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Cardiovascular risk factors linked to brain atrophy in MS
The presence of cardiovascular risk factors in patients with multiple sclerosis (MS) is associated with a greater degree of brain atrophy even in young patients who are unlikely to have small vessel disease, a new study has shown.
The results were presented by Raffaello Bonacchi, MD, Vita-Salute San Raffaele University, Milan, Italy, at at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS–ACTRIMS) 2020, this year known as MSVirtual2020. .
“Our results suggest that even low levels of exposure to cardiovascular risk factors are important in MS and might affect brain atrophy—and therefore long-term disability—even in young patients,” Dr. Bonacchi said.
“It is not only smoking,” he added. “Other cardiovascular risk factors also appear to be implicated. We found a synergistic effect of the different risk factors.”
These are only preliminary data and need to be confirmed in other studies,” he said, “but it does suggest that MS neurologists need to pay attention to comprehensive care—not just MS disease activity.
“They also need to be discussing lifestyle with their patients, evaluating their cardiovascular risk factors, and giving advice on stopping smoking, lowering blood pressure, cholesterol, etc.”
Brain changes
Dr. Bonacchi explained that previous studies have suggested a relationship between cardiovascular risk factors and changes on magnetic resonance imaging (MRI) and clinical outcomes in patients with MS that may be mediated by small vessel disease and/or inflammation.
“Small vessel disease is widespread in the population over 50 years of age, but in this study we wanted to look at the impact of cardiovascular risk factors in younger patients with MS who are not likely to have much small vessel disease to try and see whether there is still a relationship with brain atrophy or white/gray matter lesions,” he said.
Previous studies have not set an age limit for examining this relationship and they have also assessed the presence versus absence of cardiovascular risk factors, without attempting to grade the strength of exposure, he noted.
For the current study, the researchers examined several cardiovascular risk factors and in addition to just being present or absent. They also graded each risk factor as being stringent or not depending on a certain threshold.
For example, smoking was defined as a threshold of 5 pack-years (smoking 5 cigarettes a day for 20 years or 20 cigarettes a day for 5 years). And the more stringent definition was 10 pack-years.
For hypertension, the stringent definition was consistently high blood pressure levels and use of antihypertensive medication, with similar definitions used for cholesterol and diabetes.
This was a cross-sectional observational study in 124 patients with MS and 95 healthy controls. The researchers examined MRI scans and neurological exams and investigated whether the amount of cardiovascular risk factors a patient was exposed to was associated with degree of brain atrophy and white matter/gray matter volume. Results were adjusted for age, sex, disease duration, phenotype (relapsing-remitting versus progressive MS) and treatment.
Results showed no significant difference if patients were exposed to at least one classical risk factor versus no risk factors. But if a patient had at least two classical risk factors, significant differences were found in gray matter, white matter, and total brain volume.
Patients with MS and no risk factors had a mean brain volume of 1524 mL versus 1481 mL in those with at least two risk factors, a difference that was significant (P = 0.003). Mean gray matter volume was 856 mL in MS patients without cardiovascular risk factors and 836 mL in those with at least two risk factors (P = 0.01) Mean white matter volume was 668 mL in MS patients without cardiovascular risk factors and 845 mL in those with at least two risk factors (P = 0.03).
“This is one of the first studies to have graded degrees of risk factors and we found one stringent risk factor was associated with the same effects on brain atrophy as two less stringent risk factors,” Dr. Bonacchi reported.
Healthy controls showed no differences in any of the brain volume outcomes in those with or without cardiovascular risk factors.
“As our population was under aged 50 years, who are unlikely to have much small vessel disease, our results suggest that the influence of cardiovascular risk factors on brain atrophy in MS is not just mediated through small vessel disease and is probably also mediated by increased inflammation,” Dr. Bonacchi suggested.
Impact of CV risk factors
Commenting on the study, Dalia Rotstein, MD, assistant professor, department of neurology, University of Toronto, Ontario, Canada, session cochair, said: “This is an interesting study that captures the impact of cardiovascular risk factors on various measures of brain atrophy in MS.”
The cohort was quite young, under age 50, and the effect on brain atrophy was increased with more severe cardiovascular risk factors, she noted.
“The investigators compared these effects to a population of healthy controls and did not observe as substantial an effect in controls. However, they were likely underpowered for the analysis in the healthy controls because of a relatively small number of subjects with cardiovascular risk factors in this group,” Dr. Rotstein noted.
“More research is needed to determine whether the observed relationship is unique to MS and whether treating cardiovascular risk factors may help protect against neurodegeneration in MS,” she added.
Dr. Bonacchi has reported no relevant financial relationships. Dr. Rotstein has reported acting as a consultant for Roche, Alexion, Novartis, EMD Serono, and Sanofi Aventis.
SOURCE: Bonacchi R. et al. MSVirtual2020. Session PS04.05.
This article originally appeared on Medscape.com .
The presence of cardiovascular risk factors in patients with multiple sclerosis (MS) is associated with a greater degree of brain atrophy even in young patients who are unlikely to have small vessel disease, a new study has shown.
The results were presented by Raffaello Bonacchi, MD, Vita-Salute San Raffaele University, Milan, Italy, at at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS–ACTRIMS) 2020, this year known as MSVirtual2020. .
“Our results suggest that even low levels of exposure to cardiovascular risk factors are important in MS and might affect brain atrophy—and therefore long-term disability—even in young patients,” Dr. Bonacchi said.
“It is not only smoking,” he added. “Other cardiovascular risk factors also appear to be implicated. We found a synergistic effect of the different risk factors.”
These are only preliminary data and need to be confirmed in other studies,” he said, “but it does suggest that MS neurologists need to pay attention to comprehensive care—not just MS disease activity.
“They also need to be discussing lifestyle with their patients, evaluating their cardiovascular risk factors, and giving advice on stopping smoking, lowering blood pressure, cholesterol, etc.”
Brain changes
Dr. Bonacchi explained that previous studies have suggested a relationship between cardiovascular risk factors and changes on magnetic resonance imaging (MRI) and clinical outcomes in patients with MS that may be mediated by small vessel disease and/or inflammation.
“Small vessel disease is widespread in the population over 50 years of age, but in this study we wanted to look at the impact of cardiovascular risk factors in younger patients with MS who are not likely to have much small vessel disease to try and see whether there is still a relationship with brain atrophy or white/gray matter lesions,” he said.
Previous studies have not set an age limit for examining this relationship and they have also assessed the presence versus absence of cardiovascular risk factors, without attempting to grade the strength of exposure, he noted.
For the current study, the researchers examined several cardiovascular risk factors and in addition to just being present or absent. They also graded each risk factor as being stringent or not depending on a certain threshold.
For example, smoking was defined as a threshold of 5 pack-years (smoking 5 cigarettes a day for 20 years or 20 cigarettes a day for 5 years). And the more stringent definition was 10 pack-years.
For hypertension, the stringent definition was consistently high blood pressure levels and use of antihypertensive medication, with similar definitions used for cholesterol and diabetes.
This was a cross-sectional observational study in 124 patients with MS and 95 healthy controls. The researchers examined MRI scans and neurological exams and investigated whether the amount of cardiovascular risk factors a patient was exposed to was associated with degree of brain atrophy and white matter/gray matter volume. Results were adjusted for age, sex, disease duration, phenotype (relapsing-remitting versus progressive MS) and treatment.
Results showed no significant difference if patients were exposed to at least one classical risk factor versus no risk factors. But if a patient had at least two classical risk factors, significant differences were found in gray matter, white matter, and total brain volume.
Patients with MS and no risk factors had a mean brain volume of 1524 mL versus 1481 mL in those with at least two risk factors, a difference that was significant (P = 0.003). Mean gray matter volume was 856 mL in MS patients without cardiovascular risk factors and 836 mL in those with at least two risk factors (P = 0.01) Mean white matter volume was 668 mL in MS patients without cardiovascular risk factors and 845 mL in those with at least two risk factors (P = 0.03).
“This is one of the first studies to have graded degrees of risk factors and we found one stringent risk factor was associated with the same effects on brain atrophy as two less stringent risk factors,” Dr. Bonacchi reported.
Healthy controls showed no differences in any of the brain volume outcomes in those with or without cardiovascular risk factors.
“As our population was under aged 50 years, who are unlikely to have much small vessel disease, our results suggest that the influence of cardiovascular risk factors on brain atrophy in MS is not just mediated through small vessel disease and is probably also mediated by increased inflammation,” Dr. Bonacchi suggested.
Impact of CV risk factors
Commenting on the study, Dalia Rotstein, MD, assistant professor, department of neurology, University of Toronto, Ontario, Canada, session cochair, said: “This is an interesting study that captures the impact of cardiovascular risk factors on various measures of brain atrophy in MS.”
The cohort was quite young, under age 50, and the effect on brain atrophy was increased with more severe cardiovascular risk factors, she noted.
“The investigators compared these effects to a population of healthy controls and did not observe as substantial an effect in controls. However, they were likely underpowered for the analysis in the healthy controls because of a relatively small number of subjects with cardiovascular risk factors in this group,” Dr. Rotstein noted.
“More research is needed to determine whether the observed relationship is unique to MS and whether treating cardiovascular risk factors may help protect against neurodegeneration in MS,” she added.
Dr. Bonacchi has reported no relevant financial relationships. Dr. Rotstein has reported acting as a consultant for Roche, Alexion, Novartis, EMD Serono, and Sanofi Aventis.
SOURCE: Bonacchi R. et al. MSVirtual2020. Session PS04.05.
This article originally appeared on Medscape.com .
The presence of cardiovascular risk factors in patients with multiple sclerosis (MS) is associated with a greater degree of brain atrophy even in young patients who are unlikely to have small vessel disease, a new study has shown.
The results were presented by Raffaello Bonacchi, MD, Vita-Salute San Raffaele University, Milan, Italy, at at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS–ACTRIMS) 2020, this year known as MSVirtual2020. .
“Our results suggest that even low levels of exposure to cardiovascular risk factors are important in MS and might affect brain atrophy—and therefore long-term disability—even in young patients,” Dr. Bonacchi said.
“It is not only smoking,” he added. “Other cardiovascular risk factors also appear to be implicated. We found a synergistic effect of the different risk factors.”
These are only preliminary data and need to be confirmed in other studies,” he said, “but it does suggest that MS neurologists need to pay attention to comprehensive care—not just MS disease activity.
“They also need to be discussing lifestyle with their patients, evaluating their cardiovascular risk factors, and giving advice on stopping smoking, lowering blood pressure, cholesterol, etc.”
Brain changes
Dr. Bonacchi explained that previous studies have suggested a relationship between cardiovascular risk factors and changes on magnetic resonance imaging (MRI) and clinical outcomes in patients with MS that may be mediated by small vessel disease and/or inflammation.
“Small vessel disease is widespread in the population over 50 years of age, but in this study we wanted to look at the impact of cardiovascular risk factors in younger patients with MS who are not likely to have much small vessel disease to try and see whether there is still a relationship with brain atrophy or white/gray matter lesions,” he said.
Previous studies have not set an age limit for examining this relationship and they have also assessed the presence versus absence of cardiovascular risk factors, without attempting to grade the strength of exposure, he noted.
For the current study, the researchers examined several cardiovascular risk factors and in addition to just being present or absent. They also graded each risk factor as being stringent or not depending on a certain threshold.
For example, smoking was defined as a threshold of 5 pack-years (smoking 5 cigarettes a day for 20 years or 20 cigarettes a day for 5 years). And the more stringent definition was 10 pack-years.
For hypertension, the stringent definition was consistently high blood pressure levels and use of antihypertensive medication, with similar definitions used for cholesterol and diabetes.
This was a cross-sectional observational study in 124 patients with MS and 95 healthy controls. The researchers examined MRI scans and neurological exams and investigated whether the amount of cardiovascular risk factors a patient was exposed to was associated with degree of brain atrophy and white matter/gray matter volume. Results were adjusted for age, sex, disease duration, phenotype (relapsing-remitting versus progressive MS) and treatment.
Results showed no significant difference if patients were exposed to at least one classical risk factor versus no risk factors. But if a patient had at least two classical risk factors, significant differences were found in gray matter, white matter, and total brain volume.
Patients with MS and no risk factors had a mean brain volume of 1524 mL versus 1481 mL in those with at least two risk factors, a difference that was significant (P = 0.003). Mean gray matter volume was 856 mL in MS patients without cardiovascular risk factors and 836 mL in those with at least two risk factors (P = 0.01) Mean white matter volume was 668 mL in MS patients without cardiovascular risk factors and 845 mL in those with at least two risk factors (P = 0.03).
“This is one of the first studies to have graded degrees of risk factors and we found one stringent risk factor was associated with the same effects on brain atrophy as two less stringent risk factors,” Dr. Bonacchi reported.
Healthy controls showed no differences in any of the brain volume outcomes in those with or without cardiovascular risk factors.
“As our population was under aged 50 years, who are unlikely to have much small vessel disease, our results suggest that the influence of cardiovascular risk factors on brain atrophy in MS is not just mediated through small vessel disease and is probably also mediated by increased inflammation,” Dr. Bonacchi suggested.
Impact of CV risk factors
Commenting on the study, Dalia Rotstein, MD, assistant professor, department of neurology, University of Toronto, Ontario, Canada, session cochair, said: “This is an interesting study that captures the impact of cardiovascular risk factors on various measures of brain atrophy in MS.”
The cohort was quite young, under age 50, and the effect on brain atrophy was increased with more severe cardiovascular risk factors, she noted.
“The investigators compared these effects to a population of healthy controls and did not observe as substantial an effect in controls. However, they were likely underpowered for the analysis in the healthy controls because of a relatively small number of subjects with cardiovascular risk factors in this group,” Dr. Rotstein noted.
“More research is needed to determine whether the observed relationship is unique to MS and whether treating cardiovascular risk factors may help protect against neurodegeneration in MS,” she added.
Dr. Bonacchi has reported no relevant financial relationships. Dr. Rotstein has reported acting as a consultant for Roche, Alexion, Novartis, EMD Serono, and Sanofi Aventis.
SOURCE: Bonacchi R. et al. MSVirtual2020. Session PS04.05.
This article originally appeared on Medscape.com .
FROM MSVirtual2020
Lessons for patients with MS and COVID-19
Two important lessons about managing patients with multiple sclerosis (MS) and COVID-19 have emerged from a hospital clinic in Madrid that managed COVID-infected patients with MS through the peak of the pandemic: Combined polymeric chain reaction and serology testing helped avoid disease reactivation in asymptomatic carriers during the pandemic peak, although after the peak PCR alone proved just as effective; and
Virginia Meca-Lallana, MD, a neurologist and coordinator of the demyelinating diseases unit at the Hospital of the University of the Princess in Madrid, and colleagues presented their findings in two posters at the Joint European Committee for Treatment and Research in Multiple Sclerosis-Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2020, this year known as MSVirtual2020.
“MS treatments don’t seem to make the prognosis of COVID-19 worse, but it is very important to evaluate other risk factors,” Dr. Meca-Lallana said in an interview. “MS treatments prevent the patients’ disability, and it is very important not to stop them if it isn’t necessary.”
The results arose from a multidisciplinary safety protocol involving neurology, microbiology, and preventive medicine that the University of Princess physicians developed to keep MS stable in patients diagnosed with SARS-CoV-2.
The researchers obtained 152 PCR nasopharyngeal swabs and 140 serology tests in 90 patients with MS over 3 months before starting a variety of MS treatments: Natalizumab (96 tests), ocrelizumab (36), rituximab (3), methylprednisolone (7), cladribine (4), and dimethyl fumarate (3). The protocol identified 7 asymptomatic carriers—7.8% of the total population—5 of whom had positive immunoglobulin M and G serology. The study also confirmed 5 patients with positive IgM+IgG serology post-infection, but no COVID-19 reactivations were detected after implementation of the protocol.
“The safety protocol reached its objective of avoiding disease reactivation and clinical activation in asymptomatic carriers,” Dr. Meca-Lallana said.
The second poster she presented reported on the real-world experience with SARS-CoV-2 in the MS unit at her hospital. The observational, prospective study included 41 cases, 38 of which were relapsing-remitting MS and the remainder progressive MS. The patients had MS for an average of 9 years.
“We need more patients to draw more robust conclusions, but in our patients, MS treatments seem safe in this situation,” Dr. Meca-Lallana said. “We did not discontinue treatments, and after our first results, we only delayed treatments in patients with any additional comorbidity or when coming to the hospital was not safe.”
A total of 39 patients were taking disease-modifying therapies (DMTs): 46.3% with oral agents, 39% with monoclonal antibodies, and 10% with injectable agents; 27 patients were previously treated with other DMTs. The median Expanded Disability Status Scale (EDSS) was 2.5, and 11 patients had clinical activity the previous year. Eighteen cases were confirmed by PCR or serology, or both, and 23 were diagnosed clinically.
Among the patients with MS and COVID-19, 17% were admitted to the hospital. Six patients had pneumonia, but none required admission to the intensive care unit, and no deaths occurred. Three patients had other comorbidities. Admitted patients tended to be older and had higher EDSS scores, although the difference was not statistically significant. MS worsened in 7 patients, and 10 patients stopped or paused DMTs because of the infection.
“Multiple sclerosis is a weakening illness,” Dr. Meca-Lallana said. “MS treatments do not seem to make the prognosis of COVID-19 worse, but it is very important to evaluate other risk factors.”
The SARS-CoV-2 infection does not seem to result in a more aggressive form of the disease in MS patients, and selective immunosuppression may improve their outcomes, she noted.
“MS treatments avoid the patient’s disability,” the investigator added, “and it is very important not to stop them if it isn’t necessary.”
Dr. Meca-Lallana had no relevant financial disclosures.
Two important lessons about managing patients with multiple sclerosis (MS) and COVID-19 have emerged from a hospital clinic in Madrid that managed COVID-infected patients with MS through the peak of the pandemic: Combined polymeric chain reaction and serology testing helped avoid disease reactivation in asymptomatic carriers during the pandemic peak, although after the peak PCR alone proved just as effective; and
Virginia Meca-Lallana, MD, a neurologist and coordinator of the demyelinating diseases unit at the Hospital of the University of the Princess in Madrid, and colleagues presented their findings in two posters at the Joint European Committee for Treatment and Research in Multiple Sclerosis-Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2020, this year known as MSVirtual2020.
“MS treatments don’t seem to make the prognosis of COVID-19 worse, but it is very important to evaluate other risk factors,” Dr. Meca-Lallana said in an interview. “MS treatments prevent the patients’ disability, and it is very important not to stop them if it isn’t necessary.”
The results arose from a multidisciplinary safety protocol involving neurology, microbiology, and preventive medicine that the University of Princess physicians developed to keep MS stable in patients diagnosed with SARS-CoV-2.
The researchers obtained 152 PCR nasopharyngeal swabs and 140 serology tests in 90 patients with MS over 3 months before starting a variety of MS treatments: Natalizumab (96 tests), ocrelizumab (36), rituximab (3), methylprednisolone (7), cladribine (4), and dimethyl fumarate (3). The protocol identified 7 asymptomatic carriers—7.8% of the total population—5 of whom had positive immunoglobulin M and G serology. The study also confirmed 5 patients with positive IgM+IgG serology post-infection, but no COVID-19 reactivations were detected after implementation of the protocol.
“The safety protocol reached its objective of avoiding disease reactivation and clinical activation in asymptomatic carriers,” Dr. Meca-Lallana said.
The second poster she presented reported on the real-world experience with SARS-CoV-2 in the MS unit at her hospital. The observational, prospective study included 41 cases, 38 of which were relapsing-remitting MS and the remainder progressive MS. The patients had MS for an average of 9 years.
“We need more patients to draw more robust conclusions, but in our patients, MS treatments seem safe in this situation,” Dr. Meca-Lallana said. “We did not discontinue treatments, and after our first results, we only delayed treatments in patients with any additional comorbidity or when coming to the hospital was not safe.”
A total of 39 patients were taking disease-modifying therapies (DMTs): 46.3% with oral agents, 39% with monoclonal antibodies, and 10% with injectable agents; 27 patients were previously treated with other DMTs. The median Expanded Disability Status Scale (EDSS) was 2.5, and 11 patients had clinical activity the previous year. Eighteen cases were confirmed by PCR or serology, or both, and 23 were diagnosed clinically.
Among the patients with MS and COVID-19, 17% were admitted to the hospital. Six patients had pneumonia, but none required admission to the intensive care unit, and no deaths occurred. Three patients had other comorbidities. Admitted patients tended to be older and had higher EDSS scores, although the difference was not statistically significant. MS worsened in 7 patients, and 10 patients stopped or paused DMTs because of the infection.
“Multiple sclerosis is a weakening illness,” Dr. Meca-Lallana said. “MS treatments do not seem to make the prognosis of COVID-19 worse, but it is very important to evaluate other risk factors.”
The SARS-CoV-2 infection does not seem to result in a more aggressive form of the disease in MS patients, and selective immunosuppression may improve their outcomes, she noted.
“MS treatments avoid the patient’s disability,” the investigator added, “and it is very important not to stop them if it isn’t necessary.”
Dr. Meca-Lallana had no relevant financial disclosures.
Two important lessons about managing patients with multiple sclerosis (MS) and COVID-19 have emerged from a hospital clinic in Madrid that managed COVID-infected patients with MS through the peak of the pandemic: Combined polymeric chain reaction and serology testing helped avoid disease reactivation in asymptomatic carriers during the pandemic peak, although after the peak PCR alone proved just as effective; and
Virginia Meca-Lallana, MD, a neurologist and coordinator of the demyelinating diseases unit at the Hospital of the University of the Princess in Madrid, and colleagues presented their findings in two posters at the Joint European Committee for Treatment and Research in Multiple Sclerosis-Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2020, this year known as MSVirtual2020.
“MS treatments don’t seem to make the prognosis of COVID-19 worse, but it is very important to evaluate other risk factors,” Dr. Meca-Lallana said in an interview. “MS treatments prevent the patients’ disability, and it is very important not to stop them if it isn’t necessary.”
The results arose from a multidisciplinary safety protocol involving neurology, microbiology, and preventive medicine that the University of Princess physicians developed to keep MS stable in patients diagnosed with SARS-CoV-2.
The researchers obtained 152 PCR nasopharyngeal swabs and 140 serology tests in 90 patients with MS over 3 months before starting a variety of MS treatments: Natalizumab (96 tests), ocrelizumab (36), rituximab (3), methylprednisolone (7), cladribine (4), and dimethyl fumarate (3). The protocol identified 7 asymptomatic carriers—7.8% of the total population—5 of whom had positive immunoglobulin M and G serology. The study also confirmed 5 patients with positive IgM+IgG serology post-infection, but no COVID-19 reactivations were detected after implementation of the protocol.
“The safety protocol reached its objective of avoiding disease reactivation and clinical activation in asymptomatic carriers,” Dr. Meca-Lallana said.
The second poster she presented reported on the real-world experience with SARS-CoV-2 in the MS unit at her hospital. The observational, prospective study included 41 cases, 38 of which were relapsing-remitting MS and the remainder progressive MS. The patients had MS for an average of 9 years.
“We need more patients to draw more robust conclusions, but in our patients, MS treatments seem safe in this situation,” Dr. Meca-Lallana said. “We did not discontinue treatments, and after our first results, we only delayed treatments in patients with any additional comorbidity or when coming to the hospital was not safe.”
A total of 39 patients were taking disease-modifying therapies (DMTs): 46.3% with oral agents, 39% with monoclonal antibodies, and 10% with injectable agents; 27 patients were previously treated with other DMTs. The median Expanded Disability Status Scale (EDSS) was 2.5, and 11 patients had clinical activity the previous year. Eighteen cases were confirmed by PCR or serology, or both, and 23 were diagnosed clinically.
Among the patients with MS and COVID-19, 17% were admitted to the hospital. Six patients had pneumonia, but none required admission to the intensive care unit, and no deaths occurred. Three patients had other comorbidities. Admitted patients tended to be older and had higher EDSS scores, although the difference was not statistically significant. MS worsened in 7 patients, and 10 patients stopped or paused DMTs because of the infection.
“Multiple sclerosis is a weakening illness,” Dr. Meca-Lallana said. “MS treatments do not seem to make the prognosis of COVID-19 worse, but it is very important to evaluate other risk factors.”
The SARS-CoV-2 infection does not seem to result in a more aggressive form of the disease in MS patients, and selective immunosuppression may improve their outcomes, she noted.
“MS treatments avoid the patient’s disability,” the investigator added, “and it is very important not to stop them if it isn’t necessary.”
Dr. Meca-Lallana had no relevant financial disclosures.
FROM MSVirtual2020
Exposure to DMT may delay disability accumulation in primary progressive MS
Reducing the delay to treatment initiation, as well as treating younger patients, might improve long-term disability outcomes, according to a new study.
“To optimize treatment decision-making in primary progressive MS, further profiling of the best candidates for treatment is needed,” said the researchers. The study was presented at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS–ACTRIMS) 2020, this year known as MSVirtual2020.
Ocrelizumab remains the only treatment available for patients with primary progressive MS. In clinical trials, other drugs have failed to reduce disability progression in this population. Mattia Fonderico, a doctoral student and research assistant at the University of Florence (Italy), and colleagues reviewed data from the Italian MS Registry to examine whether DMT affects the attainment of given disability outcomes.
Patients with longer exposure were younger at baseline
Patients eligible for inclusion in the study had primary progressive MS, at least three evaluations using the Expanded Disability Status Scale (EDSS), and 3 years’ follow-up. The investigators defined the baseline for untreated patients as the first EDSS evaluation. For treated patients, the baseline was the date of DMT initiation.
Using multivariable Cox regression models, Ms. Fonderico and colleagues examined the effect of DMT on the risk of reaching EDSS scores of 6 (i.e., requirement for intermittent or unilateral constant walking assistance) and 7 (i.e., restriction to a wheelchair) as a dichotomous variable and as a time-dependent covariate. The researchers adjusted the data for age at baseline, sex, first EDSS score, symptoms at onset, annualized visit rate, and annualized relapse rate. They compared outcomes with an as-treated analysis and chose cohorts with similar baseline characteristics using propensity-score matching. In addition, Ms. Fonderico and colleagues also analyzed quartiles of DMT exposure.
The investigators included 1,214 patients (671 women) in their analysis. The population’s mean age at baseline was 48.7 years, and its mean EDSS score was 4.1. A total of 626 patients (52%) received DMT during follow-up. Approximately 57% of DMTs were platform therapies, and 43% were high-efficacy therapies.
Mean follow-up duration was 11.6 years. By the end of follow-up, 994 patients (82%) reached an EDSS score of 6, and 539 (44%) reached an EDSS score of 7. Multivariable Cox regression models indicated that DMT, analyzed as a dichotomous variable, did not affect the risk of reaching EDSS 6 (adjusted hazard ratio, 1.1) or EDSS 7 (aHR, 0.93). Longer DMT exposure, however, significantly reduced the risk of reaching EDSS 7 (aHR, 0.73).
Compared with patients with shorter exposure to DMT, patients in the highest quartile of DMT exposure were younger at baseline (mean age, 44.1 years) and initiated DMT closer to disease onset (mean time to DMT initiation was 6.8 years). The propensity score matching analysis confirmed these findings.
The investigators did not consider MRI variables, which Ms. Fonderico acknowledged was a weakness of the study. In addition, they did not analyze the effect of superimposed relapses.
A new perspective on primary progressive MS?
These results suggest that primary progressive MS behaves like relapsing-remitting MS, said Gavin Giovannoni, MD, PhD, chair of neurology at Queen Mary University of London. That is, they suggest that primary progressive MS “is modifiable by a DMT and that the earlier you treat, the better the outcome.” The results also indicate that neurologists commonly prescribe DMT off label in Italy, he added.
A weakness of the study is that it was not randomized. Furthermore, “EDSS [evaluations] tend not be done properly in routine clinical practice,” said Dr. Giovannoni. Still, the study raises an important question for future research. “Why have we missed the treatment effect in previous trials?” asked Dr. Giovannoni. Whether previous trials were too short or underpowered could be investigated, he added.
Study funding was not reported. Ms. Fonderico had no relevant disclosures. Dr. Giovannoni had no relevant disclosures.
Reducing the delay to treatment initiation, as well as treating younger patients, might improve long-term disability outcomes, according to a new study.
“To optimize treatment decision-making in primary progressive MS, further profiling of the best candidates for treatment is needed,” said the researchers. The study was presented at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS–ACTRIMS) 2020, this year known as MSVirtual2020.
Ocrelizumab remains the only treatment available for patients with primary progressive MS. In clinical trials, other drugs have failed to reduce disability progression in this population. Mattia Fonderico, a doctoral student and research assistant at the University of Florence (Italy), and colleagues reviewed data from the Italian MS Registry to examine whether DMT affects the attainment of given disability outcomes.
Patients with longer exposure were younger at baseline
Patients eligible for inclusion in the study had primary progressive MS, at least three evaluations using the Expanded Disability Status Scale (EDSS), and 3 years’ follow-up. The investigators defined the baseline for untreated patients as the first EDSS evaluation. For treated patients, the baseline was the date of DMT initiation.
Using multivariable Cox regression models, Ms. Fonderico and colleagues examined the effect of DMT on the risk of reaching EDSS scores of 6 (i.e., requirement for intermittent or unilateral constant walking assistance) and 7 (i.e., restriction to a wheelchair) as a dichotomous variable and as a time-dependent covariate. The researchers adjusted the data for age at baseline, sex, first EDSS score, symptoms at onset, annualized visit rate, and annualized relapse rate. They compared outcomes with an as-treated analysis and chose cohorts with similar baseline characteristics using propensity-score matching. In addition, Ms. Fonderico and colleagues also analyzed quartiles of DMT exposure.
The investigators included 1,214 patients (671 women) in their analysis. The population’s mean age at baseline was 48.7 years, and its mean EDSS score was 4.1. A total of 626 patients (52%) received DMT during follow-up. Approximately 57% of DMTs were platform therapies, and 43% were high-efficacy therapies.
Mean follow-up duration was 11.6 years. By the end of follow-up, 994 patients (82%) reached an EDSS score of 6, and 539 (44%) reached an EDSS score of 7. Multivariable Cox regression models indicated that DMT, analyzed as a dichotomous variable, did not affect the risk of reaching EDSS 6 (adjusted hazard ratio, 1.1) or EDSS 7 (aHR, 0.93). Longer DMT exposure, however, significantly reduced the risk of reaching EDSS 7 (aHR, 0.73).
Compared with patients with shorter exposure to DMT, patients in the highest quartile of DMT exposure were younger at baseline (mean age, 44.1 years) and initiated DMT closer to disease onset (mean time to DMT initiation was 6.8 years). The propensity score matching analysis confirmed these findings.
The investigators did not consider MRI variables, which Ms. Fonderico acknowledged was a weakness of the study. In addition, they did not analyze the effect of superimposed relapses.
A new perspective on primary progressive MS?
These results suggest that primary progressive MS behaves like relapsing-remitting MS, said Gavin Giovannoni, MD, PhD, chair of neurology at Queen Mary University of London. That is, they suggest that primary progressive MS “is modifiable by a DMT and that the earlier you treat, the better the outcome.” The results also indicate that neurologists commonly prescribe DMT off label in Italy, he added.
A weakness of the study is that it was not randomized. Furthermore, “EDSS [evaluations] tend not be done properly in routine clinical practice,” said Dr. Giovannoni. Still, the study raises an important question for future research. “Why have we missed the treatment effect in previous trials?” asked Dr. Giovannoni. Whether previous trials were too short or underpowered could be investigated, he added.
Study funding was not reported. Ms. Fonderico had no relevant disclosures. Dr. Giovannoni had no relevant disclosures.
Reducing the delay to treatment initiation, as well as treating younger patients, might improve long-term disability outcomes, according to a new study.
“To optimize treatment decision-making in primary progressive MS, further profiling of the best candidates for treatment is needed,” said the researchers. The study was presented at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS–ACTRIMS) 2020, this year known as MSVirtual2020.
Ocrelizumab remains the only treatment available for patients with primary progressive MS. In clinical trials, other drugs have failed to reduce disability progression in this population. Mattia Fonderico, a doctoral student and research assistant at the University of Florence (Italy), and colleagues reviewed data from the Italian MS Registry to examine whether DMT affects the attainment of given disability outcomes.
Patients with longer exposure were younger at baseline
Patients eligible for inclusion in the study had primary progressive MS, at least three evaluations using the Expanded Disability Status Scale (EDSS), and 3 years’ follow-up. The investigators defined the baseline for untreated patients as the first EDSS evaluation. For treated patients, the baseline was the date of DMT initiation.
Using multivariable Cox regression models, Ms. Fonderico and colleagues examined the effect of DMT on the risk of reaching EDSS scores of 6 (i.e., requirement for intermittent or unilateral constant walking assistance) and 7 (i.e., restriction to a wheelchair) as a dichotomous variable and as a time-dependent covariate. The researchers adjusted the data for age at baseline, sex, first EDSS score, symptoms at onset, annualized visit rate, and annualized relapse rate. They compared outcomes with an as-treated analysis and chose cohorts with similar baseline characteristics using propensity-score matching. In addition, Ms. Fonderico and colleagues also analyzed quartiles of DMT exposure.
The investigators included 1,214 patients (671 women) in their analysis. The population’s mean age at baseline was 48.7 years, and its mean EDSS score was 4.1. A total of 626 patients (52%) received DMT during follow-up. Approximately 57% of DMTs were platform therapies, and 43% were high-efficacy therapies.
Mean follow-up duration was 11.6 years. By the end of follow-up, 994 patients (82%) reached an EDSS score of 6, and 539 (44%) reached an EDSS score of 7. Multivariable Cox regression models indicated that DMT, analyzed as a dichotomous variable, did not affect the risk of reaching EDSS 6 (adjusted hazard ratio, 1.1) or EDSS 7 (aHR, 0.93). Longer DMT exposure, however, significantly reduced the risk of reaching EDSS 7 (aHR, 0.73).
Compared with patients with shorter exposure to DMT, patients in the highest quartile of DMT exposure were younger at baseline (mean age, 44.1 years) and initiated DMT closer to disease onset (mean time to DMT initiation was 6.8 years). The propensity score matching analysis confirmed these findings.
The investigators did not consider MRI variables, which Ms. Fonderico acknowledged was a weakness of the study. In addition, they did not analyze the effect of superimposed relapses.
A new perspective on primary progressive MS?
These results suggest that primary progressive MS behaves like relapsing-remitting MS, said Gavin Giovannoni, MD, PhD, chair of neurology at Queen Mary University of London. That is, they suggest that primary progressive MS “is modifiable by a DMT and that the earlier you treat, the better the outcome.” The results also indicate that neurologists commonly prescribe DMT off label in Italy, he added.
A weakness of the study is that it was not randomized. Furthermore, “EDSS [evaluations] tend not be done properly in routine clinical practice,” said Dr. Giovannoni. Still, the study raises an important question for future research. “Why have we missed the treatment effect in previous trials?” asked Dr. Giovannoni. Whether previous trials were too short or underpowered could be investigated, he added.
Study funding was not reported. Ms. Fonderico had no relevant disclosures. Dr. Giovannoni had no relevant disclosures.
FROM MSVirtual 2020
ASBMR 2020: Sequential osteoporosis meds, AI, bone cancer, and more
The virtual American Society for Bone and Mineral Research 2020 annual meeting “is full of highlights,” says Lorenz Hofbauer, MD, scientific chair, but “this year you won’t lose time in the hallways to switch between the talks,” he quipped.
Nevertheless, “although we won’t be coming together face to face this year, you will have the flexibility to virtually connect with peers and colleagues from around the world,” Teresita Bellido, PhD, ASBMR president emphasized in a message to members.
Like other medical organizations, with the advent of the COVID-19 pandemic, the ASBMR had to quickly pivot to provide a virtual meeting.
The meeting will take place September 11-15 and is free for ASBMR members.
Speaking to Medscape Medical News, Bellido and Hofbauer drew attention to some of the meeting’s major themes, key sessions, and top clinical oral abstracts.
Attendees at this year’s virtual meeting will hear the latest information on optimal sequential treatment for osteoporosis, the latest research using artificial intelligence (AI), and bone and cancer, among other topics.
Sequential osteoporosis treatment a recurring theme
According to Hofbauer, from Dresden Technical University, Germany, the September 13 Cutting Edge symposium entitled, “Optimizing Sequential Osteoporosis Treatment,” is not to be missed, and the topic “will be a leitmotiv [recurrent theme] for the entire meeting.”
During this session speakers will present findings from two perspectives – basic science and clinical applications – with the latter being another recurring theme at the meeting.
Bellido, from the University of Arkansas for Medical Sciences, in Little Rock, pointed out that romosozumab (Evenity, Amgen), recently approved by the US Food and Drug Administration, is an example of how basic laboratory research can lead to important new therapies.
Anabolic therapies for osteoporosis that “build up bone” include teriparatide, abaloparatide, and now romosozumab, whereas antiresorptive therapies that stop bone resorption include the bisphosphonates (alendronate, risedronate, ibandronate, and zoledronic acid) and the monoclonal antibody denosumab, Bellido explained.
As osteoporosis treatment options have expanded, the timing and sequencing of optimal therapies have become much more complex, and so this session on sequencing, as well as the September 13 Concurrent Orals session, “Issues of Long-term Treatment and Discontinuation,” is sure to spark interest.
The ASBMR/European Calcified Tissue Society debate, entitled, “A Treat to Target Approach is Helpful for Osteoporosis Management,” is also expected to be lively and generate wide interest, according to Bellido and Hofbauer.
Michael R. McClung, MD, Oregon Osteoporosis Center, Portland, will argue against the motion and Celia Gregson, PhD, University of Bristol, UK, will argue for it. Attendees will be able to vote for/against the motion before and after the debate, and the result will indicate which speaker was more persuasive.
Bone cancer ultimately damages other tissues
The meeting will also offer attendees a close look at bone and cancer, which is an example of how “all the homeostatic processes that occur with bone not only affect bone but also impact other tissues and organs,” said Bellido.
In other words, “what happens in bone impacts other tissues – for example, skeletal muscle, the pancreas, and even frailty and fractures.”
Theresa A. Guise, MD, from the University of Texas MD Anderson Cancer Center, in Austin, will present the Louis V. Avioli Lecture on September 11, entitled, “Cancer, Bone and Beyond: An Integrated View of the Bone Microenvironment.”
“Local events in the bone microenvironment due to cancer and cancer treatment which result in pathologic bone destruction may have widespread systemic consequences that further increase morbidity and mortality,” Hofbauer noted.
Guise “will highlight cutting-edge concepts, potential mechanisms, and therapy for bone metastases,” he said.
These concepts will also be discussed in more detail during a 2-day virtual premeeting symposium, presented on September 9 and 10 by the ASBMR along with the Cancer and Bone Society, entitled, “The Seed and Soil: Therapeutic Targets for Cancer in Bone.”
The symposium will cover tumor dormancy, imaging, adiposity in the bone tumor microenvironment, a history of bone-targeted therapies in cancer, advances in breast cancer bone metastasis, and new approaches in myeloma bone disease.
“We have evidence from breast cancer, multiple myeloma, as well as from prostate cancer,” Bellido noted, that “all those cancer cells make their home in bone and transform the bone in such a way that not only the bone is damaged but also other tissues.”
“We have skeletal muscle weakness (that is directed by the effects that occur in bone), as well as changes in the pancreas – all directed by proteins and genes in bone cells.”
AI, bench to bedside research
“Every field is moving towards the use of AI,” Bellido noted, and the September 11 plenary symposium entitled, “Artificial Intelligence and Precision Medicine in Musculoskeletal Health,” will shed light on how AI is being used to study bone health.
The session “will give us a glimpse of the future,” said Hofbauer.
Session topics include principles of applications to research and clinical care in bone and mineral research; how AI can help detect rare diseases; and combining genomics with medical data using AI in precision medicine for drug discovery.
“The Bench to Bedside presentation on ‘Beta Blockers and Bone’ is a great example of translational research, while the Basic Symposium on ‘Bones, Guts and Brains’ provides inspiring and thought-provoking insights into novel physiology and tempting teleology,” Hofbauer explained.
“Another fascinating Cutting Edge symposium,” he added, “is on ‘Inspiring Mechanistic Bone Stories from Around the Animal Kingdom,’ a must-see for those employing preclinical animal models.”
For more insight into early research and a research pioneer, attendees can listen to Selma Masri, PhD, from the University of California, Irvine, who will deliver the Gerald D. Aurbach Lecture entitled, “The Scientific Legacy of Paolo Sassone-Corsi: A Tour Through the Fields of Transcriptional Regulation, Epigenetics, Metabolism and Circadian Rhythms.”
Masri’s lab is dissecting how genetic disruption of the circadian clock in mouse models affects cancer, and she will discuss the work and legacy of the late Sassone-Corsi, as well as the future of the field.
Rare disease, fragility fractures
The ASBMR meeting will also feature the latest research into rare diseases and fragility fractures.
Rare diseases are often about “more bone or less bone,” said Bellido. “Understanding the mechanisms of these rare diseases can give us very important clues of treating the more common diseases.”
A fragility fracture is a diagnosis of osteoporosis, but most are not treated, she continued. “This is equivalent to having, for example, a heart attack and leaving the hospital after the incident was resolved and not treating it.”
“We’re trying to address this gap,” she said, and a symposium on September 14 will present some of the latest knowledge.
During the “Long-term Management of Fragility Fracture” symposium, speakers will discuss reducing mortality with antiosteoporotic treatment, new scenarios to prevent postfracture frailty, as well as fracture and postfracture management – surgeon and nursing perspectives.
COVID-19, nutrition, microbiome, and top 5 clinical abstracts
In addition to plenary sessions and symposiums, there are many oral abstracts and posters on important studies in the field of bone health, including, for example, a topical study of vitamin D and COVID-19.
There are also many abstracts on nutrition, the microbiome, and treating bone loss, said Bellido.
“We have a huge increase in the number of abstracts submitted from South America and Australia compared to previous years,” she noted, “and a 10% increase (from 50% to 61%) in the number of abstracts submitted by young investigators, which is crucial.”
Close to 1000 abstracts (988) were submitted, two thirds of which were clinical.
The top 5 clinical abstracts reflect important current issues in the field, said Hofbauer.
“One major theme is on long-term and sequential therapy efficacy and safety,” he said. And “burosumab is a game-changing new drug, and nutritional aspects are evergreens [perennial favorites], especially in the elderly population.”
The top 5 clinical oral abstracts at the ASBMR 2020 meeting are:
- Dairy supplementation reduces fractures and falls in institutionalized older adults: A cluster-randomized placebo-controlled trial (abstract 1022).
- Treatment with zoledronate subsequent to denosumab in osteoporosis: A randomized trial (abstract 1065).
- Efficacy of burosumab in adults with X-linked hypophosphatemia (XLH): A subgroup analysis of a randomized, double-blind, placebo-controlled, phase 3 study (abstract 1044).
- High-dose vitamin D supplementation affects bone density differently in females than males (abstract 1019).
- Bisphosphonate use and risk of atypical femoral fractures: A nationwide Danish analysis with blinded radiographic review (abstract 1061).
This article first appeared on Medscape.com.
The virtual American Society for Bone and Mineral Research 2020 annual meeting “is full of highlights,” says Lorenz Hofbauer, MD, scientific chair, but “this year you won’t lose time in the hallways to switch between the talks,” he quipped.
Nevertheless, “although we won’t be coming together face to face this year, you will have the flexibility to virtually connect with peers and colleagues from around the world,” Teresita Bellido, PhD, ASBMR president emphasized in a message to members.
Like other medical organizations, with the advent of the COVID-19 pandemic, the ASBMR had to quickly pivot to provide a virtual meeting.
The meeting will take place September 11-15 and is free for ASBMR members.
Speaking to Medscape Medical News, Bellido and Hofbauer drew attention to some of the meeting’s major themes, key sessions, and top clinical oral abstracts.
Attendees at this year’s virtual meeting will hear the latest information on optimal sequential treatment for osteoporosis, the latest research using artificial intelligence (AI), and bone and cancer, among other topics.
Sequential osteoporosis treatment a recurring theme
According to Hofbauer, from Dresden Technical University, Germany, the September 13 Cutting Edge symposium entitled, “Optimizing Sequential Osteoporosis Treatment,” is not to be missed, and the topic “will be a leitmotiv [recurrent theme] for the entire meeting.”
During this session speakers will present findings from two perspectives – basic science and clinical applications – with the latter being another recurring theme at the meeting.
Bellido, from the University of Arkansas for Medical Sciences, in Little Rock, pointed out that romosozumab (Evenity, Amgen), recently approved by the US Food and Drug Administration, is an example of how basic laboratory research can lead to important new therapies.
Anabolic therapies for osteoporosis that “build up bone” include teriparatide, abaloparatide, and now romosozumab, whereas antiresorptive therapies that stop bone resorption include the bisphosphonates (alendronate, risedronate, ibandronate, and zoledronic acid) and the monoclonal antibody denosumab, Bellido explained.
As osteoporosis treatment options have expanded, the timing and sequencing of optimal therapies have become much more complex, and so this session on sequencing, as well as the September 13 Concurrent Orals session, “Issues of Long-term Treatment and Discontinuation,” is sure to spark interest.
The ASBMR/European Calcified Tissue Society debate, entitled, “A Treat to Target Approach is Helpful for Osteoporosis Management,” is also expected to be lively and generate wide interest, according to Bellido and Hofbauer.
Michael R. McClung, MD, Oregon Osteoporosis Center, Portland, will argue against the motion and Celia Gregson, PhD, University of Bristol, UK, will argue for it. Attendees will be able to vote for/against the motion before and after the debate, and the result will indicate which speaker was more persuasive.
Bone cancer ultimately damages other tissues
The meeting will also offer attendees a close look at bone and cancer, which is an example of how “all the homeostatic processes that occur with bone not only affect bone but also impact other tissues and organs,” said Bellido.
In other words, “what happens in bone impacts other tissues – for example, skeletal muscle, the pancreas, and even frailty and fractures.”
Theresa A. Guise, MD, from the University of Texas MD Anderson Cancer Center, in Austin, will present the Louis V. Avioli Lecture on September 11, entitled, “Cancer, Bone and Beyond: An Integrated View of the Bone Microenvironment.”
“Local events in the bone microenvironment due to cancer and cancer treatment which result in pathologic bone destruction may have widespread systemic consequences that further increase morbidity and mortality,” Hofbauer noted.
Guise “will highlight cutting-edge concepts, potential mechanisms, and therapy for bone metastases,” he said.
These concepts will also be discussed in more detail during a 2-day virtual premeeting symposium, presented on September 9 and 10 by the ASBMR along with the Cancer and Bone Society, entitled, “The Seed and Soil: Therapeutic Targets for Cancer in Bone.”
The symposium will cover tumor dormancy, imaging, adiposity in the bone tumor microenvironment, a history of bone-targeted therapies in cancer, advances in breast cancer bone metastasis, and new approaches in myeloma bone disease.
“We have evidence from breast cancer, multiple myeloma, as well as from prostate cancer,” Bellido noted, that “all those cancer cells make their home in bone and transform the bone in such a way that not only the bone is damaged but also other tissues.”
“We have skeletal muscle weakness (that is directed by the effects that occur in bone), as well as changes in the pancreas – all directed by proteins and genes in bone cells.”
AI, bench to bedside research
“Every field is moving towards the use of AI,” Bellido noted, and the September 11 plenary symposium entitled, “Artificial Intelligence and Precision Medicine in Musculoskeletal Health,” will shed light on how AI is being used to study bone health.
The session “will give us a glimpse of the future,” said Hofbauer.
Session topics include principles of applications to research and clinical care in bone and mineral research; how AI can help detect rare diseases; and combining genomics with medical data using AI in precision medicine for drug discovery.
“The Bench to Bedside presentation on ‘Beta Blockers and Bone’ is a great example of translational research, while the Basic Symposium on ‘Bones, Guts and Brains’ provides inspiring and thought-provoking insights into novel physiology and tempting teleology,” Hofbauer explained.
“Another fascinating Cutting Edge symposium,” he added, “is on ‘Inspiring Mechanistic Bone Stories from Around the Animal Kingdom,’ a must-see for those employing preclinical animal models.”
For more insight into early research and a research pioneer, attendees can listen to Selma Masri, PhD, from the University of California, Irvine, who will deliver the Gerald D. Aurbach Lecture entitled, “The Scientific Legacy of Paolo Sassone-Corsi: A Tour Through the Fields of Transcriptional Regulation, Epigenetics, Metabolism and Circadian Rhythms.”
Masri’s lab is dissecting how genetic disruption of the circadian clock in mouse models affects cancer, and she will discuss the work and legacy of the late Sassone-Corsi, as well as the future of the field.
Rare disease, fragility fractures
The ASBMR meeting will also feature the latest research into rare diseases and fragility fractures.
Rare diseases are often about “more bone or less bone,” said Bellido. “Understanding the mechanisms of these rare diseases can give us very important clues of treating the more common diseases.”
A fragility fracture is a diagnosis of osteoporosis, but most are not treated, she continued. “This is equivalent to having, for example, a heart attack and leaving the hospital after the incident was resolved and not treating it.”
“We’re trying to address this gap,” she said, and a symposium on September 14 will present some of the latest knowledge.
During the “Long-term Management of Fragility Fracture” symposium, speakers will discuss reducing mortality with antiosteoporotic treatment, new scenarios to prevent postfracture frailty, as well as fracture and postfracture management – surgeon and nursing perspectives.
COVID-19, nutrition, microbiome, and top 5 clinical abstracts
In addition to plenary sessions and symposiums, there are many oral abstracts and posters on important studies in the field of bone health, including, for example, a topical study of vitamin D and COVID-19.
There are also many abstracts on nutrition, the microbiome, and treating bone loss, said Bellido.
“We have a huge increase in the number of abstracts submitted from South America and Australia compared to previous years,” she noted, “and a 10% increase (from 50% to 61%) in the number of abstracts submitted by young investigators, which is crucial.”
Close to 1000 abstracts (988) were submitted, two thirds of which were clinical.
The top 5 clinical abstracts reflect important current issues in the field, said Hofbauer.
“One major theme is on long-term and sequential therapy efficacy and safety,” he said. And “burosumab is a game-changing new drug, and nutritional aspects are evergreens [perennial favorites], especially in the elderly population.”
The top 5 clinical oral abstracts at the ASBMR 2020 meeting are:
- Dairy supplementation reduces fractures and falls in institutionalized older adults: A cluster-randomized placebo-controlled trial (abstract 1022).
- Treatment with zoledronate subsequent to denosumab in osteoporosis: A randomized trial (abstract 1065).
- Efficacy of burosumab in adults with X-linked hypophosphatemia (XLH): A subgroup analysis of a randomized, double-blind, placebo-controlled, phase 3 study (abstract 1044).
- High-dose vitamin D supplementation affects bone density differently in females than males (abstract 1019).
- Bisphosphonate use and risk of atypical femoral fractures: A nationwide Danish analysis with blinded radiographic review (abstract 1061).
This article first appeared on Medscape.com.
The virtual American Society for Bone and Mineral Research 2020 annual meeting “is full of highlights,” says Lorenz Hofbauer, MD, scientific chair, but “this year you won’t lose time in the hallways to switch between the talks,” he quipped.
Nevertheless, “although we won’t be coming together face to face this year, you will have the flexibility to virtually connect with peers and colleagues from around the world,” Teresita Bellido, PhD, ASBMR president emphasized in a message to members.
Like other medical organizations, with the advent of the COVID-19 pandemic, the ASBMR had to quickly pivot to provide a virtual meeting.
The meeting will take place September 11-15 and is free for ASBMR members.
Speaking to Medscape Medical News, Bellido and Hofbauer drew attention to some of the meeting’s major themes, key sessions, and top clinical oral abstracts.
Attendees at this year’s virtual meeting will hear the latest information on optimal sequential treatment for osteoporosis, the latest research using artificial intelligence (AI), and bone and cancer, among other topics.
Sequential osteoporosis treatment a recurring theme
According to Hofbauer, from Dresden Technical University, Germany, the September 13 Cutting Edge symposium entitled, “Optimizing Sequential Osteoporosis Treatment,” is not to be missed, and the topic “will be a leitmotiv [recurrent theme] for the entire meeting.”
During this session speakers will present findings from two perspectives – basic science and clinical applications – with the latter being another recurring theme at the meeting.
Bellido, from the University of Arkansas for Medical Sciences, in Little Rock, pointed out that romosozumab (Evenity, Amgen), recently approved by the US Food and Drug Administration, is an example of how basic laboratory research can lead to important new therapies.
Anabolic therapies for osteoporosis that “build up bone” include teriparatide, abaloparatide, and now romosozumab, whereas antiresorptive therapies that stop bone resorption include the bisphosphonates (alendronate, risedronate, ibandronate, and zoledronic acid) and the monoclonal antibody denosumab, Bellido explained.
As osteoporosis treatment options have expanded, the timing and sequencing of optimal therapies have become much more complex, and so this session on sequencing, as well as the September 13 Concurrent Orals session, “Issues of Long-term Treatment and Discontinuation,” is sure to spark interest.
The ASBMR/European Calcified Tissue Society debate, entitled, “A Treat to Target Approach is Helpful for Osteoporosis Management,” is also expected to be lively and generate wide interest, according to Bellido and Hofbauer.
Michael R. McClung, MD, Oregon Osteoporosis Center, Portland, will argue against the motion and Celia Gregson, PhD, University of Bristol, UK, will argue for it. Attendees will be able to vote for/against the motion before and after the debate, and the result will indicate which speaker was more persuasive.
Bone cancer ultimately damages other tissues
The meeting will also offer attendees a close look at bone and cancer, which is an example of how “all the homeostatic processes that occur with bone not only affect bone but also impact other tissues and organs,” said Bellido.
In other words, “what happens in bone impacts other tissues – for example, skeletal muscle, the pancreas, and even frailty and fractures.”
Theresa A. Guise, MD, from the University of Texas MD Anderson Cancer Center, in Austin, will present the Louis V. Avioli Lecture on September 11, entitled, “Cancer, Bone and Beyond: An Integrated View of the Bone Microenvironment.”
“Local events in the bone microenvironment due to cancer and cancer treatment which result in pathologic bone destruction may have widespread systemic consequences that further increase morbidity and mortality,” Hofbauer noted.
Guise “will highlight cutting-edge concepts, potential mechanisms, and therapy for bone metastases,” he said.
These concepts will also be discussed in more detail during a 2-day virtual premeeting symposium, presented on September 9 and 10 by the ASBMR along with the Cancer and Bone Society, entitled, “The Seed and Soil: Therapeutic Targets for Cancer in Bone.”
The symposium will cover tumor dormancy, imaging, adiposity in the bone tumor microenvironment, a history of bone-targeted therapies in cancer, advances in breast cancer bone metastasis, and new approaches in myeloma bone disease.
“We have evidence from breast cancer, multiple myeloma, as well as from prostate cancer,” Bellido noted, that “all those cancer cells make their home in bone and transform the bone in such a way that not only the bone is damaged but also other tissues.”
“We have skeletal muscle weakness (that is directed by the effects that occur in bone), as well as changes in the pancreas – all directed by proteins and genes in bone cells.”
AI, bench to bedside research
“Every field is moving towards the use of AI,” Bellido noted, and the September 11 plenary symposium entitled, “Artificial Intelligence and Precision Medicine in Musculoskeletal Health,” will shed light on how AI is being used to study bone health.
The session “will give us a glimpse of the future,” said Hofbauer.
Session topics include principles of applications to research and clinical care in bone and mineral research; how AI can help detect rare diseases; and combining genomics with medical data using AI in precision medicine for drug discovery.
“The Bench to Bedside presentation on ‘Beta Blockers and Bone’ is a great example of translational research, while the Basic Symposium on ‘Bones, Guts and Brains’ provides inspiring and thought-provoking insights into novel physiology and tempting teleology,” Hofbauer explained.
“Another fascinating Cutting Edge symposium,” he added, “is on ‘Inspiring Mechanistic Bone Stories from Around the Animal Kingdom,’ a must-see for those employing preclinical animal models.”
For more insight into early research and a research pioneer, attendees can listen to Selma Masri, PhD, from the University of California, Irvine, who will deliver the Gerald D. Aurbach Lecture entitled, “The Scientific Legacy of Paolo Sassone-Corsi: A Tour Through the Fields of Transcriptional Regulation, Epigenetics, Metabolism and Circadian Rhythms.”
Masri’s lab is dissecting how genetic disruption of the circadian clock in mouse models affects cancer, and she will discuss the work and legacy of the late Sassone-Corsi, as well as the future of the field.
Rare disease, fragility fractures
The ASBMR meeting will also feature the latest research into rare diseases and fragility fractures.
Rare diseases are often about “more bone or less bone,” said Bellido. “Understanding the mechanisms of these rare diseases can give us very important clues of treating the more common diseases.”
A fragility fracture is a diagnosis of osteoporosis, but most are not treated, she continued. “This is equivalent to having, for example, a heart attack and leaving the hospital after the incident was resolved and not treating it.”
“We’re trying to address this gap,” she said, and a symposium on September 14 will present some of the latest knowledge.
During the “Long-term Management of Fragility Fracture” symposium, speakers will discuss reducing mortality with antiosteoporotic treatment, new scenarios to prevent postfracture frailty, as well as fracture and postfracture management – surgeon and nursing perspectives.
COVID-19, nutrition, microbiome, and top 5 clinical abstracts
In addition to plenary sessions and symposiums, there are many oral abstracts and posters on important studies in the field of bone health, including, for example, a topical study of vitamin D and COVID-19.
There are also many abstracts on nutrition, the microbiome, and treating bone loss, said Bellido.
“We have a huge increase in the number of abstracts submitted from South America and Australia compared to previous years,” she noted, “and a 10% increase (from 50% to 61%) in the number of abstracts submitted by young investigators, which is crucial.”
Close to 1000 abstracts (988) were submitted, two thirds of which were clinical.
The top 5 clinical abstracts reflect important current issues in the field, said Hofbauer.
“One major theme is on long-term and sequential therapy efficacy and safety,” he said. And “burosumab is a game-changing new drug, and nutritional aspects are evergreens [perennial favorites], especially in the elderly population.”
The top 5 clinical oral abstracts at the ASBMR 2020 meeting are:
- Dairy supplementation reduces fractures and falls in institutionalized older adults: A cluster-randomized placebo-controlled trial (abstract 1022).
- Treatment with zoledronate subsequent to denosumab in osteoporosis: A randomized trial (abstract 1065).
- Efficacy of burosumab in adults with X-linked hypophosphatemia (XLH): A subgroup analysis of a randomized, double-blind, placebo-controlled, phase 3 study (abstract 1044).
- High-dose vitamin D supplementation affects bone density differently in females than males (abstract 1019).
- Bisphosphonate use and risk of atypical femoral fractures: A nationwide Danish analysis with blinded radiographic review (abstract 1061).
This article first appeared on Medscape.com.
Distinguishing COVID-19 from flu in kids remains challenging
For children with COVID-19, rates of hospitalization, ICU admission, and ventilator use were similar to those of children with influenza, but rates differed in other respects, according to results of a study published online Sept. 11 in JAMA Network Open.
As winter approaches, distinguishing patients with COVID-19 from those with influenza will become a problem. To assist with that, Xiaoyan Song, PhD, director of the office of infection control and epidemiology at Children’s National Hospital in Washington, D.C., and colleagues investigated commonalities and differences between the clinical symptoms of COVID-19 and influenza in children.
“Distinguishing COVID-19 from flu and other respiratory viral infections remains a challenge to clinicians. Although our study showed that patients with COVID-19 were more likely than patients with flu to report fever, gastrointestinal, and other clinical symptoms at the time of diagnosis, the two groups do have many overlapping clinical symptoms,” Dr. Song said. “Until future data show us otherwise, clinicians need to prepare for managing coinfections of COVID-19 with flu and/or other respiratory viral infections in the upcoming flu season.”
The retrospective cohort study included 315 children diagnosed with laboratory-confirmed COVID-19 between March 25 and May 15, 2020, and 1,402 children diagnosed with laboratory-confirmed seasonal influenza A or influenza B between Oct. 1, 2019, and June 6, 2020, at Children’s National Hospital. The investigation excluded asymptomatic patients who tested positive for COVID-19.
Patients with COVID-19 and patients with influenza were similar with respect to rates of hospitalization (17% vs. 21%; odds ratio, 0.8; 95% confidence interval, 0.6-1.1; P = .15), admission to the ICU (6% vs. 7%; OR, 0.8; 95% CI, 0.5-1.3; P = .42), and use of mechanical ventilation (3% vs. 2%; OR, 1.5; 95% CI, 0.9-2.6; P =.17).
The difference in the duration of ventilation for the two groups was not statistically significant. None of the patients who had COVID-19 or influenza B died, but two patients with influenza A did.
No patients had coinfections, which the researchers attribute to the mid-March shutdown of many schools, which they believe limited the spread of seasonal influenza.
Patients who were hospitalized with COVID-19 were older (median age, 9.7 years; range, 0.06-23.2 years) than those hospitalized with either type of influenza (median age, 4.2 years; range, 0.04-23.1). Patients older than 15 years made up 37% of patients with COVID-19 but only 6% of those with influenza.
Among patients hospitalized with COVID-19, 65% had at least one underlying medical condition, compared with 42% of those hospitalized for either type of influenza (OR, 2.6; 95% CI, 1.4-4.7; P = .002).
The most common underlying condition was neurologic problems from global developmental delay or seizures, identified in 11 patients (20%) hospitalized with COVID-19 and in 24 patients (8%) hospitalized with influenza (OR, 2.8; 95% CI, 1.3-6.2; P = .002). There was no significant difference between the two groups with respect to a history of asthma, cardiac disease, hematologic disease, and cancer.
For both groups, fever and cough were the most frequently reported symptoms at the time of diagnosis. However, more patients hospitalized with COVID-19 reported fever (76% vs. 55%; OR, 2.6; 95% CI, 1.4-5.1; P = 01), diarrhea or vomiting (26% vs. 12%; OR, 2.5; 95% CI, 1.2-5.0; P = .01), headache (11% vs. 3%; OR, 3.9; 95% CI, 1.3-11.5; P = .01), myalgia (22% vs. 7%; OR, 3.9; 95% CI, 1.8-8.5; P = .001), or chest pain (11% vs. 3%; OR, 3.9; 95% CI, 1.3-11.5; P = .01).
The researchers found no statistically significant differences between the two groups in rates of cough, congestion, sore throat, or shortness of breath.
Comparison of the symptom spectrum between COVID-19 and flu differed with respect to influenza type. More patients with COVID-19 reported fever, cough, diarrhea and vomiting, and myalgia than patients hospitalized with influenza A. But rates of fever, cough, diarrhea or vomiting, headache, or chest pain didn’t differ significantly in patients with COVID-19 and those with influenza B.
Larry K. Kociolek, MD, medical director of infection prevention and control at Ann and Robert H. Lurie Children’s Hospital of Chicago, noted the lower age of patients with flu. “Differentiating the two infections, which is difficult if not impossible based on symptoms alone, may have prognostic implications, depending on the age of the child. Because this study was performed outside peak influenza season, when coinfections would be less likely to occur, we must be vigilant about the potential clinical implications of influenza and SARS-CoV-2 coinfection this fall and winter.”
Clinicians will still have to use a combination of symptoms, examinations, and testing to distinguish the two diseases, said Aimee Sznewajs, MD, medical director of the pediatric hospital medicine department at Children’s Minnesota, Minneapolis. “We will continue to test for influenza and COVID-19 prior to hospitalizations and make decisions about whether to hospitalize based on other clinical factors, such as dehydration, oxygen requirement, and vital sign changes.”
Dr. Sznewajs stressed the importance of maintaining public health strategies, including “ensuring all children get the flu vaccine, encouraging mask wearing and hand hygiene, adequate testing to determine which virus is present, and other mitigation measures if the prevalence of COVID-19 is increasing in the community.”
Dr. Song reiterated those points, noting that clinicians need to make the most of the options they have. “Clinicians already have many great tools on hand. It is extremely important to get the flu vaccine now, especially for kids with underlying medical conditions. Diagnostic tests are available for both COVID-19 and flu. Antiviral treatment for flu is available. Judicious use of these tools will protect the health of providers, kids, and well-being at large.”
The authors noted several limitations for the study, including its retrospective design, that the data came from a single center, and that different platforms were used to detect the viruses.
A version of this article originally appeared on Medscape.com.
For children with COVID-19, rates of hospitalization, ICU admission, and ventilator use were similar to those of children with influenza, but rates differed in other respects, according to results of a study published online Sept. 11 in JAMA Network Open.
As winter approaches, distinguishing patients with COVID-19 from those with influenza will become a problem. To assist with that, Xiaoyan Song, PhD, director of the office of infection control and epidemiology at Children’s National Hospital in Washington, D.C., and colleagues investigated commonalities and differences between the clinical symptoms of COVID-19 and influenza in children.
“Distinguishing COVID-19 from flu and other respiratory viral infections remains a challenge to clinicians. Although our study showed that patients with COVID-19 were more likely than patients with flu to report fever, gastrointestinal, and other clinical symptoms at the time of diagnosis, the two groups do have many overlapping clinical symptoms,” Dr. Song said. “Until future data show us otherwise, clinicians need to prepare for managing coinfections of COVID-19 with flu and/or other respiratory viral infections in the upcoming flu season.”
The retrospective cohort study included 315 children diagnosed with laboratory-confirmed COVID-19 between March 25 and May 15, 2020, and 1,402 children diagnosed with laboratory-confirmed seasonal influenza A or influenza B between Oct. 1, 2019, and June 6, 2020, at Children’s National Hospital. The investigation excluded asymptomatic patients who tested positive for COVID-19.
Patients with COVID-19 and patients with influenza were similar with respect to rates of hospitalization (17% vs. 21%; odds ratio, 0.8; 95% confidence interval, 0.6-1.1; P = .15), admission to the ICU (6% vs. 7%; OR, 0.8; 95% CI, 0.5-1.3; P = .42), and use of mechanical ventilation (3% vs. 2%; OR, 1.5; 95% CI, 0.9-2.6; P =.17).
The difference in the duration of ventilation for the two groups was not statistically significant. None of the patients who had COVID-19 or influenza B died, but two patients with influenza A did.
No patients had coinfections, which the researchers attribute to the mid-March shutdown of many schools, which they believe limited the spread of seasonal influenza.
Patients who were hospitalized with COVID-19 were older (median age, 9.7 years; range, 0.06-23.2 years) than those hospitalized with either type of influenza (median age, 4.2 years; range, 0.04-23.1). Patients older than 15 years made up 37% of patients with COVID-19 but only 6% of those with influenza.
Among patients hospitalized with COVID-19, 65% had at least one underlying medical condition, compared with 42% of those hospitalized for either type of influenza (OR, 2.6; 95% CI, 1.4-4.7; P = .002).
The most common underlying condition was neurologic problems from global developmental delay or seizures, identified in 11 patients (20%) hospitalized with COVID-19 and in 24 patients (8%) hospitalized with influenza (OR, 2.8; 95% CI, 1.3-6.2; P = .002). There was no significant difference between the two groups with respect to a history of asthma, cardiac disease, hematologic disease, and cancer.
For both groups, fever and cough were the most frequently reported symptoms at the time of diagnosis. However, more patients hospitalized with COVID-19 reported fever (76% vs. 55%; OR, 2.6; 95% CI, 1.4-5.1; P = 01), diarrhea or vomiting (26% vs. 12%; OR, 2.5; 95% CI, 1.2-5.0; P = .01), headache (11% vs. 3%; OR, 3.9; 95% CI, 1.3-11.5; P = .01), myalgia (22% vs. 7%; OR, 3.9; 95% CI, 1.8-8.5; P = .001), or chest pain (11% vs. 3%; OR, 3.9; 95% CI, 1.3-11.5; P = .01).
The researchers found no statistically significant differences between the two groups in rates of cough, congestion, sore throat, or shortness of breath.
Comparison of the symptom spectrum between COVID-19 and flu differed with respect to influenza type. More patients with COVID-19 reported fever, cough, diarrhea and vomiting, and myalgia than patients hospitalized with influenza A. But rates of fever, cough, diarrhea or vomiting, headache, or chest pain didn’t differ significantly in patients with COVID-19 and those with influenza B.
Larry K. Kociolek, MD, medical director of infection prevention and control at Ann and Robert H. Lurie Children’s Hospital of Chicago, noted the lower age of patients with flu. “Differentiating the two infections, which is difficult if not impossible based on symptoms alone, may have prognostic implications, depending on the age of the child. Because this study was performed outside peak influenza season, when coinfections would be less likely to occur, we must be vigilant about the potential clinical implications of influenza and SARS-CoV-2 coinfection this fall and winter.”
Clinicians will still have to use a combination of symptoms, examinations, and testing to distinguish the two diseases, said Aimee Sznewajs, MD, medical director of the pediatric hospital medicine department at Children’s Minnesota, Minneapolis. “We will continue to test for influenza and COVID-19 prior to hospitalizations and make decisions about whether to hospitalize based on other clinical factors, such as dehydration, oxygen requirement, and vital sign changes.”
Dr. Sznewajs stressed the importance of maintaining public health strategies, including “ensuring all children get the flu vaccine, encouraging mask wearing and hand hygiene, adequate testing to determine which virus is present, and other mitigation measures if the prevalence of COVID-19 is increasing in the community.”
Dr. Song reiterated those points, noting that clinicians need to make the most of the options they have. “Clinicians already have many great tools on hand. It is extremely important to get the flu vaccine now, especially for kids with underlying medical conditions. Diagnostic tests are available for both COVID-19 and flu. Antiviral treatment for flu is available. Judicious use of these tools will protect the health of providers, kids, and well-being at large.”
The authors noted several limitations for the study, including its retrospective design, that the data came from a single center, and that different platforms were used to detect the viruses.
A version of this article originally appeared on Medscape.com.
For children with COVID-19, rates of hospitalization, ICU admission, and ventilator use were similar to those of children with influenza, but rates differed in other respects, according to results of a study published online Sept. 11 in JAMA Network Open.
As winter approaches, distinguishing patients with COVID-19 from those with influenza will become a problem. To assist with that, Xiaoyan Song, PhD, director of the office of infection control and epidemiology at Children’s National Hospital in Washington, D.C., and colleagues investigated commonalities and differences between the clinical symptoms of COVID-19 and influenza in children.
“Distinguishing COVID-19 from flu and other respiratory viral infections remains a challenge to clinicians. Although our study showed that patients with COVID-19 were more likely than patients with flu to report fever, gastrointestinal, and other clinical symptoms at the time of diagnosis, the two groups do have many overlapping clinical symptoms,” Dr. Song said. “Until future data show us otherwise, clinicians need to prepare for managing coinfections of COVID-19 with flu and/or other respiratory viral infections in the upcoming flu season.”
The retrospective cohort study included 315 children diagnosed with laboratory-confirmed COVID-19 between March 25 and May 15, 2020, and 1,402 children diagnosed with laboratory-confirmed seasonal influenza A or influenza B between Oct. 1, 2019, and June 6, 2020, at Children’s National Hospital. The investigation excluded asymptomatic patients who tested positive for COVID-19.
Patients with COVID-19 and patients with influenza were similar with respect to rates of hospitalization (17% vs. 21%; odds ratio, 0.8; 95% confidence interval, 0.6-1.1; P = .15), admission to the ICU (6% vs. 7%; OR, 0.8; 95% CI, 0.5-1.3; P = .42), and use of mechanical ventilation (3% vs. 2%; OR, 1.5; 95% CI, 0.9-2.6; P =.17).
The difference in the duration of ventilation for the two groups was not statistically significant. None of the patients who had COVID-19 or influenza B died, but two patients with influenza A did.
No patients had coinfections, which the researchers attribute to the mid-March shutdown of many schools, which they believe limited the spread of seasonal influenza.
Patients who were hospitalized with COVID-19 were older (median age, 9.7 years; range, 0.06-23.2 years) than those hospitalized with either type of influenza (median age, 4.2 years; range, 0.04-23.1). Patients older than 15 years made up 37% of patients with COVID-19 but only 6% of those with influenza.
Among patients hospitalized with COVID-19, 65% had at least one underlying medical condition, compared with 42% of those hospitalized for either type of influenza (OR, 2.6; 95% CI, 1.4-4.7; P = .002).
The most common underlying condition was neurologic problems from global developmental delay or seizures, identified in 11 patients (20%) hospitalized with COVID-19 and in 24 patients (8%) hospitalized with influenza (OR, 2.8; 95% CI, 1.3-6.2; P = .002). There was no significant difference between the two groups with respect to a history of asthma, cardiac disease, hematologic disease, and cancer.
For both groups, fever and cough were the most frequently reported symptoms at the time of diagnosis. However, more patients hospitalized with COVID-19 reported fever (76% vs. 55%; OR, 2.6; 95% CI, 1.4-5.1; P = 01), diarrhea or vomiting (26% vs. 12%; OR, 2.5; 95% CI, 1.2-5.0; P = .01), headache (11% vs. 3%; OR, 3.9; 95% CI, 1.3-11.5; P = .01), myalgia (22% vs. 7%; OR, 3.9; 95% CI, 1.8-8.5; P = .001), or chest pain (11% vs. 3%; OR, 3.9; 95% CI, 1.3-11.5; P = .01).
The researchers found no statistically significant differences between the two groups in rates of cough, congestion, sore throat, or shortness of breath.
Comparison of the symptom spectrum between COVID-19 and flu differed with respect to influenza type. More patients with COVID-19 reported fever, cough, diarrhea and vomiting, and myalgia than patients hospitalized with influenza A. But rates of fever, cough, diarrhea or vomiting, headache, or chest pain didn’t differ significantly in patients with COVID-19 and those with influenza B.
Larry K. Kociolek, MD, medical director of infection prevention and control at Ann and Robert H. Lurie Children’s Hospital of Chicago, noted the lower age of patients with flu. “Differentiating the two infections, which is difficult if not impossible based on symptoms alone, may have prognostic implications, depending on the age of the child. Because this study was performed outside peak influenza season, when coinfections would be less likely to occur, we must be vigilant about the potential clinical implications of influenza and SARS-CoV-2 coinfection this fall and winter.”
Clinicians will still have to use a combination of symptoms, examinations, and testing to distinguish the two diseases, said Aimee Sznewajs, MD, medical director of the pediatric hospital medicine department at Children’s Minnesota, Minneapolis. “We will continue to test for influenza and COVID-19 prior to hospitalizations and make decisions about whether to hospitalize based on other clinical factors, such as dehydration, oxygen requirement, and vital sign changes.”
Dr. Sznewajs stressed the importance of maintaining public health strategies, including “ensuring all children get the flu vaccine, encouraging mask wearing and hand hygiene, adequate testing to determine which virus is present, and other mitigation measures if the prevalence of COVID-19 is increasing in the community.”
Dr. Song reiterated those points, noting that clinicians need to make the most of the options they have. “Clinicians already have many great tools on hand. It is extremely important to get the flu vaccine now, especially for kids with underlying medical conditions. Diagnostic tests are available for both COVID-19 and flu. Antiviral treatment for flu is available. Judicious use of these tools will protect the health of providers, kids, and well-being at large.”
The authors noted several limitations for the study, including its retrospective design, that the data came from a single center, and that different platforms were used to detect the viruses.
A version of this article originally appeared on Medscape.com.
AI can pinpoint COVID-19 from chest x-rays
Conventional chest x-rays combined with artificial intelligence (AI) can identify lung damage from COVID-19 and differentiate coronavirus patients from other patients, improving triage efforts, new research suggests.
The AI tool – developed by Jason Fleischer, PhD, and graduate student Mohammad Tariqul Islam, both from Princeton (N.J.) University – can distinguish COVID-19 patients from those with pneumonia or normal lung tissue with an accuracy of more than 95%.
“We were able to separate the COVID-19 patients with very high fidelity,” Dr. Fleischer said in an interview. “If you give me an x-ray now, I can say with very high confidence whether a patient has COVID-19.”
The diagnostic tool pinpoints patterns on x-ray images that are too subtle for even trained experts to notice. The precision of CT scanning is similar to that of the AI tool, but CT costs much more and has other disadvantages, said Dr. Fleischer, who presented his findings at the virtual European Respiratory Society International Congress 2020.
“CT is more expensive and uses higher doses of radiation,” he said. “Another big thing is that not everyone has tomography facilities – including a lot of rural places and developing countries – so you need something that’s on the spot.”
With machine learning, Dr. Fleischer analyzed 2,300 x-ray images: 1,018 “normal” images from patients who had neither pneumonia nor COVID-19, 1,011 from patients with pneumonia, and 271 from patients with COVID-19.
The AI tool uses a neural network to refine the number and type of lung features being tracked. A UMAP (Uniform Manifold Approximation and Projection) clustering algorithm then looks for similarities and differences in those images, he explained.
“We, as users, knew which type each x-ray was – normal, pneumonia positive, or COVID-19 positive – but the network did not,” he added.
Clinicians have observed two basic types of lung problems in COVID-19 patients: pneumonia that fills lung air sacs with fluid and dangerously low blood-oxygen levels despite nearly normal breathing patterns. Because treatment can vary according to type, it would be beneficial to quickly distinguish between them, Dr. Fleischer said.
The AI tool showed that there is a distinct difference in chest x-rays from pneumonia-positive patients and healthy people, he said. It also demonstrated two distinct clusters of COVID-19–positive chest x-rays: those that looked like pneumonia and those with a more normal presentation.
The fact that “the AI system recognizes something unique in chest x-rays from COVID-19–positive patients” indicates that the computer is able to identify visual markers for coronavirus, he explained. “We currently do not know what these markers are.”
Dr. Fleischer said his goal is not to replace physician decision-making, but to supplement it.
“I’m uncomfortable with having computers make the final decision,” he said. “They often have a narrow focus, whereas doctors have the big picture in mind.”
This AI tool is “very interesting,” especially in the context of expanding AI applications in various specialties, said Thierry Fumeaux, MD, from Nyon (Switzerland) Hospital. Some physicians currently disagree on whether a chest x-ray or CT scan is the better tool to help diagnose COVID-19.
“It seems better than the human eye and brain” to pinpoint COVID-19 lung damage, “so it’s very attractive as a technology,” Dr. Fumeaux said in an interview.
And AI can be used to supplement the efforts of busy and fatigued clinicians who might be stretched thin by large caseloads. “I cannot read 200 chest x-rays in a day, but a computer can do that in 2 minutes,” he said.
But Dr. Fumeaux offered a caveat: “Pattern recognition is promising, but at the moment I’m not aware of papers showing that, by using AI, you’re changing anything in the outcome of a patient.”
Ideally, Dr. Fleischer said he hopes that AI will soon be able to accurately indicate which treatments are most effective for individual COVID-19 patients. And the technology might eventually be used to help with treatment decisions for patients with asthma or chronic obstructive pulmonary disease, he noted.
But he needs more data before results indicate whether a COVID-19 patient would benefit from ventilator support, for example, and the tool can be used more widely. To contribute data or collaborate with Dr. Fleischer’s efforts, contact him.
“Machine learning is all about data, so you can find these correlations,” he said. “It would be nice to be able to use it to reassure a worried patient that their prognosis is good; to say that most of the people with symptoms like yours will be just fine.”
Dr. Fleischer and Dr. Fumeaux have declared no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Conventional chest x-rays combined with artificial intelligence (AI) can identify lung damage from COVID-19 and differentiate coronavirus patients from other patients, improving triage efforts, new research suggests.
The AI tool – developed by Jason Fleischer, PhD, and graduate student Mohammad Tariqul Islam, both from Princeton (N.J.) University – can distinguish COVID-19 patients from those with pneumonia or normal lung tissue with an accuracy of more than 95%.
“We were able to separate the COVID-19 patients with very high fidelity,” Dr. Fleischer said in an interview. “If you give me an x-ray now, I can say with very high confidence whether a patient has COVID-19.”
The diagnostic tool pinpoints patterns on x-ray images that are too subtle for even trained experts to notice. The precision of CT scanning is similar to that of the AI tool, but CT costs much more and has other disadvantages, said Dr. Fleischer, who presented his findings at the virtual European Respiratory Society International Congress 2020.
“CT is more expensive and uses higher doses of radiation,” he said. “Another big thing is that not everyone has tomography facilities – including a lot of rural places and developing countries – so you need something that’s on the spot.”
With machine learning, Dr. Fleischer analyzed 2,300 x-ray images: 1,018 “normal” images from patients who had neither pneumonia nor COVID-19, 1,011 from patients with pneumonia, and 271 from patients with COVID-19.
The AI tool uses a neural network to refine the number and type of lung features being tracked. A UMAP (Uniform Manifold Approximation and Projection) clustering algorithm then looks for similarities and differences in those images, he explained.
“We, as users, knew which type each x-ray was – normal, pneumonia positive, or COVID-19 positive – but the network did not,” he added.
Clinicians have observed two basic types of lung problems in COVID-19 patients: pneumonia that fills lung air sacs with fluid and dangerously low blood-oxygen levels despite nearly normal breathing patterns. Because treatment can vary according to type, it would be beneficial to quickly distinguish between them, Dr. Fleischer said.
The AI tool showed that there is a distinct difference in chest x-rays from pneumonia-positive patients and healthy people, he said. It also demonstrated two distinct clusters of COVID-19–positive chest x-rays: those that looked like pneumonia and those with a more normal presentation.
The fact that “the AI system recognizes something unique in chest x-rays from COVID-19–positive patients” indicates that the computer is able to identify visual markers for coronavirus, he explained. “We currently do not know what these markers are.”
Dr. Fleischer said his goal is not to replace physician decision-making, but to supplement it.
“I’m uncomfortable with having computers make the final decision,” he said. “They often have a narrow focus, whereas doctors have the big picture in mind.”
This AI tool is “very interesting,” especially in the context of expanding AI applications in various specialties, said Thierry Fumeaux, MD, from Nyon (Switzerland) Hospital. Some physicians currently disagree on whether a chest x-ray or CT scan is the better tool to help diagnose COVID-19.
“It seems better than the human eye and brain” to pinpoint COVID-19 lung damage, “so it’s very attractive as a technology,” Dr. Fumeaux said in an interview.
And AI can be used to supplement the efforts of busy and fatigued clinicians who might be stretched thin by large caseloads. “I cannot read 200 chest x-rays in a day, but a computer can do that in 2 minutes,” he said.
But Dr. Fumeaux offered a caveat: “Pattern recognition is promising, but at the moment I’m not aware of papers showing that, by using AI, you’re changing anything in the outcome of a patient.”
Ideally, Dr. Fleischer said he hopes that AI will soon be able to accurately indicate which treatments are most effective for individual COVID-19 patients. And the technology might eventually be used to help with treatment decisions for patients with asthma or chronic obstructive pulmonary disease, he noted.
But he needs more data before results indicate whether a COVID-19 patient would benefit from ventilator support, for example, and the tool can be used more widely. To contribute data or collaborate with Dr. Fleischer’s efforts, contact him.
“Machine learning is all about data, so you can find these correlations,” he said. “It would be nice to be able to use it to reassure a worried patient that their prognosis is good; to say that most of the people with symptoms like yours will be just fine.”
Dr. Fleischer and Dr. Fumeaux have declared no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Conventional chest x-rays combined with artificial intelligence (AI) can identify lung damage from COVID-19 and differentiate coronavirus patients from other patients, improving triage efforts, new research suggests.
The AI tool – developed by Jason Fleischer, PhD, and graduate student Mohammad Tariqul Islam, both from Princeton (N.J.) University – can distinguish COVID-19 patients from those with pneumonia or normal lung tissue with an accuracy of more than 95%.
“We were able to separate the COVID-19 patients with very high fidelity,” Dr. Fleischer said in an interview. “If you give me an x-ray now, I can say with very high confidence whether a patient has COVID-19.”
The diagnostic tool pinpoints patterns on x-ray images that are too subtle for even trained experts to notice. The precision of CT scanning is similar to that of the AI tool, but CT costs much more and has other disadvantages, said Dr. Fleischer, who presented his findings at the virtual European Respiratory Society International Congress 2020.
“CT is more expensive and uses higher doses of radiation,” he said. “Another big thing is that not everyone has tomography facilities – including a lot of rural places and developing countries – so you need something that’s on the spot.”
With machine learning, Dr. Fleischer analyzed 2,300 x-ray images: 1,018 “normal” images from patients who had neither pneumonia nor COVID-19, 1,011 from patients with pneumonia, and 271 from patients with COVID-19.
The AI tool uses a neural network to refine the number and type of lung features being tracked. A UMAP (Uniform Manifold Approximation and Projection) clustering algorithm then looks for similarities and differences in those images, he explained.
“We, as users, knew which type each x-ray was – normal, pneumonia positive, or COVID-19 positive – but the network did not,” he added.
Clinicians have observed two basic types of lung problems in COVID-19 patients: pneumonia that fills lung air sacs with fluid and dangerously low blood-oxygen levels despite nearly normal breathing patterns. Because treatment can vary according to type, it would be beneficial to quickly distinguish between them, Dr. Fleischer said.
The AI tool showed that there is a distinct difference in chest x-rays from pneumonia-positive patients and healthy people, he said. It also demonstrated two distinct clusters of COVID-19–positive chest x-rays: those that looked like pneumonia and those with a more normal presentation.
The fact that “the AI system recognizes something unique in chest x-rays from COVID-19–positive patients” indicates that the computer is able to identify visual markers for coronavirus, he explained. “We currently do not know what these markers are.”
Dr. Fleischer said his goal is not to replace physician decision-making, but to supplement it.
“I’m uncomfortable with having computers make the final decision,” he said. “They often have a narrow focus, whereas doctors have the big picture in mind.”
This AI tool is “very interesting,” especially in the context of expanding AI applications in various specialties, said Thierry Fumeaux, MD, from Nyon (Switzerland) Hospital. Some physicians currently disagree on whether a chest x-ray or CT scan is the better tool to help diagnose COVID-19.
“It seems better than the human eye and brain” to pinpoint COVID-19 lung damage, “so it’s very attractive as a technology,” Dr. Fumeaux said in an interview.
And AI can be used to supplement the efforts of busy and fatigued clinicians who might be stretched thin by large caseloads. “I cannot read 200 chest x-rays in a day, but a computer can do that in 2 minutes,” he said.
But Dr. Fumeaux offered a caveat: “Pattern recognition is promising, but at the moment I’m not aware of papers showing that, by using AI, you’re changing anything in the outcome of a patient.”
Ideally, Dr. Fleischer said he hopes that AI will soon be able to accurately indicate which treatments are most effective for individual COVID-19 patients. And the technology might eventually be used to help with treatment decisions for patients with asthma or chronic obstructive pulmonary disease, he noted.
But he needs more data before results indicate whether a COVID-19 patient would benefit from ventilator support, for example, and the tool can be used more widely. To contribute data or collaborate with Dr. Fleischer’s efforts, contact him.
“Machine learning is all about data, so you can find these correlations,” he said. “It would be nice to be able to use it to reassure a worried patient that their prognosis is good; to say that most of the people with symptoms like yours will be just fine.”
Dr. Fleischer and Dr. Fumeaux have declared no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Small weight loss produces impressive drop in type 2 diabetes risk
Intentional loss of a median of just 13% of body weight reduces the relative risk of developing type 2 diabetes by around 40% in people with obesity, among many other health benefits, shows a large real-world study in half a million adults.
Other findings associated with the same modest weight loss included a reduction in the risk of sleep apnea by 22%-27%, hypertension by 18%-25%, and dyslipidemia by 20%-22%.
Christiane Haase, PhD, of Novo Nordisk, led the work together with Nick Finer, MD, senior principal clinical scientist, Novo Nordisk.
“This is powerful evidence to say it is worthwhile to help people lose weight and that it is hugely beneficial. These are not small effects, and they show that weight loss has a huge impact on health. It’s extraordinary,” Dr. Finer asserted.
“These data show that if we treat obesity first, rather than the complications, we actually get big results in terms of health. This really should be a game-changer for those health care systems that are still prevaricating about treating obesity seriously,” he added.
The size of the study, of over 550,000 U.K. adults in primary care, makes it unique. In the real-world cohort, people who had lost 10%-25% of their body weight were followed for a mean 8 years to see how this affected their subsequent risk of obesity-related conditions. The results were presented during the virtual European and International Congress on Obesity.
“Weight loss was real-world without any artificial intervention and they experienced a real-life reduction in risk of various obesity-related conditions,” Dr. Haase said in an interview.
Carel Le Roux, MD, PhD, from the Diabetes Complications Research Centre, University College Dublin, welcomed the study because it showed those with obesity who maintained more than 10% weight loss experienced a significant reduction in the complications of obesity.
“In the study, intentional weight loss was achieved using mainly diets and exercise, but also some medications and surgical treatments. However, it did not matter how patients were able to maintain the 10% or more weight loss as regards the positive impact on complications of obesity,” he highlighted.
From a clinician standpoint, “it helps to consider all the weight-loss options available, but also for those who are not able to achieve weight-loss maintenance, to escalate treatment. This is now possible as we gain access to more effective treatments,” he added.
Also commenting on the findings, Matt Petersen, vice president of medical information and professional engagement at the American Diabetes Association, said: “It’s helpful to have further evidence that weight loss reduces risk for type 2 diabetes.”
However, “finding effective strategies to achieve and maintain long-term weight loss and maintenance remains a significant challenge,” he observed.
Large database of half a million people with obesity
For the research, anonymized data from over half a million patients documented in the Clinical Practice Research Datalink database, which holds information from 674 general practices in the United Kingdom, were linked to Hospital Episode Statistics and prescribing data to determine comorbidity outcomes.
At baseline, characteristics for the full study population included a median age of 54 years, around 50% of participants had hypertension, around 40% had dyslipidemia, and around 20% had type 2 diabetes. Less than 10% had sleep apnea, hip/knee osteoarthritis, or history of cardiovascular disease. All participants had a body mass index (BMI) of 25.0-50.0 kg/m2 at the start of the follow-up, between January 2001 and December 2010.
Patients may have been advised to lose weight, or take more exercise, or have been referred to a dietitian. Some had been prescribed antiobesity medications available between 2001 and 2010. (Novo Nordisk medications for obesity were unavailable during this period.) Less than 1% had been referred for bariatric surgery.
“This is typical of real-world management of obesity,” Dr. Haase pointed out.
Participants were divided into two categories based on their weight pattern during the 4-year period: one whose weight remained stable (492,380 individuals with BMI change within –5% to 5%) and one who lost weight (60,573 with BMI change –10% to –25%).
The median change in BMI in the weight-loss group was –13%. The researchers also extracted information on weight loss interventions and dietary advice to confirm intention to lose weight.
The benefits of losing 13% of body weight were then determined for three risk profiles: BMI reduction from 34.5 to 30 (obesity class I level); from 40.3 to 35 (obesity class II level), and from46 to 40 (obesity class III level).
Individuals with a baseline history of any particular outcome were excluded from the risk analysis for that same outcome. All analyses were adjusted for BMI, age, gender, smoking status, and baseline comorbidities.
Study strengths include the large number of participants and the relatively long follow-up period. But the observational nature of the study limits the ability to know the ways in which the participants who lost weight may have differed from those who maintained or gained weight, the authors said.
Type 2 diabetes, sleep apnea showed greatest risk reductions
The researchers looked at the risk reduction for various comorbidities after weight loss, compared with before weight loss. They also examined the risk reductions after weight loss, compared with someone who had always had a median 13% lower weight.
Effectively, the analysis provided a measure of the effect of risk reduction because of weight loss, compared with having that lower weight as a stable weight.
“The analysis asks if the person’s risk was reversed by the weight loss to the risk associated with that of the lower weight level,” explained Dr. Haase.
“We found that the risks of type 2 diabetes, dyslipidemia, and hypertension were reversed while the risk of sleep apnea and hip/knee osteoarthritis showed some residual risk,” she added.
With sleep apnea there was a risk reduction of up to 27%, compared with before weight loss.
“This is a condition that can’t be easily reversed except with mechanical sleeping devices and it is underrecognized and causes a lot of distress. There’s actually a link between sleep apnea, diabetes, and hypertension in a two-way connection,” noted Dr. Finer, who is also honorary professor of cardiovascular medicine at University College London.
“A reduction of this proportion is impressive,” he stressed.
Dyslipidemia, hypertension, and type 2 diabetes are well-known cardiovascular risk factors. “We did not see any impact on myocardial infarction,” which “might be due to length of follow-up,” noted Dr. Haase.
Response of type 2 diabetes to weight loss
Most patients in the study did not have type 2 diabetes at baseline, and Dr. Finer commented on how weight loss might affect type 2 diabetes risk.
“The complications of obesity resolve with weight loss at different speeds,” he said.
“Type 2 diabetes is very sensitive to weight loss and improvements are obvious in weeks to months.”
In contrast, reductions in risk of obstructive sleep apnea “take longer and might depend on the amount of weight lost.” And with osteoarthritis, “It’s hard to show improvement with weight loss because irreparable damage has [already] been done,” he explained.
The degree of improvement in diabetes because of weight loss is partly dependent on how long the person has had diabetes, Dr. Finer further explained. “If someone has less excess weight then the diabetes might have had a shorter duration and therefore response might be greater.”
Lucy Chambers, PhD, head of research communications at Diabetes UK, said: “We’ve known for a long time that carrying extra weight can increase your risk of developing type 2 diabetes, and this new study adds to the extensive body of evidence showing that losing some of this weight is associated with reduced risk.”
She acknowledged, however, that losing weight is difficult and that support is important: “We need government to urgently review provision of weight management services and take action to address the barriers to accessing them.”
Dr. Finer and Dr. Haase are both employees of Novo Nordisk. Dr. Le Roux reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Intentional loss of a median of just 13% of body weight reduces the relative risk of developing type 2 diabetes by around 40% in people with obesity, among many other health benefits, shows a large real-world study in half a million adults.
Other findings associated with the same modest weight loss included a reduction in the risk of sleep apnea by 22%-27%, hypertension by 18%-25%, and dyslipidemia by 20%-22%.
Christiane Haase, PhD, of Novo Nordisk, led the work together with Nick Finer, MD, senior principal clinical scientist, Novo Nordisk.
“This is powerful evidence to say it is worthwhile to help people lose weight and that it is hugely beneficial. These are not small effects, and they show that weight loss has a huge impact on health. It’s extraordinary,” Dr. Finer asserted.
“These data show that if we treat obesity first, rather than the complications, we actually get big results in terms of health. This really should be a game-changer for those health care systems that are still prevaricating about treating obesity seriously,” he added.
The size of the study, of over 550,000 U.K. adults in primary care, makes it unique. In the real-world cohort, people who had lost 10%-25% of their body weight were followed for a mean 8 years to see how this affected their subsequent risk of obesity-related conditions. The results were presented during the virtual European and International Congress on Obesity.
“Weight loss was real-world without any artificial intervention and they experienced a real-life reduction in risk of various obesity-related conditions,” Dr. Haase said in an interview.
Carel Le Roux, MD, PhD, from the Diabetes Complications Research Centre, University College Dublin, welcomed the study because it showed those with obesity who maintained more than 10% weight loss experienced a significant reduction in the complications of obesity.
“In the study, intentional weight loss was achieved using mainly diets and exercise, but also some medications and surgical treatments. However, it did not matter how patients were able to maintain the 10% or more weight loss as regards the positive impact on complications of obesity,” he highlighted.
From a clinician standpoint, “it helps to consider all the weight-loss options available, but also for those who are not able to achieve weight-loss maintenance, to escalate treatment. This is now possible as we gain access to more effective treatments,” he added.
Also commenting on the findings, Matt Petersen, vice president of medical information and professional engagement at the American Diabetes Association, said: “It’s helpful to have further evidence that weight loss reduces risk for type 2 diabetes.”
However, “finding effective strategies to achieve and maintain long-term weight loss and maintenance remains a significant challenge,” he observed.
Large database of half a million people with obesity
For the research, anonymized data from over half a million patients documented in the Clinical Practice Research Datalink database, which holds information from 674 general practices in the United Kingdom, were linked to Hospital Episode Statistics and prescribing data to determine comorbidity outcomes.
At baseline, characteristics for the full study population included a median age of 54 years, around 50% of participants had hypertension, around 40% had dyslipidemia, and around 20% had type 2 diabetes. Less than 10% had sleep apnea, hip/knee osteoarthritis, or history of cardiovascular disease. All participants had a body mass index (BMI) of 25.0-50.0 kg/m2 at the start of the follow-up, between January 2001 and December 2010.
Patients may have been advised to lose weight, or take more exercise, or have been referred to a dietitian. Some had been prescribed antiobesity medications available between 2001 and 2010. (Novo Nordisk medications for obesity were unavailable during this period.) Less than 1% had been referred for bariatric surgery.
“This is typical of real-world management of obesity,” Dr. Haase pointed out.
Participants were divided into two categories based on their weight pattern during the 4-year period: one whose weight remained stable (492,380 individuals with BMI change within –5% to 5%) and one who lost weight (60,573 with BMI change –10% to –25%).
The median change in BMI in the weight-loss group was –13%. The researchers also extracted information on weight loss interventions and dietary advice to confirm intention to lose weight.
The benefits of losing 13% of body weight were then determined for three risk profiles: BMI reduction from 34.5 to 30 (obesity class I level); from 40.3 to 35 (obesity class II level), and from46 to 40 (obesity class III level).
Individuals with a baseline history of any particular outcome were excluded from the risk analysis for that same outcome. All analyses were adjusted for BMI, age, gender, smoking status, and baseline comorbidities.
Study strengths include the large number of participants and the relatively long follow-up period. But the observational nature of the study limits the ability to know the ways in which the participants who lost weight may have differed from those who maintained or gained weight, the authors said.
Type 2 diabetes, sleep apnea showed greatest risk reductions
The researchers looked at the risk reduction for various comorbidities after weight loss, compared with before weight loss. They also examined the risk reductions after weight loss, compared with someone who had always had a median 13% lower weight.
Effectively, the analysis provided a measure of the effect of risk reduction because of weight loss, compared with having that lower weight as a stable weight.
“The analysis asks if the person’s risk was reversed by the weight loss to the risk associated with that of the lower weight level,” explained Dr. Haase.
“We found that the risks of type 2 diabetes, dyslipidemia, and hypertension were reversed while the risk of sleep apnea and hip/knee osteoarthritis showed some residual risk,” she added.
With sleep apnea there was a risk reduction of up to 27%, compared with before weight loss.
“This is a condition that can’t be easily reversed except with mechanical sleeping devices and it is underrecognized and causes a lot of distress. There’s actually a link between sleep apnea, diabetes, and hypertension in a two-way connection,” noted Dr. Finer, who is also honorary professor of cardiovascular medicine at University College London.
“A reduction of this proportion is impressive,” he stressed.
Dyslipidemia, hypertension, and type 2 diabetes are well-known cardiovascular risk factors. “We did not see any impact on myocardial infarction,” which “might be due to length of follow-up,” noted Dr. Haase.
Response of type 2 diabetes to weight loss
Most patients in the study did not have type 2 diabetes at baseline, and Dr. Finer commented on how weight loss might affect type 2 diabetes risk.
“The complications of obesity resolve with weight loss at different speeds,” he said.
“Type 2 diabetes is very sensitive to weight loss and improvements are obvious in weeks to months.”
In contrast, reductions in risk of obstructive sleep apnea “take longer and might depend on the amount of weight lost.” And with osteoarthritis, “It’s hard to show improvement with weight loss because irreparable damage has [already] been done,” he explained.
The degree of improvement in diabetes because of weight loss is partly dependent on how long the person has had diabetes, Dr. Finer further explained. “If someone has less excess weight then the diabetes might have had a shorter duration and therefore response might be greater.”
Lucy Chambers, PhD, head of research communications at Diabetes UK, said: “We’ve known for a long time that carrying extra weight can increase your risk of developing type 2 diabetes, and this new study adds to the extensive body of evidence showing that losing some of this weight is associated with reduced risk.”
She acknowledged, however, that losing weight is difficult and that support is important: “We need government to urgently review provision of weight management services and take action to address the barriers to accessing them.”
Dr. Finer and Dr. Haase are both employees of Novo Nordisk. Dr. Le Roux reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Intentional loss of a median of just 13% of body weight reduces the relative risk of developing type 2 diabetes by around 40% in people with obesity, among many other health benefits, shows a large real-world study in half a million adults.
Other findings associated with the same modest weight loss included a reduction in the risk of sleep apnea by 22%-27%, hypertension by 18%-25%, and dyslipidemia by 20%-22%.
Christiane Haase, PhD, of Novo Nordisk, led the work together with Nick Finer, MD, senior principal clinical scientist, Novo Nordisk.
“This is powerful evidence to say it is worthwhile to help people lose weight and that it is hugely beneficial. These are not small effects, and they show that weight loss has a huge impact on health. It’s extraordinary,” Dr. Finer asserted.
“These data show that if we treat obesity first, rather than the complications, we actually get big results in terms of health. This really should be a game-changer for those health care systems that are still prevaricating about treating obesity seriously,” he added.
The size of the study, of over 550,000 U.K. adults in primary care, makes it unique. In the real-world cohort, people who had lost 10%-25% of their body weight were followed for a mean 8 years to see how this affected their subsequent risk of obesity-related conditions. The results were presented during the virtual European and International Congress on Obesity.
“Weight loss was real-world without any artificial intervention and they experienced a real-life reduction in risk of various obesity-related conditions,” Dr. Haase said in an interview.
Carel Le Roux, MD, PhD, from the Diabetes Complications Research Centre, University College Dublin, welcomed the study because it showed those with obesity who maintained more than 10% weight loss experienced a significant reduction in the complications of obesity.
“In the study, intentional weight loss was achieved using mainly diets and exercise, but also some medications and surgical treatments. However, it did not matter how patients were able to maintain the 10% or more weight loss as regards the positive impact on complications of obesity,” he highlighted.
From a clinician standpoint, “it helps to consider all the weight-loss options available, but also for those who are not able to achieve weight-loss maintenance, to escalate treatment. This is now possible as we gain access to more effective treatments,” he added.
Also commenting on the findings, Matt Petersen, vice president of medical information and professional engagement at the American Diabetes Association, said: “It’s helpful to have further evidence that weight loss reduces risk for type 2 diabetes.”
However, “finding effective strategies to achieve and maintain long-term weight loss and maintenance remains a significant challenge,” he observed.
Large database of half a million people with obesity
For the research, anonymized data from over half a million patients documented in the Clinical Practice Research Datalink database, which holds information from 674 general practices in the United Kingdom, were linked to Hospital Episode Statistics and prescribing data to determine comorbidity outcomes.
At baseline, characteristics for the full study population included a median age of 54 years, around 50% of participants had hypertension, around 40% had dyslipidemia, and around 20% had type 2 diabetes. Less than 10% had sleep apnea, hip/knee osteoarthritis, or history of cardiovascular disease. All participants had a body mass index (BMI) of 25.0-50.0 kg/m2 at the start of the follow-up, between January 2001 and December 2010.
Patients may have been advised to lose weight, or take more exercise, or have been referred to a dietitian. Some had been prescribed antiobesity medications available between 2001 and 2010. (Novo Nordisk medications for obesity were unavailable during this period.) Less than 1% had been referred for bariatric surgery.
“This is typical of real-world management of obesity,” Dr. Haase pointed out.
Participants were divided into two categories based on their weight pattern during the 4-year period: one whose weight remained stable (492,380 individuals with BMI change within –5% to 5%) and one who lost weight (60,573 with BMI change –10% to –25%).
The median change in BMI in the weight-loss group was –13%. The researchers also extracted information on weight loss interventions and dietary advice to confirm intention to lose weight.
The benefits of losing 13% of body weight were then determined for three risk profiles: BMI reduction from 34.5 to 30 (obesity class I level); from 40.3 to 35 (obesity class II level), and from46 to 40 (obesity class III level).
Individuals with a baseline history of any particular outcome were excluded from the risk analysis for that same outcome. All analyses were adjusted for BMI, age, gender, smoking status, and baseline comorbidities.
Study strengths include the large number of participants and the relatively long follow-up period. But the observational nature of the study limits the ability to know the ways in which the participants who lost weight may have differed from those who maintained or gained weight, the authors said.
Type 2 diabetes, sleep apnea showed greatest risk reductions
The researchers looked at the risk reduction for various comorbidities after weight loss, compared with before weight loss. They also examined the risk reductions after weight loss, compared with someone who had always had a median 13% lower weight.
Effectively, the analysis provided a measure of the effect of risk reduction because of weight loss, compared with having that lower weight as a stable weight.
“The analysis asks if the person’s risk was reversed by the weight loss to the risk associated with that of the lower weight level,” explained Dr. Haase.
“We found that the risks of type 2 diabetes, dyslipidemia, and hypertension were reversed while the risk of sleep apnea and hip/knee osteoarthritis showed some residual risk,” she added.
With sleep apnea there was a risk reduction of up to 27%, compared with before weight loss.
“This is a condition that can’t be easily reversed except with mechanical sleeping devices and it is underrecognized and causes a lot of distress. There’s actually a link between sleep apnea, diabetes, and hypertension in a two-way connection,” noted Dr. Finer, who is also honorary professor of cardiovascular medicine at University College London.
“A reduction of this proportion is impressive,” he stressed.
Dyslipidemia, hypertension, and type 2 diabetes are well-known cardiovascular risk factors. “We did not see any impact on myocardial infarction,” which “might be due to length of follow-up,” noted Dr. Haase.
Response of type 2 diabetes to weight loss
Most patients in the study did not have type 2 diabetes at baseline, and Dr. Finer commented on how weight loss might affect type 2 diabetes risk.
“The complications of obesity resolve with weight loss at different speeds,” he said.
“Type 2 diabetes is very sensitive to weight loss and improvements are obvious in weeks to months.”
In contrast, reductions in risk of obstructive sleep apnea “take longer and might depend on the amount of weight lost.” And with osteoarthritis, “It’s hard to show improvement with weight loss because irreparable damage has [already] been done,” he explained.
The degree of improvement in diabetes because of weight loss is partly dependent on how long the person has had diabetes, Dr. Finer further explained. “If someone has less excess weight then the diabetes might have had a shorter duration and therefore response might be greater.”
Lucy Chambers, PhD, head of research communications at Diabetes UK, said: “We’ve known for a long time that carrying extra weight can increase your risk of developing type 2 diabetes, and this new study adds to the extensive body of evidence showing that losing some of this weight is associated with reduced risk.”
She acknowledged, however, that losing weight is difficult and that support is important: “We need government to urgently review provision of weight management services and take action to address the barriers to accessing them.”
Dr. Finer and Dr. Haase are both employees of Novo Nordisk. Dr. Le Roux reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Smoking increases risk of high plasma NfL levels in patients with MS
A new study has found that At the same time, patients who have stopped smoking have notably lower risk that correlates to how long ago they quit.
“Before, all the studies that were looking at the association between smoking and MS – especially in terms of severity – were using indications like the Expanded Disability Status Scale and the Multiple Sclerosis Severity Score,” said first author Ali Manouchehrinia, PhD, assistant professor at the Karolinska Institute, Stockholm. “Now, we have NfL as a biomarker for disease activity, and we can see the effect of smoking on that biomarker.”
The ultimate goal, he added, “is to tease out the effects of MS severity and disease activity from NfL, to make sure that changes or differences in NfL levels are truly caused by MS and nothing else.”
Dr. Manouchehrinia presented his team’s findings at the virtual annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.
To determine any associations between smoking and pNfL levels, the researchers began a retrospective, population-based cohort study of 2,572 Swedish MS patients with a self-reported history of cigarette smoking. Their average age was 38.2 years, slightly more than 71% were women, and their average disease duration was 4.13 years.
Blood samples were collected at each patients’ time of diagnosis to analyze concentrations of pNfL. Three age-stratified pNfL levels were classified: above the 80th (>C80), 95th (>C95), and 99th (>C99) of 1,026 non-MS controls’ percentiles.
Of the 2,572 MS patients, 292 (11.4%) were current regular smokers and 714 (27.8%) were past regular smokers. The past smokers’ median time since quitting was 2 years. Being a current smoker was associated with much higher odds of having pNfL levels at >C99, compared with never smokers (odds ratio, 1.52; 95% confidence interval, 1.12-2.05; P = .007) and past smokers (OR, 1.42; 95% CI, 1.01-1.99; P = .043).
For past smokers who quit between 6 and 10 years ago, the risk of having pNfL levels at >C99 was considerably lower (OR, 0.53; 95% CI, 0.29-0.93; P = .032), compared with current smokers, as was the risk for past smokers who quit more than 10 years ago (OR, 0.50; 95% CI, 0.29-0.84; P = .010). The odds were also lower, though not significantly, for patients who quit 1-5 years ago (OR, 0.84; 95% CI, 0.58-1.22; P = .359).
“It looks like, after 10 years, you go back to the baseline and have the same risk as the never smokers,” Dr. Manouchehrinia said. “But the damage may have already been done. Quitting smoking is good, but it’s better to not smoke at all.”
Dr. Manouchehrinia acknowledged the study’s limitations, including the need to learn more about the role NfL levels – especially plasma NfL levels – play across MS patients, along with the complications surrounding smoking as an environmental factor. He noted that, in Sweden, many people get their nicotine from snuff rather than cigarettes. “Among our MS population, we’ve seen a recent shift toward female snuff users,” which lessens the amount they smoke and could confound the results. In fact, the study indicated that snuff users had less risk of pNfL levels at >C95, compared with nonsnuff users (OR, 0.71; 95% CI, 0.51-0.97; P = .034).
The authors reported several potential conflicts of interest, including receiving research grants and lecture honoraria and serving on advisory boards for various pharmaceutical companies.
A new study has found that At the same time, patients who have stopped smoking have notably lower risk that correlates to how long ago they quit.
“Before, all the studies that were looking at the association between smoking and MS – especially in terms of severity – were using indications like the Expanded Disability Status Scale and the Multiple Sclerosis Severity Score,” said first author Ali Manouchehrinia, PhD, assistant professor at the Karolinska Institute, Stockholm. “Now, we have NfL as a biomarker for disease activity, and we can see the effect of smoking on that biomarker.”
The ultimate goal, he added, “is to tease out the effects of MS severity and disease activity from NfL, to make sure that changes or differences in NfL levels are truly caused by MS and nothing else.”
Dr. Manouchehrinia presented his team’s findings at the virtual annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.
To determine any associations between smoking and pNfL levels, the researchers began a retrospective, population-based cohort study of 2,572 Swedish MS patients with a self-reported history of cigarette smoking. Their average age was 38.2 years, slightly more than 71% were women, and their average disease duration was 4.13 years.
Blood samples were collected at each patients’ time of diagnosis to analyze concentrations of pNfL. Three age-stratified pNfL levels were classified: above the 80th (>C80), 95th (>C95), and 99th (>C99) of 1,026 non-MS controls’ percentiles.
Of the 2,572 MS patients, 292 (11.4%) were current regular smokers and 714 (27.8%) were past regular smokers. The past smokers’ median time since quitting was 2 years. Being a current smoker was associated with much higher odds of having pNfL levels at >C99, compared with never smokers (odds ratio, 1.52; 95% confidence interval, 1.12-2.05; P = .007) and past smokers (OR, 1.42; 95% CI, 1.01-1.99; P = .043).
For past smokers who quit between 6 and 10 years ago, the risk of having pNfL levels at >C99 was considerably lower (OR, 0.53; 95% CI, 0.29-0.93; P = .032), compared with current smokers, as was the risk for past smokers who quit more than 10 years ago (OR, 0.50; 95% CI, 0.29-0.84; P = .010). The odds were also lower, though not significantly, for patients who quit 1-5 years ago (OR, 0.84; 95% CI, 0.58-1.22; P = .359).
“It looks like, after 10 years, you go back to the baseline and have the same risk as the never smokers,” Dr. Manouchehrinia said. “But the damage may have already been done. Quitting smoking is good, but it’s better to not smoke at all.”
Dr. Manouchehrinia acknowledged the study’s limitations, including the need to learn more about the role NfL levels – especially plasma NfL levels – play across MS patients, along with the complications surrounding smoking as an environmental factor. He noted that, in Sweden, many people get their nicotine from snuff rather than cigarettes. “Among our MS population, we’ve seen a recent shift toward female snuff users,” which lessens the amount they smoke and could confound the results. In fact, the study indicated that snuff users had less risk of pNfL levels at >C95, compared with nonsnuff users (OR, 0.71; 95% CI, 0.51-0.97; P = .034).
The authors reported several potential conflicts of interest, including receiving research grants and lecture honoraria and serving on advisory boards for various pharmaceutical companies.
A new study has found that At the same time, patients who have stopped smoking have notably lower risk that correlates to how long ago they quit.
“Before, all the studies that were looking at the association between smoking and MS – especially in terms of severity – were using indications like the Expanded Disability Status Scale and the Multiple Sclerosis Severity Score,” said first author Ali Manouchehrinia, PhD, assistant professor at the Karolinska Institute, Stockholm. “Now, we have NfL as a biomarker for disease activity, and we can see the effect of smoking on that biomarker.”
The ultimate goal, he added, “is to tease out the effects of MS severity and disease activity from NfL, to make sure that changes or differences in NfL levels are truly caused by MS and nothing else.”
Dr. Manouchehrinia presented his team’s findings at the virtual annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.
To determine any associations between smoking and pNfL levels, the researchers began a retrospective, population-based cohort study of 2,572 Swedish MS patients with a self-reported history of cigarette smoking. Their average age was 38.2 years, slightly more than 71% were women, and their average disease duration was 4.13 years.
Blood samples were collected at each patients’ time of diagnosis to analyze concentrations of pNfL. Three age-stratified pNfL levels were classified: above the 80th (>C80), 95th (>C95), and 99th (>C99) of 1,026 non-MS controls’ percentiles.
Of the 2,572 MS patients, 292 (11.4%) were current regular smokers and 714 (27.8%) were past regular smokers. The past smokers’ median time since quitting was 2 years. Being a current smoker was associated with much higher odds of having pNfL levels at >C99, compared with never smokers (odds ratio, 1.52; 95% confidence interval, 1.12-2.05; P = .007) and past smokers (OR, 1.42; 95% CI, 1.01-1.99; P = .043).
For past smokers who quit between 6 and 10 years ago, the risk of having pNfL levels at >C99 was considerably lower (OR, 0.53; 95% CI, 0.29-0.93; P = .032), compared with current smokers, as was the risk for past smokers who quit more than 10 years ago (OR, 0.50; 95% CI, 0.29-0.84; P = .010). The odds were also lower, though not significantly, for patients who quit 1-5 years ago (OR, 0.84; 95% CI, 0.58-1.22; P = .359).
“It looks like, after 10 years, you go back to the baseline and have the same risk as the never smokers,” Dr. Manouchehrinia said. “But the damage may have already been done. Quitting smoking is good, but it’s better to not smoke at all.”
Dr. Manouchehrinia acknowledged the study’s limitations, including the need to learn more about the role NfL levels – especially plasma NfL levels – play across MS patients, along with the complications surrounding smoking as an environmental factor. He noted that, in Sweden, many people get their nicotine from snuff rather than cigarettes. “Among our MS population, we’ve seen a recent shift toward female snuff users,” which lessens the amount they smoke and could confound the results. In fact, the study indicated that snuff users had less risk of pNfL levels at >C95, compared with nonsnuff users (OR, 0.71; 95% CI, 0.51-0.97; P = .034).
The authors reported several potential conflicts of interest, including receiving research grants and lecture honoraria and serving on advisory boards for various pharmaceutical companies.
FROM ECTRIMS 2020
Obesity-related hypoventilation increased morbidity risk after bariatric surgery
Patients with obesity-associated sleep hypoventilation had a heightened risk of postoperative morbidities after bariatric surgery, according to a retrospective study.
Reena Mehra, MD, director of sleep disorders research for the Sleep Disorders Center at the Cleveland Clinic, led the team and the findings were presented at the virtual annual meeting of the Associated Professional Sleep Societies. Her research team examined the outcomes of 1,665 patients who underwent polysomnography prior to bariatric surgery performed at the Cleveland Clinic from 2011 to 2018.
More than two-thirds – 68.5% – had obesity-associated sleep hypoventilation as defined by body mass index (BMI) of ≥30 kg/m2 and either polysomnography-based end-tidal CO2 ≥45 mm Hg or serum bicarbonate ≥27 mEq/L.
These patients represent “a subset, if you will, of obesity hypoventilation syndrome – a subset that we were able to capture from our sleep studies … [because] we do CO2 monitoring during sleep studies uniformly,” Dr. Mehra said in an interview after the meeting.
Pornprapa Chindamporn, MD, a former fellow at the center and first author on the abstract, presented the findings. Patients in the study had a mean age of 45.2 ± 12.0 years and a BMI of 48.7 ± 9.0. Approximately 20% were male and 63.6% were White.
Those with obesity-associated sleep hypoventilation were more likely to be male and have a higher BMI and higher hemoglobin A1c than those without the condition. They also had a significantly higher apnea-hypopnea index (17.0 vs. 13.8) in those without the condition, she reported.
A number of outcomes (ICU stay, intubation, tracheostomy, discharge disposition, and 30-day readmission) were compared individually and as a composite outcome between those with and without obesity-associated sleep hypoventilation. While some of these postoperative morbidities were more common in patients with the condition, the differences between those with and without OHS were not statistically significant for intubation (1.5% vs. 1.3%, P = .81) and 30-day readmission (13.8% vs. 11.3%, P = .16). However, the composite outcome was significantly higher: 18.9% vs. 14.3% (P = .021), including in multivariable analysis that considered age, gender, BMI, Apnea Hypopnea Index, and diabetes.
All-cause mortality was not significantly different between the groups, likely because of its low overall rate (hazard ratio, 1.39; 95% confidence interval, 0.56-3.42).
“In this largest sample to date of systematically phenotyped obesity-associated sleep hypoventilation in patients undergoing bariatric surgery, we identified increased postoperative morbidity,” said Dr. Chindamporn, now a pulmonologist and sleep specialist practicing in Bangkok.
Dr. Mehra said in the interview that patients considering bariatric surgery are typically assessed for obstructive sleep apnea, but “not so much obesity hypoventilation syndrome or obesity-associated sleep-related hypoventilation syndrome.” The findings, “support the notion that we should be closely examining sleep-related hypoventilation in these patients.”
At the Cleveland Clinic, “clinically, we make sure we’re identifying these individuals and communicating the findings to bariatric surgery colleagues and to anesthesia,” said Dr. Mehra, also professor of medicine at Case Western Reserve University, Cleveland.
OHS is defined, according to the 2019 American Thoracic Society clinical practice guideline on evaluation and management of OHS, by the combination of obesity, sleep-disordered breathing, and awake daytime hypercapnia, after excluding other causes for hypoventilation (Am J Respir Crit Care Med. 2019;200[3]:e6-24).
A European Respiratory Society task force has proposed severity grading for OHS, with early stages defined by sleep-related hypoventilation and the highest grade of severity defined by morbidity-associated daytime hypercapnia (Eur Respir Rev. 2019;28:180097). However, Dr. Mehra said she is “not sure that we know enough [from long-term studies of OHS] to say definitively that there’s such an evolution.”
Certainly, she said, future research on OHS should consider its heterogeneity. It is possible that a subset of patients with OHS, “maybe these individuals with sleep-related hypoventilation,” are most likely to have adverse postsurgical outcomes.
Atul Malhotra, MD, professor of medicine at the University of California, San Diego, who was asked to comment on the study, said that OHS is understudied in general and particularly in the perioperative setting. “With the obesity pandemic, issues around OHS are likely to be [increasingly] important. And with increasing [use of] bariatric surgery, strategies to minimize risks are clearly needed,” he said, adding that the potential risks of nonbariatric surgery in patients with OHS require further study.
He noted that mortality rates in good hospitals “have become quite low for many elective surgeries, making it hard to show mortality benefit to most interventions.”
The ATS guideline on OHS states that it is the most severe form of obesity-induced respiratory compromise and leads to serious sequelae, including increased rates of mortality, chronic heart failure, pulmonary hypertension, and hospitalization caused by acute-on-chronic hypercapnic respiratory failure.
Dr. Chindamporn said in her presentation that she had no disclosures. Dr. Mehra’s research program is funded by the National Institute of Health, but she has also procured funding from the American College of Chest Physicians, American Heart Association, Clinical Translational Science Collaborative, and Central Society of Clinical Research. Dr. Malhotra disclosed that he is funded by the NIH and has received income from Merck and LIvanova related to medical education.
CORRECTION 9/15/2020: The original story misstated the presenter of the study. Dr. Chindamporn presented the findings.
Patients with obesity-associated sleep hypoventilation had a heightened risk of postoperative morbidities after bariatric surgery, according to a retrospective study.
Reena Mehra, MD, director of sleep disorders research for the Sleep Disorders Center at the Cleveland Clinic, led the team and the findings were presented at the virtual annual meeting of the Associated Professional Sleep Societies. Her research team examined the outcomes of 1,665 patients who underwent polysomnography prior to bariatric surgery performed at the Cleveland Clinic from 2011 to 2018.
More than two-thirds – 68.5% – had obesity-associated sleep hypoventilation as defined by body mass index (BMI) of ≥30 kg/m2 and either polysomnography-based end-tidal CO2 ≥45 mm Hg or serum bicarbonate ≥27 mEq/L.
These patients represent “a subset, if you will, of obesity hypoventilation syndrome – a subset that we were able to capture from our sleep studies … [because] we do CO2 monitoring during sleep studies uniformly,” Dr. Mehra said in an interview after the meeting.
Pornprapa Chindamporn, MD, a former fellow at the center and first author on the abstract, presented the findings. Patients in the study had a mean age of 45.2 ± 12.0 years and a BMI of 48.7 ± 9.0. Approximately 20% were male and 63.6% were White.
Those with obesity-associated sleep hypoventilation were more likely to be male and have a higher BMI and higher hemoglobin A1c than those without the condition. They also had a significantly higher apnea-hypopnea index (17.0 vs. 13.8) in those without the condition, she reported.
A number of outcomes (ICU stay, intubation, tracheostomy, discharge disposition, and 30-day readmission) were compared individually and as a composite outcome between those with and without obesity-associated sleep hypoventilation. While some of these postoperative morbidities were more common in patients with the condition, the differences between those with and without OHS were not statistically significant for intubation (1.5% vs. 1.3%, P = .81) and 30-day readmission (13.8% vs. 11.3%, P = .16). However, the composite outcome was significantly higher: 18.9% vs. 14.3% (P = .021), including in multivariable analysis that considered age, gender, BMI, Apnea Hypopnea Index, and diabetes.
All-cause mortality was not significantly different between the groups, likely because of its low overall rate (hazard ratio, 1.39; 95% confidence interval, 0.56-3.42).
“In this largest sample to date of systematically phenotyped obesity-associated sleep hypoventilation in patients undergoing bariatric surgery, we identified increased postoperative morbidity,” said Dr. Chindamporn, now a pulmonologist and sleep specialist practicing in Bangkok.
Dr. Mehra said in the interview that patients considering bariatric surgery are typically assessed for obstructive sleep apnea, but “not so much obesity hypoventilation syndrome or obesity-associated sleep-related hypoventilation syndrome.” The findings, “support the notion that we should be closely examining sleep-related hypoventilation in these patients.”
At the Cleveland Clinic, “clinically, we make sure we’re identifying these individuals and communicating the findings to bariatric surgery colleagues and to anesthesia,” said Dr. Mehra, also professor of medicine at Case Western Reserve University, Cleveland.
OHS is defined, according to the 2019 American Thoracic Society clinical practice guideline on evaluation and management of OHS, by the combination of obesity, sleep-disordered breathing, and awake daytime hypercapnia, after excluding other causes for hypoventilation (Am J Respir Crit Care Med. 2019;200[3]:e6-24).
A European Respiratory Society task force has proposed severity grading for OHS, with early stages defined by sleep-related hypoventilation and the highest grade of severity defined by morbidity-associated daytime hypercapnia (Eur Respir Rev. 2019;28:180097). However, Dr. Mehra said she is “not sure that we know enough [from long-term studies of OHS] to say definitively that there’s such an evolution.”
Certainly, she said, future research on OHS should consider its heterogeneity. It is possible that a subset of patients with OHS, “maybe these individuals with sleep-related hypoventilation,” are most likely to have adverse postsurgical outcomes.
Atul Malhotra, MD, professor of medicine at the University of California, San Diego, who was asked to comment on the study, said that OHS is understudied in general and particularly in the perioperative setting. “With the obesity pandemic, issues around OHS are likely to be [increasingly] important. And with increasing [use of] bariatric surgery, strategies to minimize risks are clearly needed,” he said, adding that the potential risks of nonbariatric surgery in patients with OHS require further study.
He noted that mortality rates in good hospitals “have become quite low for many elective surgeries, making it hard to show mortality benefit to most interventions.”
The ATS guideline on OHS states that it is the most severe form of obesity-induced respiratory compromise and leads to serious sequelae, including increased rates of mortality, chronic heart failure, pulmonary hypertension, and hospitalization caused by acute-on-chronic hypercapnic respiratory failure.
Dr. Chindamporn said in her presentation that she had no disclosures. Dr. Mehra’s research program is funded by the National Institute of Health, but she has also procured funding from the American College of Chest Physicians, American Heart Association, Clinical Translational Science Collaborative, and Central Society of Clinical Research. Dr. Malhotra disclosed that he is funded by the NIH and has received income from Merck and LIvanova related to medical education.
CORRECTION 9/15/2020: The original story misstated the presenter of the study. Dr. Chindamporn presented the findings.
Patients with obesity-associated sleep hypoventilation had a heightened risk of postoperative morbidities after bariatric surgery, according to a retrospective study.
Reena Mehra, MD, director of sleep disorders research for the Sleep Disorders Center at the Cleveland Clinic, led the team and the findings were presented at the virtual annual meeting of the Associated Professional Sleep Societies. Her research team examined the outcomes of 1,665 patients who underwent polysomnography prior to bariatric surgery performed at the Cleveland Clinic from 2011 to 2018.
More than two-thirds – 68.5% – had obesity-associated sleep hypoventilation as defined by body mass index (BMI) of ≥30 kg/m2 and either polysomnography-based end-tidal CO2 ≥45 mm Hg or serum bicarbonate ≥27 mEq/L.
These patients represent “a subset, if you will, of obesity hypoventilation syndrome – a subset that we were able to capture from our sleep studies … [because] we do CO2 monitoring during sleep studies uniformly,” Dr. Mehra said in an interview after the meeting.
Pornprapa Chindamporn, MD, a former fellow at the center and first author on the abstract, presented the findings. Patients in the study had a mean age of 45.2 ± 12.0 years and a BMI of 48.7 ± 9.0. Approximately 20% were male and 63.6% were White.
Those with obesity-associated sleep hypoventilation were more likely to be male and have a higher BMI and higher hemoglobin A1c than those without the condition. They also had a significantly higher apnea-hypopnea index (17.0 vs. 13.8) in those without the condition, she reported.
A number of outcomes (ICU stay, intubation, tracheostomy, discharge disposition, and 30-day readmission) were compared individually and as a composite outcome between those with and without obesity-associated sleep hypoventilation. While some of these postoperative morbidities were more common in patients with the condition, the differences between those with and without OHS were not statistically significant for intubation (1.5% vs. 1.3%, P = .81) and 30-day readmission (13.8% vs. 11.3%, P = .16). However, the composite outcome was significantly higher: 18.9% vs. 14.3% (P = .021), including in multivariable analysis that considered age, gender, BMI, Apnea Hypopnea Index, and diabetes.
All-cause mortality was not significantly different between the groups, likely because of its low overall rate (hazard ratio, 1.39; 95% confidence interval, 0.56-3.42).
“In this largest sample to date of systematically phenotyped obesity-associated sleep hypoventilation in patients undergoing bariatric surgery, we identified increased postoperative morbidity,” said Dr. Chindamporn, now a pulmonologist and sleep specialist practicing in Bangkok.
Dr. Mehra said in the interview that patients considering bariatric surgery are typically assessed for obstructive sleep apnea, but “not so much obesity hypoventilation syndrome or obesity-associated sleep-related hypoventilation syndrome.” The findings, “support the notion that we should be closely examining sleep-related hypoventilation in these patients.”
At the Cleveland Clinic, “clinically, we make sure we’re identifying these individuals and communicating the findings to bariatric surgery colleagues and to anesthesia,” said Dr. Mehra, also professor of medicine at Case Western Reserve University, Cleveland.
OHS is defined, according to the 2019 American Thoracic Society clinical practice guideline on evaluation and management of OHS, by the combination of obesity, sleep-disordered breathing, and awake daytime hypercapnia, after excluding other causes for hypoventilation (Am J Respir Crit Care Med. 2019;200[3]:e6-24).
A European Respiratory Society task force has proposed severity grading for OHS, with early stages defined by sleep-related hypoventilation and the highest grade of severity defined by morbidity-associated daytime hypercapnia (Eur Respir Rev. 2019;28:180097). However, Dr. Mehra said she is “not sure that we know enough [from long-term studies of OHS] to say definitively that there’s such an evolution.”
Certainly, she said, future research on OHS should consider its heterogeneity. It is possible that a subset of patients with OHS, “maybe these individuals with sleep-related hypoventilation,” are most likely to have adverse postsurgical outcomes.
Atul Malhotra, MD, professor of medicine at the University of California, San Diego, who was asked to comment on the study, said that OHS is understudied in general and particularly in the perioperative setting. “With the obesity pandemic, issues around OHS are likely to be [increasingly] important. And with increasing [use of] bariatric surgery, strategies to minimize risks are clearly needed,” he said, adding that the potential risks of nonbariatric surgery in patients with OHS require further study.
He noted that mortality rates in good hospitals “have become quite low for many elective surgeries, making it hard to show mortality benefit to most interventions.”
The ATS guideline on OHS states that it is the most severe form of obesity-induced respiratory compromise and leads to serious sequelae, including increased rates of mortality, chronic heart failure, pulmonary hypertension, and hospitalization caused by acute-on-chronic hypercapnic respiratory failure.
Dr. Chindamporn said in her presentation that she had no disclosures. Dr. Mehra’s research program is funded by the National Institute of Health, but she has also procured funding from the American College of Chest Physicians, American Heart Association, Clinical Translational Science Collaborative, and Central Society of Clinical Research. Dr. Malhotra disclosed that he is funded by the NIH and has received income from Merck and LIvanova related to medical education.
CORRECTION 9/15/2020: The original story misstated the presenter of the study. Dr. Chindamporn presented the findings.
FROM SLEEP 2020
Insomnia + COPD linked to more outpatient, ED visits
Insomnia is “highly prevalent” in veterans with chronic pulmonary obstructive disease and is significantly associated with greater COPD-related health care utilization, according to an analysis of national Veterans Health Administration data.
“The study highlights the importance of exploring potential sleep disturbances and disorders in this population and suggests that a targeted treatment for insomnia may help to improve COPD outcomes in veterans with COPD and insomnia,” said Faith Luyster, PhD, assistant professor at the University of Pittsburgh, in an interview after the virtual annual meeting of the Associated Professional Sleep Societies, where she presented the findings.
Dr. Luyster and coinvestigators used an administrative database from the Veterans Affairs Corporate Data Warehouse to identify more than 1.5 million patients with COPD who used VHA services over a 6-year period (fiscal years 2011-2017). Insomnia was defined by ICD-9/10 diagnostic codes and/or a sedative-hypnotic prescription for at least 30 doses during any of these years.
Insomnia with COPD was prevalent in this sample of veterans at 37.3%. Compared with veterans without comorbid insomnia, those who had both COPD and insomnia (575,539 of the total 1,542,642) were older (69 vs. 64 years), more likely to be female (6.3% vs. 3.7%), more likely to be Black (14% vs. 11%) and more likely to be a current smoker (46.1% vs. 35.5%).
Those with both COPD and insomnia were also more likely to have a service-connected disability rating of 50% of greater; use supplemental oxygen; be divorced, widowed, or separated; have a higher body mass index; or have other medical or psychiatric conditions – in particular obstructive sleep apnea (39% vs. 7%), depression (21% vs. 5%), and PTSD (33% vs. 3%).
P values were < .001 for all of these demographic and clinical variables, Dr. Luyster reported at the meeting.
Comorbid insomnia clearly impacted health care utilization, she said. Veterans with insomnia in addition to COPD had more outpatient and ED visits (10.5 vs 6.9, and 1.6 vs. 1.4, respectively) and more hospitalizations (2.2 vs. 1.8) with a primary diagnostic code for COPD or COPD exacerbation (P < .001).
A negative binomial regression analysis (P < .001) showed that “even after controlling for demographic and other medical conditions, COPD patients with insomnia had greater rates of health care utilization relative to COPD patients without insomnia,” Dr. Luyster said in the interview.
Prior studies have suggested that disturbed sleep is a predictor of poorer longitudinal outcomes in COPD, even after controlling for COPD severity, but have not looked specifically at insomnia, she said.
Commenting on the study Octavian C. Ioachimescu, MD, PhD, of Emory University, Atlanta, and the Atlanta VA Medical Center in Decatur, said the criteria used to define insomnia – unadjudicated ICD diagnoses as well as sedative-hypnotic prescriptions – may explain part of the reported prevalence of insomnia. Even so, the findings add to existing literature demonstrating that COPD and insomnia are both common disorders among VHA patients, and that their frequent coexistence “could have adverse consequences on the overall health, functional status, long-term outcomes, and quality of life of these patients.”
Questions of causation are yet to be answered, he said. “Is it that uncontrolled or severe airflow obstruction causing frequent nocturnal arousals, dyspnea, orthopnea, overuse of inhaled sympathomimetics and heightened anxiety leads to insomnia? Or is it that insomnia – possibly in a cluster with other affective disorders such as depression, anxiety disorders, or PTSD – elicits more frequent or more severe symptoms of shortness of breath in those with smoking-induced airway and parenchymal lung disease, making the latter diagnosis more overt than in others?
“My bet is on a bidirectional causal relationship,” said Dr. Ioachimescu, an editorial board advisor of CHEST Physician.
“Regardless of the etiology [of insomnia in veterans with COPD],” Dr. Luyster said, “it’s important that [insomnia] be addressed and treated appropriately, whether that be through pharmacological treatment, or probably more ideally through [cognitive behavioral therapy] for insomnia.”
The study did not control for COPD severity, she said, because of the difficulty of extracting this data from the VA Corporate Data Warehouse. The study was funded by the VA Competitive Career Development Fund.Dr. Luyster reported that she had no disclosures. Dr. Ioachimescu also said he had no relevant disclosures.
Insomnia is “highly prevalent” in veterans with chronic pulmonary obstructive disease and is significantly associated with greater COPD-related health care utilization, according to an analysis of national Veterans Health Administration data.
“The study highlights the importance of exploring potential sleep disturbances and disorders in this population and suggests that a targeted treatment for insomnia may help to improve COPD outcomes in veterans with COPD and insomnia,” said Faith Luyster, PhD, assistant professor at the University of Pittsburgh, in an interview after the virtual annual meeting of the Associated Professional Sleep Societies, where she presented the findings.
Dr. Luyster and coinvestigators used an administrative database from the Veterans Affairs Corporate Data Warehouse to identify more than 1.5 million patients with COPD who used VHA services over a 6-year period (fiscal years 2011-2017). Insomnia was defined by ICD-9/10 diagnostic codes and/or a sedative-hypnotic prescription for at least 30 doses during any of these years.
Insomnia with COPD was prevalent in this sample of veterans at 37.3%. Compared with veterans without comorbid insomnia, those who had both COPD and insomnia (575,539 of the total 1,542,642) were older (69 vs. 64 years), more likely to be female (6.3% vs. 3.7%), more likely to be Black (14% vs. 11%) and more likely to be a current smoker (46.1% vs. 35.5%).
Those with both COPD and insomnia were also more likely to have a service-connected disability rating of 50% of greater; use supplemental oxygen; be divorced, widowed, or separated; have a higher body mass index; or have other medical or psychiatric conditions – in particular obstructive sleep apnea (39% vs. 7%), depression (21% vs. 5%), and PTSD (33% vs. 3%).
P values were < .001 for all of these demographic and clinical variables, Dr. Luyster reported at the meeting.
Comorbid insomnia clearly impacted health care utilization, she said. Veterans with insomnia in addition to COPD had more outpatient and ED visits (10.5 vs 6.9, and 1.6 vs. 1.4, respectively) and more hospitalizations (2.2 vs. 1.8) with a primary diagnostic code for COPD or COPD exacerbation (P < .001).
A negative binomial regression analysis (P < .001) showed that “even after controlling for demographic and other medical conditions, COPD patients with insomnia had greater rates of health care utilization relative to COPD patients without insomnia,” Dr. Luyster said in the interview.
Prior studies have suggested that disturbed sleep is a predictor of poorer longitudinal outcomes in COPD, even after controlling for COPD severity, but have not looked specifically at insomnia, she said.
Commenting on the study Octavian C. Ioachimescu, MD, PhD, of Emory University, Atlanta, and the Atlanta VA Medical Center in Decatur, said the criteria used to define insomnia – unadjudicated ICD diagnoses as well as sedative-hypnotic prescriptions – may explain part of the reported prevalence of insomnia. Even so, the findings add to existing literature demonstrating that COPD and insomnia are both common disorders among VHA patients, and that their frequent coexistence “could have adverse consequences on the overall health, functional status, long-term outcomes, and quality of life of these patients.”
Questions of causation are yet to be answered, he said. “Is it that uncontrolled or severe airflow obstruction causing frequent nocturnal arousals, dyspnea, orthopnea, overuse of inhaled sympathomimetics and heightened anxiety leads to insomnia? Or is it that insomnia – possibly in a cluster with other affective disorders such as depression, anxiety disorders, or PTSD – elicits more frequent or more severe symptoms of shortness of breath in those with smoking-induced airway and parenchymal lung disease, making the latter diagnosis more overt than in others?
“My bet is on a bidirectional causal relationship,” said Dr. Ioachimescu, an editorial board advisor of CHEST Physician.
“Regardless of the etiology [of insomnia in veterans with COPD],” Dr. Luyster said, “it’s important that [insomnia] be addressed and treated appropriately, whether that be through pharmacological treatment, or probably more ideally through [cognitive behavioral therapy] for insomnia.”
The study did not control for COPD severity, she said, because of the difficulty of extracting this data from the VA Corporate Data Warehouse. The study was funded by the VA Competitive Career Development Fund.Dr. Luyster reported that she had no disclosures. Dr. Ioachimescu also said he had no relevant disclosures.
Insomnia is “highly prevalent” in veterans with chronic pulmonary obstructive disease and is significantly associated with greater COPD-related health care utilization, according to an analysis of national Veterans Health Administration data.
“The study highlights the importance of exploring potential sleep disturbances and disorders in this population and suggests that a targeted treatment for insomnia may help to improve COPD outcomes in veterans with COPD and insomnia,” said Faith Luyster, PhD, assistant professor at the University of Pittsburgh, in an interview after the virtual annual meeting of the Associated Professional Sleep Societies, where she presented the findings.
Dr. Luyster and coinvestigators used an administrative database from the Veterans Affairs Corporate Data Warehouse to identify more than 1.5 million patients with COPD who used VHA services over a 6-year period (fiscal years 2011-2017). Insomnia was defined by ICD-9/10 diagnostic codes and/or a sedative-hypnotic prescription for at least 30 doses during any of these years.
Insomnia with COPD was prevalent in this sample of veterans at 37.3%. Compared with veterans without comorbid insomnia, those who had both COPD and insomnia (575,539 of the total 1,542,642) were older (69 vs. 64 years), more likely to be female (6.3% vs. 3.7%), more likely to be Black (14% vs. 11%) and more likely to be a current smoker (46.1% vs. 35.5%).
Those with both COPD and insomnia were also more likely to have a service-connected disability rating of 50% of greater; use supplemental oxygen; be divorced, widowed, or separated; have a higher body mass index; or have other medical or psychiatric conditions – in particular obstructive sleep apnea (39% vs. 7%), depression (21% vs. 5%), and PTSD (33% vs. 3%).
P values were < .001 for all of these demographic and clinical variables, Dr. Luyster reported at the meeting.
Comorbid insomnia clearly impacted health care utilization, she said. Veterans with insomnia in addition to COPD had more outpatient and ED visits (10.5 vs 6.9, and 1.6 vs. 1.4, respectively) and more hospitalizations (2.2 vs. 1.8) with a primary diagnostic code for COPD or COPD exacerbation (P < .001).
A negative binomial regression analysis (P < .001) showed that “even after controlling for demographic and other medical conditions, COPD patients with insomnia had greater rates of health care utilization relative to COPD patients without insomnia,” Dr. Luyster said in the interview.
Prior studies have suggested that disturbed sleep is a predictor of poorer longitudinal outcomes in COPD, even after controlling for COPD severity, but have not looked specifically at insomnia, she said.
Commenting on the study Octavian C. Ioachimescu, MD, PhD, of Emory University, Atlanta, and the Atlanta VA Medical Center in Decatur, said the criteria used to define insomnia – unadjudicated ICD diagnoses as well as sedative-hypnotic prescriptions – may explain part of the reported prevalence of insomnia. Even so, the findings add to existing literature demonstrating that COPD and insomnia are both common disorders among VHA patients, and that their frequent coexistence “could have adverse consequences on the overall health, functional status, long-term outcomes, and quality of life of these patients.”
Questions of causation are yet to be answered, he said. “Is it that uncontrolled or severe airflow obstruction causing frequent nocturnal arousals, dyspnea, orthopnea, overuse of inhaled sympathomimetics and heightened anxiety leads to insomnia? Or is it that insomnia – possibly in a cluster with other affective disorders such as depression, anxiety disorders, or PTSD – elicits more frequent or more severe symptoms of shortness of breath in those with smoking-induced airway and parenchymal lung disease, making the latter diagnosis more overt than in others?
“My bet is on a bidirectional causal relationship,” said Dr. Ioachimescu, an editorial board advisor of CHEST Physician.
“Regardless of the etiology [of insomnia in veterans with COPD],” Dr. Luyster said, “it’s important that [insomnia] be addressed and treated appropriately, whether that be through pharmacological treatment, or probably more ideally through [cognitive behavioral therapy] for insomnia.”
The study did not control for COPD severity, she said, because of the difficulty of extracting this data from the VA Corporate Data Warehouse. The study was funded by the VA Competitive Career Development Fund.Dr. Luyster reported that she had no disclosures. Dr. Ioachimescu also said he had no relevant disclosures.
FROM SLEEP 2020