Federal Practitioner

Frequent visits to green spaces such as parks and community gardens are associated with a reduced use of certain prescription medications among city dwellers, a new analysis suggests.

In a cross-sectional cohort study, frequent green space visits were associated with less frequent use of psychotropic, antihypertensive, and asthma medications in urban environments.

Viewing green or so called “blue” spaces (views of lakes, rivers, or other water views) from the home was not associated with reduced medication use.

Flickr-Rickr [CC BY-SA 2.0](http://creativecommons.org/licenses/by-sa/2.0)], via Wikimedia Commons

Nature exposure a timely topic

Exposure to natural environments is thought to be beneficial for human health, but the evidence is inconsistent, Dr. Turunen said.

“The potential health benefits of nature exposure is a very timely topic in environmental epidemiology. Scientific evidence indicates that residential exposure to greenery and water bodies might be beneficial, especially for mental, cardiovascular, and respiratory health, but the findings are partly inconsistent and thus, more detailed information is needed,” she said.

In the current cross-sectional study, the investigators surveyed 16,000 residents of three urban areas in Finland – Helsinki, Espoo, and Vantaa – over the period of 12 months from 2015 to 2016, about their exposure to green and blue spaces.

Of this number, 43% responded, resulting in 7,321 participants.

In the questionnaire, green areas were defined as forests, parks, fields, meadows, boglands, and rocks, as well as any playgrounds or playing fields within those areas, and blue areas were defined as sea, lakes, and rivers. 

Residents were asked about their use of anxiolytics, hypnotics, antidepressants, antihypertensives, and asthma medication within the past 7 to 52 weeks.

They were also asked if they had any green and blue views from any of the windows of their home, and if so, how often did they look out of those windows, selecting “seldom” to “often.”

They were also asked about how much time they spent outdoors in green spaces during the months of May and September. If so, did they spend any of that time exercising? Options ranged from never to five or more times a week.

In addition, amounts of residential green and blue spaces located within a 1 km radius of the respondents’ homes were assessed from land use and land cover data.

Covariates included health behaviors, outdoor air pollution and noise, and socioeconomic status, including household income and educational attainment.

Results showed that the presence of green and blue spaces at home, and the amount of time spent viewing them, had no association with the use of the prescribed medicines.

However, greater frequency of green space visits was associated with lower odds of using the medications surveyed.

For psychotropic medications, the odds ratios were 0.67 (95% confidence interval, 0.55-0.82) for 3-4 times per week and 0.78 (95% CI, 0.63-0.96) for 5 or more times per week.

For antihypertensive meds, the ORs were 0.64 (95% CI, 0.52-0.78) for 3-4 times per week and 0.59 (95% CI, 0.48-0.74) for 5 or more times per week.

For asthma medications, the ORs were 0.74 (95% CI, 0.58-0.94) for 3-4 times per week and 0.76 (95% CI, 0.59-0.99) for 5 or more times per week.

The observed associations were attenuated by body mass index.

“We observed that those who reported visiting green spaces often had a slightly lower BMI than those who visited green spaces less often,” Dr. Turunen said. However, no consistent interactions with socioeconomic status indicators were observed.

“We are hoping to see new results from different countries and different settings,” she noted. “Longitudinal studies, especially, are needed. In epidemiology, a large body of consistent evidence is needed to draw strong conclusions and to make recommendations.”
 

Evidence mounts on the benefits of nature

There is growing evidence that exposure to nature could benefit human health, especially mental and cardiovascular health, says Jochem Klompmaker, PhD, a postdoctoral researcher in the department of environmental health at the Harvard T.H. Chan School of Public Health, Boston.

Dr. Klompmaker has researched the association between exposure to green spaces and health outcomes related to neurological diseases.

In a study recently published in JAMA Network Open, and reported by this news organization, Dr. Klompmaker and his team found that among a large cohort of about 6.7 million fee-for-service Medicare beneficiaries in the United States aged 65 or older, living in areas rich with greenery, parks, and waterways was associated with fewer hospitalizations for certain neurological disorders, including Parkinson’s disease, Alzheimer’s disease, and related dementias.

Commenting on the current study, Dr. Klompmaker noted its strengths.

“A particular strength of this study is that they used data about the amount of green and blue spaces around the residential addresses of the participants, data about green space visit frequency, and data about green and blue views from home. Most other studies only have data about the amount of green and blue spaces in general,” he said.

“The strong protective associations of frequency of green space visits make sense to me and indicate the importance of one’s actual nature exposure,” he added. “Like the results of our study, these results provide clinicians with more evidence of the importance of being close to nature and of encouraging patients to take more walks. If they live near a park, that could be a good place to be more physically active and reduce stress levels.”

The study was supported by the Academy of Finland and the Ministry of the Environment. Dr. Turunen and Dr. Klompmaker report no relevant financial relationships.

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

Frequent visits to green spaces such as parks and community gardens are associated with a reduced use of certain prescription medications among city dwellers, a new analysis suggests.

In a cross-sectional cohort study, frequent green space visits were associated with less frequent use of psychotropic, antihypertensive, and asthma medications in urban environments.

Viewing green or so called “blue” spaces (views of lakes, rivers, or other water views) from the home was not associated with reduced medication use.

Flickr-Rickr [CC BY-SA 2.0](http://creativecommons.org/licenses/by-sa/2.0)], via Wikimedia Commons

Nature exposure a timely topic

Exposure to natural environments is thought to be beneficial for human health, but the evidence is inconsistent, Dr. Turunen said.

“The potential health benefits of nature exposure is a very timely topic in environmental epidemiology. Scientific evidence indicates that residential exposure to greenery and water bodies might be beneficial, especially for mental, cardiovascular, and respiratory health, but the findings are partly inconsistent and thus, more detailed information is needed,” she said.

In the current cross-sectional study, the investigators surveyed 16,000 residents of three urban areas in Finland – Helsinki, Espoo, and Vantaa – over the period of 12 months from 2015 to 2016, about their exposure to green and blue spaces.

Of this number, 43% responded, resulting in 7,321 participants.

In the questionnaire, green areas were defined as forests, parks, fields, meadows, boglands, and rocks, as well as any playgrounds or playing fields within those areas, and blue areas were defined as sea, lakes, and rivers. 

Residents were asked about their use of anxiolytics, hypnotics, antidepressants, antihypertensives, and asthma medication within the past 7 to 52 weeks.

They were also asked if they had any green and blue views from any of the windows of their home, and if so, how often did they look out of those windows, selecting “seldom” to “often.”

They were also asked about how much time they spent outdoors in green spaces during the months of May and September. If so, did they spend any of that time exercising? Options ranged from never to five or more times a week.

In addition, amounts of residential green and blue spaces located within a 1 km radius of the respondents’ homes were assessed from land use and land cover data.

Covariates included health behaviors, outdoor air pollution and noise, and socioeconomic status, including household income and educational attainment.

Results showed that the presence of green and blue spaces at home, and the amount of time spent viewing them, had no association with the use of the prescribed medicines.

However, greater frequency of green space visits was associated with lower odds of using the medications surveyed.

For psychotropic medications, the odds ratios were 0.67 (95% confidence interval, 0.55-0.82) for 3-4 times per week and 0.78 (95% CI, 0.63-0.96) for 5 or more times per week.

For antihypertensive meds, the ORs were 0.64 (95% CI, 0.52-0.78) for 3-4 times per week and 0.59 (95% CI, 0.48-0.74) for 5 or more times per week.

For asthma medications, the ORs were 0.74 (95% CI, 0.58-0.94) for 3-4 times per week and 0.76 (95% CI, 0.59-0.99) for 5 or more times per week.

The observed associations were attenuated by body mass index.

“We observed that those who reported visiting green spaces often had a slightly lower BMI than those who visited green spaces less often,” Dr. Turunen said. However, no consistent interactions with socioeconomic status indicators were observed.

“We are hoping to see new results from different countries and different settings,” she noted. “Longitudinal studies, especially, are needed. In epidemiology, a large body of consistent evidence is needed to draw strong conclusions and to make recommendations.”
 

Evidence mounts on the benefits of nature

There is growing evidence that exposure to nature could benefit human health, especially mental and cardiovascular health, says Jochem Klompmaker, PhD, a postdoctoral researcher in the department of environmental health at the Harvard T.H. Chan School of Public Health, Boston.

Dr. Klompmaker has researched the association between exposure to green spaces and health outcomes related to neurological diseases.

In a study recently published in JAMA Network Open, and reported by this news organization, Dr. Klompmaker and his team found that among a large cohort of about 6.7 million fee-for-service Medicare beneficiaries in the United States aged 65 or older, living in areas rich with greenery, parks, and waterways was associated with fewer hospitalizations for certain neurological disorders, including Parkinson’s disease, Alzheimer’s disease, and related dementias.

Commenting on the current study, Dr. Klompmaker noted its strengths.

“A particular strength of this study is that they used data about the amount of green and blue spaces around the residential addresses of the participants, data about green space visit frequency, and data about green and blue views from home. Most other studies only have data about the amount of green and blue spaces in general,” he said.

“The strong protective associations of frequency of green space visits make sense to me and indicate the importance of one’s actual nature exposure,” he added. “Like the results of our study, these results provide clinicians with more evidence of the importance of being close to nature and of encouraging patients to take more walks. If they live near a park, that could be a good place to be more physically active and reduce stress levels.”

The study was supported by the Academy of Finland and the Ministry of the Environment. Dr. Turunen and Dr. Klompmaker report no relevant financial relationships.

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

Frequent visits to green spaces such as parks and community gardens are associated with a reduced use of certain prescription medications among city dwellers, a new analysis suggests.

In a cross-sectional cohort study, frequent green space visits were associated with less frequent use of psychotropic, antihypertensive, and asthma medications in urban environments.

Viewing green or so called “blue” spaces (views of lakes, rivers, or other water views) from the home was not associated with reduced medication use.

Flickr-Rickr [CC BY-SA 2.0](http://creativecommons.org/licenses/by-sa/2.0)], via Wikimedia Commons

Nature exposure a timely topic

Exposure to natural environments is thought to be beneficial for human health, but the evidence is inconsistent, Dr. Turunen said.

“The potential health benefits of nature exposure is a very timely topic in environmental epidemiology. Scientific evidence indicates that residential exposure to greenery and water bodies might be beneficial, especially for mental, cardiovascular, and respiratory health, but the findings are partly inconsistent and thus, more detailed information is needed,” she said.

In the current cross-sectional study, the investigators surveyed 16,000 residents of three urban areas in Finland – Helsinki, Espoo, and Vantaa – over the period of 12 months from 2015 to 2016, about their exposure to green and blue spaces.

Of this number, 43% responded, resulting in 7,321 participants.

In the questionnaire, green areas were defined as forests, parks, fields, meadows, boglands, and rocks, as well as any playgrounds or playing fields within those areas, and blue areas were defined as sea, lakes, and rivers. 

Residents were asked about their use of anxiolytics, hypnotics, antidepressants, antihypertensives, and asthma medication within the past 7 to 52 weeks.

They were also asked if they had any green and blue views from any of the windows of their home, and if so, how often did they look out of those windows, selecting “seldom” to “often.”

They were also asked about how much time they spent outdoors in green spaces during the months of May and September. If so, did they spend any of that time exercising? Options ranged from never to five or more times a week.

In addition, amounts of residential green and blue spaces located within a 1 km radius of the respondents’ homes were assessed from land use and land cover data.

Covariates included health behaviors, outdoor air pollution and noise, and socioeconomic status, including household income and educational attainment.

Results showed that the presence of green and blue spaces at home, and the amount of time spent viewing them, had no association with the use of the prescribed medicines.

However, greater frequency of green space visits was associated with lower odds of using the medications surveyed.

For psychotropic medications, the odds ratios were 0.67 (95% confidence interval, 0.55-0.82) for 3-4 times per week and 0.78 (95% CI, 0.63-0.96) for 5 or more times per week.

For antihypertensive meds, the ORs were 0.64 (95% CI, 0.52-0.78) for 3-4 times per week and 0.59 (95% CI, 0.48-0.74) for 5 or more times per week.

For asthma medications, the ORs were 0.74 (95% CI, 0.58-0.94) for 3-4 times per week and 0.76 (95% CI, 0.59-0.99) for 5 or more times per week.

The observed associations were attenuated by body mass index.

“We observed that those who reported visiting green spaces often had a slightly lower BMI than those who visited green spaces less often,” Dr. Turunen said. However, no consistent interactions with socioeconomic status indicators were observed.

“We are hoping to see new results from different countries and different settings,” she noted. “Longitudinal studies, especially, are needed. In epidemiology, a large body of consistent evidence is needed to draw strong conclusions and to make recommendations.”
 

Evidence mounts on the benefits of nature

There is growing evidence that exposure to nature could benefit human health, especially mental and cardiovascular health, says Jochem Klompmaker, PhD, a postdoctoral researcher in the department of environmental health at the Harvard T.H. Chan School of Public Health, Boston.

Dr. Klompmaker has researched the association between exposure to green spaces and health outcomes related to neurological diseases.

In a study recently published in JAMA Network Open, and reported by this news organization, Dr. Klompmaker and his team found that among a large cohort of about 6.7 million fee-for-service Medicare beneficiaries in the United States aged 65 or older, living in areas rich with greenery, parks, and waterways was associated with fewer hospitalizations for certain neurological disorders, including Parkinson’s disease, Alzheimer’s disease, and related dementias.

Commenting on the current study, Dr. Klompmaker noted its strengths.

“A particular strength of this study is that they used data about the amount of green and blue spaces around the residential addresses of the participants, data about green space visit frequency, and data about green and blue views from home. Most other studies only have data about the amount of green and blue spaces in general,” he said.

“The strong protective associations of frequency of green space visits make sense to me and indicate the importance of one’s actual nature exposure,” he added. “Like the results of our study, these results provide clinicians with more evidence of the importance of being close to nature and of encouraging patients to take more walks. If they live near a park, that could be a good place to be more physically active and reduce stress levels.”

The study was supported by the Academy of Finland and the Ministry of the Environment. Dr. Turunen and Dr. Klompmaker report no relevant financial relationships.

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

This transcript has been edited for clarity.

I’m Dr. Neil Skolnik. Today we are going to talk about the new Blood Pressure Targets in Adults With Hypertension: A Clinical Practice Guideline From the AAFP. There are very few things that we treat more often than hypertension, so you’d think the guidelines would have been clear a long time ago. Less than 10 years ago, in 2014, JNC 8 (Eighth Joint National Committee) recommended target blood pressure for individuals under 60 to be less than 140/90, and for those older than 60, less than 150/90.

Then, based primarily on the SPRINT trial (which included only people with or at significantly elevated risk for atherosclerotic cardiovascular disease), in 2017 the American Heart Association’s hypertension guidelines lowered the target BP to less than 130/80 for most individuals. It’s a little more nuanced than that, but most of us don’t remember the nuance. I’ve written about my reservations with that statement in the AHA’s journal, Circulation.

Now the American Academy of Family Physicians has updated its recommendations, and they recommend a BP less than 140/90. This is not a small change, as it often takes additional medication to achieve lower BP targets, and additional medicines lead to additional adverse effects. I’m going share with you some details from the new guideline, and then I’m going share my opinion about it.

The AAFP guideline applies to adults with hypertension, with or without cardiovascular disease. In the comprehensive literature review, the trials ran for an average of 3.7 years, and about 75% of the patients in the trials did not have preexisting cardiovascular disease.

The key to their recommendations is that target BPs lower than 140/90 did not show a statistically significant decrease in total mortality. In regard to serious adverse events, though, lower targets led to a nominal increase that didn’t reach statistical significance. Serious adverse events were defined as death or events that required hospitalization or resulted in significant disability. In regard to all other adverse events, including syncope and hypotension, there was a significant increase, with a relative risk of 1.44 (a 44% increase in adverse events). This reflected an absolute risk increase of 3%, compared with the standard target group (specifically 9.8% vs. 6.8%), with a number needed to harm of 33 over 3.7 years.

Another potential harm of low BP targets was the need for an average of one additional medicine to reach lower BP targets. One systematic review cited an eightfold higher withdrawal rate because of adverse events in the lower-target BP groups.

The AAFP guidelines said that, in the comprehensive review of the literature, while there was no difference in mortality or stroke with lower BP targets, a small additional benefit was observed in myocardial infarction – a 16% lower incidence, with a number needed to treat of 137 over 3.7 years.

So that’s the background. Let me now go over the specifics of the AAFP recommendations.

AAFP gives a strong recommendation for a standard BP target of less than 140/90. They go on to say – and grade this next statement as a weak recommendation – that, while treating to a lower BP target does not provide additional mortality benefit, a target BP of less than 135/85 can be considered to lower the risk for MI, noting that lower BP may increase harms. They state that the lower BP target could be considered based on patient preferences and values.

The AAFP guideline is incredibly helpful. The difference in the recommendations of two large societies – American Heart Association and AAFP — stems from two things. I believe that AHA focused on the composite endpoints in trials such as SPRINT, which included only high-risk patients, and the AAFP uses mortality as the driving endpoint in a broader group of patients that included both high- and lower-risk patients.

In addition, it appears that the two organizations weigh adverse events differently in coming to their conclusions. Clearly, we see more adverse events when aiming for a lower BP level, and in my experience, patients care a lot about adverse events.

Interestingly, the International Society of Hypertension recommends an “essential” BP target of less than 140/90 for most individuals, and for those under 65, they provide the option of an “optimal” BP of less than 130/80. Remember that for certain comorbidities there are also other guidelines out there. The American Diabetes Association this year revised its target BP to less than 130/80 for people with diabetes; for prevention of recurrent stroke, guidelines from the AHA/American Stroke Association in 2021 recommend BP less than 130/80, and the International Society for Hypertension as well as the AHA recommends a BP of less than 130/80 for those with established atherosclerotic cardiovascular disease.

To repeat, though, the main topic for today is that as a general target, the AAFP guidelines recommend a BP less than 140/90.

Dr. Skolnik is professor, department of family medicine, Sidney Kimmel Medical College, Philadelphia, and associate director, department of family medicine, Abington (Pa.) Jefferson Health. He disclosed conflicts of interest with AstraZeneca, Teva, Eli Lilly, Boehringer Ingelheim, Sanofi, Sanofi Pasteur, GlaxoSmithKline, Merck, and Bayer.

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

*This article was updated on 2/7/2023.

This transcript has been edited for clarity.

I’m Dr. Neil Skolnik. Today we are going to talk about the new Blood Pressure Targets in Adults With Hypertension: A Clinical Practice Guideline From the AAFP. There are very few things that we treat more often than hypertension, so you’d think the guidelines would have been clear a long time ago. Less than 10 years ago, in 2014, JNC 8 (Eighth Joint National Committee) recommended target blood pressure for individuals under 60 to be less than 140/90, and for those older than 60, less than 150/90.

Then, based primarily on the SPRINT trial (which included only people with or at significantly elevated risk for atherosclerotic cardiovascular disease), in 2017 the American Heart Association’s hypertension guidelines lowered the target BP to less than 130/80 for most individuals. It’s a little more nuanced than that, but most of us don’t remember the nuance. I’ve written about my reservations with that statement in the AHA’s journal, Circulation.

Now the American Academy of Family Physicians has updated its recommendations, and they recommend a BP less than 140/90. This is not a small change, as it often takes additional medication to achieve lower BP targets, and additional medicines lead to additional adverse effects. I’m going share with you some details from the new guideline, and then I’m going share my opinion about it.

The AAFP guideline applies to adults with hypertension, with or without cardiovascular disease. In the comprehensive literature review, the trials ran for an average of 3.7 years, and about 75% of the patients in the trials did not have preexisting cardiovascular disease.

The key to their recommendations is that target BPs lower than 140/90 did not show a statistically significant decrease in total mortality. In regard to serious adverse events, though, lower targets led to a nominal increase that didn’t reach statistical significance. Serious adverse events were defined as death or events that required hospitalization or resulted in significant disability. In regard to all other adverse events, including syncope and hypotension, there was a significant increase, with a relative risk of 1.44 (a 44% increase in adverse events). This reflected an absolute risk increase of 3%, compared with the standard target group (specifically 9.8% vs. 6.8%), with a number needed to harm of 33 over 3.7 years.

Another potential harm of low BP targets was the need for an average of one additional medicine to reach lower BP targets. One systematic review cited an eightfold higher withdrawal rate because of adverse events in the lower-target BP groups.

The AAFP guidelines said that, in the comprehensive review of the literature, while there was no difference in mortality or stroke with lower BP targets, a small additional benefit was observed in myocardial infarction – a 16% lower incidence, with a number needed to treat of 137 over 3.7 years.

So that’s the background. Let me now go over the specifics of the AAFP recommendations.

AAFP gives a strong recommendation for a standard BP target of less than 140/90. They go on to say – and grade this next statement as a weak recommendation – that, while treating to a lower BP target does not provide additional mortality benefit, a target BP of less than 135/85 can be considered to lower the risk for MI, noting that lower BP may increase harms. They state that the lower BP target could be considered based on patient preferences and values.

The AAFP guideline is incredibly helpful. The difference in the recommendations of two large societies – American Heart Association and AAFP — stems from two things. I believe that AHA focused on the composite endpoints in trials such as SPRINT, which included only high-risk patients, and the AAFP uses mortality as the driving endpoint in a broader group of patients that included both high- and lower-risk patients.

In addition, it appears that the two organizations weigh adverse events differently in coming to their conclusions. Clearly, we see more adverse events when aiming for a lower BP level, and in my experience, patients care a lot about adverse events.

Interestingly, the International Society of Hypertension recommends an “essential” BP target of less than 140/90 for most individuals, and for those under 65, they provide the option of an “optimal” BP of less than 130/80. Remember that for certain comorbidities there are also other guidelines out there. The American Diabetes Association this year revised its target BP to less than 130/80 for people with diabetes; for prevention of recurrent stroke, guidelines from the AHA/American Stroke Association in 2021 recommend BP less than 130/80, and the International Society for Hypertension as well as the AHA recommends a BP of less than 130/80 for those with established atherosclerotic cardiovascular disease.

To repeat, though, the main topic for today is that as a general target, the AAFP guidelines recommend a BP less than 140/90.

Dr. Skolnik is professor, department of family medicine, Sidney Kimmel Medical College, Philadelphia, and associate director, department of family medicine, Abington (Pa.) Jefferson Health. He disclosed conflicts of interest with AstraZeneca, Teva, Eli Lilly, Boehringer Ingelheim, Sanofi, Sanofi Pasteur, GlaxoSmithKline, Merck, and Bayer.

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

*This article was updated on 2/7/2023.

This transcript has been edited for clarity.

I’m Dr. Neil Skolnik. Today we are going to talk about the new Blood Pressure Targets in Adults With Hypertension: A Clinical Practice Guideline From the AAFP. There are very few things that we treat more often than hypertension, so you’d think the guidelines would have been clear a long time ago. Less than 10 years ago, in 2014, JNC 8 (Eighth Joint National Committee) recommended target blood pressure for individuals under 60 to be less than 140/90, and for those older than 60, less than 150/90.

Then, based primarily on the SPRINT trial (which included only people with or at significantly elevated risk for atherosclerotic cardiovascular disease), in 2017 the American Heart Association’s hypertension guidelines lowered the target BP to less than 130/80 for most individuals. It’s a little more nuanced than that, but most of us don’t remember the nuance. I’ve written about my reservations with that statement in the AHA’s journal, Circulation.

Now the American Academy of Family Physicians has updated its recommendations, and they recommend a BP less than 140/90. This is not a small change, as it often takes additional medication to achieve lower BP targets, and additional medicines lead to additional adverse effects. I’m going share with you some details from the new guideline, and then I’m going share my opinion about it.

The AAFP guideline applies to adults with hypertension, with or without cardiovascular disease. In the comprehensive literature review, the trials ran for an average of 3.7 years, and about 75% of the patients in the trials did not have preexisting cardiovascular disease.

The key to their recommendations is that target BPs lower than 140/90 did not show a statistically significant decrease in total mortality. In regard to serious adverse events, though, lower targets led to a nominal increase that didn’t reach statistical significance. Serious adverse events were defined as death or events that required hospitalization or resulted in significant disability. In regard to all other adverse events, including syncope and hypotension, there was a significant increase, with a relative risk of 1.44 (a 44% increase in adverse events). This reflected an absolute risk increase of 3%, compared with the standard target group (specifically 9.8% vs. 6.8%), with a number needed to harm of 33 over 3.7 years.

Another potential harm of low BP targets was the need for an average of one additional medicine to reach lower BP targets. One systematic review cited an eightfold higher withdrawal rate because of adverse events in the lower-target BP groups.

The AAFP guidelines said that, in the comprehensive review of the literature, while there was no difference in mortality or stroke with lower BP targets, a small additional benefit was observed in myocardial infarction – a 16% lower incidence, with a number needed to treat of 137 over 3.7 years.

So that’s the background. Let me now go over the specifics of the AAFP recommendations.

AAFP gives a strong recommendation for a standard BP target of less than 140/90. They go on to say – and grade this next statement as a weak recommendation – that, while treating to a lower BP target does not provide additional mortality benefit, a target BP of less than 135/85 can be considered to lower the risk for MI, noting that lower BP may increase harms. They state that the lower BP target could be considered based on patient preferences and values.

The AAFP guideline is incredibly helpful. The difference in the recommendations of two large societies – American Heart Association and AAFP — stems from two things. I believe that AHA focused on the composite endpoints in trials such as SPRINT, which included only high-risk patients, and the AAFP uses mortality as the driving endpoint in a broader group of patients that included both high- and lower-risk patients.

In addition, it appears that the two organizations weigh adverse events differently in coming to their conclusions. Clearly, we see more adverse events when aiming for a lower BP level, and in my experience, patients care a lot about adverse events.

Interestingly, the International Society of Hypertension recommends an “essential” BP target of less than 140/90 for most individuals, and for those under 65, they provide the option of an “optimal” BP of less than 130/80. Remember that for certain comorbidities there are also other guidelines out there. The American Diabetes Association this year revised its target BP to less than 130/80 for people with diabetes; for prevention of recurrent stroke, guidelines from the AHA/American Stroke Association in 2021 recommend BP less than 130/80, and the International Society for Hypertension as well as the AHA recommends a BP of less than 130/80 for those with established atherosclerotic cardiovascular disease.

To repeat, though, the main topic for today is that as a general target, the AAFP guidelines recommend a BP less than 140/90.

Dr. Skolnik is professor, department of family medicine, Sidney Kimmel Medical College, Philadelphia, and associate director, department of family medicine, Abington (Pa.) Jefferson Health. He disclosed conflicts of interest with AstraZeneca, Teva, Eli Lilly, Boehringer Ingelheim, Sanofi, Sanofi Pasteur, GlaxoSmithKline, Merck, and Bayer.

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

*This article was updated on 2/7/2023.

Opioids are widely regarded as a linchpin in the treatment of moderate to severe cancer-related pain and end-of-life symptoms; however, there are persistent racial and ethnic inequities in opioid access among older cancer patients, with Black patients being disproportionately affected, a new study suggests.

Black patients were more likely to undergo urine drug screening (UDS) despite being less likely to receive any opioids for pain management and receiving lower daily doses of opioids in comparison with White patients, the study found.

The inequities were particularly stark for Black men. “We found that Black men were far less likely to be prescribed reasonable doses than White men were,” said the study’s senior author, Alexi Wright, MD, MPH, a gynecologic oncologist and a researcher in the division of population sciences at Dana-Farber Cancer Institute, Boston. “And Black men were less likely to receive long-acting opioids, which are essential for many patients dying of cancer. Our findings are startling because everyone should agree that cancer patients should have equal access to pain relief at the end of life.”

The study was published on in the Journal of Clinical Oncology.

The researchers gathered data on 318,549 Medicare beneficiaries older than 65 years with poor-prognosis cancers who died between 2007 and 2019. During this time frame, for all groups, access to opioids declined and urine drug testing expanded, owing to the overall opioid epidemic in the United States. Overall, the proportion of patients near end of life (EOL) who received any opioid or long-acting opioids decreased from 42.2% to 32.7% and from 17.9% to 9.4%, respectively.

The investigators used National Drug Codes to identify all Medicare Part D claims for outpatient opioid prescriptions, excluding addiction treatments, cough suppressants, and parenteral opioids. They focused on prescriptions that were filled at least 30 days before death or hospice enrollment.

Among the study participants, the majority (85.5%) of patients were White, 29,555 patients (9.3%) were Black, and 16,636 patients (5.2%) were Hispanic.

Black and Hispanic patients were statistically less likely than White patients to receive opioid prescriptions near EOL (Black, –4.3 percentage points; Hispanic, –3.6 percentage points). They were also less likely to receive long-acting opioid prescriptions (Black, –3.1 percentage points; Hispanic, –2.2 percentage points).

“It’s not just that patients of color are less likely to get opioids, but when they do get them, they get lower doses, and they also are less likely to get long-acting opioids, which a lot of people view as sort of more potential for addiction, which isn’t necessarily true but kind of viewed with heightened concern or suspicion,” the study’s lead author, Andrea Enzinger, MD, a gastrointestinal oncologist and a researcher in Dana-Farber’s division of population sciences, said in an interview.

Dr. Enzinger added that she believes systemic racism and preconceived biases toward minorities and drug addiction may be contributing to these trends.

When Black patients did receive at least one opioid prescription, they received daily doses that were 10.5 morphine milligram equivalents (MMEs) lower than doses given to White patients. Compared with the total opioid dose filled per White decedent near EOL, the total dose filled per Black decedent was 210 MMEs lower.

“We all need to be worried about the potential for misuse or addiction, but this is the one setting that is very low on my priority list when somebody is dying. I mean, we’re looking at the last month of life, so nobody has the potential to become addicted,” Dr. Enzinger commented.

The team also evaluated rates or urine drug screening (UDS), but as these rates were relatively low, they expanded the time frame to 180 days before death or hospice. They found that disparities in UDS disproportionately affected Black men.

From 2007 to 2019, the proportion of patients who underwent UDS increased from 0.6% to 6.7% in the 180 days before death or hospice; however, Black decedents were tested more often than White or Hispanic decedents.

Black decedents were 0.5 percentage points more likely than White decedents to undergo UDS near EOL.

“The disparities in urine drug screening are modest but important, because they hint at underlying systematic racism in recommending patients for screening,” Dr. Wright said. “Screening needs to either be applied uniformly or not at all for patients in this situation.”

The researchers acknowledged that their findings likely do not represent the full spectrum of prescribing disparities and believe that the work should be expanded among younger populations. Nevertheless, the investigators believe the work highlights the persistent racial and ethnic disparities in opioid access.

The study was supported by a grant from the Agency for Healthcare Research and Policy.

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

Opioids are widely regarded as a linchpin in the treatment of moderate to severe cancer-related pain and end-of-life symptoms; however, there are persistent racial and ethnic inequities in opioid access among older cancer patients, with Black patients being disproportionately affected, a new study suggests.

Black patients were more likely to undergo urine drug screening (UDS) despite being less likely to receive any opioids for pain management and receiving lower daily doses of opioids in comparison with White patients, the study found.

The inequities were particularly stark for Black men. “We found that Black men were far less likely to be prescribed reasonable doses than White men were,” said the study’s senior author, Alexi Wright, MD, MPH, a gynecologic oncologist and a researcher in the division of population sciences at Dana-Farber Cancer Institute, Boston. “And Black men were less likely to receive long-acting opioids, which are essential for many patients dying of cancer. Our findings are startling because everyone should agree that cancer patients should have equal access to pain relief at the end of life.”

The study was published on in the Journal of Clinical Oncology.

The researchers gathered data on 318,549 Medicare beneficiaries older than 65 years with poor-prognosis cancers who died between 2007 and 2019. During this time frame, for all groups, access to opioids declined and urine drug testing expanded, owing to the overall opioid epidemic in the United States. Overall, the proportion of patients near end of life (EOL) who received any opioid or long-acting opioids decreased from 42.2% to 32.7% and from 17.9% to 9.4%, respectively.

The investigators used National Drug Codes to identify all Medicare Part D claims for outpatient opioid prescriptions, excluding addiction treatments, cough suppressants, and parenteral opioids. They focused on prescriptions that were filled at least 30 days before death or hospice enrollment.

Among the study participants, the majority (85.5%) of patients were White, 29,555 patients (9.3%) were Black, and 16,636 patients (5.2%) were Hispanic.

Black and Hispanic patients were statistically less likely than White patients to receive opioid prescriptions near EOL (Black, –4.3 percentage points; Hispanic, –3.6 percentage points). They were also less likely to receive long-acting opioid prescriptions (Black, –3.1 percentage points; Hispanic, –2.2 percentage points).

“It’s not just that patients of color are less likely to get opioids, but when they do get them, they get lower doses, and they also are less likely to get long-acting opioids, which a lot of people view as sort of more potential for addiction, which isn’t necessarily true but kind of viewed with heightened concern or suspicion,” the study’s lead author, Andrea Enzinger, MD, a gastrointestinal oncologist and a researcher in Dana-Farber’s division of population sciences, said in an interview.

Dr. Enzinger added that she believes systemic racism and preconceived biases toward minorities and drug addiction may be contributing to these trends.

When Black patients did receive at least one opioid prescription, they received daily doses that were 10.5 morphine milligram equivalents (MMEs) lower than doses given to White patients. Compared with the total opioid dose filled per White decedent near EOL, the total dose filled per Black decedent was 210 MMEs lower.

“We all need to be worried about the potential for misuse or addiction, but this is the one setting that is very low on my priority list when somebody is dying. I mean, we’re looking at the last month of life, so nobody has the potential to become addicted,” Dr. Enzinger commented.

The team also evaluated rates or urine drug screening (UDS), but as these rates were relatively low, they expanded the time frame to 180 days before death or hospice. They found that disparities in UDS disproportionately affected Black men.

From 2007 to 2019, the proportion of patients who underwent UDS increased from 0.6% to 6.7% in the 180 days before death or hospice; however, Black decedents were tested more often than White or Hispanic decedents.

Black decedents were 0.5 percentage points more likely than White decedents to undergo UDS near EOL.

“The disparities in urine drug screening are modest but important, because they hint at underlying systematic racism in recommending patients for screening,” Dr. Wright said. “Screening needs to either be applied uniformly or not at all for patients in this situation.”

The researchers acknowledged that their findings likely do not represent the full spectrum of prescribing disparities and believe that the work should be expanded among younger populations. Nevertheless, the investigators believe the work highlights the persistent racial and ethnic disparities in opioid access.

The study was supported by a grant from the Agency for Healthcare Research and Policy.

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

Opioids are widely regarded as a linchpin in the treatment of moderate to severe cancer-related pain and end-of-life symptoms; however, there are persistent racial and ethnic inequities in opioid access among older cancer patients, with Black patients being disproportionately affected, a new study suggests.

Black patients were more likely to undergo urine drug screening (UDS) despite being less likely to receive any opioids for pain management and receiving lower daily doses of opioids in comparison with White patients, the study found.

The inequities were particularly stark for Black men. “We found that Black men were far less likely to be prescribed reasonable doses than White men were,” said the study’s senior author, Alexi Wright, MD, MPH, a gynecologic oncologist and a researcher in the division of population sciences at Dana-Farber Cancer Institute, Boston. “And Black men were less likely to receive long-acting opioids, which are essential for many patients dying of cancer. Our findings are startling because everyone should agree that cancer patients should have equal access to pain relief at the end of life.”

The study was published on in the Journal of Clinical Oncology.

The researchers gathered data on 318,549 Medicare beneficiaries older than 65 years with poor-prognosis cancers who died between 2007 and 2019. During this time frame, for all groups, access to opioids declined and urine drug testing expanded, owing to the overall opioid epidemic in the United States. Overall, the proportion of patients near end of life (EOL) who received any opioid or long-acting opioids decreased from 42.2% to 32.7% and from 17.9% to 9.4%, respectively.

The investigators used National Drug Codes to identify all Medicare Part D claims for outpatient opioid prescriptions, excluding addiction treatments, cough suppressants, and parenteral opioids. They focused on prescriptions that were filled at least 30 days before death or hospice enrollment.

Among the study participants, the majority (85.5%) of patients were White, 29,555 patients (9.3%) were Black, and 16,636 patients (5.2%) were Hispanic.

Black and Hispanic patients were statistically less likely than White patients to receive opioid prescriptions near EOL (Black, –4.3 percentage points; Hispanic, –3.6 percentage points). They were also less likely to receive long-acting opioid prescriptions (Black, –3.1 percentage points; Hispanic, –2.2 percentage points).

“It’s not just that patients of color are less likely to get opioids, but when they do get them, they get lower doses, and they also are less likely to get long-acting opioids, which a lot of people view as sort of more potential for addiction, which isn’t necessarily true but kind of viewed with heightened concern or suspicion,” the study’s lead author, Andrea Enzinger, MD, a gastrointestinal oncologist and a researcher in Dana-Farber’s division of population sciences, said in an interview.

Dr. Enzinger added that she believes systemic racism and preconceived biases toward minorities and drug addiction may be contributing to these trends.

When Black patients did receive at least one opioid prescription, they received daily doses that were 10.5 morphine milligram equivalents (MMEs) lower than doses given to White patients. Compared with the total opioid dose filled per White decedent near EOL, the total dose filled per Black decedent was 210 MMEs lower.

“We all need to be worried about the potential for misuse or addiction, but this is the one setting that is very low on my priority list when somebody is dying. I mean, we’re looking at the last month of life, so nobody has the potential to become addicted,” Dr. Enzinger commented.

The team also evaluated rates or urine drug screening (UDS), but as these rates were relatively low, they expanded the time frame to 180 days before death or hospice. They found that disparities in UDS disproportionately affected Black men.

From 2007 to 2019, the proportion of patients who underwent UDS increased from 0.6% to 6.7% in the 180 days before death or hospice; however, Black decedents were tested more often than White or Hispanic decedents.

Black decedents were 0.5 percentage points more likely than White decedents to undergo UDS near EOL.

“The disparities in urine drug screening are modest but important, because they hint at underlying systematic racism in recommending patients for screening,” Dr. Wright said. “Screening needs to either be applied uniformly or not at all for patients in this situation.”

The researchers acknowledged that their findings likely do not represent the full spectrum of prescribing disparities and believe that the work should be expanded among younger populations. Nevertheless, the investigators believe the work highlights the persistent racial and ethnic disparities in opioid access.

The study was supported by a grant from the Agency for Healthcare Research and Policy.

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

Young adults who survive cancer are more likely than cancer-free siblings to be lonely and to develop emotional distress, risky behaviors, and new chronic conditions as a result, findings from a large retrospective study suggest.

Young cancer survivors were more than twice as likely to report loneliness at study baseline and follow-up. Loneliness at these times was associated with an almost 10-fold increased risk for anxiety and a nearly 18-fold increased risk for depression.

“We observed an elevated prevalence of loneliness in survivors, compared to sibling controls, and found that loneliness was associated with emotional, behavioral, and physical health morbidities,” lead study author Chiara Papini, PhD, of St. Jude Children’s Research Hospital, Memphis, and her colleagues write. “Our results highlight the importance of identifying and screening young adult survivors of childhood cancer for loneliness and the need for targeted interventions to reduce loneliness.”

The article was published online in the journal Cancer.

Most young cancer survivors in the United States reach adulthood and need to play catch-up: make up for missed school and work, become reacquainted with old friends, and develop new friendships, social networks, and intimate relationships. Meeting these needs may be hindered by adverse physical and psychosocial problems that linger or develop after treatment, which may leave cancer survivors feeling isolated.

“Young adult survivors of childhood cancer are navigating a developmental period marked by increased social expectations, during which loneliness may have significant impact on physical and mental health,” Dr. Papini and colleagues say.

To better understand the risks for loneliness among young cancer survivors, Dr. Papini and her colleagues analyzed data from the retrospective Childhood Cancer Survivor Study, which followed young survivors who had been diagnosed with a range of cancers before age 21 years. Study participants had been treated at one of 31 study sites in North America and had survived 5 years or longer after diagnosis.

The 9,664 survivors and 2,221 randomly sampled siblings ranged in age from 19 to 39 years at the time they completed a survey that assessed emotional distress at baseline and at follow‐up a median of 6.6 years. At baseline, the median age of the survivors was 27 years, and a median of 17.5 years had passed from the time of their diagnosis.

The most common diagnoses were leukemia (35%), Hodgkin lymphoma (15%), central nervous system (CNS) tumors (14%), and bone tumors (10%). More than half (56%) had received radiation therapy.

Using multivariable models, the researchers found that survivors were more likely than siblings to report moderate to extreme loneliness at either baseline or follow‐up (prevalence ratio, 1.04) and were more than two times more likely to report loneliness at both baseline and follow‐up (PR, 2.21).

Loneliness at baseline and follow‐up was associated with a much greater risk for anxiety (relative risk, 9.75) and depression (RR, 17.86). Loneliness at follow‐up was linked with increased risks for suicidal ideation (RR, 1.52), heavy or risky alcohol consumption (RR, 1.27), and any grade 2-4 new‐onset chronic health condition (RR, 1.29), especially those that were neurologic (RR, 4.37).

Survivors of CNS tumors (odds ratio, 2.59) and leukemia (OR, 2.52) were most likely to report loneliness at both baseline and follow‐up, though survivors of four other cancer types also faced an elevated risk for loneliness: neuroblastoma (OR, 2.32), bone tumor (OR, 2.12), soft tissue sarcoma (OR, 1.78), and Hodgkin lymphoma (OR, 1.69).

Treatment type appeared to matter as well. Survivors who underwent amputation (OR, 1.82) or were treated with cranial radiation greater than or equal to 20 Gy (OR, 1.56) or corticosteroids (OR, 1.31) were more likely to report loneliness at baseline and follow‐up, compared with those who reported no loneliness at both time points.

The authors acknowledge limitations to the study, including the fact that roughly 90% of survivors and siblings were White, which limits the applicability of their results to diverse groups. In addition, the responses were self-reported without external validation.

Overall, though, the findings provide a framework for clinicians to understand and identify loneliness among young cancer survivors and help them cope with their emotions.

“The Childhood Cancer Survivor Study provides the largest and the most comprehensive dataset on childhood cancer survivors and healthy-sibling comparisons, giving us powerful data on survivorship, late effects, and psychosocial and health outcomes,” Rachel M. Moore, PhD, child psychologist at Children’s Mercy Kansas City, Mo., said in an interview.

Asking a simple question – “Are you feeling lonely?” – can identify at-risk survivors and enable health care teams to provide timely interventions that address young patients’ physical and psychological needs, said Dr. Moore, who was not involved in the study.

Dr. Moore noted that within her clinical practice, “adolescent and young adult survivors frequently discuss loneliness in their daily lives. They feel different from their peers and misunderstood. Having a conversation early in survivorship care about the experience of loneliness as a product of cancer treatment can open the door to regular screening and destigmatizing mental health services.”

Supporting young people throughout their survivorship journey is important, said Rusha Bhandari, MD, medical director of the Childhood, Adolescent, and Young Adult Cancer Survivorship Program at City of Hope, Duarte, Calif. This study can help ensure that clinicians “provide comprehensive care, including psychosocial screening and support, to meet the unique needs of our young adult survivors,” said Dr. Bhandari, who also was not involved in the research.

The National Cancer Institute and the American Lebanese Syrian Associated Charities supported the study. One co-author reported receiving corporate consulting fees. Dr. Papini, the remaining co-authors, Dr. Moore, and Dr. Bhandari report no relevant financial involvements.

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

Young adults who survive cancer are more likely than cancer-free siblings to be lonely and to develop emotional distress, risky behaviors, and new chronic conditions as a result, findings from a large retrospective study suggest.

Young cancer survivors were more than twice as likely to report loneliness at study baseline and follow-up. Loneliness at these times was associated with an almost 10-fold increased risk for anxiety and a nearly 18-fold increased risk for depression.

“We observed an elevated prevalence of loneliness in survivors, compared to sibling controls, and found that loneliness was associated with emotional, behavioral, and physical health morbidities,” lead study author Chiara Papini, PhD, of St. Jude Children’s Research Hospital, Memphis, and her colleagues write. “Our results highlight the importance of identifying and screening young adult survivors of childhood cancer for loneliness and the need for targeted interventions to reduce loneliness.”

The article was published online in the journal Cancer.

Most young cancer survivors in the United States reach adulthood and need to play catch-up: make up for missed school and work, become reacquainted with old friends, and develop new friendships, social networks, and intimate relationships. Meeting these needs may be hindered by adverse physical and psychosocial problems that linger or develop after treatment, which may leave cancer survivors feeling isolated.

“Young adult survivors of childhood cancer are navigating a developmental period marked by increased social expectations, during which loneliness may have significant impact on physical and mental health,” Dr. Papini and colleagues say.

To better understand the risks for loneliness among young cancer survivors, Dr. Papini and her colleagues analyzed data from the retrospective Childhood Cancer Survivor Study, which followed young survivors who had been diagnosed with a range of cancers before age 21 years. Study participants had been treated at one of 31 study sites in North America and had survived 5 years or longer after diagnosis.

The 9,664 survivors and 2,221 randomly sampled siblings ranged in age from 19 to 39 years at the time they completed a survey that assessed emotional distress at baseline and at follow‐up a median of 6.6 years. At baseline, the median age of the survivors was 27 years, and a median of 17.5 years had passed from the time of their diagnosis.

The most common diagnoses were leukemia (35%), Hodgkin lymphoma (15%), central nervous system (CNS) tumors (14%), and bone tumors (10%). More than half (56%) had received radiation therapy.

Using multivariable models, the researchers found that survivors were more likely than siblings to report moderate to extreme loneliness at either baseline or follow‐up (prevalence ratio, 1.04) and were more than two times more likely to report loneliness at both baseline and follow‐up (PR, 2.21).

Loneliness at baseline and follow‐up was associated with a much greater risk for anxiety (relative risk, 9.75) and depression (RR, 17.86). Loneliness at follow‐up was linked with increased risks for suicidal ideation (RR, 1.52), heavy or risky alcohol consumption (RR, 1.27), and any grade 2-4 new‐onset chronic health condition (RR, 1.29), especially those that were neurologic (RR, 4.37).

Survivors of CNS tumors (odds ratio, 2.59) and leukemia (OR, 2.52) were most likely to report loneliness at both baseline and follow‐up, though survivors of four other cancer types also faced an elevated risk for loneliness: neuroblastoma (OR, 2.32), bone tumor (OR, 2.12), soft tissue sarcoma (OR, 1.78), and Hodgkin lymphoma (OR, 1.69).

Treatment type appeared to matter as well. Survivors who underwent amputation (OR, 1.82) or were treated with cranial radiation greater than or equal to 20 Gy (OR, 1.56) or corticosteroids (OR, 1.31) were more likely to report loneliness at baseline and follow‐up, compared with those who reported no loneliness at both time points.

The authors acknowledge limitations to the study, including the fact that roughly 90% of survivors and siblings were White, which limits the applicability of their results to diverse groups. In addition, the responses were self-reported without external validation.

Overall, though, the findings provide a framework for clinicians to understand and identify loneliness among young cancer survivors and help them cope with their emotions.

“The Childhood Cancer Survivor Study provides the largest and the most comprehensive dataset on childhood cancer survivors and healthy-sibling comparisons, giving us powerful data on survivorship, late effects, and psychosocial and health outcomes,” Rachel M. Moore, PhD, child psychologist at Children’s Mercy Kansas City, Mo., said in an interview.

Asking a simple question – “Are you feeling lonely?” – can identify at-risk survivors and enable health care teams to provide timely interventions that address young patients’ physical and psychological needs, said Dr. Moore, who was not involved in the study.

Dr. Moore noted that within her clinical practice, “adolescent and young adult survivors frequently discuss loneliness in their daily lives. They feel different from their peers and misunderstood. Having a conversation early in survivorship care about the experience of loneliness as a product of cancer treatment can open the door to regular screening and destigmatizing mental health services.”

Supporting young people throughout their survivorship journey is important, said Rusha Bhandari, MD, medical director of the Childhood, Adolescent, and Young Adult Cancer Survivorship Program at City of Hope, Duarte, Calif. This study can help ensure that clinicians “provide comprehensive care, including psychosocial screening and support, to meet the unique needs of our young adult survivors,” said Dr. Bhandari, who also was not involved in the research.

The National Cancer Institute and the American Lebanese Syrian Associated Charities supported the study. One co-author reported receiving corporate consulting fees. Dr. Papini, the remaining co-authors, Dr. Moore, and Dr. Bhandari report no relevant financial involvements.

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

Young adults who survive cancer are more likely than cancer-free siblings to be lonely and to develop emotional distress, risky behaviors, and new chronic conditions as a result, findings from a large retrospective study suggest.

Young cancer survivors were more than twice as likely to report loneliness at study baseline and follow-up. Loneliness at these times was associated with an almost 10-fold increased risk for anxiety and a nearly 18-fold increased risk for depression.

“We observed an elevated prevalence of loneliness in survivors, compared to sibling controls, and found that loneliness was associated with emotional, behavioral, and physical health morbidities,” lead study author Chiara Papini, PhD, of St. Jude Children’s Research Hospital, Memphis, and her colleagues write. “Our results highlight the importance of identifying and screening young adult survivors of childhood cancer for loneliness and the need for targeted interventions to reduce loneliness.”

The article was published online in the journal Cancer.

Most young cancer survivors in the United States reach adulthood and need to play catch-up: make up for missed school and work, become reacquainted with old friends, and develop new friendships, social networks, and intimate relationships. Meeting these needs may be hindered by adverse physical and psychosocial problems that linger or develop after treatment, which may leave cancer survivors feeling isolated.

“Young adult survivors of childhood cancer are navigating a developmental period marked by increased social expectations, during which loneliness may have significant impact on physical and mental health,” Dr. Papini and colleagues say.

To better understand the risks for loneliness among young cancer survivors, Dr. Papini and her colleagues analyzed data from the retrospective Childhood Cancer Survivor Study, which followed young survivors who had been diagnosed with a range of cancers before age 21 years. Study participants had been treated at one of 31 study sites in North America and had survived 5 years or longer after diagnosis.

The 9,664 survivors and 2,221 randomly sampled siblings ranged in age from 19 to 39 years at the time they completed a survey that assessed emotional distress at baseline and at follow‐up a median of 6.6 years. At baseline, the median age of the survivors was 27 years, and a median of 17.5 years had passed from the time of their diagnosis.

The most common diagnoses were leukemia (35%), Hodgkin lymphoma (15%), central nervous system (CNS) tumors (14%), and bone tumors (10%). More than half (56%) had received radiation therapy.

Using multivariable models, the researchers found that survivors were more likely than siblings to report moderate to extreme loneliness at either baseline or follow‐up (prevalence ratio, 1.04) and were more than two times more likely to report loneliness at both baseline and follow‐up (PR, 2.21).

Loneliness at baseline and follow‐up was associated with a much greater risk for anxiety (relative risk, 9.75) and depression (RR, 17.86). Loneliness at follow‐up was linked with increased risks for suicidal ideation (RR, 1.52), heavy or risky alcohol consumption (RR, 1.27), and any grade 2-4 new‐onset chronic health condition (RR, 1.29), especially those that were neurologic (RR, 4.37).

Survivors of CNS tumors (odds ratio, 2.59) and leukemia (OR, 2.52) were most likely to report loneliness at both baseline and follow‐up, though survivors of four other cancer types also faced an elevated risk for loneliness: neuroblastoma (OR, 2.32), bone tumor (OR, 2.12), soft tissue sarcoma (OR, 1.78), and Hodgkin lymphoma (OR, 1.69).

Treatment type appeared to matter as well. Survivors who underwent amputation (OR, 1.82) or were treated with cranial radiation greater than or equal to 20 Gy (OR, 1.56) or corticosteroids (OR, 1.31) were more likely to report loneliness at baseline and follow‐up, compared with those who reported no loneliness at both time points.

The authors acknowledge limitations to the study, including the fact that roughly 90% of survivors and siblings were White, which limits the applicability of their results to diverse groups. In addition, the responses were self-reported without external validation.

Overall, though, the findings provide a framework for clinicians to understand and identify loneliness among young cancer survivors and help them cope with their emotions.

“The Childhood Cancer Survivor Study provides the largest and the most comprehensive dataset on childhood cancer survivors and healthy-sibling comparisons, giving us powerful data on survivorship, late effects, and psychosocial and health outcomes,” Rachel M. Moore, PhD, child psychologist at Children’s Mercy Kansas City, Mo., said in an interview.

Asking a simple question – “Are you feeling lonely?” – can identify at-risk survivors and enable health care teams to provide timely interventions that address young patients’ physical and psychological needs, said Dr. Moore, who was not involved in the study.

Dr. Moore noted that within her clinical practice, “adolescent and young adult survivors frequently discuss loneliness in their daily lives. They feel different from their peers and misunderstood. Having a conversation early in survivorship care about the experience of loneliness as a product of cancer treatment can open the door to regular screening and destigmatizing mental health services.”

Supporting young people throughout their survivorship journey is important, said Rusha Bhandari, MD, medical director of the Childhood, Adolescent, and Young Adult Cancer Survivorship Program at City of Hope, Duarte, Calif. This study can help ensure that clinicians “provide comprehensive care, including psychosocial screening and support, to meet the unique needs of our young adult survivors,” said Dr. Bhandari, who also was not involved in the research.

The National Cancer Institute and the American Lebanese Syrian Associated Charities supported the study. One co-author reported receiving corporate consulting fees. Dr. Papini, the remaining co-authors, Dr. Moore, and Dr. Bhandari report no relevant financial involvements.

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

Elevated depressive symptoms were associated with an additional brain age of nearly 3 years, based on data from more than 600 individuals.

Previous research suggests a possible link between depression and increased risk of dementia in older adults, but the association between depression and brain health in early adulthood and midlife has not been well studied, wrote Christina S. Dintica, PhD, of the University of California, San Francisco, and colleagues.

In a study published in the Journal of Affective Disorders, the researchers identified 649 individuals aged 23-36 at baseline who were part of the Coronary Artery Risk Development in Young Adults (CARDIA) study. All participants underwent brain MRI and cognitive testing. Depressive symptoms were assessed six times over a 25-year period using the Center for Epidemiological Studies Depression scale (CES–D), and the scores were analyzed as time-weighted averages (TWA). Elevated depressive symptoms were defined as CES-D scores of 16 or higher. Brain age was assessed via high-dimensional neuroimaging. Approximately half of the participants were female, and half were Black.

Overall, each 5-point increment in TWA depression symptoms over 25 years was associated with a 1-year increase in brain age, and individuals with elevated TWA depression averaged a 3-year increase in brain age compared with those with lower levels of depression after controlling for factors including chronological age, sex, education, race, MRI scanning site, and intracranial volume, they said. The association was attenuated in a model controlling for antidepressant use, and further attenuated after adjusting for smoking, alcohol consumption, income, body mass index, diabetes, and physical exercise.

The researchers also investigated the impact of the age period of elevated depressive symptoms on brain age. Compared with low depressive symptoms, elevated TWA CES-D at ages 30-39 years, 40-49 years, and 50-59 years was associated with increased brain ages of 2.43, 3.19, and 1.82.

In addition, elevated depressive symptoms were associated with a threefold increase in the odds of poor cognitive function at midlife (odds ratio, 3.30), although these odds were reduced after adjusting for use of antidepressants (OR, 1.47).

The mechanisms of action for the link between depression and accelerated brain aging remains uncertain, the researchers wrote in their discussion. “Studies over the last 20 years have demonstrated that increased inflammation and hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis are two of the most consistent biological findings in major depression, which have been linked to premature aging,” they noted. “Alternative explanations for the link between depression and adverse brain health could be underlying factors that explain both outcomes rather independently, such as low socioeconomic status, childhood maltreatment, or shared genetic effects,” they added.

Adjustment for antidepressant use had little effect overall on the association between depressive symptom severity and brain age, they said.

The current study findings were limited by the single assessment of brain age, which prevented evaluation of the temporality of the association between brain aging and depression, the researchers noted.

However, the results were strengthened by the large and diverse cohort, long-term follow-up, and use of high-dimensional neuroimaging, they said. Longitudinal studies are needed to explore mechanisms of action and the potential benefits of antidepressants, they added.

In the meantime, monitoring and treating depressive symptoms in young adults may help promote brain health in midlife and older age, they concluded.

The CARDIA study was supported by the National Heart, Lung, and Blood Institute, the National Institute on Aging, and the Alzheimer’s Association. The researchers had no financial conflicts to disclose.

Elevated depressive symptoms were associated with an additional brain age of nearly 3 years, based on data from more than 600 individuals.

Previous research suggests a possible link between depression and increased risk of dementia in older adults, but the association between depression and brain health in early adulthood and midlife has not been well studied, wrote Christina S. Dintica, PhD, of the University of California, San Francisco, and colleagues.

In a study published in the Journal of Affective Disorders, the researchers identified 649 individuals aged 23-36 at baseline who were part of the Coronary Artery Risk Development in Young Adults (CARDIA) study. All participants underwent brain MRI and cognitive testing. Depressive symptoms were assessed six times over a 25-year period using the Center for Epidemiological Studies Depression scale (CES–D), and the scores were analyzed as time-weighted averages (TWA). Elevated depressive symptoms were defined as CES-D scores of 16 or higher. Brain age was assessed via high-dimensional neuroimaging. Approximately half of the participants were female, and half were Black.

Overall, each 5-point increment in TWA depression symptoms over 25 years was associated with a 1-year increase in brain age, and individuals with elevated TWA depression averaged a 3-year increase in brain age compared with those with lower levels of depression after controlling for factors including chronological age, sex, education, race, MRI scanning site, and intracranial volume, they said. The association was attenuated in a model controlling for antidepressant use, and further attenuated after adjusting for smoking, alcohol consumption, income, body mass index, diabetes, and physical exercise.

The researchers also investigated the impact of the age period of elevated depressive symptoms on brain age. Compared with low depressive symptoms, elevated TWA CES-D at ages 30-39 years, 40-49 years, and 50-59 years was associated with increased brain ages of 2.43, 3.19, and 1.82.

In addition, elevated depressive symptoms were associated with a threefold increase in the odds of poor cognitive function at midlife (odds ratio, 3.30), although these odds were reduced after adjusting for use of antidepressants (OR, 1.47).

The mechanisms of action for the link between depression and accelerated brain aging remains uncertain, the researchers wrote in their discussion. “Studies over the last 20 years have demonstrated that increased inflammation and hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis are two of the most consistent biological findings in major depression, which have been linked to premature aging,” they noted. “Alternative explanations for the link between depression and adverse brain health could be underlying factors that explain both outcomes rather independently, such as low socioeconomic status, childhood maltreatment, or shared genetic effects,” they added.

Adjustment for antidepressant use had little effect overall on the association between depressive symptom severity and brain age, they said.

The current study findings were limited by the single assessment of brain age, which prevented evaluation of the temporality of the association between brain aging and depression, the researchers noted.

However, the results were strengthened by the large and diverse cohort, long-term follow-up, and use of high-dimensional neuroimaging, they said. Longitudinal studies are needed to explore mechanisms of action and the potential benefits of antidepressants, they added.

In the meantime, monitoring and treating depressive symptoms in young adults may help promote brain health in midlife and older age, they concluded.

The CARDIA study was supported by the National Heart, Lung, and Blood Institute, the National Institute on Aging, and the Alzheimer’s Association. The researchers had no financial conflicts to disclose.

Elevated depressive symptoms were associated with an additional brain age of nearly 3 years, based on data from more than 600 individuals.

Previous research suggests a possible link between depression and increased risk of dementia in older adults, but the association between depression and brain health in early adulthood and midlife has not been well studied, wrote Christina S. Dintica, PhD, of the University of California, San Francisco, and colleagues.

In a study published in the Journal of Affective Disorders, the researchers identified 649 individuals aged 23-36 at baseline who were part of the Coronary Artery Risk Development in Young Adults (CARDIA) study. All participants underwent brain MRI and cognitive testing. Depressive symptoms were assessed six times over a 25-year period using the Center for Epidemiological Studies Depression scale (CES–D), and the scores were analyzed as time-weighted averages (TWA). Elevated depressive symptoms were defined as CES-D scores of 16 or higher. Brain age was assessed via high-dimensional neuroimaging. Approximately half of the participants were female, and half were Black.

Overall, each 5-point increment in TWA depression symptoms over 25 years was associated with a 1-year increase in brain age, and individuals with elevated TWA depression averaged a 3-year increase in brain age compared with those with lower levels of depression after controlling for factors including chronological age, sex, education, race, MRI scanning site, and intracranial volume, they said. The association was attenuated in a model controlling for antidepressant use, and further attenuated after adjusting for smoking, alcohol consumption, income, body mass index, diabetes, and physical exercise.

The researchers also investigated the impact of the age period of elevated depressive symptoms on brain age. Compared with low depressive symptoms, elevated TWA CES-D at ages 30-39 years, 40-49 years, and 50-59 years was associated with increased brain ages of 2.43, 3.19, and 1.82.

In addition, elevated depressive symptoms were associated with a threefold increase in the odds of poor cognitive function at midlife (odds ratio, 3.30), although these odds were reduced after adjusting for use of antidepressants (OR, 1.47).

The mechanisms of action for the link between depression and accelerated brain aging remains uncertain, the researchers wrote in their discussion. “Studies over the last 20 years have demonstrated that increased inflammation and hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis are two of the most consistent biological findings in major depression, which have been linked to premature aging,” they noted. “Alternative explanations for the link between depression and adverse brain health could be underlying factors that explain both outcomes rather independently, such as low socioeconomic status, childhood maltreatment, or shared genetic effects,” they added.

Adjustment for antidepressant use had little effect overall on the association between depressive symptom severity and brain age, they said.

The current study findings were limited by the single assessment of brain age, which prevented evaluation of the temporality of the association between brain aging and depression, the researchers noted.

However, the results were strengthened by the large and diverse cohort, long-term follow-up, and use of high-dimensional neuroimaging, they said. Longitudinal studies are needed to explore mechanisms of action and the potential benefits of antidepressants, they added.

In the meantime, monitoring and treating depressive symptoms in young adults may help promote brain health in midlife and older age, they concluded.

The CARDIA study was supported by the National Heart, Lung, and Blood Institute, the National Institute on Aging, and the Alzheimer’s Association. The researchers had no financial conflicts to disclose.

Sleep disturbances are consistently high throughout the course of psychosis, with later stages associated with distinctive brain wave activity during sleep, a new review and meta-analysis shows.

For example, compared with their healthy peers, participants in a chronic psychosis stage had reduced density, amplitude, and duration of spindles – or bursts of brainwave activity during sleep identified by electroencephalography.

“The results suggest sleep could be an important target [and] an area of research and clinical intervention that could make a difference” in the lives of patients at risk for psychosis, study investigator Fabio Ferrarelli, MD, PhD, associate professor of psychiatry and director of the Sleep and Schizophrenia Program, University of Pittsburgh School of Medicine, told this news organization.

University of Pittsburgh

‘Window of opportunity’

Researchers separate psychosis into stages. During the “clinically high-risk for psychosis” (CHR-P) stage, patients have milder symptoms but do not have a diagnosable psychotic disorder. Those in the early psychosis (EP) stage have had a first episode of psychosis. When they reach a cut-off, often at 5 years, they are considered to have chronic psychosis (CP).

Previous studies have shown that altered sleep often precedes a psychotic episode in early psychosis, and disrupted sleep contributes to predicting transition to psychosis in youth at risk for the condition. Individuals with CP commonly report sleep disturbances, such as insomnia.

Following a literature search, the investigators for this current meta-analysis selected 21 studies assessing sleep disturbance prevalence in 5,135 patients. They also selected 39 studies measuring sleep alterations subjectively (for example, sleep quality) and/or objectively (for example, sleep architecture and sleep oscillation) in 1,575 patients and 977 healthy controls.

The included studies measured the prevalence of sleep disturbances and/or sleep characteristics at different psychosis stages using polysomnography, EEG, actigraphy, or self-reports.

The pooled prevalence of sleep disturbances was 50% across clinical stages (95% confidence interval, 40%-61%). The prevalence was 54% in CHR-P, 68% in EP, and 44% in CP.

The prevalence of insomnia as the primary sleep disturbance was 34% of pooled cases, 48% of the EP group, and 27% of the CP group.

“What’s interesting is the rate of sleep disturbances is relatively stable across stages,” said Dr. Ferrarelli. “This is important because you have a window of opportunity to do some early intervention in people who are at risk that can prevent things from getting worse.”

He suggests clinicians screen for insomnia in early-course patients and perhaps recommend cognitive behavioral therapy (CBT) for insomnia. As well, they should promote sleep hygiene measures for at-risk patients, including such things as avoiding caffeine, alcohol, and screen time before bedtime and adopting a regular sleep pattern.

“These are people at risk, which means they have a 20%-30% chance of eventually developing a psychotic disorder,” said Dr. Ferrarelli. “Maybe disrupted sleep is one of the factors that can make a difference.”
 

Altered sleep architecture

To compare sleep quality between clinical and control groups, studies used total scores on the Pittsburgh Sleep Quality Index (PSQI), where a score over 5 indicates a sleep problem.

There was a significant standardized mean difference in pooled cases versus controls (SMD, 1.0; 95% CI, 0.7-1.3; P < .001). Each clinical group showed poorer sleep quality, compared with controls.

When assessing sleep architecture abnormalities, stage-specific case-control comparisons showed these were driven by EP and CP stages.

Altered sleep characteristics in both these stages included increased sleep onset latency, increased wake after sleep onset, and reduced sleep efficiency.

Compared with controls, CP was the only clinical group with more arousals. Patients with CP also had more arousals than the CHR-P group, and the number of arousals was significantly affected by medication.

The findings indicate the effects of antipsychotic medications on sleep should be closely monitored, especially in CP, the investigators write.

They add that clinicians should consider medication adjustments, such as decreased doses or switches to another compound.
 

‘Robust’ spindle results

As for spindle parameters, pooled cases showed significantly decreased spindle density (SMD, –1.06), spindle amplitude (SMD, –1.08), and spindle duration (SMD, −1.21), compared with controls. Stage-specific comparisons revealed these deficits were present in both EP and CP relative to controls.

Dr. Ferrarelli noted the results for spindle abnormalities were among “the most robust” and show that these abnormalities “tend to get worse over the course of the illness.”

The spindle data are “a lot more informative” than that provided by other sleep parameters “in the sense they can yield what could be wrong, where it could be, and potentially what you can do about it,” said Dr. Ferrarelli.

“This might be an objective measure that could be used to identify individuals who have a psychosis disorder, monitor progression of illness, and for prognostic reasons,” he added.

He noted that spindles may also represent a promising target for treatment interventions and added that non-invasive transcranial magnetic stimulation has shown promise in restoring sleep oscillations, including spindles.

Another way to evoke target-brain activity may be through auditory tones – with a patient listening to a particular sound through headphones while asleep, Dr. Ferrarelli said.
 

Reaffirms previous data

Commenting on the study, Jeffrey A. Lieberman, MD, professor and chair in psychiatry at Columbia University, New York, and a past president of the American Psychiatric Association, noted that the review “just reaffirms what has been reported by individual studies for decades.”

That so many at-risk study subjects had a sleep abnormality is not surprising, said Dr. Lieberman, who was not involved with the current research.

“How many individuals in late adolescence or early adulthood have sleep problems?” he asked. “I would venture to say it’s probably a lot. So the question is: How distinctive is this from what occurs in people who don’t develop the illness?”

The aim of sleep research in the area of schizophrenia has long been to disentangle the effects of medication and environmental factors from the disease and to be able to treat patients to normalize their sleep, said Dr. Lieberman.

“But it’s not clear from these results how one would do that,” he added.

The authors “don’t fundamentally tell us anything about the underlying cause of the illness or the pathophysiology, and they don’t really offer any kind of clear direction for clinical intervention,” he said.

The study was supported by the National Institute of Mental Health. Dr. Ferrarelli reported grants from the National Institute of Mental Health during the conduct of the study. Dr. Lieberman has reported no relevant financial relationships.

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

Sleep disturbances are consistently high throughout the course of psychosis, with later stages associated with distinctive brain wave activity during sleep, a new review and meta-analysis shows.

For example, compared with their healthy peers, participants in a chronic psychosis stage had reduced density, amplitude, and duration of spindles – or bursts of brainwave activity during sleep identified by electroencephalography.

“The results suggest sleep could be an important target [and] an area of research and clinical intervention that could make a difference” in the lives of patients at risk for psychosis, study investigator Fabio Ferrarelli, MD, PhD, associate professor of psychiatry and director of the Sleep and Schizophrenia Program, University of Pittsburgh School of Medicine, told this news organization.

University of Pittsburgh

‘Window of opportunity’

Researchers separate psychosis into stages. During the “clinically high-risk for psychosis” (CHR-P) stage, patients have milder symptoms but do not have a diagnosable psychotic disorder. Those in the early psychosis (EP) stage have had a first episode of psychosis. When they reach a cut-off, often at 5 years, they are considered to have chronic psychosis (CP).

Previous studies have shown that altered sleep often precedes a psychotic episode in early psychosis, and disrupted sleep contributes to predicting transition to psychosis in youth at risk for the condition. Individuals with CP commonly report sleep disturbances, such as insomnia.

Following a literature search, the investigators for this current meta-analysis selected 21 studies assessing sleep disturbance prevalence in 5,135 patients. They also selected 39 studies measuring sleep alterations subjectively (for example, sleep quality) and/or objectively (for example, sleep architecture and sleep oscillation) in 1,575 patients and 977 healthy controls.

The included studies measured the prevalence of sleep disturbances and/or sleep characteristics at different psychosis stages using polysomnography, EEG, actigraphy, or self-reports.

The pooled prevalence of sleep disturbances was 50% across clinical stages (95% confidence interval, 40%-61%). The prevalence was 54% in CHR-P, 68% in EP, and 44% in CP.

The prevalence of insomnia as the primary sleep disturbance was 34% of pooled cases, 48% of the EP group, and 27% of the CP group.

“What’s interesting is the rate of sleep disturbances is relatively stable across stages,” said Dr. Ferrarelli. “This is important because you have a window of opportunity to do some early intervention in people who are at risk that can prevent things from getting worse.”

He suggests clinicians screen for insomnia in early-course patients and perhaps recommend cognitive behavioral therapy (CBT) for insomnia. As well, they should promote sleep hygiene measures for at-risk patients, including such things as avoiding caffeine, alcohol, and screen time before bedtime and adopting a regular sleep pattern.

“These are people at risk, which means they have a 20%-30% chance of eventually developing a psychotic disorder,” said Dr. Ferrarelli. “Maybe disrupted sleep is one of the factors that can make a difference.”
 

Altered sleep architecture

To compare sleep quality between clinical and control groups, studies used total scores on the Pittsburgh Sleep Quality Index (PSQI), where a score over 5 indicates a sleep problem.

There was a significant standardized mean difference in pooled cases versus controls (SMD, 1.0; 95% CI, 0.7-1.3; P < .001). Each clinical group showed poorer sleep quality, compared with controls.

When assessing sleep architecture abnormalities, stage-specific case-control comparisons showed these were driven by EP and CP stages.

Altered sleep characteristics in both these stages included increased sleep onset latency, increased wake after sleep onset, and reduced sleep efficiency.

Compared with controls, CP was the only clinical group with more arousals. Patients with CP also had more arousals than the CHR-P group, and the number of arousals was significantly affected by medication.

The findings indicate the effects of antipsychotic medications on sleep should be closely monitored, especially in CP, the investigators write.

They add that clinicians should consider medication adjustments, such as decreased doses or switches to another compound.
 

‘Robust’ spindle results

As for spindle parameters, pooled cases showed significantly decreased spindle density (SMD, –1.06), spindle amplitude (SMD, –1.08), and spindle duration (SMD, −1.21), compared with controls. Stage-specific comparisons revealed these deficits were present in both EP and CP relative to controls.

Dr. Ferrarelli noted the results for spindle abnormalities were among “the most robust” and show that these abnormalities “tend to get worse over the course of the illness.”

The spindle data are “a lot more informative” than that provided by other sleep parameters “in the sense they can yield what could be wrong, where it could be, and potentially what you can do about it,” said Dr. Ferrarelli.

“This might be an objective measure that could be used to identify individuals who have a psychosis disorder, monitor progression of illness, and for prognostic reasons,” he added.

He noted that spindles may also represent a promising target for treatment interventions and added that non-invasive transcranial magnetic stimulation has shown promise in restoring sleep oscillations, including spindles.

Another way to evoke target-brain activity may be through auditory tones – with a patient listening to a particular sound through headphones while asleep, Dr. Ferrarelli said.
 

Reaffirms previous data

Commenting on the study, Jeffrey A. Lieberman, MD, professor and chair in psychiatry at Columbia University, New York, and a past president of the American Psychiatric Association, noted that the review “just reaffirms what has been reported by individual studies for decades.”

That so many at-risk study subjects had a sleep abnormality is not surprising, said Dr. Lieberman, who was not involved with the current research.

“How many individuals in late adolescence or early adulthood have sleep problems?” he asked. “I would venture to say it’s probably a lot. So the question is: How distinctive is this from what occurs in people who don’t develop the illness?”

The aim of sleep research in the area of schizophrenia has long been to disentangle the effects of medication and environmental factors from the disease and to be able to treat patients to normalize their sleep, said Dr. Lieberman.

“But it’s not clear from these results how one would do that,” he added.

The authors “don’t fundamentally tell us anything about the underlying cause of the illness or the pathophysiology, and they don’t really offer any kind of clear direction for clinical intervention,” he said.

The study was supported by the National Institute of Mental Health. Dr. Ferrarelli reported grants from the National Institute of Mental Health during the conduct of the study. Dr. Lieberman has reported no relevant financial relationships.

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

Sleep disturbances are consistently high throughout the course of psychosis, with later stages associated with distinctive brain wave activity during sleep, a new review and meta-analysis shows.

For example, compared with their healthy peers, participants in a chronic psychosis stage had reduced density, amplitude, and duration of spindles – or bursts of brainwave activity during sleep identified by electroencephalography.

“The results suggest sleep could be an important target [and] an area of research and clinical intervention that could make a difference” in the lives of patients at risk for psychosis, study investigator Fabio Ferrarelli, MD, PhD, associate professor of psychiatry and director of the Sleep and Schizophrenia Program, University of Pittsburgh School of Medicine, told this news organization.

University of Pittsburgh

‘Window of opportunity’

Researchers separate psychosis into stages. During the “clinically high-risk for psychosis” (CHR-P) stage, patients have milder symptoms but do not have a diagnosable psychotic disorder. Those in the early psychosis (EP) stage have had a first episode of psychosis. When they reach a cut-off, often at 5 years, they are considered to have chronic psychosis (CP).

Previous studies have shown that altered sleep often precedes a psychotic episode in early psychosis, and disrupted sleep contributes to predicting transition to psychosis in youth at risk for the condition. Individuals with CP commonly report sleep disturbances, such as insomnia.

Following a literature search, the investigators for this current meta-analysis selected 21 studies assessing sleep disturbance prevalence in 5,135 patients. They also selected 39 studies measuring sleep alterations subjectively (for example, sleep quality) and/or objectively (for example, sleep architecture and sleep oscillation) in 1,575 patients and 977 healthy controls.

The included studies measured the prevalence of sleep disturbances and/or sleep characteristics at different psychosis stages using polysomnography, EEG, actigraphy, or self-reports.

The pooled prevalence of sleep disturbances was 50% across clinical stages (95% confidence interval, 40%-61%). The prevalence was 54% in CHR-P, 68% in EP, and 44% in CP.

The prevalence of insomnia as the primary sleep disturbance was 34% of pooled cases, 48% of the EP group, and 27% of the CP group.

“What’s interesting is the rate of sleep disturbances is relatively stable across stages,” said Dr. Ferrarelli. “This is important because you have a window of opportunity to do some early intervention in people who are at risk that can prevent things from getting worse.”

He suggests clinicians screen for insomnia in early-course patients and perhaps recommend cognitive behavioral therapy (CBT) for insomnia. As well, they should promote sleep hygiene measures for at-risk patients, including such things as avoiding caffeine, alcohol, and screen time before bedtime and adopting a regular sleep pattern.

“These are people at risk, which means they have a 20%-30% chance of eventually developing a psychotic disorder,” said Dr. Ferrarelli. “Maybe disrupted sleep is one of the factors that can make a difference.”
 

Altered sleep architecture

To compare sleep quality between clinical and control groups, studies used total scores on the Pittsburgh Sleep Quality Index (PSQI), where a score over 5 indicates a sleep problem.

There was a significant standardized mean difference in pooled cases versus controls (SMD, 1.0; 95% CI, 0.7-1.3; P < .001). Each clinical group showed poorer sleep quality, compared with controls.

When assessing sleep architecture abnormalities, stage-specific case-control comparisons showed these were driven by EP and CP stages.

Altered sleep characteristics in both these stages included increased sleep onset latency, increased wake after sleep onset, and reduced sleep efficiency.

Compared with controls, CP was the only clinical group with more arousals. Patients with CP also had more arousals than the CHR-P group, and the number of arousals was significantly affected by medication.

The findings indicate the effects of antipsychotic medications on sleep should be closely monitored, especially in CP, the investigators write.

They add that clinicians should consider medication adjustments, such as decreased doses or switches to another compound.
 

‘Robust’ spindle results

As for spindle parameters, pooled cases showed significantly decreased spindle density (SMD, –1.06), spindle amplitude (SMD, –1.08), and spindle duration (SMD, −1.21), compared with controls. Stage-specific comparisons revealed these deficits were present in both EP and CP relative to controls.

Dr. Ferrarelli noted the results for spindle abnormalities were among “the most robust” and show that these abnormalities “tend to get worse over the course of the illness.”

The spindle data are “a lot more informative” than that provided by other sleep parameters “in the sense they can yield what could be wrong, where it could be, and potentially what you can do about it,” said Dr. Ferrarelli.

“This might be an objective measure that could be used to identify individuals who have a psychosis disorder, monitor progression of illness, and for prognostic reasons,” he added.

He noted that spindles may also represent a promising target for treatment interventions and added that non-invasive transcranial magnetic stimulation has shown promise in restoring sleep oscillations, including spindles.

Another way to evoke target-brain activity may be through auditory tones – with a patient listening to a particular sound through headphones while asleep, Dr. Ferrarelli said.
 

Reaffirms previous data

Commenting on the study, Jeffrey A. Lieberman, MD, professor and chair in psychiatry at Columbia University, New York, and a past president of the American Psychiatric Association, noted that the review “just reaffirms what has been reported by individual studies for decades.”

That so many at-risk study subjects had a sleep abnormality is not surprising, said Dr. Lieberman, who was not involved with the current research.

“How many individuals in late adolescence or early adulthood have sleep problems?” he asked. “I would venture to say it’s probably a lot. So the question is: How distinctive is this from what occurs in people who don’t develop the illness?”

The aim of sleep research in the area of schizophrenia has long been to disentangle the effects of medication and environmental factors from the disease and to be able to treat patients to normalize their sleep, said Dr. Lieberman.

“But it’s not clear from these results how one would do that,” he added.

The authors “don’t fundamentally tell us anything about the underlying cause of the illness or the pathophysiology, and they don’t really offer any kind of clear direction for clinical intervention,” he said.

The study was supported by the National Institute of Mental Health. Dr. Ferrarelli reported grants from the National Institute of Mental Health during the conduct of the study. Dr. Lieberman has reported no relevant financial relationships.

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

As physicians well know, magic wands don’t exist. If they did, every patient would recover in the exam room, prior authorization wouldn’t exist, and continuing medical education credits would be printed on bearer bonds.

But in the spirit of suspended disbelief, we asked physicians and other contributors what their three wishes would be for their patients, practice/hospital, and health systems. Because, hey – we all need to dream.
 

Suzanne C. Boulter, MD, adjunct professor of pediatrics and community and family medicine, Geisel School of Medicine at Dartmouth, Hanover, N.H.
Patients: An end to gun violence.
Practice/hospital: Adequate staffing and pediatric bed availability.
Health system: Universal access to health insurance.

Sarah G. Candler, MD, MPH, care team medical director and director of academic relations, Iora Primary Care, Northside Clinic, Houston
Patients: Systems of health that start with communities of safety, including access to affordable housing, food, transportation, and health care.
Practice/hospital: I.N.T.E.R.O.P.E.R.A.B.I.L.I.T.Y.
Health system: Clinician leadership that has the power (often aka funding) to do what’s right, not just what’s right in front of us.

Arthur L. Caplan, PhD, bioethicist, New York University Langone Health
Patients: I wish for patients in the United States greater access to affordable primary care. There are still too many people without insurance or a reasonably accessible quality provider. And I especially wish for the rapid expansion of affordable training programs to meet staffing needs, including more scholarships, 3-year programs, and more new primary care–oriented schools.
Hospital: Increased staffing, especially nursing. There are too many retirements, too much burnout, and too much privatization into boutique practices to ensure the ability to provide high-quality, safe, patient-oriented care.
Health system: I wish for health systems to seriously move into electronic medicine. While billing has become electronic, there is still much to be done to supplement diagnosis, training, and standardized data collection on key metrics. Systems are not yet behaving in a manner consistent with the hype in this regard.

Stephen Devries, MD, executive director, Gaples Institute (nonprofit) and adjunct associate professor of nutrition, Harvard School of Public Health, Boston
Patients: Patients continue to demand more from their health care professionals and insist that they are offered evidence-based counseling on nutrition and lifestyle strategies.
Practice: Quality-based reimbursement for medical services will take hold that will incentivize much-needed preventive care.
Hospital: Hospitals will more fully embrace the role of serving as true centers of health and focus as much on preventive medicine as on the more lucrative areas of high-tech treatment.

Peter D. Friedmann, MD, MPH, chief research officer, Baystate Health, Springfield, Mass.
Seconded by: Elisabeth Poorman, MD, general internist, University of Washington Clinic, Kent
Patients: Don’t forget the ongoing epidemic of substance use disorder, a major cause of premature mortality. Descheduling of cannabis and expungement of cannabis-related convictions.
Practice/hospital: Commitment of hospitals and practices to address stigma and ensure delivery of medications for opioid use disorder in primary care, the emergency department, and inpatient settings.
Health system: Reform of antiquated methadone regulations to permit office-based prescription and pharmacy dispensing to treat opioid use disorder, as is the case in most of the world.

Robert Glatter, MD, emergency physician, New York
Patients: I want all patients to understand the enormous strain the health care system has been under – not just with the pandemic, the tripledemic, and mpox [previously called monkeypox], but well before the onset of these public health crises.
Hospital: The medical profession has endured not only burnout but a growing mental health crisis, staffing shortages, a physician addiction crisis, and increased attrition in the decade leading up to the pandemic. The pandemic was like a punch in the gut, occurring at the most inopportune time one could imagine.
Health system: The intersection of health and the state of our public health deserves important mention. Unless we take action to bolster our public health infrastructure, our health care system will be in jeopardy, unable to handle the next pandemic, which could be just around the corner.

William E. Golden, MD, medical director of Arkansas Medicaid, professor of medicine and public health, University of Arkansas for Medical Sciences, Little Rock
Patients: Affordable options for diabetes and obesity management.
Health system: Greater investment by health systems and third-party payers in primary care infrastructure.

Gregory A. Hood, MD, Baptist Health, Lexington, Ky.
Patients: To embrace the gift of getting out in the world, being active, and connecting with others – having put down the screens.
Health system: To be freed from the financial gamesmanship of the insurers as they continue to serve their goals of promoting their hedge fund investing over meaningful and productive partnering with primary care physicians, and that they gain insight that they are one of the main reasons they can’t find PCPs to connect with to render care in disadvantaged environments – because they made it economically impossible to do so.

Robert H. Hopkins Jr., MD, associate professor of internal medicine and pediatrics and director of the division of general internal medicine, University of Arkansas for Medical Sciences, Little Rock
Patients/Health system: I would wish for staged implementation of universal basic health coverage for all, perhaps closest to the French or Canadian model. This would need to be coupled with expanded funding for nursing education, graduate medical education, and tracing of other health-related professionals.

Harvey Hsu, MD, Banner Health, Phoenix
Patients: More clear guidelines that are simple to understand. This can apply to colonoscopy (now age 45), immunizations, blood pressure goals. I wish medications were not as expensive so patients can take the best medicine for them and not stop taking them when they hit their donut hole in coverage.
Practice: We have been functioning on a leaner basis to cut down costs. When the pandemic hit, turnover was high and we lost PAs, nurses, front-office staff, and physicians. Having adequate staffing is probably number one on many lists. One way we dealt with lack of staffing was converting in-person visits to telehealth. Video visits are paid the same as in-person visits, but if the patient could not get their video to work, then it would be a telephone visit. Now many insurances do not even pay for telephone visits. So I would wish that we could still be reimbursed for telehealth visits.
Health system: I would wish for our health system to recognize the extra work required to take care of patients while improving quality and meeting quality measures. Allowing more time for patient visits could be one way to meet those goals or having more support staff to make sure patients get their colonoscopy/mammograms done, improve their sugars, and take their medications.

Jan L. Shifren, MD, Vincent Trustees Professor, obstetrics, gynecology, and reproductive biology, Harvard Medical School, and director of the Midlife Women’s Health Center at Massachusetts General Hospital, Boston
Patients: I wish for patients to be actively involved in all aspects of their care, well informed with shared decision-making.
Practice: I wish for the enormous time demands of electronic medical records and documentation to not distract from the pleasure of caring for patients.
Health system: Patient care remains at the center of decisions and programs.

Timothy J. Joos, MD, MPH, internal medicine/pediatrics, Seattle
Health system: I wish someone could figure out how we could be reimbursed for the quality of care we provide instead of the volume of patients we see. I wish EMRs could become less complicated and more user-friendly rather than needing advanced training to use.

Peter Kovacs, MD, medical director, Kaali Institute IVF Center, Budapest
Patients: I work as an infertility specialist, so when we talk about infectious diseases and associated risks, we talk about a minimum of two (female and male partner) and ideally three (plus the pregnancy) individuals. We have learned that SARS-CoV-2 affects reproductive health. It may compromise sperm production, could delay fertility treatment, could be associated with lower success rates; and if the treatment is successful, it may harm the pregnant woman/fetus/newborn. The best preventive measure that we can offer is vaccination. One cannot overemphasize the importance of preventive measures, paying attention to personal hygiene and social distancing. Therefore, I wish those planning to become pregnant to listen to their health care provider and accept the recommended vaccines to minimize the risk of getting infected and to minimize the risk for severe disease, especially if one undergoes successful fertility treatment and achieves a long-desired pregnancy.
Practice: During the 2022 calendar year we had many days when one or more employees were out of work on sick leave. This puts extra stress on the others to allow uncompromised work in the clinic. In addition, we all have to work in a less-comfortable environment if we consider mask use every day, all day. For health care workers, vaccination is mandated but many still are affected by milder forms of coronavirus infection and other respiratory diseases. Therefore, I wish my colleagues patience toward the preventive measures to lower the individual risk for infections. As a result, hopefully we will have a less stressful 2023.
Health system: Many resources had to be delegated to dealing with acute and chronic COVID, and this was at the expense of routine daily elective and preventive medical services. I wish the health care system to return to normal daily operations, to have the personnel and financial resources to carry on with the required preventive and elective medical services to avoid long-term consequences of not being able to provide such services. It would be sad if we had to treat otherwise preventable illnesses in the upcoming years that went undiagnosed and/or were not properly managed due to limited resources as the result of the pandemic.

Alan R. Nelson, MD, internist-endocrinologist, retired
Patients: Expansion of the FDA’s authority into over-the-counter drugs, including the veracity of their advertising claims.
Practice: Make diabetes drugs available at a reasonable cost.
Health system: With the expansion of Medicaid eligibility during COVID-19 coming to a close, federal government actions are necessary for those who once again have been dropped from coverage to have their legitimate needs met.

Kevin Powell, MD, PhD, St. Louis
Patients: To be cared for and about, and not just medically, even when illness strikes and health fails.
Hospitals: To hear the thankfulness of a grateful public for the care you provide, and to hear that above the angry noise of outraged individuals who spout vitriol and focus on how they believe others have harmed them.
Health system: A truer understanding of mercy and justice.

Margaret Thew, DNP, FNP-BC, director, department of adolescent medicine, Children’s Hospital of Wisconsin, Milwaukee
Seconded by: M. Susan Jay, MD, professor of pediatrics, chief of adolescent medicine, Medical College of Wisconsin and Children’s Hospital of Wisconsin, Milwaukee
My wish for patients, hospital, and system: health, calm, and grace.

Mark P. Trolice, MD, director of Fertility CARE, the IVF Center, Winter Park, Fla.
Patients: To be proactive in their health care and be their own advocates. Question when unclear and only consult credible resources.
Practice/hospital: Improve support of physicians and all health care providers to allow more input in their practice operations and growth.
Health system: Reduce interference of the “business of medicine” and ensure that the patient experience is the priority.

Charles P. Vega, MD, University of California, Irvine
Three minutes on a routine basis for everyone in health care to reflect on our blessings and the honor and gravity – as well as joy – that are integral to health care. Three minutes that will also help us to recognize our challenges and put them in the proper context. I know 3 minutes is not meeting any standard for reflective practice. But it’s 3 minutes more than I have right now.

Karen Breach Washington, MD, medical director of WellCare of North Carolina/Centene, Charlotte
Seconded by: Lillian M. Beard, MD, physician director, Children’s Pediatricians and Associates, Silver Spring, Md.
Patients: Access to affordable health care.
Hospital: Resources to care for patients (sufficient number of beds and a healthy staff).
Health system: Equity for all.

Andrew Wilner, MD, host of the podcast “The Art of Medicine with Dr. Andrew Wilner,” www.andrewwilner.com
Let’s put patients first! Too many extraneous considerations other than the patient’s best interest obstruct optimal patient care.

Here are just a few examples of patients coming last instead of first.

• If a patient needs to start a new medication in hospital, we shouldn’t have to wait until the patient is an outpatient because “that’s when insurance will pay.”
• If there’s a new medication that’s better than the old medication, we shouldn’t be forced to choose the old medication and provide inferior care because “that’s when insurance will pay.”
• If patients need to stay in hospital, we shouldn’t be pressured to discharge them because the hospital has decided that decreasing “length of stay” is its highest priority.

Dr. Francis Peabody said it best in 1927: “The secret of the care of the patient is in caring for the patient.” How hard is that?

In 2023, why don’t we follow Dr. Peabody’s sage advice from nearly 100 years ago and see what happens?
 

James M. Wooten, PharmD, University of Missouri–Kansas City, University Health, Kansas City, Mo.
Patients: I want patients to understand and properly realize the advantage of vaccinations – not only for COVID-19 but also for influenza. There is so much misinformation that I spend a lot of time trying to convince patients to get vaccinated. Most patients don’t realize that through their lives, most of them have already been vaccinated for something just to be able to attend school. How the COVID-19 vaccine created so much stigma makes little sense to me. I also want patients to understand that COVID-19 vaccination and boosters do not always prevent infection but will many times prevent severe infection. I believe that better patient communication and education is the key and will always be the key to improving vaccination numbers. Not only communicating and educating patients on vaccination itself but also making patients realize that personal vaccination decisions may affect what happens to your neighbor. Allowing infection means that you may be more likely to infect someone else. As a society, we must take care of each other.
Health system: It will be interesting to see what happens when vaccines are no longer reimbursed by the federal government. Understanding which vaccines work best and are better tolerated will be key to choosing appropriate vaccine brands. Health care providers will need to be very selective regarding which vaccines are selected for formulary inclusion. Thorough meta-analysis studies must be done to provide more evaluable information to allow for appropriate selection. “Knowledge is power!” Appropriate knowledge will help distinguish which vaccines work best for various patient populations.

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

As physicians well know, magic wands don’t exist. If they did, every patient would recover in the exam room, prior authorization wouldn’t exist, and continuing medical education credits would be printed on bearer bonds.

But in the spirit of suspended disbelief, we asked physicians and other contributors what their three wishes would be for their patients, practice/hospital, and health systems. Because, hey – we all need to dream.
 

Suzanne C. Boulter, MD, adjunct professor of pediatrics and community and family medicine, Geisel School of Medicine at Dartmouth, Hanover, N.H.
Patients: An end to gun violence.
Practice/hospital: Adequate staffing and pediatric bed availability.
Health system: Universal access to health insurance.

Sarah G. Candler, MD, MPH, care team medical director and director of academic relations, Iora Primary Care, Northside Clinic, Houston
Patients: Systems of health that start with communities of safety, including access to affordable housing, food, transportation, and health care.
Practice/hospital: I.N.T.E.R.O.P.E.R.A.B.I.L.I.T.Y.
Health system: Clinician leadership that has the power (often aka funding) to do what’s right, not just what’s right in front of us.

Arthur L. Caplan, PhD, bioethicist, New York University Langone Health
Patients: I wish for patients in the United States greater access to affordable primary care. There are still too many people without insurance or a reasonably accessible quality provider. And I especially wish for the rapid expansion of affordable training programs to meet staffing needs, including more scholarships, 3-year programs, and more new primary care–oriented schools.
Hospital: Increased staffing, especially nursing. There are too many retirements, too much burnout, and too much privatization into boutique practices to ensure the ability to provide high-quality, safe, patient-oriented care.
Health system: I wish for health systems to seriously move into electronic medicine. While billing has become electronic, there is still much to be done to supplement diagnosis, training, and standardized data collection on key metrics. Systems are not yet behaving in a manner consistent with the hype in this regard.

Stephen Devries, MD, executive director, Gaples Institute (nonprofit) and adjunct associate professor of nutrition, Harvard School of Public Health, Boston
Patients: Patients continue to demand more from their health care professionals and insist that they are offered evidence-based counseling on nutrition and lifestyle strategies.
Practice: Quality-based reimbursement for medical services will take hold that will incentivize much-needed preventive care.
Hospital: Hospitals will more fully embrace the role of serving as true centers of health and focus as much on preventive medicine as on the more lucrative areas of high-tech treatment.

Peter D. Friedmann, MD, MPH, chief research officer, Baystate Health, Springfield, Mass.
Seconded by: Elisabeth Poorman, MD, general internist, University of Washington Clinic, Kent
Patients: Don’t forget the ongoing epidemic of substance use disorder, a major cause of premature mortality. Descheduling of cannabis and expungement of cannabis-related convictions.
Practice/hospital: Commitment of hospitals and practices to address stigma and ensure delivery of medications for opioid use disorder in primary care, the emergency department, and inpatient settings.
Health system: Reform of antiquated methadone regulations to permit office-based prescription and pharmacy dispensing to treat opioid use disorder, as is the case in most of the world.

Robert Glatter, MD, emergency physician, New York
Patients: I want all patients to understand the enormous strain the health care system has been under – not just with the pandemic, the tripledemic, and mpox [previously called monkeypox], but well before the onset of these public health crises.
Hospital: The medical profession has endured not only burnout but a growing mental health crisis, staffing shortages, a physician addiction crisis, and increased attrition in the decade leading up to the pandemic. The pandemic was like a punch in the gut, occurring at the most inopportune time one could imagine.
Health system: The intersection of health and the state of our public health deserves important mention. Unless we take action to bolster our public health infrastructure, our health care system will be in jeopardy, unable to handle the next pandemic, which could be just around the corner.

William E. Golden, MD, medical director of Arkansas Medicaid, professor of medicine and public health, University of Arkansas for Medical Sciences, Little Rock
Patients: Affordable options for diabetes and obesity management.
Health system: Greater investment by health systems and third-party payers in primary care infrastructure.

Gregory A. Hood, MD, Baptist Health, Lexington, Ky.
Patients: To embrace the gift of getting out in the world, being active, and connecting with others – having put down the screens.
Health system: To be freed from the financial gamesmanship of the insurers as they continue to serve their goals of promoting their hedge fund investing over meaningful and productive partnering with primary care physicians, and that they gain insight that they are one of the main reasons they can’t find PCPs to connect with to render care in disadvantaged environments – because they made it economically impossible to do so.

Robert H. Hopkins Jr., MD, associate professor of internal medicine and pediatrics and director of the division of general internal medicine, University of Arkansas for Medical Sciences, Little Rock
Patients/Health system: I would wish for staged implementation of universal basic health coverage for all, perhaps closest to the French or Canadian model. This would need to be coupled with expanded funding for nursing education, graduate medical education, and tracing of other health-related professionals.

Harvey Hsu, MD, Banner Health, Phoenix
Patients: More clear guidelines that are simple to understand. This can apply to colonoscopy (now age 45), immunizations, blood pressure goals. I wish medications were not as expensive so patients can take the best medicine for them and not stop taking them when they hit their donut hole in coverage.
Practice: We have been functioning on a leaner basis to cut down costs. When the pandemic hit, turnover was high and we lost PAs, nurses, front-office staff, and physicians. Having adequate staffing is probably number one on many lists. One way we dealt with lack of staffing was converting in-person visits to telehealth. Video visits are paid the same as in-person visits, but if the patient could not get their video to work, then it would be a telephone visit. Now many insurances do not even pay for telephone visits. So I would wish that we could still be reimbursed for telehealth visits.
Health system: I would wish for our health system to recognize the extra work required to take care of patients while improving quality and meeting quality measures. Allowing more time for patient visits could be one way to meet those goals or having more support staff to make sure patients get their colonoscopy/mammograms done, improve their sugars, and take their medications.

Jan L. Shifren, MD, Vincent Trustees Professor, obstetrics, gynecology, and reproductive biology, Harvard Medical School, and director of the Midlife Women’s Health Center at Massachusetts General Hospital, Boston
Patients: I wish for patients to be actively involved in all aspects of their care, well informed with shared decision-making.
Practice: I wish for the enormous time demands of electronic medical records and documentation to not distract from the pleasure of caring for patients.
Health system: Patient care remains at the center of decisions and programs.

Timothy J. Joos, MD, MPH, internal medicine/pediatrics, Seattle
Health system: I wish someone could figure out how we could be reimbursed for the quality of care we provide instead of the volume of patients we see. I wish EMRs could become less complicated and more user-friendly rather than needing advanced training to use.

Peter Kovacs, MD, medical director, Kaali Institute IVF Center, Budapest
Patients: I work as an infertility specialist, so when we talk about infectious diseases and associated risks, we talk about a minimum of two (female and male partner) and ideally three (plus the pregnancy) individuals. We have learned that SARS-CoV-2 affects reproductive health. It may compromise sperm production, could delay fertility treatment, could be associated with lower success rates; and if the treatment is successful, it may harm the pregnant woman/fetus/newborn. The best preventive measure that we can offer is vaccination. One cannot overemphasize the importance of preventive measures, paying attention to personal hygiene and social distancing. Therefore, I wish those planning to become pregnant to listen to their health care provider and accept the recommended vaccines to minimize the risk of getting infected and to minimize the risk for severe disease, especially if one undergoes successful fertility treatment and achieves a long-desired pregnancy.
Practice: During the 2022 calendar year we had many days when one or more employees were out of work on sick leave. This puts extra stress on the others to allow uncompromised work in the clinic. In addition, we all have to work in a less-comfortable environment if we consider mask use every day, all day. For health care workers, vaccination is mandated but many still are affected by milder forms of coronavirus infection and other respiratory diseases. Therefore, I wish my colleagues patience toward the preventive measures to lower the individual risk for infections. As a result, hopefully we will have a less stressful 2023.
Health system: Many resources had to be delegated to dealing with acute and chronic COVID, and this was at the expense of routine daily elective and preventive medical services. I wish the health care system to return to normal daily operations, to have the personnel and financial resources to carry on with the required preventive and elective medical services to avoid long-term consequences of not being able to provide such services. It would be sad if we had to treat otherwise preventable illnesses in the upcoming years that went undiagnosed and/or were not properly managed due to limited resources as the result of the pandemic.

Alan R. Nelson, MD, internist-endocrinologist, retired
Patients: Expansion of the FDA’s authority into over-the-counter drugs, including the veracity of their advertising claims.
Practice: Make diabetes drugs available at a reasonable cost.
Health system: With the expansion of Medicaid eligibility during COVID-19 coming to a close, federal government actions are necessary for those who once again have been dropped from coverage to have their legitimate needs met.

Kevin Powell, MD, PhD, St. Louis
Patients: To be cared for and about, and not just medically, even when illness strikes and health fails.
Hospitals: To hear the thankfulness of a grateful public for the care you provide, and to hear that above the angry noise of outraged individuals who spout vitriol and focus on how they believe others have harmed them.
Health system: A truer understanding of mercy and justice.

Margaret Thew, DNP, FNP-BC, director, department of adolescent medicine, Children’s Hospital of Wisconsin, Milwaukee
Seconded by: M. Susan Jay, MD, professor of pediatrics, chief of adolescent medicine, Medical College of Wisconsin and Children’s Hospital of Wisconsin, Milwaukee
My wish for patients, hospital, and system: health, calm, and grace.

Mark P. Trolice, MD, director of Fertility CARE, the IVF Center, Winter Park, Fla.
Patients: To be proactive in their health care and be their own advocates. Question when unclear and only consult credible resources.
Practice/hospital: Improve support of physicians and all health care providers to allow more input in their practice operations and growth.
Health system: Reduce interference of the “business of medicine” and ensure that the patient experience is the priority.

Charles P. Vega, MD, University of California, Irvine
Three minutes on a routine basis for everyone in health care to reflect on our blessings and the honor and gravity – as well as joy – that are integral to health care. Three minutes that will also help us to recognize our challenges and put them in the proper context. I know 3 minutes is not meeting any standard for reflective practice. But it’s 3 minutes more than I have right now.

Karen Breach Washington, MD, medical director of WellCare of North Carolina/Centene, Charlotte
Seconded by: Lillian M. Beard, MD, physician director, Children’s Pediatricians and Associates, Silver Spring, Md.
Patients: Access to affordable health care.
Hospital: Resources to care for patients (sufficient number of beds and a healthy staff).
Health system: Equity for all.

Andrew Wilner, MD, host of the podcast “The Art of Medicine with Dr. Andrew Wilner,” www.andrewwilner.com
Let’s put patients first! Too many extraneous considerations other than the patient’s best interest obstruct optimal patient care.

Here are just a few examples of patients coming last instead of first.

• If a patient needs to start a new medication in hospital, we shouldn’t have to wait until the patient is an outpatient because “that’s when insurance will pay.”
• If there’s a new medication that’s better than the old medication, we shouldn’t be forced to choose the old medication and provide inferior care because “that’s when insurance will pay.”
• If patients need to stay in hospital, we shouldn’t be pressured to discharge them because the hospital has decided that decreasing “length of stay” is its highest priority.

Dr. Francis Peabody said it best in 1927: “The secret of the care of the patient is in caring for the patient.” How hard is that?

In 2023, why don’t we follow Dr. Peabody’s sage advice from nearly 100 years ago and see what happens?
 

James M. Wooten, PharmD, University of Missouri–Kansas City, University Health, Kansas City, Mo.
Patients: I want patients to understand and properly realize the advantage of vaccinations – not only for COVID-19 but also for influenza. There is so much misinformation that I spend a lot of time trying to convince patients to get vaccinated. Most patients don’t realize that through their lives, most of them have already been vaccinated for something just to be able to attend school. How the COVID-19 vaccine created so much stigma makes little sense to me. I also want patients to understand that COVID-19 vaccination and boosters do not always prevent infection but will many times prevent severe infection. I believe that better patient communication and education is the key and will always be the key to improving vaccination numbers. Not only communicating and educating patients on vaccination itself but also making patients realize that personal vaccination decisions may affect what happens to your neighbor. Allowing infection means that you may be more likely to infect someone else. As a society, we must take care of each other.
Health system: It will be interesting to see what happens when vaccines are no longer reimbursed by the federal government. Understanding which vaccines work best and are better tolerated will be key to choosing appropriate vaccine brands. Health care providers will need to be very selective regarding which vaccines are selected for formulary inclusion. Thorough meta-analysis studies must be done to provide more evaluable information to allow for appropriate selection. “Knowledge is power!” Appropriate knowledge will help distinguish which vaccines work best for various patient populations.

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

As physicians well know, magic wands don’t exist. If they did, every patient would recover in the exam room, prior authorization wouldn’t exist, and continuing medical education credits would be printed on bearer bonds.

But in the spirit of suspended disbelief, we asked physicians and other contributors what their three wishes would be for their patients, practice/hospital, and health systems. Because, hey – we all need to dream.
 

Suzanne C. Boulter, MD, adjunct professor of pediatrics and community and family medicine, Geisel School of Medicine at Dartmouth, Hanover, N.H.
Patients: An end to gun violence.
Practice/hospital: Adequate staffing and pediatric bed availability.
Health system: Universal access to health insurance.

Sarah G. Candler, MD, MPH, care team medical director and director of academic relations, Iora Primary Care, Northside Clinic, Houston
Patients: Systems of health that start with communities of safety, including access to affordable housing, food, transportation, and health care.
Practice/hospital: I.N.T.E.R.O.P.E.R.A.B.I.L.I.T.Y.
Health system: Clinician leadership that has the power (often aka funding) to do what’s right, not just what’s right in front of us.

Arthur L. Caplan, PhD, bioethicist, New York University Langone Health
Patients: I wish for patients in the United States greater access to affordable primary care. There are still too many people without insurance or a reasonably accessible quality provider. And I especially wish for the rapid expansion of affordable training programs to meet staffing needs, including more scholarships, 3-year programs, and more new primary care–oriented schools.
Hospital: Increased staffing, especially nursing. There are too many retirements, too much burnout, and too much privatization into boutique practices to ensure the ability to provide high-quality, safe, patient-oriented care.
Health system: I wish for health systems to seriously move into electronic medicine. While billing has become electronic, there is still much to be done to supplement diagnosis, training, and standardized data collection on key metrics. Systems are not yet behaving in a manner consistent with the hype in this regard.

Stephen Devries, MD, executive director, Gaples Institute (nonprofit) and adjunct associate professor of nutrition, Harvard School of Public Health, Boston
Patients: Patients continue to demand more from their health care professionals and insist that they are offered evidence-based counseling on nutrition and lifestyle strategies.
Practice: Quality-based reimbursement for medical services will take hold that will incentivize much-needed preventive care.
Hospital: Hospitals will more fully embrace the role of serving as true centers of health and focus as much on preventive medicine as on the more lucrative areas of high-tech treatment.

Peter D. Friedmann, MD, MPH, chief research officer, Baystate Health, Springfield, Mass.
Seconded by: Elisabeth Poorman, MD, general internist, University of Washington Clinic, Kent
Patients: Don’t forget the ongoing epidemic of substance use disorder, a major cause of premature mortality. Descheduling of cannabis and expungement of cannabis-related convictions.
Practice/hospital: Commitment of hospitals and practices to address stigma and ensure delivery of medications for opioid use disorder in primary care, the emergency department, and inpatient settings.
Health system: Reform of antiquated methadone regulations to permit office-based prescription and pharmacy dispensing to treat opioid use disorder, as is the case in most of the world.

Robert Glatter, MD, emergency physician, New York
Patients: I want all patients to understand the enormous strain the health care system has been under – not just with the pandemic, the tripledemic, and mpox [previously called monkeypox], but well before the onset of these public health crises.
Hospital: The medical profession has endured not only burnout but a growing mental health crisis, staffing shortages, a physician addiction crisis, and increased attrition in the decade leading up to the pandemic. The pandemic was like a punch in the gut, occurring at the most inopportune time one could imagine.
Health system: The intersection of health and the state of our public health deserves important mention. Unless we take action to bolster our public health infrastructure, our health care system will be in jeopardy, unable to handle the next pandemic, which could be just around the corner.

William E. Golden, MD, medical director of Arkansas Medicaid, professor of medicine and public health, University of Arkansas for Medical Sciences, Little Rock
Patients: Affordable options for diabetes and obesity management.
Health system: Greater investment by health systems and third-party payers in primary care infrastructure.

Gregory A. Hood, MD, Baptist Health, Lexington, Ky.
Patients: To embrace the gift of getting out in the world, being active, and connecting with others – having put down the screens.
Health system: To be freed from the financial gamesmanship of the insurers as they continue to serve their goals of promoting their hedge fund investing over meaningful and productive partnering with primary care physicians, and that they gain insight that they are one of the main reasons they can’t find PCPs to connect with to render care in disadvantaged environments – because they made it economically impossible to do so.

Robert H. Hopkins Jr., MD, associate professor of internal medicine and pediatrics and director of the division of general internal medicine, University of Arkansas for Medical Sciences, Little Rock
Patients/Health system: I would wish for staged implementation of universal basic health coverage for all, perhaps closest to the French or Canadian model. This would need to be coupled with expanded funding for nursing education, graduate medical education, and tracing of other health-related professionals.

Harvey Hsu, MD, Banner Health, Phoenix
Patients: More clear guidelines that are simple to understand. This can apply to colonoscopy (now age 45), immunizations, blood pressure goals. I wish medications were not as expensive so patients can take the best medicine for them and not stop taking them when they hit their donut hole in coverage.
Practice: We have been functioning on a leaner basis to cut down costs. When the pandemic hit, turnover was high and we lost PAs, nurses, front-office staff, and physicians. Having adequate staffing is probably number one on many lists. One way we dealt with lack of staffing was converting in-person visits to telehealth. Video visits are paid the same as in-person visits, but if the patient could not get their video to work, then it would be a telephone visit. Now many insurances do not even pay for telephone visits. So I would wish that we could still be reimbursed for telehealth visits.
Health system: I would wish for our health system to recognize the extra work required to take care of patients while improving quality and meeting quality measures. Allowing more time for patient visits could be one way to meet those goals or having more support staff to make sure patients get their colonoscopy/mammograms done, improve their sugars, and take their medications.

Jan L. Shifren, MD, Vincent Trustees Professor, obstetrics, gynecology, and reproductive biology, Harvard Medical School, and director of the Midlife Women’s Health Center at Massachusetts General Hospital, Boston
Patients: I wish for patients to be actively involved in all aspects of their care, well informed with shared decision-making.
Practice: I wish for the enormous time demands of electronic medical records and documentation to not distract from the pleasure of caring for patients.
Health system: Patient care remains at the center of decisions and programs.

Timothy J. Joos, MD, MPH, internal medicine/pediatrics, Seattle
Health system: I wish someone could figure out how we could be reimbursed for the quality of care we provide instead of the volume of patients we see. I wish EMRs could become less complicated and more user-friendly rather than needing advanced training to use.

Peter Kovacs, MD, medical director, Kaali Institute IVF Center, Budapest
Patients: I work as an infertility specialist, so when we talk about infectious diseases and associated risks, we talk about a minimum of two (female and male partner) and ideally three (plus the pregnancy) individuals. We have learned that SARS-CoV-2 affects reproductive health. It may compromise sperm production, could delay fertility treatment, could be associated with lower success rates; and if the treatment is successful, it may harm the pregnant woman/fetus/newborn. The best preventive measure that we can offer is vaccination. One cannot overemphasize the importance of preventive measures, paying attention to personal hygiene and social distancing. Therefore, I wish those planning to become pregnant to listen to their health care provider and accept the recommended vaccines to minimize the risk of getting infected and to minimize the risk for severe disease, especially if one undergoes successful fertility treatment and achieves a long-desired pregnancy.
Practice: During the 2022 calendar year we had many days when one or more employees were out of work on sick leave. This puts extra stress on the others to allow uncompromised work in the clinic. In addition, we all have to work in a less-comfortable environment if we consider mask use every day, all day. For health care workers, vaccination is mandated but many still are affected by milder forms of coronavirus infection and other respiratory diseases. Therefore, I wish my colleagues patience toward the preventive measures to lower the individual risk for infections. As a result, hopefully we will have a less stressful 2023.
Health system: Many resources had to be delegated to dealing with acute and chronic COVID, and this was at the expense of routine daily elective and preventive medical services. I wish the health care system to return to normal daily operations, to have the personnel and financial resources to carry on with the required preventive and elective medical services to avoid long-term consequences of not being able to provide such services. It would be sad if we had to treat otherwise preventable illnesses in the upcoming years that went undiagnosed and/or were not properly managed due to limited resources as the result of the pandemic.

Alan R. Nelson, MD, internist-endocrinologist, retired
Patients: Expansion of the FDA’s authority into over-the-counter drugs, including the veracity of their advertising claims.
Practice: Make diabetes drugs available at a reasonable cost.
Health system: With the expansion of Medicaid eligibility during COVID-19 coming to a close, federal government actions are necessary for those who once again have been dropped from coverage to have their legitimate needs met.

Kevin Powell, MD, PhD, St. Louis
Patients: To be cared for and about, and not just medically, even when illness strikes and health fails.
Hospitals: To hear the thankfulness of a grateful public for the care you provide, and to hear that above the angry noise of outraged individuals who spout vitriol and focus on how they believe others have harmed them.
Health system: A truer understanding of mercy and justice.

Margaret Thew, DNP, FNP-BC, director, department of adolescent medicine, Children’s Hospital of Wisconsin, Milwaukee
Seconded by: M. Susan Jay, MD, professor of pediatrics, chief of adolescent medicine, Medical College of Wisconsin and Children’s Hospital of Wisconsin, Milwaukee
My wish for patients, hospital, and system: health, calm, and grace.

Mark P. Trolice, MD, director of Fertility CARE, the IVF Center, Winter Park, Fla.
Patients: To be proactive in their health care and be their own advocates. Question when unclear and only consult credible resources.
Practice/hospital: Improve support of physicians and all health care providers to allow more input in their practice operations and growth.
Health system: Reduce interference of the “business of medicine” and ensure that the patient experience is the priority.

Charles P. Vega, MD, University of California, Irvine
Three minutes on a routine basis for everyone in health care to reflect on our blessings and the honor and gravity – as well as joy – that are integral to health care. Three minutes that will also help us to recognize our challenges and put them in the proper context. I know 3 minutes is not meeting any standard for reflective practice. But it’s 3 minutes more than I have right now.

Karen Breach Washington, MD, medical director of WellCare of North Carolina/Centene, Charlotte
Seconded by: Lillian M. Beard, MD, physician director, Children’s Pediatricians and Associates, Silver Spring, Md.
Patients: Access to affordable health care.
Hospital: Resources to care for patients (sufficient number of beds and a healthy staff).
Health system: Equity for all.

Andrew Wilner, MD, host of the podcast “The Art of Medicine with Dr. Andrew Wilner,” www.andrewwilner.com
Let’s put patients first! Too many extraneous considerations other than the patient’s best interest obstruct optimal patient care.

Here are just a few examples of patients coming last instead of first.

• If a patient needs to start a new medication in hospital, we shouldn’t have to wait until the patient is an outpatient because “that’s when insurance will pay.”
• If there’s a new medication that’s better than the old medication, we shouldn’t be forced to choose the old medication and provide inferior care because “that’s when insurance will pay.”
• If patients need to stay in hospital, we shouldn’t be pressured to discharge them because the hospital has decided that decreasing “length of stay” is its highest priority.

Dr. Francis Peabody said it best in 1927: “The secret of the care of the patient is in caring for the patient.” How hard is that?

In 2023, why don’t we follow Dr. Peabody’s sage advice from nearly 100 years ago and see what happens?
 

James M. Wooten, PharmD, University of Missouri–Kansas City, University Health, Kansas City, Mo.
Patients: I want patients to understand and properly realize the advantage of vaccinations – not only for COVID-19 but also for influenza. There is so much misinformation that I spend a lot of time trying to convince patients to get vaccinated. Most patients don’t realize that through their lives, most of them have already been vaccinated for something just to be able to attend school. How the COVID-19 vaccine created so much stigma makes little sense to me. I also want patients to understand that COVID-19 vaccination and boosters do not always prevent infection but will many times prevent severe infection. I believe that better patient communication and education is the key and will always be the key to improving vaccination numbers. Not only communicating and educating patients on vaccination itself but also making patients realize that personal vaccination decisions may affect what happens to your neighbor. Allowing infection means that you may be more likely to infect someone else. As a society, we must take care of each other.
Health system: It will be interesting to see what happens when vaccines are no longer reimbursed by the federal government. Understanding which vaccines work best and are better tolerated will be key to choosing appropriate vaccine brands. Health care providers will need to be very selective regarding which vaccines are selected for formulary inclusion. Thorough meta-analysis studies must be done to provide more evaluable information to allow for appropriate selection. “Knowledge is power!” Appropriate knowledge will help distinguish which vaccines work best for various patient populations.

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

Nonstop inflammation and immune problems top the list of potential causes of long COVID, but doctors say it’s growing clear that more than one thing is to blame for the wide swath of often debilitating symptoms that could last months or even years.

“I think that it’s a much more complex picture than just inflammation, or just autoimmunity, or just immune dysregulation. And it’s probably a combination of all three causing a cascade of effects that then manifests itself as brain fog, or shortness of breath, or chronic fatigue,” says Alexander Truong, MD, a pulmonologist and assistant professor at Emory University, Atlanta, who also runs a long-COVID clinic.

Long COVID, post–COVID-19 condition, and postacute sequelae of SARS-CoV-2 (PASC) are among the terms used by the National Institutes of Health to describe the long-term health issues faced by an estimated 10%-30% of people infected with COVID-19. Symptoms – as many as 200 – can range from inconvenient to crippling, damage multiple organ systems, come and go, and relapse. Long COVID increases the risk of worsening existing health problems and triggering new ones, including cardiovascular disease and type 2 diabetes.

So far, research suggests there is no single cause, condition, or disease that explains why some people have an extensive range of symptoms long after the early COVID-19 infection has cleared up. Many experts believe some combination of biological processes – including the virus hanging around in our bodies, inflammation, autoimmunity, tiny blood clots, immune system problems, and even the reactivation of dormant viruses such as the Epstein-Barr virus – could be the culprit, a theory also supported by a comprehensive and in-depth review of long-COVID studies published in the journal Nature Reviews Microbiology.

“It’s become clear over the last couple of years that there are different [symptoms] of long COVID … that cannot all be lumped together,” says Michael Peluso, MD, an assistant professor of medicine and an infectious diseases doctor at the University of California, San Francisco.
 

Inflammation and a virus that hangs around

Multiple studies have shown that the virus or pieces of it can remain in many parts of the body, including the kidneys, brain, heart, and gastrointestinal system, long after the early infection. 

“One major question that I think is the area of most intense investigation now is whether there is viral persistence that is driving immune dysregulation and therefore symptoms,” says Dr. Peluso.

A small Harvard University study, for example, found evidence that reservoirs of the coronavirus could linger in patients up to a year after they’re first diagnosed. 

An earlier German study found that patients with post-COVID-19 symptoms had higher levels of three cytokines – small proteins that tell the body’s immune system what to do and are involved in the growth and activity of immune system cells and blood cells. Researchers said the results supported the theory that there is persistent reprogramming of certain immune cells, and that the uncontrolled “self-fueled hyperinflammation” during the early COVID-19 infection can become continued immune cell disruption that drives long-COVID symptoms.

“Long COVID is more likely due to either an inflammatory response by the body or reservoirs of virus that the body is still trying to clear … and the symptoms we’re seeing are a side effect of that,” says Rainu Kaushal, MD, senior associate dean for clinical research at Weill Cornell Medicine in New York.

Australian researchers found that immune system recovery appeared different, compared with those who were infected with other common coronaviruses.

These findings also support concerns that some experts express over the long-term risks of COVID-19 infections in general, but especially repeat infections.

“Anything that kind of revs up inflammation in the body can boil that pot over and make the symptoms worse. That’s very easily an infection or some other insult to the body. So that’s the generalized hypothesis as to why insults to the body may worsen the symptoms,” says Dr. Truong.
 

An autoimmune condition?

But inflammation alone does not fully explain post–COVID-19 problems.

Dr. Truong and his team, for example, have been documenting inflammatory markers in patients at the post-COVID clinic he cofounded more than 2 years ago at Emory Executive Park in Atlanta. When the clinic was first launched, high-dose nonsteroidal anti-inflammatory drugs – including ibuprofen – and prednisone were prescribed to long-COVID patients.

“It didn’t make a difference at all for any of these folks,” he says, adding that there are signs that autoimmunity is at play. But he cautions that it is still too early to suggest treating long-COVID patients with medications used for other autoimmune conditions.

In autoimmune conditions such as rheumatoid arthritis, lupus, and type 1 diabetes, a person’s immune system can’t tell normal cells from foreign pathogens and attacks healthy cells. There is typically no single diagnostic test, and many share similar symptoms, making detection and diagnosis potentially difficult, according to Johns Hopkins Medicine.

A small study published in the journal  Science Translational Medicine found that, among patients who failed to regain their sense of smell long after their initial infection, there was inflammation in the nose tissue where smell nerve cells are found, even though no detectable virus remained. Fewer olfactory sensory neurons were seen, as well – findings that researchers said resembled some kind of “autoimmune-like process.”

Meanwhile, scientists in Canada found signs of autoimmunity in blood samples taken from patients who still had fatigue and shortness of breath after their initial COVID-19 infection. Two specific proteins were present a year after infection in up to 30% of patients, many of whom still had shortness of breath and fatigue, the researchers reported in the Jan. 1 issue of the European Respiratory Journal. These patients had been healthy and had no autoimmune condition or other diseases before they were infected.
 

Immune system problems

A number of studies have suggested that a problematic immune response could also explain why symptoms persist for some people.

Researchers in France, for example, found that the immune response problems in those with severe COVID-19 infections caused exaggerated or uncontrolled formation of a type of bug-fighting defense mechanism called a neutrophil extracellular trap (NET), which in turn triggers harmful inflammation that can result in multiorgan damage. These traps are netlike structures made from fibers composed mostly of DNA strings that bind, or trap, pathogens.

Long COVID is not like an acute infectious disease, says Alexander Charney, MD, PhD, the lead principal investigator of the RECOVER adult cohort at Mount Sinai in New York, and an associate professor at Icahn School of Medicine at Mount Sinai. It is more similar to other complex chronic diseases that have taken decades to understand, such as heart disease, mental illness, and rheumatologic diseases, he says.
 

Biomarkers and blood clots

Scientists are homing in on biomarkers, or detectable and measurable traits – in this case, molecular indicators – that can make diagnosing long COVID easier and give better direction for treatment. These biomarkers are also key to helping sort out the complex biology of long COVID.

In one study, data from blood samples taken from hundreds of hospitalized COVID-19 patients suggests changes are happening at the molecular level during initial severe infections. These changes may be tied to the development of longer-term symptoms, according to the study by Dr. Charney and his team at Mount Sinai published in Nature Medicine

Blood clotting issues have also been detected in long COVID patients. At least one study found signs that long-COVID patients had higher levels of a type of auto-antibody linked to the abnormal formation of clots. Researchers suspect that tiny, persistent microclots – undetectable via regular pathology tests – may be cutting off oxygen flow to tissue by blocking capillaries – and could explain many of the post-COVID symptoms described by patients.

While enormous progress has been made toward understanding long COVID, the research is still considered early and faces many challenges, including varying criteria used to define the condition, the types and quality of data used, differences in how patients are defined and recruited, and the small size of many studies. Some research also appears to conflict with other studies. And while there are specialized tools for diagnosing some aspects of the condition, standard tests often don’t detect many of the signs seen in long-COVID patients. But given the urgency and global scale of the problem, experts say more funding and support should be prioritized.

“People are suffering now, and they want answers now. ... It’s not like with COVID, where the path towards a great and meaningful solution to this unbelievable problem was clear – we need a vaccine,” says Dr. Charney. 

“It’s going to be a long haul to figure out what is going on.”

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

Nonstop inflammation and immune problems top the list of potential causes of long COVID, but doctors say it’s growing clear that more than one thing is to blame for the wide swath of often debilitating symptoms that could last months or even years.

“I think that it’s a much more complex picture than just inflammation, or just autoimmunity, or just immune dysregulation. And it’s probably a combination of all three causing a cascade of effects that then manifests itself as brain fog, or shortness of breath, or chronic fatigue,” says Alexander Truong, MD, a pulmonologist and assistant professor at Emory University, Atlanta, who also runs a long-COVID clinic.

Long COVID, post–COVID-19 condition, and postacute sequelae of SARS-CoV-2 (PASC) are among the terms used by the National Institutes of Health to describe the long-term health issues faced by an estimated 10%-30% of people infected with COVID-19. Symptoms – as many as 200 – can range from inconvenient to crippling, damage multiple organ systems, come and go, and relapse. Long COVID increases the risk of worsening existing health problems and triggering new ones, including cardiovascular disease and type 2 diabetes.

So far, research suggests there is no single cause, condition, or disease that explains why some people have an extensive range of symptoms long after the early COVID-19 infection has cleared up. Many experts believe some combination of biological processes – including the virus hanging around in our bodies, inflammation, autoimmunity, tiny blood clots, immune system problems, and even the reactivation of dormant viruses such as the Epstein-Barr virus – could be the culprit, a theory also supported by a comprehensive and in-depth review of long-COVID studies published in the journal Nature Reviews Microbiology.

“It’s become clear over the last couple of years that there are different [symptoms] of long COVID … that cannot all be lumped together,” says Michael Peluso, MD, an assistant professor of medicine and an infectious diseases doctor at the University of California, San Francisco.
 

Inflammation and a virus that hangs around

Multiple studies have shown that the virus or pieces of it can remain in many parts of the body, including the kidneys, brain, heart, and gastrointestinal system, long after the early infection. 

“One major question that I think is the area of most intense investigation now is whether there is viral persistence that is driving immune dysregulation and therefore symptoms,” says Dr. Peluso.

A small Harvard University study, for example, found evidence that reservoirs of the coronavirus could linger in patients up to a year after they’re first diagnosed. 

An earlier German study found that patients with post-COVID-19 symptoms had higher levels of three cytokines – small proteins that tell the body’s immune system what to do and are involved in the growth and activity of immune system cells and blood cells. Researchers said the results supported the theory that there is persistent reprogramming of certain immune cells, and that the uncontrolled “self-fueled hyperinflammation” during the early COVID-19 infection can become continued immune cell disruption that drives long-COVID symptoms.

“Long COVID is more likely due to either an inflammatory response by the body or reservoirs of virus that the body is still trying to clear … and the symptoms we’re seeing are a side effect of that,” says Rainu Kaushal, MD, senior associate dean for clinical research at Weill Cornell Medicine in New York.

Australian researchers found that immune system recovery appeared different, compared with those who were infected with other common coronaviruses.

These findings also support concerns that some experts express over the long-term risks of COVID-19 infections in general, but especially repeat infections.

“Anything that kind of revs up inflammation in the body can boil that pot over and make the symptoms worse. That’s very easily an infection or some other insult to the body. So that’s the generalized hypothesis as to why insults to the body may worsen the symptoms,” says Dr. Truong.
 

An autoimmune condition?

But inflammation alone does not fully explain post–COVID-19 problems.

Dr. Truong and his team, for example, have been documenting inflammatory markers in patients at the post-COVID clinic he cofounded more than 2 years ago at Emory Executive Park in Atlanta. When the clinic was first launched, high-dose nonsteroidal anti-inflammatory drugs – including ibuprofen – and prednisone were prescribed to long-COVID patients.

“It didn’t make a difference at all for any of these folks,” he says, adding that there are signs that autoimmunity is at play. But he cautions that it is still too early to suggest treating long-COVID patients with medications used for other autoimmune conditions.

In autoimmune conditions such as rheumatoid arthritis, lupus, and type 1 diabetes, a person’s immune system can’t tell normal cells from foreign pathogens and attacks healthy cells. There is typically no single diagnostic test, and many share similar symptoms, making detection and diagnosis potentially difficult, according to Johns Hopkins Medicine.

A small study published in the journal  Science Translational Medicine found that, among patients who failed to regain their sense of smell long after their initial infection, there was inflammation in the nose tissue where smell nerve cells are found, even though no detectable virus remained. Fewer olfactory sensory neurons were seen, as well – findings that researchers said resembled some kind of “autoimmune-like process.”

Meanwhile, scientists in Canada found signs of autoimmunity in blood samples taken from patients who still had fatigue and shortness of breath after their initial COVID-19 infection. Two specific proteins were present a year after infection in up to 30% of patients, many of whom still had shortness of breath and fatigue, the researchers reported in the Jan. 1 issue of the European Respiratory Journal. These patients had been healthy and had no autoimmune condition or other diseases before they were infected.
 

Immune system problems

A number of studies have suggested that a problematic immune response could also explain why symptoms persist for some people.

Researchers in France, for example, found that the immune response problems in those with severe COVID-19 infections caused exaggerated or uncontrolled formation of a type of bug-fighting defense mechanism called a neutrophil extracellular trap (NET), which in turn triggers harmful inflammation that can result in multiorgan damage. These traps are netlike structures made from fibers composed mostly of DNA strings that bind, or trap, pathogens.

Long COVID is not like an acute infectious disease, says Alexander Charney, MD, PhD, the lead principal investigator of the RECOVER adult cohort at Mount Sinai in New York, and an associate professor at Icahn School of Medicine at Mount Sinai. It is more similar to other complex chronic diseases that have taken decades to understand, such as heart disease, mental illness, and rheumatologic diseases, he says.
 

Biomarkers and blood clots

Scientists are homing in on biomarkers, or detectable and measurable traits – in this case, molecular indicators – that can make diagnosing long COVID easier and give better direction for treatment. These biomarkers are also key to helping sort out the complex biology of long COVID.

In one study, data from blood samples taken from hundreds of hospitalized COVID-19 patients suggests changes are happening at the molecular level during initial severe infections. These changes may be tied to the development of longer-term symptoms, according to the study by Dr. Charney and his team at Mount Sinai published in Nature Medicine

Blood clotting issues have also been detected in long COVID patients. At least one study found signs that long-COVID patients had higher levels of a type of auto-antibody linked to the abnormal formation of clots. Researchers suspect that tiny, persistent microclots – undetectable via regular pathology tests – may be cutting off oxygen flow to tissue by blocking capillaries – and could explain many of the post-COVID symptoms described by patients.

While enormous progress has been made toward understanding long COVID, the research is still considered early and faces many challenges, including varying criteria used to define the condition, the types and quality of data used, differences in how patients are defined and recruited, and the small size of many studies. Some research also appears to conflict with other studies. And while there are specialized tools for diagnosing some aspects of the condition, standard tests often don’t detect many of the signs seen in long-COVID patients. But given the urgency and global scale of the problem, experts say more funding and support should be prioritized.

“People are suffering now, and they want answers now. ... It’s not like with COVID, where the path towards a great and meaningful solution to this unbelievable problem was clear – we need a vaccine,” says Dr. Charney. 

“It’s going to be a long haul to figure out what is going on.”