Pulmonology

Background: Chronic obstructive pulmonary disease (COPD) is a prevalent condition that is associated with significant mortality, morbidity, and health care utilization. Use of noninvasive positive-pressure ventilation (NIPPV) in acute hypercapnic respiratory failure caused by COPD exacerbations is well established. However, the benefits of in-home NIPPV for COPD with chronic hypercapnia is unclear.

Study design: Systematic review and meta-analysis.

Setting: Multicenter catchment of 21 randomized control trials (RCTs) and 12 observational studies involving more than 51,000 patients during 1995-2019.

Synopsis: Patients included were those with COPD and hypercapnia who used NIPPV for more than 1 month. Home bilevel positive airway pressure (BiPAP), compared to no device use was associated with lower risk of mortality, all-cause hospital admission, and intubation, but no significant difference in quality of life. Noninvasive home mechanical ventilation, compared with no device was significantly associated with lower risk of hospital admission, but not a significant difference in mortality. Of note, there was no statistically significant difference in any outcome for either BiPAP or home mechanical ventilation if evidence was limited to RCTs. Importantly, on rigorous measure, the evidence was low to moderate quality or insufficient, and some outcomes analysis was based on small numbers of studies.

Bottom line: While there is suggestion of benefit on some measures with the use of home NIPPV, the evidence is not robust enough to clearly guide use.

Citation: Wilson et al. Association of home noninvasive positive pressure ventilation with clinical outcomes in chronic obstructive pulmonary disease. JAMA. 2020 Feb 4;323(5):455-65.

Dr. Sneed is assistant professor of medicine, section of hospital medicine, at the University of Virginia School of Medicine, Charlottesville.

Background: Chronic obstructive pulmonary disease (COPD) is a prevalent condition that is associated with significant mortality, morbidity, and health care utilization. Use of noninvasive positive-pressure ventilation (NIPPV) in acute hypercapnic respiratory failure caused by COPD exacerbations is well established. However, the benefits of in-home NIPPV for COPD with chronic hypercapnia is unclear.

Study design: Systematic review and meta-analysis.

Setting: Multicenter catchment of 21 randomized control trials (RCTs) and 12 observational studies involving more than 51,000 patients during 1995-2019.

Synopsis: Patients included were those with COPD and hypercapnia who used NIPPV for more than 1 month. Home bilevel positive airway pressure (BiPAP), compared to no device use was associated with lower risk of mortality, all-cause hospital admission, and intubation, but no significant difference in quality of life. Noninvasive home mechanical ventilation, compared with no device was significantly associated with lower risk of hospital admission, but not a significant difference in mortality. Of note, there was no statistically significant difference in any outcome for either BiPAP or home mechanical ventilation if evidence was limited to RCTs. Importantly, on rigorous measure, the evidence was low to moderate quality or insufficient, and some outcomes analysis was based on small numbers of studies.

Bottom line: While there is suggestion of benefit on some measures with the use of home NIPPV, the evidence is not robust enough to clearly guide use.

Citation: Wilson et al. Association of home noninvasive positive pressure ventilation with clinical outcomes in chronic obstructive pulmonary disease. JAMA. 2020 Feb 4;323(5):455-65.

Dr. Sneed is assistant professor of medicine, section of hospital medicine, at the University of Virginia School of Medicine, Charlottesville.

Background: Chronic obstructive pulmonary disease (COPD) is a prevalent condition that is associated with significant mortality, morbidity, and health care utilization. Use of noninvasive positive-pressure ventilation (NIPPV) in acute hypercapnic respiratory failure caused by COPD exacerbations is well established. However, the benefits of in-home NIPPV for COPD with chronic hypercapnia is unclear.

Study design: Systematic review and meta-analysis.

Setting: Multicenter catchment of 21 randomized control trials (RCTs) and 12 observational studies involving more than 51,000 patients during 1995-2019.

Synopsis: Patients included were those with COPD and hypercapnia who used NIPPV for more than 1 month. Home bilevel positive airway pressure (BiPAP), compared to no device use was associated with lower risk of mortality, all-cause hospital admission, and intubation, but no significant difference in quality of life. Noninvasive home mechanical ventilation, compared with no device was significantly associated with lower risk of hospital admission, but not a significant difference in mortality. Of note, there was no statistically significant difference in any outcome for either BiPAP or home mechanical ventilation if evidence was limited to RCTs. Importantly, on rigorous measure, the evidence was low to moderate quality or insufficient, and some outcomes analysis was based on small numbers of studies.

Bottom line: While there is suggestion of benefit on some measures with the use of home NIPPV, the evidence is not robust enough to clearly guide use.

Citation: Wilson et al. Association of home noninvasive positive pressure ventilation with clinical outcomes in chronic obstructive pulmonary disease. JAMA. 2020 Feb 4;323(5):455-65.

Dr. Sneed is assistant professor of medicine, section of hospital medicine, at the University of Virginia School of Medicine, Charlottesville.

Reducing exposure to air pollution may slow brain aging and reduce the risk of dementia, new research reveals. The findings have implications for individual behaviors, such as avoiding areas with poor air quality, but they also have implications for public policy, said study investigator, Xinhui Wang, PhD, assistant professor of research neurology, department of neurology, University of Southern California, Los Angeles.

“Controlling air quality has great benefits not only for the short-term, for example for pulmonary function or very broadly mortality, but can impact brain function and slow memory function decline and in the long run may reduce dementia cases.”

The findings were presented at the 2021 Alzheimer’s Association International Conference.
 

New approach

Previous research examining the impact of reducing air pollution, which has primarily examined respiratory illnesses and mortality, showed it is beneficial. However, no previous studies have examined the impact of improved air quality on cognitive function.

The current study used a subset of participants from the Women’s Health Initiative Memory Study-Epidemiology of Cognitive Health Outcomes (WHIMS-ECHO), which evaluated whether postmenopausal women derive cognitive benefit from hormone therapy.

The analysis included 2,232 community-dwelling older women aged 74-92 (mean age, 81.5 years) who did not have dementia at study enrollment.

Researchers obtained measures of participants’ annual cognitive function from 2008 to 2018. These measures included general cognitive status assessed using the Telephone Interview for Cognitive Status-modified (TICSm) and episodic memory assessed by the telephone-based California Verbal Learning Test (CVLT).

The investigators used complex geographical covariates to estimate exposure to fine particulate matter (PM_2.5) and nitrogen dioxide (NO₂), in areas where individual participants lived from 1996 to 2012. The investigators averaged measures over 3-year periods immediately preceding (recent exposure) and 10 years prior to (remote exposure) enrollment, then calculated individual-level improvements in air quality as the reduction from remote to recent exposures.

The researchers examined pollution exposure and cognitive outcomes at different times to determine causation.

“Maybe the relationship isn’t causal and is just an association, so we tried to separate the timeframe for exposure and outcome and make sure the exposure was before we measured the outcome,” said Dr. Wang.

The investigators adjusted for multiple sociodemographic, lifestyle, and clinical characteristics.
 

Reduced dementia risk

The analysis showed air quality improved significantly for both PM_2.5 and NO₂ before study enrollment. “For almost 95% of the subjects in our study, air quality improved over the 10 years,” said Dr. Wang.

During a median follow-up of 6.2 years, there was a significant decline in cognitive status and episodic memory in study participants, which makes sense, said Dr. Wang, because cognitive function naturally declines with age.

However, a 10% improvement in air quality PM_2.5 and NO₂ resulted in a respective 14% and 26% decreased risk for dementia. This translates into a level of risk seen in women 2 to 3 years younger.

Greater air quality improvement was associated with slower decline in both general cognitive status and episodic memory.

“Participants all declined in cognitive function, but living in areas with the greatest air quality improvement slowed this decline,” said Dr. Wang.

“Whether you look at global cognitive function or memory-specific function, and whether you look at PM_2.5 or NO₂, slower decline was in the range of someone who is 1-2 years younger.”

The associations did not significantly differ by age, region, education, APOE ε4 genotypes, or cardiovascular risk factors.

Patients concerned about cognitive decline can take steps to avoid exposure to pollution by wearing a mask; avoiding heavy traffic, fires, and smoke; or moving to an area with better air quality, said Dr. Wang.

“But our study mainly tried to provide some evidence for policymakers and regulators,” she added.

Another study carried out by the same investigators suggests pollution may affect various cognitive functions differently. This analysis used the same cohort, timeframe, and air quality improvement indicators as the first study but examined the association with specific cognitive domains, including episodic memory, working memory, attention/executive function, and language.

The investigators found women living in locations with greater PM_2.5 improvement performed better on tests of episodic memory (P = .002), working memory (P = .01) and attention/executive function (P = .01), but not language. Findings were similar for improved NO₂.

When looking at air quality improvement and trajectory slopes of decline across cognitive functions, only the association between improved NO₂ and slower episodic memory decline was statistically significant (P < 0.001). “The other domains were marginal or not significant,” said Dr. Wang.

“This suggests that brain regions are impacted differently,” she said, adding that various brain areas oversee different cognitive functions.
 

Important policy implications

Commenting on the research, Rebecca Edelmayer, PhD, senior director of scientific engagement, Alzheimer’s Association, said she welcomes new research on environmental factors that affect Alzheimer’s disease.

Whereas previous studies have linked longterm air pollution exposure to accumulation of Alzheimer’s disease-related brain plaques and increased risk of dementia, “these newer studies provide some of the first evidence to suggest that actually reducing pollution is associated with lower risk of all-cause dementia,” said Dr. Edelmayer.

Individuals can control some factors that contribute to dementia risk, such as exercise, diet, and physical activity, but it’s more difficult for them to control exposure to smog and pollution, she said.

“This is probably going to require changes to policy from federal and local governments and businesses, to start addressing the need to improve air quality to help reduce risk for dementia.”

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

Reducing exposure to air pollution may slow brain aging and reduce the risk of dementia, new research reveals. The findings have implications for individual behaviors, such as avoiding areas with poor air quality, but they also have implications for public policy, said study investigator, Xinhui Wang, PhD, assistant professor of research neurology, department of neurology, University of Southern California, Los Angeles.

“Controlling air quality has great benefits not only for the short-term, for example for pulmonary function or very broadly mortality, but can impact brain function and slow memory function decline and in the long run may reduce dementia cases.”

The findings were presented at the 2021 Alzheimer’s Association International Conference.
 

New approach

Previous research examining the impact of reducing air pollution, which has primarily examined respiratory illnesses and mortality, showed it is beneficial. However, no previous studies have examined the impact of improved air quality on cognitive function.

The current study used a subset of participants from the Women’s Health Initiative Memory Study-Epidemiology of Cognitive Health Outcomes (WHIMS-ECHO), which evaluated whether postmenopausal women derive cognitive benefit from hormone therapy.

The analysis included 2,232 community-dwelling older women aged 74-92 (mean age, 81.5 years) who did not have dementia at study enrollment.

Researchers obtained measures of participants’ annual cognitive function from 2008 to 2018. These measures included general cognitive status assessed using the Telephone Interview for Cognitive Status-modified (TICSm) and episodic memory assessed by the telephone-based California Verbal Learning Test (CVLT).

The investigators used complex geographical covariates to estimate exposure to fine particulate matter (PM_2.5) and nitrogen dioxide (NO₂), in areas where individual participants lived from 1996 to 2012. The investigators averaged measures over 3-year periods immediately preceding (recent exposure) and 10 years prior to (remote exposure) enrollment, then calculated individual-level improvements in air quality as the reduction from remote to recent exposures.

The researchers examined pollution exposure and cognitive outcomes at different times to determine causation.

“Maybe the relationship isn’t causal and is just an association, so we tried to separate the timeframe for exposure and outcome and make sure the exposure was before we measured the outcome,” said Dr. Wang.

The investigators adjusted for multiple sociodemographic, lifestyle, and clinical characteristics.
 

Reduced dementia risk

The analysis showed air quality improved significantly for both PM_2.5 and NO₂ before study enrollment. “For almost 95% of the subjects in our study, air quality improved over the 10 years,” said Dr. Wang.

During a median follow-up of 6.2 years, there was a significant decline in cognitive status and episodic memory in study participants, which makes sense, said Dr. Wang, because cognitive function naturally declines with age.

However, a 10% improvement in air quality PM_2.5 and NO₂ resulted in a respective 14% and 26% decreased risk for dementia. This translates into a level of risk seen in women 2 to 3 years younger.

Greater air quality improvement was associated with slower decline in both general cognitive status and episodic memory.

“Participants all declined in cognitive function, but living in areas with the greatest air quality improvement slowed this decline,” said Dr. Wang.

“Whether you look at global cognitive function or memory-specific function, and whether you look at PM_2.5 or NO₂, slower decline was in the range of someone who is 1-2 years younger.”

The associations did not significantly differ by age, region, education, APOE ε4 genotypes, or cardiovascular risk factors.

Patients concerned about cognitive decline can take steps to avoid exposure to pollution by wearing a mask; avoiding heavy traffic, fires, and smoke; or moving to an area with better air quality, said Dr. Wang.

“But our study mainly tried to provide some evidence for policymakers and regulators,” she added.

Another study carried out by the same investigators suggests pollution may affect various cognitive functions differently. This analysis used the same cohort, timeframe, and air quality improvement indicators as the first study but examined the association with specific cognitive domains, including episodic memory, working memory, attention/executive function, and language.

The investigators found women living in locations with greater PM_2.5 improvement performed better on tests of episodic memory (P = .002), working memory (P = .01) and attention/executive function (P = .01), but not language. Findings were similar for improved NO₂.

When looking at air quality improvement and trajectory slopes of decline across cognitive functions, only the association between improved NO₂ and slower episodic memory decline was statistically significant (P < 0.001). “The other domains were marginal or not significant,” said Dr. Wang.

“This suggests that brain regions are impacted differently,” she said, adding that various brain areas oversee different cognitive functions.
 

Important policy implications

Commenting on the research, Rebecca Edelmayer, PhD, senior director of scientific engagement, Alzheimer’s Association, said she welcomes new research on environmental factors that affect Alzheimer’s disease.

Whereas previous studies have linked longterm air pollution exposure to accumulation of Alzheimer’s disease-related brain plaques and increased risk of dementia, “these newer studies provide some of the first evidence to suggest that actually reducing pollution is associated with lower risk of all-cause dementia,” said Dr. Edelmayer.

Individuals can control some factors that contribute to dementia risk, such as exercise, diet, and physical activity, but it’s more difficult for them to control exposure to smog and pollution, she said.

“This is probably going to require changes to policy from federal and local governments and businesses, to start addressing the need to improve air quality to help reduce risk for dementia.”

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

Reducing exposure to air pollution may slow brain aging and reduce the risk of dementia, new research reveals. The findings have implications for individual behaviors, such as avoiding areas with poor air quality, but they also have implications for public policy, said study investigator, Xinhui Wang, PhD, assistant professor of research neurology, department of neurology, University of Southern California, Los Angeles.

“Controlling air quality has great benefits not only for the short-term, for example for pulmonary function or very broadly mortality, but can impact brain function and slow memory function decline and in the long run may reduce dementia cases.”

The findings were presented at the 2021 Alzheimer’s Association International Conference.
 

New approach

Previous research examining the impact of reducing air pollution, which has primarily examined respiratory illnesses and mortality, showed it is beneficial. However, no previous studies have examined the impact of improved air quality on cognitive function.

The current study used a subset of participants from the Women’s Health Initiative Memory Study-Epidemiology of Cognitive Health Outcomes (WHIMS-ECHO), which evaluated whether postmenopausal women derive cognitive benefit from hormone therapy.

The analysis included 2,232 community-dwelling older women aged 74-92 (mean age, 81.5 years) who did not have dementia at study enrollment.

Researchers obtained measures of participants’ annual cognitive function from 2008 to 2018. These measures included general cognitive status assessed using the Telephone Interview for Cognitive Status-modified (TICSm) and episodic memory assessed by the telephone-based California Verbal Learning Test (CVLT).

The investigators used complex geographical covariates to estimate exposure to fine particulate matter (PM_2.5) and nitrogen dioxide (NO₂), in areas where individual participants lived from 1996 to 2012. The investigators averaged measures over 3-year periods immediately preceding (recent exposure) and 10 years prior to (remote exposure) enrollment, then calculated individual-level improvements in air quality as the reduction from remote to recent exposures.

The researchers examined pollution exposure and cognitive outcomes at different times to determine causation.

“Maybe the relationship isn’t causal and is just an association, so we tried to separate the timeframe for exposure and outcome and make sure the exposure was before we measured the outcome,” said Dr. Wang.

The investigators adjusted for multiple sociodemographic, lifestyle, and clinical characteristics.
 

Reduced dementia risk

The analysis showed air quality improved significantly for both PM_2.5 and NO₂ before study enrollment. “For almost 95% of the subjects in our study, air quality improved over the 10 years,” said Dr. Wang.

During a median follow-up of 6.2 years, there was a significant decline in cognitive status and episodic memory in study participants, which makes sense, said Dr. Wang, because cognitive function naturally declines with age.

However, a 10% improvement in air quality PM_2.5 and NO₂ resulted in a respective 14% and 26% decreased risk for dementia. This translates into a level of risk seen in women 2 to 3 years younger.

Greater air quality improvement was associated with slower decline in both general cognitive status and episodic memory.

“Participants all declined in cognitive function, but living in areas with the greatest air quality improvement slowed this decline,” said Dr. Wang.

“Whether you look at global cognitive function or memory-specific function, and whether you look at PM_2.5 or NO₂, slower decline was in the range of someone who is 1-2 years younger.”

The associations did not significantly differ by age, region, education, APOE ε4 genotypes, or cardiovascular risk factors.

Patients concerned about cognitive decline can take steps to avoid exposure to pollution by wearing a mask; avoiding heavy traffic, fires, and smoke; or moving to an area with better air quality, said Dr. Wang.

“But our study mainly tried to provide some evidence for policymakers and regulators,” she added.

Another study carried out by the same investigators suggests pollution may affect various cognitive functions differently. This analysis used the same cohort, timeframe, and air quality improvement indicators as the first study but examined the association with specific cognitive domains, including episodic memory, working memory, attention/executive function, and language.

The investigators found women living in locations with greater PM_2.5 improvement performed better on tests of episodic memory (P = .002), working memory (P = .01) and attention/executive function (P = .01), but not language. Findings were similar for improved NO₂.

When looking at air quality improvement and trajectory slopes of decline across cognitive functions, only the association between improved NO₂ and slower episodic memory decline was statistically significant (P < 0.001). “The other domains were marginal or not significant,” said Dr. Wang.

“This suggests that brain regions are impacted differently,” she said, adding that various brain areas oversee different cognitive functions.
 

Important policy implications

Commenting on the research, Rebecca Edelmayer, PhD, senior director of scientific engagement, Alzheimer’s Association, said she welcomes new research on environmental factors that affect Alzheimer’s disease.

Whereas previous studies have linked longterm air pollution exposure to accumulation of Alzheimer’s disease-related brain plaques and increased risk of dementia, “these newer studies provide some of the first evidence to suggest that actually reducing pollution is associated with lower risk of all-cause dementia,” said Dr. Edelmayer.

Individuals can control some factors that contribute to dementia risk, such as exercise, diet, and physical activity, but it’s more difficult for them to control exposure to smog and pollution, she said.

“This is probably going to require changes to policy from federal and local governments and businesses, to start addressing the need to improve air quality to help reduce risk for dementia.”

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

Background: Empirical broad-spectrum antibiotics including anti-MRSA therapy are often selected because of concerns for resistant organisms. However, the outcomes of empirical anti-MRSA therapy among patients with pneumonia are unknown.

Dr. Li is assistant professor of medicine, section of hospital medicine, at the University of Virginia School of Medicine, Charlottesville.

Background: Empirical broad-spectrum antibiotics including anti-MRSA therapy are often selected because of concerns for resistant organisms. However, the outcomes of empirical anti-MRSA therapy among patients with pneumonia are unknown.

Dr. Li is assistant professor of medicine, section of hospital medicine, at the University of Virginia School of Medicine, Charlottesville.

Background: Empirical broad-spectrum antibiotics including anti-MRSA therapy are often selected because of concerns for resistant organisms. However, the outcomes of empirical anti-MRSA therapy among patients with pneumonia are unknown.

Dr. Li is assistant professor of medicine, section of hospital medicine, at the University of Virginia School of Medicine, Charlottesville.

People hospitalized with acute COVID-19 who developed acute severe respiratory distress syndrome (ARDS) had poorer exercise capacity, health-related quality of life, and overall health than the general population a median of 8 months after initial COVID diagnosis, according to a prospective cohort study.

Findings from the cohort, composed of 113 COVID-19 survivors who developed ARDS after admission to a single center before to April 16, 2020, were presented online at the 31st European Congress of Clinical Microbiology & Infectious Diseases by Judit Aranda, MD, from Complex Hospitalari Moisés Broggi in Barcelona.

Median age of the participants was 64 years, and 70% were male. At least one persistent symptom was experienced during follow-up by 81% of the cohort, with 45% reporting shortness of breath, 50% reporting muscle pain, 43% reporting memory impairment, and 46% reporting physical weakness of at least 5 on a 10-point scale.

Of the 104 participants who completed a 6-minute walk test, 30% had a decrease in oxygen saturation level of at least 4%, and 5% had an initial or final level below 88%. Of the 46 participants who underwent a pulmonary function test, 15% had a forced expiratory volume in 1 second below 70%.

And of the 49% of participants with pathologic findings on chest x-ray, most were bilateral interstitial infiltrates (88%).

In addition, more than 90% of participants developed depression, anxiety, or PTSD, Dr. Aranda reported.
 

Not the whole picture

This study shows that sicker people – “those in intensive care units with acute respiratory distress syndrome” – are “more likely to be struggling with more severe symptoms,” said Christopher Terndrup, MD, from the division of general internal medicine and geriatrics at Oregon Health & Science University, Portland.

But a Swiss study, also presented at the meeting, “shows how even mild COVID cases can lead to debilitating symptoms,” Dr. Terndrup said in an interview.

The investigation of long-term COVID symptoms in outpatients was presented online by Florian Desgranges, MD, from Lausanne (Switzerland) University Hospital. He and his colleagues found that more than half of those with a mild to moderate disease had persistent symptoms at least 3 months after diagnosis.

The prevalence of long COVID has varied in previous research, from 15% in a study of health care workers, to 46% in a study of patients with mild COVID, 52% in a study of young COVID outpatients, and 76% in a study of patients hospitalized with COVID.

Dr. Desgranges and colleagues evaluated patients seen in an ED or outpatient clinic from February to April 2020.

The 418 patients with a confirmed COVID-19 diagnosis were compared with a control group of 89 patients who presented to the same centers during the same time frame with similar symptoms – cough, shortness of breath, or fever – but had a negative SARS-CoV-2 test.

The number of patients with comorbidities was similar in the COVID and control groups (34% vs. 36%), as was median age (41 vs. 36 years) and the prevalence of women (62% vs 64%), but the proportion of health care workers was lower in the COVID group (64% vs 82%; P =.006).

Symptoms that persisted for at least 3 months were more common in the COVID than in the control group (53% vs. 37%). And patients in the COVID group reported more symptoms than those in the control group after adjustment for age, gender, smoking status, comorbidities, and timing of the survey phone call.

Levels of sleeping problems and headache were similar in the two groups.

“We have to remember that with COVID-19 came the psychosocial changes of the pandemic situation” Dr. Desgranges said.

This study suggests that some long-COVID symptoms – such as the fatigue, headache, and sleep disorders reported in the control group – could be related to the pandemic itself, which has caused psychosocial distress, Dr. Terndrup said.

Another study that looked at outpatients “has some fantastic long-term follow-up data, and shows that many patients are still engaging in rehabilitation programs nearly a year after their diagnosis,” he explained.
 

The COVID HOME study

That prospective longitudinal COVID HOME study, which assessed long-term symptoms in people who were never hospitalized for COVID, was presented online by Adriana Tami, MD, PhD, from the University Medical Center Groningen (the Netherlands).

The researchers visited the homes of patients to collect data, blood samples, and perform polymerase chain reaction (PCR) testing 1, 2, and 3 weeks after a diagnosis of COVID-19. If their PCR test was still positive, testing continued until week 6 or a negative test. In addition, participants completed questionnaires at week 2 and at months 3, 6 and 12 to assess fatigue, quality of life, and symptoms of depression and anxiety.

Three-month follow-up data were available for 134 of the 276 people initially enrolled in the study. Questionnaires were completed by 85 participants at 3 months, 62 participants at 6 months, and 10 participants at 12 months.

At least 40% of participants reported long-lasting symptoms at some point during follow-up, and at least 30% said they didn’t feel fully recovered at 12 months. The most common symptom was persistent fatigue, reported at 3, 6, and 12 months by at least 44% of participants. Other common symptoms – reported by at least 20% of respondents at 3, 6, and 12 months – were headache, mental or neurologic symptoms, and sleep disorders, shortness of breath, lack of smell or taste, and severe fatigue.

“We have a high proportion of nonhospitalized individuals who suffer from long COVID after more than 12 months,” Dr. Tami concluded, adding that the study is ongoing. “We have other variables that we want to look at, including duration viral shedding and serological results and variants.”

“These cohort studies are very helpful, but they can lead to inaccurate conclusions,” Dr. Terndrup cautioned.

They only provide pieces of the big picture, but they “do add to a growing body of knowledge about a significant portion of COVID patients still struggling with symptoms long after their initial infection. The symptoms can be quite variable but are dominated by both physical and mental fatigue, and tend to be worse in patients who were sicker at initial infection,” he said in an interview.

As a whole, these studies reinforce the need for treatment programs to help patients who suffer from long COVID, he added, but “I advise caution to folks suffering out there who seek ‘miracle cures’; across the world, we are collaborating to find solutions that are safe and effective.”

We are in desperate need of an equity lens in these studies.

“There is still a great deal to learn about long COVID,” said Dr. Terndrup. Data on underrepresented populations – such as Black, Indigenous, and people of color – are lacking from these and others studies, he explained. “We are in desperate need of an equity lens in these studies,” particularly in the United States, where there are “significant disparities” in the treatment of different populations.

However, “I do hope that this work can lead to a better understanding of how other viral infections can cause long-lasting symptoms,” said Dr. Terndrup.

“We have long proposed that after acute presentation, some microbes can cause chronic symptoms, like fatigue and widespread pain. Perhaps we can learn how to better care for these patients after learning from COVID’s significant impact on our societies across the globe.”

Dr. Aranda and Dr. Desgranges have disclosed no relevant financial relationships or study funding. The study by Dr. Tami’s team was funded by the University Medical Center Groningen Organization for Health Research and Development, and Connecting European Cohorts to Increase Common and Effective Response to SARS-CoV-2 Pandemic. Dr. Terndrup disclosed no relevant financial relationships.

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

People hospitalized with acute COVID-19 who developed acute severe respiratory distress syndrome (ARDS) had poorer exercise capacity, health-related quality of life, and overall health than the general population a median of 8 months after initial COVID diagnosis, according to a prospective cohort study.

Findings from the cohort, composed of 113 COVID-19 survivors who developed ARDS after admission to a single center before to April 16, 2020, were presented online at the 31st European Congress of Clinical Microbiology & Infectious Diseases by Judit Aranda, MD, from Complex Hospitalari Moisés Broggi in Barcelona.

Median age of the participants was 64 years, and 70% were male. At least one persistent symptom was experienced during follow-up by 81% of the cohort, with 45% reporting shortness of breath, 50% reporting muscle pain, 43% reporting memory impairment, and 46% reporting physical weakness of at least 5 on a 10-point scale.

Of the 104 participants who completed a 6-minute walk test, 30% had a decrease in oxygen saturation level of at least 4%, and 5% had an initial or final level below 88%. Of the 46 participants who underwent a pulmonary function test, 15% had a forced expiratory volume in 1 second below 70%.

And of the 49% of participants with pathologic findings on chest x-ray, most were bilateral interstitial infiltrates (88%).

In addition, more than 90% of participants developed depression, anxiety, or PTSD, Dr. Aranda reported.
 

Not the whole picture

This study shows that sicker people – “those in intensive care units with acute respiratory distress syndrome” – are “more likely to be struggling with more severe symptoms,” said Christopher Terndrup, MD, from the division of general internal medicine and geriatrics at Oregon Health & Science University, Portland.

But a Swiss study, also presented at the meeting, “shows how even mild COVID cases can lead to debilitating symptoms,” Dr. Terndrup said in an interview.

The investigation of long-term COVID symptoms in outpatients was presented online by Florian Desgranges, MD, from Lausanne (Switzerland) University Hospital. He and his colleagues found that more than half of those with a mild to moderate disease had persistent symptoms at least 3 months after diagnosis.

The prevalence of long COVID has varied in previous research, from 15% in a study of health care workers, to 46% in a study of patients with mild COVID, 52% in a study of young COVID outpatients, and 76% in a study of patients hospitalized with COVID.

Dr. Desgranges and colleagues evaluated patients seen in an ED or outpatient clinic from February to April 2020.

The 418 patients with a confirmed COVID-19 diagnosis were compared with a control group of 89 patients who presented to the same centers during the same time frame with similar symptoms – cough, shortness of breath, or fever – but had a negative SARS-CoV-2 test.

The number of patients with comorbidities was similar in the COVID and control groups (34% vs. 36%), as was median age (41 vs. 36 years) and the prevalence of women (62% vs 64%), but the proportion of health care workers was lower in the COVID group (64% vs 82%; P =.006).

Symptoms that persisted for at least 3 months were more common in the COVID than in the control group (53% vs. 37%). And patients in the COVID group reported more symptoms than those in the control group after adjustment for age, gender, smoking status, comorbidities, and timing of the survey phone call.

Levels of sleeping problems and headache were similar in the two groups.

“We have to remember that with COVID-19 came the psychosocial changes of the pandemic situation” Dr. Desgranges said.

This study suggests that some long-COVID symptoms – such as the fatigue, headache, and sleep disorders reported in the control group – could be related to the pandemic itself, which has caused psychosocial distress, Dr. Terndrup said.

Another study that looked at outpatients “has some fantastic long-term follow-up data, and shows that many patients are still engaging in rehabilitation programs nearly a year after their diagnosis,” he explained.
 

The COVID HOME study

That prospective longitudinal COVID HOME study, which assessed long-term symptoms in people who were never hospitalized for COVID, was presented online by Adriana Tami, MD, PhD, from the University Medical Center Groningen (the Netherlands).

The researchers visited the homes of patients to collect data, blood samples, and perform polymerase chain reaction (PCR) testing 1, 2, and 3 weeks after a diagnosis of COVID-19. If their PCR test was still positive, testing continued until week 6 or a negative test. In addition, participants completed questionnaires at week 2 and at months 3, 6 and 12 to assess fatigue, quality of life, and symptoms of depression and anxiety.

Three-month follow-up data were available for 134 of the 276 people initially enrolled in the study. Questionnaires were completed by 85 participants at 3 months, 62 participants at 6 months, and 10 participants at 12 months.

At least 40% of participants reported long-lasting symptoms at some point during follow-up, and at least 30% said they didn’t feel fully recovered at 12 months. The most common symptom was persistent fatigue, reported at 3, 6, and 12 months by at least 44% of participants. Other common symptoms – reported by at least 20% of respondents at 3, 6, and 12 months – were headache, mental or neurologic symptoms, and sleep disorders, shortness of breath, lack of smell or taste, and severe fatigue.

“We have a high proportion of nonhospitalized individuals who suffer from long COVID after more than 12 months,” Dr. Tami concluded, adding that the study is ongoing. “We have other variables that we want to look at, including duration viral shedding and serological results and variants.”

“These cohort studies are very helpful, but they can lead to inaccurate conclusions,” Dr. Terndrup cautioned.

They only provide pieces of the big picture, but they “do add to a growing body of knowledge about a significant portion of COVID patients still struggling with symptoms long after their initial infection. The symptoms can be quite variable but are dominated by both physical and mental fatigue, and tend to be worse in patients who were sicker at initial infection,” he said in an interview.

As a whole, these studies reinforce the need for treatment programs to help patients who suffer from long COVID, he added, but “I advise caution to folks suffering out there who seek ‘miracle cures’; across the world, we are collaborating to find solutions that are safe and effective.”

We are in desperate need of an equity lens in these studies.

“There is still a great deal to learn about long COVID,” said Dr. Terndrup. Data on underrepresented populations – such as Black, Indigenous, and people of color – are lacking from these and others studies, he explained. “We are in desperate need of an equity lens in these studies,” particularly in the United States, where there are “significant disparities” in the treatment of different populations.

However, “I do hope that this work can lead to a better understanding of how other viral infections can cause long-lasting symptoms,” said Dr. Terndrup.

“We have long proposed that after acute presentation, some microbes can cause chronic symptoms, like fatigue and widespread pain. Perhaps we can learn how to better care for these patients after learning from COVID’s significant impact on our societies across the globe.”

Dr. Aranda and Dr. Desgranges have disclosed no relevant financial relationships or study funding. The study by Dr. Tami’s team was funded by the University Medical Center Groningen Organization for Health Research and Development, and Connecting European Cohorts to Increase Common and Effective Response to SARS-CoV-2 Pandemic. Dr. Terndrup disclosed no relevant financial relationships.

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

People hospitalized with acute COVID-19 who developed acute severe respiratory distress syndrome (ARDS) had poorer exercise capacity, health-related quality of life, and overall health than the general population a median of 8 months after initial COVID diagnosis, according to a prospective cohort study.

Findings from the cohort, composed of 113 COVID-19 survivors who developed ARDS after admission to a single center before to April 16, 2020, were presented online at the 31st European Congress of Clinical Microbiology & Infectious Diseases by Judit Aranda, MD, from Complex Hospitalari Moisés Broggi in Barcelona.

Median age of the participants was 64 years, and 70% were male. At least one persistent symptom was experienced during follow-up by 81% of the cohort, with 45% reporting shortness of breath, 50% reporting muscle pain, 43% reporting memory impairment, and 46% reporting physical weakness of at least 5 on a 10-point scale.

Of the 104 participants who completed a 6-minute walk test, 30% had a decrease in oxygen saturation level of at least 4%, and 5% had an initial or final level below 88%. Of the 46 participants who underwent a pulmonary function test, 15% had a forced expiratory volume in 1 second below 70%.

And of the 49% of participants with pathologic findings on chest x-ray, most were bilateral interstitial infiltrates (88%).

In addition, more than 90% of participants developed depression, anxiety, or PTSD, Dr. Aranda reported.
 

Not the whole picture

This study shows that sicker people – “those in intensive care units with acute respiratory distress syndrome” – are “more likely to be struggling with more severe symptoms,” said Christopher Terndrup, MD, from the division of general internal medicine and geriatrics at Oregon Health & Science University, Portland.

But a Swiss study, also presented at the meeting, “shows how even mild COVID cases can lead to debilitating symptoms,” Dr. Terndrup said in an interview.

The investigation of long-term COVID symptoms in outpatients was presented online by Florian Desgranges, MD, from Lausanne (Switzerland) University Hospital. He and his colleagues found that more than half of those with a mild to moderate disease had persistent symptoms at least 3 months after diagnosis.

The prevalence of long COVID has varied in previous research, from 15% in a study of health care workers, to 46% in a study of patients with mild COVID, 52% in a study of young COVID outpatients, and 76% in a study of patients hospitalized with COVID.

Dr. Desgranges and colleagues evaluated patients seen in an ED or outpatient clinic from February to April 2020.

The 418 patients with a confirmed COVID-19 diagnosis were compared with a control group of 89 patients who presented to the same centers during the same time frame with similar symptoms – cough, shortness of breath, or fever – but had a negative SARS-CoV-2 test.

The number of patients with comorbidities was similar in the COVID and control groups (34% vs. 36%), as was median age (41 vs. 36 years) and the prevalence of women (62% vs 64%), but the proportion of health care workers was lower in the COVID group (64% vs 82%; P =.006).

Symptoms that persisted for at least 3 months were more common in the COVID than in the control group (53% vs. 37%). And patients in the COVID group reported more symptoms than those in the control group after adjustment for age, gender, smoking status, comorbidities, and timing of the survey phone call.

Levels of sleeping problems and headache were similar in the two groups.

“We have to remember that with COVID-19 came the psychosocial changes of the pandemic situation” Dr. Desgranges said.

This study suggests that some long-COVID symptoms – such as the fatigue, headache, and sleep disorders reported in the control group – could be related to the pandemic itself, which has caused psychosocial distress, Dr. Terndrup said.

Another study that looked at outpatients “has some fantastic long-term follow-up data, and shows that many patients are still engaging in rehabilitation programs nearly a year after their diagnosis,” he explained.
 

The COVID HOME study

That prospective longitudinal COVID HOME study, which assessed long-term symptoms in people who were never hospitalized for COVID, was presented online by Adriana Tami, MD, PhD, from the University Medical Center Groningen (the Netherlands).

The researchers visited the homes of patients to collect data, blood samples, and perform polymerase chain reaction (PCR) testing 1, 2, and 3 weeks after a diagnosis of COVID-19. If their PCR test was still positive, testing continued until week 6 or a negative test. In addition, participants completed questionnaires at week 2 and at months 3, 6 and 12 to assess fatigue, quality of life, and symptoms of depression and anxiety.

Three-month follow-up data were available for 134 of the 276 people initially enrolled in the study. Questionnaires were completed by 85 participants at 3 months, 62 participants at 6 months, and 10 participants at 12 months.

At least 40% of participants reported long-lasting symptoms at some point during follow-up, and at least 30% said they didn’t feel fully recovered at 12 months. The most common symptom was persistent fatigue, reported at 3, 6, and 12 months by at least 44% of participants. Other common symptoms – reported by at least 20% of respondents at 3, 6, and 12 months – were headache, mental or neurologic symptoms, and sleep disorders, shortness of breath, lack of smell or taste, and severe fatigue.

“We have a high proportion of nonhospitalized individuals who suffer from long COVID after more than 12 months,” Dr. Tami concluded, adding that the study is ongoing. “We have other variables that we want to look at, including duration viral shedding and serological results and variants.”

“These cohort studies are very helpful, but they can lead to inaccurate conclusions,” Dr. Terndrup cautioned.

They only provide pieces of the big picture, but they “do add to a growing body of knowledge about a significant portion of COVID patients still struggling with symptoms long after their initial infection. The symptoms can be quite variable but are dominated by both physical and mental fatigue, and tend to be worse in patients who were sicker at initial infection,” he said in an interview.

As a whole, these studies reinforce the need for treatment programs to help patients who suffer from long COVID, he added, but “I advise caution to folks suffering out there who seek ‘miracle cures’; across the world, we are collaborating to find solutions that are safe and effective.”

We are in desperate need of an equity lens in these studies.

“There is still a great deal to learn about long COVID,” said Dr. Terndrup. Data on underrepresented populations – such as Black, Indigenous, and people of color – are lacking from these and others studies, he explained. “We are in desperate need of an equity lens in these studies,” particularly in the United States, where there are “significant disparities” in the treatment of different populations.

However, “I do hope that this work can lead to a better understanding of how other viral infections can cause long-lasting symptoms,” said Dr. Terndrup.

“We have long proposed that after acute presentation, some microbes can cause chronic symptoms, like fatigue and widespread pain. Perhaps we can learn how to better care for these patients after learning from COVID’s significant impact on our societies across the globe.”

Dr. Aranda and Dr. Desgranges have disclosed no relevant financial relationships or study funding. The study by Dr. Tami’s team was funded by the University Medical Center Groningen Organization for Health Research and Development, and Connecting European Cohorts to Increase Common and Effective Response to SARS-CoV-2 Pandemic. Dr. Terndrup disclosed no relevant financial relationships.

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

Lower doses of linezolid in the BPaL drug regimen (bedaquiline, pretomanid, and linezolid) significantly reduce the adverse events associated with the treatment for patients with highly drug-resistant tuberculosis (TB) without compromising its high efficacy, new research shows.

“The ZeNix trial shows that reduced doses and/or shorter durations of linezolid appear to have high efficacy and improved safety,” said first author Francesca Conradie, MB, BCh, of the clinical HIV research unit, faculty of health sciences, University of Witwatersrand, Johannesburg, South Africa, in presenting the findings at the virtual meeting of the International AIDS Society conference.

As recently reported in the pivotal Nix-TB trial, the BPaL regimen yielded a 90% treatment success rate among people with highly drug-resistant forms of TB.

However, a 6-month regimen that included linezolid 1,200 mg resulted in toxic effects: 81% of patients in the study experienced peripheral neuropathy, and myelosuppression occurred in 48%. These effects often led to dose reductions or treatment interruption.

Adjustments in the dose of linezolid in the new ZeNix trial substantially reduced peripheral neuropathy to 13% and myelosuppression to 7%, with no significant reduction in the treatment response.

Importantly, the results were similar among patients with and those without HIV. This is of note because TB is the leading cause of death among patients with HIV.

“In the ZeNix trial, only 20% of patients were HIV infected, but in the [previous] Nix-TB trial, 30% were infected, so we have experience now in about 70 patients who were infected, and the outcomes were no different,” Dr. Conradie said in an interview.

Experts say the findings represent an important turn in the steep challenge of tackling highly resistant TB.

“In our opinion, these are exciting results that could change treatment guidelines for highly drug-resistant tuberculosis, with real benefits for the patients,” said Hendrik Streeck, MD, International AIDS Society cochair and director of the Institute of Virology and the Institute for HIV Research at the University Bonn (Germany), in a press conference.

Payam Nahid, MD, MPH, director of the Center for Tuberculosis at theUniversity of California, San Francisco, agreed.

“The results of this trial will impact global practices in treating drug-resistant TB as well as the design and conduct of future TB clinical trials,” Dr. Nahid said in an interview.
 

ZeNix trial

The phase 3 ZeNix trial included 181 patients with highly resistant TB in South Africa, Russia, Georgia, and Moldova. The mean age of the patients was 37 years; 67.4% were men, 63.5% were White, and 19.9% were HIV positive.

All patients were treated for 6 months with bedaquiline 200 mg daily for 8 weeks followed by 100 mg daily for 18 weeks, as well as pretomanid 200 mg daily.

The patients were randomly assigned to receive one of four daily doses of linezolid: 1,200 mg for 6 months (the original dose from the Nix-TB trial; n = 45) or 2 months (n = 46), or 600 mg for 6 or 2 months (45 patients each).

Percentages of patients with HIV were equal among the four groups, at about 20% each.

The primary outcomes – resolution of clinical disease and a negative culture status after 6 months – were observed across all linezolid dose groups. The success rate was 93% for those receiving 1,200 mg for 6 months, 89% for those receiving 1,200 mg for 2 months, 91% for those receiving 600 mg for 6 months, and 84% for those receiving 600 mg for 2 months.

With regard to the key adverse events of peripheral neuropathy and myelosuppression, manifested as anemia, the highest rates were among those who received linezolid 1,200 mg for 6 month, at 38% and 22%, respectively, compared with 24% and 17.4% among those who received 1,200 mg for 2 months, 24% and 2% among those who received 600 mg for 6 months, and 13% and 6.7% among those who received 600 mg for 2 months.

Four cases of optic neuropathy occurred among those who received 1,200 mg for 6 months; all cases resolved.

Patients who received 1,200 mg for 6 months required the highest number of linezolid dose modifications; 51% required changes that included reduction, interruption, or discontinuation, compared with 28% among those who received 1,200 mg for 2 months and 13% each in the other two groups.

On the basis of these results, “my personal opinion is that 600 mg at 6 months [of linezolid] is most likely the best strategy for the treatment of this highly resistant treatment population group,” Dr. Conradie told this news organization.
 

Findings represent ‘great news’ in addressing concerns

Dr. Nahid further commented that the results are highly encouraging in light of the ongoing concerns about the effects of linezolid in the BPaL regimen.

“This is great news,” he said. “The ZeNix trial addresses a key concern that providers and patients have had regarding the safety and tolerability of taking 6 months of linezolid at 1200 mg/d as part of the BPaL regimen.

“The findings that doses lower and durations shorter than the current 1,200 mg linezolid daily for 6 months will significantly expand the usability of the BPaL regimen worldwide.”

The inclusion of patients with HIV was essential in the trial, he noted.

“There are drug-drug interactions to be considered, among other factors that impact drug exposure,” Dr. Nahid said.

“Inclusion of patients living with HIV in this study means that any modifications to the BPaL regimen considered by the WHO [World Health Organization] and other policy decision makers will include data from this key population,” he said. “Of course, more data are needed on safety, tolerability, and efficacy on BPaL in general, and there are international cohorts and demonstration projects underway that will enhance our understanding of the regimen in HIV and in other special populations.”

The authors, Dr. Streeck, and Dr. Nahid have disclosed no relevant financial relationships.

This article was updated 7/21/21.

Lower doses of linezolid in the BPaL drug regimen (bedaquiline, pretomanid, and linezolid) significantly reduce the adverse events associated with the treatment for patients with highly drug-resistant tuberculosis (TB) without compromising its high efficacy, new research shows.

“The ZeNix trial shows that reduced doses and/or shorter durations of linezolid appear to have high efficacy and improved safety,” said first author Francesca Conradie, MB, BCh, of the clinical HIV research unit, faculty of health sciences, University of Witwatersrand, Johannesburg, South Africa, in presenting the findings at the virtual meeting of the International AIDS Society conference.

As recently reported in the pivotal Nix-TB trial, the BPaL regimen yielded a 90% treatment success rate among people with highly drug-resistant forms of TB.

However, a 6-month regimen that included linezolid 1,200 mg resulted in toxic effects: 81% of patients in the study experienced peripheral neuropathy, and myelosuppression occurred in 48%. These effects often led to dose reductions or treatment interruption.

Adjustments in the dose of linezolid in the new ZeNix trial substantially reduced peripheral neuropathy to 13% and myelosuppression to 7%, with no significant reduction in the treatment response.

Importantly, the results were similar among patients with and those without HIV. This is of note because TB is the leading cause of death among patients with HIV.

“In the ZeNix trial, only 20% of patients were HIV infected, but in the [previous] Nix-TB trial, 30% were infected, so we have experience now in about 70 patients who were infected, and the outcomes were no different,” Dr. Conradie said in an interview.

Experts say the findings represent an important turn in the steep challenge of tackling highly resistant TB.

“In our opinion, these are exciting results that could change treatment guidelines for highly drug-resistant tuberculosis, with real benefits for the patients,” said Hendrik Streeck, MD, International AIDS Society cochair and director of the Institute of Virology and the Institute for HIV Research at the University Bonn (Germany), in a press conference.

Payam Nahid, MD, MPH, director of the Center for Tuberculosis at theUniversity of California, San Francisco, agreed.

“The results of this trial will impact global practices in treating drug-resistant TB as well as the design and conduct of future TB clinical trials,” Dr. Nahid said in an interview.
 

ZeNix trial

The phase 3 ZeNix trial included 181 patients with highly resistant TB in South Africa, Russia, Georgia, and Moldova. The mean age of the patients was 37 years; 67.4% were men, 63.5% were White, and 19.9% were HIV positive.

All patients were treated for 6 months with bedaquiline 200 mg daily for 8 weeks followed by 100 mg daily for 18 weeks, as well as pretomanid 200 mg daily.

The patients were randomly assigned to receive one of four daily doses of linezolid: 1,200 mg for 6 months (the original dose from the Nix-TB trial; n = 45) or 2 months (n = 46), or 600 mg for 6 or 2 months (45 patients each).

Percentages of patients with HIV were equal among the four groups, at about 20% each.

The primary outcomes – resolution of clinical disease and a negative culture status after 6 months – were observed across all linezolid dose groups. The success rate was 93% for those receiving 1,200 mg for 6 months, 89% for those receiving 1,200 mg for 2 months, 91% for those receiving 600 mg for 6 months, and 84% for those receiving 600 mg for 2 months.

With regard to the key adverse events of peripheral neuropathy and myelosuppression, manifested as anemia, the highest rates were among those who received linezolid 1,200 mg for 6 month, at 38% and 22%, respectively, compared with 24% and 17.4% among those who received 1,200 mg for 2 months, 24% and 2% among those who received 600 mg for 6 months, and 13% and 6.7% among those who received 600 mg for 2 months.

Four cases of optic neuropathy occurred among those who received 1,200 mg for 6 months; all cases resolved.

Patients who received 1,200 mg for 6 months required the highest number of linezolid dose modifications; 51% required changes that included reduction, interruption, or discontinuation, compared with 28% among those who received 1,200 mg for 2 months and 13% each in the other two groups.

On the basis of these results, “my personal opinion is that 600 mg at 6 months [of linezolid] is most likely the best strategy for the treatment of this highly resistant treatment population group,” Dr. Conradie told this news organization.
 

Findings represent ‘great news’ in addressing concerns

Dr. Nahid further commented that the results are highly encouraging in light of the ongoing concerns about the effects of linezolid in the BPaL regimen.

“This is great news,” he said. “The ZeNix trial addresses a key concern that providers and patients have had regarding the safety and tolerability of taking 6 months of linezolid at 1200 mg/d as part of the BPaL regimen.

“The findings that doses lower and durations shorter than the current 1,200 mg linezolid daily for 6 months will significantly expand the usability of the BPaL regimen worldwide.”

The inclusion of patients with HIV was essential in the trial, he noted.

“There are drug-drug interactions to be considered, among other factors that impact drug exposure,” Dr. Nahid said.

“Inclusion of patients living with HIV in this study means that any modifications to the BPaL regimen considered by the WHO [World Health Organization] and other policy decision makers will include data from this key population,” he said. “Of course, more data are needed on safety, tolerability, and efficacy on BPaL in general, and there are international cohorts and demonstration projects underway that will enhance our understanding of the regimen in HIV and in other special populations.”

The authors, Dr. Streeck, and Dr. Nahid have disclosed no relevant financial relationships.

This article was updated 7/21/21.

Lower doses of linezolid in the BPaL drug regimen (bedaquiline, pretomanid, and linezolid) significantly reduce the adverse events associated with the treatment for patients with highly drug-resistant tuberculosis (TB) without compromising its high efficacy, new research shows.

“The ZeNix trial shows that reduced doses and/or shorter durations of linezolid appear to have high efficacy and improved safety,” said first author Francesca Conradie, MB, BCh, of the clinical HIV research unit, faculty of health sciences, University of Witwatersrand, Johannesburg, South Africa, in presenting the findings at the virtual meeting of the International AIDS Society conference.

As recently reported in the pivotal Nix-TB trial, the BPaL regimen yielded a 90% treatment success rate among people with highly drug-resistant forms of TB.

However, a 6-month regimen that included linezolid 1,200 mg resulted in toxic effects: 81% of patients in the study experienced peripheral neuropathy, and myelosuppression occurred in 48%. These effects often led to dose reductions or treatment interruption.

Adjustments in the dose of linezolid in the new ZeNix trial substantially reduced peripheral neuropathy to 13% and myelosuppression to 7%, with no significant reduction in the treatment response.

Importantly, the results were similar among patients with and those without HIV. This is of note because TB is the leading cause of death among patients with HIV.

“In the ZeNix trial, only 20% of patients were HIV infected, but in the [previous] Nix-TB trial, 30% were infected, so we have experience now in about 70 patients who were infected, and the outcomes were no different,” Dr. Conradie said in an interview.

Experts say the findings represent an important turn in the steep challenge of tackling highly resistant TB.

“In our opinion, these are exciting results that could change treatment guidelines for highly drug-resistant tuberculosis, with real benefits for the patients,” said Hendrik Streeck, MD, International AIDS Society cochair and director of the Institute of Virology and the Institute for HIV Research at the University Bonn (Germany), in a press conference.

Payam Nahid, MD, MPH, director of the Center for Tuberculosis at theUniversity of California, San Francisco, agreed.

“The results of this trial will impact global practices in treating drug-resistant TB as well as the design and conduct of future TB clinical trials,” Dr. Nahid said in an interview.
 

ZeNix trial

The phase 3 ZeNix trial included 181 patients with highly resistant TB in South Africa, Russia, Georgia, and Moldova. The mean age of the patients was 37 years; 67.4% were men, 63.5% were White, and 19.9% were HIV positive.

All patients were treated for 6 months with bedaquiline 200 mg daily for 8 weeks followed by 100 mg daily for 18 weeks, as well as pretomanid 200 mg daily.

The patients were randomly assigned to receive one of four daily doses of linezolid: 1,200 mg for 6 months (the original dose from the Nix-TB trial; n = 45) or 2 months (n = 46), or 600 mg for 6 or 2 months (45 patients each).

Percentages of patients with HIV were equal among the four groups, at about 20% each.

The primary outcomes – resolution of clinical disease and a negative culture status after 6 months – were observed across all linezolid dose groups. The success rate was 93% for those receiving 1,200 mg for 6 months, 89% for those receiving 1,200 mg for 2 months, 91% for those receiving 600 mg for 6 months, and 84% for those receiving 600 mg for 2 months.

With regard to the key adverse events of peripheral neuropathy and myelosuppression, manifested as anemia, the highest rates were among those who received linezolid 1,200 mg for 6 month, at 38% and 22%, respectively, compared with 24% and 17.4% among those who received 1,200 mg for 2 months, 24% and 2% among those who received 600 mg for 6 months, and 13% and 6.7% among those who received 600 mg for 2 months.

Four cases of optic neuropathy occurred among those who received 1,200 mg for 6 months; all cases resolved.

Patients who received 1,200 mg for 6 months required the highest number of linezolid dose modifications; 51% required changes that included reduction, interruption, or discontinuation, compared with 28% among those who received 1,200 mg for 2 months and 13% each in the other two groups.

On the basis of these results, “my personal opinion is that 600 mg at 6 months [of linezolid] is most likely the best strategy for the treatment of this highly resistant treatment population group,” Dr. Conradie told this news organization.
 

Findings represent ‘great news’ in addressing concerns

Dr. Nahid further commented that the results are highly encouraging in light of the ongoing concerns about the effects of linezolid in the BPaL regimen.

“This is great news,” he said. “The ZeNix trial addresses a key concern that providers and patients have had regarding the safety and tolerability of taking 6 months of linezolid at 1200 mg/d as part of the BPaL regimen.

“The findings that doses lower and durations shorter than the current 1,200 mg linezolid daily for 6 months will significantly expand the usability of the BPaL regimen worldwide.”

The inclusion of patients with HIV was essential in the trial, he noted.

“There are drug-drug interactions to be considered, among other factors that impact drug exposure,” Dr. Nahid said.

“Inclusion of patients living with HIV in this study means that any modifications to the BPaL regimen considered by the WHO [World Health Organization] and other policy decision makers will include data from this key population,” he said. “Of course, more data are needed on safety, tolerability, and efficacy on BPaL in general, and there are international cohorts and demonstration projects underway that will enhance our understanding of the regimen in HIV and in other special populations.”

The authors, Dr. Streeck, and Dr. Nahid have disclosed no relevant financial relationships.

This article was updated 7/21/21.

A standard medical face mask is more effective at preventing the wearer from inhaling aerosols without causing substantial breathing resistance than various cloth, medical, or respirator masks, new research shows.

“Medical face masks with good filtration efficacies can provide even better protective effects than KN95 respirators,” Christian Sterr, MD, from Philipps University of Marburg (Germany), and colleagues wrote. “FFP2 respirators, on the other hand, could be useful in high-risk situations but require greater breathing effort and therefore physical stress for users.”

Extensive evidence has shown that face masks are an excellent form of source control, preventing infectious people from spreading the SARS-CoV-2 virus into the environment. But evidence has been less clear about how well masks protect the wearer from inhaling particles containing the virus.

The researchers conducted three experiments to test 32 different face masks. The findings were presented at the 31st European Congress of Clinical Microbiology & Infectious Diseases and published online in PLOS One .

First they tested pressure drop, which “relates to how easily air can pass through the material,” said Chris Cappa, PhD, professor of civil and environmental engineering at the University of California, Davis, who was not involved with the study.

“Higher pressure drops mean that there is greater resistance to the air passing through. A higher pressure drop will typically mean breathing through the material will be slightly more challenging, compared to a low pressure drop. There is no relationship between pressure drop and the mask effectiveness,” he said in an interview.

Pressure drop was lowest with type II medical face masks, the typical three-ply surgical masks designed to stop large particles expelled by the wearer from entering the environment, was highest with respirators, including KN95 and FFP2 masks, and varied with the different cloth masks tested.

Next the researchers compared filtration efficacy, which “refers to how well the material removes particles from the air that passes through the mask material,” Dr. Cappa explained. They did this by placing each mask over the opening to an air collector that measured how many particles got through. “A mask that has 100% filtration efficacy will remove all particles from the air that passes through it and 0% means that no particles are removed.”

Cloth masks had the lowest filtration efficacy, at 28%. Certified face masks that met European Standards had a relatively high efficacy, at 70%; for uncertified face masks, filtration efficacy was 63%. As expected, KN95 and FFP2 masks had the highest filtration efficacy, at 94% and 98%, respectively.Finally, the researchers tested as-worn filtration efficacies. They placed each mask on a dummy head with an artificial airway that collected airborne particles. They then pumped a mixture of aerosol particles – ranging in size from 0.3 to 2.0 mcm – and particle-free pressurized air into the air-proof acrylic chamber in which the head was placed.

In this experiment, cloth masks and noncertified face masks were least effective, filtering less than 20% of aerosols. Interestingly, the cloth face mask with the highest filtration on its own (84%) had the lowest filtration efficacy (9%), apparently because of its very high pressure drop (breathing resistance). When more effort is required to breathe through a mask, more air can bypass the filtration system.

A standard medical face mask is more effective at preventing the wearer from inhaling aerosols without causing substantial breathing resistance than various cloth, medical, or respirator masks, new research shows.

“Medical face masks with good filtration efficacies can provide even better protective effects than KN95 respirators,” Christian Sterr, MD, from Philipps University of Marburg (Germany), and colleagues wrote. “FFP2 respirators, on the other hand, could be useful in high-risk situations but require greater breathing effort and therefore physical stress for users.”

Extensive evidence has shown that face masks are an excellent form of source control, preventing infectious people from spreading the SARS-CoV-2 virus into the environment. But evidence has been less clear about how well masks protect the wearer from inhaling particles containing the virus.

The researchers conducted three experiments to test 32 different face masks. The findings were presented at the 31st European Congress of Clinical Microbiology & Infectious Diseases and published online in PLOS One .

First they tested pressure drop, which “relates to how easily air can pass through the material,” said Chris Cappa, PhD, professor of civil and environmental engineering at the University of California, Davis, who was not involved with the study.

“Higher pressure drops mean that there is greater resistance to the air passing through. A higher pressure drop will typically mean breathing through the material will be slightly more challenging, compared to a low pressure drop. There is no relationship between pressure drop and the mask effectiveness,” he said in an interview.

Pressure drop was lowest with type II medical face masks, the typical three-ply surgical masks designed to stop large particles expelled by the wearer from entering the environment, was highest with respirators, including KN95 and FFP2 masks, and varied with the different cloth masks tested.

Next the researchers compared filtration efficacy, which “refers to how well the material removes particles from the air that passes through the mask material,” Dr. Cappa explained. They did this by placing each mask over the opening to an air collector that measured how many particles got through. “A mask that has 100% filtration efficacy will remove all particles from the air that passes through it and 0% means that no particles are removed.”

Cloth masks had the lowest filtration efficacy, at 28%. Certified face masks that met European Standards had a relatively high efficacy, at 70%; for uncertified face masks, filtration efficacy was 63%. As expected, KN95 and FFP2 masks had the highest filtration efficacy, at 94% and 98%, respectively.Finally, the researchers tested as-worn filtration efficacies. They placed each mask on a dummy head with an artificial airway that collected airborne particles. They then pumped a mixture of aerosol particles – ranging in size from 0.3 to 2.0 mcm – and particle-free pressurized air into the air-proof acrylic chamber in which the head was placed.

In this experiment, cloth masks and noncertified face masks were least effective, filtering less than 20% of aerosols. Interestingly, the cloth face mask with the highest filtration on its own (84%) had the lowest filtration efficacy (9%), apparently because of its very high pressure drop (breathing resistance). When more effort is required to breathe through a mask, more air can bypass the filtration system.

A standard medical face mask is more effective at preventing the wearer from inhaling aerosols without causing substantial breathing resistance than various cloth, medical, or respirator masks, new research shows.

“Medical face masks with good filtration efficacies can provide even better protective effects than KN95 respirators,” Christian Sterr, MD, from Philipps University of Marburg (Germany), and colleagues wrote. “FFP2 respirators, on the other hand, could be useful in high-risk situations but require greater breathing effort and therefore physical stress for users.”

Extensive evidence has shown that face masks are an excellent form of source control, preventing infectious people from spreading the SARS-CoV-2 virus into the environment. But evidence has been less clear about how well masks protect the wearer from inhaling particles containing the virus.

The researchers conducted three experiments to test 32 different face masks. The findings were presented at the 31st European Congress of Clinical Microbiology & Infectious Diseases and published online in PLOS One .

First they tested pressure drop, which “relates to how easily air can pass through the material,” said Chris Cappa, PhD, professor of civil and environmental engineering at the University of California, Davis, who was not involved with the study.

“Higher pressure drops mean that there is greater resistance to the air passing through. A higher pressure drop will typically mean breathing through the material will be slightly more challenging, compared to a low pressure drop. There is no relationship between pressure drop and the mask effectiveness,” he said in an interview.

Pressure drop was lowest with type II medical face masks, the typical three-ply surgical masks designed to stop large particles expelled by the wearer from entering the environment, was highest with respirators, including KN95 and FFP2 masks, and varied with the different cloth masks tested.

Next the researchers compared filtration efficacy, which “refers to how well the material removes particles from the air that passes through the mask material,” Dr. Cappa explained. They did this by placing each mask over the opening to an air collector that measured how many particles got through. “A mask that has 100% filtration efficacy will remove all particles from the air that passes through it and 0% means that no particles are removed.”

Cloth masks had the lowest filtration efficacy, at 28%. Certified face masks that met European Standards had a relatively high efficacy, at 70%; for uncertified face masks, filtration efficacy was 63%. As expected, KN95 and FFP2 masks had the highest filtration efficacy, at 94% and 98%, respectively.Finally, the researchers tested as-worn filtration efficacies. They placed each mask on a dummy head with an artificial airway that collected airborne particles. They then pumped a mixture of aerosol particles – ranging in size from 0.3 to 2.0 mcm – and particle-free pressurized air into the air-proof acrylic chamber in which the head was placed.

In this experiment, cloth masks and noncertified face masks were least effective, filtering less than 20% of aerosols. Interestingly, the cloth face mask with the highest filtration on its own (84%) had the lowest filtration efficacy (9%), apparently because of its very high pressure drop (breathing resistance). When more effort is required to breathe through a mask, more air can bypass the filtration system.

Some people recovering from COVID-19 fare worse than current or previous cancer patients when referred to outpatient rehabilitation services, a new study from the CDC demonstrates.

People experiencing ongoing or “long-haul” symptoms after COVID-19 illness were more likely to report pain, challenges with physical activities, and “substantially worse health,” compared with people needing rehabilitation because of cancer, lead author Jessica Rogers-Brown, PhD, and colleagues report.

The study was published online July 9 in Morbidity and Mortality Weekly Report (MMWR).

The CDC investigators compared the self-reported physical and mental health symptoms, physical endurance, and use of health services of 1,295 outpatients recovering from COVID-19 and a control group of another 2,395 outpatients rehabilitating from a previous or current cancer diagnosis who had not experienced COVID-19.

Researchers used electronic health record data from January 2020 to March 2021 in the Select Medical network of outpatient clinics. The study included patients from 36 states and the District of Columbia.

Compared with people referred for cancer rehabilitation, those with COVID-19 symptoms lasting beyond 4 weeks were 2.3 times more likely to report pain, 1.8 times more likely to report worse physical health, and 1.6 times more likely to report difficulty with physical activities, an adjusted odds ratio analysis reveals.

The COVID-19 rehabilitation group also performed significantly worse on a 6-minute walk test, suggesting less physical endurance than people recovering from cancer (P < .001). They also used more rehabilitation services overall than the control group.

The researchers suggest services tailored to the unique physical and mental health rehabilitation needs of the post–COVID-19 patient population could be warranted.

The study does not suggest all people recovering with COVID-19 will fare worse than people recovering from cancer, the authors caution. They note that “these results should not be interpreted to mean that post–COVID-19 patients overall had poorer physical and mental health than patients with cancer.”

“Instead, results indicate that post–COVID-19 patients specifically referred to a large physical rehabilitation network had poorer health measures than those referred for cancer, which indicates that some patients recovering from COVID-19 had substantial rehabilitation needs.”

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

Some people recovering from COVID-19 fare worse than current or previous cancer patients when referred to outpatient rehabilitation services, a new study from the CDC demonstrates.

People experiencing ongoing or “long-haul” symptoms after COVID-19 illness were more likely to report pain, challenges with physical activities, and “substantially worse health,” compared with people needing rehabilitation because of cancer, lead author Jessica Rogers-Brown, PhD, and colleagues report.

The study was published online July 9 in Morbidity and Mortality Weekly Report (MMWR).

The CDC investigators compared the self-reported physical and mental health symptoms, physical endurance, and use of health services of 1,295 outpatients recovering from COVID-19 and a control group of another 2,395 outpatients rehabilitating from a previous or current cancer diagnosis who had not experienced COVID-19.

Researchers used electronic health record data from January 2020 to March 2021 in the Select Medical network of outpatient clinics. The study included patients from 36 states and the District of Columbia.

Compared with people referred for cancer rehabilitation, those with COVID-19 symptoms lasting beyond 4 weeks were 2.3 times more likely to report pain, 1.8 times more likely to report worse physical health, and 1.6 times more likely to report difficulty with physical activities, an adjusted odds ratio analysis reveals.

The COVID-19 rehabilitation group also performed significantly worse on a 6-minute walk test, suggesting less physical endurance than people recovering from cancer (P < .001). They also used more rehabilitation services overall than the control group.

The researchers suggest services tailored to the unique physical and mental health rehabilitation needs of the post–COVID-19 patient population could be warranted.

The study does not suggest all people recovering with COVID-19 will fare worse than people recovering from cancer, the authors caution. They note that “these results should not be interpreted to mean that post–COVID-19 patients overall had poorer physical and mental health than patients with cancer.”

“Instead, results indicate that post–COVID-19 patients specifically referred to a large physical rehabilitation network had poorer health measures than those referred for cancer, which indicates that some patients recovering from COVID-19 had substantial rehabilitation needs.”

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

Some people recovering from COVID-19 fare worse than current or previous cancer patients when referred to outpatient rehabilitation services, a new study from the CDC demonstrates.

People experiencing ongoing or “long-haul” symptoms after COVID-19 illness were more likely to report pain, challenges with physical activities, and “substantially worse health,” compared with people needing rehabilitation because of cancer, lead author Jessica Rogers-Brown, PhD, and colleagues report.

The study was published online July 9 in Morbidity and Mortality Weekly Report (MMWR).

The CDC investigators compared the self-reported physical and mental health symptoms, physical endurance, and use of health services of 1,295 outpatients recovering from COVID-19 and a control group of another 2,395 outpatients rehabilitating from a previous or current cancer diagnosis who had not experienced COVID-19.

Researchers used electronic health record data from January 2020 to March 2021 in the Select Medical network of outpatient clinics. The study included patients from 36 states and the District of Columbia.

Compared with people referred for cancer rehabilitation, those with COVID-19 symptoms lasting beyond 4 weeks were 2.3 times more likely to report pain, 1.8 times more likely to report worse physical health, and 1.6 times more likely to report difficulty with physical activities, an adjusted odds ratio analysis reveals.

The COVID-19 rehabilitation group also performed significantly worse on a 6-minute walk test, suggesting less physical endurance than people recovering from cancer (P < .001). They also used more rehabilitation services overall than the control group.

The researchers suggest services tailored to the unique physical and mental health rehabilitation needs of the post–COVID-19 patient population could be warranted.

The study does not suggest all people recovering with COVID-19 will fare worse than people recovering from cancer, the authors caution. They note that “these results should not be interpreted to mean that post–COVID-19 patients overall had poorer physical and mental health than patients with cancer.”

“Instead, results indicate that post–COVID-19 patients specifically referred to a large physical rehabilitation network had poorer health measures than those referred for cancer, which indicates that some patients recovering from COVID-19 had substantial rehabilitation needs.”

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

Sublingual immunotherapy (SLIT) emerged over a century ago as a gentler alternative to allergy shots. It uses the same antigens found in allergy shots, delivering them through tablets or drops under the tongue rather than by injecting them into the skin.

Yet injection immunotherapy has been the mainstay of allergy treatment in the United States. Allergy shots are “the bread and butter, keeping the lights on at allergy practices,” said allergist Sakina Bajowala, MD, of Kaneland Allergy and Asthma Center, in the Chicago area. So even “when environmental SLIT showed quite clearly that it had efficacy, people were so slow to adapt.”

SLIT – a daily treatment that builds protection from allergens gradually over years with few side effects – is popular around the globe, particularly for environmental allergies. But only a handful of clinics offer food SLIT. Even though recent trials in peanut-allergic children show that SLIT is far safer than oral immunotherapy and about as effective as the Food and Drug Administration–approved peanut-allergy product and has lasting benefits for toddlers, many allergists lack experience with customized immunotherapies and hesitate to offer an unregulated treatment for which the evidence base is still emerging.
 

Why hasn’t food allergy SLIT caught on?

One issue is that there is scant evidence from randomized, controlled trials. The treatments that clinics offer often hinge on insurance coverage, and increasingly, insurers only cover FDA-approved products. FDA approval requires thousands of patients being enrolled in long, expensive studies to prove the treatment’s merit. In a similar vein, doctors are trained to question methods that lack a strong publication base, for good reason.

Yet SLIT caught the attention of pioneering physicians who were intrigued by this “low-and-slow” immune-modifying approach, despite limited published evidence, and they sought real-world experience.

The late physician David Morris, MD, came across SLIT in the 1960s while searching for alternative ways to help mold-allergic farmers who were suffering terrible side effects from allergy shots. Dr. Morris attended conferences, learned more about sublingual techniques, got board certified in allergy, and opened Allergy Associates of La Crosse (Wis.), in 1970 to offer SLIT as a treatment for food and environmental allergies.

Dr. Morris and colleagues developed a protocol to create custom SLIT drops tailored to individual patients’ clinical histories and allergy test results. The method has been used to treat more than 200,000 patients. It has been used by allergist Nikhila Schroeder, MD, MEng, who learned SLIT methods while treating nearly 1,000 patients at Allergy Associates. In 2018, she opened her own direct-care SLIT practice, Allergenuity Health, in the Charlotte metropolitan area of North Carolina (see part 2 of this series).

Dr. Bajowala’s clinic offers SLIT in addition to oral immunotherapy (OIT). She was encouraged by the recent toddler SLIT data but wondered whether it would translate to a real-world setting. According to her calculations, the published protocol – according to which participants receive up to 4 mg/d over 6 months and continue receiving a daily maintenance dose of 4 mg for 3 years – would cost $10,000 per patient.

With this dosing regimen, the intervention is unaffordable, Dr. Bajowala said. And “there’s no way to make it cheaper because that’s the raw materials cost. It does not include labor or bottles or profit at all. That’s just $10,000 in peanut extract.”

Owing to cost, Dr. Bajowala’s clinic generally uses SLIT as a bridge to OIT. Her food allergy patients receive up to 1 mg/d and remain at that dose for a month or so before transitioning to OIT, “for which the supplies are orders of magnitude cheaper,” she said.

Dr. Schroeder said there is evidence for efficacy at microgram and even nanogram dosing – much lower than used in the recent food SLIT trials. Maintenance doses range from 50 ng/d to 25 mcg/d for environmental SLIT and 4-37 mcg/d for food SLIT, she said. The La Crosse method uses even lower dose ranges.

However, dosing information is not readily available, Dr. Schroeder noted. She has spent years scrutinizing articles and compiling information from allergen extract suppliers – all the while treating hundreds of SLIT patients. “I have had to expend a lot of time and effort,” said Dr. Schroeder. “It’s really hard to explain quickly.”

In the published literature, SLIT dosing recommendations vary widely. According to a 2007 analysis, environmental allergy symptoms improved with doses over a 1,000-fold range. What’s more, success did not scale with increased dosing and seemed to depend more on frequency and duration of treatment.

There are fewer studies regarding food SLIT. The most promising data come from recent trials of peanut-allergic children led by Edwin Kim, MD, director of the UNC Food Allergy Initiative, University of North Carolina at Chapel Hill. Still, “I am nervous to tell people to go do this based on 150 kids at one site,” Dr. Kim said. “We need to have a gigantic study across multiple sites that actually confirms what we have found in our single center.”

Because there are few published trials of food SLIT, confusion about which doses are optimal, how early to start, and how long the benefits last will be a barrier for many clinicians, said Douglas Mack, MD, FRCPC, assistant clinical professor in pediatrics at McMaster University, Hamilton, Ont.

Much could be learned from Allergy Associates of La Crosse, Allergenuity Health, and other clinics with SLIT experience involving thousands of patients. But that real-world data are messy and difficult to publish. Plus, it is hard for private allergists to find time to review charts, analyze data, and draft papers alongside seeing patients and running a clinic – especially without students and interns, who typically assist with academic research, Dr. Schroeder said.

Ruchi Gupta, MD, MPH, professor of pediatrics and medicine at Northwestern University, Chicago, and colleagues worked with a La Crosse team 6 or 7 years ago to try to analyze and publish SLIT outcomes for 121 peanut-allergic children who were treated for food and environmental allergies at the Wisconsin clinic. The researchers had hoped to publish an article describing caregiver-reported and clinical outcomes.

Among 73 caregivers who responded to a survey, more than half reported improved eczema, asthma, and environmental allergy symptoms, and virtually all families said SLIT calmed anxieties and minimized fear of allergic reactions. However, the clinical outcomes – skinprick test results, immune changes, and oral food challenges – were not as robust. And the data were incomplete. Some patients had traveled to La Crosse for SLIT drops but underwent skin and blood testing with their local allergist. Compiling records is “so much harder when you’re not doing a prospective clinical trial,” Dr. Gupta said.

The caregiver-reported outcomes were presented as a poster at the 2015 annual meeting of the American College of Allergy, Asthma, and Immunology and the 2016 annual meeting of the Pediatric Academic Society, said Jeff Kessler, MBA, FACHE, who is practice executive at La Crosse. However, with only self-reported data and no convincing lab metrics, the findings were never submitted for publication.

Others are eager to see clearer proof that SLIT works at doses lower than those published in the most recent trials. “If we can get efficacy with lower doses, that means we can increase accessibility, because we can lower the cost,” Dr. Bajowala said.

Robert Wood, MD, professor of pediatrics and director of pediatric allergy and immunology at Johns Hopkins University, Baltimore, has a pending grant proposal for a multifood trial of SLIT. “It’s a big missing piece,” he said.

Dr. Mack said that in Canada there was “almost an instant change in group think” when the Canadian Society of Allergy and Clinical Immunology published guidelines in support of OIT. With the new guidelines, “people are less concerned about liability. Once they start getting into OIT, I think you’re going to see SLIT coming right along for the ride.”

The shift will be slower in the United States, which has 20 times as many practicing allergists as Canada. Nevertheless, “I totally think SLIT has a place at the table,” Dr. Mack said. “I hope we start to see more high-quality data and people start to use it and experiment with it a bit and see how it works.”

A version of this article first appeared on Medscape.com. This is part three of a three-part series. Part one is here. Part two is here.

Sublingual immunotherapy (SLIT) emerged over a century ago as a gentler alternative to allergy shots. It uses the same antigens found in allergy shots, delivering them through tablets or drops under the tongue rather than by injecting them into the skin.

Yet injection immunotherapy has been the mainstay of allergy treatment in the United States. Allergy shots are “the bread and butter, keeping the lights on at allergy practices,” said allergist Sakina Bajowala, MD, of Kaneland Allergy and Asthma Center, in the Chicago area. So even “when environmental SLIT showed quite clearly that it had efficacy, people were so slow to adapt.”

SLIT – a daily treatment that builds protection from allergens gradually over years with few side effects – is popular around the globe, particularly for environmental allergies. But only a handful of clinics offer food SLIT. Even though recent trials in peanut-allergic children show that SLIT is far safer than oral immunotherapy and about as effective as the Food and Drug Administration–approved peanut-allergy product and has lasting benefits for toddlers, many allergists lack experience with customized immunotherapies and hesitate to offer an unregulated treatment for which the evidence base is still emerging.
 

Why hasn’t food allergy SLIT caught on?

One issue is that there is scant evidence from randomized, controlled trials. The treatments that clinics offer often hinge on insurance coverage, and increasingly, insurers only cover FDA-approved products. FDA approval requires thousands of patients being enrolled in long, expensive studies to prove the treatment’s merit. In a similar vein, doctors are trained to question methods that lack a strong publication base, for good reason.

Yet SLIT caught the attention of pioneering physicians who were intrigued by this “low-and-slow” immune-modifying approach, despite limited published evidence, and they sought real-world experience.

The late physician David Morris, MD, came across SLIT in the 1960s while searching for alternative ways to help mold-allergic farmers who were suffering terrible side effects from allergy shots. Dr. Morris attended conferences, learned more about sublingual techniques, got board certified in allergy, and opened Allergy Associates of La Crosse (Wis.), in 1970 to offer SLIT as a treatment for food and environmental allergies.

Dr. Morris and colleagues developed a protocol to create custom SLIT drops tailored to individual patients’ clinical histories and allergy test results. The method has been used to treat more than 200,000 patients. It has been used by allergist Nikhila Schroeder, MD, MEng, who learned SLIT methods while treating nearly 1,000 patients at Allergy Associates. In 2018, she opened her own direct-care SLIT practice, Allergenuity Health, in the Charlotte metropolitan area of North Carolina (see part 2 of this series).

Dr. Bajowala’s clinic offers SLIT in addition to oral immunotherapy (OIT). She was encouraged by the recent toddler SLIT data but wondered whether it would translate to a real-world setting. According to her calculations, the published protocol – according to which participants receive up to 4 mg/d over 6 months and continue receiving a daily maintenance dose of 4 mg for 3 years – would cost $10,000 per patient.

With this dosing regimen, the intervention is unaffordable, Dr. Bajowala said. And “there’s no way to make it cheaper because that’s the raw materials cost. It does not include labor or bottles or profit at all. That’s just $10,000 in peanut extract.”

Owing to cost, Dr. Bajowala’s clinic generally uses SLIT as a bridge to OIT. Her food allergy patients receive up to 1 mg/d and remain at that dose for a month or so before transitioning to OIT, “for which the supplies are orders of magnitude cheaper,” she said.

Dr. Schroeder said there is evidence for efficacy at microgram and even nanogram dosing – much lower than used in the recent food SLIT trials. Maintenance doses range from 50 ng/d to 25 mcg/d for environmental SLIT and 4-37 mcg/d for food SLIT, she said. The La Crosse method uses even lower dose ranges.

However, dosing information is not readily available, Dr. Schroeder noted. She has spent years scrutinizing articles and compiling information from allergen extract suppliers – all the while treating hundreds of SLIT patients. “I have had to expend a lot of time and effort,” said Dr. Schroeder. “It’s really hard to explain quickly.”

In the published literature, SLIT dosing recommendations vary widely. According to a 2007 analysis, environmental allergy symptoms improved with doses over a 1,000-fold range. What’s more, success did not scale with increased dosing and seemed to depend more on frequency and duration of treatment.

There are fewer studies regarding food SLIT. The most promising data come from recent trials of peanut-allergic children led by Edwin Kim, MD, director of the UNC Food Allergy Initiative, University of North Carolina at Chapel Hill. Still, “I am nervous to tell people to go do this based on 150 kids at one site,” Dr. Kim said. “We need to have a gigantic study across multiple sites that actually confirms what we have found in our single center.”

Because there are few published trials of food SLIT, confusion about which doses are optimal, how early to start, and how long the benefits last will be a barrier for many clinicians, said Douglas Mack, MD, FRCPC, assistant clinical professor in pediatrics at McMaster University, Hamilton, Ont.

Much could be learned from Allergy Associates of La Crosse, Allergenuity Health, and other clinics with SLIT experience involving thousands of patients. But that real-world data are messy and difficult to publish. Plus, it is hard for private allergists to find time to review charts, analyze data, and draft papers alongside seeing patients and running a clinic – especially without students and interns, who typically assist with academic research, Dr. Schroeder said.

Ruchi Gupta, MD, MPH, professor of pediatrics and medicine at Northwestern University, Chicago, and colleagues worked with a La Crosse team 6 or 7 years ago to try to analyze and publish SLIT outcomes for 121 peanut-allergic children who were treated for food and environmental allergies at the Wisconsin clinic. The researchers had hoped to publish an article describing caregiver-reported and clinical outcomes.

Among 73 caregivers who responded to a survey, more than half reported improved eczema, asthma, and environmental allergy symptoms, and virtually all families said SLIT calmed anxieties and minimized fear of allergic reactions. However, the clinical outcomes – skinprick test results, immune changes, and oral food challenges – were not as robust. And the data were incomplete. Some patients had traveled to La Crosse for SLIT drops but underwent skin and blood testing with their local allergist. Compiling records is “so much harder when you’re not doing a prospective clinical trial,” Dr. Gupta said.

The caregiver-reported outcomes were presented as a poster at the 2015 annual meeting of the American College of Allergy, Asthma, and Immunology and the 2016 annual meeting of the Pediatric Academic Society, said Jeff Kessler, MBA, FACHE, who is practice executive at La Crosse. However, with only self-reported data and no convincing lab metrics, the findings were never submitted for publication.

Others are eager to see clearer proof that SLIT works at doses lower than those published in the most recent trials. “If we can get efficacy with lower doses, that means we can increase accessibility, because we can lower the cost,” Dr. Bajowala said.

Robert Wood, MD, professor of pediatrics and director of pediatric allergy and immunology at Johns Hopkins University, Baltimore, has a pending grant proposal for a multifood trial of SLIT. “It’s a big missing piece,” he said.

Dr. Mack said that in Canada there was “almost an instant change in group think” when the Canadian Society of Allergy and Clinical Immunology published guidelines in support of OIT. With the new guidelines, “people are less concerned about liability. Once they start getting into OIT, I think you’re going to see SLIT coming right along for the ride.”

The shift will be slower in the United States, which has 20 times as many practicing allergists as Canada. Nevertheless, “I totally think SLIT has a place at the table,” Dr. Mack said. “I hope we start to see more high-quality data and people start to use it and experiment with it a bit and see how it works.”

A version of this article first appeared on Medscape.com. This is part three of a three-part series. Part one is here. Part two is here.

Sublingual immunotherapy (SLIT) emerged over a century ago as a gentler alternative to allergy shots. It uses the same antigens found in allergy shots, delivering them through tablets or drops under the tongue rather than by injecting them into the skin.

Yet injection immunotherapy has been the mainstay of allergy treatment in the United States. Allergy shots are “the bread and butter, keeping the lights on at allergy practices,” said allergist Sakina Bajowala, MD, of Kaneland Allergy and Asthma Center, in the Chicago area. So even “when environmental SLIT showed quite clearly that it had efficacy, people were so slow to adapt.”

SLIT – a daily treatment that builds protection from allergens gradually over years with few side effects – is popular around the globe, particularly for environmental allergies. But only a handful of clinics offer food SLIT. Even though recent trials in peanut-allergic children show that SLIT is far safer than oral immunotherapy and about as effective as the Food and Drug Administration–approved peanut-allergy product and has lasting benefits for toddlers, many allergists lack experience with customized immunotherapies and hesitate to offer an unregulated treatment for which the evidence base is still emerging.
 

Why hasn’t food allergy SLIT caught on?

One issue is that there is scant evidence from randomized, controlled trials. The treatments that clinics offer often hinge on insurance coverage, and increasingly, insurers only cover FDA-approved products. FDA approval requires thousands of patients being enrolled in long, expensive studies to prove the treatment’s merit. In a similar vein, doctors are trained to question methods that lack a strong publication base, for good reason.

Yet SLIT caught the attention of pioneering physicians who were intrigued by this “low-and-slow” immune-modifying approach, despite limited published evidence, and they sought real-world experience.

The late physician David Morris, MD, came across SLIT in the 1960s while searching for alternative ways to help mold-allergic farmers who were suffering terrible side effects from allergy shots. Dr. Morris attended conferences, learned more about sublingual techniques, got board certified in allergy, and opened Allergy Associates of La Crosse (Wis.), in 1970 to offer SLIT as a treatment for food and environmental allergies.

Dr. Morris and colleagues developed a protocol to create custom SLIT drops tailored to individual patients’ clinical histories and allergy test results. The method has been used to treat more than 200,000 patients. It has been used by allergist Nikhila Schroeder, MD, MEng, who learned SLIT methods while treating nearly 1,000 patients at Allergy Associates. In 2018, she opened her own direct-care SLIT practice, Allergenuity Health, in the Charlotte metropolitan area of North Carolina (see part 2 of this series).

Dr. Bajowala’s clinic offers SLIT in addition to oral immunotherapy (OIT). She was encouraged by the recent toddler SLIT data but wondered whether it would translate to a real-world setting. According to her calculations, the published protocol – according to which participants receive up to 4 mg/d over 6 months and continue receiving a daily maintenance dose of 4 mg for 3 years – would cost $10,000 per patient.

With this dosing regimen, the intervention is unaffordable, Dr. Bajowala said. And “there’s no way to make it cheaper because that’s the raw materials cost. It does not include labor or bottles or profit at all. That’s just $10,000 in peanut extract.”

Owing to cost, Dr. Bajowala’s clinic generally uses SLIT as a bridge to OIT. Her food allergy patients receive up to 1 mg/d and remain at that dose for a month or so before transitioning to OIT, “for which the supplies are orders of magnitude cheaper,” she said.

Dr. Schroeder said there is evidence for efficacy at microgram and even nanogram dosing – much lower than used in the recent food SLIT trials. Maintenance doses range from 50 ng/d to 25 mcg/d for environmental SLIT and 4-37 mcg/d for food SLIT, she said. The La Crosse method uses even lower dose ranges.

However, dosing information is not readily available, Dr. Schroeder noted. She has spent years scrutinizing articles and compiling information from allergen extract suppliers – all the while treating hundreds of SLIT patients. “I have had to expend a lot of time and effort,” said Dr. Schroeder. “It’s really hard to explain quickly.”

In the published literature, SLIT dosing recommendations vary widely. According to a 2007 analysis, environmental allergy symptoms improved with doses over a 1,000-fold range. What’s more, success did not scale with increased dosing and seemed to depend more on frequency and duration of treatment.

There are fewer studies regarding food SLIT. The most promising data come from recent trials of peanut-allergic children led by Edwin Kim, MD, director of the UNC Food Allergy Initiative, University of North Carolina at Chapel Hill. Still, “I am nervous to tell people to go do this based on 150 kids at one site,” Dr. Kim said. “We need to have a gigantic study across multiple sites that actually confirms what we have found in our single center.”

Because there are few published trials of food SLIT, confusion about which doses are optimal, how early to start, and how long the benefits last will be a barrier for many clinicians, said Douglas Mack, MD, FRCPC, assistant clinical professor in pediatrics at McMaster University, Hamilton, Ont.

Much could be learned from Allergy Associates of La Crosse, Allergenuity Health, and other clinics with SLIT experience involving thousands of patients. But that real-world data are messy and difficult to publish. Plus, it is hard for private allergists to find time to review charts, analyze data, and draft papers alongside seeing patients and running a clinic – especially without students and interns, who typically assist with academic research, Dr. Schroeder said.

Ruchi Gupta, MD, MPH, professor of pediatrics and medicine at Northwestern University, Chicago, and colleagues worked with a La Crosse team 6 or 7 years ago to try to analyze and publish SLIT outcomes for 121 peanut-allergic children who were treated for food and environmental allergies at the Wisconsin clinic. The researchers had hoped to publish an article describing caregiver-reported and clinical outcomes.

Among 73 caregivers who responded to a survey, more than half reported improved eczema, asthma, and environmental allergy symptoms, and virtually all families said SLIT calmed anxieties and minimized fear of allergic reactions. However, the clinical outcomes – skinprick test results, immune changes, and oral food challenges – were not as robust. And the data were incomplete. Some patients had traveled to La Crosse for SLIT drops but underwent skin and blood testing with their local allergist. Compiling records is “so much harder when you’re not doing a prospective clinical trial,” Dr. Gupta said.

The caregiver-reported outcomes were presented as a poster at the 2015 annual meeting of the American College of Allergy, Asthma, and Immunology and the 2016 annual meeting of the Pediatric Academic Society, said Jeff Kessler, MBA, FACHE, who is practice executive at La Crosse. However, with only self-reported data and no convincing lab metrics, the findings were never submitted for publication.

Others are eager to see clearer proof that SLIT works at doses lower than those published in the most recent trials. “If we can get efficacy with lower doses, that means we can increase accessibility, because we can lower the cost,” Dr. Bajowala said.

Robert Wood, MD, professor of pediatrics and director of pediatric allergy and immunology at Johns Hopkins University, Baltimore, has a pending grant proposal for a multifood trial of SLIT. “It’s a big missing piece,” he said.

Dr. Mack said that in Canada there was “almost an instant change in group think” when the Canadian Society of Allergy and Clinical Immunology published guidelines in support of OIT. With the new guidelines, “people are less concerned about liability. Once they start getting into OIT, I think you’re going to see SLIT coming right along for the ride.”

The shift will be slower in the United States, which has 20 times as many practicing allergists as Canada. Nevertheless, “I totally think SLIT has a place at the table,” Dr. Mack said. “I hope we start to see more high-quality data and people start to use it and experiment with it a bit and see how it works.”

A version of this article first appeared on Medscape.com. This is part three of a three-part series. Part one is here. Part two is here.

Sleep-disordered breathing is common in patients with neuromuscular disease and is increasingly addressed with noninvasive ventilation, but its patterns go beyond obstructive sleep apnea (OSA) and include hypoventilation, hypoxemia, central sleep apnea, pseudocentrals, periodic breathing, and Cheyne-Stokes respiration, Gaurav Singh, MD, MPH said at the virtual annual meeting of the Associated Professional Sleep Societies.

The prevalence of sleep-related disordered breathing surpasses 40% in patients diagnosed with neuromuscular disease, but “sleep disordered breathing [in these patients] does not equal obstructive sleep apnea,” said Dr. Singh, staff physician at the Veteran Affairs Palo Alto (Calif.) Health Care System in the section of pulmonary, critical care and sleep medicine, and an affiliated clinical assistant professor at Stanford (Calif.) University.

“The most common sleep-related breathing disorder in neuromuscular disease is probably hypopnea and hypoventilation with the sawtooth pattern of dips in oxygen saturation that occur during REM sleep,” he said. As neuromuscular diseases progress, hypoventilation may occur during non-REM sleep as well.

Evaluation is usually performed with polysomnography and pulmonary function testing, he said, but supplementary testing including serum bicarbonate levels, arterial blood gases, and echocardiography to assess for left ventricular ejection fraction and cardiomyopathy may be useful as well.

While a sleep study is not required per Centers for Medicare & Medicaid coverage criteria for the use of respiratory assist devices in patients with neuromuscular disease, polysomnography is valuable for identifying early nocturnal respiratory impairment before the appearance of symptoms and daytime abnormalities in gas exchange, and is better than home testing for distinguishing different types of events (including pseudocentrals). It also is helpful for determining the appropriate pressures needed for ventilatory support and for assessing the need for a backup rate, Dr. Singh said.

Commonly used types of noninvasive ventilation include bilevel positive airway pressure on the spontaneous/timed or pressure control modes, with or without volume-assured pressure support, he said.

Expiratory positive airway pressure (EPAP) is usually set low initially to help decrease the work of breathing and improve triggering, then titrated up to ensure that upper airway obstructive events are treated. Pressure support (the difference between the inspiratory positive airway pressure and EPAP) is set to achieve target tidal volume and to rest the respiratory muscles. And inspiratory time is set “on the longer end” to achieve maximal target volume and ensure appropriate gas exchange, Dr. Singh said.

Data from randomized controlled trials evaluating the effectiveness of NIV are limited, he said. A study published 15 years ago showed a survival benefit and improvement in quality of life measures in patients with amyotrophic lateral sclerosis (ALS) with normal or moderately impaired bulbar function but not in those with severe bulbar weakness.

Regarding the timing of initiating NIV, a retrospective study published several years ago looked at almost 200 ALS patients and evaluated differences in survival amongst those started earlier with NIV (forced vital capacity ≥80%) and those started later (FVC <80%). At 36 months from diagnosis, mortality was 35% for the early group and 53% for the later group. “Improved survival was driven by benefit in patients with non–bulbar-onset ALS, compared with bulbar-onset disease,” Dr. Singh said.

“This study and several other similar studies seem to indicate that the earlier NIV [noninvasive ventilation] is started in patients with neuromuscular disease, the better in terms of improving survival and other relevant measures such as quality of life,” he said.

Asked about Dr. Singh’s presentation, Michelle Cao, DO, clinical associate professor at Stanford University, said that NIV is an “invaluable tool in the treatment of conditions leading to chronic respiratory failure,” such as neuromuscular disease, and that it’s important to incorporate NIV training for future pulmonary, critical care and sleep physicians. Dr. Cao directs the adult NIV program for the neuromuscular medical program at Stanford Health Care.

Saiprakash B. Venkateshiah, MD, of Emory University, Atlanta, also said in introducing Dr. Singh at the meeting that earlier diagnosis and appropriate NIV therapy “may improve quality of life and possibly even lower survival in certain disorders.”

In addition, he noted that sleep disturbances “may be the earliest sign of muscle weakness in [patients with neuromuscular disease], sometimes being detected before their underlying neuromuscular disease is diagnosed.”

Dr. Singh, Dr. Cao, and Dr. Venkateshiah each reported that they had no potential conflicts of interest.

Sleep-disordered breathing is common in patients with neuromuscular disease and is increasingly addressed with noninvasive ventilation, but its patterns go beyond obstructive sleep apnea (OSA) and include hypoventilation, hypoxemia, central sleep apnea, pseudocentrals, periodic breathing, and Cheyne-Stokes respiration, Gaurav Singh, MD, MPH said at the virtual annual meeting of the Associated Professional Sleep Societies.

The prevalence of sleep-related disordered breathing surpasses 40% in patients diagnosed with neuromuscular disease, but “sleep disordered breathing [in these patients] does not equal obstructive sleep apnea,” said Dr. Singh, staff physician at the Veteran Affairs Palo Alto (Calif.) Health Care System in the section of pulmonary, critical care and sleep medicine, and an affiliated clinical assistant professor at Stanford (Calif.) University.

“The most common sleep-related breathing disorder in neuromuscular disease is probably hypopnea and hypoventilation with the sawtooth pattern of dips in oxygen saturation that occur during REM sleep,” he said. As neuromuscular diseases progress, hypoventilation may occur during non-REM sleep as well.

Evaluation is usually performed with polysomnography and pulmonary function testing, he said, but supplementary testing including serum bicarbonate levels, arterial blood gases, and echocardiography to assess for left ventricular ejection fraction and cardiomyopathy may be useful as well.

While a sleep study is not required per Centers for Medicare & Medicaid coverage criteria for the use of respiratory assist devices in patients with neuromuscular disease, polysomnography is valuable for identifying early nocturnal respiratory impairment before the appearance of symptoms and daytime abnormalities in gas exchange, and is better than home testing for distinguishing different types of events (including pseudocentrals). It also is helpful for determining the appropriate pressures needed for ventilatory support and for assessing the need for a backup rate, Dr. Singh said.

Commonly used types of noninvasive ventilation include bilevel positive airway pressure on the spontaneous/timed or pressure control modes, with or without volume-assured pressure support, he said.

Expiratory positive airway pressure (EPAP) is usually set low initially to help decrease the work of breathing and improve triggering, then titrated up to ensure that upper airway obstructive events are treated. Pressure support (the difference between the inspiratory positive airway pressure and EPAP) is set to achieve target tidal volume and to rest the respiratory muscles. And inspiratory time is set “on the longer end” to achieve maximal target volume and ensure appropriate gas exchange, Dr. Singh said.

Data from randomized controlled trials evaluating the effectiveness of NIV are limited, he said. A study published 15 years ago showed a survival benefit and improvement in quality of life measures in patients with amyotrophic lateral sclerosis (ALS) with normal or moderately impaired bulbar function but not in those with severe bulbar weakness.

Regarding the timing of initiating NIV, a retrospective study published several years ago looked at almost 200 ALS patients and evaluated differences in survival amongst those started earlier with NIV (forced vital capacity ≥80%) and those started later (FVC <80%). At 36 months from diagnosis, mortality was 35% for the early group and 53% for the later group. “Improved survival was driven by benefit in patients with non–bulbar-onset ALS, compared with bulbar-onset disease,” Dr. Singh said.

“This study and several other similar studies seem to indicate that the earlier NIV [noninvasive ventilation] is started in patients with neuromuscular disease, the better in terms of improving survival and other relevant measures such as quality of life,” he said.

Asked about Dr. Singh’s presentation, Michelle Cao, DO, clinical associate professor at Stanford University, said that NIV is an “invaluable tool in the treatment of conditions leading to chronic respiratory failure,” such as neuromuscular disease, and that it’s important to incorporate NIV training for future pulmonary, critical care and sleep physicians. Dr. Cao directs the adult NIV program for the neuromuscular medical program at Stanford Health Care.

Saiprakash B. Venkateshiah, MD, of Emory University, Atlanta, also said in introducing Dr. Singh at the meeting that earlier diagnosis and appropriate NIV therapy “may improve quality of life and possibly even lower survival in certain disorders.”

In addition, he noted that sleep disturbances “may be the earliest sign of muscle weakness in [patients with neuromuscular disease], sometimes being detected before their underlying neuromuscular disease is diagnosed.”

Dr. Singh, Dr. Cao, and Dr. Venkateshiah each reported that they had no potential conflicts of interest.

Sleep-disordered breathing is common in patients with neuromuscular disease and is increasingly addressed with noninvasive ventilation, but its patterns go beyond obstructive sleep apnea (OSA) and include hypoventilation, hypoxemia, central sleep apnea, pseudocentrals, periodic breathing, and Cheyne-Stokes respiration, Gaurav Singh, MD, MPH said at the virtual annual meeting of the Associated Professional Sleep Societies.

The prevalence of sleep-related disordered breathing surpasses 40% in patients diagnosed with neuromuscular disease, but “sleep disordered breathing [in these patients] does not equal obstructive sleep apnea,” said Dr. Singh, staff physician at the Veteran Affairs Palo Alto (Calif.) Health Care System in the section of pulmonary, critical care and sleep medicine, and an affiliated clinical assistant professor at Stanford (Calif.) University.

“The most common sleep-related breathing disorder in neuromuscular disease is probably hypopnea and hypoventilation with the sawtooth pattern of dips in oxygen saturation that occur during REM sleep,” he said. As neuromuscular diseases progress, hypoventilation may occur during non-REM sleep as well.

Evaluation is usually performed with polysomnography and pulmonary function testing, he said, but supplementary testing including serum bicarbonate levels, arterial blood gases, and echocardiography to assess for left ventricular ejection fraction and cardiomyopathy may be useful as well.

While a sleep study is not required per Centers for Medicare & Medicaid coverage criteria for the use of respiratory assist devices in patients with neuromuscular disease, polysomnography is valuable for identifying early nocturnal respiratory impairment before the appearance of symptoms and daytime abnormalities in gas exchange, and is better than home testing for distinguishing different types of events (including pseudocentrals). It also is helpful for determining the appropriate pressures needed for ventilatory support and for assessing the need for a backup rate, Dr. Singh said.

Commonly used types of noninvasive ventilation include bilevel positive airway pressure on the spontaneous/timed or pressure control modes, with or without volume-assured pressure support, he said.

Expiratory positive airway pressure (EPAP) is usually set low initially to help decrease the work of breathing and improve triggering, then titrated up to ensure that upper airway obstructive events are treated. Pressure support (the difference between the inspiratory positive airway pressure and EPAP) is set to achieve target tidal volume and to rest the respiratory muscles. And inspiratory time is set “on the longer end” to achieve maximal target volume and ensure appropriate gas exchange, Dr. Singh said.

Data from randomized controlled trials evaluating the effectiveness of NIV are limited, he said. A study published 15 years ago showed a survival benefit and improvement in quality of life measures in patients with amyotrophic lateral sclerosis (ALS) with normal or moderately impaired bulbar function but not in those with severe bulbar weakness.

Regarding the timing of initiating NIV, a retrospective study published several years ago looked at almost 200 ALS patients and evaluated differences in survival amongst those started earlier with NIV (forced vital capacity ≥80%) and those started later (FVC <80%). At 36 months from diagnosis, mortality was 35% for the early group and 53% for the later group. “Improved survival was driven by benefit in patients with non–bulbar-onset ALS, compared with bulbar-onset disease,” Dr. Singh said.

“This study and several other similar studies seem to indicate that the earlier NIV [noninvasive ventilation] is started in patients with neuromuscular disease, the better in terms of improving survival and other relevant measures such as quality of life,” he said.

Asked about Dr. Singh’s presentation, Michelle Cao, DO, clinical associate professor at Stanford University, said that NIV is an “invaluable tool in the treatment of conditions leading to chronic respiratory failure,” such as neuromuscular disease, and that it’s important to incorporate NIV training for future pulmonary, critical care and sleep physicians. Dr. Cao directs the adult NIV program for the neuromuscular medical program at Stanford Health Care.

Saiprakash B. Venkateshiah, MD, of Emory University, Atlanta, also said in introducing Dr. Singh at the meeting that earlier diagnosis and appropriate NIV therapy “may improve quality of life and possibly even lower survival in certain disorders.”

In addition, he noted that sleep disturbances “may be the earliest sign of muscle weakness in [patients with neuromuscular disease], sometimes being detected before their underlying neuromuscular disease is diagnosed.”

Dr. Singh, Dr. Cao, and Dr. Venkateshiah each reported that they had no potential conflicts of interest.

The stark realities of antimicrobial resistance – including rising rates of difficult-to-treat infections, lack of a robust pipeline of future antimicrobials, and COVID-19 treatments that leave people more vulnerable to infections – remain urgent priorities, experts say.

For some patients, the pandemic and antimicrobial resistance (AMR) are intertwined.

“One patient I’m seeing now in service really underscores how the two interact,” Vance Fowler, MD, said during a June 30 media briefing sponsored by the Infectious Diseases Society of America (IDSA). A man in his mid-40s, married with a small child, developed COVID-19 in early January 2021. He was intubated, spent about 1 month in the ICU, and managed to survive.

“But since then he has been struck with a series of progressively more drug resistant bacteria,” said Dr. Fowler, professor of medicine at Duke University, Durham, N.C., and chair of the IDSA Antimicrobial Resistance Committee.

The patient acquired Pseudomonas ventilator-associated pneumonia. Although the infection initially responded to standard antibiotics, he has experienced relapses over the past few months. Through these multiple infections the Pseudomonas grew increasingly pan-resistant to treatment.

The only remaining antimicrobial agent for this patient, Dr. Fowler said, is “a case study in what we are describing ... a drug that is used relatively infrequently, that is fairly expensive, but for that particular patient is absolutely vital.”
 

A ‘terrifying’ personal experience

Tori Kinamon, a Duke University medical student and Food and Drug Administration antibacterial drug resistance fellow, joined Dr. Fowler at the IDSA briefing. She shared her personal journey of surviving a methicillin-resistant Staphylococcus aureus (MRSA) infection, one that sparked her interest in becoming a physician.

“I had a very frightening and unexpected confrontation with antimicrobial resistance when I was a freshman in college,” Ms. Kinamon said.

A few days after competing in a Division One gymnastics championship, she felt a gradual onset of pain in her left hamstring. The pain grew acutely worse and, within days, her leg become red, swollen, and painful to the touch.

Ms. Kinamon was admitted to the hospital for suspected cellulitis and put on intravenous antibiotics.

“However, my clinical condition continued to decline,” she recalled. “Imaging studies revealed a 15-cm abscess deep in my hamstring.”

The limb- and life-threatening infection left her wondering if she would come out of surgery with both legs.

“Ultimately, I had eight surgeries in 2 weeks,” she said.

“As a 19-year-old collegiate athlete, that’s terrifying. And I never imagined that something like that would happen to me – until it did,” said Ms. Kinamon, who is an NCAA infection prevention advocate.

When Ms. Kinamon’s kidneys could no longer tolerate vancomycin, she was switched to daptomycin.

“I reflect quite frequently on how having that one extra drug in the stockpile had a significant impact on my outcome,” she said.
 

Incentivizing new antimicrobial agents

A lack of new antimicrobials in development is not a new story.

“There’s been a chill that’s been sustained on the antibiotic development field. Most large pharmaceutical companies have left the area of anti-infectants and the bulk of research and development is now in small pharmaceutical companies,” Dr. Fowler said. “And they’re struggling.”

One potential solution is the Pasteur Act, a bipartisan bill reintroduced in Congress and supported by IDSA. The bill encourages pharmaceutical companies to develop new antimicrobial agents with funding not linked to sales or use of the drugs.

Furthermore, the bill emphasizes appropriate use of these agents through effective stewardship programs.

Although some institutions shifted resources away from AMR out of necessity when COVID-19 struck, “I can say certainly from our experience at Duke that at least stewardship was alive and well. It was not relegated to the side,” Dr. Fowler said.

“In fact,” he added, “if anything, COVID really emphasized the importance of stewardship” by helping clinicians with guidance on the use of remdesivir and other antivirals during the pandemic.

Also, in some instances, treatments used to keep people with COVID-19 alive can paradoxically place them at higher risk for other infections, Dr. Fowler said, citing corticosteroids as an example.
 

Everyone’s concern

AMR isn’t just an issue in hospital settings, either. Ms. Kinamon reiterated that she picked up the infection in an athletic environment.

“Antimicrobial resistance is not just a problem for ICU patients in the hospital. I was the healthiest I had ever been and just very nearly escaped death due to one of these infections,” she said. ”As rates of resistance rise as these pathogens become more virulent, AMR is becoming more and more of a community threat,” she added.

Furthermore, consumers are partially to blame as well, Dr. Fowler noted.

“It’s interesting when you look at the surveys of the numbers of patients that have used someone else’s antibiotics” or leftover antimicrobial agents from a prior infection.

“It’s really startling ... that’s the sort of antibiotic overuse that directly contributes to antibacterial resistance,” he said.
 

Reasons for optimism

Promising advances in diagnostics, treatment, and prevention of AMRs are underway, Dr. Fowler said.

“It always gets me really excited to talk about it. It’s amazing what technology and scientific discovery can bring to this discussion and to this threat,” he said.

For example, there is a “silent revolution” in diagnostics with the aim to rapidly provide life-saving actionable data on a real patient in nearly real time.

Traditionally, “you start off by treating what should be there” while awaiting results of tests to narrow down therapy, Dr. Fowler said. However, a whole host of new platforms are in development to reduce the time to susceptibility results. This kind of technology has “the potential to transform our ability to take care of patients, giving them the right drug at the right time and no more,” he said.

Another promising avenue of research involves bacteriophages. Dr. Fowler is principal investigator on a clinical trial underway to evaluate bacteriophages as adjunct therapy for MRSA bacteremia.

When it comes to prevention on AMR infections in the future, “I continue to be optimistic about the possibility of vaccines to prevent many of these infections,” Dr. Fowler said, adding that companies are working on vaccines against these kinds of infections caused by MRSA or Escherichia coli, for example.
 

Patient outcomes

The man in his 40s with the multidrug resistant Pseudomonas infections “is now to the point where he’s walking in the halls and I think he’ll get out of the hospital eventually,” Dr. Fowler said.

“But his life is forever changed,” he added.

Ms. Kinamon’s recovery from MRSA included time in the ICU, 1 month in a regular hospital setting, and 5 months at home.

“It sparked my interest in antibiotic research and development because I see myself as a direct beneficiary of the stockpile of antibiotics that were available to treat my infection,” Ms. Kinamon said. “Now as a medical student working with patients who have similar infections, I feel a deep empathy and connectedness to them because they ask the same questions that I did.”

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

The stark realities of antimicrobial resistance – including rising rates of difficult-to-treat infections, lack of a robust pipeline of future antimicrobials, and COVID-19 treatments that leave people more vulnerable to infections – remain urgent priorities, experts say.

For some patients, the pandemic and antimicrobial resistance (AMR) are intertwined.

“One patient I’m seeing now in service really underscores how the two interact,” Vance Fowler, MD, said during a June 30 media briefing sponsored by the Infectious Diseases Society of America (IDSA). A man in his mid-40s, married with a small child, developed COVID-19 in early January 2021. He was intubated, spent about 1 month in the ICU, and managed to survive.

“But since then he has been struck with a series of progressively more drug resistant bacteria,” said Dr. Fowler, professor of medicine at Duke University, Durham, N.C., and chair of the IDSA Antimicrobial Resistance Committee.

The patient acquired Pseudomonas ventilator-associated pneumonia. Although the infection initially responded to standard antibiotics, he has experienced relapses over the past few months. Through these multiple infections the Pseudomonas grew increasingly pan-resistant to treatment.

The only remaining antimicrobial agent for this patient, Dr. Fowler said, is “a case study in what we are describing ... a drug that is used relatively infrequently, that is fairly expensive, but for that particular patient is absolutely vital.”
 

A ‘terrifying’ personal experience

Tori Kinamon, a Duke University medical student and Food and Drug Administration antibacterial drug resistance fellow, joined Dr. Fowler at the IDSA briefing. She shared her personal journey of surviving a methicillin-resistant Staphylococcus aureus (MRSA) infection, one that sparked her interest in becoming a physician.

“I had a very frightening and unexpected confrontation with antimicrobial resistance when I was a freshman in college,” Ms. Kinamon said.

A few days after competing in a Division One gymnastics championship, she felt a gradual onset of pain in her left hamstring. The pain grew acutely worse and, within days, her leg become red, swollen, and painful to the touch.

Ms. Kinamon was admitted to the hospital for suspected cellulitis and put on intravenous antibiotics.

“However, my clinical condition continued to decline,” she recalled. “Imaging studies revealed a 15-cm abscess deep in my hamstring.”

The limb- and life-threatening infection left her wondering if she would come out of surgery with both legs.

“Ultimately, I had eight surgeries in 2 weeks,” she said.

“As a 19-year-old collegiate athlete, that’s terrifying. And I never imagined that something like that would happen to me – until it did,” said Ms. Kinamon, who is an NCAA infection prevention advocate.

When Ms. Kinamon’s kidneys could no longer tolerate vancomycin, she was switched to daptomycin.

“I reflect quite frequently on how having that one extra drug in the stockpile had a significant impact on my outcome,” she said.
 

Incentivizing new antimicrobial agents

A lack of new antimicrobials in development is not a new story.

“There’s been a chill that’s been sustained on the antibiotic development field. Most large pharmaceutical companies have left the area of anti-infectants and the bulk of research and development is now in small pharmaceutical companies,” Dr. Fowler said. “And they’re struggling.”

One potential solution is the Pasteur Act, a bipartisan bill reintroduced in Congress and supported by IDSA. The bill encourages pharmaceutical companies to develop new antimicrobial agents with funding not linked to sales or use of the drugs.

Furthermore, the bill emphasizes appropriate use of these agents through effective stewardship programs.

Although some institutions shifted resources away from AMR out of necessity when COVID-19 struck, “I can say certainly from our experience at Duke that at least stewardship was alive and well. It was not relegated to the side,” Dr. Fowler said.

“In fact,” he added, “if anything, COVID really emphasized the importance of stewardship” by helping clinicians with guidance on the use of remdesivir and other antivirals during the pandemic.

Also, in some instances, treatments used to keep people with COVID-19 alive can paradoxically place them at higher risk for other infections, Dr. Fowler said, citing corticosteroids as an example.
 

Everyone’s concern

AMR isn’t just an issue in hospital settings, either. Ms. Kinamon reiterated that she picked up the infection in an athletic environment.

“Antimicrobial resistance is not just a problem for ICU patients in the hospital. I was the healthiest I had ever been and just very nearly escaped death due to one of these infections,” she said. ”As rates of resistance rise as these pathogens become more virulent, AMR is becoming more and more of a community threat,” she added.

Furthermore, consumers are partially to blame as well, Dr. Fowler noted.

“It’s interesting when you look at the surveys of the numbers of patients that have used someone else’s antibiotics” or leftover antimicrobial agents from a prior infection.

“It’s really startling ... that’s the sort of antibiotic overuse that directly contributes to antibacterial resistance,” he said.
 

Reasons for optimism

Promising advances in diagnostics, treatment, and prevention of AMRs are underway, Dr. Fowler said.

“It always gets me really excited to talk about it. It’s amazing what technology and scientific discovery can bring to this discussion and to this threat,” he said.

For example, there is a “silent revolution” in diagnostics with the aim to rapidly provide life-saving actionable data on a real patient in nearly real time.

Traditionally, “you start off by treating what should be there” while awaiting results of tests to narrow down therapy, Dr. Fowler said. However, a whole host of new platforms are in development to reduce the time to susceptibility results. This kind of technology has “the potential to transform our ability to take care of patients, giving them the right drug at the right time and no more,” he said.

Another promising avenue of research involves bacteriophages. Dr. Fowler is principal investigator on a clinical trial underway to evaluate bacteriophages as adjunct therapy for MRSA bacteremia.

When it comes to prevention on AMR infections in the future, “I continue to be optimistic about the possibility of vaccines to prevent many of these infections,” Dr. Fowler said, adding that companies are working on vaccines against these kinds of infections caused by MRSA or Escherichia coli, for example.
 

Patient outcomes

The man in his 40s with the multidrug resistant Pseudomonas infections “is now to the point where he’s walking in the halls and I think he’ll get out of the hospital eventually,” Dr. Fowler said.

“But his life is forever changed,” he added.

Ms. Kinamon’s recovery from MRSA included time in the ICU, 1 month in a regular hospital setting, and 5 months at home.

“It sparked my interest in antibiotic research and development because I see myself as a direct beneficiary of the stockpile of antibiotics that were available to treat my infection,” Ms. Kinamon said. “Now as a medical student working with patients who have similar infections, I feel a deep empathy and connectedness to them because they ask the same questions that I did.”

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

The stark realities of antimicrobial resistance – including rising rates of difficult-to-treat infections, lack of a robust pipeline of future antimicrobials, and COVID-19 treatments that leave people more vulnerable to infections – remain urgent priorities, experts say.

For some patients, the pandemic and antimicrobial resistance (AMR) are intertwined.

“One patient I’m seeing now in service really underscores how the two interact,” Vance Fowler, MD, said during a June 30 media briefing sponsored by the Infectious Diseases Society of America (IDSA). A man in his mid-40s, married with a small child, developed COVID-19 in early January 2021. He was intubated, spent about 1 month in the ICU, and managed to survive.

“But since then he has been struck with a series of progressively more drug resistant bacteria,” said Dr. Fowler, professor of medicine at Duke University, Durham, N.C., and chair of the IDSA Antimicrobial Resistance Committee.

The patient acquired Pseudomonas ventilator-associated pneumonia. Although the infection initially responded to standard antibiotics, he has experienced relapses over the past few months. Through these multiple infections the Pseudomonas grew increasingly pan-resistant to treatment.

The only remaining antimicrobial agent for this patient, Dr. Fowler said, is “a case study in what we are describing ... a drug that is used relatively infrequently, that is fairly expensive, but for that particular patient is absolutely vital.”
 

A ‘terrifying’ personal experience

Tori Kinamon, a Duke University medical student and Food and Drug Administration antibacterial drug resistance fellow, joined Dr. Fowler at the IDSA briefing. She shared her personal journey of surviving a methicillin-resistant Staphylococcus aureus (MRSA) infection, one that sparked her interest in becoming a physician.

“I had a very frightening and unexpected confrontation with antimicrobial resistance when I was a freshman in college,” Ms. Kinamon said.

A few days after competing in a Division One gymnastics championship, she felt a gradual onset of pain in her left hamstring. The pain grew acutely worse and, within days, her leg become red, swollen, and painful to the touch.

Ms. Kinamon was admitted to the hospital for suspected cellulitis and put on intravenous antibiotics.

“However, my clinical condition continued to decline,” she recalled. “Imaging studies revealed a 15-cm abscess deep in my hamstring.”

The limb- and life-threatening infection left her wondering if she would come out of surgery with both legs.

“Ultimately, I had eight surgeries in 2 weeks,” she said.

“As a 19-year-old collegiate athlete, that’s terrifying. And I never imagined that something like that would happen to me – until it did,” said Ms. Kinamon, who is an NCAA infection prevention advocate.

When Ms. Kinamon’s kidneys could no longer tolerate vancomycin, she was switched to daptomycin.

“I reflect quite frequently on how having that one extra drug in the stockpile had a significant impact on my outcome,” she said.
 

Incentivizing new antimicrobial agents

A lack of new antimicrobials in development is not a new story.

“There’s been a chill that’s been sustained on the antibiotic development field. Most large pharmaceutical companies have left the area of anti-infectants and the bulk of research and development is now in small pharmaceutical companies,” Dr. Fowler said. “And they’re struggling.”

One potential solution is the Pasteur Act, a bipartisan bill reintroduced in Congress and supported by IDSA. The bill encourages pharmaceutical companies to develop new antimicrobial agents with funding not linked to sales or use of the drugs.

Furthermore, the bill emphasizes appropriate use of these agents through effective stewardship programs.

Although some institutions shifted resources away from AMR out of necessity when COVID-19 struck, “I can say certainly from our experience at Duke that at least stewardship was alive and well. It was not relegated to the side,” Dr. Fowler said.

“In fact,” he added, “if anything, COVID really emphasized the importance of stewardship” by helping clinicians with guidance on the use of remdesivir and other antivirals during the pandemic.

Also, in some instances, treatments used to keep people with COVID-19 alive can paradoxically place them at higher risk for other infections, Dr. Fowler said, citing corticosteroids as an example.
 

Everyone’s concern

AMR isn’t just an issue in hospital settings, either. Ms. Kinamon reiterated that she picked up the infection in an athletic environment.

“Antimicrobial resistance is not just a problem for ICU patients in the hospital. I was the healthiest I had ever been and just very nearly escaped death due to one of these infections,” she said. ”As rates of resistance rise as these pathogens become more virulent, AMR is becoming more and more of a community threat,” she added.

Furthermore, consumers are partially to blame as well, Dr. Fowler noted.

“It’s interesting when you look at the surveys of the numbers of patients that have used someone else’s antibiotics” or leftover antimicrobial agents from a prior infection.

“It’s really startling ... that’s the sort of antibiotic overuse that directly contributes to antibacterial resistance,” he said.
 

Reasons for optimism

Promising advances in diagnostics, treatment, and prevention of AMRs are underway, Dr. Fowler said.

“It always gets me really excited to talk about it. It’s amazing what technology and scientific discovery can bring to this discussion and to this threat,” he said.

For example, there is a “silent revolution” in diagnostics with the aim to rapidly provide life-saving actionable data on a real patient in nearly real time.

Traditionally, “you start off by treating what should be there” while awaiting results of tests to narrow down therapy, Dr. Fowler said. However, a whole host of new platforms are in development to reduce the time to susceptibility results. This kind of technology has “the potential to transform our ability to take care of patients, giving them the right drug at the right time and no more,” he said.

Another promising avenue of research involves bacteriophages. Dr. Fowler is principal investigator on a clinical trial underway to evaluate bacteriophages as adjunct therapy for MRSA bacteremia.

When it comes to prevention on AMR infections in the future, “I continue to be optimistic about the possibility of vaccines to prevent many of these infections,” Dr. Fowler said, adding that companies are working on vaccines against these kinds of infections caused by MRSA or Escherichia coli, for example.
 

Patient outcomes

The man in his 40s with the multidrug resistant Pseudomonas infections “is now to the point where he’s walking in the halls and I think he’ll get out of the hospital eventually,” Dr. Fowler said.

“But his life is forever changed,” he added.

Ms. Kinamon’s recovery from MRSA included time in the ICU, 1 month in a regular hospital setting, and 5 months at home.

“It sparked my interest in antibiotic research and development because I see myself as a direct beneficiary of the stockpile of antibiotics that were available to treat my infection,” Ms. Kinamon said. “Now as a medical student working with patients who have similar infections, I feel a deep empathy and connectedness to them because they ask the same questions that I did.”

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