continuing oral antibiotics over the next 2-4 weeks, and 21 improved without antibiotics.

Additionally, the detection of a respiratory virus at the start of an exacerbation was not associated with antibiotic failure at 14 days, the researchers noted.

The findings were limited by several factors including the use of data from randomized trials that were not designed to address the question in the current study, the researchers noted. Other limitations included incomplete clinical data and lack of data on inflammatory indices, potential antibiotic-resistant pathogens in nonresponders, and the follow-up period of only 14 days, they said.

However, the results suggest a role for patient and exacerbation phenotypes in management of bronchiectasis in clinical practice and promoting antimicrobial stewardship, the researchers wrote. “Although there is benefit in treating exacerbations early to avoid treatment failure and subsequent intravenous antibiotics, future research also needs to identify exacerbations that can be managed without antibiotics,” they concluded.

The BEST-1 and BEST-2 studies were supported by the Australian National Health and Medical Research Council and the NHMRC Centre for Research Excellence in Lung Health of Aboriginal and Torres Strait Islander Children. Dr. Goyal had no financial conflicts to disclose.
 

A potentially protective role for vitamin D in the pathogenesis of chronic obstructive pulmonary disease (COPD) is suggested by the finding that serum 25-hydroxyvitamin D (25[OH]D) concentrations are inversely associated with COPD incidence and mortality. COPD risk was 23% higher in people within the lowest quintile vs. the fourth quintile of 25(OH)D concentrations, according to research appearing in BMJ Open Respiratory Research.

While low vitamin D status has been linked to increased inflammatory diseases risk and to the regulation of pathogenic mechanisms in COPD, epidemiological evidence regarding the associations of 25(OH)D concentrations with COPD incidence and survival remains inconclusive, Zheng Zhu, MD, of Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, China, and colleagues wrote.

From UK Biobank data recorded from 403,648 participants (mean age 56.4 years; 54% women) who were free of COPD at baseline and had 25(OH)D measurements, researchers estimated hazard ratios and 95% confidence intervals for the associations of 25(OH)D concentrations with COPD risk and survival. After median follow-up of 12.3 years (ending Sept. 30, 2021), with 11,008 COPD cases recorded, beyond the COPD and mortality increase (HR, 1.23; 95% CI, 1.16-1.31) in the lowest quintile of 25(OH)D concentrations, risk for overall death was 38% higher, as well (HR, 1.38; 95% CI, 1.22-1.56). Serum concentrations were greater than 64.6 nmol/L in the highest (quintile 5) and less than 31.7 nmol/L in the lowest (quintile 1). Also, men and current smokers had higher COPD and mortality risk (P interaction for both: < .05).

While event rates tracked generally inversely with 25(OH)D concentrations, overall the event curves were non-linear. Dr Zhu and associates reported that the decreasing risk of COPD appeared to be lowest at 55 nmol/L of 25(OH)D within quintile 4 (51.8 to < 64.6 nmol/L). Furthermore, lower prediagnostic 25(OH)D concentrations were associated with a significant decrease in overall and COPD-specific survival.

Smoking is the most commonly encountered risk factor for COPD, the researchers noted, and their findings indicated that 25(OH)D concentrations were inversely associated with COPD risk in both smokers and never-smokers. In a fully adjusted model, compared with quintile 4, the quintile 1 increase in COPD risk was 25% in never-smokers and 23% in smokers.

“Our findings imply that vitamin D might play a role in progression of COPD,” the authors stated. They added, “Whether lower concentrations of 25(OH)D are causal or contributory to COPD risk may spur future long-duration and large-scale RCTs.”

“Vitamin D has an important function in the immune system and lower serum levels have been implicated in a variety of inflammatory diseases,” commented associate professor of medicine Diego J. Maselli, MD, who is chief of the division of pulmonary diseases & critical care at UT Health San Antonio. “Patients with COPD often have lower levels of vitamin D compared to healthy individuals. COPD patients with low serum levels of vitamin D may have a higher risk of exacerbations and worse lung function.”

He added, “The research by Zhu and colleagues adds to the field of study and highlights the potential role of vitamin D in the pathophysiology of COPD. It is important to remember that these associations do not establish causality, as patients with chronic and debilitating diseases may have limited sunlight exposure, poor nutritional intake, and other behaviors that may affect vitamin D levels. There are mixed results in studies evaluating the role of supplementing vitamin D in COPD with regards to disease progression and exacerbation reduction. While there are some studies that report that supplementation of vitamin D can reduce COPD exacerbations, there is still a need for randomized controlled studies that explore if the supplementation of vitamin D can prevent the development of COPD, particularly in those who actively smoke. Yet, it is reasonable to evaluate the serum vitamin D levels in COPD patients who have had exacerbations and supplement when there is a severe deficiency.” 

Given that the majority of participants in this study were from the United Kingdom, the researchers stated, a study limitation is that findings might not apply to other populations.

No disclosures were reported by Dr. Zhu or by Dr. Maselli.

A potentially protective role for vitamin D in the pathogenesis of chronic obstructive pulmonary disease (COPD) is suggested by the finding that serum 25-hydroxyvitamin D (25[OH]D) concentrations are inversely associated with COPD incidence and mortality. COPD risk was 23% higher in people within the lowest quintile vs. the fourth quintile of 25(OH)D concentrations, according to research appearing in BMJ Open Respiratory Research.

While low vitamin D status has been linked to increased inflammatory diseases risk and to the regulation of pathogenic mechanisms in COPD, epidemiological evidence regarding the associations of 25(OH)D concentrations with COPD incidence and survival remains inconclusive, Zheng Zhu, MD, of Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, China, and colleagues wrote.

From UK Biobank data recorded from 403,648 participants (mean age 56.4 years; 54% women) who were free of COPD at baseline and had 25(OH)D measurements, researchers estimated hazard ratios and 95% confidence intervals for the associations of 25(OH)D concentrations with COPD risk and survival. After median follow-up of 12.3 years (ending Sept. 30, 2021), with 11,008 COPD cases recorded, beyond the COPD and mortality increase (HR, 1.23; 95% CI, 1.16-1.31) in the lowest quintile of 25(OH)D concentrations, risk for overall death was 38% higher, as well (HR, 1.38; 95% CI, 1.22-1.56). Serum concentrations were greater than 64.6 nmol/L in the highest (quintile 5) and less than 31.7 nmol/L in the lowest (quintile 1). Also, men and current smokers had higher COPD and mortality risk (P interaction for both: < .05).

While event rates tracked generally inversely with 25(OH)D concentrations, overall the event curves were non-linear. Dr Zhu and associates reported that the decreasing risk of COPD appeared to be lowest at 55 nmol/L of 25(OH)D within quintile 4 (51.8 to < 64.6 nmol/L). Furthermore, lower prediagnostic 25(OH)D concentrations were associated with a significant decrease in overall and COPD-specific survival.

Smoking is the most commonly encountered risk factor for COPD, the researchers noted, and their findings indicated that 25(OH)D concentrations were inversely associated with COPD risk in both smokers and never-smokers. In a fully adjusted model, compared with quintile 4, the quintile 1 increase in COPD risk was 25% in never-smokers and 23% in smokers.

“Our findings imply that vitamin D might play a role in progression of COPD,” the authors stated. They added, “Whether lower concentrations of 25(OH)D are causal or contributory to COPD risk may spur future long-duration and large-scale RCTs.”

“Vitamin D has an important function in the immune system and lower serum levels have been implicated in a variety of inflammatory diseases,” commented associate professor of medicine Diego J. Maselli, MD, who is chief of the division of pulmonary diseases & critical care at UT Health San Antonio. “Patients with COPD often have lower levels of vitamin D compared to healthy individuals. COPD patients with low serum levels of vitamin D may have a higher risk of exacerbations and worse lung function.”

He added, “The research by Zhu and colleagues adds to the field of study and highlights the potential role of vitamin D in the pathophysiology of COPD. It is important to remember that these associations do not establish causality, as patients with chronic and debilitating diseases may have limited sunlight exposure, poor nutritional intake, and other behaviors that may affect vitamin D levels. There are mixed results in studies evaluating the role of supplementing vitamin D in COPD with regards to disease progression and exacerbation reduction. While there are some studies that report that supplementation of vitamin D can reduce COPD exacerbations, there is still a need for randomized controlled studies that explore if the supplementation of vitamin D can prevent the development of COPD, particularly in those who actively smoke. Yet, it is reasonable to evaluate the serum vitamin D levels in COPD patients who have had exacerbations and supplement when there is a severe deficiency.” 

Given that the majority of participants in this study were from the United Kingdom, the researchers stated, a study limitation is that findings might not apply to other populations.

No disclosures were reported by Dr. Zhu or by Dr. Maselli.

A potentially protective role for vitamin D in the pathogenesis of chronic obstructive pulmonary disease (COPD) is suggested by the finding that serum 25-hydroxyvitamin D (25[OH]D) concentrations are inversely associated with COPD incidence and mortality. COPD risk was 23% higher in people within the lowest quintile vs. the fourth quintile of 25(OH)D concentrations, according to research appearing in BMJ Open Respiratory Research.

While low vitamin D status has been linked to increased inflammatory diseases risk and to the regulation of pathogenic mechanisms in COPD, epidemiological evidence regarding the associations of 25(OH)D concentrations with COPD incidence and survival remains inconclusive, Zheng Zhu, MD, of Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, China, and colleagues wrote.

From UK Biobank data recorded from 403,648 participants (mean age 56.4 years; 54% women) who were free of COPD at baseline and had 25(OH)D measurements, researchers estimated hazard ratios and 95% confidence intervals for the associations of 25(OH)D concentrations with COPD risk and survival. After median follow-up of 12.3 years (ending Sept. 30, 2021), with 11,008 COPD cases recorded, beyond the COPD and mortality increase (HR, 1.23; 95% CI, 1.16-1.31) in the lowest quintile of 25(OH)D concentrations, risk for overall death was 38% higher, as well (HR, 1.38; 95% CI, 1.22-1.56). Serum concentrations were greater than 64.6 nmol/L in the highest (quintile 5) and less than 31.7 nmol/L in the lowest (quintile 1). Also, men and current smokers had higher COPD and mortality risk (P interaction for both: < .05).

While event rates tracked generally inversely with 25(OH)D concentrations, overall the event curves were non-linear. Dr Zhu and associates reported that the decreasing risk of COPD appeared to be lowest at 55 nmol/L of 25(OH)D within quintile 4 (51.8 to < 64.6 nmol/L). Furthermore, lower prediagnostic 25(OH)D concentrations were associated with a significant decrease in overall and COPD-specific survival.

Smoking is the most commonly encountered risk factor for COPD, the researchers noted, and their findings indicated that 25(OH)D concentrations were inversely associated with COPD risk in both smokers and never-smokers. In a fully adjusted model, compared with quintile 4, the quintile 1 increase in COPD risk was 25% in never-smokers and 23% in smokers.

“Our findings imply that vitamin D might play a role in progression of COPD,” the authors stated. They added, “Whether lower concentrations of 25(OH)D are causal or contributory to COPD risk may spur future long-duration and large-scale RCTs.”

“Vitamin D has an important function in the immune system and lower serum levels have been implicated in a variety of inflammatory diseases,” commented associate professor of medicine Diego J. Maselli, MD, who is chief of the division of pulmonary diseases & critical care at UT Health San Antonio. “Patients with COPD often have lower levels of vitamin D compared to healthy individuals. COPD patients with low serum levels of vitamin D may have a higher risk of exacerbations and worse lung function.”

He added, “The research by Zhu and colleagues adds to the field of study and highlights the potential role of vitamin D in the pathophysiology of COPD. It is important to remember that these associations do not establish causality, as patients with chronic and debilitating diseases may have limited sunlight exposure, poor nutritional intake, and other behaviors that may affect vitamin D levels. There are mixed results in studies evaluating the role of supplementing vitamin D in COPD with regards to disease progression and exacerbation reduction. While there are some studies that report that supplementation of vitamin D can reduce COPD exacerbations, there is still a need for randomized controlled studies that explore if the supplementation of vitamin D can prevent the development of COPD, particularly in those who actively smoke. Yet, it is reasonable to evaluate the serum vitamin D levels in COPD patients who have had exacerbations and supplement when there is a severe deficiency.” 

Given that the majority of participants in this study were from the United Kingdom, the researchers stated, a study limitation is that findings might not apply to other populations.

No disclosures were reported by Dr. Zhu or by Dr. Maselli.

Retinal thickness may be a potential biomarker for predicting disability for patients newly diagnosed with relapsing multiple sclerosis (MS), new research suggests.

The researchers measured retinal thickness using optical coherence tomography (OCT) within 3 months of diagnosis for more than 230 patients with MS and found that thinning of the retina was associated with a more than fourfold increased risk of Expanded Disability Status Scale (EDSS) scores of at least 3.0.

The OCT “basically tells you how much nerve layer is left in the glass,” said study investigator Gabriel Bsteh, MD, PhD, department of neurology, Medical University of Vienna.

This “could potentially inform treatment strategies, but that is another direction which will be investigated hopefully in the near future,” he added. However, the imaging technique cannot be used for all patients and is currently not widely available.

Dr. Bsteh presented the results at the annual meeting of the European Academy of Neurology.


 

Retinal layers of interest

OCT produces images of the retina and measures its thickness, Dr. Bsteh explained. Of greatest interest and relevance to patients with MS are two layers – the peripapillary retinal nerve fiber layer (pRNFL) and the ganglion cell and inner plexiform layer (GCL), which are associated with “future physical and cognitive disability and brain atrophy, and are reliable biomarkers of axonal damage.”

However, he said, what is not yet known is whether the baseline thickness of these two layers independently predicts progression of disability in patients with newly diagnosed disease within the framework of all of the other known risk factors.

To investigate, the team used data from ViennOCTiMS, an ongoing prospective observational cohort study conducted in Vienna and Innsbruck. For the analysis, they included patients newly diagnosed with relapsing MS using the 2017 McDonald criteria.

Study participants were required to undergo a spectral-domain OCT scan within 90 days of diagnosis and within 270 days of symptom onset. They also had to undergo follow-up of at least 12 months.

Among 231 patients included in the study, 74 were female, and the mean age was 30.3 years.

Dr. Bsteh noted that disease duration was short. There was a median of 45 days between initial diagnosis and the OCT scan. The median number of T2 lesions on MRI was 11, with 59.3% of patients had at least 10 lesions.

At baseline, 13.0% of patients were not receiving drug therapy, although they were advised to do so, said Dr. Bsteh. A total of 59.7% of patients received “moderately effective” disease-modifying treatments, while 27.3% were treated with “highly effective” DMTs.
 

Independent predictors of disability

To determine the contribution of retinal thickness to the risk of developing EDSS of 3.0 or more, the researchers conducted a multivariate analysis that accounted for patient age and sex, the type of first relapse, the remission of first relapse symptoms, the presence of oligoclonal bands, the baseline number of T2 lesions, and the use and type of DMT.

After approximately 96 months of follow-up, a pRNFL thickness of 88 mcm or less at baseline was associated with a hazard ratio for EDSS of at least 3.0 versus a thickness of greater than 88 mcm of 4.0 (P < .001), Dr. Bsteh reported.

Similarly, a GCL thickness of less than 77 mcm at baseline was associated with a HR for EDSS of at least 3.0 of 5.1 (P < .001).

Subgroup analysis indicated that both measures of retinal thickness were indeed independent predictors of EDSS. Dr. Bsteh said: “It was encouraging to see that all the unknown prognostic factor factors performed within the expected framework.”

For example, there was a notable association between the risk of EDSS of at least 3.0 and patient age, as well as with incomplete remission and a greater number of lesions on MRI.

Dr. Bsteh said it was also “very encouraging” to find that high-efficacy DMT was associated with a reduced risk of EDSS of at least 3.0.
 

Strengths, limitations

Turning to the relatively recently described progression independent of relapse activity, Dr. Bsteh showed that both pRNFL of 88 mcm or less and GCL less than 77 mcm were significantly associated with the development of PIRA, compared with greater thickness, at HRs of 3.1 and 4.1, respectively (P < .001 for both).

Subgroup analysis again supported the independent contribution of retinal thickness to the risk of PIRA and revealed similar associations with known risk factors, although the contribution of highly effective DMT was of borderline significance for this outcome.

Interestingly, neither pRNFL of 88 mcm or less nor GCL less than 77 mcm was significantly associated with the time to second clinical attack, “which is basically the correlation of the inflammatory activity” in MS, said Dr. Bsteh.

This, he continued, “goes back to the basic theory that EDSS, PIRA, and neurodegenerative problems are associated with the OCT but not the degree of inflammatory activity.

“As good as all that sounds, there are of course, some limitations” to the study, Dr. Bsteh acknowledged.

The most important limitation is that the changes measured on OCT were “not specific to multiple sclerosis,” and the thickness of the layers “can be influenced by a lot of other factors,” in particular by eye conditions such as glaucoma and diabetes mellitus.

In addition, OCT is not reliable for patients with myopia of more than four to six diopters and for those with retinal comorbidities, such as optic drusen. Dr. Bsteh also pointed out that automatic segmentation in OCT requires stringent quality control.

However, the “biggest problem for the deployment of OCT in the clinical routine is its lack of availability. It’s not very easy for neurologists to procure an OCT,” said Dr. Bsteh.

“You can always create it with your ophthalmologist of trust, but you have to know what you’re looking for,” he added.
 

Important research

Commenting on the study, Giancarlo Comi, MD, honorary professor of neurology at the Università Vita Salute San Raffaele and founder and director of the Institute of Experimental Neurology at the Scientific Institute San Raffaele, both in Milan, characterized the research as “very, very important and interesting.”

However, he said that he was a “bit surprised” that it showed no association between OCT measures and the second clinical attack, noting that longitudinal research by his team found such an association.

Dr. Comi added that the “key point” from the current study is that there was no such association in the early phase of the disease, which suggests that the amount of inflammatory activity “is not so relevant” in determining the degree of damage seen on OCT at that point.

Dr. Bsteh said he partially agreed with Dr. Comi, adding that “it depends on what you adjust for.

“If we did the same analysis without adjusting for the number of MRI lesions, we would see an association with second clinical attack,” he said. However, the aim of the current study was to determine the independent contribution of retinal thickness, “and that’s why we tried to adjust to everything which was available to us.”

Dr. Bsteh also underlined that it was a cross-sectional analysis conducted “very, very early” in the MS disease course, and “so the inflammatory activity did not yet have a chance to influence the thickness on the OCT.”

Had OCT been performed later in the disease course, inflammatory activity might have influenced the findings, but the intention of the study was to use it “as an early marker to try to stratify patients who are at risk, and [those] who are maybe a little less at risk, and inform the treatment strategy.”

Maria Assunta Rocca, MD, associate professor of neurology at Università Vita Salute San Raffaele, and head of neuroimaging of the CNS white matter unit at IRCCS San Raffaele Scientific Institute, Milan, who cochaired the session in which the study was presented, asked whether the researchers analyzed patients with optic neuritis separately from those without and whether it affected the predictive factors.

Dr. Bsteh said that OCT cannot be used for patients with bilateral optic neuritis and so they were excluded from the study, but for patients who were affected unilaterally, the contralateral eye was assessed.

This underlines why OCT contributes the most when used early on the disease course. “The longer the disease has time, the higher the likelihood that optic neuritis has developed,” he said.

Funding for the study was provided by Mindset Technologies. All authors are, or were, employees and/or shareholders of Mindset Technologies. Dr. Bsteh has relationships with Biogen, Celgene/Bristol-Myers Squibb, Lilly, Merck, Novartis, Roche, Sanofi Genzyme, and Teva.

A version of this article appeared on Medscape.com.

Retinal thickness may be a potential biomarker for predicting disability for patients newly diagnosed with relapsing multiple sclerosis (MS), new research suggests.

The researchers measured retinal thickness using optical coherence tomography (OCT) within 3 months of diagnosis for more than 230 patients with MS and found that thinning of the retina was associated with a more than fourfold increased risk of Expanded Disability Status Scale (EDSS) scores of at least 3.0.

The OCT “basically tells you how much nerve layer is left in the glass,” said study investigator Gabriel Bsteh, MD, PhD, department of neurology, Medical University of Vienna.

This “could potentially inform treatment strategies, but that is another direction which will be investigated hopefully in the near future,” he added. However, the imaging technique cannot be used for all patients and is currently not widely available.

Dr. Bsteh presented the results at the annual meeting of the European Academy of Neurology.


 

Retinal layers of interest

OCT produces images of the retina and measures its thickness, Dr. Bsteh explained. Of greatest interest and relevance to patients with MS are two layers – the peripapillary retinal nerve fiber layer (pRNFL) and the ganglion cell and inner plexiform layer (GCL), which are associated with “future physical and cognitive disability and brain atrophy, and are reliable biomarkers of axonal damage.”

However, he said, what is not yet known is whether the baseline thickness of these two layers independently predicts progression of disability in patients with newly diagnosed disease within the framework of all of the other known risk factors.

To investigate, the team used data from ViennOCTiMS, an ongoing prospective observational cohort study conducted in Vienna and Innsbruck. For the analysis, they included patients newly diagnosed with relapsing MS using the 2017 McDonald criteria.

Study participants were required to undergo a spectral-domain OCT scan within 90 days of diagnosis and within 270 days of symptom onset. They also had to undergo follow-up of at least 12 months.

Among 231 patients included in the study, 74 were female, and the mean age was 30.3 years.

Dr. Bsteh noted that disease duration was short. There was a median of 45 days between initial diagnosis and the OCT scan. The median number of T2 lesions on MRI was 11, with 59.3% of patients had at least 10 lesions.

At baseline, 13.0% of patients were not receiving drug therapy, although they were advised to do so, said Dr. Bsteh. A total of 59.7% of patients received “moderately effective” disease-modifying treatments, while 27.3% were treated with “highly effective” DMTs.
 

Independent predictors of disability

To determine the contribution of retinal thickness to the risk of developing EDSS of 3.0 or more, the researchers conducted a multivariate analysis that accounted for patient age and sex, the type of first relapse, the remission of first relapse symptoms, the presence of oligoclonal bands, the baseline number of T2 lesions, and the use and type of DMT.

After approximately 96 months of follow-up, a pRNFL thickness of 88 mcm or less at baseline was associated with a hazard ratio for EDSS of at least 3.0 versus a thickness of greater than 88 mcm of 4.0 (P < .001), Dr. Bsteh reported.

Similarly, a GCL thickness of less than 77 mcm at baseline was associated with a HR for EDSS of at least 3.0 of 5.1 (P < .001).

Subgroup analysis indicated that both measures of retinal thickness were indeed independent predictors of EDSS. Dr. Bsteh said: “It was encouraging to see that all the unknown prognostic factor factors performed within the expected framework.”

For example, there was a notable association between the risk of EDSS of at least 3.0 and patient age, as well as with incomplete remission and a greater number of lesions on MRI.

Dr. Bsteh said it was also “very encouraging” to find that high-efficacy DMT was associated with a reduced risk of EDSS of at least 3.0.
 

Strengths, limitations

Turning to the relatively recently described progression independent of relapse activity, Dr. Bsteh showed that both pRNFL of 88 mcm or less and GCL less than 77 mcm were significantly associated with the development of PIRA, compared with greater thickness, at HRs of 3.1 and 4.1, respectively (P < .001 for both).

Subgroup analysis again supported the independent contribution of retinal thickness to the risk of PIRA and revealed similar associations with known risk factors, although the contribution of highly effective DMT was of borderline significance for this outcome.

Interestingly, neither pRNFL of 88 mcm or less nor GCL less than 77 mcm was significantly associated with the time to second clinical attack, “which is basically the correlation of the inflammatory activity” in MS, said Dr. Bsteh.

This, he continued, “goes back to the basic theory that EDSS, PIRA, and neurodegenerative problems are associated with the OCT but not the degree of inflammatory activity.

“As good as all that sounds, there are of course, some limitations” to the study, Dr. Bsteh acknowledged.

The most important limitation is that the changes measured on OCT were “not specific to multiple sclerosis,” and the thickness of the layers “can be influenced by a lot of other factors,” in particular by eye conditions such as glaucoma and diabetes mellitus.

In addition, OCT is not reliable for patients with myopia of more than four to six diopters and for those with retinal comorbidities, such as optic drusen. Dr. Bsteh also pointed out that automatic segmentation in OCT requires stringent quality control.

However, the “biggest problem for the deployment of OCT in the clinical routine is its lack of availability. It’s not very easy for neurologists to procure an OCT,” said Dr. Bsteh.

“You can always create it with your ophthalmologist of trust, but you have to know what you’re looking for,” he added.
 

Important research

Commenting on the study, Giancarlo Comi, MD, honorary professor of neurology at the Università Vita Salute San Raffaele and founder and director of the Institute of Experimental Neurology at the Scientific Institute San Raffaele, both in Milan, characterized the research as “very, very important and interesting.”

However, he said that he was a “bit surprised” that it showed no association between OCT measures and the second clinical attack, noting that longitudinal research by his team found such an association.

Dr. Comi added that the “key point” from the current study is that there was no such association in the early phase of the disease, which suggests that the amount of inflammatory activity “is not so relevant” in determining the degree of damage seen on OCT at that point.

Dr. Bsteh said he partially agreed with Dr. Comi, adding that “it depends on what you adjust for.

“If we did the same analysis without adjusting for the number of MRI lesions, we would see an association with second clinical attack,” he said. However, the aim of the current study was to determine the independent contribution of retinal thickness, “and that’s why we tried to adjust to everything which was available to us.”

Dr. Bsteh also underlined that it was a cross-sectional analysis conducted “very, very early” in the MS disease course, and “so the inflammatory activity did not yet have a chance to influence the thickness on the OCT.”

Had OCT been performed later in the disease course, inflammatory activity might have influenced the findings, but the intention of the study was to use it “as an early marker to try to stratify patients who are at risk, and [those] who are maybe a little less at risk, and inform the treatment strategy.”

Maria Assunta Rocca, MD, associate professor of neurology at Università Vita Salute San Raffaele, and head of neuroimaging of the CNS white matter unit at IRCCS San Raffaele Scientific Institute, Milan, who cochaired the session in which the study was presented, asked whether the researchers analyzed patients with optic neuritis separately from those without and whether it affected the predictive factors.

Dr. Bsteh said that OCT cannot be used for patients with bilateral optic neuritis and so they were excluded from the study, but for patients who were affected unilaterally, the contralateral eye was assessed.

This underlines why OCT contributes the most when used early on the disease course. “The longer the disease has time, the higher the likelihood that optic neuritis has developed,” he said.

Funding for the study was provided by Mindset Technologies. All authors are, or were, employees and/or shareholders of Mindset Technologies. Dr. Bsteh has relationships with Biogen, Celgene/Bristol-Myers Squibb, Lilly, Merck, Novartis, Roche, Sanofi Genzyme, and Teva.

A version of this article appeared on Medscape.com.

Retinal thickness may be a potential biomarker for predicting disability for patients newly diagnosed with relapsing multiple sclerosis (MS), new research suggests.

The researchers measured retinal thickness using optical coherence tomography (OCT) within 3 months of diagnosis for more than 230 patients with MS and found that thinning of the retina was associated with a more than fourfold increased risk of Expanded Disability Status Scale (EDSS) scores of at least 3.0.

The OCT “basically tells you how much nerve layer is left in the glass,” said study investigator Gabriel Bsteh, MD, PhD, department of neurology, Medical University of Vienna.

This “could potentially inform treatment strategies, but that is another direction which will be investigated hopefully in the near future,” he added. However, the imaging technique cannot be used for all patients and is currently not widely available.

Dr. Bsteh presented the results at the annual meeting of the European Academy of Neurology.


 

Retinal layers of interest

OCT produces images of the retina and measures its thickness, Dr. Bsteh explained. Of greatest interest and relevance to patients with MS are two layers – the peripapillary retinal nerve fiber layer (pRNFL) and the ganglion cell and inner plexiform layer (GCL), which are associated with “future physical and cognitive disability and brain atrophy, and are reliable biomarkers of axonal damage.”

However, he said, what is not yet known is whether the baseline thickness of these two layers independently predicts progression of disability in patients with newly diagnosed disease within the framework of all of the other known risk factors.

To investigate, the team used data from ViennOCTiMS, an ongoing prospective observational cohort study conducted in Vienna and Innsbruck. For the analysis, they included patients newly diagnosed with relapsing MS using the 2017 McDonald criteria.

Study participants were required to undergo a spectral-domain OCT scan within 90 days of diagnosis and within 270 days of symptom onset. They also had to undergo follow-up of at least 12 months.

Among 231 patients included in the study, 74 were female, and the mean age was 30.3 years.

Dr. Bsteh noted that disease duration was short. There was a median of 45 days between initial diagnosis and the OCT scan. The median number of T2 lesions on MRI was 11, with 59.3% of patients had at least 10 lesions.

At baseline, 13.0% of patients were not receiving drug therapy, although they were advised to do so, said Dr. Bsteh. A total of 59.7% of patients received “moderately effective” disease-modifying treatments, while 27.3% were treated with “highly effective” DMTs.
 

Independent predictors of disability

To determine the contribution of retinal thickness to the risk of developing EDSS of 3.0 or more, the researchers conducted a multivariate analysis that accounted for patient age and sex, the type of first relapse, the remission of first relapse symptoms, the presence of oligoclonal bands, the baseline number of T2 lesions, and the use and type of DMT.

After approximately 96 months of follow-up, a pRNFL thickness of 88 mcm or less at baseline was associated with a hazard ratio for EDSS of at least 3.0 versus a thickness of greater than 88 mcm of 4.0 (P < .001), Dr. Bsteh reported.

Similarly, a GCL thickness of less than 77 mcm at baseline was associated with a HR for EDSS of at least 3.0 of 5.1 (P < .001).

Subgroup analysis indicated that both measures of retinal thickness were indeed independent predictors of EDSS. Dr. Bsteh said: “It was encouraging to see that all the unknown prognostic factor factors performed within the expected framework.”

For example, there was a notable association between the risk of EDSS of at least 3.0 and patient age, as well as with incomplete remission and a greater number of lesions on MRI.

Dr. Bsteh said it was also “very encouraging” to find that high-efficacy DMT was associated with a reduced risk of EDSS of at least 3.0.
 

Strengths, limitations

Turning to the relatively recently described progression independent of relapse activity, Dr. Bsteh showed that both pRNFL of 88 mcm or less and GCL less than 77 mcm were significantly associated with the development of PIRA, compared with greater thickness, at HRs of 3.1 and 4.1, respectively (P < .001 for both).

Subgroup analysis again supported the independent contribution of retinal thickness to the risk of PIRA and revealed similar associations with known risk factors, although the contribution of highly effective DMT was of borderline significance for this outcome.

Interestingly, neither pRNFL of 88 mcm or less nor GCL less than 77 mcm was significantly associated with the time to second clinical attack, “which is basically the correlation of the inflammatory activity” in MS, said Dr. Bsteh.

This, he continued, “goes back to the basic theory that EDSS, PIRA, and neurodegenerative problems are associated with the OCT but not the degree of inflammatory activity.

“As good as all that sounds, there are of course, some limitations” to the study, Dr. Bsteh acknowledged.

The most important limitation is that the changes measured on OCT were “not specific to multiple sclerosis,” and the thickness of the layers “can be influenced by a lot of other factors,” in particular by eye conditions such as glaucoma and diabetes mellitus.

In addition, OCT is not reliable for patients with myopia of more than four to six diopters and for those with retinal comorbidities, such as optic drusen. Dr. Bsteh also pointed out that automatic segmentation in OCT requires stringent quality control.

However, the “biggest problem for the deployment of OCT in the clinical routine is its lack of availability. It’s not very easy for neurologists to procure an OCT,” said Dr. Bsteh.

“You can always create it with your ophthalmologist of trust, but you have to know what you’re looking for,” he added.
 

Important research

Commenting on the study, Giancarlo Comi, MD, honorary professor of neurology at the Università Vita Salute San Raffaele and founder and director of the Institute of Experimental Neurology at the Scientific Institute San Raffaele, both in Milan, characterized the research as “very, very important and interesting.”

However, he said that he was a “bit surprised” that it showed no association between OCT measures and the second clinical attack, noting that longitudinal research by his team found such an association.

Dr. Comi added that the “key point” from the current study is that there was no such association in the early phase of the disease, which suggests that the amount of inflammatory activity “is not so relevant” in determining the degree of damage seen on OCT at that point.

Dr. Bsteh said he partially agreed with Dr. Comi, adding that “it depends on what you adjust for.

“If we did the same analysis without adjusting for the number of MRI lesions, we would see an association with second clinical attack,” he said. However, the aim of the current study was to determine the independent contribution of retinal thickness, “and that’s why we tried to adjust to everything which was available to us.”

Dr. Bsteh also underlined that it was a cross-sectional analysis conducted “very, very early” in the MS disease course, and “so the inflammatory activity did not yet have a chance to influence the thickness on the OCT.”

Had OCT been performed later in the disease course, inflammatory activity might have influenced the findings, but the intention of the study was to use it “as an early marker to try to stratify patients who are at risk, and [those] who are maybe a little less at risk, and inform the treatment strategy.”

Maria Assunta Rocca, MD, associate professor of neurology at Università Vita Salute San Raffaele, and head of neuroimaging of the CNS white matter unit at IRCCS San Raffaele Scientific Institute, Milan, who cochaired the session in which the study was presented, asked whether the researchers analyzed patients with optic neuritis separately from those without and whether it affected the predictive factors.

Dr. Bsteh said that OCT cannot be used for patients with bilateral optic neuritis and so they were excluded from the study, but for patients who were affected unilaterally, the contralateral eye was assessed.

This underlines why OCT contributes the most when used early on the disease course. “The longer the disease has time, the higher the likelihood that optic neuritis has developed,” he said.

Funding for the study was provided by Mindset Technologies. All authors are, or were, employees and/or shareholders of Mindset Technologies. Dr. Bsteh has relationships with Biogen, Celgene/Bristol-Myers Squibb, Lilly, Merck, Novartis, Roche, Sanofi Genzyme, and Teva.

A version of this article appeared on Medscape.com.

Opioid initiation for older adults with dementia is linked to a significantly increased risk of death, especially in the first 2 weeks, when the risk is elevated 11-fold, new research shows.

“We expected that opioids would be associated with an increased risk of death, but we are surprised by the magnitude,” study investigator Christina Jensen-Dahm, MD, PhD, with the Danish Dementia Research Centre, Copenhagen University Hospital, Rigshospitalet, Denmark, told this news organization.

“It’s important that physicians carefully evaluate the risk and benefits if considering initiating an opioid, and this is particularly important in elderly with dementia,” Dr. Jensen-Dahm added.

The findings were presented at the Alzheimer’s Association International Conference.
 

Risky business

Using Danish nationwide registries, the researchers analyzed data on all 75,471 adults in Denmark who were aged 65 and older and had been diagnosed with dementia between 2008 and 2018. A total of 31,619 individuals (42%) filled a prescription for an opioid. These “exposed” individuals were matched to 63,235 unexposed individuals.

Among the exposed group, 10,474 (33%) died within 180 days after starting opioid therapy, compared with 3,980 (6.4%) in the unexposed group.

After adjusting for potential differences between groups, new use of an opioid was associated with a greater than fourfold excess mortality risk (adjusted hazard ratio, 4.16; 95% confidence interval, 4.00-4.33).

New use of a strong opioid – defined as morphine, oxycodone, ketobemidone, hydromorphone, pethidine, buprenorphine, and fentanyl – was associated with a greater than sixfold increase in mortality risk (aHR, 6.42; 95% CI, 6.08-6.79).

Among those who used fentanyl patches as their first opioid, 65% died within the first 180 days, compared with 6.7% in the unexposed – an eightfold increased mortality risk (aHR, 8.04; 95% CI, 7.01-9.22).

For all opioids, the risk was greatest in the first 14 days, with a nearly 11-fold increased risk of mortality (aHR, 10.8; 95% CI, 9.74-11.99). However, there remained a twofold increase in risk after taking opioids for 90 days (aHR, 2.32; 95% CI, 2.17-2.48).

“Opioids are associated with severe and well-known side effects, such as sedation, confusion, respiratory depression, falls, and in the most severe cases, death. In the general population, opioids have been associated with an increased risk of death, and similar to ours, greatest in the first 14 days,” said Dr. Jensen-Dahm.
 

Need to weigh risks, benefits

Commenting on the study, Percy Griffin, PhD, director of scientific engagement at the Alzheimer’s Association, told this news organization that the use of strong opioids has “increased considerably over the past decade among older people with dementia. Opioid therapy should only be considered for pain if the benefits are anticipated to outweigh the risks in individuals who are living with dementia.”

“Opioids are very powerful drugs, and while we need to see additional research in more diverse populations, these initial findings indicate they may put older adults with dementia at much higher risk of death,” Nicole Purcell, DO, neurologist and senior director of clinical practice at the Alzheimer’s Association, added in a conference statement.

“Pain should not go undiagnosed or untreated, in particular in people living with dementia, who may not be able to effectively articulate the location and severity of the pain,” Dr. Purcell added.

These new findings further emphasize the need for discussion between patient, family, and physician. Decisions about prescribing pain medication should be thought through carefully, and if used, there needs to be careful monitoring of the patient, said Dr. Purcell.

The study was supported by a grant from the Capital Region of Denmark. Dr. Jensen-Dahm, Dr. Griffin, and Dr. Purcell have no relevant disclosures.

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

Opioid initiation for older adults with dementia is linked to a significantly increased risk of death, especially in the first 2 weeks, when the risk is elevated 11-fold, new research shows.

“We expected that opioids would be associated with an increased risk of death, but we are surprised by the magnitude,” study investigator Christina Jensen-Dahm, MD, PhD, with the Danish Dementia Research Centre, Copenhagen University Hospital, Rigshospitalet, Denmark, told this news organization.

“It’s important that physicians carefully evaluate the risk and benefits if considering initiating an opioid, and this is particularly important in elderly with dementia,” Dr. Jensen-Dahm added.

The findings were presented at the Alzheimer’s Association International Conference.
 

Risky business

Using Danish nationwide registries, the researchers analyzed data on all 75,471 adults in Denmark who were aged 65 and older and had been diagnosed with dementia between 2008 and 2018. A total of 31,619 individuals (42%) filled a prescription for an opioid. These “exposed” individuals were matched to 63,235 unexposed individuals.

Among the exposed group, 10,474 (33%) died within 180 days after starting opioid therapy, compared with 3,980 (6.4%) in the unexposed group.

After adjusting for potential differences between groups, new use of an opioid was associated with a greater than fourfold excess mortality risk (adjusted hazard ratio, 4.16; 95% confidence interval, 4.00-4.33).

New use of a strong opioid – defined as morphine, oxycodone, ketobemidone, hydromorphone, pethidine, buprenorphine, and fentanyl – was associated with a greater than sixfold increase in mortality risk (aHR, 6.42; 95% CI, 6.08-6.79).

Among those who used fentanyl patches as their first opioid, 65% died within the first 180 days, compared with 6.7% in the unexposed – an eightfold increased mortality risk (aHR, 8.04; 95% CI, 7.01-9.22).

For all opioids, the risk was greatest in the first 14 days, with a nearly 11-fold increased risk of mortality (aHR, 10.8; 95% CI, 9.74-11.99). However, there remained a twofold increase in risk after taking opioids for 90 days (aHR, 2.32; 95% CI, 2.17-2.48).

“Opioids are associated with severe and well-known side effects, such as sedation, confusion, respiratory depression, falls, and in the most severe cases, death. In the general population, opioids have been associated with an increased risk of death, and similar to ours, greatest in the first 14 days,” said Dr. Jensen-Dahm.
 

Need to weigh risks, benefits

Commenting on the study, Percy Griffin, PhD, director of scientific engagement at the Alzheimer’s Association, told this news organization that the use of strong opioids has “increased considerably over the past decade among older people with dementia. Opioid therapy should only be considered for pain if the benefits are anticipated to outweigh the risks in individuals who are living with dementia.”

“Opioids are very powerful drugs, and while we need to see additional research in more diverse populations, these initial findings indicate they may put older adults with dementia at much higher risk of death,” Nicole Purcell, DO, neurologist and senior director of clinical practice at the Alzheimer’s Association, added in a conference statement.

“Pain should not go undiagnosed or untreated, in particular in people living with dementia, who may not be able to effectively articulate the location and severity of the pain,” Dr. Purcell added.

These new findings further emphasize the need for discussion between patient, family, and physician. Decisions about prescribing pain medication should be thought through carefully, and if used, there needs to be careful monitoring of the patient, said Dr. Purcell.

The study was supported by a grant from the Capital Region of Denmark. Dr. Jensen-Dahm, Dr. Griffin, and Dr. Purcell have no relevant disclosures.

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

Opioid initiation for older adults with dementia is linked to a significantly increased risk of death, especially in the first 2 weeks, when the risk is elevated 11-fold, new research shows.

“We expected that opioids would be associated with an increased risk of death, but we are surprised by the magnitude,” study investigator Christina Jensen-Dahm, MD, PhD, with the Danish Dementia Research Centre, Copenhagen University Hospital, Rigshospitalet, Denmark, told this news organization.

“It’s important that physicians carefully evaluate the risk and benefits if considering initiating an opioid, and this is particularly important in elderly with dementia,” Dr. Jensen-Dahm added.

The findings were presented at the Alzheimer’s Association International Conference.
 

Risky business

Using Danish nationwide registries, the researchers analyzed data on all 75,471 adults in Denmark who were aged 65 and older and had been diagnosed with dementia between 2008 and 2018. A total of 31,619 individuals (42%) filled a prescription for an opioid. These “exposed” individuals were matched to 63,235 unexposed individuals.

Among the exposed group, 10,474 (33%) died within 180 days after starting opioid therapy, compared with 3,980 (6.4%) in the unexposed group.

After adjusting for potential differences between groups, new use of an opioid was associated with a greater than fourfold excess mortality risk (adjusted hazard ratio, 4.16; 95% confidence interval, 4.00-4.33).

New use of a strong opioid – defined as morphine, oxycodone, ketobemidone, hydromorphone, pethidine, buprenorphine, and fentanyl – was associated with a greater than sixfold increase in mortality risk (aHR, 6.42; 95% CI, 6.08-6.79).

Among those who used fentanyl patches as their first opioid, 65% died within the first 180 days, compared with 6.7% in the unexposed – an eightfold increased mortality risk (aHR, 8.04; 95% CI, 7.01-9.22).

For all opioids, the risk was greatest in the first 14 days, with a nearly 11-fold increased risk of mortality (aHR, 10.8; 95% CI, 9.74-11.99). However, there remained a twofold increase in risk after taking opioids for 90 days (aHR, 2.32; 95% CI, 2.17-2.48).

“Opioids are associated with severe and well-known side effects, such as sedation, confusion, respiratory depression, falls, and in the most severe cases, death. In the general population, opioids have been associated with an increased risk of death, and similar to ours, greatest in the first 14 days,” said Dr. Jensen-Dahm.
 

Need to weigh risks, benefits

Commenting on the study, Percy Griffin, PhD, director of scientific engagement at the Alzheimer’s Association, told this news organization that the use of strong opioids has “increased considerably over the past decade among older people with dementia. Opioid therapy should only be considered for pain if the benefits are anticipated to outweigh the risks in individuals who are living with dementia.”

“Opioids are very powerful drugs, and while we need to see additional research in more diverse populations, these initial findings indicate they may put older adults with dementia at much higher risk of death,” Nicole Purcell, DO, neurologist and senior director of clinical practice at the Alzheimer’s Association, added in a conference statement.

“Pain should not go undiagnosed or untreated, in particular in people living with dementia, who may not be able to effectively articulate the location and severity of the pain,” Dr. Purcell added.

These new findings further emphasize the need for discussion between patient, family, and physician. Decisions about prescribing pain medication should be thought through carefully, and if used, there needs to be careful monitoring of the patient, said Dr. Purcell.

The study was supported by a grant from the Capital Region of Denmark. Dr. Jensen-Dahm, Dr. Griffin, and Dr. Purcell have no relevant disclosures.

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

Nearly 90% of diabetes management in the United States is provided by primary care clinicians; diabetes is the fifth most common reason for a primary care visit. State-of-the-art technology such as continuous glucose monitors (CGMs) will inevitably transform the management of diabetes in primary care. Clinicians and staff must be ready to educate, counsel, and support primary care patients in the use of CGMs.

CGMs (also called glucose sensors) are small, minimally invasive devices that attach to the skin of the upper arm or trunk. A tiny electrode in the subcutaneous space prompts an enzyme reaction that measures the interstitial (rather than blood) glucose concentration, typically every 5 minutes. The results are displayed on an accompanying reader or transmitted to an app on the user’s mobile phone.

CGMs could eliminate the need for finger-stick blood glucose testing, which until now, has been the much-despised gold standard for self-monitoring of glucose levels in diabetes. Despite being relatively inexpensive and accurate, finger-stick glucose tests are inconvenient and often painful. But of greater significance is this downside: Finger-stick monitoring reveals the patient’s blood glucose concentration at a single point in time, which can be difficult to interpret. Is the blood glucose rising or falling? Multiple finger-stick tests are required to determine the trend of a patient’s glucose levels or the response to food or exercise.

In contrast, the graphic display from a CGM sensor is more like a movie, telling a story as it unfolds. Uninterrupted data provide valuable feedback to patients about the effects of diet, physical activity, stress, or pain on their glucose levels. And for the first time, it’s easy to determine the proportion of time the patient spends in or out of the target glucose range.

Incorporating new technology into your practice may seem like a burden, but the reward is better information that leads to better management of diabetes. If you’re new to glucose sensors, many excellent resources are available to learn how to use them.

I recommend starting with a website called diabeteswise.org, which has both a patient-facing and clinician-facing version. This unbranded site serves as a kind of Consumer Reports for diabetes technology, allowing both patients and professionals to compare and contrast currently available CGM devices.

DiabetesWisePro  has information ranging from CGM device fundamentals and best practices to CGM prescribing and reimbursement.

Clinical Diabetes also provides multiple tools to help incorporate these devices into primary care clinical practice, including:

• Continuous Glucose Monitoring: Optimizing Diabetes Care (CME course).

• Diabetes Technology in Primary Care.

The next article in this series will cover two types of CGMs used in primary care: professional and personal devices.

Dr. Shubrook is a professor in the department of primary care, Touro University California College of Osteopathic Medicine, Vallejo, Calif., and director of diabetes services, Solano County Family Health Services, Fairfield, Calif. He disclosed ties with Abbott, Astra Zeneca, Bayer, Nevro, and Novo Nordisk.

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

Nearly 90% of diabetes management in the United States is provided by primary care clinicians; diabetes is the fifth most common reason for a primary care visit. State-of-the-art technology such as continuous glucose monitors (CGMs) will inevitably transform the management of diabetes in primary care. Clinicians and staff must be ready to educate, counsel, and support primary care patients in the use of CGMs.

CGMs (also called glucose sensors) are small, minimally invasive devices that attach to the skin of the upper arm or trunk. A tiny electrode in the subcutaneous space prompts an enzyme reaction that measures the interstitial (rather than blood) glucose concentration, typically every 5 minutes. The results are displayed on an accompanying reader or transmitted to an app on the user’s mobile phone.

CGMs could eliminate the need for finger-stick blood glucose testing, which until now, has been the much-despised gold standard for self-monitoring of glucose levels in diabetes. Despite being relatively inexpensive and accurate, finger-stick glucose tests are inconvenient and often painful. But of greater significance is this downside: Finger-stick monitoring reveals the patient’s blood glucose concentration at a single point in time, which can be difficult to interpret. Is the blood glucose rising or falling? Multiple finger-stick tests are required to determine the trend of a patient’s glucose levels or the response to food or exercise.

In contrast, the graphic display from a CGM sensor is more like a movie, telling a story as it unfolds. Uninterrupted data provide valuable feedback to patients about the effects of diet, physical activity, stress, or pain on their glucose levels. And for the first time, it’s easy to determine the proportion of time the patient spends in or out of the target glucose range.

Incorporating new technology into your practice may seem like a burden, but the reward is better information that leads to better management of diabetes. If you’re new to glucose sensors, many excellent resources are available to learn how to use them.

I recommend starting with a website called diabeteswise.org, which has both a patient-facing and clinician-facing version. This unbranded site serves as a kind of Consumer Reports for diabetes technology, allowing both patients and professionals to compare and contrast currently available CGM devices.

DiabetesWisePro  has information ranging from CGM device fundamentals and best practices to CGM prescribing and reimbursement.

Clinical Diabetes also provides multiple tools to help incorporate these devices into primary care clinical practice, including:

• Continuous Glucose Monitoring: Optimizing Diabetes Care (CME course).

• Diabetes Technology in Primary Care.

The next article in this series will cover two types of CGMs used in primary care: professional and personal devices.

Dr. Shubrook is a professor in the department of primary care, Touro University California College of Osteopathic Medicine, Vallejo, Calif., and director of diabetes services, Solano County Family Health Services, Fairfield, Calif. He disclosed ties with Abbott, Astra Zeneca, Bayer, Nevro, and Novo Nordisk.

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

Nearly 90% of diabetes management in the United States is provided by primary care clinicians; diabetes is the fifth most common reason for a primary care visit. State-of-the-art technology such as continuous glucose monitors (CGMs) will inevitably transform the management of diabetes in primary care. Clinicians and staff must be ready to educate, counsel, and support primary care patients in the use of CGMs.

CGMs (also called glucose sensors) are small, minimally invasive devices that attach to the skin of the upper arm or trunk. A tiny electrode in the subcutaneous space prompts an enzyme reaction that measures the interstitial (rather than blood) glucose concentration, typically every 5 minutes. The results are displayed on an accompanying reader or transmitted to an app on the user’s mobile phone.

CGMs could eliminate the need for finger-stick blood glucose testing, which until now, has been the much-despised gold standard for self-monitoring of glucose levels in diabetes. Despite being relatively inexpensive and accurate, finger-stick glucose tests are inconvenient and often painful. But of greater significance is this downside: Finger-stick monitoring reveals the patient’s blood glucose concentration at a single point in time, which can be difficult to interpret. Is the blood glucose rising or falling? Multiple finger-stick tests are required to determine the trend of a patient’s glucose levels or the response to food or exercise.

In contrast, the graphic display from a CGM sensor is more like a movie, telling a story as it unfolds. Uninterrupted data provide valuable feedback to patients about the effects of diet, physical activity, stress, or pain on their glucose levels. And for the first time, it’s easy to determine the proportion of time the patient spends in or out of the target glucose range.

Incorporating new technology into your practice may seem like a burden, but the reward is better information that leads to better management of diabetes. If you’re new to glucose sensors, many excellent resources are available to learn how to use them.

I recommend starting with a website called diabeteswise.org, which has both a patient-facing and clinician-facing version. This unbranded site serves as a kind of Consumer Reports for diabetes technology, allowing both patients and professionals to compare and contrast currently available CGM devices.

DiabetesWisePro  has information ranging from CGM device fundamentals and best practices to CGM prescribing and reimbursement.

Clinical Diabetes also provides multiple tools to help incorporate these devices into primary care clinical practice, including:

• Continuous Glucose Monitoring: Optimizing Diabetes Care (CME course).

• Diabetes Technology in Primary Care.

The next article in this series will cover two types of CGMs used in primary care: professional and personal devices.

Dr. Shubrook is a professor in the department of primary care, Touro University California College of Osteopathic Medicine, Vallejo, Calif., and director of diabetes services, Solano County Family Health Services, Fairfield, Calif. He disclosed ties with Abbott, Astra Zeneca, Bayer, Nevro, and Novo Nordisk.

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

In Colorado and Wyoming, nearly every baby born since 2020 is tested for signs of a mutation in the SMN1 gene, an indicator of spinal muscular atrophy (SMA). And in 4 years, genetic counselor Melissa Gibbons has seen 24 positive results. She has prepped 24 different pediatricians and family doctors to deliver the news: A seemingly perfect newborn likely has a lethal genetic disease.

Most of these clinicians had never cared for a child with SMA before, nor did they know that lifesaving gene therapy for the condition now exists. Still, the physicians were foundational to getting babies emergency treatment and monitoring the child’s safety after the fact.

“They are boots on the ground for this kind of [work],” Ms. Gibbons, who is the newborn screen coordinator for SMA in both states, told this news organization. “I’m not even sure they realize it.” As of today, the U.S. Food and Drug Administration has approved 16 gene therapies for the treatment of rare and debilitating diseases once considered lethal, such as SMA and cerebral adrenoleukodystrophy.

The newest addition to the list of approvals is Elevidys, Sarepta’s gene therapy for Duchenne muscular dystrophy (DMD). These conditions can now be mitigated, abated for years at a time, and even cured using treatments that tweak a patient’s DNA or RNA.

Hundreds of treatments are under development using the same mechanism. Viruses, liposomes, and other vectors of all kinds are being used to usher new genes into cells, correcting faulty copies or equipping a cell to fight disease. Cells gain the ability to make lifesaving proteins – proteins that heal wounds, restore muscle function, and fight cancer.

Within the decade, a significant fraction of the pediatric population will have gone through gene therapy, experts told this news organization. And primary care stands to be a linchpin in the scale-up of this kind of precision genetic medicine. Pediatricians and general practitioners will be central to finding and monitoring the patients that need these treatments. But the time and support doctors will need to fill that role remain scarce.

“This is a world we are creating right now, quite literally,” said Stanley Nelson, MD, director of the center for Duchenne muscular dystrophy at the University of California, Los Angeles. These cases – some before gene therapy and some after – will show up in primary care offices before the textbook is written.
 

Unknown side effects, new diseases

Even now, gene therapy is sequestered away in large academic medical research centers. The diagnosis, decision-making, and aftercare are handled by subspecialists working on clinical trials. While the research is ongoing, trial sponsors are keeping a close eye on enrolled patients. But that’s only until these drugs get market approval, Phil Beales, MD, chief medical officer at Congenica, a digital health company specializing in genome analysis support, said. Afterward, “the trialists will no longer have a role in looking after those patients.”

At that point, the role of primary care clinicians will be critically important. Although they probably will not manage gene-therapy patients on their own – comanaging them instead with subspecialists – they will be involved in the ordering and monitoring of safety labs and other tests.

General practitioners “need to know side effects because they are going to deal with side effects when someone calls them in the middle of the night,” said Dr. Beales, who also is chief executive officer of Axovia Therapeutics, a biotech company developing gene therapies.

Some of the side effects that come with gene therapy are established. Adeno-associated virus (AAV) or AAV-mediated gene therapies carry an increased risk for damage to the heart and liver, Dr. Nelson said. Other side effects are less well known and could be specific to the treatment and the tissue it targets. Primary care will be critical in detecting these unexpected side effects and expediting visits with subspecialists, he said.

In rural Wyoming, pediatricians and family doctors are especially important, Ms. Gibbons said. In the 30-90 days after gene therapy, patients need a lot of follow-up for safety reasons.

But aftercare for gene therapy will be more than just monitoring and managing side effects. The diseases themselves will change. Patients will be living with conditions that once were lethal.

In some cases, gene therapy may largely eliminate the disease. The data suggest that thalassemia, for example, can be largely cured for decades with one infusion of a patient’s genetically modified hematopoietic stem cells made using bluebird bio’s Zynteglo, according to Christy Duncan, MD, medical director of clinical research at the gene therapy program at Boston Children’s Hospital.

But other gene therapies, like the one for DMD, will offer a “spectrum of benefits,” Dr. Nelson said. They will be lifesaving, but the signs of the disease will linger. Clinicians will be learning alongside specialists what the new disease state for DMD and other rare diseases looks like after gene therapy.

“As we get hundreds of such therapies, [post–gene therapy] will amount to a substantial part of the pediatric population,” Dr. Nelson said.
 

Finding patients

Many of these rare diseases that plague young patients are unmistakable. Children with moderate or severe dystrophic epidermolysis bullosa, for instance, carry a mutation that prevents them from making type VII collagen. The babies suffer wounds and excessive bleeding and tend to receive a quick diagnosis within the first 6 months of life, according to Andy Orth, chief commercial officer at Krystal Bio, manufacturer of a new wound-healing gene therapy, Vyjuvek, for the disorder.

Other rare neurologic or muscular diseases can go undiagnosed for years. Until recently, drug companies and researchers have had little motivation to speed up the timeline because early diagnosis of a disease like DMD would not change the outcome, Dr. Nelson said.

But with gene therapy, prognoses are changing. And finding diseases early could soon mean preserving muscular function or preventing neurologic damage, Dr. Duncan said.

Newborn sequencing “is not standard of care yet, but it’s certainly coming,” Josh Peterson, MD, MPH, director of the center for precision medicine at Vanderbilt University Medical Center, in Nashville, Tenn., told this news organization.

A recent survey of 238 specialists in rare diseases found that roughly 90% believe whole-genome sequencing should be available to all newborns. And 80% of those experts endorse 42 genes as disease predictors. Screening for rare diseases at birth could reveal a host of conditions in the first week of life and expedite treatment. But this strategy will often rely on primary care and pediatricians interpreting the results.

Most pediatricians think sequencing is a great idea, but they do not feel comfortable doing it themselves, Dr. Peterson said. The good news, he said, is that manufacturers have made screening tests straightforward. Some drug companies even offer free screenings for gene therapy candidates.

Dr. Peterson predicts pediatricians will need to be equipped to deliver negative results on their own, which will be the case for around 97%-99% of patients. They also will need to be clear on whether a negative result is definitive or if more testing is warranted.

Positive results are more nuanced. Genetic counseling is the ideal resource when delivering this kind of news to patients, but counselors are a scarce resource nationally – and particularly in rural areas, Dr. Nelson said. Physicians likely will have to rely on their own counseling training to some degree.

“I feel very strongly that genetic counselors are in short supply,” Ms. Gibbons in Colorado said. Patients need a friendly resource who can talk them through the disease and how it works. And that discussion is not a one-off, she said.

The number of board-certified genetic counselors in the United States has doubled to more than 6,000 in the past 10 years – a pace that is expected to continue, according to the National Society of Genetic Counselors. “However, the geographical distribution of genetic counselors is most concentrated in urban centers.”

Equally important to the counseling experience, according to Dr. Duncan at Boston Children’s, is a primary care physician’s network of connections. The best newborn screening rollouts across the country have succeeded because clinicians knew where to send people next and how to get families the help they needed, she said.

But she also cautioned that this learning curve will soon be overwhelming. As gene therapy expands, it may be difficult for primary care doctors to keep up with the science, treatment studies, and commercially available therapies. “It’s asking too much,” Dr. Duncan said.

The structure of primary care already stretches practitioners thin and will “affect how well precision medicine can be adopted and disseminated,” Dr. Peterson said. “I think that is a key issue.”

Artificial intelligence may offer a partial solution. Some genetic counseling models already exist, but their utility for clinicians so far is limited, Dr. Beales said. But he said he expects these tools to improve rapidly to help clinicians and patients. On the patient’s end, they may be able to answer questions and supplement basic genetic counseling. On the physician’s end, algorithms could help triage patients and help move them along to the next steps in the care pathway for these rare diseases.
 

The whole patient

Primary care physicians will not be expected to be experts in gene therapy or solely in charge of patient safety. They will have support from industry and subspecialists leading the development of these treatments, experts agreed.

But generalists should expect to be drawn into multidisciplinary care teams, be the sounding boards for patients making decisions about gene therapy, help arrange insurance coverage, and be the recipients of late-night phone calls about side effects.

All that, while never losing sight of the child’s holistic health. In children so sick, specialists, subspecialists, and even parents tend to focus only on the rare disease. The team can “get distracted from good normal routine care,” Dr. Nelson said. But these children aren’t exempt from check-ups, vaccine regimens, or the other diseases of childhood.

“In a world where we mitigate that core disease,” he said, “we need a partner in the general pediatrics community” investing in their long-term health.

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

In Colorado and Wyoming, nearly every baby born since 2020 is tested for signs of a mutation in the SMN1 gene, an indicator of spinal muscular atrophy (SMA). And in 4 years, genetic counselor Melissa Gibbons has seen 24 positive results. She has prepped 24 different pediatricians and family doctors to deliver the news: A seemingly perfect newborn likely has a lethal genetic disease.

Most of these clinicians had never cared for a child with SMA before, nor did they know that lifesaving gene therapy for the condition now exists. Still, the physicians were foundational to getting babies emergency treatment and monitoring the child’s safety after the fact.

“They are boots on the ground for this kind of [work],” Ms. Gibbons, who is the newborn screen coordinator for SMA in both states, told this news organization. “I’m not even sure they realize it.” As of today, the U.S. Food and Drug Administration has approved 16 gene therapies for the treatment of rare and debilitating diseases once considered lethal, such as SMA and cerebral adrenoleukodystrophy.

The newest addition to the list of approvals is Elevidys, Sarepta’s gene therapy for Duchenne muscular dystrophy (DMD). These conditions can now be mitigated, abated for years at a time, and even cured using treatments that tweak a patient’s DNA or RNA.

Hundreds of treatments are under development using the same mechanism. Viruses, liposomes, and other vectors of all kinds are being used to usher new genes into cells, correcting faulty copies or equipping a cell to fight disease. Cells gain the ability to make lifesaving proteins – proteins that heal wounds, restore muscle function, and fight cancer.

Within the decade, a significant fraction of the pediatric population will have gone through gene therapy, experts told this news organization. And primary care stands to be a linchpin in the scale-up of this kind of precision genetic medicine. Pediatricians and general practitioners will be central to finding and monitoring the patients that need these treatments. But the time and support doctors will need to fill that role remain scarce.

“This is a world we are creating right now, quite literally,” said Stanley Nelson, MD, director of the center for Duchenne muscular dystrophy at the University of California, Los Angeles. These cases – some before gene therapy and some after – will show up in primary care offices before the textbook is written.
 

Unknown side effects, new diseases

Even now, gene therapy is sequestered away in large academic medical research centers. The diagnosis, decision-making, and aftercare are handled by subspecialists working on clinical trials. While the research is ongoing, trial sponsors are keeping a close eye on enrolled patients. But that’s only until these drugs get market approval, Phil Beales, MD, chief medical officer at Congenica, a digital health company specializing in genome analysis support, said. Afterward, “the trialists will no longer have a role in looking after those patients.”

At that point, the role of primary care clinicians will be critically important. Although they probably will not manage gene-therapy patients on their own – comanaging them instead with subspecialists – they will be involved in the ordering and monitoring of safety labs and other tests.

General practitioners “need to know side effects because they are going to deal with side effects when someone calls them in the middle of the night,” said Dr. Beales, who also is chief executive officer of Axovia Therapeutics, a biotech company developing gene therapies.

Some of the side effects that come with gene therapy are established. Adeno-associated virus (AAV) or AAV-mediated gene therapies carry an increased risk for damage to the heart and liver, Dr. Nelson said. Other side effects are less well known and could be specific to the treatment and the tissue it targets. Primary care will be critical in detecting these unexpected side effects and expediting visits with subspecialists, he said.

In rural Wyoming, pediatricians and family doctors are especially important, Ms. Gibbons said. In the 30-90 days after gene therapy, patients need a lot of follow-up for safety reasons.

But aftercare for gene therapy will be more than just monitoring and managing side effects. The diseases themselves will change. Patients will be living with conditions that once were lethal.

In some cases, gene therapy may largely eliminate the disease. The data suggest that thalassemia, for example, can be largely cured for decades with one infusion of a patient’s genetically modified hematopoietic stem cells made using bluebird bio’s Zynteglo, according to Christy Duncan, MD, medical director of clinical research at the gene therapy program at Boston Children’s Hospital.

But other gene therapies, like the one for DMD, will offer a “spectrum of benefits,” Dr. Nelson said. They will be lifesaving, but the signs of the disease will linger. Clinicians will be learning alongside specialists what the new disease state for DMD and other rare diseases looks like after gene therapy.

“As we get hundreds of such therapies, [post–gene therapy] will amount to a substantial part of the pediatric population,” Dr. Nelson said.
 

Finding patients

Many of these rare diseases that plague young patients are unmistakable. Children with moderate or severe dystrophic epidermolysis bullosa, for instance, carry a mutation that prevents them from making type VII collagen. The babies suffer wounds and excessive bleeding and tend to receive a quick diagnosis within the first 6 months of life, according to Andy Orth, chief commercial officer at Krystal Bio, manufacturer of a new wound-healing gene therapy, Vyjuvek, for the disorder.

Other rare neurologic or muscular diseases can go undiagnosed for years. Until recently, drug companies and researchers have had little motivation to speed up the timeline because early diagnosis of a disease like DMD would not change the outcome, Dr. Nelson said.

But with gene therapy, prognoses are changing. And finding diseases early could soon mean preserving muscular function or preventing neurologic damage, Dr. Duncan said.

Newborn sequencing “is not standard of care yet, but it’s certainly coming,” Josh Peterson, MD, MPH, director of the center for precision medicine at Vanderbilt University Medical Center, in Nashville, Tenn., told this news organization.

A recent survey of 238 specialists in rare diseases found that roughly 90% believe whole-genome sequencing should be available to all newborns. And 80% of those experts endorse 42 genes as disease predictors. Screening for rare diseases at birth could reveal a host of conditions in the first week of life and expedite treatment. But this strategy will often rely on primary care and pediatricians interpreting the results.

Most pediatricians think sequencing is a great idea, but they do not feel comfortable doing it themselves, Dr. Peterson said. The good news, he said, is that manufacturers have made screening tests straightforward. Some drug companies even offer free screenings for gene therapy candidates.

Dr. Peterson predicts pediatricians will need to be equipped to deliver negative results on their own, which will be the case for around 97%-99% of patients. They also will need to be clear on whether a negative result is definitive or if more testing is warranted.

Positive results are more nuanced. Genetic counseling is the ideal resource when delivering this kind of news to patients, but counselors are a scarce resource nationally – and particularly in rural areas, Dr. Nelson said. Physicians likely will have to rely on their own counseling training to some degree.

“I feel very strongly that genetic counselors are in short supply,” Ms. Gibbons in Colorado said. Patients need a friendly resource who can talk them through the disease and how it works. And that discussion is not a one-off, she said.

The number of board-certified genetic counselors in the United States has doubled to more than 6,000 in the past 10 years – a pace that is expected to continue, according to the National Society of Genetic Counselors. “However, the geographical distribution of genetic counselors is most concentrated in urban centers.”

Equally important to the counseling experience, according to Dr. Duncan at Boston Children’s, is a primary care physician’s network of connections. The best newborn screening rollouts across the country have succeeded because clinicians knew where to send people next and how to get families the help they needed, she said.

But she also cautioned that this learning curve will soon be overwhelming. As gene therapy expands, it may be difficult for primary care doctors to keep up with the science, treatment studies, and commercially available therapies. “It’s asking too much,” Dr. Duncan said.

The structure of primary care already stretches practitioners thin and will “affect how well precision medicine can be adopted and disseminated,” Dr. Peterson said. “I think that is a key issue.”

Artificial intelligence may offer a partial solution. Some genetic counseling models already exist, but their utility for clinicians so far is limited, Dr. Beales said. But he said he expects these tools to improve rapidly to help clinicians and patients. On the patient’s end, they may be able to answer questions and supplement basic genetic counseling. On the physician’s end, algorithms could help triage patients and help move them along to the next steps in the care pathway for these rare diseases.
 

The whole patient

Primary care physicians will not be expected to be experts in gene therapy or solely in charge of patient safety. They will have support from industry and subspecialists leading the development of these treatments, experts agreed.

But generalists should expect to be drawn into multidisciplinary care teams, be the sounding boards for patients making decisions about gene therapy, help arrange insurance coverage, and be the recipients of late-night phone calls about side effects.

All that, while never losing sight of the child’s holistic health. In children so sick, specialists, subspecialists, and even parents tend to focus only on the rare disease. The team can “get distracted from good normal routine care,” Dr. Nelson said. But these children aren’t exempt from check-ups, vaccine regimens, or the other diseases of childhood.

“In a world where we mitigate that core disease,” he said, “we need a partner in the general pediatrics community” investing in their long-term health.

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

In Colorado and Wyoming, nearly every baby born since 2020 is tested for signs of a mutation in the SMN1 gene, an indicator of spinal muscular atrophy (SMA). And in 4 years, genetic counselor Melissa Gibbons has seen 24 positive results. She has prepped 24 different pediatricians and family doctors to deliver the news: A seemingly perfect newborn likely has a lethal genetic disease.

Most of these clinicians had never cared for a child with SMA before, nor did they know that lifesaving gene therapy for the condition now exists. Still, the physicians were foundational to getting babies emergency treatment and monitoring the child’s safety after the fact.

“They are boots on the ground for this kind of [work],” Ms. Gibbons, who is the newborn screen coordinator for SMA in both states, told this news organization. “I’m not even sure they realize it.” As of today, the U.S. Food and Drug Administration has approved 16 gene therapies for the treatment of rare and debilitating diseases once considered lethal, such as SMA and cerebral adrenoleukodystrophy.

The newest addition to the list of approvals is Elevidys, Sarepta’s gene therapy for Duchenne muscular dystrophy (DMD). These conditions can now be mitigated, abated for years at a time, and even cured using treatments that tweak a patient’s DNA or RNA.

Hundreds of treatments are under development using the same mechanism. Viruses, liposomes, and other vectors of all kinds are being used to usher new genes into cells, correcting faulty copies or equipping a cell to fight disease. Cells gain the ability to make lifesaving proteins – proteins that heal wounds, restore muscle function, and fight cancer.

Within the decade, a significant fraction of the pediatric population will have gone through gene therapy, experts told this news organization. And primary care stands to be a linchpin in the scale-up of this kind of precision genetic medicine. Pediatricians and general practitioners will be central to finding and monitoring the patients that need these treatments. But the time and support doctors will need to fill that role remain scarce.

“This is a world we are creating right now, quite literally,” said Stanley Nelson, MD, director of the center for Duchenne muscular dystrophy at the University of California, Los Angeles. These cases – some before gene therapy and some after – will show up in primary care offices before the textbook is written.
 

Unknown side effects, new diseases

Even now, gene therapy is sequestered away in large academic medical research centers. The diagnosis, decision-making, and aftercare are handled by subspecialists working on clinical trials. While the research is ongoing, trial sponsors are keeping a close eye on enrolled patients. But that’s only until these drugs get market approval, Phil Beales, MD, chief medical officer at Congenica, a digital health company specializing in genome analysis support, said. Afterward, “the trialists will no longer have a role in looking after those patients.”

At that point, the role of primary care clinicians will be critically important. Although they probably will not manage gene-therapy patients on their own – comanaging them instead with subspecialists – they will be involved in the ordering and monitoring of safety labs and other tests.

General practitioners “need to know side effects because they are going to deal with side effects when someone calls them in the middle of the night,” said Dr. Beales, who also is chief executive officer of Axovia Therapeutics, a biotech company developing gene therapies.

Some of the side effects that come with gene therapy are established. Adeno-associated virus (AAV) or AAV-mediated gene therapies carry an increased risk for damage to the heart and liver, Dr. Nelson said. Other side effects are less well known and could be specific to the treatment and the tissue it targets. Primary care will be critical in detecting these unexpected side effects and expediting visits with subspecialists, he said.

In rural Wyoming, pediatricians and family doctors are especially important, Ms. Gibbons said. In the 30-90 days after gene therapy, patients need a lot of follow-up for safety reasons.

But aftercare for gene therapy will be more than just monitoring and managing side effects. The diseases themselves will change. Patients will be living with conditions that once were lethal.

In some cases, gene therapy may largely eliminate the disease. The data suggest that thalassemia, for example, can be largely cured for decades with one infusion of a patient’s genetically modified hematopoietic stem cells made using bluebird bio’s Zynteglo, according to Christy Duncan, MD, medical director of clinical research at the gene therapy program at Boston Children’s Hospital.

But other gene therapies, like the one for DMD, will offer a “spectrum of benefits,” Dr. Nelson said. They will be lifesaving, but the signs of the disease will linger. Clinicians will be learning alongside specialists what the new disease state for DMD and other rare diseases looks like after gene therapy.

“As we get hundreds of such therapies, [post–gene therapy] will amount to a substantial part of the pediatric population,” Dr. Nelson said.
 

Finding patients

Many of these rare diseases that plague young patients are unmistakable. Children with moderate or severe dystrophic epidermolysis bullosa, for instance, carry a mutation that prevents them from making type VII collagen. The babies suffer wounds and excessive bleeding and tend to receive a quick diagnosis within the first 6 months of life, according to Andy Orth, chief commercial officer at Krystal Bio, manufacturer of a new wound-healing gene therapy, Vyjuvek, for the disorder.

Other rare neurologic or muscular diseases can go undiagnosed for years. Until recently, drug companies and researchers have had little motivation to speed up the timeline because early diagnosis of a disease like DMD would not change the outcome, Dr. Nelson said.

But with gene therapy, prognoses are changing. And finding diseases early could soon mean preserving muscular function or preventing neurologic damage, Dr. Duncan said.

Newborn sequencing “is not standard of care yet, but it’s certainly coming,” Josh Peterson, MD, MPH, director of the center for precision medicine at Vanderbilt University Medical Center, in Nashville, Tenn., told this news organization.

A recent survey of 238 specialists in rare diseases found that roughly 90% believe whole-genome sequencing should be available to all newborns. And 80% of those experts endorse 42 genes as disease predictors. Screening for rare diseases at birth could reveal a host of conditions in the first week of life and expedite treatment. But this strategy will often rely on primary care and pediatricians interpreting the results.

Most pediatricians think sequencing is a great idea, but they do not feel comfortable doing it themselves, Dr. Peterson said. The good news, he said, is that manufacturers have made screening tests straightforward. Some drug companies even offer free screenings for gene therapy candidates.

Dr. Peterson predicts pediatricians will need to be equipped to deliver negative results on their own, which will be the case for around 97%-99% of patients. They also will need to be clear on whether a negative result is definitive or if more testing is warranted.

Positive results are more nuanced. Genetic counseling is the ideal resource when delivering this kind of news to patients, but counselors are a scarce resource nationally – and particularly in rural areas, Dr. Nelson said. Physicians likely will have to rely on their own counseling training to some degree.

“I feel very strongly that genetic counselors are in short supply,” Ms. Gibbons in Colorado said. Patients need a friendly resource who can talk them through the disease and how it works. And that discussion is not a one-off, she said.

The number of board-certified genetic counselors in the United States has doubled to more than 6,000 in the past 10 years – a pace that is expected to continue, according to the National Society of Genetic Counselors. “However, the geographical distribution of genetic counselors is most concentrated in urban centers.”

Equally important to the counseling experience, according to Dr. Duncan at Boston Children’s, is a primary care physician’s network of connections. The best newborn screening rollouts across the country have succeeded because clinicians knew where to send people next and how to get families the help they needed, she said.

But she also cautioned that this learning curve will soon be overwhelming. As gene therapy expands, it may be difficult for primary care doctors to keep up with the science, treatment studies, and commercially available therapies. “It’s asking too much,” Dr. Duncan said.

The structure of primary care already stretches practitioners thin and will “affect how well precision medicine can be adopted and disseminated,” Dr. Peterson said. “I think that is a key issue.”

Artificial intelligence may offer a partial solution. Some genetic counseling models already exist, but their utility for clinicians so far is limited, Dr. Beales said. But he said he expects these tools to improve rapidly to help clinicians and patients. On the patient’s end, they may be able to answer questions and supplement basic genetic counseling. On the physician’s end, algorithms could help triage patients and help move them along to the next steps in the care pathway for these rare diseases.
 

The whole patient

Primary care physicians will not be expected to be experts in gene therapy or solely in charge of patient safety. They will have support from industry and subspecialists leading the development of these treatments, experts agreed.

But generalists should expect to be drawn into multidisciplinary care teams, be the sounding boards for patients making decisions about gene therapy, help arrange insurance coverage, and be the recipients of late-night phone calls about side effects.

All that, while never losing sight of the child’s holistic health. In children so sick, specialists, subspecialists, and even parents tend to focus only on the rare disease. The team can “get distracted from good normal routine care,” Dr. Nelson said. But these children aren’t exempt from check-ups, vaccine regimens, or the other diseases of childhood.

“In a world where we mitigate that core disease,” he said, “we need a partner in the general pediatrics community” investing in their long-term health.

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

A 12-week multidimensional “brain fitness program” provides multiple benefits for individuals with attention-deficit/hyperactive disorder, postconcussion syndrome (PCS), and memory loss, new research shows.

The program, which consists of targeted cognitive training and EEG-based neurofeedback, coupled with meditation and diet/lifestyle coaching, led to improvements in memory, attention, mood, alertness, and sleep.

The program promotes “neuroplasticity and was equally effective for patients with all three conditions,” program creator Majid Fotuhi, MD, PhD, said in an interview.

Patients with mild to moderate cognitive symptoms often see “remarkable” results within 3 months of consistently following the program, said Dr. Fotuhi, adjunct professor of neuroscience at George Washington University, Washington, and medical director of NeuroGrow Brain Fitness Center, McLean, Va.

“It actually makes intuitive sense that a healthier and stronger brain would function better and that patients of all ages with various cognitive or emotional symptoms would all benefit from improving the biology of their brain,” Dr. Fotuhi added.

The study was published online in the Journal of Alzheimer’s Disease Reports.
 

Personalized program

The findings are based on 223 children and adults who completed the 12-week NeuroGrow Brain Fitness Program (NeuroGrow BFP), including 71 with ADHD, 88 with PCS, and 64 with memory loss, defined as diagnosed mild cognitive impairment or subjective cognitive decline.

As part of the program, participants undergo a complete neurocognitive evaluation, including tests for verbal memory, complex attention, processing speed, executive functioning, and the Neurocognitive Index.

They also complete questionnaires regarding sleep, mood, diet, exercise, and anxiety/depression, and they undergo quantitative EEG at the beginning and end of the program.

A comparison of before and after neurocognitive test scores showed that all three patient subgroups experienced statistically significant improvements on most measures, the study team reports.

After completing the program, 60%-90% of patients scored higher on cognitive tests and reported having fewer cognitive, sleep, and emotional symptoms.

In all subgroups, the most significant improvement was observed in executive functioning.

“These preliminary findings appear to show that multimodal interventions which are known to increase neuroplasticity in the brain, when personalized, can have benefits for patients with cognitive symptoms from a variety of neurological conditions,” the investigators wrote.

The study’s strengths include a large, community-based sample of patients of different ages who had disruptive symptoms and abnormalities as determined using objective cognitive tests whose progress was monitored by objective and subjective measures.

The chief limitation is the lack of a control or placebo group.

“Though it is difficult to find a comparable group of patients with the exact same profile of cognitive deficits and brain-related symptoms, studying a larger group of patients – and comparing them with a wait-list group – may make it possible to do a more definitive assessment of the NeuroGrow BFP,” the researchers noted.

Dr. Fotuhi said the “secret to the success” of the program is that it involves a full assessment of all cognitive and neurobehavioral symptoms for each patient. This allows for individualized and targeted interventions for specific concerns and symptoms.

He said there is a need to recognize that patients who present to a neurology practice with a single complaint, such as a problem with memory or attention, often have other problems, such as anxiety/depression, stress, insomnia, sedentary lifestyle, obesity, diabetes, sleep apnea, or alcohol overuse.

“Each of these factors can affect their cognitive abilities and need a multimodal set of interventions in order to see full resolution of their cognitive symptoms,” Dr. Fotuhi said.

He has created a series of educational videos to demonstrate the program’s benefits.

The self-pay cost for the NeuroGrow BFP assessment and treatment sessions is approximately $7,000.

Dr. Fotuhi said all of the interventions included in the program are readily available at low cost.

He suggested that health care professionals who lack time or staff for conducting a comprehensive neurocognitive assessment for their patients can provide them with a copy of the Brain Health Index.

“Patients can then be instructed to work on the individual components of their brain health on their own – and measure their brain health index on a weekly basis,” Dr. Fotuhi said. “Private practices or academic centers can use the detailed information I have provided in my paper to develop their own brain fitness program.”
 

Not ready for prime time

Commenting on the study, Percy Griffin, PhD, director of scientific engagement for the Alzheimer’s Association, noted that “nonpharmacologic interventions can help alleviate some of the symptoms associated with dementia.

“The current study investigates nonpharmacologic interventions in a small number of patients with ADHD, postconcussion syndrome, or memory loss. The researchers found improvements on most measures following the brain rehabilitation program.

“While this is interesting, more work is needed in larger, more diverse cohorts before these programs can be applied broadly. Nonpharmacologic interventions are a helpful tool that need to be studied further in future studies,” Dr. Griffin added.

Funding for the study was provided by the NeuroGrow Brain Fitness Center. Dr. Fotuhi, the owner of NeuroGrow, was involved in data analysis, writing, editing, approval, and decision to publish. Dr. Griffin reported no disclosures.

A version of this article appeared on Medscape.com.

A 12-week multidimensional “brain fitness program” provides multiple benefits for individuals with attention-deficit/hyperactive disorder, postconcussion syndrome (PCS), and memory loss, new research shows.

The program, which consists of targeted cognitive training and EEG-based neurofeedback, coupled with meditation and diet/lifestyle coaching, led to improvements in memory, attention, mood, alertness, and sleep.

The program promotes “neuroplasticity and was equally effective for patients with all three conditions,” program creator Majid Fotuhi, MD, PhD, said in an interview.

Patients with mild to moderate cognitive symptoms often see “remarkable” results within 3 months of consistently following the program, said Dr. Fotuhi, adjunct professor of neuroscience at George Washington University, Washington, and medical director of NeuroGrow Brain Fitness Center, McLean, Va.

“It actually makes intuitive sense that a healthier and stronger brain would function better and that patients of all ages with various cognitive or emotional symptoms would all benefit from improving the biology of their brain,” Dr. Fotuhi added.

The study was published online in the Journal of Alzheimer’s Disease Reports.
 

Personalized program

The findings are based on 223 children and adults who completed the 12-week NeuroGrow Brain Fitness Program (NeuroGrow BFP), including 71 with ADHD, 88 with PCS, and 64 with memory loss, defined as diagnosed mild cognitive impairment or subjective cognitive decline.

As part of the program, participants undergo a complete neurocognitive evaluation, including tests for verbal memory, complex attention, processing speed, executive functioning, and the Neurocognitive Index.

They also complete questionnaires regarding sleep, mood, diet, exercise, and anxiety/depression, and they undergo quantitative EEG at the beginning and end of the program.

A comparison of before and after neurocognitive test scores showed that all three patient subgroups experienced statistically significant improvements on most measures, the study team reports.

After completing the program, 60%-90% of patients scored higher on cognitive tests and reported having fewer cognitive, sleep, and emotional symptoms.

In all subgroups, the most significant improvement was observed in executive functioning.

“These preliminary findings appear to show that multimodal interventions which are known to increase neuroplasticity in the brain, when personalized, can have benefits for patients with cognitive symptoms from a variety of neurological conditions,” the investigators wrote.

The study’s strengths include a large, community-based sample of patients of different ages who had disruptive symptoms and abnormalities as determined using objective cognitive tests whose progress was monitored by objective and subjective measures.

The chief limitation is the lack of a control or placebo group.

“Though it is difficult to find a comparable group of patients with the exact same profile of cognitive deficits and brain-related symptoms, studying a larger group of patients – and comparing them with a wait-list group – may make it possible to do a more definitive assessment of the NeuroGrow BFP,” the researchers noted.

Dr. Fotuhi said the “secret to the success” of the program is that it involves a full assessment of all cognitive and neurobehavioral symptoms for each patient. This allows for individualized and targeted interventions for specific concerns and symptoms.

He said there is a need to recognize that patients who present to a neurology practice with a single complaint, such as a problem with memory or attention, often have other problems, such as anxiety/depression, stress, insomnia, sedentary lifestyle, obesity, diabetes, sleep apnea, or alcohol overuse.

“Each of these factors can affect their cognitive abilities and need a multimodal set of interventions in order to see full resolution of their cognitive symptoms,” Dr. Fotuhi said.

He has created a series of educational videos to demonstrate the program’s benefits.

The self-pay cost for the NeuroGrow BFP assessment and treatment sessions is approximately $7,000.

Dr. Fotuhi said all of the interventions included in the program are readily available at low cost.

He suggested that health care professionals who lack time or staff for conducting a comprehensive neurocognitive assessment for their patients can provide them with a copy of the Brain Health Index.

“Patients can then be instructed to work on the individual components of their brain health on their own – and measure their brain health index on a weekly basis,” Dr. Fotuhi said. “Private practices or academic centers can use the detailed information I have provided in my paper to develop their own brain fitness program.”
 

Not ready for prime time

Commenting on the study, Percy Griffin, PhD, director of scientific engagement for the Alzheimer’s Association, noted that “nonpharmacologic interventions can help alleviate some of the symptoms associated with dementia.

“The current study investigates nonpharmacologic interventions in a small number of patients with ADHD, postconcussion syndrome, or memory loss. The researchers found improvements on most measures following the brain rehabilitation program.

“While this is interesting, more work is needed in larger, more diverse cohorts before these programs can be applied broadly. Nonpharmacologic interventions are a helpful tool that need to be studied further in future studies,” Dr. Griffin added.

Funding for the study was provided by the NeuroGrow Brain Fitness Center. Dr. Fotuhi, the owner of NeuroGrow, was involved in data analysis, writing, editing, approval, and decision to publish. Dr. Griffin reported no disclosures.

A version of this article appeared on Medscape.com.

A 12-week multidimensional “brain fitness program” provides multiple benefits for individuals with attention-deficit/hyperactive disorder, postconcussion syndrome (PCS), and memory loss, new research shows.

The program, which consists of targeted cognitive training and EEG-based neurofeedback, coupled with meditation and diet/lifestyle coaching, led to improvements in memory, attention, mood, alertness, and sleep.

The program promotes “neuroplasticity and was equally effective for patients with all three conditions,” program creator Majid Fotuhi, MD, PhD, said in an interview.

Patients with mild to moderate cognitive symptoms often see “remarkable” results within 3 months of consistently following the program, said Dr. Fotuhi, adjunct professor of neuroscience at George Washington University, Washington, and medical director of NeuroGrow Brain Fitness Center, McLean, Va.

“It actually makes intuitive sense that a healthier and stronger brain would function better and that patients of all ages with various cognitive or emotional symptoms would all benefit from improving the biology of their brain,” Dr. Fotuhi added.

The study was published online in the Journal of Alzheimer’s Disease Reports.
 

Personalized program

The findings are based on 223 children and adults who completed the 12-week NeuroGrow Brain Fitness Program (NeuroGrow BFP), including 71 with ADHD, 88 with PCS, and 64 with memory loss, defined as diagnosed mild cognitive impairment or subjective cognitive decline.

As part of the program, participants undergo a complete neurocognitive evaluation, including tests for verbal memory, complex attention, processing speed, executive functioning, and the Neurocognitive Index.

They also complete questionnaires regarding sleep, mood, diet, exercise, and anxiety/depression, and they undergo quantitative EEG at the beginning and end of the program.

A comparison of before and after neurocognitive test scores showed that all three patient subgroups experienced statistically significant improvements on most measures, the study team reports.

After completing the program, 60%-90% of patients scored higher on cognitive tests and reported having fewer cognitive, sleep, and emotional symptoms.

In all subgroups, the most significant improvement was observed in executive functioning.

“These preliminary findings appear to show that multimodal interventions which are known to increase neuroplasticity in the brain, when personalized, can have benefits for patients with cognitive symptoms from a variety of neurological conditions,” the investigators wrote.

The study’s strengths include a large, community-based sample of patients of different ages who had disruptive symptoms and abnormalities as determined using objective cognitive tests whose progress was monitored by objective and subjective measures.

The chief limitation is the lack of a control or placebo group.

“Though it is difficult to find a comparable group of patients with the exact same profile of cognitive deficits and brain-related symptoms, studying a larger group of patients – and comparing them with a wait-list group – may make it possible to do a more definitive assessment of the NeuroGrow BFP,” the researchers noted.

Dr. Fotuhi said the “secret to the success” of the program is that it involves a full assessment of all cognitive and neurobehavioral symptoms for each patient. This allows for individualized and targeted interventions for specific concerns and symptoms.

He said there is a need to recognize that patients who present to a neurology practice with a single complaint, such as a problem with memory or attention, often have other problems, such as anxiety/depression, stress, insomnia, sedentary lifestyle, obesity, diabetes, sleep apnea, or alcohol overuse.

“Each of these factors can affect their cognitive abilities and need a multimodal set of interventions in order to see full resolution of their cognitive symptoms,” Dr. Fotuhi said.

He has created a series of educational videos to demonstrate the program’s benefits.

The self-pay cost for the NeuroGrow BFP assessment and treatment sessions is approximately $7,000.

Dr. Fotuhi said all of the interventions included in the program are readily available at low cost.

He suggested that health care professionals who lack time or staff for conducting a comprehensive neurocognitive assessment for their patients can provide them with a copy of the Brain Health Index.

“Patients can then be instructed to work on the individual components of their brain health on their own – and measure their brain health index on a weekly basis,” Dr. Fotuhi said. “Private practices or academic centers can use the detailed information I have provided in my paper to develop their own brain fitness program.”
 

Not ready for prime time

Commenting on the study, Percy Griffin, PhD, director of scientific engagement for the Alzheimer’s Association, noted that “nonpharmacologic interventions can help alleviate some of the symptoms associated with dementia.

“The current study investigates nonpharmacologic interventions in a small number of patients with ADHD, postconcussion syndrome, or memory loss. The researchers found improvements on most measures following the brain rehabilitation program.

“While this is interesting, more work is needed in larger, more diverse cohorts before these programs can be applied broadly. Nonpharmacologic interventions are a helpful tool that need to be studied further in future studies,” Dr. Griffin added.

Funding for the study was provided by the NeuroGrow Brain Fitness Center. Dr. Fotuhi, the owner of NeuroGrow, was involved in data analysis, writing, editing, approval, and decision to publish. Dr. Griffin reported no disclosures.

A version of this article appeared on Medscape.com.

Church architecture describes visually the idea of the sacred, which is a fundamental need of man.

– Mario Botta, Swiss architect

My parents are visiting the Holy See today – prima volta in Italia! My mom waited years for this. She isn’t meeting the Pope or attending Mass. Yet, in the Whatsapp pics they sent me, you can see tears well up as she experiences St. Peter’s Basilica. It’s a visceral response to what is just a building and a poignant example of the significance of spaces.

More than just appreciating an edifice’s grandeur or exquisiteness, we are wired to connect with spaces emotionally. Beautiful or significant buildings move us, they make us feel something. Churches, synagogues, or mosques are good examples. They combine spiritual and aesthetic allure. But so too do gorgeous hotels, Apple stores, and posh restaurants. We crave the richness of an environment experienced through our five senses. The glory of sunlight through stained glass, the smell of luxurious scent pumped into a lobby, the weight of a silky new iPhone in your hand. We also have a sixth sense, that feeling we get from knowing that we are standing in a sacred place. A physical space that connects us with something wider and deeper than ourselves.

Dr. Jeffrey Benabio

Every day when I cover patient messages, I offer some patients an immediate, free solution to their problem. Just today I exchanged emails with a patient thinking I had addressed her concern by reassuring her that it was a benign seborrheic keratosis. Done. She then replied, “Thanks so much, Dr. Benabio! I still would like to schedule an appointment to come in person.” So much for the efficiency of digital medicine.

Before dismissing these patients as Luddites, understand what they want is the doctor’s office experience. The sights, the smells, the sacredness of what happens here. It is no coincidence that the first clinics were temples. In ancient Greece and Rome, the sick and the gashed made pilgrimages to one of at least 300 Asclepieia, temples of healing. During the medieval period, monasteries doubled as housing for the sick until the church began constructing stand-alone hospitals, often in cross-shaped design with an altar in the middle (eventually that became the nurses station, but without the wine).

Patients entrust us with their lives and their loved ones’ lives and a visit takes on far more significance than a simple service transaction. Forty years on, I can recall visits to Dr. Bellin’s office. He saw pediatric patients out of his Victorian home office with broad, creaky hardwood floors, stained glass, and cast iron radiators. The scent of isopropyl soaked cotton balls and typewriter ink is unforgettable. Far from sterile, it was warm, safe. It was a sacred place, one for which we still sometimes drive by when doing the tour of where I grew up.

We shall forge ahead and continue to offer virtual channels to serve our patients just as any service industry. But don’t force them there. At the same time Starbucks has been building its digital app, it is also building Starbucks Reserve Roasteries. Immense cathedral edifices with warm woods and luxurious brass, the smell of roasting coffee and warm leather perfuming the air. It is where patrons will travel long distances and endure long waits to pay a lot more for a cup of coffee.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

Church architecture describes visually the idea of the sacred, which is a fundamental need of man.

– Mario Botta, Swiss architect

My parents are visiting the Holy See today – prima volta in Italia! My mom waited years for this. She isn’t meeting the Pope or attending Mass. Yet, in the Whatsapp pics they sent me, you can see tears well up as she experiences St. Peter’s Basilica. It’s a visceral response to what is just a building and a poignant example of the significance of spaces.

More than just appreciating an edifice’s grandeur or exquisiteness, we are wired to connect with spaces emotionally. Beautiful or significant buildings move us, they make us feel something. Churches, synagogues, or mosques are good examples. They combine spiritual and aesthetic allure. But so too do gorgeous hotels, Apple stores, and posh restaurants. We crave the richness of an environment experienced through our five senses. The glory of sunlight through stained glass, the smell of luxurious scent pumped into a lobby, the weight of a silky new iPhone in your hand. We also have a sixth sense, that feeling we get from knowing that we are standing in a sacred place. A physical space that connects us with something wider and deeper than ourselves.

Dr. Jeffrey Benabio

Every day when I cover patient messages, I offer some patients an immediate, free solution to their problem. Just today I exchanged emails with a patient thinking I had addressed her concern by reassuring her that it was a benign seborrheic keratosis. Done. She then replied, “Thanks so much, Dr. Benabio! I still would like to schedule an appointment to come in person.” So much for the efficiency of digital medicine.

Before dismissing these patients as Luddites, understand what they want is the doctor’s office experience. The sights, the smells, the sacredness of what happens here. It is no coincidence that the first clinics were temples. In ancient Greece and Rome, the sick and the gashed made pilgrimages to one of at least 300 Asclepieia, temples of healing. During the medieval period, monasteries doubled as housing for the sick until the church began constructing stand-alone hospitals, often in cross-shaped design with an altar in the middle (eventually that became the nurses station, but without the wine).

Patients entrust us with their lives and their loved ones’ lives and a visit takes on far more significance than a simple service transaction. Forty years on, I can recall visits to Dr. Bellin’s office. He saw pediatric patients out of his Victorian home office with broad, creaky hardwood floors, stained glass, and cast iron radiators. The scent of isopropyl soaked cotton balls and typewriter ink is unforgettable. Far from sterile, it was warm, safe. It was a sacred place, one for which we still sometimes drive by when doing the tour of where I grew up.

We shall forge ahead and continue to offer virtual channels to serve our patients just as any service industry. But don’t force them there. At the same time Starbucks has been building its digital app, it is also building Starbucks Reserve Roasteries. Immense cathedral edifices with warm woods and luxurious brass, the smell of roasting coffee and warm leather perfuming the air. It is where patrons will travel long distances and endure long waits to pay a lot more for a cup of coffee.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

Church architecture describes visually the idea of the sacred, which is a fundamental need of man.

– Mario Botta, Swiss architect

My parents are visiting the Holy See today – prima volta in Italia! My mom waited years for this. She isn’t meeting the Pope or attending Mass. Yet, in the Whatsapp pics they sent me, you can see tears well up as she experiences St. Peter’s Basilica. It’s a visceral response to what is just a building and a poignant example of the significance of spaces.

More than just appreciating an edifice’s grandeur or exquisiteness, we are wired to connect with spaces emotionally. Beautiful or significant buildings move us, they make us feel something. Churches, synagogues, or mosques are good examples. They combine spiritual and aesthetic allure. But so too do gorgeous hotels, Apple stores, and posh restaurants. We crave the richness of an environment experienced through our five senses. The glory of sunlight through stained glass, the smell of luxurious scent pumped into a lobby, the weight of a silky new iPhone in your hand. We also have a sixth sense, that feeling we get from knowing that we are standing in a sacred place. A physical space that connects us with something wider and deeper than ourselves.

Dr. Jeffrey Benabio

Every day when I cover patient messages, I offer some patients an immediate, free solution to their problem. Just today I exchanged emails with a patient thinking I had addressed her concern by reassuring her that it was a benign seborrheic keratosis. Done. She then replied, “Thanks so much, Dr. Benabio! I still would like to schedule an appointment to come in person.” So much for the efficiency of digital medicine.

Before dismissing these patients as Luddites, understand what they want is the doctor’s office experience. The sights, the smells, the sacredness of what happens here. It is no coincidence that the first clinics were temples. In ancient Greece and Rome, the sick and the gashed made pilgrimages to one of at least 300 Asclepieia, temples of healing. During the medieval period, monasteries doubled as housing for the sick until the church began constructing stand-alone hospitals, often in cross-shaped design with an altar in the middle (eventually that became the nurses station, but without the wine).

Patients entrust us with their lives and their loved ones’ lives and a visit takes on far more significance than a simple service transaction. Forty years on, I can recall visits to Dr. Bellin’s office. He saw pediatric patients out of his Victorian home office with broad, creaky hardwood floors, stained glass, and cast iron radiators. The scent of isopropyl soaked cotton balls and typewriter ink is unforgettable. Far from sterile, it was warm, safe. It was a sacred place, one for which we still sometimes drive by when doing the tour of where I grew up.

We shall forge ahead and continue to offer virtual channels to serve our patients just as any service industry. But don’t force them there. At the same time Starbucks has been building its digital app, it is also building Starbucks Reserve Roasteries. Immense cathedral edifices with warm woods and luxurious brass, the smell of roasting coffee and warm leather perfuming the air. It is where patrons will travel long distances and endure long waits to pay a lot more for a cup of coffee.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

Like hundreds of other medical experts, Leana Wen, MD, an emergency physician and former Baltimore health commissioner, was an early and avid supporter of COVID vaccines and their ability to prevent severe disease, hospitalization, and death from SARS-CoV-2 infections.

When 51-year-old Scott Eli Harris, of Aubrey, Tex., heard of Dr. Wen’s stance in July 2021, the self-described “fifth-generation U.S. Army veteran and a sniper” sent Dr. Wen an electronic invective laden with racist language and very specific threats to shoot her.

Mr. Harris pled guilty to transmitting threats via interstate commerce last February and began serving 6 months in federal prison in the fall of 2022, but his threats wouldn’t be the last for Dr. Wen. Just 2 days after Mr. Harris was sentenced, charges were unsealed against another man in Massachusetts, who threatened that Dr. Wen would “end up in pieces” if she continued “pushing” her thoughts publicly.’

Dr. Wen has plenty of company. In an August 2022 survey of emergency doctors conducted by the American College of Emergency Physicians, 85% of respondents said violence against them is increasing. One in four doctors said they’re being assaulted by patients and their family and friends multiple times a week, compared with just 8% of doctors who said as much in 2018. About 64% of emergency physicians reported receiving verbal assaults and threats of violence; 40% reported being hit or slapped, and 26% were kicked.

This uptick of violence and threats against physicians didn’t come out of nowhere; violence against health care workers has been gradually increasing over the past decade. Health care providers can attest to the hostility that particular topics have sparked for years: vaccines in pediatrics, abortion in ob.gyn., and gender-affirming care in endocrinology.

But the pandemic fueled the fire. While there have always been hot-button issues in medicine, the ire they arouse today is more intense than ever before. The proliferation of misinformation (often via social media) and the politicization of public health and medicine are at the center of the problem.
 

‘The people attacking are themselves victims’

The misinformation problem first came to a head in one area of public health: vaccines. The pandemic accelerated antagonism in medicine – thanks, in part, to decades of antivaccine activism.

The antivaccine movement, which has ebbed and flowed in the United States and across the globe since the first vaccine, experienced a new wave in the early 2000s with the combination of concerns about thimerosal in vaccines and a now disproven link between autism and the MMR vaccine. But that movement grew. It picked up steam when activists gained political clout after a 2014 measles outbreak at Disneyland led California schools to tighten up policies regarding vaccinations for kids who enrolled. These stronger public school vaccination laws ran up against religious freedom arguments from antivaccine advocates.

Use of social media continues to grow, and with it, the spread of misinformation. A recent study found that Facebook “users’ social media habits doubled, and in some cases, tripled the amount of fake news they shared.”

In the face of growing confusion, health care providers and public health experts have often struggled to treat their patients – and communicate to the public – without appearing political.

“The people that are doing the attacking are in some ways themselves victims,” said Peter Hotez, MD, PhD, dean of the National School of Tropical Medicine at Baylor College of Medicine, Houston. “They’re victims of the antiscience, antihealth ecosystem coming out of Fox News, the House Freedom Caucus, the CPAC conference, coming out of contrarian intellectuals.”

Many of Dr. Hotez’s colleagues don’t want to talk about the political right as an enabler of scientific disinformation, he said, but that doesn’t change what the evidence shows. The vast majority of state and national bills opposing vaccination, gender-affirming care, comprehensive reproductive care, and other evidence-based medical care often come from Republican legislators.
 

When politics and health care collide

“We’re in an incredible status quo,” said William Schaffner, MD, the previous director of the Infectious Diseases Society of America and a professor of infectious diseases and preventive medicine at Vanderbilt University, Nashville, Tenn. “You can’t get away from the politics, because you have [political] candidates espousing certain concepts that are antithetical to good public health.”

In March 2023, Florida Gov. Ron DeSantis’s surgeon general, Joseph Ladapo, MD, PhD, warned that COVID vaccines are harmful to young men, prompting rebukes from federal health authorities. It later came out that Dr. Ladapo had changed some of the results of the study before issuing his warning. But long before 2023, there emerged an increasing gap in COVID deaths between red states and blue states, mirroring the vaccination rates in those states. The redder the state, the higher the death toll.

It’s not just Republican Party culture warriors; medical misinformation is also finding increasing purchase on the far left. Robert F. Kennedy Jr. and Marianne Williamson, both of whom have launched long-shot challenges to President Biden for the 2024 Democratic nomination, had promoted antivaccine ideas long before the COVID pandemic. Mr. Kennedy continues to spread misinformation.

In June 2023, Joe Rogan hosted Mr. Kennedy, on his podcast. During the episode, Mr. Rogan listened uncritically as Mr. Kennedy told his millions of listeners that vaccines cause autism and that 5G causes cancer, among other fringe, often-debunked theories.

Dr. Hotez, a prominent misinformation debunker who was also part of a team that designed a low-cost COVID-19 vaccine, wrote on Twitter that the episode was “just awful.”

The backlash began almost immediately. Mr. Rogan, who has over 11 million followers on Twitter, responded with a public challenge for Dr. Hotez to debate Mr. Kennedy on Mr. Rogan’s show, with a reward of $100,000 to the charity of Dr. Hotez’s choice. More offers streamed in, including from Elon Musk, who tweeted that Dr. Hotez was “afraid of a public debate, because he knows he’s wrong.” More supporters of Mr. Kennedy and Mr. Rogan piled on.

Vaccine skeptics even showed up at Dr. Hotez’s house, filming him as he was returning from buying a Father’s Day cake and taunting him to debate Mr. Kennedy.
 

A turn in the pandemic

For a precious few weeks at the start of the pandemic, it felt as though the country was all in this together. There were arguments against closing schools and shutting down businesses, but for the most part, the nation had about 4 solid weeks of solidarity.

As masking mandates changed and the public health establishment lost the confidence of Americans, the veneer of solidarity began to chip away.

“Things were changing so rapidly during the pandemic that it was very hard for staff and patients to understand the changing guidelines, whether it was visitor constraints or masking,” said Carrie Nelson, the chief medical officer at the telehealth company AmWell, who worked as a supervisor at a large health care system in the Midwest until 2021.

In the midst of the public health crisis, former President Trump was downplaying the severity of the disease and was silencing officials from the Centers for Disease Control and Prevention, such as Nancy Messonier, who warned from the very beginning of the pandemic’s potential.

When the vaccines came out, the latent antivaccine movement flared up once again. And this time – unlike in decades past – the debate over vaccines had become partisan.

“Before the pandemic,” said Christopher Thomas, an emergency physician on the West Coast who requested that a pseudonym be used because of personal threats he has received, “patients wouldn’t really challenge me or throw out weird questions.” It’s not that he never encountered pushback, but the stakes felt lower, and people largely deferred to his medical expertise. “If we got a parent who had not vaccinated their child, I would totally engage back then,” Dr. Thomas said.

But the pandemic – and America’s response to it – changed the conversation. “The rhetoric ... switched from downplaying the virus to demonizing the vaccines,” Dr. Thomas said.
 

The toll on health care professionals

By the time vaccines were available, the public had begun to conflate doctors with public health experts, since both were “pushing” the vaccine.

“Most people probably don’t really know the difference between clinical medicine and public health,” said Richard Pan, MD, MPH, a pediatrician and California legislator who sponsored two bills – now laws – that strengthened state childhood vaccination requirements.

At first, it was clearly public health officials, such as Anthony Fauci, MD, who were the face of measures to mitigate the virus. But as doctors became the enforcers of those measures, the line between physicians and public health officials blurred.

A lot of the anger then shifted toward doctors, nurses, and other health care professionals, Dr. Pan said, “because we were, of course, the ones who would be administering the vaccines. They don’t really think of their doctor as a government person until your doctor is carrying a [government] message.”

Given the pressures and struggles of the past few years, it’s no surprise that burnout among health care professionals is high. According to an April 2023 study by the National Council of State Boards of Nursing and the National Forum of State Nursing Workforce Centers, an estimated 800,000 nurses expect to leave the profession by 2027, driven first and foremost by “stress and burnout.”

All of these departures in medicine’s “great resignation” have left hospitals and health care organizations even more short staffed, thereby increasing even more the pressure and burnout on those left.

The pandemic had already badly exacerbated the already widespread problem of burnout in the medical field, which Ms. Nelson said has contributed to the tension.

“The burnout problem that we have in health care is not a good basis for the development of a good therapeutic relationship,” Ms. Nelson said. “Burnout is fraught with apathy and desensitization to human emotions. It takes away the empathy that we once had for people that we see.”
 

What comes next?

Almost exactly 3 years after the world learned about SARS-CoV-2, Biden declared an end to the coronavirus public health emergency in April 2023. Yet, Americans continue to die from COVID, and the anger that bloomed and spread has not abated.

“I think we’re in a new steady state of violence in health care settings,” Ms. Nelson said. “It’s not gone down, because people are still very distressed.” That’s evident from the high prevalence of mental health conditions, the financial strain of first the pandemic and then inflation, and the overall traumatic impact the pandemic had on people, whether they recognize it or not.

The first step to solving any problem is, as the saying goes, to admit that there is a problem.

“I think people need to start stepping out of their comfort bubbles and start to look at things that make them uncomfortable,” Dr. Thomas said, but he doesn’t see that happening any time soon. “I’ve been very let down by physicians and embarrassed by the American physician organizations.”

The medical board in his state, he said, has stood by as some doctors continue misrepresenting medical evidence. “That’s been really, really hard on me. I didn’t think that the medical boards would go so far as to look the other way for something that was this tremendously bad.”

There are others who can take the lead – if they’re willing.

“There are some things the medical societies and academic health centers can do,” Dr. Hotez said, “starting with building up a culture of physicians and health care providers feeling comfortable in the public domain.” He said the messaging when he was getting his degrees was not to engage the public and not to talk to journalists because that was “self-promotion” or “grandstanding.” But the world is different now. Health care professionals need training in public engagement and communication, he said, and the culture needs to change so that health care providers feel comfortable speaking out without feeling “the sword of Damocles over their heads” every time they talk to a reporter, Dr. Hotez said.

There may be no silver bullet to solve the big-picture trust problem in medicine and public health. No TV appearance or quote in an article can solve it. But on an individual level — through careful relationship building with patients – doctors can strengthen that trust.

Telehealth may help with that, but there’s a fine balance there, Ms. Nelson cautioned. On the one hand, with the doctor and the patient each in their own private spaces, where they feel safe and comfortable, the overall experience can be more therapeutic and less stressful. At the same time, telehealth can pile on change-management tasks that can exacerbate burnout, “so it’s a delicate thing we have to approach.”

One very thin silver lining that could emerge from the way in which patients have begun to try to take charge of their care.

“They should fully understand the reasoning behind the recommendations that physicians are making,” Ms. Nelson said. “I’d like to see us get to a happy medium where it’s a partnership. We can’t go back to the old school where the doctor knows best and you don’t ever question him.

“What we need is the partnership, and I would love to see that as the silver lining, but the anger has got to settle down in order for that kind of productive thing to happen.”

As for the big picture? There’s a limit to what even society’s “miracle workers” can do. “The biggest priority right now for the health system is to protect their staff whatever way they can and do some training in deescalation,” Ms. Nelson said. “But I don’t think health care can solve the societal issues that seem to be creating this.”

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

Like hundreds of other medical experts, Leana Wen, MD, an emergency physician and former Baltimore health commissioner, was an early and avid supporter of COVID vaccines and their ability to prevent severe disease, hospitalization, and death from SARS-CoV-2 infections.

When 51-year-old Scott Eli Harris, of Aubrey, Tex., heard of Dr. Wen’s stance in July 2021, the self-described “fifth-generation U.S. Army veteran and a sniper” sent Dr. Wen an electronic invective laden with racist language and very specific threats to shoot her.

Mr. Harris pled guilty to transmitting threats via interstate commerce last February and began serving 6 months in federal prison in the fall of 2022, but his threats wouldn’t be the last for Dr. Wen. Just 2 days after Mr. Harris was sentenced, charges were unsealed against another man in Massachusetts, who threatened that Dr. Wen would “end up in pieces” if she continued “pushing” her thoughts publicly.’

Dr. Wen has plenty of company. In an August 2022 survey of emergency doctors conducted by the American College of Emergency Physicians, 85% of respondents said violence against them is increasing. One in four doctors said they’re being assaulted by patients and their family and friends multiple times a week, compared with just 8% of doctors who said as much in 2018. About 64% of emergency physicians reported receiving verbal assaults and threats of violence; 40% reported being hit or slapped, and 26% were kicked.

This uptick of violence and threats against physicians didn’t come out of nowhere; violence against health care workers has been gradually increasing over the past decade. Health care providers can attest to the hostility that particular topics have sparked for years: vaccines in pediatrics, abortion in ob.gyn., and gender-affirming care in endocrinology.

But the pandemic fueled the fire. While there have always been hot-button issues in medicine, the ire they arouse today is more intense than ever before. The proliferation of misinformation (often via social media) and the politicization of public health and medicine are at the center of the problem.
 

‘The people attacking are themselves victims’

The misinformation problem first came to a head in one area of public health: vaccines. The pandemic accelerated antagonism in medicine – thanks, in part, to decades of antivaccine activism.

The antivaccine movement, which has ebbed and flowed in the United States and across the globe since the first vaccine, experienced a new wave in the early 2000s with the combination of concerns about thimerosal in vaccines and a now disproven link between autism and the MMR vaccine. But that movement grew. It picked up steam when activists gained political clout after a 2014 measles outbreak at Disneyland led California schools to tighten up policies regarding vaccinations for kids who enrolled. These stronger public school vaccination laws ran up against religious freedom arguments from antivaccine advocates.

Use of social media continues to grow, and with it, the spread of misinformation. A recent study found that Facebook “users’ social media habits doubled, and in some cases, tripled the amount of fake news they shared.”

In the face of growing confusion, health care providers and public health experts have often struggled to treat their patients – and communicate to the public – without appearing political.

“The people that are doing the attacking are in some ways themselves victims,” said Peter Hotez, MD, PhD, dean of the National School of Tropical Medicine at Baylor College of Medicine, Houston. “They’re victims of the antiscience, antihealth ecosystem coming out of Fox News, the House Freedom Caucus, the CPAC conference, coming out of contrarian intellectuals.”

Many of Dr. Hotez’s colleagues don’t want to talk about the political right as an enabler of scientific disinformation, he said, but that doesn’t change what the evidence shows. The vast majority of state and national bills opposing vaccination, gender-affirming care, comprehensive reproductive care, and other evidence-based medical care often come from Republican legislators.
 

When politics and health care collide

“We’re in an incredible status quo,” said William Schaffner, MD, the previous director of the Infectious Diseases Society of America and a professor of infectious diseases and preventive medicine at Vanderbilt University, Nashville, Tenn. “You can’t get away from the politics, because you have [political] candidates espousing certain concepts that are antithetical to good public health.”

In March 2023, Florida Gov. Ron DeSantis’s surgeon general, Joseph Ladapo, MD, PhD, warned that COVID vaccines are harmful to young men, prompting rebukes from federal health authorities. It later came out that Dr. Ladapo had changed some of the results of the study before issuing his warning. But long before 2023, there emerged an increasing gap in COVID deaths between red states and blue states, mirroring the vaccination rates in those states. The redder the state, the higher the death toll.

It’s not just Republican Party culture warriors; medical misinformation is also finding increasing purchase on the far left. Robert F. Kennedy Jr. and Marianne Williamson, both of whom have launched long-shot challenges to President Biden for the 2024 Democratic nomination, had promoted antivaccine ideas long before the COVID pandemic. Mr. Kennedy continues to spread misinformation.

In June 2023, Joe Rogan hosted Mr. Kennedy, on his podcast. During the episode, Mr. Rogan listened uncritically as Mr. Kennedy told his millions of listeners that vaccines cause autism and that 5G causes cancer, among other fringe, often-debunked theories.

Dr. Hotez, a prominent misinformation debunker who was also part of a team that designed a low-cost COVID-19 vaccine, wrote on Twitter that the episode was “just awful.”

The backlash began almost immediately. Mr. Rogan, who has over 11 million followers on Twitter, responded with a public challenge for Dr. Hotez to debate Mr. Kennedy on Mr. Rogan’s show, with a reward of $100,000 to the charity of Dr. Hotez’s choice. More offers streamed in, including from Elon Musk, who tweeted that Dr. Hotez was “afraid of a public debate, because he knows he’s wrong.” More supporters of Mr. Kennedy and Mr. Rogan piled on.

Vaccine skeptics even showed up at Dr. Hotez’s house, filming him as he was returning from buying a Father’s Day cake and taunting him to debate Mr. Kennedy.
 

A turn in the pandemic

For a precious few weeks at the start of the pandemic, it felt as though the country was all in this together. There were arguments against closing schools and shutting down businesses, but for the most part, the nation had about 4 solid weeks of solidarity.

As masking mandates changed and the public health establishment lost the confidence of Americans, the veneer of solidarity began to chip away.

“Things were changing so rapidly during the pandemic that it was very hard for staff and patients to understand the changing guidelines, whether it was visitor constraints or masking,” said Carrie Nelson, the chief medical officer at the telehealth company AmWell, who worked as a supervisor at a large health care system in the Midwest until 2021.

In the midst of the public health crisis, former President Trump was downplaying the severity of the disease and was silencing officials from the Centers for Disease Control and Prevention, such as Nancy Messonier, who warned from the very beginning of the pandemic’s potential.

When the vaccines came out, the latent antivaccine movement flared up once again. And this time – unlike in decades past – the debate over vaccines had become partisan.

“Before the pandemic,” said Christopher Thomas, an emergency physician on the West Coast who requested that a pseudonym be used because of personal threats he has received, “patients wouldn’t really challenge me or throw out weird questions.” It’s not that he never encountered pushback, but the stakes felt lower, and people largely deferred to his medical expertise. “If we got a parent who had not vaccinated their child, I would totally engage back then,” Dr. Thomas said.

But the pandemic – and America’s response to it – changed the conversation. “The rhetoric ... switched from downplaying the virus to demonizing the vaccines,” Dr. Thomas said.
 

The toll on health care professionals

By the time vaccines were available, the public had begun to conflate doctors with public health experts, since both were “pushing” the vaccine.

“Most people probably don’t really know the difference between clinical medicine and public health,” said Richard Pan, MD, MPH, a pediatrician and California legislator who sponsored two bills – now laws – that strengthened state childhood vaccination requirements.

At first, it was clearly public health officials, such as Anthony Fauci, MD, who were the face of measures to mitigate the virus. But as doctors became the enforcers of those measures, the line between physicians and public health officials blurred.

A lot of the anger then shifted toward doctors, nurses, and other health care professionals, Dr. Pan said, “because we were, of course, the ones who would be administering the vaccines. They don’t really think of their doctor as a government person until your doctor is carrying a [government] message.”

Given the pressures and struggles of the past few years, it’s no surprise that burnout among health care professionals is high. According to an April 2023 study by the National Council of State Boards of Nursing and the National Forum of State Nursing Workforce Centers, an estimated 800,000 nurses expect to leave the profession by 2027, driven first and foremost by “stress and burnout.”

All of these departures in medicine’s “great resignation” have left hospitals and health care organizations even more short staffed, thereby increasing even more the pressure and burnout on those left.

The pandemic had already badly exacerbated the already widespread problem of burnout in the medical field, which Ms. Nelson said has contributed to the tension.

“The burnout problem that we have in health care is not a good basis for the development of a good therapeutic relationship,” Ms. Nelson said. “Burnout is fraught with apathy and desensitization to human emotions. It takes away the empathy that we once had for people that we see.”
 

What comes next?

Almost exactly 3 years after the world learned about SARS-CoV-2, Biden declared an end to the coronavirus public health emergency in April 2023. Yet, Americans continue to die from COVID, and the anger that bloomed and spread has not abated.

“I think we’re in a new steady state of violence in health care settings,” Ms. Nelson said. “It’s not gone down, because people are still very distressed.” That’s evident from the high prevalence of mental health conditions, the financial strain of first the pandemic and then inflation, and the overall traumatic impact the pandemic had on people, whether they recognize it or not.

The first step to solving any problem is, as the saying goes, to admit that there is a problem.

“I think people need to start stepping out of their comfort bubbles and start to look at things that make them uncomfortable,” Dr. Thomas said, but he doesn’t see that happening any time soon. “I’ve been very let down by physicians and embarrassed by the American physician organizations.”

The medical board in his state, he said, has stood by as some doctors continue misrepresenting medical evidence. “That’s been really, really hard on me. I didn’t think that the medical boards would go so far as to look the other way for something that was this tremendously bad.”

There are others who can take the lead – if they’re willing.

“There are some things the medical societies and academic health centers can do,” Dr. Hotez said, “starting with building up a culture of physicians and health care providers feeling comfortable in the public domain.” He said the messaging when he was getting his degrees was not to engage the public and not to talk to journalists because that was “self-promotion” or “grandstanding.” But the world is different now. Health care professionals need training in public engagement and communication, he said, and the culture needs to change so that health care providers feel comfortable speaking out without feeling “the sword of Damocles over their heads” every time they talk to a reporter, Dr. Hotez said.

There may be no silver bullet to solve the big-picture trust problem in medicine and public health. No TV appearance or quote in an article can solve it. But on an individual level — through careful relationship building with patients – doctors can strengthen that trust.

Telehealth may help with that, but there’s a fine balance there, Ms. Nelson cautioned. On the one hand, with the doctor and the patient each in their own private spaces, where they feel safe and comfortable, the overall experience can be more therapeutic and less stressful. At the same time, telehealth can pile on change-management tasks that can exacerbate burnout, “so it’s a delicate thing we have to approach.”

One very thin silver lining that could emerge from the way in which patients have begun to try to take charge of their care.

“They should fully understand the reasoning behind the recommendations that physicians are making,” Ms. Nelson said. “I’d like to see us get to a happy medium where it’s a partnership. We can’t go back to the old school where the doctor knows best and you don’t ever question him.

“What we need is the partnership, and I would love to see that as the silver lining, but the anger has got to settle down in order for that kind of productive thing to happen.”

As for the big picture? There’s a limit to what even society’s “miracle workers” can do. “The biggest priority right now for the health system is to protect their staff whatever way they can and do some training in deescalation,” Ms. Nelson said. “But I don’t think health care can solve the societal issues that seem to be creating this.”

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

Like hundreds of other medical experts, Leana Wen, MD, an emergency physician and former Baltimore health commissioner, was an early and avid supporter of COVID vaccines and their ability to prevent severe disease, hospitalization, and death from SARS-CoV-2 infections.

When 51-year-old Scott Eli Harris, of Aubrey, Tex., heard of Dr. Wen’s stance in July 2021, the self-described “fifth-generation U.S. Army veteran and a sniper” sent Dr. Wen an electronic invective laden with racist language and very specific threats to shoot her.

Mr. Harris pled guilty to transmitting threats via interstate commerce last February and began serving 6 months in federal prison in the fall of 2022, but his threats wouldn’t be the last for Dr. Wen. Just 2 days after Mr. Harris was sentenced, charges were unsealed against another man in Massachusetts, who threatened that Dr. Wen would “end up in pieces” if she continued “pushing” her thoughts publicly.’

Dr. Wen has plenty of company. In an August 2022 survey of emergency doctors conducted by the American College of Emergency Physicians, 85% of respondents said violence against them is increasing. One in four doctors said they’re being assaulted by patients and their family and friends multiple times a week, compared with just 8% of doctors who said as much in 2018. About 64% of emergency physicians reported receiving verbal assaults and threats of violence; 40% reported being hit or slapped, and 26% were kicked.

This uptick of violence and threats against physicians didn’t come out of nowhere; violence against health care workers has been gradually increasing over the past decade. Health care providers can attest to the hostility that particular topics have sparked for years: vaccines in pediatrics, abortion in ob.gyn., and gender-affirming care in endocrinology.

But the pandemic fueled the fire. While there have always been hot-button issues in medicine, the ire they arouse today is more intense than ever before. The proliferation of misinformation (often via social media) and the politicization of public health and medicine are at the center of the problem.
 

‘The people attacking are themselves victims’

The misinformation problem first came to a head in one area of public health: vaccines. The pandemic accelerated antagonism in medicine – thanks, in part, to decades of antivaccine activism.

The antivaccine movement, which has ebbed and flowed in the United States and across the globe since the first vaccine, experienced a new wave in the early 2000s with the combination of concerns about thimerosal in vaccines and a now disproven link between autism and the MMR vaccine. But that movement grew. It picked up steam when activists gained political clout after a 2014 measles outbreak at Disneyland led California schools to tighten up policies regarding vaccinations for kids who enrolled. These stronger public school vaccination laws ran up against religious freedom arguments from antivaccine advocates.

Use of social media continues to grow, and with it, the spread of misinformation. A recent study found that Facebook “users’ social media habits doubled, and in some cases, tripled the amount of fake news they shared.”

In the face of growing confusion, health care providers and public health experts have often struggled to treat their patients – and communicate to the public – without appearing political.

“The people that are doing the attacking are in some ways themselves victims,” said Peter Hotez, MD, PhD, dean of the National School of Tropical Medicine at Baylor College of Medicine, Houston. “They’re victims of the antiscience, antihealth ecosystem coming out of Fox News, the House Freedom Caucus, the CPAC conference, coming out of contrarian intellectuals.”

Many of Dr. Hotez’s colleagues don’t want to talk about the political right as an enabler of scientific disinformation, he said, but that doesn’t change what the evidence shows. The vast majority of state and national bills opposing vaccination, gender-affirming care, comprehensive reproductive care, and other evidence-based medical care often come from Republican legislators.
 

When politics and health care collide

“We’re in an incredible status quo,” said William Schaffner, MD, the previous director of the Infectious Diseases Society of America and a professor of infectious diseases and preventive medicine at Vanderbilt University, Nashville, Tenn. “You can’t get away from the politics, because you have [political] candidates espousing certain concepts that are antithetical to good public health.”

In March 2023, Florida Gov. Ron DeSantis’s surgeon general, Joseph Ladapo, MD, PhD, warned that COVID vaccines are harmful to young men, prompting rebukes from federal health authorities. It later came out that Dr. Ladapo had changed some of the results of the study before issuing his warning. But long before 2023, there emerged an increasing gap in COVID deaths between red states and blue states, mirroring the vaccination rates in those states. The redder the state, the higher the death toll.

It’s not just Republican Party culture warriors; medical misinformation is also finding increasing purchase on the far left. Robert F. Kennedy Jr. and Marianne Williamson, both of whom have launched long-shot challenges to President Biden for the 2024 Democratic nomination, had promoted antivaccine ideas long before the COVID pandemic. Mr. Kennedy continues to spread misinformation.

In June 2023, Joe Rogan hosted Mr. Kennedy, on his podcast. During the episode, Mr. Rogan listened uncritically as Mr. Kennedy told his millions of listeners that vaccines cause autism and that 5G causes cancer, among other fringe, often-debunked theories.

Dr. Hotez, a prominent misinformation debunker who was also part of a team that designed a low-cost COVID-19 vaccine, wrote on Twitter that the episode was “just awful.”

The backlash began almost immediately. Mr. Rogan, who has over 11 million followers on Twitter, responded with a public challenge for Dr. Hotez to debate Mr. Kennedy on Mr. Rogan’s show, with a reward of $100,000 to the charity of Dr. Hotez’s choice. More offers streamed in, including from Elon Musk, who tweeted that Dr. Hotez was “afraid of a public debate, because he knows he’s wrong.” More supporters of Mr. Kennedy and Mr. Rogan piled on.

Vaccine skeptics even showed up at Dr. Hotez’s house, filming him as he was returning from buying a Father’s Day cake and taunting him to debate Mr. Kennedy.
 

A turn in the pandemic

For a precious few weeks at the start of the pandemic, it felt as though the country was all in this together. There were arguments against closing schools and shutting down businesses, but for the most part, the nation had about 4 solid weeks of solidarity.

As masking mandates changed and the public health establishment lost the confidence of Americans, the veneer of solidarity began to chip away.

“Things were changing so rapidly during the pandemic that it was very hard for staff and patients to understand the changing guidelines, whether it was visitor constraints or masking,” said Carrie Nelson, the chief medical officer at the telehealth company AmWell, who worked as a supervisor at a large health care system in the Midwest until 2021.

In the midst of the public health crisis, former President Trump was downplaying the severity of the disease and was silencing officials from the Centers for Disease Control and Prevention, such as Nancy Messonier, who warned from the very beginning of the pandemic’s potential.

When the vaccines came out, the latent antivaccine movement flared up once again. And this time – unlike in decades past – the debate over vaccines had become partisan.

“Before the pandemic,” said Christopher Thomas, an emergency physician on the West Coast who requested that a pseudonym be used because of personal threats he has received, “patients wouldn’t really challenge me or throw out weird questions.” It’s not that he never encountered pushback, but the stakes felt lower, and people largely deferred to his medical expertise. “If we got a parent who had not vaccinated their child, I would totally engage back then,” Dr. Thomas said.

But the pandemic – and America’s response to it – changed the conversation. “The rhetoric ... switched from downplaying the virus to demonizing the vaccines,” Dr. Thomas said.
 

The toll on health care professionals

By the time vaccines were available, the public had begun to conflate doctors with public health experts, since both were “pushing” the vaccine.

“Most people probably don’t really know the difference between clinical medicine and public health,” said Richard Pan, MD, MPH, a pediatrician and California legislator who sponsored two bills – now laws – that strengthened state childhood vaccination requirements.

At first, it was clearly public health officials, such as Anthony Fauci, MD, who were the face of measures to mitigate the virus. But as doctors became the enforcers of those measures, the line between physicians and public health officials blurred.

A lot of the anger then shifted toward doctors, nurses, and other health care professionals, Dr. Pan said, “because we were, of course, the ones who would be administering the vaccines. They don’t really think of their doctor as a government person until your doctor is carrying a [government] message.”

Given the pressures and struggles of the past few years, it’s no surprise that burnout among health care professionals is high. According to an April 2023 study by the National Council of State Boards of Nursing and the National Forum of State Nursing Workforce Centers, an estimated 800,000 nurses expect to leave the profession by 2027, driven first and foremost by “stress and burnout.”

All of these departures in medicine’s “great resignation” have left hospitals and health care organizations even more short staffed, thereby increasing even more the pressure and burnout on those left.

The pandemic had already badly exacerbated the already widespread problem of burnout in the medical field, which Ms. Nelson said has contributed to the tension.

“The burnout problem that we have in health care is not a good basis for the development of a good therapeutic relationship,” Ms. Nelson said. “Burnout is fraught with apathy and desensitization to human emotions. It takes away the empathy that we once had for people that we see.”
 

What comes next?

Almost exactly 3 years after the world learned about SARS-CoV-2, Biden declared an end to the coronavirus public health emergency in April 2023. Yet, Americans continue to die from COVID, and the anger that bloomed and spread has not abated.

“I think we’re in a new steady state of violence in health care settings,” Ms. Nelson said. “It’s not gone down, because people are still very distressed.” That’s evident from the high prevalence of mental health conditions, the financial strain of first the pandemic and then inflation, and the overall traumatic impact the pandemic had on people, whether they recognize it or not.

The first step to solving any problem is, as the saying goes, to admit that there is a problem.

“I think people need to start stepping out of their comfort bubbles and start to look at things that make them uncomfortable,” Dr. Thomas said, but he doesn’t see that happening any time soon. “I’ve been very let down by physicians and embarrassed by the American physician organizations.”

The medical board in his state, he said, has stood by as some doctors continue misrepresenting medical evidence. “That’s been really, really hard on me. I didn’t think that the medical boards would go so far as to look the other way for something that was this tremendously bad.”

There are others who can take the lead – if they’re willing.

“There are some things the medical societies and academic health centers can do,” Dr. Hotez said, “starting with building up a culture of physicians and health care providers feeling comfortable in the public domain.” He said the messaging when he was getting his degrees was not to engage the public and not to talk to journalists because that was “self-promotion” or “grandstanding.” But the world is different now. Health care professionals need training in public engagement and communication, he said, and the culture needs to change so that health care providers feel comfortable speaking out without feeling “the sword of Damocles over their heads” every time they talk to a reporter, Dr. Hotez said.

There may be no silver bullet to solve the big-picture trust problem in medicine and public health. No TV appearance or quote in an article can solve it. But on an individual level — through careful relationship building with patients – doctors can strengthen that trust.

Telehealth may help with that, but there’s a fine balance there, Ms. Nelson cautioned. On the one hand, with the doctor and the patient each in their own private spaces, where they feel safe and comfortable, the overall experience can be more therapeutic and less stressful. At the same time, telehealth can pile on change-management tasks that can exacerbate burnout, “so it’s a delicate thing we have to approach.”

One very thin silver lining that could emerge from the way in which patients have begun to try to take charge of their care.

“They should fully understand the reasoning behind the recommendations that physicians are making,” Ms. Nelson said. “I’d like to see us get to a happy medium where it’s a partnership. We can’t go back to the old school where the doctor knows best and you don’t ever question him.

“What we need is the partnership, and I would love to see that as the silver lining, but the anger has got to settle down in order for that kind of productive thing to happen.”

As for the big picture? There’s a limit to what even society’s “miracle workers” can do. “The biggest priority right now for the health system is to protect their staff whatever way they can and do some training in deescalation,” Ms. Nelson said. “But I don’t think health care can solve the societal issues that seem to be creating this.”

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