Rheumatology News

More than 40 medical conditions were positively associated with having a new diagnosis of osteoarthritis according to research presented at the OARSI 2022 World Congress.

“Some of the associations that we have found are previously known, such as of course, obesity, which is a known risk factor, but also other musculoskeletal conditions, depression, and reflux disease,” said Anne Kamps, an MD and PhD student at Erasmus University Medical Centre in Rotterdam, the Netherlands.

“But there are also some remarkable associations that we have found that are less well known, such as liver cirrhosis, thromboembolic disease, sinusitis, allergy, and migraine,” said Dr. Kamps during her presentation at the conference, sponsored by the Osteoarthritis Research Society International.

The results are “very interesting starting points for future research, because of course, this was an explorative study,” she added. Indeed, is still not known whether the comorbidities found share the same risk factors as OA, or if they have a causal effect and add to development of osteoarthritis.
 

Comorbidity and OA

One of the issues in managing osteoarthritis so far is that it’s often addressed as one disease, commented Andrea Dell’isola, PT, PhD, a postdoctoral researcher from Lund University who was not involved in the study.

“All of the treatments that have been developed and the treatment process are tailored to take care of one single disease,” he explained. However, “when we look at the characteristics of people with osteoarthritis, we see that roughly 70% of them have other conditions on top of their joint disease.” This high comorbidity rate is significantly higher than in “healthy” people of the same age and sex, he added.

“So, this means that either there is something linked to osteoarthritis that makes people frailer and more likely to develop other diseases, or there may be links between these other diseases, that we often call comorbidities, and osteoarthritis,” Dr. Dell’isola observed.

While the work Dr. Kamps presented looked at the rate of comorbidities that existed before the diagnosis of OA, some of Dr. Dell’isola’s recent research has considered the rate of developing comorbid disease in the years following an OA diagnosis. Associations were found between having hip or knee OA and an increased risk for coexisting depression, cardiovascular diseases, back pain, osteoporosis, and, in the case of knee OA only, diabetes. “It’s interesting to see that certain diseases seem to have a bidirectional association. This means that they can both precede and follow osteoarthritis,” said Dr. Dell’isola. These are just associations, not causation, he stressed, but they might help identify people visiting a doctor for other reasons who may be at risk for developing OA.

“One of the biggest challenges is that once a person develops osteoarthritis, there is not any treatment that can really change their disease,” he added.

Perhaps, “if we can target certain conditions that increase the risk of developing osteoarthritis, and maybe convince people to exercise earlier, or undergo some lifestyle changes early on, we can maybe prevent or delay the onset of the disease,” he suggested.
 

Results and perspective

Dr. Kamps and associates performed a nested case-control study using data from a large Dutch general practice database. All new cases of OA – which included hip, knee, and other peripheral OA – that were logged between the start of 2006 and the end of 2019 were considered and matched to one to four control subjects of a similar age, sex, and type of general practice. In all, there were just under 80,000 people with newly diagnosed OA who were matched to just over 318,000 controls; the mean age in both groups was 64 years.

Of 58 comorbidities that were assessed, 42 showed a positive association with OA and had odds ratios of 1 or more. The highest associations were found for fibromyalgia (OR, 1.9), obesity (1.8), polymyalgia rheumatica (1.5), spinal disc herniation (1.4), and gout (1.4). A further 13 comorbidities had an OR of about 1, and 3 (all neuropsychiatric conditions – dementia, schizophrenia, and multiple sclerosis) had an OR of below 1.

Dr. Kamps conceded that this type of research has its limitations, the two most important being the coding behavior of the GP and the consulting behavior of patients.

“It’s known that the prevalence of osteoarthritis is underestimated if you only use the diagnostic codes, because some GPs will write the diagnosis in free text or use symptom ICPC codes,” she said.

“We have matched on general practice, so the cases and controls were from the same general practice and therefore we hope that this potential underestimation is balanced and did not affect our odds ratios.”

One of the important outcomes for this research is that it will hopefully be used to inform future clinical practice guidelines, said Dr. Dell’isola.

“Guidelines in osteoarthritis report that is important to screen for comorbidities, but they give no indication on how to deal with the presence of multimorbidity,” he added. Looking at which comorbidities may be associated with OA diagnosis could potentially help to give a bit more of a prescriptive guide on what to look out for.

“Maybe people with a certain disease profile should be screened a bit more often by their doctor. For example, if someone has their blood pressure and diabetes under control, maybe there should be also a bit more attention to their joint health and encouragement to do exercise, not only for being active per se, but maybe also to reinforce their lower limbs,” he explained.

The study was funded by the Foundation for Research in Rheumatology (FOREUM). Dr. Kamps and Dr. Dell’isola, had no conflicts of interest to disclose.
 

More than 40 medical conditions were positively associated with having a new diagnosis of osteoarthritis according to research presented at the OARSI 2022 World Congress.

“Some of the associations that we have found are previously known, such as of course, obesity, which is a known risk factor, but also other musculoskeletal conditions, depression, and reflux disease,” said Anne Kamps, an MD and PhD student at Erasmus University Medical Centre in Rotterdam, the Netherlands.

“But there are also some remarkable associations that we have found that are less well known, such as liver cirrhosis, thromboembolic disease, sinusitis, allergy, and migraine,” said Dr. Kamps during her presentation at the conference, sponsored by the Osteoarthritis Research Society International.

The results are “very interesting starting points for future research, because of course, this was an explorative study,” she added. Indeed, is still not known whether the comorbidities found share the same risk factors as OA, or if they have a causal effect and add to development of osteoarthritis.
 

Comorbidity and OA

One of the issues in managing osteoarthritis so far is that it’s often addressed as one disease, commented Andrea Dell’isola, PT, PhD, a postdoctoral researcher from Lund University who was not involved in the study.

“All of the treatments that have been developed and the treatment process are tailored to take care of one single disease,” he explained. However, “when we look at the characteristics of people with osteoarthritis, we see that roughly 70% of them have other conditions on top of their joint disease.” This high comorbidity rate is significantly higher than in “healthy” people of the same age and sex, he added.

“So, this means that either there is something linked to osteoarthritis that makes people frailer and more likely to develop other diseases, or there may be links between these other diseases, that we often call comorbidities, and osteoarthritis,” Dr. Dell’isola observed.

While the work Dr. Kamps presented looked at the rate of comorbidities that existed before the diagnosis of OA, some of Dr. Dell’isola’s recent research has considered the rate of developing comorbid disease in the years following an OA diagnosis. Associations were found between having hip or knee OA and an increased risk for coexisting depression, cardiovascular diseases, back pain, osteoporosis, and, in the case of knee OA only, diabetes. “It’s interesting to see that certain diseases seem to have a bidirectional association. This means that they can both precede and follow osteoarthritis,” said Dr. Dell’isola. These are just associations, not causation, he stressed, but they might help identify people visiting a doctor for other reasons who may be at risk for developing OA.

“One of the biggest challenges is that once a person develops osteoarthritis, there is not any treatment that can really change their disease,” he added.

Perhaps, “if we can target certain conditions that increase the risk of developing osteoarthritis, and maybe convince people to exercise earlier, or undergo some lifestyle changes early on, we can maybe prevent or delay the onset of the disease,” he suggested.
 

Results and perspective

Dr. Kamps and associates performed a nested case-control study using data from a large Dutch general practice database. All new cases of OA – which included hip, knee, and other peripheral OA – that were logged between the start of 2006 and the end of 2019 were considered and matched to one to four control subjects of a similar age, sex, and type of general practice. In all, there were just under 80,000 people with newly diagnosed OA who were matched to just over 318,000 controls; the mean age in both groups was 64 years.

Of 58 comorbidities that were assessed, 42 showed a positive association with OA and had odds ratios of 1 or more. The highest associations were found for fibromyalgia (OR, 1.9), obesity (1.8), polymyalgia rheumatica (1.5), spinal disc herniation (1.4), and gout (1.4). A further 13 comorbidities had an OR of about 1, and 3 (all neuropsychiatric conditions – dementia, schizophrenia, and multiple sclerosis) had an OR of below 1.

Dr. Kamps conceded that this type of research has its limitations, the two most important being the coding behavior of the GP and the consulting behavior of patients.

“It’s known that the prevalence of osteoarthritis is underestimated if you only use the diagnostic codes, because some GPs will write the diagnosis in free text or use symptom ICPC codes,” she said.

“We have matched on general practice, so the cases and controls were from the same general practice and therefore we hope that this potential underestimation is balanced and did not affect our odds ratios.”

One of the important outcomes for this research is that it will hopefully be used to inform future clinical practice guidelines, said Dr. Dell’isola.

“Guidelines in osteoarthritis report that is important to screen for comorbidities, but they give no indication on how to deal with the presence of multimorbidity,” he added. Looking at which comorbidities may be associated with OA diagnosis could potentially help to give a bit more of a prescriptive guide on what to look out for.

“Maybe people with a certain disease profile should be screened a bit more often by their doctor. For example, if someone has their blood pressure and diabetes under control, maybe there should be also a bit more attention to their joint health and encouragement to do exercise, not only for being active per se, but maybe also to reinforce their lower limbs,” he explained.

The study was funded by the Foundation for Research in Rheumatology (FOREUM). Dr. Kamps and Dr. Dell’isola, had no conflicts of interest to disclose.
 

More than 40 medical conditions were positively associated with having a new diagnosis of osteoarthritis according to research presented at the OARSI 2022 World Congress.

“Some of the associations that we have found are previously known, such as of course, obesity, which is a known risk factor, but also other musculoskeletal conditions, depression, and reflux disease,” said Anne Kamps, an MD and PhD student at Erasmus University Medical Centre in Rotterdam, the Netherlands.

“But there are also some remarkable associations that we have found that are less well known, such as liver cirrhosis, thromboembolic disease, sinusitis, allergy, and migraine,” said Dr. Kamps during her presentation at the conference, sponsored by the Osteoarthritis Research Society International.

The results are “very interesting starting points for future research, because of course, this was an explorative study,” she added. Indeed, is still not known whether the comorbidities found share the same risk factors as OA, or if they have a causal effect and add to development of osteoarthritis.
 

Comorbidity and OA

One of the issues in managing osteoarthritis so far is that it’s often addressed as one disease, commented Andrea Dell’isola, PT, PhD, a postdoctoral researcher from Lund University who was not involved in the study.

“All of the treatments that have been developed and the treatment process are tailored to take care of one single disease,” he explained. However, “when we look at the characteristics of people with osteoarthritis, we see that roughly 70% of them have other conditions on top of their joint disease.” This high comorbidity rate is significantly higher than in “healthy” people of the same age and sex, he added.

“So, this means that either there is something linked to osteoarthritis that makes people frailer and more likely to develop other diseases, or there may be links between these other diseases, that we often call comorbidities, and osteoarthritis,” Dr. Dell’isola observed.

While the work Dr. Kamps presented looked at the rate of comorbidities that existed before the diagnosis of OA, some of Dr. Dell’isola’s recent research has considered the rate of developing comorbid disease in the years following an OA diagnosis. Associations were found between having hip or knee OA and an increased risk for coexisting depression, cardiovascular diseases, back pain, osteoporosis, and, in the case of knee OA only, diabetes. “It’s interesting to see that certain diseases seem to have a bidirectional association. This means that they can both precede and follow osteoarthritis,” said Dr. Dell’isola. These are just associations, not causation, he stressed, but they might help identify people visiting a doctor for other reasons who may be at risk for developing OA.

“One of the biggest challenges is that once a person develops osteoarthritis, there is not any treatment that can really change their disease,” he added.

Perhaps, “if we can target certain conditions that increase the risk of developing osteoarthritis, and maybe convince people to exercise earlier, or undergo some lifestyle changes early on, we can maybe prevent or delay the onset of the disease,” he suggested.
 

Results and perspective

Dr. Kamps and associates performed a nested case-control study using data from a large Dutch general practice database. All new cases of OA – which included hip, knee, and other peripheral OA – that were logged between the start of 2006 and the end of 2019 were considered and matched to one to four control subjects of a similar age, sex, and type of general practice. In all, there were just under 80,000 people with newly diagnosed OA who were matched to just over 318,000 controls; the mean age in both groups was 64 years.

Of 58 comorbidities that were assessed, 42 showed a positive association with OA and had odds ratios of 1 or more. The highest associations were found for fibromyalgia (OR, 1.9), obesity (1.8), polymyalgia rheumatica (1.5), spinal disc herniation (1.4), and gout (1.4). A further 13 comorbidities had an OR of about 1, and 3 (all neuropsychiatric conditions – dementia, schizophrenia, and multiple sclerosis) had an OR of below 1.

Dr. Kamps conceded that this type of research has its limitations, the two most important being the coding behavior of the GP and the consulting behavior of patients.

“It’s known that the prevalence of osteoarthritis is underestimated if you only use the diagnostic codes, because some GPs will write the diagnosis in free text or use symptom ICPC codes,” she said.

“We have matched on general practice, so the cases and controls were from the same general practice and therefore we hope that this potential underestimation is balanced and did not affect our odds ratios.”

One of the important outcomes for this research is that it will hopefully be used to inform future clinical practice guidelines, said Dr. Dell’isola.

“Guidelines in osteoarthritis report that is important to screen for comorbidities, but they give no indication on how to deal with the presence of multimorbidity,” he added. Looking at which comorbidities may be associated with OA diagnosis could potentially help to give a bit more of a prescriptive guide on what to look out for.

“Maybe people with a certain disease profile should be screened a bit more often by their doctor. For example, if someone has their blood pressure and diabetes under control, maybe there should be also a bit more attention to their joint health and encouragement to do exercise, not only for being active per se, but maybe also to reinforce their lower limbs,” he explained.

The study was funded by the Foundation for Research in Rheumatology (FOREUM). Dr. Kamps and Dr. Dell’isola, had no conflicts of interest to disclose.
 

Patients with COVID-19, especially those with an altered sense of smell, have significantly more axon and microvasculopathy damage in the brain’s olfactory tissue versus non-COVID patients. These new findings from a postmortem study may explain long-term loss of smell in some patients with the virus.

“The striking axonal pathology in some cases indicates that olfactory dysfunction in COVID-19 may be severe and permanent,” the investigators led by Cheng-Ying Ho, MD, PhD, associate professor, department of pathology, Johns Hopkins University School of Medicine, Baltimore, write.

“The results show the damage caused by COVID can extend beyond the nasal cavity and involve the brain,” Dr. Ho told this news organization.

The study was published online April 11 in JAMA Neurology.
 

A more thorough investigation

Patients infected with SARS-CoV-2, which causes COVID-19, present with a wide range of symptoms. In addition to respiratory illnesses, they may exhibit various nonrespiratory manifestations of COVID-19.

One of the most prevalent of these is olfactory dysfunction. Research shows such dysfunction, including anosmia (loss of smell), hyposmia (reduced sense of smell), and parosmia (smells that are distorted or unpleasant), affects 30%-60% of patients with COVID-19, said Dr. Ho.

However, these statistics come from research before the advent of the Omicron variant, which evidence suggests causes less smell loss in patients with COVID, she said.

Previous studies in this area mainly focused on the lining of the nasal cavity. “We wanted to go a step beyond to see how the olfactory bulb was affected by COVID infection,” said Dr. Ho.

The study included 23 deceased patients with confirmed COVID-19 ranging in age from 28 to 93 years at death (median 62 years, 60.9% men). It also included 14 controls who tested negative for COVID-19, ranging in age from 20 to 77 years (median 53.5 years, 50% men).

Researchers collected postmortem tissue from the brain, lung, and other organs and reviewed pertinent clinical information.

Most patients with COVID died of COVID pneumonia or related complications, although some died from a different cause. Some had an active COVID infection and others were “post infection, meaning they were in the recovery stage,” said Dr. Ho.

Six patients with COVID-19 and eight controls had significant brain pathology.

Compared with controls, those with COVID-19 showed significantly worse olfactory axonal damage. The mean axon pathology score (range 1-3 with 3 the worst) was 1.921 in patients with COVID-19 and 1.198 in controls (95% confidence interval, 0.444-1.002; P < .001).

The mean axon density in the lateral olfactory tract was significantly less in patients with COVID-19 than in controls (P = .002), indicating a 23% loss of olfactory axons in the COVID group.

Comparing COVID patients with and without reported loss of smell, researchers found those with an altered sense of smell had significantly more severe olfactory axon pathology.
 

Vascular damage

Patients with COVID also had worse vascular damage. The mean microvasculopathy score (range, 1-3) was 1.907 in patients with COVID-19 and 1.405 in controls (95% CI, 0.259-0.745; P < .001).

There was no evidence of the virus in the olfactory tissue of most patients, suggesting the olfactory pathology was likely caused by vascular damage, said Dr. Ho.

What’s unique about SARS-CoV-2 is that, although it’s a respiratory virus, it’s capable of infecting endothelial cells lining vessels.

“Other respiratory viruses only attack the airways and won’t attack vessels, but vascular damage has been seen in the heart and lung in COVID patients, and our study showed the same findings in the olfactory bulb,” Dr. Ho explained.

The researchers divided patients with COVID by infection severity: mild, moderate, severe, and critical. Interestingly, those with the most severe olfactory pathology were the ones with milder infections, said Dr. Ho.

She noted other studies have reported patients with mild infection are more likely to lose the sense of smell than those with severe infection, but she’s skeptical about this finding.

“Patients with severe COVID are usually hospitalized and intubated, so it’s hard to get them to tell you whether they’ve lost smell or not; they have other more important issues to deal with like respiratory failure,” said Dr. Ho.

Advanced age is associated with neuropathologic changes, such as tau deposits, so the researchers conducted an analysis factoring in age-related brain changes. They found a COVID-19 diagnosis remained associated with increased axonal pathology, reduced axonal density, and increased vascular pathology.

“This means that the COVID patients had more severe olfactory pathology not just because they had more tau pathology,” Dr. Ho added.
 

New guidance for patients

Commenting for this news organization, Davangere P. Devanand, MD, professor of psychiatry and neurology and director of geriatric psychiatry, Columbia University Irving Medical Center, New York, said the findings indicate the damage from COVID in the olfactory pathway may not be reversible as was previously thought.

“This has been suggested before as a possibility, but the autopsy findings in this case series indicate clearly that there may be permanent damage,” he said.

The results highlight the need to monitor patients with COVID for a smell deficit, said Dr. Devanand. 

“Assuring patients of a full recovery in smell and taste may not be sound advice, although recovery does occur in many patients,” he added.

He praised the study design, especially the blinding of raters, but noted a number of weaknesses, including the small sample size and the age and gender discrepancies between the groups.

Another possible limitation was inclusion of patients with Alzheimer’s and Lewy body pathology, said Dr. Devanand.

“These patients typically already have pathology in the olfactory pathways, which means we don’t know if it was COVID or the underlying brain pathology contributing to smell difficulties in these patients,” he said.

He noted that, unlike deceased COVID cases in the study, patients who survive COVID may not experience axonal and microvascular injury in olfactory neurons and pathways and their sense of smell may make a full return.

Dr. Devanand said he would have liked more detailed information on the clinical history and course of study participants and whether these factors affected the pathology findings.

The study was supported by grants from the National Institutes of Health.

Dr. Ho and Dr. Devanand have reported no relevant financial disclosures.

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

Patients with COVID-19, especially those with an altered sense of smell, have significantly more axon and microvasculopathy damage in the brain’s olfactory tissue versus non-COVID patients. These new findings from a postmortem study may explain long-term loss of smell in some patients with the virus.

“The striking axonal pathology in some cases indicates that olfactory dysfunction in COVID-19 may be severe and permanent,” the investigators led by Cheng-Ying Ho, MD, PhD, associate professor, department of pathology, Johns Hopkins University School of Medicine, Baltimore, write.

“The results show the damage caused by COVID can extend beyond the nasal cavity and involve the brain,” Dr. Ho told this news organization.

The study was published online April 11 in JAMA Neurology.
 

A more thorough investigation

Patients infected with SARS-CoV-2, which causes COVID-19, present with a wide range of symptoms. In addition to respiratory illnesses, they may exhibit various nonrespiratory manifestations of COVID-19.

One of the most prevalent of these is olfactory dysfunction. Research shows such dysfunction, including anosmia (loss of smell), hyposmia (reduced sense of smell), and parosmia (smells that are distorted or unpleasant), affects 30%-60% of patients with COVID-19, said Dr. Ho.

However, these statistics come from research before the advent of the Omicron variant, which evidence suggests causes less smell loss in patients with COVID, she said.

Previous studies in this area mainly focused on the lining of the nasal cavity. “We wanted to go a step beyond to see how the olfactory bulb was affected by COVID infection,” said Dr. Ho.

The study included 23 deceased patients with confirmed COVID-19 ranging in age from 28 to 93 years at death (median 62 years, 60.9% men). It also included 14 controls who tested negative for COVID-19, ranging in age from 20 to 77 years (median 53.5 years, 50% men).

Researchers collected postmortem tissue from the brain, lung, and other organs and reviewed pertinent clinical information.

Most patients with COVID died of COVID pneumonia or related complications, although some died from a different cause. Some had an active COVID infection and others were “post infection, meaning they were in the recovery stage,” said Dr. Ho.

Six patients with COVID-19 and eight controls had significant brain pathology.

Compared with controls, those with COVID-19 showed significantly worse olfactory axonal damage. The mean axon pathology score (range 1-3 with 3 the worst) was 1.921 in patients with COVID-19 and 1.198 in controls (95% confidence interval, 0.444-1.002; P < .001).

The mean axon density in the lateral olfactory tract was significantly less in patients with COVID-19 than in controls (P = .002), indicating a 23% loss of olfactory axons in the COVID group.

Comparing COVID patients with and without reported loss of smell, researchers found those with an altered sense of smell had significantly more severe olfactory axon pathology.
 

Vascular damage

Patients with COVID also had worse vascular damage. The mean microvasculopathy score (range, 1-3) was 1.907 in patients with COVID-19 and 1.405 in controls (95% CI, 0.259-0.745; P < .001).

There was no evidence of the virus in the olfactory tissue of most patients, suggesting the olfactory pathology was likely caused by vascular damage, said Dr. Ho.

What’s unique about SARS-CoV-2 is that, although it’s a respiratory virus, it’s capable of infecting endothelial cells lining vessels.

“Other respiratory viruses only attack the airways and won’t attack vessels, but vascular damage has been seen in the heart and lung in COVID patients, and our study showed the same findings in the olfactory bulb,” Dr. Ho explained.

The researchers divided patients with COVID by infection severity: mild, moderate, severe, and critical. Interestingly, those with the most severe olfactory pathology were the ones with milder infections, said Dr. Ho.

She noted other studies have reported patients with mild infection are more likely to lose the sense of smell than those with severe infection, but she’s skeptical about this finding.

“Patients with severe COVID are usually hospitalized and intubated, so it’s hard to get them to tell you whether they’ve lost smell or not; they have other more important issues to deal with like respiratory failure,” said Dr. Ho.

Advanced age is associated with neuropathologic changes, such as tau deposits, so the researchers conducted an analysis factoring in age-related brain changes. They found a COVID-19 diagnosis remained associated with increased axonal pathology, reduced axonal density, and increased vascular pathology.

“This means that the COVID patients had more severe olfactory pathology not just because they had more tau pathology,” Dr. Ho added.
 

New guidance for patients

Commenting for this news organization, Davangere P. Devanand, MD, professor of psychiatry and neurology and director of geriatric psychiatry, Columbia University Irving Medical Center, New York, said the findings indicate the damage from COVID in the olfactory pathway may not be reversible as was previously thought.

“This has been suggested before as a possibility, but the autopsy findings in this case series indicate clearly that there may be permanent damage,” he said.

The results highlight the need to monitor patients with COVID for a smell deficit, said Dr. Devanand. 

“Assuring patients of a full recovery in smell and taste may not be sound advice, although recovery does occur in many patients,” he added.

He praised the study design, especially the blinding of raters, but noted a number of weaknesses, including the small sample size and the age and gender discrepancies between the groups.

Another possible limitation was inclusion of patients with Alzheimer’s and Lewy body pathology, said Dr. Devanand.

“These patients typically already have pathology in the olfactory pathways, which means we don’t know if it was COVID or the underlying brain pathology contributing to smell difficulties in these patients,” he said.

He noted that, unlike deceased COVID cases in the study, patients who survive COVID may not experience axonal and microvascular injury in olfactory neurons and pathways and their sense of smell may make a full return.

Dr. Devanand said he would have liked more detailed information on the clinical history and course of study participants and whether these factors affected the pathology findings.

The study was supported by grants from the National Institutes of Health.

Dr. Ho and Dr. Devanand have reported no relevant financial disclosures.

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

Patients with COVID-19, especially those with an altered sense of smell, have significantly more axon and microvasculopathy damage in the brain’s olfactory tissue versus non-COVID patients. These new findings from a postmortem study may explain long-term loss of smell in some patients with the virus.

“The striking axonal pathology in some cases indicates that olfactory dysfunction in COVID-19 may be severe and permanent,” the investigators led by Cheng-Ying Ho, MD, PhD, associate professor, department of pathology, Johns Hopkins University School of Medicine, Baltimore, write.

“The results show the damage caused by COVID can extend beyond the nasal cavity and involve the brain,” Dr. Ho told this news organization.

The study was published online April 11 in JAMA Neurology.
 

A more thorough investigation

Patients infected with SARS-CoV-2, which causes COVID-19, present with a wide range of symptoms. In addition to respiratory illnesses, they may exhibit various nonrespiratory manifestations of COVID-19.

One of the most prevalent of these is olfactory dysfunction. Research shows such dysfunction, including anosmia (loss of smell), hyposmia (reduced sense of smell), and parosmia (smells that are distorted or unpleasant), affects 30%-60% of patients with COVID-19, said Dr. Ho.

However, these statistics come from research before the advent of the Omicron variant, which evidence suggests causes less smell loss in patients with COVID, she said.

Previous studies in this area mainly focused on the lining of the nasal cavity. “We wanted to go a step beyond to see how the olfactory bulb was affected by COVID infection,” said Dr. Ho.

The study included 23 deceased patients with confirmed COVID-19 ranging in age from 28 to 93 years at death (median 62 years, 60.9% men). It also included 14 controls who tested negative for COVID-19, ranging in age from 20 to 77 years (median 53.5 years, 50% men).

Researchers collected postmortem tissue from the brain, lung, and other organs and reviewed pertinent clinical information.

Most patients with COVID died of COVID pneumonia or related complications, although some died from a different cause. Some had an active COVID infection and others were “post infection, meaning they were in the recovery stage,” said Dr. Ho.

Six patients with COVID-19 and eight controls had significant brain pathology.

Compared with controls, those with COVID-19 showed significantly worse olfactory axonal damage. The mean axon pathology score (range 1-3 with 3 the worst) was 1.921 in patients with COVID-19 and 1.198 in controls (95% confidence interval, 0.444-1.002; P < .001).

The mean axon density in the lateral olfactory tract was significantly less in patients with COVID-19 than in controls (P = .002), indicating a 23% loss of olfactory axons in the COVID group.

Comparing COVID patients with and without reported loss of smell, researchers found those with an altered sense of smell had significantly more severe olfactory axon pathology.
 

Vascular damage

Patients with COVID also had worse vascular damage. The mean microvasculopathy score (range, 1-3) was 1.907 in patients with COVID-19 and 1.405 in controls (95% CI, 0.259-0.745; P < .001).

There was no evidence of the virus in the olfactory tissue of most patients, suggesting the olfactory pathology was likely caused by vascular damage, said Dr. Ho.

What’s unique about SARS-CoV-2 is that, although it’s a respiratory virus, it’s capable of infecting endothelial cells lining vessels.

“Other respiratory viruses only attack the airways and won’t attack vessels, but vascular damage has been seen in the heart and lung in COVID patients, and our study showed the same findings in the olfactory bulb,” Dr. Ho explained.

The researchers divided patients with COVID by infection severity: mild, moderate, severe, and critical. Interestingly, those with the most severe olfactory pathology were the ones with milder infections, said Dr. Ho.

She noted other studies have reported patients with mild infection are more likely to lose the sense of smell than those with severe infection, but she’s skeptical about this finding.

“Patients with severe COVID are usually hospitalized and intubated, so it’s hard to get them to tell you whether they’ve lost smell or not; they have other more important issues to deal with like respiratory failure,” said Dr. Ho.

Advanced age is associated with neuropathologic changes, such as tau deposits, so the researchers conducted an analysis factoring in age-related brain changes. They found a COVID-19 diagnosis remained associated with increased axonal pathology, reduced axonal density, and increased vascular pathology.

“This means that the COVID patients had more severe olfactory pathology not just because they had more tau pathology,” Dr. Ho added.
 

New guidance for patients

Commenting for this news organization, Davangere P. Devanand, MD, professor of psychiatry and neurology and director of geriatric psychiatry, Columbia University Irving Medical Center, New York, said the findings indicate the damage from COVID in the olfactory pathway may not be reversible as was previously thought.

“This has been suggested before as a possibility, but the autopsy findings in this case series indicate clearly that there may be permanent damage,” he said.

The results highlight the need to monitor patients with COVID for a smell deficit, said Dr. Devanand. 

“Assuring patients of a full recovery in smell and taste may not be sound advice, although recovery does occur in many patients,” he added.

He praised the study design, especially the blinding of raters, but noted a number of weaknesses, including the small sample size and the age and gender discrepancies between the groups.

Another possible limitation was inclusion of patients with Alzheimer’s and Lewy body pathology, said Dr. Devanand.

“These patients typically already have pathology in the olfactory pathways, which means we don’t know if it was COVID or the underlying brain pathology contributing to smell difficulties in these patients,” he said.

He noted that, unlike deceased COVID cases in the study, patients who survive COVID may not experience axonal and microvascular injury in olfactory neurons and pathways and their sense of smell may make a full return.

Dr. Devanand said he would have liked more detailed information on the clinical history and course of study participants and whether these factors affected the pathology findings.

The study was supported by grants from the National Institutes of Health.

Dr. Ho and Dr. Devanand have reported no relevant financial disclosures.

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

The vast majority of children and young people with rheumatic and musculoskeletal diseases (RMDs) and COVID-19 are not hospitalized, according to the most significant global investigation of short-term COVID-19 outcomes in this patient group to date.

In the study, only 1 in 15 (7%) children and young people (younger than 19 years) with RMDs and COVID-19 were hospitalized, and even then, they experienced only mild symptoms; 4 of 5 of those hospitalized did not require supplemental oxygen or ventilatory support.

The study also found that those with severe systemic RMDs and obesity were more likely to be hospitalized than children with juvenile idiopathic arthritis (JIA).

Treatment with biologics, such as tumor necrosis factor inhibitors, did not appear to be associated with more severe COVID-19; however, the study found that children and young people with obesity (body mass index ≥ 30) were more likely to be hospitalized, although only 6% of patients in this study had a BMI in this category. Three patients died – two from areas of lower resources who were diagnosed with systemic lupus erythematosus (SLE) at approximately the same time they were diagnosed with COVID-19, and one with a preexisting autoinflammatory syndrome who was being treated with low-dose glucocorticoids and methotrexate.

Published in Annals of the Rheumatic Diseases, the study was led by Kimme L. Hyrich, MD, PhD, and Lianne Kearsley-Fleet, PhD, both from the University of Manchester (England). Dr. Hyrich is also a consultant rheumatologist at Manchester University Hospitals NHS Foundation Trust.

In an interview, Dr. Hyrich explained that overall these data are reassuring and show that the majority of children and young people with RMDs are not at high risk of severe COVID-19.

“Many parents and families with children who have RMDs have lived with great fear over the pandemic about whether or not their children are at an increased risk of severe COVID-19,” said Dr. Hyrich. “Many are immunosuppressed or take other immunomodulatory medications. This has also had a great impact on schooling and children’s well-being.”

In the study, children with SLE, mixed connective tissue disease (MCTD), or vasculitis were more likely to have severe COVID-19. “[This] is not surprising given the typically greater systemic involvement and need for more aggressive immunosuppressive therapy than the majority of individuals with JIA,” the researchers wrote.

Dr. Hyrich added: “There may be times when children are on particularly high doses of immunosuppression or their disease is particularly active, when they may need more protection, and rheumatology teams can advise parents and young people about this.”

Studies such as those by Zimmerman and Curtis and Viner and colleagues have found that generally, children with no underlying disease are less susceptible to symptomatic COVID-19 and that reports of death are rare. Findings show that the younger the child, the less likely they will be symptomatic.

Adult data suggest a higher risk of COVID-related death among patients with arthritis, lupus, or psoriasis. A recent systematic review of the literature suggested that increased risk of COVID-related death only applies to subgroups of people with RMDs.

However, whether children and young people with RMDs are likely to have more severe COVID-19 and whether there is additional risk attributable to either their underlying disease or its therapy remain unknown. The goal of the study by Dr. Hyrich and colleagues was to address these questions.

The global analysis aimed to describe characteristics of those children and young people (younger than 19 years) with preexisting RMDs who also had COVID-19; to describe outcomes following COVID-19; and to identify characteristics associated with more severe COVID-19 outcomes.

Data were drawn from the European Alliance of Associations for Rheumatology COVID-19 Registry, the Childhood Arthritis and Rheumatology Research Alliance Registry, and the CARRA-sponsored COVID-19 Global Paediatric Rheumatology Database.

Demographic information included primary RMD diagnosis; RMD disease activity (remission, low, moderate, high, or unknown); RMD treatments, including glucocorticoid use and which disease-modifying antirheumatic drug (DMARD) the patient was taking at the time of COVID-19; and comorbidities (none, ocular inflammation, interstitial lung disease, asthma, diabetes, obesity, hypertension, cerebrovascular accident, renal disease, inflammatory bowel disease, and heart disease).

With respect to COVID-19, information collected included diagnosis date, whether the case was presumptive or confirmed, clinical symptoms, hospitalization and/or death because of COVID-19, and whether the patient stopped receiving rheumatic therapies.

Rheumatology diagnoses were categorized into four groups: JIA; SLE, MCTD, vasculitis, or other RMD; autoinflammatory syndromes; and “other,” including chronic recurrent multifocal osteomyelitis, sarcoidosis, or ocular inflammation.

Of the 607 children and young people with reported SARS-CoV-2 infection from 25 different countries (464 from the EULAR COVID-19 Registry), 499 (82%) cases were polymerase chain reaction confirmed, and 399 (66%) patients were female (median age, 14 years). Most (62%) had JIA: 37%, polyarticular JIA; 30%, oligoarticular JIA; 12%, enthesitis-related JIA; 9%, systemic JIA; 4%, psoriatic JIA; and 9%, JIA of unknown subcategory. Furthermore, 13% of patients had autoinflammatory syndromes, 8% with SLE or MCTD, 3% with vasculitis, and 2% with inflammatory myopathy.

No associations were seen between DMARD treatment (conventional-synthetic, biologic/targeted-synthetic, or combination therapy), compared with no DMARD treatment, glucocorticoid use, and hospitalization.

Owing to substantial differences in reporting of race and ethnicity between data sources, the researchers were unable to analyze whether Black, Asian, and minority ethnic groups with pediatric RMDs are at higher risk of COVID-19–related death, compared with those of White ethnicity, as has been reported for the general population.

The study also did not account for variants of SARS-CoV-2 other than to note that data were collected prior to the spread of the Omicron variant. Also, the registries did not capture vaccination status (though very few children had received vaccines at the time of data collection) or information on long COVID or multisystem inflammatory syndrome in children.

Dr. Hyrich and Dr. Kearsley-Fleet have disclosed no relevant financial relationships.

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

The vast majority of children and young people with rheumatic and musculoskeletal diseases (RMDs) and COVID-19 are not hospitalized, according to the most significant global investigation of short-term COVID-19 outcomes in this patient group to date.

In the study, only 1 in 15 (7%) children and young people (younger than 19 years) with RMDs and COVID-19 were hospitalized, and even then, they experienced only mild symptoms; 4 of 5 of those hospitalized did not require supplemental oxygen or ventilatory support.

The study also found that those with severe systemic RMDs and obesity were more likely to be hospitalized than children with juvenile idiopathic arthritis (JIA).

Treatment with biologics, such as tumor necrosis factor inhibitors, did not appear to be associated with more severe COVID-19; however, the study found that children and young people with obesity (body mass index ≥ 30) were more likely to be hospitalized, although only 6% of patients in this study had a BMI in this category. Three patients died – two from areas of lower resources who were diagnosed with systemic lupus erythematosus (SLE) at approximately the same time they were diagnosed with COVID-19, and one with a preexisting autoinflammatory syndrome who was being treated with low-dose glucocorticoids and methotrexate.

Published in Annals of the Rheumatic Diseases, the study was led by Kimme L. Hyrich, MD, PhD, and Lianne Kearsley-Fleet, PhD, both from the University of Manchester (England). Dr. Hyrich is also a consultant rheumatologist at Manchester University Hospitals NHS Foundation Trust.

In an interview, Dr. Hyrich explained that overall these data are reassuring and show that the majority of children and young people with RMDs are not at high risk of severe COVID-19.

“Many parents and families with children who have RMDs have lived with great fear over the pandemic about whether or not their children are at an increased risk of severe COVID-19,” said Dr. Hyrich. “Many are immunosuppressed or take other immunomodulatory medications. This has also had a great impact on schooling and children’s well-being.”

In the study, children with SLE, mixed connective tissue disease (MCTD), or vasculitis were more likely to have severe COVID-19. “[This] is not surprising given the typically greater systemic involvement and need for more aggressive immunosuppressive therapy than the majority of individuals with JIA,” the researchers wrote.

Dr. Hyrich added: “There may be times when children are on particularly high doses of immunosuppression or their disease is particularly active, when they may need more protection, and rheumatology teams can advise parents and young people about this.”

Studies such as those by Zimmerman and Curtis and Viner and colleagues have found that generally, children with no underlying disease are less susceptible to symptomatic COVID-19 and that reports of death are rare. Findings show that the younger the child, the less likely they will be symptomatic.

Adult data suggest a higher risk of COVID-related death among patients with arthritis, lupus, or psoriasis. A recent systematic review of the literature suggested that increased risk of COVID-related death only applies to subgroups of people with RMDs.

However, whether children and young people with RMDs are likely to have more severe COVID-19 and whether there is additional risk attributable to either their underlying disease or its therapy remain unknown. The goal of the study by Dr. Hyrich and colleagues was to address these questions.

The global analysis aimed to describe characteristics of those children and young people (younger than 19 years) with preexisting RMDs who also had COVID-19; to describe outcomes following COVID-19; and to identify characteristics associated with more severe COVID-19 outcomes.

Data were drawn from the European Alliance of Associations for Rheumatology COVID-19 Registry, the Childhood Arthritis and Rheumatology Research Alliance Registry, and the CARRA-sponsored COVID-19 Global Paediatric Rheumatology Database.

Demographic information included primary RMD diagnosis; RMD disease activity (remission, low, moderate, high, or unknown); RMD treatments, including glucocorticoid use and which disease-modifying antirheumatic drug (DMARD) the patient was taking at the time of COVID-19; and comorbidities (none, ocular inflammation, interstitial lung disease, asthma, diabetes, obesity, hypertension, cerebrovascular accident, renal disease, inflammatory bowel disease, and heart disease).

With respect to COVID-19, information collected included diagnosis date, whether the case was presumptive or confirmed, clinical symptoms, hospitalization and/or death because of COVID-19, and whether the patient stopped receiving rheumatic therapies.

Rheumatology diagnoses were categorized into four groups: JIA; SLE, MCTD, vasculitis, or other RMD; autoinflammatory syndromes; and “other,” including chronic recurrent multifocal osteomyelitis, sarcoidosis, or ocular inflammation.

Of the 607 children and young people with reported SARS-CoV-2 infection from 25 different countries (464 from the EULAR COVID-19 Registry), 499 (82%) cases were polymerase chain reaction confirmed, and 399 (66%) patients were female (median age, 14 years). Most (62%) had JIA: 37%, polyarticular JIA; 30%, oligoarticular JIA; 12%, enthesitis-related JIA; 9%, systemic JIA; 4%, psoriatic JIA; and 9%, JIA of unknown subcategory. Furthermore, 13% of patients had autoinflammatory syndromes, 8% with SLE or MCTD, 3% with vasculitis, and 2% with inflammatory myopathy.

No associations were seen between DMARD treatment (conventional-synthetic, biologic/targeted-synthetic, or combination therapy), compared with no DMARD treatment, glucocorticoid use, and hospitalization.

Owing to substantial differences in reporting of race and ethnicity between data sources, the researchers were unable to analyze whether Black, Asian, and minority ethnic groups with pediatric RMDs are at higher risk of COVID-19–related death, compared with those of White ethnicity, as has been reported for the general population.

The study also did not account for variants of SARS-CoV-2 other than to note that data were collected prior to the spread of the Omicron variant. Also, the registries did not capture vaccination status (though very few children had received vaccines at the time of data collection) or information on long COVID or multisystem inflammatory syndrome in children.

Dr. Hyrich and Dr. Kearsley-Fleet have disclosed no relevant financial relationships.

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

The vast majority of children and young people with rheumatic and musculoskeletal diseases (RMDs) and COVID-19 are not hospitalized, according to the most significant global investigation of short-term COVID-19 outcomes in this patient group to date.

In the study, only 1 in 15 (7%) children and young people (younger than 19 years) with RMDs and COVID-19 were hospitalized, and even then, they experienced only mild symptoms; 4 of 5 of those hospitalized did not require supplemental oxygen or ventilatory support.

The study also found that those with severe systemic RMDs and obesity were more likely to be hospitalized than children with juvenile idiopathic arthritis (JIA).

Treatment with biologics, such as tumor necrosis factor inhibitors, did not appear to be associated with more severe COVID-19; however, the study found that children and young people with obesity (body mass index ≥ 30) were more likely to be hospitalized, although only 6% of patients in this study had a BMI in this category. Three patients died – two from areas of lower resources who were diagnosed with systemic lupus erythematosus (SLE) at approximately the same time they were diagnosed with COVID-19, and one with a preexisting autoinflammatory syndrome who was being treated with low-dose glucocorticoids and methotrexate.

Published in Annals of the Rheumatic Diseases, the study was led by Kimme L. Hyrich, MD, PhD, and Lianne Kearsley-Fleet, PhD, both from the University of Manchester (England). Dr. Hyrich is also a consultant rheumatologist at Manchester University Hospitals NHS Foundation Trust.

In an interview, Dr. Hyrich explained that overall these data are reassuring and show that the majority of children and young people with RMDs are not at high risk of severe COVID-19.

“Many parents and families with children who have RMDs have lived with great fear over the pandemic about whether or not their children are at an increased risk of severe COVID-19,” said Dr. Hyrich. “Many are immunosuppressed or take other immunomodulatory medications. This has also had a great impact on schooling and children’s well-being.”

In the study, children with SLE, mixed connective tissue disease (MCTD), or vasculitis were more likely to have severe COVID-19. “[This] is not surprising given the typically greater systemic involvement and need for more aggressive immunosuppressive therapy than the majority of individuals with JIA,” the researchers wrote.

Dr. Hyrich added: “There may be times when children are on particularly high doses of immunosuppression or their disease is particularly active, when they may need more protection, and rheumatology teams can advise parents and young people about this.”

Studies such as those by Zimmerman and Curtis and Viner and colleagues have found that generally, children with no underlying disease are less susceptible to symptomatic COVID-19 and that reports of death are rare. Findings show that the younger the child, the less likely they will be symptomatic.

Adult data suggest a higher risk of COVID-related death among patients with arthritis, lupus, or psoriasis. A recent systematic review of the literature suggested that increased risk of COVID-related death only applies to subgroups of people with RMDs.

However, whether children and young people with RMDs are likely to have more severe COVID-19 and whether there is additional risk attributable to either their underlying disease or its therapy remain unknown. The goal of the study by Dr. Hyrich and colleagues was to address these questions.

The global analysis aimed to describe characteristics of those children and young people (younger than 19 years) with preexisting RMDs who also had COVID-19; to describe outcomes following COVID-19; and to identify characteristics associated with more severe COVID-19 outcomes.

Data were drawn from the European Alliance of Associations for Rheumatology COVID-19 Registry, the Childhood Arthritis and Rheumatology Research Alliance Registry, and the CARRA-sponsored COVID-19 Global Paediatric Rheumatology Database.

Demographic information included primary RMD diagnosis; RMD disease activity (remission, low, moderate, high, or unknown); RMD treatments, including glucocorticoid use and which disease-modifying antirheumatic drug (DMARD) the patient was taking at the time of COVID-19; and comorbidities (none, ocular inflammation, interstitial lung disease, asthma, diabetes, obesity, hypertension, cerebrovascular accident, renal disease, inflammatory bowel disease, and heart disease).

With respect to COVID-19, information collected included diagnosis date, whether the case was presumptive or confirmed, clinical symptoms, hospitalization and/or death because of COVID-19, and whether the patient stopped receiving rheumatic therapies.

Rheumatology diagnoses were categorized into four groups: JIA; SLE, MCTD, vasculitis, or other RMD; autoinflammatory syndromes; and “other,” including chronic recurrent multifocal osteomyelitis, sarcoidosis, or ocular inflammation.

Of the 607 children and young people with reported SARS-CoV-2 infection from 25 different countries (464 from the EULAR COVID-19 Registry), 499 (82%) cases were polymerase chain reaction confirmed, and 399 (66%) patients were female (median age, 14 years). Most (62%) had JIA: 37%, polyarticular JIA; 30%, oligoarticular JIA; 12%, enthesitis-related JIA; 9%, systemic JIA; 4%, psoriatic JIA; and 9%, JIA of unknown subcategory. Furthermore, 13% of patients had autoinflammatory syndromes, 8% with SLE or MCTD, 3% with vasculitis, and 2% with inflammatory myopathy.

No associations were seen between DMARD treatment (conventional-synthetic, biologic/targeted-synthetic, or combination therapy), compared with no DMARD treatment, glucocorticoid use, and hospitalization.

Owing to substantial differences in reporting of race and ethnicity between data sources, the researchers were unable to analyze whether Black, Asian, and minority ethnic groups with pediatric RMDs are at higher risk of COVID-19–related death, compared with those of White ethnicity, as has been reported for the general population.

The study also did not account for variants of SARS-CoV-2 other than to note that data were collected prior to the spread of the Omicron variant. Also, the registries did not capture vaccination status (though very few children had received vaccines at the time of data collection) or information on long COVID or multisystem inflammatory syndrome in children.

Dr. Hyrich and Dr. Kearsley-Fleet have disclosed no relevant financial relationships.

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

Early meniscal surgery does not appear to be better than a program of exercise and education in improving knee outcomes in young adults with meniscal tears, according to the results of the randomized controlled DREAM trial presented at the OARSI 2022 World Congress.

Indeed, similar clinically relevant improvements in knee pain, function, and quality of life at 12 months were seen among participants in both study arms.

“Our results highlight that decisions on surgery or nonsurgical treatment must depend on preferences and values and needs of the individuals consulting their surgeon,” Søren T. Skou, PT, MSc, PhD, reported during one of the opening sessions at the meeting sponsored by the Osteoarthritis Research Society International.

The lack of superiority was contrary to the expectations of the researchers who hypothesized that early surgical intervention in adults aged between 18 and 40 years would be more beneficial than an active rehabilitation program with later surgery if needed.

Although the results do tie in with the results of other trials and systematic reviews in older adults the reason for looking at young adults specifically, aside from the obvious differences and the origin of meniscal tears, was that no study had previously looked at this population, Dr. Skou explained.
 

Assembling the DREAM team

The DREAM (Danish RCT on Exercise versus Arthroscopic Meniscal Surgery for Young Adults) trial “was a collaborative effort among many clinicians in Denmark – physical therapists, exercise physiologists, and surgeons,” Dr. Skou observed.

In total, 121 adults with MRI-verified meniscal tears who were eligible for surgery were recruited and randomized to either the early meniscal surgery group (n = 60) or to the exercise and education group (n = 61). The mean age was just below 30 years and 28% were female

Meniscal surgery, which was either an arthroscopic partial meniscectomy or meniscal repair, was performed at seven specialist centers. The exercise and education program was delivered by trained physical therapists working at 19 participating centers. The latter consisted of 24 sessions of group-based exercise therapy and education held over a period of 12 weeks.

Participants randomized to the exercise and education arm had the option of later meniscal surgery, with one in four eventually undergoing this procedure.
 

No gain in pain

The primary outcome measure was the difference in the mean of four of the subscales of the Knee Injury and Osteoarthritis Outcome Score (KOOS4) from baseline to 12-month assessment. The KOOS4 looks at knee pain, symptoms, function in sport and recreation, and quality of life.

“We considered a 10-point difference between groups as clinically relevant,” said Dr. Skou, but “adjusting for the baseline differences, we found no [statistical] differences or clinically relevant differences between groups.”

Improvement was seen in both groups. In an intention-to-treat analysis the KOOS4 scores improved by 19.2 points and 16.4 points respectively in the surgery and exercise and education groups, with a mean adjusted difference of 5.4 (95% confidence interval, –0.7 to 11.4). There was also no difference in a per protocol analysis, which considered only those participants who received the treatment strategy they were allocated (mean adjusted difference, 5.7; 95% CI, –0.9 to 12.4).

Secondary outcomes were also similarly improved in both groups with clinically relevant increases in all four KOOS subscale scores and in the Western Ontario Meniscal Evaluation Tool (WOMET).

While there were some statistical differences between the groups, such as better KOOS pain, symptoms, and WOMET scores in the surgery group, these were felt unlikely to be clinically relevant. Likewise, there was a statistically greater improvement in muscle strength in the exercise and education group than surgery group.

There was no statistical difference in the number of serious adverse events, including worsening of symptoms with or without acute onset during activity and lateral meniscal cysts, with four reported in the surgical group and seven in the exercise and education group.
 

Views on results

The results of the trial, published in NEJM Evidence, garnered attention on Twitter with several physiotherapists noting the data were positive for the nonsurgical management of meniscal tears in younger adults.

During discussion at the meeting, Nadine Foster, PhD, NIHR Professor of Musculoskeletal Health in Primary Care at Keele (England) University, asked if a larger cohort might not swing the results in favor of surgery.

She said: “Congratulations on this trial. The challenge: Your 95% CIs suggest a larger trial would have concluded superiority of surgery?”

Dr. Skou responded: “Most likely the true difference is outside the clinically relevant difference, but obviously, we cannot exclude that there is actually a clinically relevant difference between groups.”

Martin Englund, MD, Phd, of Lund (Sweden) University Hospital in Sweden, pointed out that 16 patients in the exercise and education group had “crossed over” and undergone surgery. “Were there any differences for those patients?” he asked.

“We looked at whether there was a difference between those – obviously only having 16 participants, we’re not able to do any statistical comparisons – but looking just visually at the data, they seem to improve to the same extent as those undergoing nonsurgical only,” Dr. Skou said.

The 2-year MRI data are currently being examined and will “obviously also be very interesting,” he added.

The DREAM trial was funded by the Danish Council for Independent Research, IMK Almene Fond, Lundbeck Foundation, Spar Nord Foundation, Danish Rheumatism Association, Association of Danish Physiotherapists Research Fund, Research Council at Næstved-Slagelse-Ringsted Hospitals, and Region Zealand. Dr. Skou had no financial or other conflicts of interest to disclose.

Early meniscal surgery does not appear to be better than a program of exercise and education in improving knee outcomes in young adults with meniscal tears, according to the results of the randomized controlled DREAM trial presented at the OARSI 2022 World Congress.

Indeed, similar clinically relevant improvements in knee pain, function, and quality of life at 12 months were seen among participants in both study arms.

“Our results highlight that decisions on surgery or nonsurgical treatment must depend on preferences and values and needs of the individuals consulting their surgeon,” Søren T. Skou, PT, MSc, PhD, reported during one of the opening sessions at the meeting sponsored by the Osteoarthritis Research Society International.

The lack of superiority was contrary to the expectations of the researchers who hypothesized that early surgical intervention in adults aged between 18 and 40 years would be more beneficial than an active rehabilitation program with later surgery if needed.

Although the results do tie in with the results of other trials and systematic reviews in older adults the reason for looking at young adults specifically, aside from the obvious differences and the origin of meniscal tears, was that no study had previously looked at this population, Dr. Skou explained.
 

Assembling the DREAM team

The DREAM (Danish RCT on Exercise versus Arthroscopic Meniscal Surgery for Young Adults) trial “was a collaborative effort among many clinicians in Denmark – physical therapists, exercise physiologists, and surgeons,” Dr. Skou observed.

In total, 121 adults with MRI-verified meniscal tears who were eligible for surgery were recruited and randomized to either the early meniscal surgery group (n = 60) or to the exercise and education group (n = 61). The mean age was just below 30 years and 28% were female

Meniscal surgery, which was either an arthroscopic partial meniscectomy or meniscal repair, was performed at seven specialist centers. The exercise and education program was delivered by trained physical therapists working at 19 participating centers. The latter consisted of 24 sessions of group-based exercise therapy and education held over a period of 12 weeks.

Participants randomized to the exercise and education arm had the option of later meniscal surgery, with one in four eventually undergoing this procedure.
 

No gain in pain

The primary outcome measure was the difference in the mean of four of the subscales of the Knee Injury and Osteoarthritis Outcome Score (KOOS4) from baseline to 12-month assessment. The KOOS4 looks at knee pain, symptoms, function in sport and recreation, and quality of life.

“We considered a 10-point difference between groups as clinically relevant,” said Dr. Skou, but “adjusting for the baseline differences, we found no [statistical] differences or clinically relevant differences between groups.”

Improvement was seen in both groups. In an intention-to-treat analysis the KOOS4 scores improved by 19.2 points and 16.4 points respectively in the surgery and exercise and education groups, with a mean adjusted difference of 5.4 (95% confidence interval, –0.7 to 11.4). There was also no difference in a per protocol analysis, which considered only those participants who received the treatment strategy they were allocated (mean adjusted difference, 5.7; 95% CI, –0.9 to 12.4).

Secondary outcomes were also similarly improved in both groups with clinically relevant increases in all four KOOS subscale scores and in the Western Ontario Meniscal Evaluation Tool (WOMET).

While there were some statistical differences between the groups, such as better KOOS pain, symptoms, and WOMET scores in the surgery group, these were felt unlikely to be clinically relevant. Likewise, there was a statistically greater improvement in muscle strength in the exercise and education group than surgery group.

There was no statistical difference in the number of serious adverse events, including worsening of symptoms with or without acute onset during activity and lateral meniscal cysts, with four reported in the surgical group and seven in the exercise and education group.
 

Views on results

The results of the trial, published in NEJM Evidence, garnered attention on Twitter with several physiotherapists noting the data were positive for the nonsurgical management of meniscal tears in younger adults.

During discussion at the meeting, Nadine Foster, PhD, NIHR Professor of Musculoskeletal Health in Primary Care at Keele (England) University, asked if a larger cohort might not swing the results in favor of surgery.

She said: “Congratulations on this trial. The challenge: Your 95% CIs suggest a larger trial would have concluded superiority of surgery?”

Dr. Skou responded: “Most likely the true difference is outside the clinically relevant difference, but obviously, we cannot exclude that there is actually a clinically relevant difference between groups.”

Martin Englund, MD, Phd, of Lund (Sweden) University Hospital in Sweden, pointed out that 16 patients in the exercise and education group had “crossed over” and undergone surgery. “Were there any differences for those patients?” he asked.

“We looked at whether there was a difference between those – obviously only having 16 participants, we’re not able to do any statistical comparisons – but looking just visually at the data, they seem to improve to the same extent as those undergoing nonsurgical only,” Dr. Skou said.

The 2-year MRI data are currently being examined and will “obviously also be very interesting,” he added.

The DREAM trial was funded by the Danish Council for Independent Research, IMK Almene Fond, Lundbeck Foundation, Spar Nord Foundation, Danish Rheumatism Association, Association of Danish Physiotherapists Research Fund, Research Council at Næstved-Slagelse-Ringsted Hospitals, and Region Zealand. Dr. Skou had no financial or other conflicts of interest to disclose.

Early meniscal surgery does not appear to be better than a program of exercise and education in improving knee outcomes in young adults with meniscal tears, according to the results of the randomized controlled DREAM trial presented at the OARSI 2022 World Congress.

Indeed, similar clinically relevant improvements in knee pain, function, and quality of life at 12 months were seen among participants in both study arms.

“Our results highlight that decisions on surgery or nonsurgical treatment must depend on preferences and values and needs of the individuals consulting their surgeon,” Søren T. Skou, PT, MSc, PhD, reported during one of the opening sessions at the meeting sponsored by the Osteoarthritis Research Society International.

The lack of superiority was contrary to the expectations of the researchers who hypothesized that early surgical intervention in adults aged between 18 and 40 years would be more beneficial than an active rehabilitation program with later surgery if needed.

Although the results do tie in with the results of other trials and systematic reviews in older adults the reason for looking at young adults specifically, aside from the obvious differences and the origin of meniscal tears, was that no study had previously looked at this population, Dr. Skou explained.
 

Assembling the DREAM team

The DREAM (Danish RCT on Exercise versus Arthroscopic Meniscal Surgery for Young Adults) trial “was a collaborative effort among many clinicians in Denmark – physical therapists, exercise physiologists, and surgeons,” Dr. Skou observed.

In total, 121 adults with MRI-verified meniscal tears who were eligible for surgery were recruited and randomized to either the early meniscal surgery group (n = 60) or to the exercise and education group (n = 61). The mean age was just below 30 years and 28% were female

Meniscal surgery, which was either an arthroscopic partial meniscectomy or meniscal repair, was performed at seven specialist centers. The exercise and education program was delivered by trained physical therapists working at 19 participating centers. The latter consisted of 24 sessions of group-based exercise therapy and education held over a period of 12 weeks.

Participants randomized to the exercise and education arm had the option of later meniscal surgery, with one in four eventually undergoing this procedure.
 

No gain in pain

The primary outcome measure was the difference in the mean of four of the subscales of the Knee Injury and Osteoarthritis Outcome Score (KOOS4) from baseline to 12-month assessment. The KOOS4 looks at knee pain, symptoms, function in sport and recreation, and quality of life.

“We considered a 10-point difference between groups as clinically relevant,” said Dr. Skou, but “adjusting for the baseline differences, we found no [statistical] differences or clinically relevant differences between groups.”

Improvement was seen in both groups. In an intention-to-treat analysis the KOOS4 scores improved by 19.2 points and 16.4 points respectively in the surgery and exercise and education groups, with a mean adjusted difference of 5.4 (95% confidence interval, –0.7 to 11.4). There was also no difference in a per protocol analysis, which considered only those participants who received the treatment strategy they were allocated (mean adjusted difference, 5.7; 95% CI, –0.9 to 12.4).

Secondary outcomes were also similarly improved in both groups with clinically relevant increases in all four KOOS subscale scores and in the Western Ontario Meniscal Evaluation Tool (WOMET).

While there were some statistical differences between the groups, such as better KOOS pain, symptoms, and WOMET scores in the surgery group, these were felt unlikely to be clinically relevant. Likewise, there was a statistically greater improvement in muscle strength in the exercise and education group than surgery group.

There was no statistical difference in the number of serious adverse events, including worsening of symptoms with or without acute onset during activity and lateral meniscal cysts, with four reported in the surgical group and seven in the exercise and education group.
 

Views on results

The results of the trial, published in NEJM Evidence, garnered attention on Twitter with several physiotherapists noting the data were positive for the nonsurgical management of meniscal tears in younger adults.

During discussion at the meeting, Nadine Foster, PhD, NIHR Professor of Musculoskeletal Health in Primary Care at Keele (England) University, asked if a larger cohort might not swing the results in favor of surgery.

She said: “Congratulations on this trial. The challenge: Your 95% CIs suggest a larger trial would have concluded superiority of surgery?”

Dr. Skou responded: “Most likely the true difference is outside the clinically relevant difference, but obviously, we cannot exclude that there is actually a clinically relevant difference between groups.”

Martin Englund, MD, Phd, of Lund (Sweden) University Hospital in Sweden, pointed out that 16 patients in the exercise and education group had “crossed over” and undergone surgery. “Were there any differences for those patients?” he asked.

“We looked at whether there was a difference between those – obviously only having 16 participants, we’re not able to do any statistical comparisons – but looking just visually at the data, they seem to improve to the same extent as those undergoing nonsurgical only,” Dr. Skou said.

The 2-year MRI data are currently being examined and will “obviously also be very interesting,” he added.

The DREAM trial was funded by the Danish Council for Independent Research, IMK Almene Fond, Lundbeck Foundation, Spar Nord Foundation, Danish Rheumatism Association, Association of Danish Physiotherapists Research Fund, Research Council at Næstved-Slagelse-Ringsted Hospitals, and Region Zealand. Dr. Skou had no financial or other conflicts of interest to disclose.

Bone strength and microarchitecture remained stronger at 24 months after treatment with denosumab compared to risedronate, in a study of 110 adults using glucocorticoids.

Patients using glucocorticoids are at increased risk for vertebral and nonvertebral fractures at both the start of treatment or as treatment continues, wrote Piet Geusens, MD, of Maastricht University, the Netherlands, and colleagues.

Imaging data collected via high-resolution peripheral quantitative computed tomography (HR-pQCT) allow for the assessment of bone microarchitecture and strength, but specific data comparing the impact of bone treatment in patients using glucocorticoids are lacking, they said.

In a study published in the Journal of Bone and Mineral Research, the researchers identified a subset of 56 patients randomized to denosumab and 54 to risedronate patients out of a total of 590 patients who were enrolled in a phase 3 randomized, controlled trial of denosumab vs. risedronate for bone mineral density. The main results of the larger trial – presented at EULAR 2018 – showed greater increases in bone strength with denosumab over risedronate in patients receiving glucocorticoids.

In the current study, the researchers reviewed HR-pQCT scans of the distal radius and tibia at baseline, 12 months, and 24 months. Bone strength and microarchitecture were defined in terms of failure load (FL) as a primary outcome. Patients also were divided into subpopulations of those initiating glucocorticoid treatment (GC-I) and continuing treatment (GC-C).

Baseline characteristics were mainly balanced among the treatment groups within the GC-I and GC-C categories.

Among the GC-I patients, in the denosumab group, FL increased significantly from baseline to 12 months at the radius at tibia (1.8% and 1.7%, respectively) but did not change significantly in the risedronate group, which translated to a significant treatment difference between the drugs of 3.3% for radius and 2.5% for tibia.

At 24 months, the radius measure of FL was unchanged from baseline in denosumab patients but significantly decreased in risedronate patients, with a difference of –4.1%, which translated to a significant between-treatment difference at the radius of 5.6% (P < .001). Changes at the tibia were not significantly different between the groups at 24 months.

Among the GC-C patients, FL was unchanged from baseline to 12 months for both the denosumab and risedronate groups. However, FL significantly increased with denosumab (4.3%) and remained unchanged in the risedronate group.

The researchers also found significant differences between denosumab and risedronate in percentage changes in cortical bone mineral density, and less prominent changes and differences in trabecular bone mineral density.

The study findings were limited by several factors including the use of the HR-pQCT scanner, which limits the measurement of trabecular microarchitecture, and the use of only standard HR-pQCT parameters, which do not allow insight into endosteal changes, and the inability to correct for multiplicity of data, the researchers noted.

However, the results support the superiority of denosumab over risedronate for preventing FL and total bone mineral density loss at the radius and tibia in new glucocorticoid users, and for increasing FL and total bone mineral density at the radius in long-term glucocorticoid users, they said.

Denosumab therefore could be a useful therapeutic option and could inform decision-making in patients initiating GC-therapy or on long-term GC-therapy, they concluded.

The study was supported by Amgen. Dr. Geusens disclosed grants from Amgen, Celgene, Lilly, Merck, Pfizer, Roche, UCB, Fresenius, Mylan, and Sandoz, and grants and other funding from AbbVie, outside the current study.

Bone strength and microarchitecture remained stronger at 24 months after treatment with denosumab compared to risedronate, in a study of 110 adults using glucocorticoids.

Patients using glucocorticoids are at increased risk for vertebral and nonvertebral fractures at both the start of treatment or as treatment continues, wrote Piet Geusens, MD, of Maastricht University, the Netherlands, and colleagues.

Imaging data collected via high-resolution peripheral quantitative computed tomography (HR-pQCT) allow for the assessment of bone microarchitecture and strength, but specific data comparing the impact of bone treatment in patients using glucocorticoids are lacking, they said.

In a study published in the Journal of Bone and Mineral Research, the researchers identified a subset of 56 patients randomized to denosumab and 54 to risedronate patients out of a total of 590 patients who were enrolled in a phase 3 randomized, controlled trial of denosumab vs. risedronate for bone mineral density. The main results of the larger trial – presented at EULAR 2018 – showed greater increases in bone strength with denosumab over risedronate in patients receiving glucocorticoids.

In the current study, the researchers reviewed HR-pQCT scans of the distal radius and tibia at baseline, 12 months, and 24 months. Bone strength and microarchitecture were defined in terms of failure load (FL) as a primary outcome. Patients also were divided into subpopulations of those initiating glucocorticoid treatment (GC-I) and continuing treatment (GC-C).

Baseline characteristics were mainly balanced among the treatment groups within the GC-I and GC-C categories.

Among the GC-I patients, in the denosumab group, FL increased significantly from baseline to 12 months at the radius at tibia (1.8% and 1.7%, respectively) but did not change significantly in the risedronate group, which translated to a significant treatment difference between the drugs of 3.3% for radius and 2.5% for tibia.

At 24 months, the radius measure of FL was unchanged from baseline in denosumab patients but significantly decreased in risedronate patients, with a difference of –4.1%, which translated to a significant between-treatment difference at the radius of 5.6% (P < .001). Changes at the tibia were not significantly different between the groups at 24 months.

Among the GC-C patients, FL was unchanged from baseline to 12 months for both the denosumab and risedronate groups. However, FL significantly increased with denosumab (4.3%) and remained unchanged in the risedronate group.

The researchers also found significant differences between denosumab and risedronate in percentage changes in cortical bone mineral density, and less prominent changes and differences in trabecular bone mineral density.

The study findings were limited by several factors including the use of the HR-pQCT scanner, which limits the measurement of trabecular microarchitecture, and the use of only standard HR-pQCT parameters, which do not allow insight into endosteal changes, and the inability to correct for multiplicity of data, the researchers noted.

However, the results support the superiority of denosumab over risedronate for preventing FL and total bone mineral density loss at the radius and tibia in new glucocorticoid users, and for increasing FL and total bone mineral density at the radius in long-term glucocorticoid users, they said.

Denosumab therefore could be a useful therapeutic option and could inform decision-making in patients initiating GC-therapy or on long-term GC-therapy, they concluded.

The study was supported by Amgen. Dr. Geusens disclosed grants from Amgen, Celgene, Lilly, Merck, Pfizer, Roche, UCB, Fresenius, Mylan, and Sandoz, and grants and other funding from AbbVie, outside the current study.

Bone strength and microarchitecture remained stronger at 24 months after treatment with denosumab compared to risedronate, in a study of 110 adults using glucocorticoids.

Patients using glucocorticoids are at increased risk for vertebral and nonvertebral fractures at both the start of treatment or as treatment continues, wrote Piet Geusens, MD, of Maastricht University, the Netherlands, and colleagues.

Imaging data collected via high-resolution peripheral quantitative computed tomography (HR-pQCT) allow for the assessment of bone microarchitecture and strength, but specific data comparing the impact of bone treatment in patients using glucocorticoids are lacking, they said.

In a study published in the Journal of Bone and Mineral Research, the researchers identified a subset of 56 patients randomized to denosumab and 54 to risedronate patients out of a total of 590 patients who were enrolled in a phase 3 randomized, controlled trial of denosumab vs. risedronate for bone mineral density. The main results of the larger trial – presented at EULAR 2018 – showed greater increases in bone strength with denosumab over risedronate in patients receiving glucocorticoids.

In the current study, the researchers reviewed HR-pQCT scans of the distal radius and tibia at baseline, 12 months, and 24 months. Bone strength and microarchitecture were defined in terms of failure load (FL) as a primary outcome. Patients also were divided into subpopulations of those initiating glucocorticoid treatment (GC-I) and continuing treatment (GC-C).

Baseline characteristics were mainly balanced among the treatment groups within the GC-I and GC-C categories.

Among the GC-I patients, in the denosumab group, FL increased significantly from baseline to 12 months at the radius at tibia (1.8% and 1.7%, respectively) but did not change significantly in the risedronate group, which translated to a significant treatment difference between the drugs of 3.3% for radius and 2.5% for tibia.

At 24 months, the radius measure of FL was unchanged from baseline in denosumab patients but significantly decreased in risedronate patients, with a difference of –4.1%, which translated to a significant between-treatment difference at the radius of 5.6% (P < .001). Changes at the tibia were not significantly different between the groups at 24 months.

Among the GC-C patients, FL was unchanged from baseline to 12 months for both the denosumab and risedronate groups. However, FL significantly increased with denosumab (4.3%) and remained unchanged in the risedronate group.

The researchers also found significant differences between denosumab and risedronate in percentage changes in cortical bone mineral density, and less prominent changes and differences in trabecular bone mineral density.

The study findings were limited by several factors including the use of the HR-pQCT scanner, which limits the measurement of trabecular microarchitecture, and the use of only standard HR-pQCT parameters, which do not allow insight into endosteal changes, and the inability to correct for multiplicity of data, the researchers noted.

However, the results support the superiority of denosumab over risedronate for preventing FL and total bone mineral density loss at the radius and tibia in new glucocorticoid users, and for increasing FL and total bone mineral density at the radius in long-term glucocorticoid users, they said.

Denosumab therefore could be a useful therapeutic option and could inform decision-making in patients initiating GC-therapy or on long-term GC-therapy, they concluded.

The study was supported by Amgen. Dr. Geusens disclosed grants from Amgen, Celgene, Lilly, Merck, Pfizer, Roche, UCB, Fresenius, Mylan, and Sandoz, and grants and other funding from AbbVie, outside the current study.

Though overall COVID-19 case counts continue to drop nationally, that’s not the story in every U.S. state.

About half the states have reported increases in COVID cases fueled by the Omicron subvariant, Axios reported. Alaska, Vermont, and Rhode Island had the highest increases, with more than 20 new cases per 100,000 people.

Nationally, the statistics are encouraging, with the 7-day average of daily cases around 26,000 on April 6, down from around 41,000 on March 6, according to the Centers for Disease Control and Prevention. The number of deaths has dropped to an average of around 600 a day, down 34% from 2 weeks ago.

National health officials have said some spots would have a lot of COVID cases.

“Looking across the country, we see that 95% of counties are reporting low COVID-19 community levels, which represent over 97% of the U.S. population,” CDC Director Rochelle Walensky, MD, said April 5 at a White House news briefing.

“If we look more closely at the local level, we find a handful of counties where we are seeing increases in both cases and markers of more severe disease, like hospitalizations and in-patient bed capacity, which have resulted in an increased COVID-19 community level in some areas.”

Meanwhile, the Commonwealth Fund issued a report April 8 saying the U.S. vaccine program had prevented an estimated 2.2 million deaths and 17 million hospitalizations.

If the vaccine program didn’t exist, the United States would have had another 66 million COVID infections and spent about $900 billion more on health care, the foundation said.

The United States has reported about 982,000 COVID-related deaths so far with about 80 million COVID cases, according to the CDC.

“Our findings highlight the profound and ongoing impact of the vaccination program in reducing infections, hospitalizations, and deaths,” the Commonwealth Fund said.

“Investing in vaccination programs also has produced substantial cost savings – approximately the size of one-fifth of annual national health expenditures – by dramatically reducing the amount spent on COVID-19 hospitalizations.”

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

Though overall COVID-19 case counts continue to drop nationally, that’s not the story in every U.S. state.

About half the states have reported increases in COVID cases fueled by the Omicron subvariant, Axios reported. Alaska, Vermont, and Rhode Island had the highest increases, with more than 20 new cases per 100,000 people.

Nationally, the statistics are encouraging, with the 7-day average of daily cases around 26,000 on April 6, down from around 41,000 on March 6, according to the Centers for Disease Control and Prevention. The number of deaths has dropped to an average of around 600 a day, down 34% from 2 weeks ago.

National health officials have said some spots would have a lot of COVID cases.

“Looking across the country, we see that 95% of counties are reporting low COVID-19 community levels, which represent over 97% of the U.S. population,” CDC Director Rochelle Walensky, MD, said April 5 at a White House news briefing.

“If we look more closely at the local level, we find a handful of counties where we are seeing increases in both cases and markers of more severe disease, like hospitalizations and in-patient bed capacity, which have resulted in an increased COVID-19 community level in some areas.”

Meanwhile, the Commonwealth Fund issued a report April 8 saying the U.S. vaccine program had prevented an estimated 2.2 million deaths and 17 million hospitalizations.

If the vaccine program didn’t exist, the United States would have had another 66 million COVID infections and spent about $900 billion more on health care, the foundation said.

The United States has reported about 982,000 COVID-related deaths so far with about 80 million COVID cases, according to the CDC.

“Our findings highlight the profound and ongoing impact of the vaccination program in reducing infections, hospitalizations, and deaths,” the Commonwealth Fund said.

“Investing in vaccination programs also has produced substantial cost savings – approximately the size of one-fifth of annual national health expenditures – by dramatically reducing the amount spent on COVID-19 hospitalizations.”

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

Though overall COVID-19 case counts continue to drop nationally, that’s not the story in every U.S. state.

About half the states have reported increases in COVID cases fueled by the Omicron subvariant, Axios reported. Alaska, Vermont, and Rhode Island had the highest increases, with more than 20 new cases per 100,000 people.

Nationally, the statistics are encouraging, with the 7-day average of daily cases around 26,000 on April 6, down from around 41,000 on March 6, according to the Centers for Disease Control and Prevention. The number of deaths has dropped to an average of around 600 a day, down 34% from 2 weeks ago.

National health officials have said some spots would have a lot of COVID cases.

“Looking across the country, we see that 95% of counties are reporting low COVID-19 community levels, which represent over 97% of the U.S. population,” CDC Director Rochelle Walensky, MD, said April 5 at a White House news briefing.

“If we look more closely at the local level, we find a handful of counties where we are seeing increases in both cases and markers of more severe disease, like hospitalizations and in-patient bed capacity, which have resulted in an increased COVID-19 community level in some areas.”

Meanwhile, the Commonwealth Fund issued a report April 8 saying the U.S. vaccine program had prevented an estimated 2.2 million deaths and 17 million hospitalizations.

If the vaccine program didn’t exist, the United States would have had another 66 million COVID infections and spent about $900 billion more on health care, the foundation said.

The United States has reported about 982,000 COVID-related deaths so far with about 80 million COVID cases, according to the CDC.

“Our findings highlight the profound and ongoing impact of the vaccination program in reducing infections, hospitalizations, and deaths,” the Commonwealth Fund said.

“Investing in vaccination programs also has produced substantial cost savings – approximately the size of one-fifth of annual national health expenditures – by dramatically reducing the amount spent on COVID-19 hospitalizations.”

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

A small number of patient and physician-reported outcomes, as well as laboratory and clinical factors, may help to predict the response of patients with ankylosing spondylitis (AS) to treatment with tumor necrosis factor (TNF) inhibitors when they have never taken them before, according to an analysis of data from nearly 2,000 individuals in 10 clinical trials.

TNF inhibitors are recommended for patients with AS whose symptoms persist despite use of NSAIDs, Runsheng Wang, MD, adjunct assistant professor at Columbia University Medical Center, New York, and a practicing rheumatologist at Garden State Rheumatology Consultants, Union, N.J., and colleagues wrote. Randomized, controlled clinical trials have shown that TNF inhibitors are effective in treating AS, but approximately half of patients fail to achieve notable improvement, which suggests the need for a predictive model.

“In clinical practice, before starting a treatment, physicians and patients want to know how likely a patient would be to respond to the treatment, particularly when more than one treatment option is available,” Dr. Wang said in an interview. “In this study, we developed predictive models that can potentially answer this question.”

The results suggest that the models in the study can be used to personalize clinical decision-making for patients with AS, whether to promote confidence in choosing a TNF inhibitor or to terminate treatment in nonresponders who had a higher probability of nonresponse at baseline, the researchers wrote. Similar models for other biologic treatments can help prioritize treatment options.

The predictive models are practical for clinical use because the variables in the reduced models – can be collected easily during patient visits, Dr. Wang explained. However, data from clinical practice are needed to further validate the study findings.

In a retrospective cohort study published in JAMA Network Open, the researchers analyzed data from 10 randomized, controlled clinical trials of TNF inhibitor treatment in patients with active AS conducted during 2002-2016. The study population included 1,899 adults with active AS who received an originator TNF inhibitor for at least 12 weeks, and the training set included 1,207 individuals. In the training set, the mean age of the participants was 39 years, and 75% were men.

The outcomes included major response and no response based on change in AS Disease Activity Score (ASDAS) from baseline to 12 weeks, and the researchers used machine-learning algorithms to estimate the probability of major response or no response. Major response was defined as a decrease in ASDAS of 2.0 or greater; no response was defined as a decrease in ASDAS of less than 1.1.

In the training set, a total of 407 patients (33.7%) had a major response, and 414 (34.3%) had no response.

The key features in the full, 21-variable model that increased the probability of a major response were higher C-reactive protein (CRP) levels, higher patient global assessment (PGA) of disease activity, and Bath AS Disease Activity Index (BASDAI) question 2 scores. (Question 2 asks for the overall level of back, hip, or neck pain associated with AS.) The probability of a major response decreased with higher body mass index and Bath AS Functional Index (BASFI) scores.

The key features in the model that increased the probability of no response were older age and higher BASFI scores. The probability of no response decreased with higher CRP levels, higher BASDAI question 2 scores, and higher PGA scores.

Overall, the researchers found that models using smaller subsets of variables (three or five variables in total) that would be easier to gather clinically yielded similar predictive performance.

The models were externally validated in a testing set of 692 individuals. Baseline characteristics were similar in the testing and training sets. In the testing set, the full models demonstrated moderate to high accuracy of 0.71 in the random forest model for major response and 0.76 in the random forest model for no response, with similar results in the reduced models.

At a prevalence of 25% for major response, the positive predictive values (PPVs) for random forest and logistic regression models ranged from 0.49 to 0.60, and the negative predictive values (NPVs) ranged from 0.82 to 0.84. At a prevalence of 25% for no response, PPVs ranged from 0.61 to 0.77, and NPVs ranged from 0.81 to 0.83.

The study findings were limited by several factors including the lack of data on smoking, which has been linked both to shorter treatment adherence and worse response to TNF inhibitors; the inclusion of only TNF inhibitor–naive patients; and the exclusion of NSAIDs from the models, the researchers wrote.

Dr. Wang disclosed support from the Rheumatology Research Foundation. The study’s two other authors disclosed receiving support from the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The study was based on an analysis of data from AbbVie and Pfizer that were made available through Vivli.

A small number of patient and physician-reported outcomes, as well as laboratory and clinical factors, may help to predict the response of patients with ankylosing spondylitis (AS) to treatment with tumor necrosis factor (TNF) inhibitors when they have never taken them before, according to an analysis of data from nearly 2,000 individuals in 10 clinical trials.

TNF inhibitors are recommended for patients with AS whose symptoms persist despite use of NSAIDs, Runsheng Wang, MD, adjunct assistant professor at Columbia University Medical Center, New York, and a practicing rheumatologist at Garden State Rheumatology Consultants, Union, N.J., and colleagues wrote. Randomized, controlled clinical trials have shown that TNF inhibitors are effective in treating AS, but approximately half of patients fail to achieve notable improvement, which suggests the need for a predictive model.

“In clinical practice, before starting a treatment, physicians and patients want to know how likely a patient would be to respond to the treatment, particularly when more than one treatment option is available,” Dr. Wang said in an interview. “In this study, we developed predictive models that can potentially answer this question.”

The results suggest that the models in the study can be used to personalize clinical decision-making for patients with AS, whether to promote confidence in choosing a TNF inhibitor or to terminate treatment in nonresponders who had a higher probability of nonresponse at baseline, the researchers wrote. Similar models for other biologic treatments can help prioritize treatment options.

The predictive models are practical for clinical use because the variables in the reduced models – can be collected easily during patient visits, Dr. Wang explained. However, data from clinical practice are needed to further validate the study findings.

In a retrospective cohort study published in JAMA Network Open, the researchers analyzed data from 10 randomized, controlled clinical trials of TNF inhibitor treatment in patients with active AS conducted during 2002-2016. The study population included 1,899 adults with active AS who received an originator TNF inhibitor for at least 12 weeks, and the training set included 1,207 individuals. In the training set, the mean age of the participants was 39 years, and 75% were men.

The outcomes included major response and no response based on change in AS Disease Activity Score (ASDAS) from baseline to 12 weeks, and the researchers used machine-learning algorithms to estimate the probability of major response or no response. Major response was defined as a decrease in ASDAS of 2.0 or greater; no response was defined as a decrease in ASDAS of less than 1.1.

In the training set, a total of 407 patients (33.7%) had a major response, and 414 (34.3%) had no response.

The key features in the full, 21-variable model that increased the probability of a major response were higher C-reactive protein (CRP) levels, higher patient global assessment (PGA) of disease activity, and Bath AS Disease Activity Index (BASDAI) question 2 scores. (Question 2 asks for the overall level of back, hip, or neck pain associated with AS.) The probability of a major response decreased with higher body mass index and Bath AS Functional Index (BASFI) scores.

The key features in the model that increased the probability of no response were older age and higher BASFI scores. The probability of no response decreased with higher CRP levels, higher BASDAI question 2 scores, and higher PGA scores.

Overall, the researchers found that models using smaller subsets of variables (three or five variables in total) that would be easier to gather clinically yielded similar predictive performance.

The models were externally validated in a testing set of 692 individuals. Baseline characteristics were similar in the testing and training sets. In the testing set, the full models demonstrated moderate to high accuracy of 0.71 in the random forest model for major response and 0.76 in the random forest model for no response, with similar results in the reduced models.

At a prevalence of 25% for major response, the positive predictive values (PPVs) for random forest and logistic regression models ranged from 0.49 to 0.60, and the negative predictive values (NPVs) ranged from 0.82 to 0.84. At a prevalence of 25% for no response, PPVs ranged from 0.61 to 0.77, and NPVs ranged from 0.81 to 0.83.

The study findings were limited by several factors including the lack of data on smoking, which has been linked both to shorter treatment adherence and worse response to TNF inhibitors; the inclusion of only TNF inhibitor–naive patients; and the exclusion of NSAIDs from the models, the researchers wrote.

Dr. Wang disclosed support from the Rheumatology Research Foundation. The study’s two other authors disclosed receiving support from the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The study was based on an analysis of data from AbbVie and Pfizer that were made available through Vivli.

A small number of patient and physician-reported outcomes, as well as laboratory and clinical factors, may help to predict the response of patients with ankylosing spondylitis (AS) to treatment with tumor necrosis factor (TNF) inhibitors when they have never taken them before, according to an analysis of data from nearly 2,000 individuals in 10 clinical trials.

TNF inhibitors are recommended for patients with AS whose symptoms persist despite use of NSAIDs, Runsheng Wang, MD, adjunct assistant professor at Columbia University Medical Center, New York, and a practicing rheumatologist at Garden State Rheumatology Consultants, Union, N.J., and colleagues wrote. Randomized, controlled clinical trials have shown that TNF inhibitors are effective in treating AS, but approximately half of patients fail to achieve notable improvement, which suggests the need for a predictive model.

“In clinical practice, before starting a treatment, physicians and patients want to know how likely a patient would be to respond to the treatment, particularly when more than one treatment option is available,” Dr. Wang said in an interview. “In this study, we developed predictive models that can potentially answer this question.”

The results suggest that the models in the study can be used to personalize clinical decision-making for patients with AS, whether to promote confidence in choosing a TNF inhibitor or to terminate treatment in nonresponders who had a higher probability of nonresponse at baseline, the researchers wrote. Similar models for other biologic treatments can help prioritize treatment options.

The predictive models are practical for clinical use because the variables in the reduced models – can be collected easily during patient visits, Dr. Wang explained. However, data from clinical practice are needed to further validate the study findings.

In a retrospective cohort study published in JAMA Network Open, the researchers analyzed data from 10 randomized, controlled clinical trials of TNF inhibitor treatment in patients with active AS conducted during 2002-2016. The study population included 1,899 adults with active AS who received an originator TNF inhibitor for at least 12 weeks, and the training set included 1,207 individuals. In the training set, the mean age of the participants was 39 years, and 75% were men.

The outcomes included major response and no response based on change in AS Disease Activity Score (ASDAS) from baseline to 12 weeks, and the researchers used machine-learning algorithms to estimate the probability of major response or no response. Major response was defined as a decrease in ASDAS of 2.0 or greater; no response was defined as a decrease in ASDAS of less than 1.1.

In the training set, a total of 407 patients (33.7%) had a major response, and 414 (34.3%) had no response.

The key features in the full, 21-variable model that increased the probability of a major response were higher C-reactive protein (CRP) levels, higher patient global assessment (PGA) of disease activity, and Bath AS Disease Activity Index (BASDAI) question 2 scores. (Question 2 asks for the overall level of back, hip, or neck pain associated with AS.) The probability of a major response decreased with higher body mass index and Bath AS Functional Index (BASFI) scores.

The key features in the model that increased the probability of no response were older age and higher BASFI scores. The probability of no response decreased with higher CRP levels, higher BASDAI question 2 scores, and higher PGA scores.

Overall, the researchers found that models using smaller subsets of variables (three or five variables in total) that would be easier to gather clinically yielded similar predictive performance.

The models were externally validated in a testing set of 692 individuals. Baseline characteristics were similar in the testing and training sets. In the testing set, the full models demonstrated moderate to high accuracy of 0.71 in the random forest model for major response and 0.76 in the random forest model for no response, with similar results in the reduced models.

At a prevalence of 25% for major response, the positive predictive values (PPVs) for random forest and logistic regression models ranged from 0.49 to 0.60, and the negative predictive values (NPVs) ranged from 0.82 to 0.84. At a prevalence of 25% for no response, PPVs ranged from 0.61 to 0.77, and NPVs ranged from 0.81 to 0.83.

The study findings were limited by several factors including the lack of data on smoking, which has been linked both to shorter treatment adherence and worse response to TNF inhibitors; the inclusion of only TNF inhibitor–naive patients; and the exclusion of NSAIDs from the models, the researchers wrote.

Dr. Wang disclosed support from the Rheumatology Research Foundation. The study’s two other authors disclosed receiving support from the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The study was based on an analysis of data from AbbVie and Pfizer that were made available through Vivli.

In a deep dive into obscure Chinese language transplant journals, a pair of researchers from Australia and Israel have added a new layer of horror to what’s already known about forced organ harvesting in China.

Searching for documentation that vital organs are being harvested from nonconsenting executed prisoners, a practice that the China Tribunal confirmed “beyond any reasonable doubt” in 2020, Jacob Lavee, MD, an Israeli heart transplant surgeon, and Matthew Roberston, a PhD student at Australian National University, uncovered something even more shocking: that vital organs are being explanted from patients who are still alive.

“We have shown for the first time that the transplant surgeons are the executioners – that the mode of execution is organ procurement. These are self-admissions of executing the patient,” Dr. Lavee told this news organization. “Up until now, there has been what we call circumstantial evidence of this, but our paper is what you’d call the smoking gun, because it’s in the words of the physicians themselves that they are doing it. In the words of these surgeons, intubation was done only after the beginning of surgery, which means the patients were breathing spontaneously up until the moment the operation started ... meaning they were not brain dead.”

The research, published in the American Journal of Transplantation, involved intricate analysis of thousands of Chinese language transplant articles and identified 71 articles in which transplant surgeons describe starting organ procurement surgery before declaring their patients brain dead.

“What we found were improper, illegitimate, nonexistent, or false declarations of brain death,” Mr. Robertson said in an interview. He explained that this violates what’s known as the dead donor rule, which is fundamental in transplant ethics. “The surgeons wrote that the donor was brain dead, but according to everything we know about medical science, they could not possibly have been brain dead because there was no apnea test performed. Brain death is not just something you say, there’s this whole battery of tests, and the key is the apnea test, [in which] the patient is already intubated and ventilated, they turn the machine off, and they’re looking for carbon dioxide in the blood above a certain level.”

Mr. Robertson and Dr. Lavee have painstakingly documented “incriminating sentences” in each of the 71 articles proving that brain death had not occurred before the organ explantation procedure began. “There were two criteria by which we claimed a problematic brain death declaration,” said Mr. Robertson, who translated the Chinese. “One was where the patient was not ventilated and was only intubated after they were declared brain dead; the other was that the intubation took place immediately prior to the surgery beginning.”

“It was mind-boggling,” said Dr. Lavee, from Tel Aviv University. “When I first started reading, my initial reaction is, ‘This can’t be.’ I read it once, and again, and I insisted that Matt get another independent translation of the Chinese just to be sure. I told him, ‘There’s no way a physician, a surgeon could write this – it doesn’t make sense.’ But the more of these papers we read, we saw it was a pattern – and they didn’t come out of a single medical center, they are spread all over China.”

For the analysis, Mr. Robertson wrote code and customized an algorithm to examine 124,770 medical articles from official Chinese databases between 1980 and 2020. The 71 articles revealing cases involving problematic brain death came from 56 hospitals (of which 12 were military) in 33 cities across 15 provinces, they report. In total, 348 surgeons, nurses, anesthesiologists, and other medical workers or researchers were listed as authors of these publications.

Why would these medical personnel write such self-incriminating evidence? The researchers say it’s unclear. “They don’t think anyone’s reading this stuff,” Mr. Robertson suggests. “Sometimes it’s revealed in just five or six characters in a paper of eight pages.” Dr. Lavee wonders if it’s also ignorance. “If this has been a practice for 20 or 30 years in China, I guess nobody at that time was aware they were doing something wrong, although how to declare brain death is something that is known in China. They’ve published a lot about it.”

The article is “evidence that this barbarity continues and is a very valuable contribution that continues to bring attention to an enormous human rights violation,” said Arthur Caplan, PhD, head of the Division of Medical Ethics at New York University’s Grossman School of Medicine. “What they’ve reported has been going on for many, many years, the data are very clear that China’s doing many more transplants than they have cadaver organ donors,” he said, adding that the country’s well-documented and lucrative involvement in transplant tourism “means you have to have a donor ready when the would-be recipient appears; you have to have a matched organ available, and that’s hard to do waiting on a cadaver donor.”

Although the researchers found no incriminating publications after 2015, they speculate that this is likely due to growing awareness among Chinese surgeons that publishing the information would attract international condemnation. “We think these practices are continuing to go on,” said Dr. Lavee. He acknowledged that a voluntary organ donation program is slowly developing in parallel to this. He said, given China’s place as the world’s second largest transplant country behind the U.S., as well as its low rate of voluntary donation, it’s reasonable to conclude that the main source of organs remains prisoners on death row.

Dr. Caplan and the researchers have called for academic institutions and medical journals to resume their previous boycotts of Chinese transplant publications and speakers, but as long as China denies the practices, economic and political leaders will turn a blind eye. “In the past, I don’t think the question of China’s medical professional involvement in the execution of donors has been taken as seriously as it should have,” said Mr. Robertson. “I certainly hope that with the publication of this paper in the leading journal in the field, this will change.”

The study was supported by the Google Cloud Research Credits program, the Australian Government Research Training Program Scholarship, and the Victims of Communism Memorial Foundation. Mr. Robertson, Dr. Lavee, and Dr. Caplan have disclosed no relevant financial relationships.

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

In a deep dive into obscure Chinese language transplant journals, a pair of researchers from Australia and Israel have added a new layer of horror to what’s already known about forced organ harvesting in China.

Searching for documentation that vital organs are being harvested from nonconsenting executed prisoners, a practice that the China Tribunal confirmed “beyond any reasonable doubt” in 2020, Jacob Lavee, MD, an Israeli heart transplant surgeon, and Matthew Roberston, a PhD student at Australian National University, uncovered something even more shocking: that vital organs are being explanted from patients who are still alive.

“We have shown for the first time that the transplant surgeons are the executioners – that the mode of execution is organ procurement. These are self-admissions of executing the patient,” Dr. Lavee told this news organization. “Up until now, there has been what we call circumstantial evidence of this, but our paper is what you’d call the smoking gun, because it’s in the words of the physicians themselves that they are doing it. In the words of these surgeons, intubation was done only after the beginning of surgery, which means the patients were breathing spontaneously up until the moment the operation started ... meaning they were not brain dead.”

The research, published in the American Journal of Transplantation, involved intricate analysis of thousands of Chinese language transplant articles and identified 71 articles in which transplant surgeons describe starting organ procurement surgery before declaring their patients brain dead.

“What we found were improper, illegitimate, nonexistent, or false declarations of brain death,” Mr. Robertson said in an interview. He explained that this violates what’s known as the dead donor rule, which is fundamental in transplant ethics. “The surgeons wrote that the donor was brain dead, but according to everything we know about medical science, they could not possibly have been brain dead because there was no apnea test performed. Brain death is not just something you say, there’s this whole battery of tests, and the key is the apnea test, [in which] the patient is already intubated and ventilated, they turn the machine off, and they’re looking for carbon dioxide in the blood above a certain level.”

Mr. Robertson and Dr. Lavee have painstakingly documented “incriminating sentences” in each of the 71 articles proving that brain death had not occurred before the organ explantation procedure began. “There were two criteria by which we claimed a problematic brain death declaration,” said Mr. Robertson, who translated the Chinese. “One was where the patient was not ventilated and was only intubated after they were declared brain dead; the other was that the intubation took place immediately prior to the surgery beginning.”

“It was mind-boggling,” said Dr. Lavee, from Tel Aviv University. “When I first started reading, my initial reaction is, ‘This can’t be.’ I read it once, and again, and I insisted that Matt get another independent translation of the Chinese just to be sure. I told him, ‘There’s no way a physician, a surgeon could write this – it doesn’t make sense.’ But the more of these papers we read, we saw it was a pattern – and they didn’t come out of a single medical center, they are spread all over China.”

For the analysis, Mr. Robertson wrote code and customized an algorithm to examine 124,770 medical articles from official Chinese databases between 1980 and 2020. The 71 articles revealing cases involving problematic brain death came from 56 hospitals (of which 12 were military) in 33 cities across 15 provinces, they report. In total, 348 surgeons, nurses, anesthesiologists, and other medical workers or researchers were listed as authors of these publications.

Why would these medical personnel write such self-incriminating evidence? The researchers say it’s unclear. “They don’t think anyone’s reading this stuff,” Mr. Robertson suggests. “Sometimes it’s revealed in just five or six characters in a paper of eight pages.” Dr. Lavee wonders if it’s also ignorance. “If this has been a practice for 20 or 30 years in China, I guess nobody at that time was aware they were doing something wrong, although how to declare brain death is something that is known in China. They’ve published a lot about it.”

The article is “evidence that this barbarity continues and is a very valuable contribution that continues to bring attention to an enormous human rights violation,” said Arthur Caplan, PhD, head of the Division of Medical Ethics at New York University’s Grossman School of Medicine. “What they’ve reported has been going on for many, many years, the data are very clear that China’s doing many more transplants than they have cadaver organ donors,” he said, adding that the country’s well-documented and lucrative involvement in transplant tourism “means you have to have a donor ready when the would-be recipient appears; you have to have a matched organ available, and that’s hard to do waiting on a cadaver donor.”

Although the researchers found no incriminating publications after 2015, they speculate that this is likely due to growing awareness among Chinese surgeons that publishing the information would attract international condemnation. “We think these practices are continuing to go on,” said Dr. Lavee. He acknowledged that a voluntary organ donation program is slowly developing in parallel to this. He said, given China’s place as the world’s second largest transplant country behind the U.S., as well as its low rate of voluntary donation, it’s reasonable to conclude that the main source of organs remains prisoners on death row.

Dr. Caplan and the researchers have called for academic institutions and medical journals to resume their previous boycotts of Chinese transplant publications and speakers, but as long as China denies the practices, economic and political leaders will turn a blind eye. “In the past, I don’t think the question of China’s medical professional involvement in the execution of donors has been taken as seriously as it should have,” said Mr. Robertson. “I certainly hope that with the publication of this paper in the leading journal in the field, this will change.”

The study was supported by the Google Cloud Research Credits program, the Australian Government Research Training Program Scholarship, and the Victims of Communism Memorial Foundation. Mr. Robertson, Dr. Lavee, and Dr. Caplan have disclosed no relevant financial relationships.

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

In a deep dive into obscure Chinese language transplant journals, a pair of researchers from Australia and Israel have added a new layer of horror to what’s already known about forced organ harvesting in China.

Searching for documentation that vital organs are being harvested from nonconsenting executed prisoners, a practice that the China Tribunal confirmed “beyond any reasonable doubt” in 2020, Jacob Lavee, MD, an Israeli heart transplant surgeon, and Matthew Roberston, a PhD student at Australian National University, uncovered something even more shocking: that vital organs are being explanted from patients who are still alive.

“We have shown for the first time that the transplant surgeons are the executioners – that the mode of execution is organ procurement. These are self-admissions of executing the patient,” Dr. Lavee told this news organization. “Up until now, there has been what we call circumstantial evidence of this, but our paper is what you’d call the smoking gun, because it’s in the words of the physicians themselves that they are doing it. In the words of these surgeons, intubation was done only after the beginning of surgery, which means the patients were breathing spontaneously up until the moment the operation started ... meaning they were not brain dead.”

The research, published in the American Journal of Transplantation, involved intricate analysis of thousands of Chinese language transplant articles and identified 71 articles in which transplant surgeons describe starting organ procurement surgery before declaring their patients brain dead.

“What we found were improper, illegitimate, nonexistent, or false declarations of brain death,” Mr. Robertson said in an interview. He explained that this violates what’s known as the dead donor rule, which is fundamental in transplant ethics. “The surgeons wrote that the donor was brain dead, but according to everything we know about medical science, they could not possibly have been brain dead because there was no apnea test performed. Brain death is not just something you say, there’s this whole battery of tests, and the key is the apnea test, [in which] the patient is already intubated and ventilated, they turn the machine off, and they’re looking for carbon dioxide in the blood above a certain level.”

Mr. Robertson and Dr. Lavee have painstakingly documented “incriminating sentences” in each of the 71 articles proving that brain death had not occurred before the organ explantation procedure began. “There were two criteria by which we claimed a problematic brain death declaration,” said Mr. Robertson, who translated the Chinese. “One was where the patient was not ventilated and was only intubated after they were declared brain dead; the other was that the intubation took place immediately prior to the surgery beginning.”

“It was mind-boggling,” said Dr. Lavee, from Tel Aviv University. “When I first started reading, my initial reaction is, ‘This can’t be.’ I read it once, and again, and I insisted that Matt get another independent translation of the Chinese just to be sure. I told him, ‘There’s no way a physician, a surgeon could write this – it doesn’t make sense.’ But the more of these papers we read, we saw it was a pattern – and they didn’t come out of a single medical center, they are spread all over China.”

For the analysis, Mr. Robertson wrote code and customized an algorithm to examine 124,770 medical articles from official Chinese databases between 1980 and 2020. The 71 articles revealing cases involving problematic brain death came from 56 hospitals (of which 12 were military) in 33 cities across 15 provinces, they report. In total, 348 surgeons, nurses, anesthesiologists, and other medical workers or researchers were listed as authors of these publications.

Why would these medical personnel write such self-incriminating evidence? The researchers say it’s unclear. “They don’t think anyone’s reading this stuff,” Mr. Robertson suggests. “Sometimes it’s revealed in just five or six characters in a paper of eight pages.” Dr. Lavee wonders if it’s also ignorance. “If this has been a practice for 20 or 30 years in China, I guess nobody at that time was aware they were doing something wrong, although how to declare brain death is something that is known in China. They’ve published a lot about it.”

The article is “evidence that this barbarity continues and is a very valuable contribution that continues to bring attention to an enormous human rights violation,” said Arthur Caplan, PhD, head of the Division of Medical Ethics at New York University’s Grossman School of Medicine. “What they’ve reported has been going on for many, many years, the data are very clear that China’s doing many more transplants than they have cadaver organ donors,” he said, adding that the country’s well-documented and lucrative involvement in transplant tourism “means you have to have a donor ready when the would-be recipient appears; you have to have a matched organ available, and that’s hard to do waiting on a cadaver donor.”

Although the researchers found no incriminating publications after 2015, they speculate that this is likely due to growing awareness among Chinese surgeons that publishing the information would attract international condemnation. “We think these practices are continuing to go on,” said Dr. Lavee. He acknowledged that a voluntary organ donation program is slowly developing in parallel to this. He said, given China’s place as the world’s second largest transplant country behind the U.S., as well as its low rate of voluntary donation, it’s reasonable to conclude that the main source of organs remains prisoners on death row.

Dr. Caplan and the researchers have called for academic institutions and medical journals to resume their previous boycotts of Chinese transplant publications and speakers, but as long as China denies the practices, economic and political leaders will turn a blind eye. “In the past, I don’t think the question of China’s medical professional involvement in the execution of donors has been taken as seriously as it should have,” said Mr. Robertson. “I certainly hope that with the publication of this paper in the leading journal in the field, this will change.”

The study was supported by the Google Cloud Research Credits program, the Australian Government Research Training Program Scholarship, and the Victims of Communism Memorial Foundation. Mr. Robertson, Dr. Lavee, and Dr. Caplan have disclosed no relevant financial relationships.

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

BOSTON – Treatment with apremilast (Otezla) did not significantly affect vascular inflammation in patients with psoriasis but was associated with a generally beneficial effect on biomarkers associated with heart disease, lipid metabolism, and glucose metabolism, in a study presented at the 2022 American Academy of Dermatology annual meeting.

In the phase 4, open-label, single arm trial, participants also lost subcutaneous and visceral fat after 16 weeks on the oral medication, a phosphodiesterase 4 (PDE4) inhibitor, and maintained that loss at 52 weeks.

People with psoriasis have an increased risk of obesity, type 2 diabetes, and cardiovascular events. Patients with more significant psoriasis “tend to die about 5 years younger than they should, based on their risk factors for mortality,” Joel Gelfand, MD, MSCE, professor of dermatology and epidemiology and vice chair of clinical research in dermatology at the University of Pennsylvania Perelman School of Medicine, Philadelphia, told this news organization.

He led the research and presented the findings at the AAD meeting March 26. “As a result, there has been a keen interest in understanding how psoriasis therapies impact cardiovascular risk, the idea being that by controlling inflammation, you may lower the risk of these patients developing cardiovascular disease over time,” he said.

Previous trials looking at the effect of psoriasis therapies on vascular inflammation “have been, for the most part, inconclusive,” Michael Garshick, MD, a cardiologist at NYU Langone Health, told this news organization. Dr. Garshick was not involved with the research. A 2021 systematic review of psoriasis clinicals trials reported that the tumor necrosis factor (TNF) blocker adalimumab (Humira) and phototherapy had the greatest effect on cardiometabolic markers, while ustekinumab (Stelara), an interleukin (IL)-12 and IL-23 antagonist, was the only treatment that improved vascular inflammation. These variable findings make this area “ripe for study,” noted Dr. Garshick.

To observe how apremilast, which is approved by the FDA for treating psoriasis and psoriatic arthritis, affected vascular inflammation, adiposity, and blood-based cardiometabolic markers, Dr. Gelfand organized an open-label study in adults with moderate-to-severe psoriasis. All participants were 18 years or older, had psoriasis for at least 6 months, and were candidates for systemic therapy. All patients underwent FDG PET/CT scans to assess aortic vascular inflammation and had blood work at baseline. Of the 70 patients originally enrolled in the study, 60 remained in the study at week 16, including 57 who underwent imaging for the second time. Thirty-nine participants remained in the study until week 52, and all except one had another scan.

The average age of participants was 47 years, and their mean BMI was 30. More than 80% of participants were White (83%) and 77% were male. The study population had lived with psoriasis for an average of 16 years and 8 patients also had psoriatic arthritis. At baseline, on average, participants had a Psoriasis Area and Severity Index (PASI) score of 18.62, a dermatology life quality index (DLQI) score of 11.60, and 22% of participants’ BSA (body surface area) were affected. The mean TBRmax, the marker for vascular inflammation, was 1.61.

Treatment responses were as expected for apremilast, with 35% of patients achieving PASI 75 and 65% of participants reporting DLQI scores of 5 or less by 16 weeks. At 52 weeks, 31% of the cohort had achieved PASI 75, and 67% reported DLQI score of 5 or higher. All psoriasis endpoints had improved since baseline (P = .001).

Throughout the study period, there was no significant change in TBRmax. However, in a sensitivity analysis, the 16 patients with a baseline TBRmax  of 1.6 or higher had an absolute reduction of 0.21 in TBR by week 52. “That suggests that maybe a subset of people who have higher levels of aortic inflammation at baseline may experience some reduction that portend, potentially, some health benefits over time,” Dr. Gelfand said. “Ultimately, I wouldn’t hang my hat on the finding,” he said, noting that additional research comparing the treatment to placebo is necessary.

Both visceral and subcutaneous adipose tissue (VAT and SAT) decreased by week 16, and this reduction was maintained through week 52. In the first 16 weeks of the study, VAT decreased by 5.32% (P = .0009), and SAT decreased by 5.53% (P = .0005). From baseline to 52 weeks, VAT decreased by 5.52% (P = .0148), and SAT decreased by 5.50% (P = .0096). There were no significant differences between week 16 and week 52 in VAT or SAT.

Of the 68 blood biomarkers analyzed, there were significant decreases in the inflammatory markers ferritin (P = .015) and IL-beta (P = .006), the lipid metabolism biomarker HDL-cholesterol efflux (P = .008), and ketone bodies (P = .006). There were also increases in the inflammatory marker IL-8 (P = .003), the lipid metabolism marker ApoA (P = .05), and insulin (P = .05). Ferritin was the only biomarker that was reduced on both week 16 and week 52.

“If you want to be a purist, this was a negative trial,” said Dr. Garshick, because apremilast was not found to decrease vascular inflammation; however, he noted that the biomarker changes “were hopeful secondary endpoints.” It could be, he said, that another outcome measure may be better able to show changes in vascular inflammation compared with FDG. “It’s always hard to figure out what a good surrogate endpoint is in cardiovascular trials,” he noted, “so it may be that FDG/PET is too noisy or not reliable enough to see the outcome that we want to see.”

Dr. Gelfand reports consulting fees/grants from Amgen, AbbVie, BMS, Boehringer Ingelheim, Janssen Biologics, Novartis Corp, Pfizer, and UCB (DSMB). He serves as the Deputy Editor for the Journal of Investigative Dermatology and the Chief Medical Editor at Healio Psoriatic Disease and receives honoraria for both roles. Dr. Garshick has received consulting fees from AbbVie.

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

BOSTON – Treatment with apremilast (Otezla) did not significantly affect vascular inflammation in patients with psoriasis but was associated with a generally beneficial effect on biomarkers associated with heart disease, lipid metabolism, and glucose metabolism, in a study presented at the 2022 American Academy of Dermatology annual meeting.

In the phase 4, open-label, single arm trial, participants also lost subcutaneous and visceral fat after 16 weeks on the oral medication, a phosphodiesterase 4 (PDE4) inhibitor, and maintained that loss at 52 weeks.

People with psoriasis have an increased risk of obesity, type 2 diabetes, and cardiovascular events. Patients with more significant psoriasis “tend to die about 5 years younger than they should, based on their risk factors for mortality,” Joel Gelfand, MD, MSCE, professor of dermatology and epidemiology and vice chair of clinical research in dermatology at the University of Pennsylvania Perelman School of Medicine, Philadelphia, told this news organization.

He led the research and presented the findings at the AAD meeting March 26. “As a result, there has been a keen interest in understanding how psoriasis therapies impact cardiovascular risk, the idea being that by controlling inflammation, you may lower the risk of these patients developing cardiovascular disease over time,” he said.

Previous trials looking at the effect of psoriasis therapies on vascular inflammation “have been, for the most part, inconclusive,” Michael Garshick, MD, a cardiologist at NYU Langone Health, told this news organization. Dr. Garshick was not involved with the research. A 2021 systematic review of psoriasis clinicals trials reported that the tumor necrosis factor (TNF) blocker adalimumab (Humira) and phototherapy had the greatest effect on cardiometabolic markers, while ustekinumab (Stelara), an interleukin (IL)-12 and IL-23 antagonist, was the only treatment that improved vascular inflammation. These variable findings make this area “ripe for study,” noted Dr. Garshick.

To observe how apremilast, which is approved by the FDA for treating psoriasis and psoriatic arthritis, affected vascular inflammation, adiposity, and blood-based cardiometabolic markers, Dr. Gelfand organized an open-label study in adults with moderate-to-severe psoriasis. All participants were 18 years or older, had psoriasis for at least 6 months, and were candidates for systemic therapy. All patients underwent FDG PET/CT scans to assess aortic vascular inflammation and had blood work at baseline. Of the 70 patients originally enrolled in the study, 60 remained in the study at week 16, including 57 who underwent imaging for the second time. Thirty-nine participants remained in the study until week 52, and all except one had another scan.

The average age of participants was 47 years, and their mean BMI was 30. More than 80% of participants were White (83%) and 77% were male. The study population had lived with psoriasis for an average of 16 years and 8 patients also had psoriatic arthritis. At baseline, on average, participants had a Psoriasis Area and Severity Index (PASI) score of 18.62, a dermatology life quality index (DLQI) score of 11.60, and 22% of participants’ BSA (body surface area) were affected. The mean TBRmax, the marker for vascular inflammation, was 1.61.

Treatment responses were as expected for apremilast, with 35% of patients achieving PASI 75 and 65% of participants reporting DLQI scores of 5 or less by 16 weeks. At 52 weeks, 31% of the cohort had achieved PASI 75, and 67% reported DLQI score of 5 or higher. All psoriasis endpoints had improved since baseline (P = .001).

Throughout the study period, there was no significant change in TBRmax. However, in a sensitivity analysis, the 16 patients with a baseline TBRmax  of 1.6 or higher had an absolute reduction of 0.21 in TBR by week 52. “That suggests that maybe a subset of people who have higher levels of aortic inflammation at baseline may experience some reduction that portend, potentially, some health benefits over time,” Dr. Gelfand said. “Ultimately, I wouldn’t hang my hat on the finding,” he said, noting that additional research comparing the treatment to placebo is necessary.

Both visceral and subcutaneous adipose tissue (VAT and SAT) decreased by week 16, and this reduction was maintained through week 52. In the first 16 weeks of the study, VAT decreased by 5.32% (P = .0009), and SAT decreased by 5.53% (P = .0005). From baseline to 52 weeks, VAT decreased by 5.52% (P = .0148), and SAT decreased by 5.50% (P = .0096). There were no significant differences between week 16 and week 52 in VAT or SAT.

Of the 68 blood biomarkers analyzed, there were significant decreases in the inflammatory markers ferritin (P = .015) and IL-beta (P = .006), the lipid metabolism biomarker HDL-cholesterol efflux (P = .008), and ketone bodies (P = .006). There were also increases in the inflammatory marker IL-8 (P = .003), the lipid metabolism marker ApoA (P = .05), and insulin (P = .05). Ferritin was the only biomarker that was reduced on both week 16 and week 52.

“If you want to be a purist, this was a negative trial,” said Dr. Garshick, because apremilast was not found to decrease vascular inflammation; however, he noted that the biomarker changes “were hopeful secondary endpoints.” It could be, he said, that another outcome measure may be better able to show changes in vascular inflammation compared with FDG. “It’s always hard to figure out what a good surrogate endpoint is in cardiovascular trials,” he noted, “so it may be that FDG/PET is too noisy or not reliable enough to see the outcome that we want to see.”

Dr. Gelfand reports consulting fees/grants from Amgen, AbbVie, BMS, Boehringer Ingelheim, Janssen Biologics, Novartis Corp, Pfizer, and UCB (DSMB). He serves as the Deputy Editor for the Journal of Investigative Dermatology and the Chief Medical Editor at Healio Psoriatic Disease and receives honoraria for both roles. Dr. Garshick has received consulting fees from AbbVie.

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

BOSTON – Treatment with apremilast (Otezla) did not significantly affect vascular inflammation in patients with psoriasis but was associated with a generally beneficial effect on biomarkers associated with heart disease, lipid metabolism, and glucose metabolism, in a study presented at the 2022 American Academy of Dermatology annual meeting.

In the phase 4, open-label, single arm trial, participants also lost subcutaneous and visceral fat after 16 weeks on the oral medication, a phosphodiesterase 4 (PDE4) inhibitor, and maintained that loss at 52 weeks.

People with psoriasis have an increased risk of obesity, type 2 diabetes, and cardiovascular events. Patients with more significant psoriasis “tend to die about 5 years younger than they should, based on their risk factors for mortality,” Joel Gelfand, MD, MSCE, professor of dermatology and epidemiology and vice chair of clinical research in dermatology at the University of Pennsylvania Perelman School of Medicine, Philadelphia, told this news organization.

He led the research and presented the findings at the AAD meeting March 26. “As a result, there has been a keen interest in understanding how psoriasis therapies impact cardiovascular risk, the idea being that by controlling inflammation, you may lower the risk of these patients developing cardiovascular disease over time,” he said.

Previous trials looking at the effect of psoriasis therapies on vascular inflammation “have been, for the most part, inconclusive,” Michael Garshick, MD, a cardiologist at NYU Langone Health, told this news organization. Dr. Garshick was not involved with the research. A 2021 systematic review of psoriasis clinicals trials reported that the tumor necrosis factor (TNF) blocker adalimumab (Humira) and phototherapy had the greatest effect on cardiometabolic markers, while ustekinumab (Stelara), an interleukin (IL)-12 and IL-23 antagonist, was the only treatment that improved vascular inflammation. These variable findings make this area “ripe for study,” noted Dr. Garshick.

To observe how apremilast, which is approved by the FDA for treating psoriasis and psoriatic arthritis, affected vascular inflammation, adiposity, and blood-based cardiometabolic markers, Dr. Gelfand organized an open-label study in adults with moderate-to-severe psoriasis. All participants were 18 years or older, had psoriasis for at least 6 months, and were candidates for systemic therapy. All patients underwent FDG PET/CT scans to assess aortic vascular inflammation and had blood work at baseline. Of the 70 patients originally enrolled in the study, 60 remained in the study at week 16, including 57 who underwent imaging for the second time. Thirty-nine participants remained in the study until week 52, and all except one had another scan.

The average age of participants was 47 years, and their mean BMI was 30. More than 80% of participants were White (83%) and 77% were male. The study population had lived with psoriasis for an average of 16 years and 8 patients also had psoriatic arthritis. At baseline, on average, participants had a Psoriasis Area and Severity Index (PASI) score of 18.62, a dermatology life quality index (DLQI) score of 11.60, and 22% of participants’ BSA (body surface area) were affected. The mean TBRmax, the marker for vascular inflammation, was 1.61.

Treatment responses were as expected for apremilast, with 35% of patients achieving PASI 75 and 65% of participants reporting DLQI scores of 5 or less by 16 weeks. At 52 weeks, 31% of the cohort had achieved PASI 75, and 67% reported DLQI score of 5 or higher. All psoriasis endpoints had improved since baseline (P = .001).

Throughout the study period, there was no significant change in TBRmax. However, in a sensitivity analysis, the 16 patients with a baseline TBRmax  of 1.6 or higher had an absolute reduction of 0.21 in TBR by week 52. “That suggests that maybe a subset of people who have higher levels of aortic inflammation at baseline may experience some reduction that portend, potentially, some health benefits over time,” Dr. Gelfand said. “Ultimately, I wouldn’t hang my hat on the finding,” he said, noting that additional research comparing the treatment to placebo is necessary.

Both visceral and subcutaneous adipose tissue (VAT and SAT) decreased by week 16, and this reduction was maintained through week 52. In the first 16 weeks of the study, VAT decreased by 5.32% (P = .0009), and SAT decreased by 5.53% (P = .0005). From baseline to 52 weeks, VAT decreased by 5.52% (P = .0148), and SAT decreased by 5.50% (P = .0096). There were no significant differences between week 16 and week 52 in VAT or SAT.

Of the 68 blood biomarkers analyzed, there were significant decreases in the inflammatory markers ferritin (P = .015) and IL-beta (P = .006), the lipid metabolism biomarker HDL-cholesterol efflux (P = .008), and ketone bodies (P = .006). There were also increases in the inflammatory marker IL-8 (P = .003), the lipid metabolism marker ApoA (P = .05), and insulin (P = .05). Ferritin was the only biomarker that was reduced on both week 16 and week 52.

“If you want to be a purist, this was a negative trial,” said Dr. Garshick, because apremilast was not found to decrease vascular inflammation; however, he noted that the biomarker changes “were hopeful secondary endpoints.” It could be, he said, that another outcome measure may be better able to show changes in vascular inflammation compared with FDG. “It’s always hard to figure out what a good surrogate endpoint is in cardiovascular trials,” he noted, “so it may be that FDG/PET is too noisy or not reliable enough to see the outcome that we want to see.”

Dr. Gelfand reports consulting fees/grants from Amgen, AbbVie, BMS, Boehringer Ingelheim, Janssen Biologics, Novartis Corp, Pfizer, and UCB (DSMB). He serves as the Deputy Editor for the Journal of Investigative Dermatology and the Chief Medical Editor at Healio Psoriatic Disease and receives honoraria for both roles. Dr. Garshick has received consulting fees from AbbVie.

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

Approximately one in five patients who presented with headache during the acute phase of COVID-19 developed chronic daily headache, according to a study published in Cephalalgia. The greater the headache’s intensity during the acute phase, the greater the likelihood that it would persist.

The research, carried out by members of the Headache Study Group of the Spanish Society of Neurology, evaluated the evolution of headache in more than 900 Spanish patients. Because they found that headache intensity during the acute phase was associated with a more prolonged duration of headache, the team stressed the importance of promptly evaluating patients who have had COVID-19 and who then experience persistent headache.
 

Long-term evolution unknown

Headache is a common symptom of COVID-19, but its long-term evolution remains unknown. The objective of this study was to evaluate the long-term duration of headache in patients who presented with this symptom during the acute phase of the disease.

Recruitment for this multicenter study took place in March and April 2020. The 905 patients who were enrolled came from six level 3 hospitals in Spain. All completed 9 months of neurologic follow-up.

Their median age was 51 years, 66.5% were women, and more than half (52.7%) had a history of primary headache. About half of the patients required hospitalization (50.5%); the rest were treated as outpatients. The most common headache phenotype was holocranial (67.8%) of severe intensity (50.6%).
 

Persistent headache common

In the 96.6% cases for which data were available, the median duration of headache was 14 days. The headache persisted at 1 month in 31.1% of patients, at 2 months in 21.5%, at 3 months in 19%, at 6 months in 16.8%, and at 9 months in 16.0%.

“The median duration of COVID-19 headache is around 2 weeks,” David García Azorín, MD, PhD, a member of the Spanish Society of Neurology and one of the coauthors of the study, said in an interview. “However, almost 20% of patients experience it for longer than that. When still present at 2 months, the headache is more likely to follow a chronic daily pattern.” Dr. García Azorín is a neurologist and clinical researcher at the headache unit of the Hospital Clínico Universitario in Valladolid, Spain.

“So, if the headache isn’t letting up, it’s important to make the most of that window of opportunity and provide treatment in that period of 6-12 weeks,” he continued. “To do this, the best option is to carry out preventive treatment so that the patient will have a better chance of recovering.”

Study participants whose headache persisted at 9 months were older and were mostly women. They were less likely to have had pneumonia or to have experienced stabbing pain, photophobia, or phonophobia. They reported that the headache got worse when they engaged in physical activity but less frequently manifested as a throbbing headache.
 

Secondary tension headaches

On the other hand, Jaime Rodríguez Vico, MD, head of the headache unit at the Jiménez Díaz Foundation Hospital in Madrid, said in an interview that, according to his case studies, the most striking characteristics of post–COVID-19 headaches “in general are secondary, with similarities to tension headaches that patients are able to differentiate from other clinical types of headache. In patients with migraine, very often we see that we’re dealing with a trigger. In other words, more migraines – and more intense ones at that – are brought about.”

He added: “Generally, post–COVID-19 headache usually lasts 1-2 weeks, but we have cases of it lasting several months and even over a year with persistent daily headache. These more persistent cases are probably connected to another type of pathology that makes them more susceptible to becoming chronic, something that occurs in another type of primary headache known as new daily persistent headache.”
 

Primary headache exacerbation