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Retinal imaging can predict cardiovascular mortality
according to a new study using data from the UK Biobank Eye and Vision Consortium and the European Prospective Investigation into Cancer (EPIC)–Norfolk study.
The researchers, from St. George’s University of London, Cambridge University, Kingston University, Moorfields Eye Hospital, and University College London, developed a method of artificial intelligence (AI)–enabled imaging of the retina’s vascular network that could accurately predict CVD and death, without the need for blood tests or blood pressure measurement.
The system “paves the way for a highly effective, noninvasive screening test for people at medium to high risk of circulatory disease that doesn’t have to be done in a clinic,” they said. “In the general population it could be used as a noncontact form of systemic vascular health check, to triage those at medium-high risk of circulatory mortality for further clinical risk assessment and appropriate intervention.” Optometry specialists welcomed the prospect and hailed it as “an exciting development.”
Retinal vessels give an accurate early indicator of CVD
The study, published online in the British Journal of Ophthalmology, was based on previous research showing that the width of retinal arterioles and venules seen on retinal imaging may provide an accurate early indicator of CVD, whereas current risk prediction frameworks aren’t always reliable in identifying people who will go on to develop or die of circulatory diseases.
The researchers developed a fully automated AI-enabled algorithm, called Quantitative Analysis of Retinal vessels Topology and Size (QUARTZ), to assess the potential of retinal vasculature imaging plus known risk factors to predict vascular health and death. They applied QUARTZ to retinal images from 88,052 UK Biobank participants aged 40-69 years, looking specifically at the width, vessel area, and degree of tortuosity of the retinal microvasculature, to develop prediction models for stroke, heart attack, and death from circulatory disease.
They then applied these models to the retinal images of 7,411 participants, aged 48-92 years, in the EPIC-Norfolk study. They then compared the performance of QUARTZ with the widely used Framingham Risk Scores framework.
The participants in the two studies were tracked for an average of 7.7 and 9.1 years, respectively, during which time there were 327 circulatory disease deaths among 64,144 UK Biobank participants (average age, 56.8 years) and 201 circulatory deaths among 5,862 EPIC-Norfolk participants (average age, 67.6 years).
Vessel characteristics important predictors of CVD mortality
Results from the QUARTZ models showed that in all participants, arteriolar and venular width, venular tortuosity, and width variation were important predictors of circulatory disease death. In addition, in women, but not in men, arteriolar and venular area were separate factors that contributed to risk prediction.
Overall, the predictive models, based on age, smoking, and medical history (antihypertensive or cholesterol lowering medication, diabetes, and history of stroke or MI) as well as retinal vasculature, captured between half and two-thirds of circulatory disease deaths in those most at risk, the authors said.
Compared with Framingham Risk Scores (FRS), the retinal vasculature (RV) models captured about 5% more cases of stroke in UK Biobank men, 8% more cases in UK Biobank women, and 3% more cases among EPIC-Norfolk men most at risk, but nearly 2% fewer cases among EPIC-Norfolk women. However, the team said that, while adding RV to FRS resulted in only marginal changes in prediction of stroke or MI, a simpler noninvasive risk score based on age, sex, smoking status, medical history, and RV “yielded comparable performance to FRS, without the need for blood sampling or BP measurement.”
Vasculometry low cost, noninvasive and with high street availability
They concluded: “Retinal imaging is established within clinic and hospital eye care and in optometric practices in the U.S. and U.K. AI-enabled vasculometry risk prediction is fully automated, low cost, noninvasive and has the potential for reaching a higher proportion of the population in the community because of “high street” availability and because blood sampling or sphygmomanometry are not needed.
“[Retinal vasculature] is a microvascular marker, hence offers better prediction for circulatory mortality and stroke, compared with MI, which is more macrovascular, except perhaps in women.
“In the general population it could be used as a noncontact form of systemic vascular health check, to triage those at medium-high risk of circulatory mortality for further clinical risk assessment and appropriate intervention.”
In the United Kingdom, for example, it could be included in the primary care NHS Health Check for those aged 41-74 years, they suggested. In addition, “high street” retinal scanning could directly feed into primary medical services and help achieve greater screening coverage for older age groups, who are likely to attend an optometric practice for visual correction, especially with the onset of presbyopia. “This would offer a novel approach to identify those at high risk of circulatory mortality, which is not currently screened for,” the team said.
Test could help to identify high-risk individuals
In a linked editorial, Ify Mordi, MD, and Emanuele Trucco, MD, of the University of Dundee (Scotland), said that CVD remains a significant cause of mortality and morbidity and the most common cause of death worldwide, accounting for a quarter of all U.K. deaths – and its burden is increasing. “Identification of individuals at high risk is particularly important,” they said, but current clinical risk scores to identify those at risk “are unfortunately not perfect,” so miss some of those who might benefit from preventative therapy.
“The retina is the only location that allows non-invasive direct visualisation of the vasculature, potentially providing a rich source of information.” In the new study, the measurements derived with the software tool, QUARTZ, were significantly associated with CVD, they said, with similar predictive performance to the Framingham clinical risk score.
“The results strengthen the evidence from several similar studies that the retina can be a useful and potentially disruptive source of information for CVD risk in personalised medicine.” However, a number of questions remain about how this knowledge could be integrated into clinical care, including who would conduct such a retinal screening program and who would act on the findings?
The editorial concluded: “What is now needed is for ophthalmologists, cardiologists, primary care physicians, and computer scientists to work together to design studies to determine whether using this information improves clinical outcome, and, if so, to work with regulatory bodies, scientific societies and healthcare systems to optimize clinical work flows and enable practical implementation in routine practice.”
‘Exciting development that could improve outcomes’
Asked to comment, Farah Topia, clinical and regulatory adviser at the Association of Optometrists, said: “This is an exciting development that could improve outcomes for many patients by enabling earlier detection of serious health risks. Patients attend optometric practice for a variety of reasons and this interaction could be used to a greater extent to help detect disease earlier. With optometrists available on every High Street, in the heart of communities, it’s an element of primary care that can be accessed quickly and easily, and optometrists are also already trained to have health and lifestyle discussion with patients.”
She added: “Retinal photographs are regularly taken when patients visit an optometrist, so being able to further enhance this process using AI is exciting.
“We look forward to seeing how this area develops and how optometrists can work together with other healthcare sectors to improve patient outcomes and ease the burden the NHS currently faces.”
The study was funded by the Medical Research Council Population and Systems Medicine Board and the British Heart Foundation.
A version of this article first appeared on Medscape UK.
according to a new study using data from the UK Biobank Eye and Vision Consortium and the European Prospective Investigation into Cancer (EPIC)–Norfolk study.
The researchers, from St. George’s University of London, Cambridge University, Kingston University, Moorfields Eye Hospital, and University College London, developed a method of artificial intelligence (AI)–enabled imaging of the retina’s vascular network that could accurately predict CVD and death, without the need for blood tests or blood pressure measurement.
The system “paves the way for a highly effective, noninvasive screening test for people at medium to high risk of circulatory disease that doesn’t have to be done in a clinic,” they said. “In the general population it could be used as a noncontact form of systemic vascular health check, to triage those at medium-high risk of circulatory mortality for further clinical risk assessment and appropriate intervention.” Optometry specialists welcomed the prospect and hailed it as “an exciting development.”
Retinal vessels give an accurate early indicator of CVD
The study, published online in the British Journal of Ophthalmology, was based on previous research showing that the width of retinal arterioles and venules seen on retinal imaging may provide an accurate early indicator of CVD, whereas current risk prediction frameworks aren’t always reliable in identifying people who will go on to develop or die of circulatory diseases.
The researchers developed a fully automated AI-enabled algorithm, called Quantitative Analysis of Retinal vessels Topology and Size (QUARTZ), to assess the potential of retinal vasculature imaging plus known risk factors to predict vascular health and death. They applied QUARTZ to retinal images from 88,052 UK Biobank participants aged 40-69 years, looking specifically at the width, vessel area, and degree of tortuosity of the retinal microvasculature, to develop prediction models for stroke, heart attack, and death from circulatory disease.
They then applied these models to the retinal images of 7,411 participants, aged 48-92 years, in the EPIC-Norfolk study. They then compared the performance of QUARTZ with the widely used Framingham Risk Scores framework.
The participants in the two studies were tracked for an average of 7.7 and 9.1 years, respectively, during which time there were 327 circulatory disease deaths among 64,144 UK Biobank participants (average age, 56.8 years) and 201 circulatory deaths among 5,862 EPIC-Norfolk participants (average age, 67.6 years).
Vessel characteristics important predictors of CVD mortality
Results from the QUARTZ models showed that in all participants, arteriolar and venular width, venular tortuosity, and width variation were important predictors of circulatory disease death. In addition, in women, but not in men, arteriolar and venular area were separate factors that contributed to risk prediction.
Overall, the predictive models, based on age, smoking, and medical history (antihypertensive or cholesterol lowering medication, diabetes, and history of stroke or MI) as well as retinal vasculature, captured between half and two-thirds of circulatory disease deaths in those most at risk, the authors said.
Compared with Framingham Risk Scores (FRS), the retinal vasculature (RV) models captured about 5% more cases of stroke in UK Biobank men, 8% more cases in UK Biobank women, and 3% more cases among EPIC-Norfolk men most at risk, but nearly 2% fewer cases among EPIC-Norfolk women. However, the team said that, while adding RV to FRS resulted in only marginal changes in prediction of stroke or MI, a simpler noninvasive risk score based on age, sex, smoking status, medical history, and RV “yielded comparable performance to FRS, without the need for blood sampling or BP measurement.”
Vasculometry low cost, noninvasive and with high street availability
They concluded: “Retinal imaging is established within clinic and hospital eye care and in optometric practices in the U.S. and U.K. AI-enabled vasculometry risk prediction is fully automated, low cost, noninvasive and has the potential for reaching a higher proportion of the population in the community because of “high street” availability and because blood sampling or sphygmomanometry are not needed.
“[Retinal vasculature] is a microvascular marker, hence offers better prediction for circulatory mortality and stroke, compared with MI, which is more macrovascular, except perhaps in women.
“In the general population it could be used as a noncontact form of systemic vascular health check, to triage those at medium-high risk of circulatory mortality for further clinical risk assessment and appropriate intervention.”
In the United Kingdom, for example, it could be included in the primary care NHS Health Check for those aged 41-74 years, they suggested. In addition, “high street” retinal scanning could directly feed into primary medical services and help achieve greater screening coverage for older age groups, who are likely to attend an optometric practice for visual correction, especially with the onset of presbyopia. “This would offer a novel approach to identify those at high risk of circulatory mortality, which is not currently screened for,” the team said.
Test could help to identify high-risk individuals
In a linked editorial, Ify Mordi, MD, and Emanuele Trucco, MD, of the University of Dundee (Scotland), said that CVD remains a significant cause of mortality and morbidity and the most common cause of death worldwide, accounting for a quarter of all U.K. deaths – and its burden is increasing. “Identification of individuals at high risk is particularly important,” they said, but current clinical risk scores to identify those at risk “are unfortunately not perfect,” so miss some of those who might benefit from preventative therapy.
“The retina is the only location that allows non-invasive direct visualisation of the vasculature, potentially providing a rich source of information.” In the new study, the measurements derived with the software tool, QUARTZ, were significantly associated with CVD, they said, with similar predictive performance to the Framingham clinical risk score.
“The results strengthen the evidence from several similar studies that the retina can be a useful and potentially disruptive source of information for CVD risk in personalised medicine.” However, a number of questions remain about how this knowledge could be integrated into clinical care, including who would conduct such a retinal screening program and who would act on the findings?
The editorial concluded: “What is now needed is for ophthalmologists, cardiologists, primary care physicians, and computer scientists to work together to design studies to determine whether using this information improves clinical outcome, and, if so, to work with regulatory bodies, scientific societies and healthcare systems to optimize clinical work flows and enable practical implementation in routine practice.”
‘Exciting development that could improve outcomes’
Asked to comment, Farah Topia, clinical and regulatory adviser at the Association of Optometrists, said: “This is an exciting development that could improve outcomes for many patients by enabling earlier detection of serious health risks. Patients attend optometric practice for a variety of reasons and this interaction could be used to a greater extent to help detect disease earlier. With optometrists available on every High Street, in the heart of communities, it’s an element of primary care that can be accessed quickly and easily, and optometrists are also already trained to have health and lifestyle discussion with patients.”
She added: “Retinal photographs are regularly taken when patients visit an optometrist, so being able to further enhance this process using AI is exciting.
“We look forward to seeing how this area develops and how optometrists can work together with other healthcare sectors to improve patient outcomes and ease the burden the NHS currently faces.”
The study was funded by the Medical Research Council Population and Systems Medicine Board and the British Heart Foundation.
A version of this article first appeared on Medscape UK.
according to a new study using data from the UK Biobank Eye and Vision Consortium and the European Prospective Investigation into Cancer (EPIC)–Norfolk study.
The researchers, from St. George’s University of London, Cambridge University, Kingston University, Moorfields Eye Hospital, and University College London, developed a method of artificial intelligence (AI)–enabled imaging of the retina’s vascular network that could accurately predict CVD and death, without the need for blood tests or blood pressure measurement.
The system “paves the way for a highly effective, noninvasive screening test for people at medium to high risk of circulatory disease that doesn’t have to be done in a clinic,” they said. “In the general population it could be used as a noncontact form of systemic vascular health check, to triage those at medium-high risk of circulatory mortality for further clinical risk assessment and appropriate intervention.” Optometry specialists welcomed the prospect and hailed it as “an exciting development.”
Retinal vessels give an accurate early indicator of CVD
The study, published online in the British Journal of Ophthalmology, was based on previous research showing that the width of retinal arterioles and venules seen on retinal imaging may provide an accurate early indicator of CVD, whereas current risk prediction frameworks aren’t always reliable in identifying people who will go on to develop or die of circulatory diseases.
The researchers developed a fully automated AI-enabled algorithm, called Quantitative Analysis of Retinal vessels Topology and Size (QUARTZ), to assess the potential of retinal vasculature imaging plus known risk factors to predict vascular health and death. They applied QUARTZ to retinal images from 88,052 UK Biobank participants aged 40-69 years, looking specifically at the width, vessel area, and degree of tortuosity of the retinal microvasculature, to develop prediction models for stroke, heart attack, and death from circulatory disease.
They then applied these models to the retinal images of 7,411 participants, aged 48-92 years, in the EPIC-Norfolk study. They then compared the performance of QUARTZ with the widely used Framingham Risk Scores framework.
The participants in the two studies were tracked for an average of 7.7 and 9.1 years, respectively, during which time there were 327 circulatory disease deaths among 64,144 UK Biobank participants (average age, 56.8 years) and 201 circulatory deaths among 5,862 EPIC-Norfolk participants (average age, 67.6 years).
Vessel characteristics important predictors of CVD mortality
Results from the QUARTZ models showed that in all participants, arteriolar and venular width, venular tortuosity, and width variation were important predictors of circulatory disease death. In addition, in women, but not in men, arteriolar and venular area were separate factors that contributed to risk prediction.
Overall, the predictive models, based on age, smoking, and medical history (antihypertensive or cholesterol lowering medication, diabetes, and history of stroke or MI) as well as retinal vasculature, captured between half and two-thirds of circulatory disease deaths in those most at risk, the authors said.
Compared with Framingham Risk Scores (FRS), the retinal vasculature (RV) models captured about 5% more cases of stroke in UK Biobank men, 8% more cases in UK Biobank women, and 3% more cases among EPIC-Norfolk men most at risk, but nearly 2% fewer cases among EPIC-Norfolk women. However, the team said that, while adding RV to FRS resulted in only marginal changes in prediction of stroke or MI, a simpler noninvasive risk score based on age, sex, smoking status, medical history, and RV “yielded comparable performance to FRS, without the need for blood sampling or BP measurement.”
Vasculometry low cost, noninvasive and with high street availability
They concluded: “Retinal imaging is established within clinic and hospital eye care and in optometric practices in the U.S. and U.K. AI-enabled vasculometry risk prediction is fully automated, low cost, noninvasive and has the potential for reaching a higher proportion of the population in the community because of “high street” availability and because blood sampling or sphygmomanometry are not needed.
“[Retinal vasculature] is a microvascular marker, hence offers better prediction for circulatory mortality and stroke, compared with MI, which is more macrovascular, except perhaps in women.
“In the general population it could be used as a noncontact form of systemic vascular health check, to triage those at medium-high risk of circulatory mortality for further clinical risk assessment and appropriate intervention.”
In the United Kingdom, for example, it could be included in the primary care NHS Health Check for those aged 41-74 years, they suggested. In addition, “high street” retinal scanning could directly feed into primary medical services and help achieve greater screening coverage for older age groups, who are likely to attend an optometric practice for visual correction, especially with the onset of presbyopia. “This would offer a novel approach to identify those at high risk of circulatory mortality, which is not currently screened for,” the team said.
Test could help to identify high-risk individuals
In a linked editorial, Ify Mordi, MD, and Emanuele Trucco, MD, of the University of Dundee (Scotland), said that CVD remains a significant cause of mortality and morbidity and the most common cause of death worldwide, accounting for a quarter of all U.K. deaths – and its burden is increasing. “Identification of individuals at high risk is particularly important,” they said, but current clinical risk scores to identify those at risk “are unfortunately not perfect,” so miss some of those who might benefit from preventative therapy.
“The retina is the only location that allows non-invasive direct visualisation of the vasculature, potentially providing a rich source of information.” In the new study, the measurements derived with the software tool, QUARTZ, were significantly associated with CVD, they said, with similar predictive performance to the Framingham clinical risk score.
“The results strengthen the evidence from several similar studies that the retina can be a useful and potentially disruptive source of information for CVD risk in personalised medicine.” However, a number of questions remain about how this knowledge could be integrated into clinical care, including who would conduct such a retinal screening program and who would act on the findings?
The editorial concluded: “What is now needed is for ophthalmologists, cardiologists, primary care physicians, and computer scientists to work together to design studies to determine whether using this information improves clinical outcome, and, if so, to work with regulatory bodies, scientific societies and healthcare systems to optimize clinical work flows and enable practical implementation in routine practice.”
‘Exciting development that could improve outcomes’
Asked to comment, Farah Topia, clinical and regulatory adviser at the Association of Optometrists, said: “This is an exciting development that could improve outcomes for many patients by enabling earlier detection of serious health risks. Patients attend optometric practice for a variety of reasons and this interaction could be used to a greater extent to help detect disease earlier. With optometrists available on every High Street, in the heart of communities, it’s an element of primary care that can be accessed quickly and easily, and optometrists are also already trained to have health and lifestyle discussion with patients.”
She added: “Retinal photographs are regularly taken when patients visit an optometrist, so being able to further enhance this process using AI is exciting.
“We look forward to seeing how this area develops and how optometrists can work together with other healthcare sectors to improve patient outcomes and ease the burden the NHS currently faces.”
The study was funded by the Medical Research Council Population and Systems Medicine Board and the British Heart Foundation.
A version of this article first appeared on Medscape UK.
FROM THE BRITISH JOURNAL OF OPHTHALMOLOGY
Sore throat becoming dominant COVID symptom: Reports
according to recent reports in the United Kingdom.
The shift could be a cause of concern for the fall. As the main symptoms of the coronavirus change, people could spread the virus without realizing it.
“Many people are still using the government guidelines about symptoms, which are wrong,” Tim Spector, a professor of genetic epidemiology at King’s College London, told the Independent.
Prof. Spector cofounded the COVID ZOE app, which is part of the world’s largest COVID-19 study. Throughout the pandemic, researchers have used data from the app to track changes in symptoms.
“At the moment, COVID starts in two-thirds of people with a sore throat,” he said. “Fever and loss of smell are really rare now, so many old people may not think they’ve got COVID. They’d say it’s a cold and not be tested.”
COVID-19 infections in the United Kingdom increased 14% at the end of September, according to data from the U.K.’s Office for National Statistics. More than 1.1 million people tested positive during the week ending Sept. 20, up from 927,000 cases the week before. The numbers continue to increase in England and Wales, with an uncertain trend in Northern Ireland and Scotland.
The fall wave of infections has likely arrived in the United Kingdom, Prof. Spector told the Independent. Omicron variants continue to evolve and are escaping immunity from previous infection and vaccination, which he expects to continue into the winter.
But with reduced testing and surveillance of new variants, public health experts have voiced concerns about tracking the latest variants and COVID-19 trends.
“We can only detect variants or know what’s coming by doing sequencing from PCR testing, and that’s not going on anywhere near the extent it was a year ago,” Lawrence Young, a professor of virology at the University of Warwick, Coventry, England, told the Independent.
“People are going to get various infections over the winter but won’t know what they are because free tests aren’t available,” he said. “It’s going to be a problem.”
COVID-19 cases are also increasing across Europe, which could mark the first regional spike since the BA.5 wave, according to the latest data from the European CDC. (In the past, increases in Europe have signaled a trend to come in other regions.)
People aged 65 and older have been hit the hardest, the data shows, with cases rising 9% from the previous week. Hospitalizations remain stable for now, although 14 of 27 countries in the European region have noted an upward trend.
“Changes in population mixing following the summer break are likely to be the main driver of these increases, with no indication of changes in the distribution of circulating variants,” the European CDC said.
For now, most COVID-19 numbers are still falling in the United States, according to a weekly CDC update published Sept. 30. About 47,000 cases are being reported each day, marking a 13% decrease from the week before. Hospitalizations dropped 7%, and deaths dropped 6%.
At the same time, test positivity rose slightly last week, from 9.6% to 9.8%. Wastewater surveillance indicates that 53% of sites in the United States reported a decrease in virus levels, while 41% reported an increase last week.
The CDC encouraged people to get the updated Omicron-targeted booster shot for the fall. About 7.5 million Americans have received the updated vaccine. Half of the eligible population in the United States hasn’t received any booster dose yet.
“Bivalent boosters help restore protection that might have gone down since your last dose – and they also give extra protection for you and those around you against all lineages of the Omicron variant,” the CDC wrote. “The more people who stay up to date on vaccinations, the better chance we have of avoiding a possible surge in COVID-19 illness later this fall and winter.”
A version of this article first appeared on WebMD.com.
according to recent reports in the United Kingdom.
The shift could be a cause of concern for the fall. As the main symptoms of the coronavirus change, people could spread the virus without realizing it.
“Many people are still using the government guidelines about symptoms, which are wrong,” Tim Spector, a professor of genetic epidemiology at King’s College London, told the Independent.
Prof. Spector cofounded the COVID ZOE app, which is part of the world’s largest COVID-19 study. Throughout the pandemic, researchers have used data from the app to track changes in symptoms.
“At the moment, COVID starts in two-thirds of people with a sore throat,” he said. “Fever and loss of smell are really rare now, so many old people may not think they’ve got COVID. They’d say it’s a cold and not be tested.”
COVID-19 infections in the United Kingdom increased 14% at the end of September, according to data from the U.K.’s Office for National Statistics. More than 1.1 million people tested positive during the week ending Sept. 20, up from 927,000 cases the week before. The numbers continue to increase in England and Wales, with an uncertain trend in Northern Ireland and Scotland.
The fall wave of infections has likely arrived in the United Kingdom, Prof. Spector told the Independent. Omicron variants continue to evolve and are escaping immunity from previous infection and vaccination, which he expects to continue into the winter.
But with reduced testing and surveillance of new variants, public health experts have voiced concerns about tracking the latest variants and COVID-19 trends.
“We can only detect variants or know what’s coming by doing sequencing from PCR testing, and that’s not going on anywhere near the extent it was a year ago,” Lawrence Young, a professor of virology at the University of Warwick, Coventry, England, told the Independent.
“People are going to get various infections over the winter but won’t know what they are because free tests aren’t available,” he said. “It’s going to be a problem.”
COVID-19 cases are also increasing across Europe, which could mark the first regional spike since the BA.5 wave, according to the latest data from the European CDC. (In the past, increases in Europe have signaled a trend to come in other regions.)
People aged 65 and older have been hit the hardest, the data shows, with cases rising 9% from the previous week. Hospitalizations remain stable for now, although 14 of 27 countries in the European region have noted an upward trend.
“Changes in population mixing following the summer break are likely to be the main driver of these increases, with no indication of changes in the distribution of circulating variants,” the European CDC said.
For now, most COVID-19 numbers are still falling in the United States, according to a weekly CDC update published Sept. 30. About 47,000 cases are being reported each day, marking a 13% decrease from the week before. Hospitalizations dropped 7%, and deaths dropped 6%.
At the same time, test positivity rose slightly last week, from 9.6% to 9.8%. Wastewater surveillance indicates that 53% of sites in the United States reported a decrease in virus levels, while 41% reported an increase last week.
The CDC encouraged people to get the updated Omicron-targeted booster shot for the fall. About 7.5 million Americans have received the updated vaccine. Half of the eligible population in the United States hasn’t received any booster dose yet.
“Bivalent boosters help restore protection that might have gone down since your last dose – and they also give extra protection for you and those around you against all lineages of the Omicron variant,” the CDC wrote. “The more people who stay up to date on vaccinations, the better chance we have of avoiding a possible surge in COVID-19 illness later this fall and winter.”
A version of this article first appeared on WebMD.com.
according to recent reports in the United Kingdom.
The shift could be a cause of concern for the fall. As the main symptoms of the coronavirus change, people could spread the virus without realizing it.
“Many people are still using the government guidelines about symptoms, which are wrong,” Tim Spector, a professor of genetic epidemiology at King’s College London, told the Independent.
Prof. Spector cofounded the COVID ZOE app, which is part of the world’s largest COVID-19 study. Throughout the pandemic, researchers have used data from the app to track changes in symptoms.
“At the moment, COVID starts in two-thirds of people with a sore throat,” he said. “Fever and loss of smell are really rare now, so many old people may not think they’ve got COVID. They’d say it’s a cold and not be tested.”
COVID-19 infections in the United Kingdom increased 14% at the end of September, according to data from the U.K.’s Office for National Statistics. More than 1.1 million people tested positive during the week ending Sept. 20, up from 927,000 cases the week before. The numbers continue to increase in England and Wales, with an uncertain trend in Northern Ireland and Scotland.
The fall wave of infections has likely arrived in the United Kingdom, Prof. Spector told the Independent. Omicron variants continue to evolve and are escaping immunity from previous infection and vaccination, which he expects to continue into the winter.
But with reduced testing and surveillance of new variants, public health experts have voiced concerns about tracking the latest variants and COVID-19 trends.
“We can only detect variants or know what’s coming by doing sequencing from PCR testing, and that’s not going on anywhere near the extent it was a year ago,” Lawrence Young, a professor of virology at the University of Warwick, Coventry, England, told the Independent.
“People are going to get various infections over the winter but won’t know what they are because free tests aren’t available,” he said. “It’s going to be a problem.”
COVID-19 cases are also increasing across Europe, which could mark the first regional spike since the BA.5 wave, according to the latest data from the European CDC. (In the past, increases in Europe have signaled a trend to come in other regions.)
People aged 65 and older have been hit the hardest, the data shows, with cases rising 9% from the previous week. Hospitalizations remain stable for now, although 14 of 27 countries in the European region have noted an upward trend.
“Changes in population mixing following the summer break are likely to be the main driver of these increases, with no indication of changes in the distribution of circulating variants,” the European CDC said.
For now, most COVID-19 numbers are still falling in the United States, according to a weekly CDC update published Sept. 30. About 47,000 cases are being reported each day, marking a 13% decrease from the week before. Hospitalizations dropped 7%, and deaths dropped 6%.
At the same time, test positivity rose slightly last week, from 9.6% to 9.8%. Wastewater surveillance indicates that 53% of sites in the United States reported a decrease in virus levels, while 41% reported an increase last week.
The CDC encouraged people to get the updated Omicron-targeted booster shot for the fall. About 7.5 million Americans have received the updated vaccine. Half of the eligible population in the United States hasn’t received any booster dose yet.
“Bivalent boosters help restore protection that might have gone down since your last dose – and they also give extra protection for you and those around you against all lineages of the Omicron variant,” the CDC wrote. “The more people who stay up to date on vaccinations, the better chance we have of avoiding a possible surge in COVID-19 illness later this fall and winter.”
A version of this article first appeared on WebMD.com.
Breakthrough COVID studies lend support to use of new boosters in immunosuppressed patients
People with immune-mediated inflammatory diseases who are taking immunosuppressants don’t mount as strong of an immune defense against the Omicron variant as they did against the original SARS-CoV-2 wild-type virus, according to two studies published in Annals of the Rheumatic Diseases. One of the studies further showed that vaccinated individuals taking immunosuppressants have poorer cross-neutralizing responses to Omicron than do healthy vaccinated individuals, even after three doses of the COVID-19 mRNA vaccines.
“We carefully suggest that if Omicron-specific vaccination can be administered, it may be an effective way to reduce the risk of breakthrough infections in patients with autoimmune rheumatic disease,” Sang Tae Choi, MD, PhD, of the University College of Medicine, Seoul, Korea, and one of the authors of the study on cross-neutralizing protection, told this news organization. “However, further research is needed on Omicron-specific vaccine effectiveness in patients with immune dysfunctions. We believe that these study results can be of great benefit in determining the strategy of vaccination in the future.”
The earlier study, published in July, examined the ability of COVID-19 vaccines to induce cross-reactive antibody responses against Omicron infections in patients with autoimmune rheumatic diseases (ARDs). The observational study involved 149 patients with ARDs and 94 health care workers as controls, all of whom provided blood samples a median 15 weeks after their second COVID vaccine dose or a median 8 weeks after their third dose. A little more than two-thirds of the patients (68.5%) had received a third mRNA vaccine dose. None of the participants previously had COVID-19.
The researchers compared the rate of breakthrough infections with the Omicron variant to the neutralizing responses in patients’ blood, specifically the cross-neutralizing antibody responses because the original mRNA vaccines targeted a different variant than Omicron. Breakthrough infections were assessed by survey questions.
“Our findings suggested that neither primary series vaccinations nor booster doses are sufficient to induce Omicron-neutralizing responses above the threshold in patients with ARDs, although responses were noticeably increased following the third dose of an mRNA vaccine,” write Woo-Joong Kim, of the Chung-Ang University College of Medicine, Seoul, Korea, and his colleagues. “This impairment of cross-neutralization responses across most of our patients contrasts starkly with a potent elicitation of the Omicron-neutralizing responses after the third vaccination in healthy recipients.”
The average neutralizing responses against the original SARS-CoV-2 strain were similar in both groups: 76% in patients with ARDs and 72% in health care workers after the second dose. The mean response after a third dose was 97% in health care workers and 88% in patients.
The average cross-neutralizing response against the Omicron variant was far lower, particularly in those with rheumatic disease: only 11.5%, which rose to 27% after the third dose. Only 39% of the patient sera showed neutralization of Omicron, even after the third dose. Meanwhile, the mean cross-neutralizing response in health care workers was 18% after the second dose and 50% after the third.
When the researchers compared seropositivity rates against the original virus to neutralizing responses against Omicron, the association between these was stronger in health care workers than in those with ARDs. In fact, among patients with ARDs who seroconverted, only 41% showed any response against Omicron. Among all the patients, most of those who didn’t respond to Omicron (93.5%) had initially seroconverted.
The researchers also looked at the ability to neutralize Omicron on the basis of disease in those who received three doses of the vaccine. About half of those with lupus (52%) showed any neutralization against Omicron, compared with 25% of those with rheumatoid arthritis, 37.5% of those with ankylosing spondylitis, 33% of those with Behçet snydrome, and all of those with adult-onset Still’s disease.
The rate of breakthrough infections was lower in patients (19%) than in health care workers (33%). A similar pattern was seen in the more recent study published Sept. 5. Researchers used data from a prospective cohort study in the Netherlands to examine incidence and severity of Omicron breakthrough infections in patients with immune-mediated inflammatory diseases. The researchers compared infection rates and severity among 1,593 vaccinated patients with inflammatory disease who were taking immunosuppressants and 579 vaccinated controls (418 patients with inflammatory disease not on immunosuppressants and 161 healthy controls).
One in five patients with inflammatory disease (21%) were taking immunosuppressants that substantially impair antibodies, such as anti-CD20 therapy, S1P modulators, or mycophenolate mofetil combination therapy, and 48% of these patients seroconverted after primary vaccination, compared with 96% of patients taking other immunosuppressants and 98% of controls.
Breakthrough infection rates were similar between the control group (31%) and those taking immunosuppressants (30%). Only three participants had severe disease requiring hospitalization: one control and two patients taking immunosuppressants.
“In both studies, the controls had similar or higher rates of breakthrough infections, compared with the immunosuppressed,” noted Alfred Kim, MD, an assistant professor of medicine at Washington University, St Louis, but he added, “one has to consider differences in mitigation strategies, such as masking, that may explain these findings.” That is, patients taking immunosuppressants may be taking fewer risks in the community or have fewer potential exposures, especially in the Korean study, wherein the controls were health care workers.
A greater disparity in infections occurred when considering seroconversion rates. Breakthrough incidence was 38% among those taking immunosuppressants who did not seroconvert, compared with 29% among those who did. A similar trend was seen in breakthrough incidence between those taking strongly antibody-impairing immunosuppressants (36% breakthrough rate) and those taking other immunosuppressants (28%).
Among those taking immunosuppressants who seroconverted, a primary series of vaccination reduced the risk of a breakthrough infection by 29%. Protection became more robust with a booster or prior infection, both of which reduced breakthrough infection risk by 39% in those taking immunosuppressants who seroconverted.
“We demonstrate in patients with immune-mediated inflammatory diseases on immunosuppressants that additional vaccinations are associated with decreased risk of SARS-CoV-2 Omicron breakthrough infections,” wrote Eileen W. Stalman, MD, PhD, of Amsterdam UMC in the Netherlands, and her colleagues.
Though neither study broke down immune response or breakthrough infection based on individual medications, Kim said that previous research allows one to extrapolate “that prior culprits of poor vaccine responses [such as B-cell depleting drugs, mycophenolate, and TNF [tumor necrosis factor] inhibitors will continue to bear the greatest burden in breakthrough infection, including Omicron.”
Overall, he found the data from both studies relatively consistent with one another.
“Those on immunosuppression, particularly mechanisms that have been established as risk factors for poor vaccine responses, are at risk of breakthrough infection during the era of Omicron,” Dr. Kim said.
The earlier study from Korea also found that “the median time between the third-dose vaccination and the date of confirmed breakthrough infection in patients with ARDs was significantly shorter, compared with that in health care workers” at just 93 days in patients versus 122 days in health care workers. They postulated that this population’s limited neutralization of Omicron explained this short-lived protection.
Most of the patients with breakthrough infections (74%) in that study showed no neutralization against Omicron, including the only two hospitalized patients, both of whom had strong responses against the original SARS-CoV-2 strain. The significant decline over time of neutralization against Omicron suggested “the potential for a substantial loss of the protection from breakthrough infection,” the authors write.
“The third dose of an mRNA vaccine could improve the cross-neutralization of the SARS-CoV-2 Omicron variant in patients with autoimmune rheumatic disease [although] more than half of the patients failed to generate Omicron-neutralizing antibodies,” Tae Choi said in an interview. “Our study sheds light on the relative deficiency of the Omicron-specific neutralizing responses in patients with autoimmune rheumatic disease and their anticipated vulnerability to breakthrough infection.”
The message for clinicians, Dr. Kim said, is to “continue to urge our patients to maintain additional and boosting doses per guidance, use pre-exposure prophylaxis such as Evusheld, and continue other mitigation strategies as they have done.”
The Dutch study was funded by The Netherlands Organization for Health Research and Development; the Korean study used no external funding.
The authors of the Korean study had no disclosures. The Dutch study’s authors reported a wide range of disclosures involving more than a dozen pharmaceutical companies but not including Pfizer or Moderna. Dr. Kim’s industry disclosures include Alexion, ANI, AstraZeneca, Aurinia, Exagen, Foghorn Therapeutics, GlaxoSmithKline, Kypha, and Pfizer.
A version of this article first appeared on Medscape.com.
People with immune-mediated inflammatory diseases who are taking immunosuppressants don’t mount as strong of an immune defense against the Omicron variant as they did against the original SARS-CoV-2 wild-type virus, according to two studies published in Annals of the Rheumatic Diseases. One of the studies further showed that vaccinated individuals taking immunosuppressants have poorer cross-neutralizing responses to Omicron than do healthy vaccinated individuals, even after three doses of the COVID-19 mRNA vaccines.
“We carefully suggest that if Omicron-specific vaccination can be administered, it may be an effective way to reduce the risk of breakthrough infections in patients with autoimmune rheumatic disease,” Sang Tae Choi, MD, PhD, of the University College of Medicine, Seoul, Korea, and one of the authors of the study on cross-neutralizing protection, told this news organization. “However, further research is needed on Omicron-specific vaccine effectiveness in patients with immune dysfunctions. We believe that these study results can be of great benefit in determining the strategy of vaccination in the future.”
The earlier study, published in July, examined the ability of COVID-19 vaccines to induce cross-reactive antibody responses against Omicron infections in patients with autoimmune rheumatic diseases (ARDs). The observational study involved 149 patients with ARDs and 94 health care workers as controls, all of whom provided blood samples a median 15 weeks after their second COVID vaccine dose or a median 8 weeks after their third dose. A little more than two-thirds of the patients (68.5%) had received a third mRNA vaccine dose. None of the participants previously had COVID-19.
The researchers compared the rate of breakthrough infections with the Omicron variant to the neutralizing responses in patients’ blood, specifically the cross-neutralizing antibody responses because the original mRNA vaccines targeted a different variant than Omicron. Breakthrough infections were assessed by survey questions.
“Our findings suggested that neither primary series vaccinations nor booster doses are sufficient to induce Omicron-neutralizing responses above the threshold in patients with ARDs, although responses were noticeably increased following the third dose of an mRNA vaccine,” write Woo-Joong Kim, of the Chung-Ang University College of Medicine, Seoul, Korea, and his colleagues. “This impairment of cross-neutralization responses across most of our patients contrasts starkly with a potent elicitation of the Omicron-neutralizing responses after the third vaccination in healthy recipients.”
The average neutralizing responses against the original SARS-CoV-2 strain were similar in both groups: 76% in patients with ARDs and 72% in health care workers after the second dose. The mean response after a third dose was 97% in health care workers and 88% in patients.
The average cross-neutralizing response against the Omicron variant was far lower, particularly in those with rheumatic disease: only 11.5%, which rose to 27% after the third dose. Only 39% of the patient sera showed neutralization of Omicron, even after the third dose. Meanwhile, the mean cross-neutralizing response in health care workers was 18% after the second dose and 50% after the third.
When the researchers compared seropositivity rates against the original virus to neutralizing responses against Omicron, the association between these was stronger in health care workers than in those with ARDs. In fact, among patients with ARDs who seroconverted, only 41% showed any response against Omicron. Among all the patients, most of those who didn’t respond to Omicron (93.5%) had initially seroconverted.
The researchers also looked at the ability to neutralize Omicron on the basis of disease in those who received three doses of the vaccine. About half of those with lupus (52%) showed any neutralization against Omicron, compared with 25% of those with rheumatoid arthritis, 37.5% of those with ankylosing spondylitis, 33% of those with Behçet snydrome, and all of those with adult-onset Still’s disease.
The rate of breakthrough infections was lower in patients (19%) than in health care workers (33%). A similar pattern was seen in the more recent study published Sept. 5. Researchers used data from a prospective cohort study in the Netherlands to examine incidence and severity of Omicron breakthrough infections in patients with immune-mediated inflammatory diseases. The researchers compared infection rates and severity among 1,593 vaccinated patients with inflammatory disease who were taking immunosuppressants and 579 vaccinated controls (418 patients with inflammatory disease not on immunosuppressants and 161 healthy controls).
One in five patients with inflammatory disease (21%) were taking immunosuppressants that substantially impair antibodies, such as anti-CD20 therapy, S1P modulators, or mycophenolate mofetil combination therapy, and 48% of these patients seroconverted after primary vaccination, compared with 96% of patients taking other immunosuppressants and 98% of controls.
Breakthrough infection rates were similar between the control group (31%) and those taking immunosuppressants (30%). Only three participants had severe disease requiring hospitalization: one control and two patients taking immunosuppressants.
“In both studies, the controls had similar or higher rates of breakthrough infections, compared with the immunosuppressed,” noted Alfred Kim, MD, an assistant professor of medicine at Washington University, St Louis, but he added, “one has to consider differences in mitigation strategies, such as masking, that may explain these findings.” That is, patients taking immunosuppressants may be taking fewer risks in the community or have fewer potential exposures, especially in the Korean study, wherein the controls were health care workers.
A greater disparity in infections occurred when considering seroconversion rates. Breakthrough incidence was 38% among those taking immunosuppressants who did not seroconvert, compared with 29% among those who did. A similar trend was seen in breakthrough incidence between those taking strongly antibody-impairing immunosuppressants (36% breakthrough rate) and those taking other immunosuppressants (28%).
Among those taking immunosuppressants who seroconverted, a primary series of vaccination reduced the risk of a breakthrough infection by 29%. Protection became more robust with a booster or prior infection, both of which reduced breakthrough infection risk by 39% in those taking immunosuppressants who seroconverted.
“We demonstrate in patients with immune-mediated inflammatory diseases on immunosuppressants that additional vaccinations are associated with decreased risk of SARS-CoV-2 Omicron breakthrough infections,” wrote Eileen W. Stalman, MD, PhD, of Amsterdam UMC in the Netherlands, and her colleagues.
Though neither study broke down immune response or breakthrough infection based on individual medications, Kim said that previous research allows one to extrapolate “that prior culprits of poor vaccine responses [such as B-cell depleting drugs, mycophenolate, and TNF [tumor necrosis factor] inhibitors will continue to bear the greatest burden in breakthrough infection, including Omicron.”
Overall, he found the data from both studies relatively consistent with one another.
“Those on immunosuppression, particularly mechanisms that have been established as risk factors for poor vaccine responses, are at risk of breakthrough infection during the era of Omicron,” Dr. Kim said.
The earlier study from Korea also found that “the median time between the third-dose vaccination and the date of confirmed breakthrough infection in patients with ARDs was significantly shorter, compared with that in health care workers” at just 93 days in patients versus 122 days in health care workers. They postulated that this population’s limited neutralization of Omicron explained this short-lived protection.
Most of the patients with breakthrough infections (74%) in that study showed no neutralization against Omicron, including the only two hospitalized patients, both of whom had strong responses against the original SARS-CoV-2 strain. The significant decline over time of neutralization against Omicron suggested “the potential for a substantial loss of the protection from breakthrough infection,” the authors write.
“The third dose of an mRNA vaccine could improve the cross-neutralization of the SARS-CoV-2 Omicron variant in patients with autoimmune rheumatic disease [although] more than half of the patients failed to generate Omicron-neutralizing antibodies,” Tae Choi said in an interview. “Our study sheds light on the relative deficiency of the Omicron-specific neutralizing responses in patients with autoimmune rheumatic disease and their anticipated vulnerability to breakthrough infection.”
The message for clinicians, Dr. Kim said, is to “continue to urge our patients to maintain additional and boosting doses per guidance, use pre-exposure prophylaxis such as Evusheld, and continue other mitigation strategies as they have done.”
The Dutch study was funded by The Netherlands Organization for Health Research and Development; the Korean study used no external funding.
The authors of the Korean study had no disclosures. The Dutch study’s authors reported a wide range of disclosures involving more than a dozen pharmaceutical companies but not including Pfizer or Moderna. Dr. Kim’s industry disclosures include Alexion, ANI, AstraZeneca, Aurinia, Exagen, Foghorn Therapeutics, GlaxoSmithKline, Kypha, and Pfizer.
A version of this article first appeared on Medscape.com.
People with immune-mediated inflammatory diseases who are taking immunosuppressants don’t mount as strong of an immune defense against the Omicron variant as they did against the original SARS-CoV-2 wild-type virus, according to two studies published in Annals of the Rheumatic Diseases. One of the studies further showed that vaccinated individuals taking immunosuppressants have poorer cross-neutralizing responses to Omicron than do healthy vaccinated individuals, even after three doses of the COVID-19 mRNA vaccines.
“We carefully suggest that if Omicron-specific vaccination can be administered, it may be an effective way to reduce the risk of breakthrough infections in patients with autoimmune rheumatic disease,” Sang Tae Choi, MD, PhD, of the University College of Medicine, Seoul, Korea, and one of the authors of the study on cross-neutralizing protection, told this news organization. “However, further research is needed on Omicron-specific vaccine effectiveness in patients with immune dysfunctions. We believe that these study results can be of great benefit in determining the strategy of vaccination in the future.”
The earlier study, published in July, examined the ability of COVID-19 vaccines to induce cross-reactive antibody responses against Omicron infections in patients with autoimmune rheumatic diseases (ARDs). The observational study involved 149 patients with ARDs and 94 health care workers as controls, all of whom provided blood samples a median 15 weeks after their second COVID vaccine dose or a median 8 weeks after their third dose. A little more than two-thirds of the patients (68.5%) had received a third mRNA vaccine dose. None of the participants previously had COVID-19.
The researchers compared the rate of breakthrough infections with the Omicron variant to the neutralizing responses in patients’ blood, specifically the cross-neutralizing antibody responses because the original mRNA vaccines targeted a different variant than Omicron. Breakthrough infections were assessed by survey questions.
“Our findings suggested that neither primary series vaccinations nor booster doses are sufficient to induce Omicron-neutralizing responses above the threshold in patients with ARDs, although responses were noticeably increased following the third dose of an mRNA vaccine,” write Woo-Joong Kim, of the Chung-Ang University College of Medicine, Seoul, Korea, and his colleagues. “This impairment of cross-neutralization responses across most of our patients contrasts starkly with a potent elicitation of the Omicron-neutralizing responses after the third vaccination in healthy recipients.”
The average neutralizing responses against the original SARS-CoV-2 strain were similar in both groups: 76% in patients with ARDs and 72% in health care workers after the second dose. The mean response after a third dose was 97% in health care workers and 88% in patients.
The average cross-neutralizing response against the Omicron variant was far lower, particularly in those with rheumatic disease: only 11.5%, which rose to 27% after the third dose. Only 39% of the patient sera showed neutralization of Omicron, even after the third dose. Meanwhile, the mean cross-neutralizing response in health care workers was 18% after the second dose and 50% after the third.
When the researchers compared seropositivity rates against the original virus to neutralizing responses against Omicron, the association between these was stronger in health care workers than in those with ARDs. In fact, among patients with ARDs who seroconverted, only 41% showed any response against Omicron. Among all the patients, most of those who didn’t respond to Omicron (93.5%) had initially seroconverted.
The researchers also looked at the ability to neutralize Omicron on the basis of disease in those who received three doses of the vaccine. About half of those with lupus (52%) showed any neutralization against Omicron, compared with 25% of those with rheumatoid arthritis, 37.5% of those with ankylosing spondylitis, 33% of those with Behçet snydrome, and all of those with adult-onset Still’s disease.
The rate of breakthrough infections was lower in patients (19%) than in health care workers (33%). A similar pattern was seen in the more recent study published Sept. 5. Researchers used data from a prospective cohort study in the Netherlands to examine incidence and severity of Omicron breakthrough infections in patients with immune-mediated inflammatory diseases. The researchers compared infection rates and severity among 1,593 vaccinated patients with inflammatory disease who were taking immunosuppressants and 579 vaccinated controls (418 patients with inflammatory disease not on immunosuppressants and 161 healthy controls).
One in five patients with inflammatory disease (21%) were taking immunosuppressants that substantially impair antibodies, such as anti-CD20 therapy, S1P modulators, or mycophenolate mofetil combination therapy, and 48% of these patients seroconverted after primary vaccination, compared with 96% of patients taking other immunosuppressants and 98% of controls.
Breakthrough infection rates were similar between the control group (31%) and those taking immunosuppressants (30%). Only three participants had severe disease requiring hospitalization: one control and two patients taking immunosuppressants.
“In both studies, the controls had similar or higher rates of breakthrough infections, compared with the immunosuppressed,” noted Alfred Kim, MD, an assistant professor of medicine at Washington University, St Louis, but he added, “one has to consider differences in mitigation strategies, such as masking, that may explain these findings.” That is, patients taking immunosuppressants may be taking fewer risks in the community or have fewer potential exposures, especially in the Korean study, wherein the controls were health care workers.
A greater disparity in infections occurred when considering seroconversion rates. Breakthrough incidence was 38% among those taking immunosuppressants who did not seroconvert, compared with 29% among those who did. A similar trend was seen in breakthrough incidence between those taking strongly antibody-impairing immunosuppressants (36% breakthrough rate) and those taking other immunosuppressants (28%).
Among those taking immunosuppressants who seroconverted, a primary series of vaccination reduced the risk of a breakthrough infection by 29%. Protection became more robust with a booster or prior infection, both of which reduced breakthrough infection risk by 39% in those taking immunosuppressants who seroconverted.
“We demonstrate in patients with immune-mediated inflammatory diseases on immunosuppressants that additional vaccinations are associated with decreased risk of SARS-CoV-2 Omicron breakthrough infections,” wrote Eileen W. Stalman, MD, PhD, of Amsterdam UMC in the Netherlands, and her colleagues.
Though neither study broke down immune response or breakthrough infection based on individual medications, Kim said that previous research allows one to extrapolate “that prior culprits of poor vaccine responses [such as B-cell depleting drugs, mycophenolate, and TNF [tumor necrosis factor] inhibitors will continue to bear the greatest burden in breakthrough infection, including Omicron.”
Overall, he found the data from both studies relatively consistent with one another.
“Those on immunosuppression, particularly mechanisms that have been established as risk factors for poor vaccine responses, are at risk of breakthrough infection during the era of Omicron,” Dr. Kim said.
The earlier study from Korea also found that “the median time between the third-dose vaccination and the date of confirmed breakthrough infection in patients with ARDs was significantly shorter, compared with that in health care workers” at just 93 days in patients versus 122 days in health care workers. They postulated that this population’s limited neutralization of Omicron explained this short-lived protection.
Most of the patients with breakthrough infections (74%) in that study showed no neutralization against Omicron, including the only two hospitalized patients, both of whom had strong responses against the original SARS-CoV-2 strain. The significant decline over time of neutralization against Omicron suggested “the potential for a substantial loss of the protection from breakthrough infection,” the authors write.
“The third dose of an mRNA vaccine could improve the cross-neutralization of the SARS-CoV-2 Omicron variant in patients with autoimmune rheumatic disease [although] more than half of the patients failed to generate Omicron-neutralizing antibodies,” Tae Choi said in an interview. “Our study sheds light on the relative deficiency of the Omicron-specific neutralizing responses in patients with autoimmune rheumatic disease and their anticipated vulnerability to breakthrough infection.”
The message for clinicians, Dr. Kim said, is to “continue to urge our patients to maintain additional and boosting doses per guidance, use pre-exposure prophylaxis such as Evusheld, and continue other mitigation strategies as they have done.”
The Dutch study was funded by The Netherlands Organization for Health Research and Development; the Korean study used no external funding.
The authors of the Korean study had no disclosures. The Dutch study’s authors reported a wide range of disclosures involving more than a dozen pharmaceutical companies but not including Pfizer or Moderna. Dr. Kim’s industry disclosures include Alexion, ANI, AstraZeneca, Aurinia, Exagen, Foghorn Therapeutics, GlaxoSmithKline, Kypha, and Pfizer.
A version of this article first appeared on Medscape.com.
Balanced fat intake links with less type 2 diabetes
Researchers published the study covered in this summary on Preprints with The Lancet as a preprint that has not yet been peer reviewed.
Key takeaways
- Adults in China who consumed a “balanced,” moderate ratio (middle three quintiles) of animal-to-vegetable cooking oil had a lower rate of developing type 2 diabetes during a median follow-up of 8.6 years, compared with those who consumed the lowest ratio (first quintile), after multivariable adjustment using prospectively collected data.
- The results also indicate that increasing animal cooking oil (such as lard, tallow, or butter) and vegetable cooking oil (such as peanut or soybean oil) consumption were each positively associated with a higher rate of developing type 2 diabetes.
- Those who consumed the highest ratio (fifth quintile) of animal-to-vegetable cooking oil had a nonsignificant difference in their rate of developing type 2 diabetes, compared with those in the first quintile.
Why this matters
- The findings suggest that consuming a diet with a “balanced” moderate intake of animal and vegetable oil might lower the risk of type 2 diabetes, which would reduce disease burden and health care expenditures.
- The results imply that using a single source of cooking oil, either animal or vegetable, contributes to the incidence of type 2 diabetes.
- This is the first large epidemiological study showing a relationship between the ratio of animal- and vegetable-derived fats in people’s diets and their risk for incident type 2 diabetes.
Study design
- The researchers used data collected prospectively starting in 2010-2012 from 7,274 adult residents of Guizhou province, China, with follow-up assessment in 2020 after a median of 8.6 years.
- At baseline, participants underwent an oral glucose tolerance test and provided information on demographics, family medical history, and personal medical history, including whether they had been diagnosed with type 2 diabetes or were taking antihyperglycemic medications. The study did not include anyone with a history of diabetes.
- Data on intake of animal and vegetable cooking oil came from a dietary questionnaire.
- The authors calculated hazard ratios for development of type 2 diabetes after adjusting for multiple potential confounders.
Key results
- The study cohort averaged 44 years old, and 53% were women.
- During a median follow-up of 8.6 years, 747 people developed type 2 diabetes.
- Compared with those who had the lowest intake of animal cooking oil (first quintile), those with the highest intake (fifth quintile) had a significant 28% increased relative rate for developing type 2 diabetes after adjustment for several potential confounders.
- Compared with those with the lowest intake of vegetable cooking oil, those with the highest intake had a significant 56% increased rate of developing type 2 diabetes after adjustment.
- Compared with adults with the lowest animal-to-vegetable cooking oil ratio (first quintile), those in the second, third, and fourth quintiles for this ratio had significantly lower adjusted relative rates of developing type 2 diabetes, with adjusted hazard ratios of 0.79, 0.65, and 0.68, respectively. Those in the highest quintile (fifth quintile) did not have a significantly different risk, compared with the first quintile.
- The protective effect of a balanced ratio of animal-to-vegetable cooking oils was stronger in people who lived in rural districts and in those who had obesity.
Limitations
- The dietary information came from participants’ self-reports, which may have produced biased data.
- The study only included information about animal and vegetable cooking oil consumed at home.
- There may have been residual confounding from variables not included in the study.
- The time of diagnosis of type 2 diabetes may have been inaccurate because follow-up occurred only once.
- The study may have underestimated the incidence of type 2 diabetes because of a lack of information about hemoglobin A1c levels at follow-up.
Disclosures
- The study did not receive commercial funding.
- The authors reported no financial disclosures.
This is a summary of a preprint article “The consumption ratio of animal cooking oil to vegetable cooking oil and reduced risk of type 2 diabetes mellitus: A prospective cohort study in Southwest China” written by researchers primarily from Zunyi Medical University, China, on Preprints with The Lancet. This study has not yet been peer reviewed. The full text of the study can be found on papers.ssrn.com.
A version of this article first appeared on Medscape.com.
Researchers published the study covered in this summary on Preprints with The Lancet as a preprint that has not yet been peer reviewed.
Key takeaways
- Adults in China who consumed a “balanced,” moderate ratio (middle three quintiles) of animal-to-vegetable cooking oil had a lower rate of developing type 2 diabetes during a median follow-up of 8.6 years, compared with those who consumed the lowest ratio (first quintile), after multivariable adjustment using prospectively collected data.
- The results also indicate that increasing animal cooking oil (such as lard, tallow, or butter) and vegetable cooking oil (such as peanut or soybean oil) consumption were each positively associated with a higher rate of developing type 2 diabetes.
- Those who consumed the highest ratio (fifth quintile) of animal-to-vegetable cooking oil had a nonsignificant difference in their rate of developing type 2 diabetes, compared with those in the first quintile.
Why this matters
- The findings suggest that consuming a diet with a “balanced” moderate intake of animal and vegetable oil might lower the risk of type 2 diabetes, which would reduce disease burden and health care expenditures.
- The results imply that using a single source of cooking oil, either animal or vegetable, contributes to the incidence of type 2 diabetes.
- This is the first large epidemiological study showing a relationship between the ratio of animal- and vegetable-derived fats in people’s diets and their risk for incident type 2 diabetes.
Study design
- The researchers used data collected prospectively starting in 2010-2012 from 7,274 adult residents of Guizhou province, China, with follow-up assessment in 2020 after a median of 8.6 years.
- At baseline, participants underwent an oral glucose tolerance test and provided information on demographics, family medical history, and personal medical history, including whether they had been diagnosed with type 2 diabetes or were taking antihyperglycemic medications. The study did not include anyone with a history of diabetes.
- Data on intake of animal and vegetable cooking oil came from a dietary questionnaire.
- The authors calculated hazard ratios for development of type 2 diabetes after adjusting for multiple potential confounders.
Key results
- The study cohort averaged 44 years old, and 53% were women.
- During a median follow-up of 8.6 years, 747 people developed type 2 diabetes.
- Compared with those who had the lowest intake of animal cooking oil (first quintile), those with the highest intake (fifth quintile) had a significant 28% increased relative rate for developing type 2 diabetes after adjustment for several potential confounders.
- Compared with those with the lowest intake of vegetable cooking oil, those with the highest intake had a significant 56% increased rate of developing type 2 diabetes after adjustment.
- Compared with adults with the lowest animal-to-vegetable cooking oil ratio (first quintile), those in the second, third, and fourth quintiles for this ratio had significantly lower adjusted relative rates of developing type 2 diabetes, with adjusted hazard ratios of 0.79, 0.65, and 0.68, respectively. Those in the highest quintile (fifth quintile) did not have a significantly different risk, compared with the first quintile.
- The protective effect of a balanced ratio of animal-to-vegetable cooking oils was stronger in people who lived in rural districts and in those who had obesity.
Limitations
- The dietary information came from participants’ self-reports, which may have produced biased data.
- The study only included information about animal and vegetable cooking oil consumed at home.
- There may have been residual confounding from variables not included in the study.
- The time of diagnosis of type 2 diabetes may have been inaccurate because follow-up occurred only once.
- The study may have underestimated the incidence of type 2 diabetes because of a lack of information about hemoglobin A1c levels at follow-up.
Disclosures
- The study did not receive commercial funding.
- The authors reported no financial disclosures.
This is a summary of a preprint article “The consumption ratio of animal cooking oil to vegetable cooking oil and reduced risk of type 2 diabetes mellitus: A prospective cohort study in Southwest China” written by researchers primarily from Zunyi Medical University, China, on Preprints with The Lancet. This study has not yet been peer reviewed. The full text of the study can be found on papers.ssrn.com.
A version of this article first appeared on Medscape.com.
Researchers published the study covered in this summary on Preprints with The Lancet as a preprint that has not yet been peer reviewed.
Key takeaways
- Adults in China who consumed a “balanced,” moderate ratio (middle three quintiles) of animal-to-vegetable cooking oil had a lower rate of developing type 2 diabetes during a median follow-up of 8.6 years, compared with those who consumed the lowest ratio (first quintile), after multivariable adjustment using prospectively collected data.
- The results also indicate that increasing animal cooking oil (such as lard, tallow, or butter) and vegetable cooking oil (such as peanut or soybean oil) consumption were each positively associated with a higher rate of developing type 2 diabetes.
- Those who consumed the highest ratio (fifth quintile) of animal-to-vegetable cooking oil had a nonsignificant difference in their rate of developing type 2 diabetes, compared with those in the first quintile.
Why this matters
- The findings suggest that consuming a diet with a “balanced” moderate intake of animal and vegetable oil might lower the risk of type 2 diabetes, which would reduce disease burden and health care expenditures.
- The results imply that using a single source of cooking oil, either animal or vegetable, contributes to the incidence of type 2 diabetes.
- This is the first large epidemiological study showing a relationship between the ratio of animal- and vegetable-derived fats in people’s diets and their risk for incident type 2 diabetes.
Study design
- The researchers used data collected prospectively starting in 2010-2012 from 7,274 adult residents of Guizhou province, China, with follow-up assessment in 2020 after a median of 8.6 years.
- At baseline, participants underwent an oral glucose tolerance test and provided information on demographics, family medical history, and personal medical history, including whether they had been diagnosed with type 2 diabetes or were taking antihyperglycemic medications. The study did not include anyone with a history of diabetes.
- Data on intake of animal and vegetable cooking oil came from a dietary questionnaire.
- The authors calculated hazard ratios for development of type 2 diabetes after adjusting for multiple potential confounders.
Key results
- The study cohort averaged 44 years old, and 53% were women.
- During a median follow-up of 8.6 years, 747 people developed type 2 diabetes.
- Compared with those who had the lowest intake of animal cooking oil (first quintile), those with the highest intake (fifth quintile) had a significant 28% increased relative rate for developing type 2 diabetes after adjustment for several potential confounders.
- Compared with those with the lowest intake of vegetable cooking oil, those with the highest intake had a significant 56% increased rate of developing type 2 diabetes after adjustment.
- Compared with adults with the lowest animal-to-vegetable cooking oil ratio (first quintile), those in the second, third, and fourth quintiles for this ratio had significantly lower adjusted relative rates of developing type 2 diabetes, with adjusted hazard ratios of 0.79, 0.65, and 0.68, respectively. Those in the highest quintile (fifth quintile) did not have a significantly different risk, compared with the first quintile.
- The protective effect of a balanced ratio of animal-to-vegetable cooking oils was stronger in people who lived in rural districts and in those who had obesity.
Limitations
- The dietary information came from participants’ self-reports, which may have produced biased data.
- The study only included information about animal and vegetable cooking oil consumed at home.
- There may have been residual confounding from variables not included in the study.
- The time of diagnosis of type 2 diabetes may have been inaccurate because follow-up occurred only once.
- The study may have underestimated the incidence of type 2 diabetes because of a lack of information about hemoglobin A1c levels at follow-up.
Disclosures
- The study did not receive commercial funding.
- The authors reported no financial disclosures.
This is a summary of a preprint article “The consumption ratio of animal cooking oil to vegetable cooking oil and reduced risk of type 2 diabetes mellitus: A prospective cohort study in Southwest China” written by researchers primarily from Zunyi Medical University, China, on Preprints with The Lancet. This study has not yet been peer reviewed. The full text of the study can be found on papers.ssrn.com.
A version of this article first appeared on Medscape.com.
Sleep apnea: Is the sleep industry part of the problem? A reporter seeks answers
Editor's Note: We periodically publish patient viewpoints on specific issues of interest to our audience.
I woke up in a strange bedroom with 24 electrodes glued all over my body and a plastic mask attached to a hose covering my face.
The lab technician who watched me all night via video feed told me that I had “wicked sleep apnea” and that it was “central sleep apnea” – a type that originates in the brain and fails to tell the muscles to inhale.
As a journalist– and one terrified by the diagnosis – I set out to do my own research. After a few weeks of sleuthing and interviewing experts, I reached two important conclusions.
First, I had moderate apnea, if that, and it could be treated without the elaborate machines, mouthpieces, or other devices that specialists who had consulted on my care were talking about.
Second, I was on a conveyor belt.
It all began with a desire for answers: I had been feeling drowsy during the day, and my wife told me I snored. Both can mean obstructive sleep apnea. With obstructive sleep apnea, the mouth and throat relax when a person is unconscious, sometimes blocking or narrowing the airway. That interrupts breathing, as well as sleep. Without treatment, the resulting disruption in oxygen flow might increase the risk of developing certain cardiovascular diseases.
So I contacted a sleep-treatment center, and doctors gave me an at-home test ($365). Two weeks later, they told me I had “high-moderate” sleep apnea and needed to acquire a continuous positive airway pressure (CPAP) machine, at a cost of about $600.
Though I had hoped to get the equipment and adjust the settings to see what worked best, my doctors said I had to come to the sleep lab for an overnight test ($1,900) to have them “titrate” the optimal CPAP air pressure.
“How do you treat central sleep apnea?” I worriedly asked the technician after that first overnight stay. She said something about an adaptive servo-ventilation machine ($4,000). And one pricey lab sleepover wasn’t enough, she said. I needed to come back for another.
(Most procedures and devices mentioned in this article were covered or would have been covered by insurance – in my case, Medicare, plus a supplemental plan. Unnecessary care is a big reason Americans’ insurance costs – premiums, copays, and deductibles – tend to rise year after year.)
As a journalist who spent years covering the business of health care, I found there was more motivating my expensive testing cascade than concerns about my health.
The American Academy of Sleep Medicine, a nonprofit based near Chicago, decides what is sleep apnea and how to treat it. Working with sleep societies around the world, it publishes the International Classification of Sleep Disorders, relied on by doctors everywhere to diagnose and categorize disease.
But behind that effort lie considerable conflicts of interest. Like so much of U.S. health care, sleep medicine turns out to be a thriving industry. AASM finances its operations in part with payments from CPAP machine manufacturers and other companies that stand to profit from expensive treatments and expansive definitions of apnea and other sleep disorders.
Zoll Itamar, which makes the at-home testing device I used, as well as implantable nerve-stimulation hardware for central sleep apnea, is a $60,000, “platinum” partner in AASM’s Industry Engagement Program. So is Avadel Pharmaceuticals, which is testing a drug to treat narcolepsy, characterized by intense daytime sleepiness.
Other sponsors include the maker of an anti-insomnia drug; another company with a narcolepsy drug; Fisher & Paykel Healthcare, which makes CPAP machines and masks; and Inspire Medical Systems, maker of a heavily advertised surgical implant, costing tens of thousands of dollars, to treat apnea.
Corporate sponsors for Sleep 2022, a convention AASM put on in Charlotte, N.C., with other professional societies, included many of those companies, plus Philips Respironics and ResMed, two of the biggest CPAP machine makers.
In a statement, AASM spokesperson Jennifer Gibson said a conflict-of-interest policy and a noninterference pledge from industry funders protect the integrity of the academy’s work. Industry donations account for about $170,000 of AASM’s annual revenue of about $15 million. Other revenue comes from educational materials and membership and accreditation fees.
Here’s what else I found. Almost everybody breathes irregularly sometime at night, especially during REM sleep, characterized by rapid eye movement and dreams. Blood oxygen levels also fluctuate slightly.
But recent European studies have shown that standards under the International Classification of Sleep Disorders would doom huge portions of the general population to a sleep apnea diagnosis – whether or not people had complaints of daytime tiredness or other sleep problems.
A study in Lausanne, Switzerland, showed that 50% of local men and 23% of the women 40 or older were positive for sleep apnea under such criteria.
Such rates of disease are “extraordinarily high,” “astronomical,” and “implausible,” Dirk Pevernagie, PhD, a scientist at Ghent (Belgium) University Hospital, wrote with colleagues 2 years ago in a comprehensive study in the Journal of Sleep Research.
“Right now, there is no real evidence for the criteria that have been put forward to diagnose obstructive sleep apnea and rate its severity,” he said in an interview.
Likewise, 19% of middle-aged subjects in a 2016 Icelandic study appeared to have moderate to severe “apnea” under one definition in the International Classification of Sleep Disorders even though many reported no drowsiness.
“Most of them were really surprised,” said Erna Sif Arnardóttir, who led the study and is running a large European program to refine detection and treatment of apnea.
Nevertheless, the official AASM journal recommends extremely broad screening for sleep apnea, looking for patients who have what it defines as illness. Everybody 18 and older should be screened every year for apnea if they have diabetes, obesity, untreated high blood pressure, or heart disease – even if they have never complained about sleep problems, the group says.
AASM “continually evaluates the definitions, criteria and recommendations used in the identification of sleep apnea and other sleep disorders,” Ms. Gibson said in the statement. Meanwhile, routine screening by primary care doctors “is a simple way” of gauging whether a high-risk patient may have obstructive sleep apnea, the statement said.
The U.S. Preventive Services Task Force, an authoritative body that reviews the effectiveness of preventive care, takes a conservative view, more like that of the European researchers, concluding there is “insufficient” evidence to support widespread screening among patients with no symptoms.
Many insurers refuse to pay for CPAP machines and other treatments prescribed for people at the outer edges of the AASM’s apnea definition. But AASM is pressuring them to come around.
After all my reporting, I concluded that my apnea is real, though moderate. My alarming reading in the overnight lab – diagnosed quickly as central sleep apnea – was a byproduct of the testing machinery itself. That’s a well-described phenomenon that occurs in 5% to 15% of patients.
And when I looked closely at the results of my at-home diagnostic test, I had an epiphany: My overall score was 26 breathing interruptions and blood-oxygen level declines, on average, per hour – enough to put me in the “high-moderate” category for apnea. But when I looked at the data sorted according to sleeping positions, I saw that I scored much better when I slept on my side: only 10 interruptions in an hour.
So I did a little experiment: I bought a $25 pulse oximeter with a smartphone app that records oxygen dips and breathing interruptions. When I slept on my side, there were hardly any.
Now I sleep on my side. I snore less. I wake up refreshed. I’m not daytime drowsy.
None of my specialists mentioned turning on to my side – known in medical parlance as “positional therapy” – though the intervention is recognized as effective by many researchers. Sleeping on one’s back contributes to snoring and blockages, especially as people age and the muscles in the throat become looser.
“Positional patients ... can sleep in the lateral position and sleep quite well,” said Arie Oksenberg, PhD, a sleep researcher formerly at Loewenstein Hospital in Ra’anana, Israel.
But it’s not easy to find this in the official AASM treatment guidelines, which instead go right to the money-making options like CPAP machines, surgery, central apnea, and mouth appliances.
Dealing with apnea by shifting slightly in bed gets little more than a couple of paragraphs in AASM’s guideline on “other” treatments and a little box on a long and complex decision chart.
A third or more of patients wear CPAPs only a few hours a night or stop using them. It turns out people don’t like machines in their beds.
“Positional therapy is an effective treatment option for some patients,” said Ms. Gibson. But she said there are concerns about whether patients will sleep on their sides long term and whether trying to stay in one position might cause sleep interruptions itself.
It’s true that side-sleeping doesn’t help everybody. And it often takes practice. (Some people tape a tennis ball to their pajamas to keep them off their backs.) Even conservative sleep doctors say CPAP machines are the best solution for many patients.
But there is a largely overlooked alternative.
“Are we missing a simple treatment for most adult sleep apnea patients?” was the name of a 2013 paper that Dr. Oksenberg and a colleague wrote about positional therapy.
In my case, the answer was “yes.”
KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.
Editor's Note: We periodically publish patient viewpoints on specific issues of interest to our audience.
I woke up in a strange bedroom with 24 electrodes glued all over my body and a plastic mask attached to a hose covering my face.
The lab technician who watched me all night via video feed told me that I had “wicked sleep apnea” and that it was “central sleep apnea” – a type that originates in the brain and fails to tell the muscles to inhale.
As a journalist– and one terrified by the diagnosis – I set out to do my own research. After a few weeks of sleuthing and interviewing experts, I reached two important conclusions.
First, I had moderate apnea, if that, and it could be treated without the elaborate machines, mouthpieces, or other devices that specialists who had consulted on my care were talking about.
Second, I was on a conveyor belt.
It all began with a desire for answers: I had been feeling drowsy during the day, and my wife told me I snored. Both can mean obstructive sleep apnea. With obstructive sleep apnea, the mouth and throat relax when a person is unconscious, sometimes blocking or narrowing the airway. That interrupts breathing, as well as sleep. Without treatment, the resulting disruption in oxygen flow might increase the risk of developing certain cardiovascular diseases.
So I contacted a sleep-treatment center, and doctors gave me an at-home test ($365). Two weeks later, they told me I had “high-moderate” sleep apnea and needed to acquire a continuous positive airway pressure (CPAP) machine, at a cost of about $600.
Though I had hoped to get the equipment and adjust the settings to see what worked best, my doctors said I had to come to the sleep lab for an overnight test ($1,900) to have them “titrate” the optimal CPAP air pressure.
“How do you treat central sleep apnea?” I worriedly asked the technician after that first overnight stay. She said something about an adaptive servo-ventilation machine ($4,000). And one pricey lab sleepover wasn’t enough, she said. I needed to come back for another.
(Most procedures and devices mentioned in this article were covered or would have been covered by insurance – in my case, Medicare, plus a supplemental plan. Unnecessary care is a big reason Americans’ insurance costs – premiums, copays, and deductibles – tend to rise year after year.)
As a journalist who spent years covering the business of health care, I found there was more motivating my expensive testing cascade than concerns about my health.
The American Academy of Sleep Medicine, a nonprofit based near Chicago, decides what is sleep apnea and how to treat it. Working with sleep societies around the world, it publishes the International Classification of Sleep Disorders, relied on by doctors everywhere to diagnose and categorize disease.
But behind that effort lie considerable conflicts of interest. Like so much of U.S. health care, sleep medicine turns out to be a thriving industry. AASM finances its operations in part with payments from CPAP machine manufacturers and other companies that stand to profit from expensive treatments and expansive definitions of apnea and other sleep disorders.
Zoll Itamar, which makes the at-home testing device I used, as well as implantable nerve-stimulation hardware for central sleep apnea, is a $60,000, “platinum” partner in AASM’s Industry Engagement Program. So is Avadel Pharmaceuticals, which is testing a drug to treat narcolepsy, characterized by intense daytime sleepiness.
Other sponsors include the maker of an anti-insomnia drug; another company with a narcolepsy drug; Fisher & Paykel Healthcare, which makes CPAP machines and masks; and Inspire Medical Systems, maker of a heavily advertised surgical implant, costing tens of thousands of dollars, to treat apnea.
Corporate sponsors for Sleep 2022, a convention AASM put on in Charlotte, N.C., with other professional societies, included many of those companies, plus Philips Respironics and ResMed, two of the biggest CPAP machine makers.
In a statement, AASM spokesperson Jennifer Gibson said a conflict-of-interest policy and a noninterference pledge from industry funders protect the integrity of the academy’s work. Industry donations account for about $170,000 of AASM’s annual revenue of about $15 million. Other revenue comes from educational materials and membership and accreditation fees.
Here’s what else I found. Almost everybody breathes irregularly sometime at night, especially during REM sleep, characterized by rapid eye movement and dreams. Blood oxygen levels also fluctuate slightly.
But recent European studies have shown that standards under the International Classification of Sleep Disorders would doom huge portions of the general population to a sleep apnea diagnosis – whether or not people had complaints of daytime tiredness or other sleep problems.
A study in Lausanne, Switzerland, showed that 50% of local men and 23% of the women 40 or older were positive for sleep apnea under such criteria.
Such rates of disease are “extraordinarily high,” “astronomical,” and “implausible,” Dirk Pevernagie, PhD, a scientist at Ghent (Belgium) University Hospital, wrote with colleagues 2 years ago in a comprehensive study in the Journal of Sleep Research.
“Right now, there is no real evidence for the criteria that have been put forward to diagnose obstructive sleep apnea and rate its severity,” he said in an interview.
Likewise, 19% of middle-aged subjects in a 2016 Icelandic study appeared to have moderate to severe “apnea” under one definition in the International Classification of Sleep Disorders even though many reported no drowsiness.
“Most of them were really surprised,” said Erna Sif Arnardóttir, who led the study and is running a large European program to refine detection and treatment of apnea.
Nevertheless, the official AASM journal recommends extremely broad screening for sleep apnea, looking for patients who have what it defines as illness. Everybody 18 and older should be screened every year for apnea if they have diabetes, obesity, untreated high blood pressure, or heart disease – even if they have never complained about sleep problems, the group says.
AASM “continually evaluates the definitions, criteria and recommendations used in the identification of sleep apnea and other sleep disorders,” Ms. Gibson said in the statement. Meanwhile, routine screening by primary care doctors “is a simple way” of gauging whether a high-risk patient may have obstructive sleep apnea, the statement said.
The U.S. Preventive Services Task Force, an authoritative body that reviews the effectiveness of preventive care, takes a conservative view, more like that of the European researchers, concluding there is “insufficient” evidence to support widespread screening among patients with no symptoms.
Many insurers refuse to pay for CPAP machines and other treatments prescribed for people at the outer edges of the AASM’s apnea definition. But AASM is pressuring them to come around.
After all my reporting, I concluded that my apnea is real, though moderate. My alarming reading in the overnight lab – diagnosed quickly as central sleep apnea – was a byproduct of the testing machinery itself. That’s a well-described phenomenon that occurs in 5% to 15% of patients.
And when I looked closely at the results of my at-home diagnostic test, I had an epiphany: My overall score was 26 breathing interruptions and blood-oxygen level declines, on average, per hour – enough to put me in the “high-moderate” category for apnea. But when I looked at the data sorted according to sleeping positions, I saw that I scored much better when I slept on my side: only 10 interruptions in an hour.
So I did a little experiment: I bought a $25 pulse oximeter with a smartphone app that records oxygen dips and breathing interruptions. When I slept on my side, there were hardly any.
Now I sleep on my side. I snore less. I wake up refreshed. I’m not daytime drowsy.
None of my specialists mentioned turning on to my side – known in medical parlance as “positional therapy” – though the intervention is recognized as effective by many researchers. Sleeping on one’s back contributes to snoring and blockages, especially as people age and the muscles in the throat become looser.
“Positional patients ... can sleep in the lateral position and sleep quite well,” said Arie Oksenberg, PhD, a sleep researcher formerly at Loewenstein Hospital in Ra’anana, Israel.
But it’s not easy to find this in the official AASM treatment guidelines, which instead go right to the money-making options like CPAP machines, surgery, central apnea, and mouth appliances.
Dealing with apnea by shifting slightly in bed gets little more than a couple of paragraphs in AASM’s guideline on “other” treatments and a little box on a long and complex decision chart.
A third or more of patients wear CPAPs only a few hours a night or stop using them. It turns out people don’t like machines in their beds.
“Positional therapy is an effective treatment option for some patients,” said Ms. Gibson. But she said there are concerns about whether patients will sleep on their sides long term and whether trying to stay in one position might cause sleep interruptions itself.
It’s true that side-sleeping doesn’t help everybody. And it often takes practice. (Some people tape a tennis ball to their pajamas to keep them off their backs.) Even conservative sleep doctors say CPAP machines are the best solution for many patients.
But there is a largely overlooked alternative.
“Are we missing a simple treatment for most adult sleep apnea patients?” was the name of a 2013 paper that Dr. Oksenberg and a colleague wrote about positional therapy.
In my case, the answer was “yes.”
KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.
Editor's Note: We periodically publish patient viewpoints on specific issues of interest to our audience.
I woke up in a strange bedroom with 24 electrodes glued all over my body and a plastic mask attached to a hose covering my face.
The lab technician who watched me all night via video feed told me that I had “wicked sleep apnea” and that it was “central sleep apnea” – a type that originates in the brain and fails to tell the muscles to inhale.
As a journalist– and one terrified by the diagnosis – I set out to do my own research. After a few weeks of sleuthing and interviewing experts, I reached two important conclusions.
First, I had moderate apnea, if that, and it could be treated without the elaborate machines, mouthpieces, or other devices that specialists who had consulted on my care were talking about.
Second, I was on a conveyor belt.
It all began with a desire for answers: I had been feeling drowsy during the day, and my wife told me I snored. Both can mean obstructive sleep apnea. With obstructive sleep apnea, the mouth and throat relax when a person is unconscious, sometimes blocking or narrowing the airway. That interrupts breathing, as well as sleep. Without treatment, the resulting disruption in oxygen flow might increase the risk of developing certain cardiovascular diseases.
So I contacted a sleep-treatment center, and doctors gave me an at-home test ($365). Two weeks later, they told me I had “high-moderate” sleep apnea and needed to acquire a continuous positive airway pressure (CPAP) machine, at a cost of about $600.
Though I had hoped to get the equipment and adjust the settings to see what worked best, my doctors said I had to come to the sleep lab for an overnight test ($1,900) to have them “titrate” the optimal CPAP air pressure.
“How do you treat central sleep apnea?” I worriedly asked the technician after that first overnight stay. She said something about an adaptive servo-ventilation machine ($4,000). And one pricey lab sleepover wasn’t enough, she said. I needed to come back for another.
(Most procedures and devices mentioned in this article were covered or would have been covered by insurance – in my case, Medicare, plus a supplemental plan. Unnecessary care is a big reason Americans’ insurance costs – premiums, copays, and deductibles – tend to rise year after year.)
As a journalist who spent years covering the business of health care, I found there was more motivating my expensive testing cascade than concerns about my health.
The American Academy of Sleep Medicine, a nonprofit based near Chicago, decides what is sleep apnea and how to treat it. Working with sleep societies around the world, it publishes the International Classification of Sleep Disorders, relied on by doctors everywhere to diagnose and categorize disease.
But behind that effort lie considerable conflicts of interest. Like so much of U.S. health care, sleep medicine turns out to be a thriving industry. AASM finances its operations in part with payments from CPAP machine manufacturers and other companies that stand to profit from expensive treatments and expansive definitions of apnea and other sleep disorders.
Zoll Itamar, which makes the at-home testing device I used, as well as implantable nerve-stimulation hardware for central sleep apnea, is a $60,000, “platinum” partner in AASM’s Industry Engagement Program. So is Avadel Pharmaceuticals, which is testing a drug to treat narcolepsy, characterized by intense daytime sleepiness.
Other sponsors include the maker of an anti-insomnia drug; another company with a narcolepsy drug; Fisher & Paykel Healthcare, which makes CPAP machines and masks; and Inspire Medical Systems, maker of a heavily advertised surgical implant, costing tens of thousands of dollars, to treat apnea.
Corporate sponsors for Sleep 2022, a convention AASM put on in Charlotte, N.C., with other professional societies, included many of those companies, plus Philips Respironics and ResMed, two of the biggest CPAP machine makers.
In a statement, AASM spokesperson Jennifer Gibson said a conflict-of-interest policy and a noninterference pledge from industry funders protect the integrity of the academy’s work. Industry donations account for about $170,000 of AASM’s annual revenue of about $15 million. Other revenue comes from educational materials and membership and accreditation fees.
Here’s what else I found. Almost everybody breathes irregularly sometime at night, especially during REM sleep, characterized by rapid eye movement and dreams. Blood oxygen levels also fluctuate slightly.
But recent European studies have shown that standards under the International Classification of Sleep Disorders would doom huge portions of the general population to a sleep apnea diagnosis – whether or not people had complaints of daytime tiredness or other sleep problems.
A study in Lausanne, Switzerland, showed that 50% of local men and 23% of the women 40 or older were positive for sleep apnea under such criteria.
Such rates of disease are “extraordinarily high,” “astronomical,” and “implausible,” Dirk Pevernagie, PhD, a scientist at Ghent (Belgium) University Hospital, wrote with colleagues 2 years ago in a comprehensive study in the Journal of Sleep Research.
“Right now, there is no real evidence for the criteria that have been put forward to diagnose obstructive sleep apnea and rate its severity,” he said in an interview.
Likewise, 19% of middle-aged subjects in a 2016 Icelandic study appeared to have moderate to severe “apnea” under one definition in the International Classification of Sleep Disorders even though many reported no drowsiness.
“Most of them were really surprised,” said Erna Sif Arnardóttir, who led the study and is running a large European program to refine detection and treatment of apnea.
Nevertheless, the official AASM journal recommends extremely broad screening for sleep apnea, looking for patients who have what it defines as illness. Everybody 18 and older should be screened every year for apnea if they have diabetes, obesity, untreated high blood pressure, or heart disease – even if they have never complained about sleep problems, the group says.
AASM “continually evaluates the definitions, criteria and recommendations used in the identification of sleep apnea and other sleep disorders,” Ms. Gibson said in the statement. Meanwhile, routine screening by primary care doctors “is a simple way” of gauging whether a high-risk patient may have obstructive sleep apnea, the statement said.
The U.S. Preventive Services Task Force, an authoritative body that reviews the effectiveness of preventive care, takes a conservative view, more like that of the European researchers, concluding there is “insufficient” evidence to support widespread screening among patients with no symptoms.
Many insurers refuse to pay for CPAP machines and other treatments prescribed for people at the outer edges of the AASM’s apnea definition. But AASM is pressuring them to come around.
After all my reporting, I concluded that my apnea is real, though moderate. My alarming reading in the overnight lab – diagnosed quickly as central sleep apnea – was a byproduct of the testing machinery itself. That’s a well-described phenomenon that occurs in 5% to 15% of patients.
And when I looked closely at the results of my at-home diagnostic test, I had an epiphany: My overall score was 26 breathing interruptions and blood-oxygen level declines, on average, per hour – enough to put me in the “high-moderate” category for apnea. But when I looked at the data sorted according to sleeping positions, I saw that I scored much better when I slept on my side: only 10 interruptions in an hour.
So I did a little experiment: I bought a $25 pulse oximeter with a smartphone app that records oxygen dips and breathing interruptions. When I slept on my side, there were hardly any.
Now I sleep on my side. I snore less. I wake up refreshed. I’m not daytime drowsy.
None of my specialists mentioned turning on to my side – known in medical parlance as “positional therapy” – though the intervention is recognized as effective by many researchers. Sleeping on one’s back contributes to snoring and blockages, especially as people age and the muscles in the throat become looser.
“Positional patients ... can sleep in the lateral position and sleep quite well,” said Arie Oksenberg, PhD, a sleep researcher formerly at Loewenstein Hospital in Ra’anana, Israel.
But it’s not easy to find this in the official AASM treatment guidelines, which instead go right to the money-making options like CPAP machines, surgery, central apnea, and mouth appliances.
Dealing with apnea by shifting slightly in bed gets little more than a couple of paragraphs in AASM’s guideline on “other” treatments and a little box on a long and complex decision chart.
A third or more of patients wear CPAPs only a few hours a night or stop using them. It turns out people don’t like machines in their beds.
“Positional therapy is an effective treatment option for some patients,” said Ms. Gibson. But she said there are concerns about whether patients will sleep on their sides long term and whether trying to stay in one position might cause sleep interruptions itself.
It’s true that side-sleeping doesn’t help everybody. And it often takes practice. (Some people tape a tennis ball to their pajamas to keep them off their backs.) Even conservative sleep doctors say CPAP machines are the best solution for many patients.
But there is a largely overlooked alternative.
“Are we missing a simple treatment for most adult sleep apnea patients?” was the name of a 2013 paper that Dr. Oksenberg and a colleague wrote about positional therapy.
In my case, the answer was “yes.”
KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.
Folic acid tied to a reduction in suicide attempts
new research suggests.
After adjusting for multiple factors, results from a large pharmaco-epidemiological study showed taking folic acid was associated with a 44% reduction in suicide events.
“These results are really putting folic acid squarely on the map as a potential for large-scale, population-level prevention,” lead author Robert D. Gibbons, PhD, professor of biostatistics, Center for Health Statistics, University of Chicago, said in an interview.
“Folic acid is safe, inexpensive, and generally available, and if future randomized controlled trials show this association is beyond a shadow of a doubt causal, we have a new tool in the arsenal,” Dr. Gibbons said.
Having such a tool would be extremely important given that suicide is such a significant public health crisis worldwide, he added.
The findings were published online in JAMA Psychiatry.
Previous research ‘fairly thin’
Folate, the naturally occurring form of B9, is essential for neurogenesis, nucleotide synthesis, and methylation of homocysteine. Past research has suggested that taking folate can prevent neural tube and heart defects in the fetus during pregnancy – and may prevent strokes and reduce age-related hearing loss in adults.
In psychiatry, the role of folate has been recognized for more than a decade. It may enhance the effects of antidepressants; and folate deficiency can predict poorer response to SSRIs.
This has led to recommendations for folate augmentation in patients with low or normal levels at the start of depression treatment.
Although previous research has shown a link between folic acid and suicidality, the findings have been “fairly thin,” with studies being “generally small, and many are case series,” Dr. Gibbons said.
The current study follows an earlier analysis that used a novel statistical methodology for generating drug safety signals that was developed by Dr. Gibbons and colleagues. That study compared rates of suicide attempts before and after initiation of 922 drugs with at least 3,000 prescriptions.
Its results showed 10 drugs were associated with increased risk after exposure, with the strongest associations for alprazolam, butalbital, hydrocodone, and combination codeine/promethazine. In addition, 44 drugs were associated with decreased risk, many of which were antidepressants and antipsychotics.
“One of the most interesting findings in terms of the decreased risk was for folic acid,” said Dr. Gibbons.
He and his colleagues initially thought this was because of women taking folic acid during pregnancy. But when restricting the analysis to men, they found the same effect.
Their next step was to carry out the current large-scale pharmaco-epidemiological study.
Prescriptions for pain
The researchers used a health claims database that included 164 million enrollees. The study cohort was comprised of 866,586 adults with private health insurance (81.3% women; 10.4% aged 60 years and older) who filled a folic acid prescription between 2012 and 2017.
More than half of the folic acid prescriptions were associated with pain disorders. About 48% were for a single agent at a dosage of 1 mg/d, which is the upper tolerable limit for adults – including in pregnancy and lactation.
Other single-agent daily dosages ranging from 0.4 mg to 5 mg accounted for 0.11% of prescriptions. The remainder were multivitamins.
The participants were followed for 24 months. The within-person analysis compared suicide attempts or self-harm events resulting in an outpatient visit or inpatient admission during periods of folic acid treatment versus during periods without treatment.
During the study period, the overall suicidal event rate was 133 per 100,000 population, which is one-fourth the national rate reported by the National Institutes of Health of 600 per 100,000.
After adjusting for age, sex, diagnoses related to suicidal behavior and folic acid deficiency, history of folate-reducing medications, and history of suicidal events, the estimated hazard ratio for suicide events when taking folic acid was 0.56 (95% confidence interal, 0.48-0.65) – which indicates a 44% reduction in suicide events.
“This is a very large decrease and is extremely significant and exciting,” Dr. Gibbons said.
He noted the decrease in suicidal events may have been even greater considering the study captured only prescription folic acid, and participants may also have also taken over-the-counter products.
“The 44% reduction in suicide attempts may actually be an underestimate,” said Dr. Gibbons.
Age and sex did not moderate the association between folic acid and suicide attempts, and a similar association was found in women of childbearing age.
Provocative results?
The investigators also assessed a negative control group of 236,610 individuals using cyanocobalamin during the study period. Cyanocobalamin is a form of vitamin B12 that is essential for metabolism, blood cell synthesis, and the nervous system. It does not contain folic acid and is commonly used to treat anemia.
Results showed no association between cyanocobalamin and suicidal events in the adjusted analysis (HR, 1.01; 95% CI, 0.80-1.27) or unadjusted analysis (HR, 1.02; 95% CI, 0.80-1.28).
Dr. Gibbons noted this result boosts the argument that the association between folic acid and reduced suicidal attempts “isn’t just about health-seeking behavior like taking vitamin supplements.”
Another sensitivity analysis showed every additional month of treatment was associated with a 5% reduction in the suicidal event rate.
“This means the longer you take folic acid, the greater the benefit, which is what you would expect to see if there was a real association between a treatment and an outcome,” said Dr. Gibbons.
The new results “are so provocative that they really mandate the need for a well-controlled randomized controlled trial of folic acid and suicide events,” possibly in a high-risk population such as veterans, he noted.
Such a study could use longitudinal assessments of suicidal events, such as the validated Computerized Adaptive Test Suicide Scale, he added. This continuous scale of suicidality ranges from subclinical, signifying helplessness, hopelessness, and loss of pleasure, to suicide attempts and completion.
As for study limitations, the investigators noted that this study was observational, so there could be selection effects. And using claims data likely underrepresented the number of suicidal events because of incomplete reporting. As the researchers pointed out, the rate of suicidal events in this study was much lower than the national rate.
Other limitations cited were that the association between folic acid and suicidal events may be explained by healthy user bias; and although the investigators conducted a sensitivity analysis in women of childbearing age, they did not have data on women actively planning for a pregnancy.
‘Impressive, encouraging’
In a comment, Shirley Yen, PhD, associate professor of psychology, Beth Israel Deaconess Medical Center and Harvard Medical School, both in Boston, described the new findings as “quite impressive” and “extremely encouraging.”
However, she noted “it’s too premature” to suggest widespread use of folic acid in patients with depressive symptoms.
Dr. Yen, who has researched suicide risks previously, was not involved with the current study.
She did agree with the investigators that the results call for “more robustly controlled studies. These could include double-blind, randomized, controlled trials that could “more formally assess” all folic acid usage as opposed to prescriptions only, Dr. Yen said.
The study was funded by the NIH, the Agency for Healthcare Research and Quality, and the Center of Excellence for Suicide Prevention. Dr. Gibbons reported serving as an expert witness in cases for the Department of Justice; receiving expert witness fees from Merck, GlaxoSmithKline, Pfizer, and Wyeth; and having founded Adaptive Testing Technologies, which distributes the Computerized Adaptive Test Suicide Scale. Dr. Yen reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new research suggests.
After adjusting for multiple factors, results from a large pharmaco-epidemiological study showed taking folic acid was associated with a 44% reduction in suicide events.
“These results are really putting folic acid squarely on the map as a potential for large-scale, population-level prevention,” lead author Robert D. Gibbons, PhD, professor of biostatistics, Center for Health Statistics, University of Chicago, said in an interview.
“Folic acid is safe, inexpensive, and generally available, and if future randomized controlled trials show this association is beyond a shadow of a doubt causal, we have a new tool in the arsenal,” Dr. Gibbons said.
Having such a tool would be extremely important given that suicide is such a significant public health crisis worldwide, he added.
The findings were published online in JAMA Psychiatry.
Previous research ‘fairly thin’
Folate, the naturally occurring form of B9, is essential for neurogenesis, nucleotide synthesis, and methylation of homocysteine. Past research has suggested that taking folate can prevent neural tube and heart defects in the fetus during pregnancy – and may prevent strokes and reduce age-related hearing loss in adults.
In psychiatry, the role of folate has been recognized for more than a decade. It may enhance the effects of antidepressants; and folate deficiency can predict poorer response to SSRIs.
This has led to recommendations for folate augmentation in patients with low or normal levels at the start of depression treatment.
Although previous research has shown a link between folic acid and suicidality, the findings have been “fairly thin,” with studies being “generally small, and many are case series,” Dr. Gibbons said.
The current study follows an earlier analysis that used a novel statistical methodology for generating drug safety signals that was developed by Dr. Gibbons and colleagues. That study compared rates of suicide attempts before and after initiation of 922 drugs with at least 3,000 prescriptions.
Its results showed 10 drugs were associated with increased risk after exposure, with the strongest associations for alprazolam, butalbital, hydrocodone, and combination codeine/promethazine. In addition, 44 drugs were associated with decreased risk, many of which were antidepressants and antipsychotics.
“One of the most interesting findings in terms of the decreased risk was for folic acid,” said Dr. Gibbons.
He and his colleagues initially thought this was because of women taking folic acid during pregnancy. But when restricting the analysis to men, they found the same effect.
Their next step was to carry out the current large-scale pharmaco-epidemiological study.
Prescriptions for pain
The researchers used a health claims database that included 164 million enrollees. The study cohort was comprised of 866,586 adults with private health insurance (81.3% women; 10.4% aged 60 years and older) who filled a folic acid prescription between 2012 and 2017.
More than half of the folic acid prescriptions were associated with pain disorders. About 48% were for a single agent at a dosage of 1 mg/d, which is the upper tolerable limit for adults – including in pregnancy and lactation.
Other single-agent daily dosages ranging from 0.4 mg to 5 mg accounted for 0.11% of prescriptions. The remainder were multivitamins.
The participants were followed for 24 months. The within-person analysis compared suicide attempts or self-harm events resulting in an outpatient visit or inpatient admission during periods of folic acid treatment versus during periods without treatment.
During the study period, the overall suicidal event rate was 133 per 100,000 population, which is one-fourth the national rate reported by the National Institutes of Health of 600 per 100,000.
After adjusting for age, sex, diagnoses related to suicidal behavior and folic acid deficiency, history of folate-reducing medications, and history of suicidal events, the estimated hazard ratio for suicide events when taking folic acid was 0.56 (95% confidence interal, 0.48-0.65) – which indicates a 44% reduction in suicide events.
“This is a very large decrease and is extremely significant and exciting,” Dr. Gibbons said.
He noted the decrease in suicidal events may have been even greater considering the study captured only prescription folic acid, and participants may also have also taken over-the-counter products.
“The 44% reduction in suicide attempts may actually be an underestimate,” said Dr. Gibbons.
Age and sex did not moderate the association between folic acid and suicide attempts, and a similar association was found in women of childbearing age.
Provocative results?
The investigators also assessed a negative control group of 236,610 individuals using cyanocobalamin during the study period. Cyanocobalamin is a form of vitamin B12 that is essential for metabolism, blood cell synthesis, and the nervous system. It does not contain folic acid and is commonly used to treat anemia.
Results showed no association between cyanocobalamin and suicidal events in the adjusted analysis (HR, 1.01; 95% CI, 0.80-1.27) or unadjusted analysis (HR, 1.02; 95% CI, 0.80-1.28).
Dr. Gibbons noted this result boosts the argument that the association between folic acid and reduced suicidal attempts “isn’t just about health-seeking behavior like taking vitamin supplements.”
Another sensitivity analysis showed every additional month of treatment was associated with a 5% reduction in the suicidal event rate.
“This means the longer you take folic acid, the greater the benefit, which is what you would expect to see if there was a real association between a treatment and an outcome,” said Dr. Gibbons.
The new results “are so provocative that they really mandate the need for a well-controlled randomized controlled trial of folic acid and suicide events,” possibly in a high-risk population such as veterans, he noted.
Such a study could use longitudinal assessments of suicidal events, such as the validated Computerized Adaptive Test Suicide Scale, he added. This continuous scale of suicidality ranges from subclinical, signifying helplessness, hopelessness, and loss of pleasure, to suicide attempts and completion.
As for study limitations, the investigators noted that this study was observational, so there could be selection effects. And using claims data likely underrepresented the number of suicidal events because of incomplete reporting. As the researchers pointed out, the rate of suicidal events in this study was much lower than the national rate.
Other limitations cited were that the association between folic acid and suicidal events may be explained by healthy user bias; and although the investigators conducted a sensitivity analysis in women of childbearing age, they did not have data on women actively planning for a pregnancy.
‘Impressive, encouraging’
In a comment, Shirley Yen, PhD, associate professor of psychology, Beth Israel Deaconess Medical Center and Harvard Medical School, both in Boston, described the new findings as “quite impressive” and “extremely encouraging.”
However, she noted “it’s too premature” to suggest widespread use of folic acid in patients with depressive symptoms.
Dr. Yen, who has researched suicide risks previously, was not involved with the current study.
She did agree with the investigators that the results call for “more robustly controlled studies. These could include double-blind, randomized, controlled trials that could “more formally assess” all folic acid usage as opposed to prescriptions only, Dr. Yen said.
The study was funded by the NIH, the Agency for Healthcare Research and Quality, and the Center of Excellence for Suicide Prevention. Dr. Gibbons reported serving as an expert witness in cases for the Department of Justice; receiving expert witness fees from Merck, GlaxoSmithKline, Pfizer, and Wyeth; and having founded Adaptive Testing Technologies, which distributes the Computerized Adaptive Test Suicide Scale. Dr. Yen reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new research suggests.
After adjusting for multiple factors, results from a large pharmaco-epidemiological study showed taking folic acid was associated with a 44% reduction in suicide events.
“These results are really putting folic acid squarely on the map as a potential for large-scale, population-level prevention,” lead author Robert D. Gibbons, PhD, professor of biostatistics, Center for Health Statistics, University of Chicago, said in an interview.
“Folic acid is safe, inexpensive, and generally available, and if future randomized controlled trials show this association is beyond a shadow of a doubt causal, we have a new tool in the arsenal,” Dr. Gibbons said.
Having such a tool would be extremely important given that suicide is such a significant public health crisis worldwide, he added.
The findings were published online in JAMA Psychiatry.
Previous research ‘fairly thin’
Folate, the naturally occurring form of B9, is essential for neurogenesis, nucleotide synthesis, and methylation of homocysteine. Past research has suggested that taking folate can prevent neural tube and heart defects in the fetus during pregnancy – and may prevent strokes and reduce age-related hearing loss in adults.
In psychiatry, the role of folate has been recognized for more than a decade. It may enhance the effects of antidepressants; and folate deficiency can predict poorer response to SSRIs.
This has led to recommendations for folate augmentation in patients with low or normal levels at the start of depression treatment.
Although previous research has shown a link between folic acid and suicidality, the findings have been “fairly thin,” with studies being “generally small, and many are case series,” Dr. Gibbons said.
The current study follows an earlier analysis that used a novel statistical methodology for generating drug safety signals that was developed by Dr. Gibbons and colleagues. That study compared rates of suicide attempts before and after initiation of 922 drugs with at least 3,000 prescriptions.
Its results showed 10 drugs were associated with increased risk after exposure, with the strongest associations for alprazolam, butalbital, hydrocodone, and combination codeine/promethazine. In addition, 44 drugs were associated with decreased risk, many of which were antidepressants and antipsychotics.
“One of the most interesting findings in terms of the decreased risk was for folic acid,” said Dr. Gibbons.
He and his colleagues initially thought this was because of women taking folic acid during pregnancy. But when restricting the analysis to men, they found the same effect.
Their next step was to carry out the current large-scale pharmaco-epidemiological study.
Prescriptions for pain
The researchers used a health claims database that included 164 million enrollees. The study cohort was comprised of 866,586 adults with private health insurance (81.3% women; 10.4% aged 60 years and older) who filled a folic acid prescription between 2012 and 2017.
More than half of the folic acid prescriptions were associated with pain disorders. About 48% were for a single agent at a dosage of 1 mg/d, which is the upper tolerable limit for adults – including in pregnancy and lactation.
Other single-agent daily dosages ranging from 0.4 mg to 5 mg accounted for 0.11% of prescriptions. The remainder were multivitamins.
The participants were followed for 24 months. The within-person analysis compared suicide attempts or self-harm events resulting in an outpatient visit or inpatient admission during periods of folic acid treatment versus during periods without treatment.
During the study period, the overall suicidal event rate was 133 per 100,000 population, which is one-fourth the national rate reported by the National Institutes of Health of 600 per 100,000.
After adjusting for age, sex, diagnoses related to suicidal behavior and folic acid deficiency, history of folate-reducing medications, and history of suicidal events, the estimated hazard ratio for suicide events when taking folic acid was 0.56 (95% confidence interal, 0.48-0.65) – which indicates a 44% reduction in suicide events.
“This is a very large decrease and is extremely significant and exciting,” Dr. Gibbons said.
He noted the decrease in suicidal events may have been even greater considering the study captured only prescription folic acid, and participants may also have also taken over-the-counter products.
“The 44% reduction in suicide attempts may actually be an underestimate,” said Dr. Gibbons.
Age and sex did not moderate the association between folic acid and suicide attempts, and a similar association was found in women of childbearing age.
Provocative results?
The investigators also assessed a negative control group of 236,610 individuals using cyanocobalamin during the study period. Cyanocobalamin is a form of vitamin B12 that is essential for metabolism, blood cell synthesis, and the nervous system. It does not contain folic acid and is commonly used to treat anemia.
Results showed no association between cyanocobalamin and suicidal events in the adjusted analysis (HR, 1.01; 95% CI, 0.80-1.27) or unadjusted analysis (HR, 1.02; 95% CI, 0.80-1.28).
Dr. Gibbons noted this result boosts the argument that the association between folic acid and reduced suicidal attempts “isn’t just about health-seeking behavior like taking vitamin supplements.”
Another sensitivity analysis showed every additional month of treatment was associated with a 5% reduction in the suicidal event rate.
“This means the longer you take folic acid, the greater the benefit, which is what you would expect to see if there was a real association between a treatment and an outcome,” said Dr. Gibbons.
The new results “are so provocative that they really mandate the need for a well-controlled randomized controlled trial of folic acid and suicide events,” possibly in a high-risk population such as veterans, he noted.
Such a study could use longitudinal assessments of suicidal events, such as the validated Computerized Adaptive Test Suicide Scale, he added. This continuous scale of suicidality ranges from subclinical, signifying helplessness, hopelessness, and loss of pleasure, to suicide attempts and completion.
As for study limitations, the investigators noted that this study was observational, so there could be selection effects. And using claims data likely underrepresented the number of suicidal events because of incomplete reporting. As the researchers pointed out, the rate of suicidal events in this study was much lower than the national rate.
Other limitations cited were that the association between folic acid and suicidal events may be explained by healthy user bias; and although the investigators conducted a sensitivity analysis in women of childbearing age, they did not have data on women actively planning for a pregnancy.
‘Impressive, encouraging’
In a comment, Shirley Yen, PhD, associate professor of psychology, Beth Israel Deaconess Medical Center and Harvard Medical School, both in Boston, described the new findings as “quite impressive” and “extremely encouraging.”
However, she noted “it’s too premature” to suggest widespread use of folic acid in patients with depressive symptoms.
Dr. Yen, who has researched suicide risks previously, was not involved with the current study.
She did agree with the investigators that the results call for “more robustly controlled studies. These could include double-blind, randomized, controlled trials that could “more formally assess” all folic acid usage as opposed to prescriptions only, Dr. Yen said.
The study was funded by the NIH, the Agency for Healthcare Research and Quality, and the Center of Excellence for Suicide Prevention. Dr. Gibbons reported serving as an expert witness in cases for the Department of Justice; receiving expert witness fees from Merck, GlaxoSmithKline, Pfizer, and Wyeth; and having founded Adaptive Testing Technologies, which distributes the Computerized Adaptive Test Suicide Scale. Dr. Yen reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA PSYCHIATRY
COVID attacks DNA in heart, unlike flu, study says
, according to a study published in Immunology.
The study looked at the hearts of patients who died from COVID-19, the flu, and other causes. The findings could provide clues about why coronavirus has led to complications such as ongoing heart issues.
“We found a lot of DNA damage that was unique to the COVID-19 patients, which wasn’t present in the flu patients,” Arutha Kulasinghe, one of the lead study authors and a research fellow at the University of Queensland, Brisbane, Australia, told the Brisbane Times.
“So in this study, COVID-19 and flu look very different in the way they affect the heart,” he said.
Dr. Kulasinghe and colleagues analyzed the hearts of seven COVID-19 patients, two flu patients, and six patients who died from other causes. They used transcriptomic profiling, which looks at the DNA landscape of an organ, to investigate heart tissue from the patients.
Because of previous studies about heart problems associated with COVID-19, he and colleagues expected to find extreme inflammation in the heart. Instead, they found that inflammation signals had been suppressed in the heart, and markers for DNA damage and repair were much higher. They’re still unsure of the underlying cause.
“The indications here are that there’s DNA damage here, it’s not inflammation,” Dr. Kulasinghe said. “There’s something else going on that we need to figure out.”
The damage was similar to the way chronic diseases such as diabetes and cancer appear in the heart, he said, with heart tissue showing DNA damage signals.
Dr. Kulasinghe said he hopes other studies can build on the findings to develop risk models to understand which patients may face a higher risk of serious COVID-19 complications. In turn, this could help doctors provide early treatment. For instance, all seven COVID-19 patients had other chronic diseases, such as diabetes, hypertension, and heart disease.
“Ideally in the future, if you have cardiovascular disease, if you’re obese or have other complications, and you’ve got a signature in your blood that indicates you are at risk of severe disease, then we can risk-stratify patients when they are diagnosed,” he said.
The research is a preliminary step, Dr. Kulasinghe said, because of the small sample size. This type of study is often difficult to conduct because researchers have to wait for the availability of organs, as well as request permission from families for postmortem autopsies and biopsies, to be able to look at the effects on dead tissues.
“Our challenge now is to draw a clinical finding from this, which we can’t at this stage,” he added. “But it’s a really fundamental biological difference we’re observing [between COVID-19 and flu], which we need to validate with larger studies.”
A version of this article first appeared on WebMD.com.
, according to a study published in Immunology.
The study looked at the hearts of patients who died from COVID-19, the flu, and other causes. The findings could provide clues about why coronavirus has led to complications such as ongoing heart issues.
“We found a lot of DNA damage that was unique to the COVID-19 patients, which wasn’t present in the flu patients,” Arutha Kulasinghe, one of the lead study authors and a research fellow at the University of Queensland, Brisbane, Australia, told the Brisbane Times.
“So in this study, COVID-19 and flu look very different in the way they affect the heart,” he said.
Dr. Kulasinghe and colleagues analyzed the hearts of seven COVID-19 patients, two flu patients, and six patients who died from other causes. They used transcriptomic profiling, which looks at the DNA landscape of an organ, to investigate heart tissue from the patients.
Because of previous studies about heart problems associated with COVID-19, he and colleagues expected to find extreme inflammation in the heart. Instead, they found that inflammation signals had been suppressed in the heart, and markers for DNA damage and repair were much higher. They’re still unsure of the underlying cause.
“The indications here are that there’s DNA damage here, it’s not inflammation,” Dr. Kulasinghe said. “There’s something else going on that we need to figure out.”
The damage was similar to the way chronic diseases such as diabetes and cancer appear in the heart, he said, with heart tissue showing DNA damage signals.
Dr. Kulasinghe said he hopes other studies can build on the findings to develop risk models to understand which patients may face a higher risk of serious COVID-19 complications. In turn, this could help doctors provide early treatment. For instance, all seven COVID-19 patients had other chronic diseases, such as diabetes, hypertension, and heart disease.
“Ideally in the future, if you have cardiovascular disease, if you’re obese or have other complications, and you’ve got a signature in your blood that indicates you are at risk of severe disease, then we can risk-stratify patients when they are diagnosed,” he said.
The research is a preliminary step, Dr. Kulasinghe said, because of the small sample size. This type of study is often difficult to conduct because researchers have to wait for the availability of organs, as well as request permission from families for postmortem autopsies and biopsies, to be able to look at the effects on dead tissues.
“Our challenge now is to draw a clinical finding from this, which we can’t at this stage,” he added. “But it’s a really fundamental biological difference we’re observing [between COVID-19 and flu], which we need to validate with larger studies.”
A version of this article first appeared on WebMD.com.
, according to a study published in Immunology.
The study looked at the hearts of patients who died from COVID-19, the flu, and other causes. The findings could provide clues about why coronavirus has led to complications such as ongoing heart issues.
“We found a lot of DNA damage that was unique to the COVID-19 patients, which wasn’t present in the flu patients,” Arutha Kulasinghe, one of the lead study authors and a research fellow at the University of Queensland, Brisbane, Australia, told the Brisbane Times.
“So in this study, COVID-19 and flu look very different in the way they affect the heart,” he said.
Dr. Kulasinghe and colleagues analyzed the hearts of seven COVID-19 patients, two flu patients, and six patients who died from other causes. They used transcriptomic profiling, which looks at the DNA landscape of an organ, to investigate heart tissue from the patients.
Because of previous studies about heart problems associated with COVID-19, he and colleagues expected to find extreme inflammation in the heart. Instead, they found that inflammation signals had been suppressed in the heart, and markers for DNA damage and repair were much higher. They’re still unsure of the underlying cause.
“The indications here are that there’s DNA damage here, it’s not inflammation,” Dr. Kulasinghe said. “There’s something else going on that we need to figure out.”
The damage was similar to the way chronic diseases such as diabetes and cancer appear in the heart, he said, with heart tissue showing DNA damage signals.
Dr. Kulasinghe said he hopes other studies can build on the findings to develop risk models to understand which patients may face a higher risk of serious COVID-19 complications. In turn, this could help doctors provide early treatment. For instance, all seven COVID-19 patients had other chronic diseases, such as diabetes, hypertension, and heart disease.
“Ideally in the future, if you have cardiovascular disease, if you’re obese or have other complications, and you’ve got a signature in your blood that indicates you are at risk of severe disease, then we can risk-stratify patients when they are diagnosed,” he said.
The research is a preliminary step, Dr. Kulasinghe said, because of the small sample size. This type of study is often difficult to conduct because researchers have to wait for the availability of organs, as well as request permission from families for postmortem autopsies and biopsies, to be able to look at the effects on dead tissues.
“Our challenge now is to draw a clinical finding from this, which we can’t at this stage,” he added. “But it’s a really fundamental biological difference we’re observing [between COVID-19 and flu], which we need to validate with larger studies.”
A version of this article first appeared on WebMD.com.
FROM IMMUNOLOGY
Ancient DNA discoveries lead to Nobel Prize in medicine and help explain how humans evolved
It all started with a 40,000-year-old bone. That Neanderthal bone contained enough DNA that Dr. Pääbo could start decades of research showing us modern humans, Homo sapiens, are genetically distinct from other now-extinct hominins such as Neanderthals and Denisovans.
The connection to physiology and medicine comes from the genes some modern humans carry from these ancient relatives. For example, Neanderthal genes transferred to Homo sapiens can explain how our immune systems react to different infections. Dr. Pääbo also discovered that a copy of a gene from another extinct relative, the Denisovans, gives modern-day Tibetans a survival advantage for living at high altitudes.
“Svante Pääbo accomplished something seemingly impossible: sequencing the genome of the Neanderthal, an extinct relative of present-day humans. He also made the sensational discovery of a previously unknown hominin, Denisova,” the Nobel Committee stated in a news release announcing the award. “Importantly, [Dr.] Pääbo also found that gene transfer had occurred from these now extinct hominins to Homo sapiens following the migration out of Africa around 70,000 years ago.”
Dr. Pääbo’s scientific discoveries only happened by pairing ancient DNA evidence with modern technology. An initial discovery occurred when Dr. Pääbo worked at the University of Munich (Germany), where he sequenced mitochondrial DNA from the 40,000-year-old Neanderthal bone. The sequencing of the human genome in the 1990s coupled with genomic DNA recovered from ancient bones allowed Dr. Pääbo to compare our DNA with that of Neanderthals and Denisovans. A lot of this work happened at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, which Dr. Pääbo founded in 1999 and where he still works today.
In 2008, a different 40,000-year-old fragment from a finger bone was discovered in a Denisova cave in the southern part of Siberia. Fortunately for Dr. Pääbo and his team, the DNA was well preserved and could be sequenced.
“The results caused a sensation: the DNA sequence was unique when compared to all known sequences from Neanderthals and present-day humans,” the Nobel Committee said.
In a big picture sense, Dr. Pääbo’s research helps answer where modern-day humans come from and how we interacted with our hominin relatives tens of thousands of years ago. His research is so pioneering that it created a new field of science called paleogenomics, the Nobel Committee noted.
“On behalf of The Physiological Society, I am delighted to congratulate Svante Pääbo for being awarded the Nobel Prize. His pioneering research shines a light on the physiology that makes humans unique from their ancestors,” David Paterson, DPhil, president of The Physiological Society, said in a statement.
“This is an important science discovery in evolutionary biology,” Dr. Paterson added. “Ascribing physiological function to highly conserved mitochondrial genes has been important in our understanding in high-altitude acclimatization as populations move and adapt to new environments, and how genetic variants affect us on a day-to-day basis in health and disease.”
A version of this article first appeared on Medscape.com.
It all started with a 40,000-year-old bone. That Neanderthal bone contained enough DNA that Dr. Pääbo could start decades of research showing us modern humans, Homo sapiens, are genetically distinct from other now-extinct hominins such as Neanderthals and Denisovans.
The connection to physiology and medicine comes from the genes some modern humans carry from these ancient relatives. For example, Neanderthal genes transferred to Homo sapiens can explain how our immune systems react to different infections. Dr. Pääbo also discovered that a copy of a gene from another extinct relative, the Denisovans, gives modern-day Tibetans a survival advantage for living at high altitudes.
“Svante Pääbo accomplished something seemingly impossible: sequencing the genome of the Neanderthal, an extinct relative of present-day humans. He also made the sensational discovery of a previously unknown hominin, Denisova,” the Nobel Committee stated in a news release announcing the award. “Importantly, [Dr.] Pääbo also found that gene transfer had occurred from these now extinct hominins to Homo sapiens following the migration out of Africa around 70,000 years ago.”
Dr. Pääbo’s scientific discoveries only happened by pairing ancient DNA evidence with modern technology. An initial discovery occurred when Dr. Pääbo worked at the University of Munich (Germany), where he sequenced mitochondrial DNA from the 40,000-year-old Neanderthal bone. The sequencing of the human genome in the 1990s coupled with genomic DNA recovered from ancient bones allowed Dr. Pääbo to compare our DNA with that of Neanderthals and Denisovans. A lot of this work happened at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, which Dr. Pääbo founded in 1999 and where he still works today.
In 2008, a different 40,000-year-old fragment from a finger bone was discovered in a Denisova cave in the southern part of Siberia. Fortunately for Dr. Pääbo and his team, the DNA was well preserved and could be sequenced.
“The results caused a sensation: the DNA sequence was unique when compared to all known sequences from Neanderthals and present-day humans,” the Nobel Committee said.
In a big picture sense, Dr. Pääbo’s research helps answer where modern-day humans come from and how we interacted with our hominin relatives tens of thousands of years ago. His research is so pioneering that it created a new field of science called paleogenomics, the Nobel Committee noted.
“On behalf of The Physiological Society, I am delighted to congratulate Svante Pääbo for being awarded the Nobel Prize. His pioneering research shines a light on the physiology that makes humans unique from their ancestors,” David Paterson, DPhil, president of The Physiological Society, said in a statement.
“This is an important science discovery in evolutionary biology,” Dr. Paterson added. “Ascribing physiological function to highly conserved mitochondrial genes has been important in our understanding in high-altitude acclimatization as populations move and adapt to new environments, and how genetic variants affect us on a day-to-day basis in health and disease.”
A version of this article first appeared on Medscape.com.
It all started with a 40,000-year-old bone. That Neanderthal bone contained enough DNA that Dr. Pääbo could start decades of research showing us modern humans, Homo sapiens, are genetically distinct from other now-extinct hominins such as Neanderthals and Denisovans.
The connection to physiology and medicine comes from the genes some modern humans carry from these ancient relatives. For example, Neanderthal genes transferred to Homo sapiens can explain how our immune systems react to different infections. Dr. Pääbo also discovered that a copy of a gene from another extinct relative, the Denisovans, gives modern-day Tibetans a survival advantage for living at high altitudes.
“Svante Pääbo accomplished something seemingly impossible: sequencing the genome of the Neanderthal, an extinct relative of present-day humans. He also made the sensational discovery of a previously unknown hominin, Denisova,” the Nobel Committee stated in a news release announcing the award. “Importantly, [Dr.] Pääbo also found that gene transfer had occurred from these now extinct hominins to Homo sapiens following the migration out of Africa around 70,000 years ago.”
Dr. Pääbo’s scientific discoveries only happened by pairing ancient DNA evidence with modern technology. An initial discovery occurred when Dr. Pääbo worked at the University of Munich (Germany), where he sequenced mitochondrial DNA from the 40,000-year-old Neanderthal bone. The sequencing of the human genome in the 1990s coupled with genomic DNA recovered from ancient bones allowed Dr. Pääbo to compare our DNA with that of Neanderthals and Denisovans. A lot of this work happened at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, which Dr. Pääbo founded in 1999 and where he still works today.
In 2008, a different 40,000-year-old fragment from a finger bone was discovered in a Denisova cave in the southern part of Siberia. Fortunately for Dr. Pääbo and his team, the DNA was well preserved and could be sequenced.
“The results caused a sensation: the DNA sequence was unique when compared to all known sequences from Neanderthals and present-day humans,” the Nobel Committee said.
In a big picture sense, Dr. Pääbo’s research helps answer where modern-day humans come from and how we interacted with our hominin relatives tens of thousands of years ago. His research is so pioneering that it created a new field of science called paleogenomics, the Nobel Committee noted.
“On behalf of The Physiological Society, I am delighted to congratulate Svante Pääbo for being awarded the Nobel Prize. His pioneering research shines a light on the physiology that makes humans unique from their ancestors,” David Paterson, DPhil, president of The Physiological Society, said in a statement.
“This is an important science discovery in evolutionary biology,” Dr. Paterson added. “Ascribing physiological function to highly conserved mitochondrial genes has been important in our understanding in high-altitude acclimatization as populations move and adapt to new environments, and how genetic variants affect us on a day-to-day basis in health and disease.”
A version of this article first appeared on Medscape.com.
Physician bias may prevent quality care for patients with disabilities
For Tara Lagu, MD, the realization that the health care system was broken for patients with disabilities came when a woman she had been treating seemed to keep ignoring Dr. Lagu’s request to see a urologist.
When Dr. Lagu asked the patient’s two attentive daughters about the delay, their response surprised her. The women said they couldn’t find a urologist who was willing to see a patient in a wheelchair.
Surprised and a bit doubtful, Dr. Lagu checked around. She found that, indeed, the only way to get her patient in to see the type of physician required was to send her by ambulance.
“It opened my eyes to how hard it is for patients with disabilities to navigate the health care system,” Dr. Lagu said.
Dr. Lagu, director of the Center for Health Services and Outcomes Research at Northwestern University in Chicago, decided to take a closer look at how her colleagues in medicine care for – or not, as the case proved – the roughly one in four American adults, and millions of children, with disabilities.
In a series of three focus groups, Dr. Lagu and colleagues identified a range of obstacles – including some physician attitudes – that prevent people with disabilities from getting adequate care.
For the study, published in Health Affairs, the researchers interviewed 22 physicians in three groups: Nonrural primary care physicians, rural primary care physicians, and specialists in rheumatology, neurology, obstetrics/gynecology, orthopedics, and ophthalmology.
During the interviews, conducted in the fall of 2018, participants were asked about providing care for five specific types of disabilities: mobility, hearing, vision, mental health, and intellectual limitations.
Lack of experience, logistics often cited
Some physicians admitted that limited resources and training left them without the space and necessary knowledge to properly care for patients with disabilities. They felt they lacked the expertise or exposure to care for individuals with disabilities, nor did they have enough time and space to properly accommodate these patients, according to the researchers. Some said they struggled to coordinate care for individuals with disabilities and did not know which types of accessible equipment, such as adjustable tables and chair scales, were needed or how to use them.
Several physicians also noted that they are inadequately reimbursed for the special accommodations – including additional staff, equipment, and time – required to care for these patients. One primary care physician said he hired a sign-language interpreter for a patient but the bill for the services exceeded the amount insurance reimbursed. As a result, he said, he spent $30 of his own money per visit to see the patient.
Because of these limitations, some physicians in the focus groups said they try to turn away patients with disabilities. Both specialists and general practitioners said they had told patients with disabilities that they didn’t feel they could provide the care needed, and suggested they look elsewhere. A few were surprisingly – even upsettingly – honest, Dr. Lagu said, making statements such as: “I am not the doctor for you.”
‘We really need a rewrite’
Previous work has shown that people with disabilities have worse health outcomes, such as undetected cancer, obesity, and cardiovascular disease.
But “the disability itself isn’t what leads to worse outcomes,” said Allison Kessler, MD, section chief of the Renée Crown Center for Spinal Cord Innovation and associate director of the Shirley Ryan AbilityLab in Chicago*. This study does a good job at highlighting “the need for change on multiple levels,” said Dr. Kessler, who was not a member of the study team.
“People with disabilities have all these disparities in access and outcomes. We’ve never understood why. I think the why is complicated,” Dr. Lagu added. “I think this study suggests some of the negative outcomes are due to explicit bias.”
“It’s also clear that the current framework of health care in the United States does not lend to allowing physicians and medical providers the time needed to adequately address patient issues – those with disabilities or just multiple complex problems,” Colin O’Reilly, DO, vice president and chief medical officer at Children’s Specialized Hospital, an acute rehabilitation facility affiliated with RWJBarnabas Health, in New Brunswick, N.J. “We really need a rewrite.”
However, Dr. O’Reilly said, such a small study population with no control group and no mention of physician resources makes it difficult to come to a strong conclusion about physician bias and discriminatory attitudes against individuals with disabilities.
Dr. Lagu agreed, saying this research “is not conclusive in any way.” The excuses doctors use to discharge patients with disabilities, such as “we don’t accept your insurance,” “we aren’t taking new patients,” and “we can’t provide you with the appropriate care,” could be legitimate, the study authors wrote. But the “disparities in care for people with disabilities suggest that there is a pattern of more frequently denying care to them than people without a disability,” they added.
Dr. Kessler said many of her patients have told her they experience barriers to care. Some say finding an office with the necessary equipment is a challenge or that they often don’t feel welcome.
The Americans With Disabilities Act (ADA) is a federal civil rights law that prohibits discrimination against individuals with disabilities in all public and private places that are open to the general public, including medical offices.
“It is difficult to enforce the ADA in medical settings,” the researchers noted. “Explanations physicians gave in this study could, for any single case of denying care, be legitimate.” Knowing whether a particular instance of denial of care represents discrimination related to disability is “nearly impossible,” they wrote.
All the experts agreed that the study adds valuable insight into an ongoing health disparity. And while system and policy changes are required, Dr. Kessler said, individual physicians can take steps to improve the situation.
A physician in an academic setting can look at the curriculum and the medical school and see about increasing exposure to patients with disabilities earlier in training. In a practice, physicians can retrain staff to ask every patient if an accommodation is needed. “Each one of those changes can only help us move our system in the right direction,” Dr. Kessler said.
The study was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development.
*Correction, 10/5/22: This article includes a corrected title for Dr. Allison Kessler.
A version of this article first appeared on Medscape.com.
For Tara Lagu, MD, the realization that the health care system was broken for patients with disabilities came when a woman she had been treating seemed to keep ignoring Dr. Lagu’s request to see a urologist.
When Dr. Lagu asked the patient’s two attentive daughters about the delay, their response surprised her. The women said they couldn’t find a urologist who was willing to see a patient in a wheelchair.
Surprised and a bit doubtful, Dr. Lagu checked around. She found that, indeed, the only way to get her patient in to see the type of physician required was to send her by ambulance.
“It opened my eyes to how hard it is for patients with disabilities to navigate the health care system,” Dr. Lagu said.
Dr. Lagu, director of the Center for Health Services and Outcomes Research at Northwestern University in Chicago, decided to take a closer look at how her colleagues in medicine care for – or not, as the case proved – the roughly one in four American adults, and millions of children, with disabilities.
In a series of three focus groups, Dr. Lagu and colleagues identified a range of obstacles – including some physician attitudes – that prevent people with disabilities from getting adequate care.
For the study, published in Health Affairs, the researchers interviewed 22 physicians in three groups: Nonrural primary care physicians, rural primary care physicians, and specialists in rheumatology, neurology, obstetrics/gynecology, orthopedics, and ophthalmology.
During the interviews, conducted in the fall of 2018, participants were asked about providing care for five specific types of disabilities: mobility, hearing, vision, mental health, and intellectual limitations.
Lack of experience, logistics often cited
Some physicians admitted that limited resources and training left them without the space and necessary knowledge to properly care for patients with disabilities. They felt they lacked the expertise or exposure to care for individuals with disabilities, nor did they have enough time and space to properly accommodate these patients, according to the researchers. Some said they struggled to coordinate care for individuals with disabilities and did not know which types of accessible equipment, such as adjustable tables and chair scales, were needed or how to use them.
Several physicians also noted that they are inadequately reimbursed for the special accommodations – including additional staff, equipment, and time – required to care for these patients. One primary care physician said he hired a sign-language interpreter for a patient but the bill for the services exceeded the amount insurance reimbursed. As a result, he said, he spent $30 of his own money per visit to see the patient.
Because of these limitations, some physicians in the focus groups said they try to turn away patients with disabilities. Both specialists and general practitioners said they had told patients with disabilities that they didn’t feel they could provide the care needed, and suggested they look elsewhere. A few were surprisingly – even upsettingly – honest, Dr. Lagu said, making statements such as: “I am not the doctor for you.”
‘We really need a rewrite’
Previous work has shown that people with disabilities have worse health outcomes, such as undetected cancer, obesity, and cardiovascular disease.
But “the disability itself isn’t what leads to worse outcomes,” said Allison Kessler, MD, section chief of the Renée Crown Center for Spinal Cord Innovation and associate director of the Shirley Ryan AbilityLab in Chicago*. This study does a good job at highlighting “the need for change on multiple levels,” said Dr. Kessler, who was not a member of the study team.
“People with disabilities have all these disparities in access and outcomes. We’ve never understood why. I think the why is complicated,” Dr. Lagu added. “I think this study suggests some of the negative outcomes are due to explicit bias.”
“It’s also clear that the current framework of health care in the United States does not lend to allowing physicians and medical providers the time needed to adequately address patient issues – those with disabilities or just multiple complex problems,” Colin O’Reilly, DO, vice president and chief medical officer at Children’s Specialized Hospital, an acute rehabilitation facility affiliated with RWJBarnabas Health, in New Brunswick, N.J. “We really need a rewrite.”
However, Dr. O’Reilly said, such a small study population with no control group and no mention of physician resources makes it difficult to come to a strong conclusion about physician bias and discriminatory attitudes against individuals with disabilities.
Dr. Lagu agreed, saying this research “is not conclusive in any way.” The excuses doctors use to discharge patients with disabilities, such as “we don’t accept your insurance,” “we aren’t taking new patients,” and “we can’t provide you with the appropriate care,” could be legitimate, the study authors wrote. But the “disparities in care for people with disabilities suggest that there is a pattern of more frequently denying care to them than people without a disability,” they added.
Dr. Kessler said many of her patients have told her they experience barriers to care. Some say finding an office with the necessary equipment is a challenge or that they often don’t feel welcome.
The Americans With Disabilities Act (ADA) is a federal civil rights law that prohibits discrimination against individuals with disabilities in all public and private places that are open to the general public, including medical offices.
“It is difficult to enforce the ADA in medical settings,” the researchers noted. “Explanations physicians gave in this study could, for any single case of denying care, be legitimate.” Knowing whether a particular instance of denial of care represents discrimination related to disability is “nearly impossible,” they wrote.
All the experts agreed that the study adds valuable insight into an ongoing health disparity. And while system and policy changes are required, Dr. Kessler said, individual physicians can take steps to improve the situation.
A physician in an academic setting can look at the curriculum and the medical school and see about increasing exposure to patients with disabilities earlier in training. In a practice, physicians can retrain staff to ask every patient if an accommodation is needed. “Each one of those changes can only help us move our system in the right direction,” Dr. Kessler said.
The study was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development.
*Correction, 10/5/22: This article includes a corrected title for Dr. Allison Kessler.
A version of this article first appeared on Medscape.com.
For Tara Lagu, MD, the realization that the health care system was broken for patients with disabilities came when a woman she had been treating seemed to keep ignoring Dr. Lagu’s request to see a urologist.
When Dr. Lagu asked the patient’s two attentive daughters about the delay, their response surprised her. The women said they couldn’t find a urologist who was willing to see a patient in a wheelchair.
Surprised and a bit doubtful, Dr. Lagu checked around. She found that, indeed, the only way to get her patient in to see the type of physician required was to send her by ambulance.
“It opened my eyes to how hard it is for patients with disabilities to navigate the health care system,” Dr. Lagu said.
Dr. Lagu, director of the Center for Health Services and Outcomes Research at Northwestern University in Chicago, decided to take a closer look at how her colleagues in medicine care for – or not, as the case proved – the roughly one in four American adults, and millions of children, with disabilities.
In a series of three focus groups, Dr. Lagu and colleagues identified a range of obstacles – including some physician attitudes – that prevent people with disabilities from getting adequate care.
For the study, published in Health Affairs, the researchers interviewed 22 physicians in three groups: Nonrural primary care physicians, rural primary care physicians, and specialists in rheumatology, neurology, obstetrics/gynecology, orthopedics, and ophthalmology.
During the interviews, conducted in the fall of 2018, participants were asked about providing care for five specific types of disabilities: mobility, hearing, vision, mental health, and intellectual limitations.
Lack of experience, logistics often cited
Some physicians admitted that limited resources and training left them without the space and necessary knowledge to properly care for patients with disabilities. They felt they lacked the expertise or exposure to care for individuals with disabilities, nor did they have enough time and space to properly accommodate these patients, according to the researchers. Some said they struggled to coordinate care for individuals with disabilities and did not know which types of accessible equipment, such as adjustable tables and chair scales, were needed or how to use them.
Several physicians also noted that they are inadequately reimbursed for the special accommodations – including additional staff, equipment, and time – required to care for these patients. One primary care physician said he hired a sign-language interpreter for a patient but the bill for the services exceeded the amount insurance reimbursed. As a result, he said, he spent $30 of his own money per visit to see the patient.
Because of these limitations, some physicians in the focus groups said they try to turn away patients with disabilities. Both specialists and general practitioners said they had told patients with disabilities that they didn’t feel they could provide the care needed, and suggested they look elsewhere. A few were surprisingly – even upsettingly – honest, Dr. Lagu said, making statements such as: “I am not the doctor for you.”
‘We really need a rewrite’
Previous work has shown that people with disabilities have worse health outcomes, such as undetected cancer, obesity, and cardiovascular disease.
But “the disability itself isn’t what leads to worse outcomes,” said Allison Kessler, MD, section chief of the Renée Crown Center for Spinal Cord Innovation and associate director of the Shirley Ryan AbilityLab in Chicago*. This study does a good job at highlighting “the need for change on multiple levels,” said Dr. Kessler, who was not a member of the study team.
“People with disabilities have all these disparities in access and outcomes. We’ve never understood why. I think the why is complicated,” Dr. Lagu added. “I think this study suggests some of the negative outcomes are due to explicit bias.”
“It’s also clear that the current framework of health care in the United States does not lend to allowing physicians and medical providers the time needed to adequately address patient issues – those with disabilities or just multiple complex problems,” Colin O’Reilly, DO, vice president and chief medical officer at Children’s Specialized Hospital, an acute rehabilitation facility affiliated with RWJBarnabas Health, in New Brunswick, N.J. “We really need a rewrite.”
However, Dr. O’Reilly said, such a small study population with no control group and no mention of physician resources makes it difficult to come to a strong conclusion about physician bias and discriminatory attitudes against individuals with disabilities.
Dr. Lagu agreed, saying this research “is not conclusive in any way.” The excuses doctors use to discharge patients with disabilities, such as “we don’t accept your insurance,” “we aren’t taking new patients,” and “we can’t provide you with the appropriate care,” could be legitimate, the study authors wrote. But the “disparities in care for people with disabilities suggest that there is a pattern of more frequently denying care to them than people without a disability,” they added.
Dr. Kessler said many of her patients have told her they experience barriers to care. Some say finding an office with the necessary equipment is a challenge or that they often don’t feel welcome.
The Americans With Disabilities Act (ADA) is a federal civil rights law that prohibits discrimination against individuals with disabilities in all public and private places that are open to the general public, including medical offices.
“It is difficult to enforce the ADA in medical settings,” the researchers noted. “Explanations physicians gave in this study could, for any single case of denying care, be legitimate.” Knowing whether a particular instance of denial of care represents discrimination related to disability is “nearly impossible,” they wrote.
All the experts agreed that the study adds valuable insight into an ongoing health disparity. And while system and policy changes are required, Dr. Kessler said, individual physicians can take steps to improve the situation.
A physician in an academic setting can look at the curriculum and the medical school and see about increasing exposure to patients with disabilities earlier in training. In a practice, physicians can retrain staff to ask every patient if an accommodation is needed. “Each one of those changes can only help us move our system in the right direction,” Dr. Kessler said.
The study was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development.
*Correction, 10/5/22: This article includes a corrected title for Dr. Allison Kessler.
A version of this article first appeared on Medscape.com.
Cutaneous Eruption in an Immunocompromised Patient
The Diagnosis: Secondary Syphilis
Histopathology revealed a lichenoid interface dermatitis with psoriasiform hyperplasia (Figure 1A). A single spirochete was identified using immunohistochemical staining (Figure 1B). Laboratory workup revealed positive IgG and IgM treponemal antibodies and reactive rapid plasma reagin titer of 1:2048. A VDRL test performed on a cerebrospinal fluid specimen also was reactive at 1:8. A diagnosis of secondary syphilis with neurologic involvement was made, and the patient was treated with intravenous penicillin G for 14 days. Following treatment, his rapid plasma reagin decreased 4-fold with an improvement in his ocular and cutaneous symptoms.
Mucocutaneus manifestations of secondary syphilis are multitudinous. As in our patient, the classic presentation is a generalized morbilliform and papulosquamous eruption involving the palms (Figure 2) and soles. Split papules at the oral commissures, mucosal patches, and condyloma lata are the characteristic mucosal lesions of secondary syphilis.1 Patchy nonscarring alopecia is not uncommon and can be the only manifestation of secondary syphilis.2 The histopathologic features of secondary syphilis vary depending on the location and type of the skin eruption. Psoriasiform or lichenoid changes commonly occur in the epidermis and dermoepidermal junction.3 The dermal inflammatory patterns that have been described include granulomatous, nodular, and superficial and deep perivascular inflammation. The infiltrate often is composed of lymphocytes, plasma cells, and histocytes. Reactive endothelial cells and perineural plasma cell infiltrates also are common histologic features.3,4 Spirochetes can be identified in most cases using immunohistochemical staining; however, the absence of spirochetes does not exclude syphilis.3 The sensitivity of immunohistochemical staining in secondary syphilis is reported to be 71% to 100% with a very high specificity.5 The treatment for all stages of syphilis is benzathine penicillin G, and the route of administration and duration of treatment depend on the stage of disease.6
A broad differential diagnosis must be considered when encountering skin eruptions in patients with HIV. Psoriasis usually presents as circumscribed erythematous plaques with dry and silvery scaling and a predilection for the extensor surfaces of the limbs, sacrum, scalp, and nails. Nail manifestations include distal onycholysis, irregular pitting, oil spots, salmon patches, and subungual hyperkeratosis. Alopecia occasionally may be seen within scalp lesions7; however, the constellation of alopecia with a moth-eaten appearance, subungual hyperkeratosis, papulosquamous eruption, and split papules was more suggestive of secondary syphilis in our patient. In immunocompromised patients, crusted scabies can be considered for the diagnosis of papulosquamous eruptions involving the palms and soles. It often presents with symmetric, mildly pruritic, psoriasiform dermatitis that favors acral sites, but widespread involvement can be observed.8 Areas of the scalp and face can be affected in infants, elderly patients, and immunocompromised individuals. Unlike in secondary syphilis, patchy alopecia, split papules, and ocular symptoms typically are not observed in scabies.
Sarcoidosis is common in Black individuals, and similar to syphilis, it is considered a great imitator of other dermatologic diseases. Frequently, it presents as redviolaceous papules, nodules, or plaques; however, rare variants including psoriasiform, ichthyosiform, verrucous, and lichenoid skin eruptions can occur. Nail dystrophy, split papules, and alopecia also have been observed.9 Ocular involvement is common and frequently presents as uveitis.10 The pathologic hallmark of sarcoidosis is noncaseating granulomatous inflammation, which also may occur in syphilitic lesions9; however, a papulosquamous eruption involving the palms and soles, positive serology, and the finding of interface lichenoid dermatitis with psoriasiform hyperplasia confirmed the diagnosis of secondary syphilis in our patient. Pityriasis rubra pilaris is a rare papulosquamous disorder that can be associated with HIV (type VI/HIVassociated follicular syndrome). It presents with generalized red-orange keratotic papules and often is associated with acne conglobata, hidradenitis suppurativa, and lichen spinulosus.11 Unlike in secondary syphilis, patchy alopecia, split papules, and ocular symptoms typically are not observed in pityriasis rubra pilaris.
This case highlights many classical findings of secondary syphilis and demonstrates that, while helpful, routine skin biopsy may not be required. Treatment should be guided by clinical presentation and serologic testing while reserving skin biopsy for equivocal cases.
- Forrestel AK, Kovarik CL, Katz KA. Sexually acquired syphilis: historical aspects, microbiology, epidemiology, and clinical manifestations. J Am Acad Dermatol. 2020;82:1-14.
- Balagula Y, Mattei PL, Wisco OJ, et al. The great imitator revisited: the spectrum of atypical cutaneous manifestations of secondary syphilis. Int J Dermatol. 2014;53:1434-1441.
- Hoang MP, High WA, Molberg KH. Secondary syphilis: a histologic and immunohistochemical evaluation. J Cutan Pathol. 2004; 31:595-599.
- Flamm A, Parikh K, Xie Q, et al. Histologic features of secondary syphilis: a multicenter retrospective review. J Am Acad Dermatol. 2015;73:1025-1030.
- Forrestel AK, Kovarik CL, Katz KA. Sexually acquired syphilis: laboratory diagnosis, management, and prevention [published online February 8, 2020]. J Am Acad Dermatol. 2020;82:17-28.
- Ghanem KG, Ram S, Rice PA. The modern epidemic of syphilis. N Engl J Med. 2020;382:845-854.
- Boehncke WH, Schön MP. Psoriasis. Lancet. 2015;386:983-994.
- Karthikeyan K. Crusted scabies. Indian J Dermatol Venereol Leprol. 2009;75:340-347.
- Haimovic A, Sanchez M, Judson MA, et al. Sarcoidosis: a comprehensive review and update for the dermatologist: part I. cutaneous disease. J Am Acad Dermatol. 2012;66:699.e1-718.
- Haimovic A, Sanchez M, Judson MA, et al. Sarcoidosis: a comprehensive review and update for the dermatologist: part II. extracutaneous disease. J Am Acad Dermatol. 2012;66:719.e1-730.
- Miralles E, Núñez M, De Las Heras M, et al. Pityriasis rubra pilaris and human immunodeficiency virus infection. Br J Dermatol. 1995;133:990-993.
The Diagnosis: Secondary Syphilis
Histopathology revealed a lichenoid interface dermatitis with psoriasiform hyperplasia (Figure 1A). A single spirochete was identified using immunohistochemical staining (Figure 1B). Laboratory workup revealed positive IgG and IgM treponemal antibodies and reactive rapid plasma reagin titer of 1:2048. A VDRL test performed on a cerebrospinal fluid specimen also was reactive at 1:8. A diagnosis of secondary syphilis with neurologic involvement was made, and the patient was treated with intravenous penicillin G for 14 days. Following treatment, his rapid plasma reagin decreased 4-fold with an improvement in his ocular and cutaneous symptoms.
Mucocutaneus manifestations of secondary syphilis are multitudinous. As in our patient, the classic presentation is a generalized morbilliform and papulosquamous eruption involving the palms (Figure 2) and soles. Split papules at the oral commissures, mucosal patches, and condyloma lata are the characteristic mucosal lesions of secondary syphilis.1 Patchy nonscarring alopecia is not uncommon and can be the only manifestation of secondary syphilis.2 The histopathologic features of secondary syphilis vary depending on the location and type of the skin eruption. Psoriasiform or lichenoid changes commonly occur in the epidermis and dermoepidermal junction.3 The dermal inflammatory patterns that have been described include granulomatous, nodular, and superficial and deep perivascular inflammation. The infiltrate often is composed of lymphocytes, plasma cells, and histocytes. Reactive endothelial cells and perineural plasma cell infiltrates also are common histologic features.3,4 Spirochetes can be identified in most cases using immunohistochemical staining; however, the absence of spirochetes does not exclude syphilis.3 The sensitivity of immunohistochemical staining in secondary syphilis is reported to be 71% to 100% with a very high specificity.5 The treatment for all stages of syphilis is benzathine penicillin G, and the route of administration and duration of treatment depend on the stage of disease.6
A broad differential diagnosis must be considered when encountering skin eruptions in patients with HIV. Psoriasis usually presents as circumscribed erythematous plaques with dry and silvery scaling and a predilection for the extensor surfaces of the limbs, sacrum, scalp, and nails. Nail manifestations include distal onycholysis, irregular pitting, oil spots, salmon patches, and subungual hyperkeratosis. Alopecia occasionally may be seen within scalp lesions7; however, the constellation of alopecia with a moth-eaten appearance, subungual hyperkeratosis, papulosquamous eruption, and split papules was more suggestive of secondary syphilis in our patient. In immunocompromised patients, crusted scabies can be considered for the diagnosis of papulosquamous eruptions involving the palms and soles. It often presents with symmetric, mildly pruritic, psoriasiform dermatitis that favors acral sites, but widespread involvement can be observed.8 Areas of the scalp and face can be affected in infants, elderly patients, and immunocompromised individuals. Unlike in secondary syphilis, patchy alopecia, split papules, and ocular symptoms typically are not observed in scabies.
Sarcoidosis is common in Black individuals, and similar to syphilis, it is considered a great imitator of other dermatologic diseases. Frequently, it presents as redviolaceous papules, nodules, or plaques; however, rare variants including psoriasiform, ichthyosiform, verrucous, and lichenoid skin eruptions can occur. Nail dystrophy, split papules, and alopecia also have been observed.9 Ocular involvement is common and frequently presents as uveitis.10 The pathologic hallmark of sarcoidosis is noncaseating granulomatous inflammation, which also may occur in syphilitic lesions9; however, a papulosquamous eruption involving the palms and soles, positive serology, and the finding of interface lichenoid dermatitis with psoriasiform hyperplasia confirmed the diagnosis of secondary syphilis in our patient. Pityriasis rubra pilaris is a rare papulosquamous disorder that can be associated with HIV (type VI/HIVassociated follicular syndrome). It presents with generalized red-orange keratotic papules and often is associated with acne conglobata, hidradenitis suppurativa, and lichen spinulosus.11 Unlike in secondary syphilis, patchy alopecia, split papules, and ocular symptoms typically are not observed in pityriasis rubra pilaris.
This case highlights many classical findings of secondary syphilis and demonstrates that, while helpful, routine skin biopsy may not be required. Treatment should be guided by clinical presentation and serologic testing while reserving skin biopsy for equivocal cases.
The Diagnosis: Secondary Syphilis
Histopathology revealed a lichenoid interface dermatitis with psoriasiform hyperplasia (Figure 1A). A single spirochete was identified using immunohistochemical staining (Figure 1B). Laboratory workup revealed positive IgG and IgM treponemal antibodies and reactive rapid plasma reagin titer of 1:2048. A VDRL test performed on a cerebrospinal fluid specimen also was reactive at 1:8. A diagnosis of secondary syphilis with neurologic involvement was made, and the patient was treated with intravenous penicillin G for 14 days. Following treatment, his rapid plasma reagin decreased 4-fold with an improvement in his ocular and cutaneous symptoms.
Mucocutaneus manifestations of secondary syphilis are multitudinous. As in our patient, the classic presentation is a generalized morbilliform and papulosquamous eruption involving the palms (Figure 2) and soles. Split papules at the oral commissures, mucosal patches, and condyloma lata are the characteristic mucosal lesions of secondary syphilis.1 Patchy nonscarring alopecia is not uncommon and can be the only manifestation of secondary syphilis.2 The histopathologic features of secondary syphilis vary depending on the location and type of the skin eruption. Psoriasiform or lichenoid changes commonly occur in the epidermis and dermoepidermal junction.3 The dermal inflammatory patterns that have been described include granulomatous, nodular, and superficial and deep perivascular inflammation. The infiltrate often is composed of lymphocytes, plasma cells, and histocytes. Reactive endothelial cells and perineural plasma cell infiltrates also are common histologic features.3,4 Spirochetes can be identified in most cases using immunohistochemical staining; however, the absence of spirochetes does not exclude syphilis.3 The sensitivity of immunohistochemical staining in secondary syphilis is reported to be 71% to 100% with a very high specificity.5 The treatment for all stages of syphilis is benzathine penicillin G, and the route of administration and duration of treatment depend on the stage of disease.6
A broad differential diagnosis must be considered when encountering skin eruptions in patients with HIV. Psoriasis usually presents as circumscribed erythematous plaques with dry and silvery scaling and a predilection for the extensor surfaces of the limbs, sacrum, scalp, and nails. Nail manifestations include distal onycholysis, irregular pitting, oil spots, salmon patches, and subungual hyperkeratosis. Alopecia occasionally may be seen within scalp lesions7; however, the constellation of alopecia with a moth-eaten appearance, subungual hyperkeratosis, papulosquamous eruption, and split papules was more suggestive of secondary syphilis in our patient. In immunocompromised patients, crusted scabies can be considered for the diagnosis of papulosquamous eruptions involving the palms and soles. It often presents with symmetric, mildly pruritic, psoriasiform dermatitis that favors acral sites, but widespread involvement can be observed.8 Areas of the scalp and face can be affected in infants, elderly patients, and immunocompromised individuals. Unlike in secondary syphilis, patchy alopecia, split papules, and ocular symptoms typically are not observed in scabies.
Sarcoidosis is common in Black individuals, and similar to syphilis, it is considered a great imitator of other dermatologic diseases. Frequently, it presents as redviolaceous papules, nodules, or plaques; however, rare variants including psoriasiform, ichthyosiform, verrucous, and lichenoid skin eruptions can occur. Nail dystrophy, split papules, and alopecia also have been observed.9 Ocular involvement is common and frequently presents as uveitis.10 The pathologic hallmark of sarcoidosis is noncaseating granulomatous inflammation, which also may occur in syphilitic lesions9; however, a papulosquamous eruption involving the palms and soles, positive serology, and the finding of interface lichenoid dermatitis with psoriasiform hyperplasia confirmed the diagnosis of secondary syphilis in our patient. Pityriasis rubra pilaris is a rare papulosquamous disorder that can be associated with HIV (type VI/HIVassociated follicular syndrome). It presents with generalized red-orange keratotic papules and often is associated with acne conglobata, hidradenitis suppurativa, and lichen spinulosus.11 Unlike in secondary syphilis, patchy alopecia, split papules, and ocular symptoms typically are not observed in pityriasis rubra pilaris.
This case highlights many classical findings of secondary syphilis and demonstrates that, while helpful, routine skin biopsy may not be required. Treatment should be guided by clinical presentation and serologic testing while reserving skin biopsy for equivocal cases.
- Forrestel AK, Kovarik CL, Katz KA. Sexually acquired syphilis: historical aspects, microbiology, epidemiology, and clinical manifestations. J Am Acad Dermatol. 2020;82:1-14.
- Balagula Y, Mattei PL, Wisco OJ, et al. The great imitator revisited: the spectrum of atypical cutaneous manifestations of secondary syphilis. Int J Dermatol. 2014;53:1434-1441.
- Hoang MP, High WA, Molberg KH. Secondary syphilis: a histologic and immunohistochemical evaluation. J Cutan Pathol. 2004; 31:595-599.
- Flamm A, Parikh K, Xie Q, et al. Histologic features of secondary syphilis: a multicenter retrospective review. J Am Acad Dermatol. 2015;73:1025-1030.
- Forrestel AK, Kovarik CL, Katz KA. Sexually acquired syphilis: laboratory diagnosis, management, and prevention [published online February 8, 2020]. J Am Acad Dermatol. 2020;82:17-28.
- Ghanem KG, Ram S, Rice PA. The modern epidemic of syphilis. N Engl J Med. 2020;382:845-854.
- Boehncke WH, Schön MP. Psoriasis. Lancet. 2015;386:983-994.
- Karthikeyan K. Crusted scabies. Indian J Dermatol Venereol Leprol. 2009;75:340-347.
- Haimovic A, Sanchez M, Judson MA, et al. Sarcoidosis: a comprehensive review and update for the dermatologist: part I. cutaneous disease. J Am Acad Dermatol. 2012;66:699.e1-718.
- Haimovic A, Sanchez M, Judson MA, et al. Sarcoidosis: a comprehensive review and update for the dermatologist: part II. extracutaneous disease. J Am Acad Dermatol. 2012;66:719.e1-730.
- Miralles E, Núñez M, De Las Heras M, et al. Pityriasis rubra pilaris and human immunodeficiency virus infection. Br J Dermatol. 1995;133:990-993.
- Forrestel AK, Kovarik CL, Katz KA. Sexually acquired syphilis: historical aspects, microbiology, epidemiology, and clinical manifestations. J Am Acad Dermatol. 2020;82:1-14.
- Balagula Y, Mattei PL, Wisco OJ, et al. The great imitator revisited: the spectrum of atypical cutaneous manifestations of secondary syphilis. Int J Dermatol. 2014;53:1434-1441.
- Hoang MP, High WA, Molberg KH. Secondary syphilis: a histologic and immunohistochemical evaluation. J Cutan Pathol. 2004; 31:595-599.
- Flamm A, Parikh K, Xie Q, et al. Histologic features of secondary syphilis: a multicenter retrospective review. J Am Acad Dermatol. 2015;73:1025-1030.
- Forrestel AK, Kovarik CL, Katz KA. Sexually acquired syphilis: laboratory diagnosis, management, and prevention [published online February 8, 2020]. J Am Acad Dermatol. 2020;82:17-28.
- Ghanem KG, Ram S, Rice PA. The modern epidemic of syphilis. N Engl J Med. 2020;382:845-854.
- Boehncke WH, Schön MP. Psoriasis. Lancet. 2015;386:983-994.
- Karthikeyan K. Crusted scabies. Indian J Dermatol Venereol Leprol. 2009;75:340-347.
- Haimovic A, Sanchez M, Judson MA, et al. Sarcoidosis: a comprehensive review and update for the dermatologist: part I. cutaneous disease. J Am Acad Dermatol. 2012;66:699.e1-718.
- Haimovic A, Sanchez M, Judson MA, et al. Sarcoidosis: a comprehensive review and update for the dermatologist: part II. extracutaneous disease. J Am Acad Dermatol. 2012;66:719.e1-730.
- Miralles E, Núñez M, De Las Heras M, et al. Pityriasis rubra pilaris and human immunodeficiency virus infection. Br J Dermatol. 1995;133:990-993.
A 29-year-old Black man with long-standing untreated HIV presented with mildly pruritic, scaly plaques on the palms and soles of 2 weeks’ duration. His medical history was notable for primary syphilis treated approximately 1 year prior. A review of symptoms was positive for blurry vision and floaters but negative for constitutional symptoms. Physical examination revealed well-defined scaly plaques over the palms, soles, and elbows with subungual hyperkeratosis. Patches of nonscarring alopecia over the scalp and split papules at the oral commissures also were noted. There were no palpable lymph nodes or genital involvement. Eye examination showed conjunctival injection and 20 cells per field in the vitreous humor. Laboratory evaluation revealed an HIV viral load of 31,623 copies/mL and a CD4 count of 47 cells/μL (reference range, 362–1531 cells/μL). A shave biopsy of the left elbow was performed for histopathologic evaluation.