Clinical Endocrinology News

For patients with acute myocardial infarction (MI) and mild subclinical hypothyroidism (SCH), treatment with levothyroxine does not improve left ventricular function, according to results of the Thyroid in Acute Myocardial Infarction (ThyrAMI-2) trial.

“SCH is common, affecting approximately 10% of the adult population, and has been associated with worse outcomes in patients with cardiovascular disease in observational studies,” Salman Razvi, MD, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, England, said in an interview.

This study shows that levothyroxine treatment for patients with SCH and acute MI is “unlikely to be of benefit,” he said.

“This study says that treating the thyroid failure does not help nor harm such patients,” Terry F. Davies, MD, director, division of endocrinology, diabetes, and bone diseases, Mount Sinai Beth Israel Medical Center, New York, said in an interview. He was not involved in the study, which was published online July 21 in JAMA.

Participants included 95 adults (mean age, 63.5 years; 72 men) with persistent mild SCH who presented with acute MI at six hospitals in the United Kingdom. Most (69%) had ST-segment elevation MI.

Inclusion criteria were age older than 18 years and serum thyrotropin level >4.0 mU/L with a normal free thyroxine level on two occasions 7-10 days apart and with one thyrotropin value <10 mU/L.

Forty-six participants were randomly allocated to receive levothyroxine starting at 25 mcg titrated to aim for serum thyrotropin levels between 0.4 and 2.5 mU/L and 49 to matching placebo capsules taken once daily for 52 weeks.

The primary outcome was left ventricular ejection fraction (LVEF) at 52 weeks, assessed via MRI, with adjustment for age, sex, acute MI type, affected coronary artery territory, and baseline LVEF.

Secondary outcomes were LV volume, infarct size, adverse events, and patient-reported outcome measures of health status, health-related quality of life, and depression.

The median daily dose of levothyroxine at the end of the study was 50 mcg. Adherence to study medication was 94% during the course of the study.

At week 52, mean LVEF improved from 51.3% at baseline to 53.8% in the levothyroxine group and from 54.0% to 56.1% in the placebo group.

The difference was not significant between groups, with an adjusted between-group difference of 0.76% (95% confidence interval, –0.93% to 2.46%; P = .37).

There were also no significant differences in any of the secondary outcomes. There were 15 (33.3%) cardiovascular adverse events in the levothyroxine group and 18 (36.7%) in the placebo group.

Recent clinical practice guidelines have highlighted a lack of high-quality data to make recommendations regarding the management of mild SCH, particularly for patients with cardiovascular disease, Dr. Razvi and colleagues noted in their article.

“On the basis of these findings, screening for and subsequent treatment of subclinical hypothyroidism in patients with acute myocardial infarction to preserve LV function is not justified,” they concluded.

Important caveats

The investigators noted several important caveats and limitations. The trial recruited patients with mild SCH because this group constitutes the majority of patients with SCH and for whom there is the “greatest uncertainty” regarding treatment efficacy. It’s not known whether targeting treatment for individuals with more severe disease may be beneficial.

The therapeutic benefit of levothyroxine may have been blunted, owing to the delay between coronary occlusion and the start of levothyroxine (median delay, 17 days). It’s unclear whether earlier treatment or treatment for a longer period may be beneficial.

But Dr. Davies noted that “treatment is usually avoided in the emergency situation,” and therefore he doesn’t think the treatment delay is a limitation; rather, “it would appear prudent,” he said in the interview.

“The real issues with an otherwise very careful study is the small size of the population despite the statistical assessment that this was all that was needed and, secondly, the small dose of thyroxine used,” Dr. Davies said.

The authors agree that the low dose of levothyroxine is a limitation. The median dose at the end of the study – 50 mcg daily – is “lower than that used in other trials that have demonstrated a benefit of treatment on endothelial function and lipid profiles,” they pointed out.

Dr. Davies noted that thyroid tests are “usually routine” for patients with MI. “Mild subclinical thyroid failure has been associated with worse cardiac outcomes, [but] treating such patients with thyroid hormone is very controversial since thyroid hormone can induce arrhythmias,” he said.

The study was supported in part by the National Institute for Health Research (NIHR) at the University of Leeds. Dr. Razvi received grants from the NIHR and nonfinancial support from Amdipharm Pharmaceuticals UK during the conduct of the study and personal fees from Merck and Abbott Pharmaceuticals outside the submitted work. Dr. Davies has disclosed no relevant financial relationships.
 

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

For patients with acute myocardial infarction (MI) and mild subclinical hypothyroidism (SCH), treatment with levothyroxine does not improve left ventricular function, according to results of the Thyroid in Acute Myocardial Infarction (ThyrAMI-2) trial.

“SCH is common, affecting approximately 10% of the adult population, and has been associated with worse outcomes in patients with cardiovascular disease in observational studies,” Salman Razvi, MD, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, England, said in an interview.

This study shows that levothyroxine treatment for patients with SCH and acute MI is “unlikely to be of benefit,” he said.

“This study says that treating the thyroid failure does not help nor harm such patients,” Terry F. Davies, MD, director, division of endocrinology, diabetes, and bone diseases, Mount Sinai Beth Israel Medical Center, New York, said in an interview. He was not involved in the study, which was published online July 21 in JAMA.

Participants included 95 adults (mean age, 63.5 years; 72 men) with persistent mild SCH who presented with acute MI at six hospitals in the United Kingdom. Most (69%) had ST-segment elevation MI.

Inclusion criteria were age older than 18 years and serum thyrotropin level >4.0 mU/L with a normal free thyroxine level on two occasions 7-10 days apart and with one thyrotropin value <10 mU/L.

Forty-six participants were randomly allocated to receive levothyroxine starting at 25 mcg titrated to aim for serum thyrotropin levels between 0.4 and 2.5 mU/L and 49 to matching placebo capsules taken once daily for 52 weeks.

The primary outcome was left ventricular ejection fraction (LVEF) at 52 weeks, assessed via MRI, with adjustment for age, sex, acute MI type, affected coronary artery territory, and baseline LVEF.

Secondary outcomes were LV volume, infarct size, adverse events, and patient-reported outcome measures of health status, health-related quality of life, and depression.

The median daily dose of levothyroxine at the end of the study was 50 mcg. Adherence to study medication was 94% during the course of the study.

At week 52, mean LVEF improved from 51.3% at baseline to 53.8% in the levothyroxine group and from 54.0% to 56.1% in the placebo group.

The difference was not significant between groups, with an adjusted between-group difference of 0.76% (95% confidence interval, –0.93% to 2.46%; P = .37).

There were also no significant differences in any of the secondary outcomes. There were 15 (33.3%) cardiovascular adverse events in the levothyroxine group and 18 (36.7%) in the placebo group.

Recent clinical practice guidelines have highlighted a lack of high-quality data to make recommendations regarding the management of mild SCH, particularly for patients with cardiovascular disease, Dr. Razvi and colleagues noted in their article.

“On the basis of these findings, screening for and subsequent treatment of subclinical hypothyroidism in patients with acute myocardial infarction to preserve LV function is not justified,” they concluded.

Important caveats

The investigators noted several important caveats and limitations. The trial recruited patients with mild SCH because this group constitutes the majority of patients with SCH and for whom there is the “greatest uncertainty” regarding treatment efficacy. It’s not known whether targeting treatment for individuals with more severe disease may be beneficial.

The therapeutic benefit of levothyroxine may have been blunted, owing to the delay between coronary occlusion and the start of levothyroxine (median delay, 17 days). It’s unclear whether earlier treatment or treatment for a longer period may be beneficial.

But Dr. Davies noted that “treatment is usually avoided in the emergency situation,” and therefore he doesn’t think the treatment delay is a limitation; rather, “it would appear prudent,” he said in the interview.

“The real issues with an otherwise very careful study is the small size of the population despite the statistical assessment that this was all that was needed and, secondly, the small dose of thyroxine used,” Dr. Davies said.

The authors agree that the low dose of levothyroxine is a limitation. The median dose at the end of the study – 50 mcg daily – is “lower than that used in other trials that have demonstrated a benefit of treatment on endothelial function and lipid profiles,” they pointed out.

Dr. Davies noted that thyroid tests are “usually routine” for patients with MI. “Mild subclinical thyroid failure has been associated with worse cardiac outcomes, [but] treating such patients with thyroid hormone is very controversial since thyroid hormone can induce arrhythmias,” he said.

The study was supported in part by the National Institute for Health Research (NIHR) at the University of Leeds. Dr. Razvi received grants from the NIHR and nonfinancial support from Amdipharm Pharmaceuticals UK during the conduct of the study and personal fees from Merck and Abbott Pharmaceuticals outside the submitted work. Dr. Davies has disclosed no relevant financial relationships.
 

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

For patients with acute myocardial infarction (MI) and mild subclinical hypothyroidism (SCH), treatment with levothyroxine does not improve left ventricular function, according to results of the Thyroid in Acute Myocardial Infarction (ThyrAMI-2) trial.

“SCH is common, affecting approximately 10% of the adult population, and has been associated with worse outcomes in patients with cardiovascular disease in observational studies,” Salman Razvi, MD, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, England, said in an interview.

This study shows that levothyroxine treatment for patients with SCH and acute MI is “unlikely to be of benefit,” he said.

“This study says that treating the thyroid failure does not help nor harm such patients,” Terry F. Davies, MD, director, division of endocrinology, diabetes, and bone diseases, Mount Sinai Beth Israel Medical Center, New York, said in an interview. He was not involved in the study, which was published online July 21 in JAMA.

Participants included 95 adults (mean age, 63.5 years; 72 men) with persistent mild SCH who presented with acute MI at six hospitals in the United Kingdom. Most (69%) had ST-segment elevation MI.

Inclusion criteria were age older than 18 years and serum thyrotropin level >4.0 mU/L with a normal free thyroxine level on two occasions 7-10 days apart and with one thyrotropin value <10 mU/L.

Forty-six participants were randomly allocated to receive levothyroxine starting at 25 mcg titrated to aim for serum thyrotropin levels between 0.4 and 2.5 mU/L and 49 to matching placebo capsules taken once daily for 52 weeks.

The primary outcome was left ventricular ejection fraction (LVEF) at 52 weeks, assessed via MRI, with adjustment for age, sex, acute MI type, affected coronary artery territory, and baseline LVEF.

Secondary outcomes were LV volume, infarct size, adverse events, and patient-reported outcome measures of health status, health-related quality of life, and depression.

The median daily dose of levothyroxine at the end of the study was 50 mcg. Adherence to study medication was 94% during the course of the study.

At week 52, mean LVEF improved from 51.3% at baseline to 53.8% in the levothyroxine group and from 54.0% to 56.1% in the placebo group.

The difference was not significant between groups, with an adjusted between-group difference of 0.76% (95% confidence interval, –0.93% to 2.46%; P = .37).

There were also no significant differences in any of the secondary outcomes. There were 15 (33.3%) cardiovascular adverse events in the levothyroxine group and 18 (36.7%) in the placebo group.

Recent clinical practice guidelines have highlighted a lack of high-quality data to make recommendations regarding the management of mild SCH, particularly for patients with cardiovascular disease, Dr. Razvi and colleagues noted in their article.

“On the basis of these findings, screening for and subsequent treatment of subclinical hypothyroidism in patients with acute myocardial infarction to preserve LV function is not justified,” they concluded.

Important caveats

The investigators noted several important caveats and limitations. The trial recruited patients with mild SCH because this group constitutes the majority of patients with SCH and for whom there is the “greatest uncertainty” regarding treatment efficacy. It’s not known whether targeting treatment for individuals with more severe disease may be beneficial.

The therapeutic benefit of levothyroxine may have been blunted, owing to the delay between coronary occlusion and the start of levothyroxine (median delay, 17 days). It’s unclear whether earlier treatment or treatment for a longer period may be beneficial.

But Dr. Davies noted that “treatment is usually avoided in the emergency situation,” and therefore he doesn’t think the treatment delay is a limitation; rather, “it would appear prudent,” he said in the interview.

“The real issues with an otherwise very careful study is the small size of the population despite the statistical assessment that this was all that was needed and, secondly, the small dose of thyroxine used,” Dr. Davies said.

The authors agree that the low dose of levothyroxine is a limitation. The median dose at the end of the study – 50 mcg daily – is “lower than that used in other trials that have demonstrated a benefit of treatment on endothelial function and lipid profiles,” they pointed out.

Dr. Davies noted that thyroid tests are “usually routine” for patients with MI. “Mild subclinical thyroid failure has been associated with worse cardiac outcomes, [but] treating such patients with thyroid hormone is very controversial since thyroid hormone can induce arrhythmias,” he said.

The study was supported in part by the National Institute for Health Research (NIHR) at the University of Leeds. Dr. Razvi received grants from the NIHR and nonfinancial support from Amdipharm Pharmaceuticals UK during the conduct of the study and personal fees from Merck and Abbott Pharmaceuticals outside the submitted work. Dr. Davies has disclosed no relevant financial relationships.
 

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

As if the management of patients with severe COVID-19 infections is not complicated enough, an estimated 50%-60% of patients admitted to an ICU with the disease will have some form of cardiovascular involvement, which further increases their already high risk for morbidity and mortality.

Multimodality cardiovascular imaging, chosen wisely, can both help to direct management of cardiovascular complications associated with COVID-19 and lessen risk of exposure of health care workers to SARS-CoV-2, said members of an expert panel from the American College of Cardiology Cardiovascular Imaging Leadership Council.

“When we face a patient with known or suspected COVID-19, it’s not like any other disease because we face potential exposure risk to personnel doing imaging studies and also to other patients,” corresponding author Marcelo F. Di Carli, MD, of Brigham and Women’s Hospital Boston said in an interview.

“Any imaging study that is being considered should be performed only if we think it will help us make a change in the way that we’re going to treat that particular patient. This is true for imaging in any disease – why would you do an imaging study that will make no difference in treatment? – but the stakes are even higher in COVID-19,” he said.

The panel’s recommendations for cardiovascular imaging in patients with COVID-19 are outlined in a guidance document published online in the Journal of the American College of Cardiology.
 

Testing and biomarkers

The guidance begins by highlighting the importance of diagnostic testing for COVID-19 infection and the use of universal precautions for health care personnel performing imaging studies, as well as disinfection of imaging equipment and rooms after each use.

Circulating biomarkers that measure end-organ stress or injury, inflammation, hypoperfusion, and activation of thrombosis/hemostasis pathways may be prognostically useful, but “almost none of the widely measured biomarkers represent a specific trigger for imaging outside of that supported by clinical judgment,” the guidance states.

In contrast, low to moderate, nonrising concentrations of markers for myocardial stress, such as B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP), or of myocardial injury, such as cardiac troponins (cTn), may be helpful for excluding the need for imaging.

“Importantly, clinicians should be aware that most patients with abnormal BNP/NT-proBNP or cTn do not have acute heart failure or myocardial infarction; and rise in concentration of either class of biomarker presumably reflects complex processes including direct myocardial stress/injury related to systemic illness,” the panel members wrote.
 

Oldies but goodies

“One thing that we found out in our review of the literature and in our experiences in our own work settings is that cardiac ultrasound plays a huge role in this disease – like in any disease – but this one in particular,” Dr. Di Carli said. “One of the most feared complications in COVID-19 leads to inflammation of the heart muscle, which then leads to heart dysfunction. And of course cardiac ultrasound, because of its portability, can be performed at bedside to help clinicians ascertain an abnormality in the heart.”

Cardiac CT is also extremely helpful for determining whether patients with ECG findings suggestive of infarction have suffered an actual thrombotic event.

“These patients may best be served by a noninvasive study as compared to an invasive coronary angiogram,” he said.
 

Clinical scenarios

Cardiologists may be called in to consult on the evaluation of possible cardiogenic components of pulmonary abnormalities in patients who present with dyspnea and chest x-rays showing airspace or interstitial infiltrates suggestive of pneumonia, the authors noted.

“Clinicians will rely on history, physical exam, ECG [electrocardiogram] and biomarkers, and recent cardiac imaging tests if available. Underlying cardiac history including [coronary artery disease], cardiomyopathy, heart failure, and arrhythmia should be sought, and frequent contributors to decompensation should be eliminated,” they wrote.

For patients with suspected cardiac injury, either point-of-care ultrasound or limited echocardiography can be used for the initial evaluation, with additional, more advanced technologies called into play for specific clinical scenarios outlined in the guidance.

For example, the guidance recommends that patients with chest pain and abnormal ECG readings with clinical concern for ST-elevation acute coronary syndrome or high clinical risk for in-hospital mortality from conditions such as cardiogenic shock, dynamic ST-segment changes, or left ventricular ejection fraction less than 40% thought to be caused by non–ST-elevation myocardial infarction be referred for emergent coronary angiography and reperfusion.

In contrast, in patients with chest pain and abnormal ECG but equivocal symptoms, atypical or equivocal ECG abnormalities, or late presentations, point-of-care ultrasound or limited echocardiogram could be used to look for regional wall motion abnormalities and left ventricular ejection fraction, whereas in patients with chest pain and ST-elevation without clear evidence of ST-elevation myocardial infarction, coronary CT angiography can help to rule out ACS and point to alternate diagnoses, the authors said.

The guidance also offers recommendations for imaging in patients with hemodynamic instability (shock or hypotension), patients with new left ventricular dysfunction in the absence of shock or hypotension, and patients with subacute and chronic-phase disease.

Development of the guidance document was supported by the ACC. Dr. Di Carli disclosed institutional grant support from Gilead Sciences and Spectrum Dynamics, and consulting income from Janssen and Bayer.

SOURCE: Rudski L et al. J Am Coll Cardiol. 2020 Jul 22. doi: 10.1016/j.jacc.2020.06.080.

As if the management of patients with severe COVID-19 infections is not complicated enough, an estimated 50%-60% of patients admitted to an ICU with the disease will have some form of cardiovascular involvement, which further increases their already high risk for morbidity and mortality.

Multimodality cardiovascular imaging, chosen wisely, can both help to direct management of cardiovascular complications associated with COVID-19 and lessen risk of exposure of health care workers to SARS-CoV-2, said members of an expert panel from the American College of Cardiology Cardiovascular Imaging Leadership Council.

“When we face a patient with known or suspected COVID-19, it’s not like any other disease because we face potential exposure risk to personnel doing imaging studies and also to other patients,” corresponding author Marcelo F. Di Carli, MD, of Brigham and Women’s Hospital Boston said in an interview.

“Any imaging study that is being considered should be performed only if we think it will help us make a change in the way that we’re going to treat that particular patient. This is true for imaging in any disease – why would you do an imaging study that will make no difference in treatment? – but the stakes are even higher in COVID-19,” he said.

The panel’s recommendations for cardiovascular imaging in patients with COVID-19 are outlined in a guidance document published online in the Journal of the American College of Cardiology.
 

Testing and biomarkers

The guidance begins by highlighting the importance of diagnostic testing for COVID-19 infection and the use of universal precautions for health care personnel performing imaging studies, as well as disinfection of imaging equipment and rooms after each use.

Circulating biomarkers that measure end-organ stress or injury, inflammation, hypoperfusion, and activation of thrombosis/hemostasis pathways may be prognostically useful, but “almost none of the widely measured biomarkers represent a specific trigger for imaging outside of that supported by clinical judgment,” the guidance states.

In contrast, low to moderate, nonrising concentrations of markers for myocardial stress, such as B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP), or of myocardial injury, such as cardiac troponins (cTn), may be helpful for excluding the need for imaging.

“Importantly, clinicians should be aware that most patients with abnormal BNP/NT-proBNP or cTn do not have acute heart failure or myocardial infarction; and rise in concentration of either class of biomarker presumably reflects complex processes including direct myocardial stress/injury related to systemic illness,” the panel members wrote.
 

Oldies but goodies

“One thing that we found out in our review of the literature and in our experiences in our own work settings is that cardiac ultrasound plays a huge role in this disease – like in any disease – but this one in particular,” Dr. Di Carli said. “One of the most feared complications in COVID-19 leads to inflammation of the heart muscle, which then leads to heart dysfunction. And of course cardiac ultrasound, because of its portability, can be performed at bedside to help clinicians ascertain an abnormality in the heart.”

Cardiac CT is also extremely helpful for determining whether patients with ECG findings suggestive of infarction have suffered an actual thrombotic event.

“These patients may best be served by a noninvasive study as compared to an invasive coronary angiogram,” he said.
 

Clinical scenarios

Cardiologists may be called in to consult on the evaluation of possible cardiogenic components of pulmonary abnormalities in patients who present with dyspnea and chest x-rays showing airspace or interstitial infiltrates suggestive of pneumonia, the authors noted.

“Clinicians will rely on history, physical exam, ECG [electrocardiogram] and biomarkers, and recent cardiac imaging tests if available. Underlying cardiac history including [coronary artery disease], cardiomyopathy, heart failure, and arrhythmia should be sought, and frequent contributors to decompensation should be eliminated,” they wrote.

For patients with suspected cardiac injury, either point-of-care ultrasound or limited echocardiography can be used for the initial evaluation, with additional, more advanced technologies called into play for specific clinical scenarios outlined in the guidance.

For example, the guidance recommends that patients with chest pain and abnormal ECG readings with clinical concern for ST-elevation acute coronary syndrome or high clinical risk for in-hospital mortality from conditions such as cardiogenic shock, dynamic ST-segment changes, or left ventricular ejection fraction less than 40% thought to be caused by non–ST-elevation myocardial infarction be referred for emergent coronary angiography and reperfusion.

In contrast, in patients with chest pain and abnormal ECG but equivocal symptoms, atypical or equivocal ECG abnormalities, or late presentations, point-of-care ultrasound or limited echocardiogram could be used to look for regional wall motion abnormalities and left ventricular ejection fraction, whereas in patients with chest pain and ST-elevation without clear evidence of ST-elevation myocardial infarction, coronary CT angiography can help to rule out ACS and point to alternate diagnoses, the authors said.

The guidance also offers recommendations for imaging in patients with hemodynamic instability (shock or hypotension), patients with new left ventricular dysfunction in the absence of shock or hypotension, and patients with subacute and chronic-phase disease.

Development of the guidance document was supported by the ACC. Dr. Di Carli disclosed institutional grant support from Gilead Sciences and Spectrum Dynamics, and consulting income from Janssen and Bayer.

SOURCE: Rudski L et al. J Am Coll Cardiol. 2020 Jul 22. doi: 10.1016/j.jacc.2020.06.080.

As if the management of patients with severe COVID-19 infections is not complicated enough, an estimated 50%-60% of patients admitted to an ICU with the disease will have some form of cardiovascular involvement, which further increases their already high risk for morbidity and mortality.

Multimodality cardiovascular imaging, chosen wisely, can both help to direct management of cardiovascular complications associated with COVID-19 and lessen risk of exposure of health care workers to SARS-CoV-2, said members of an expert panel from the American College of Cardiology Cardiovascular Imaging Leadership Council.

“When we face a patient with known or suspected COVID-19, it’s not like any other disease because we face potential exposure risk to personnel doing imaging studies and also to other patients,” corresponding author Marcelo F. Di Carli, MD, of Brigham and Women’s Hospital Boston said in an interview.

“Any imaging study that is being considered should be performed only if we think it will help us make a change in the way that we’re going to treat that particular patient. This is true for imaging in any disease – why would you do an imaging study that will make no difference in treatment? – but the stakes are even higher in COVID-19,” he said.

The panel’s recommendations for cardiovascular imaging in patients with COVID-19 are outlined in a guidance document published online in the Journal of the American College of Cardiology.
 

Testing and biomarkers

The guidance begins by highlighting the importance of diagnostic testing for COVID-19 infection and the use of universal precautions for health care personnel performing imaging studies, as well as disinfection of imaging equipment and rooms after each use.

Circulating biomarkers that measure end-organ stress or injury, inflammation, hypoperfusion, and activation of thrombosis/hemostasis pathways may be prognostically useful, but “almost none of the widely measured biomarkers represent a specific trigger for imaging outside of that supported by clinical judgment,” the guidance states.

In contrast, low to moderate, nonrising concentrations of markers for myocardial stress, such as B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP), or of myocardial injury, such as cardiac troponins (cTn), may be helpful for excluding the need for imaging.

“Importantly, clinicians should be aware that most patients with abnormal BNP/NT-proBNP or cTn do not have acute heart failure or myocardial infarction; and rise in concentration of either class of biomarker presumably reflects complex processes including direct myocardial stress/injury related to systemic illness,” the panel members wrote.
 

Oldies but goodies

“One thing that we found out in our review of the literature and in our experiences in our own work settings is that cardiac ultrasound plays a huge role in this disease – like in any disease – but this one in particular,” Dr. Di Carli said. “One of the most feared complications in COVID-19 leads to inflammation of the heart muscle, which then leads to heart dysfunction. And of course cardiac ultrasound, because of its portability, can be performed at bedside to help clinicians ascertain an abnormality in the heart.”

Cardiac CT is also extremely helpful for determining whether patients with ECG findings suggestive of infarction have suffered an actual thrombotic event.

“These patients may best be served by a noninvasive study as compared to an invasive coronary angiogram,” he said.
 

Clinical scenarios

Cardiologists may be called in to consult on the evaluation of possible cardiogenic components of pulmonary abnormalities in patients who present with dyspnea and chest x-rays showing airspace or interstitial infiltrates suggestive of pneumonia, the authors noted.

“Clinicians will rely on history, physical exam, ECG [electrocardiogram] and biomarkers, and recent cardiac imaging tests if available. Underlying cardiac history including [coronary artery disease], cardiomyopathy, heart failure, and arrhythmia should be sought, and frequent contributors to decompensation should be eliminated,” they wrote.

For patients with suspected cardiac injury, either point-of-care ultrasound or limited echocardiography can be used for the initial evaluation, with additional, more advanced technologies called into play for specific clinical scenarios outlined in the guidance.

For example, the guidance recommends that patients with chest pain and abnormal ECG readings with clinical concern for ST-elevation acute coronary syndrome or high clinical risk for in-hospital mortality from conditions such as cardiogenic shock, dynamic ST-segment changes, or left ventricular ejection fraction less than 40% thought to be caused by non–ST-elevation myocardial infarction be referred for emergent coronary angiography and reperfusion.

In contrast, in patients with chest pain and abnormal ECG but equivocal symptoms, atypical or equivocal ECG abnormalities, or late presentations, point-of-care ultrasound or limited echocardiogram could be used to look for regional wall motion abnormalities and left ventricular ejection fraction, whereas in patients with chest pain and ST-elevation without clear evidence of ST-elevation myocardial infarction, coronary CT angiography can help to rule out ACS and point to alternate diagnoses, the authors said.

The guidance also offers recommendations for imaging in patients with hemodynamic instability (shock or hypotension), patients with new left ventricular dysfunction in the absence of shock or hypotension, and patients with subacute and chronic-phase disease.

Development of the guidance document was supported by the ACC. Dr. Di Carli disclosed institutional grant support from Gilead Sciences and Spectrum Dynamics, and consulting income from Janssen and Bayer.

SOURCE: Rudski L et al. J Am Coll Cardiol. 2020 Jul 22. doi: 10.1016/j.jacc.2020.06.080.

Treatment with high-dose methylprednisolone plus tocilizumab (Actemra, Genentech) as needed was associated with faster respiratory recovery, a lower likelihood of mechanical ventilation, and fewer in-hospital deaths compared with supportive care alone among people with COVID-19 experiencing a hyperinflammatory state known as a cytokine storm.

Compared with historic controls, participants in the treatment group were 79% more likely to achieve at least a two-stage improvement in respiratory status, for example.

“COVID-19-associated cytokine storm syndrome [CSS] is an important complication of severe acute respiratory syndrome coronavirus-2 infection in up to 25% of the patients,” lead author Sofia Ramiro, MD, PhD, said in an interview.

Furthermore, CSS often leads to death in this population, said Dr. Ramiro, a consultant rheumatologist and senior researcher at Leiden University Medical Center and Zuyderland Medical Center in Heerlen, the Netherlands.

Results of the COVID High-Intensity Immunosuppression in Cytokine Storm Syndrome (CHIC) study were published online July 20 in Annals of the Rheumatic Diseases.
 

Contrary to guidance?

The World Health Organization (WHO) cautions against administering corticosteroids to some critically ill patients with COVID-19. “WHO recommends against the routine use of systemic corticosteroids for treatment of viral pneumonia,” according to an interim guidance document on the clinical management of COVID-19 published May 27.

Dr. Ramiro and colleagues make a distinction, however, noting “the risk profile of such a short course of glucocorticoid for treatment of CSS needs to be separated from preexisting chronic use of glucocorticoid for conditions like rheumatic and musculoskeletal diseases.”

Participants in the current study tolerated immunosuppressive therapy well without evidence of impaired viral clearance or bacterial superinfection, they added.

Other experts disagree with recent recommendations to use corticosteroids to treat a hyperimmune response or suspected adrenal insufficiency in the setting of refractory shock in patients with COVID-19.

Information about immunosuppressive therapy and CSS linked to COVID-19 remains anecdotal, however, Dr. Ramiro and colleagues noted.

The researchers assessed outcomes of 86 individuals with COVID-19-associated CSS treated with high-dose methylprednisolone plus/minus tocilizumab, an anti-interleukin-6 receptor monoclonal antibody. They compared them with another 86 patients with COVID-19 treated with supportive care before initiation of the combination therapy protocol.

Participants with CSS had an oxygen saturation of 94% or lower at rest or tachypnea exceeding 30 breaths per minute.

They also had at least two of the following: C-reactive protein > 100 mg/L; serum ferritin > 900 mcg/L at one occasion or a twofold increase at admission within 48 hours; or D-dimer levels > 1,500 mcg/L.

The treatment group received methylprednisolone 250 mg intravenously on day 1, followed by 80 mg intravenously on days 2-5. Investigators permitted a 2-day extension if indicated.

Those who failed to clinically improve or experienced respiratory decline could also receive intravenous tocilizumab on day 2 or after. The agent was dosed at 8 mg/kg body weight during a single infusion from day 2-5 up to a maximum of 800 mg.

In all, 37 participants received tocilizumab, including two participants who received a second dose 5 days after initial treatment.  

Except for one patient in the treatment group, all participants also received antibiotic treatment and nearly 80% received chloroquine.
 

Mechanical ventilation and mortality

The primary outcome of at least a two-stage improvement in respiratory status on a WHO scale associated with treatment yielded a hazard ratio (HR) of 1.79. The treatment group achieved this improvement a median 7 days earlier than controls.

Mechanical ventilation to treat respiratory deterioration was 71% less likely for the treatment group versus controls (HR, 0.29).

The treatment group were also 65% less likely to die in hospital (HR, 0.35) than were controls.

The researchers also reported a significant difference in the number of deaths at day 14 in the treatment vs. control group, at 10 vs. 33 patients (P < .0001).
 

Glucocorticoid sufficient for many

In a sensitivity analysis excluding patients who received tocilizumab, the benefits of treatment remained statistically significant, “suggesting that a clinically relevant treatment effect can be reached by high-dose glucocorticoids alone,” the researchers noted.

This finding suggests “that the timely administration of high-dose glucocorticoids alone may provide significant benefit in more than half of the patients, and that tocilizumab is only needed in those cases that had insufficient clinical improvement on methylprednisolone alone,” they added.

“This is an important finding given the limited availability of tocilizumab in many countries and tocilizumab’s high costs.”

Complications were fairly balanced between groups. For example, bacterial infections during hospitalization were diagnosed in eight patients in the treatment group versus seven in the control group.

In addition, cardiac arrhythmias occurred in both groups, but slightly less frequently in the treatment group (P = .265), and there was a trend towards more pulmonary embolisms in the treatment group (P = .059).
 

Strengths and limitations

“A treatment with high-dose glucocorticoids is a convenient choice since glucocorticoids are safe, widely available, and inexpensive,” the researchers noted. “Longer follow-up, however, is needed to give final resolution about the safety and efficacy of the strategy.”

A strength of the study was “meticulous selection of those patients more likely to benefit from immunosuppressive treatment, namely patients with a CSS,” she added.

The study featured a prospective, observational design for the treatment group and retrospective analysis of the historic controls. “Methodologically, the main limitation of the study is not being a randomized controlled trial,” she noted.

“Ethically it has shown to be very rewarding to consciously decide against a randomized control trial, as we are talking about a disease that if only treated with supportive care can lead to mortality up to almost 50% from COVID-19-associated CSS,” Dr. Ramiro said.

Going forward, Dr. Ramiro plans to continue monitoring patients who experienced CSS to assess their outcome post-COVID-19 infection. “We want to focus on cardiorespiratory, functional, and quality of life outcomes,” she said. “We will also compare the outcomes between patients that have received immunosuppression with those that haven’t.”
 

‘Quite interesting’ results

“We desperately need better evidence to guide the management of patients hospitalized with COVID-19,” Nihar R. Desai, MD, MPH, who was not affiliated with the study, said in an interview.

“These data from the Netherlands are quite interesting and provide another signal to support the use of corticosteroids, with tocilizumab if needed, among hospitalized patients with COVID-19 to improve outcomes,” added Dr. Desai, associate professor of medicine and investigator at the Center for Outcomes Research and Evaluation, Yale University, New Haven, Conn.

“While these data are not randomized and have a relatively small sample size, we had recently seen the results of the RECOVERY trial, a UK-based randomized trial demonstrating the benefit of steroids in COVID-19,” he said.

“Taken together, these studies seem to suggest that there is a benefit with steroid therapy.” Further validation of these results is warranted, he added.
“While not a randomized clinical trial, and thus susceptible to unmeasured bias, the study adds to mounting evidence that supports targeting the excessive inflammation found in some patients with COVID-19,” Jared Radbel, MD, a pulmonologist, critical care specialist, and assistant professor of medicine at Rutgers Robert Wood Johnson Medical School, New Brunswick, N.J., said in an interview.

Dr. Radbel added that he is part of a multicenter group that has submitted a manuscript examining outcomes of critically ill patients with COVID-19 treated with tocilizumab.

Dr. Ramiro, Dr. Desai, and Dr. Radbel have disclosed no relevant financial relationships.
 

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

Treatment with high-dose methylprednisolone plus tocilizumab (Actemra, Genentech) as needed was associated with faster respiratory recovery, a lower likelihood of mechanical ventilation, and fewer in-hospital deaths compared with supportive care alone among people with COVID-19 experiencing a hyperinflammatory state known as a cytokine storm.

Compared with historic controls, participants in the treatment group were 79% more likely to achieve at least a two-stage improvement in respiratory status, for example.

“COVID-19-associated cytokine storm syndrome [CSS] is an important complication of severe acute respiratory syndrome coronavirus-2 infection in up to 25% of the patients,” lead author Sofia Ramiro, MD, PhD, said in an interview.

Furthermore, CSS often leads to death in this population, said Dr. Ramiro, a consultant rheumatologist and senior researcher at Leiden University Medical Center and Zuyderland Medical Center in Heerlen, the Netherlands.

Results of the COVID High-Intensity Immunosuppression in Cytokine Storm Syndrome (CHIC) study were published online July 20 in Annals of the Rheumatic Diseases.
 

Contrary to guidance?

The World Health Organization (WHO) cautions against administering corticosteroids to some critically ill patients with COVID-19. “WHO recommends against the routine use of systemic corticosteroids for treatment of viral pneumonia,” according to an interim guidance document on the clinical management of COVID-19 published May 27.

Dr. Ramiro and colleagues make a distinction, however, noting “the risk profile of such a short course of glucocorticoid for treatment of CSS needs to be separated from preexisting chronic use of glucocorticoid for conditions like rheumatic and musculoskeletal diseases.”

Participants in the current study tolerated immunosuppressive therapy well without evidence of impaired viral clearance or bacterial superinfection, they added.

Other experts disagree with recent recommendations to use corticosteroids to treat a hyperimmune response or suspected adrenal insufficiency in the setting of refractory shock in patients with COVID-19.

Information about immunosuppressive therapy and CSS linked to COVID-19 remains anecdotal, however, Dr. Ramiro and colleagues noted.

The researchers assessed outcomes of 86 individuals with COVID-19-associated CSS treated with high-dose methylprednisolone plus/minus tocilizumab, an anti-interleukin-6 receptor monoclonal antibody. They compared them with another 86 patients with COVID-19 treated with supportive care before initiation of the combination therapy protocol.

Participants with CSS had an oxygen saturation of 94% or lower at rest or tachypnea exceeding 30 breaths per minute.

They also had at least two of the following: C-reactive protein > 100 mg/L; serum ferritin > 900 mcg/L at one occasion or a twofold increase at admission within 48 hours; or D-dimer levels > 1,500 mcg/L.

The treatment group received methylprednisolone 250 mg intravenously on day 1, followed by 80 mg intravenously on days 2-5. Investigators permitted a 2-day extension if indicated.

Those who failed to clinically improve or experienced respiratory decline could also receive intravenous tocilizumab on day 2 or after. The agent was dosed at 8 mg/kg body weight during a single infusion from day 2-5 up to a maximum of 800 mg.

In all, 37 participants received tocilizumab, including two participants who received a second dose 5 days after initial treatment.  

Except for one patient in the treatment group, all participants also received antibiotic treatment and nearly 80% received chloroquine.
 

Mechanical ventilation and mortality

The primary outcome of at least a two-stage improvement in respiratory status on a WHO scale associated with treatment yielded a hazard ratio (HR) of 1.79. The treatment group achieved this improvement a median 7 days earlier than controls.

Mechanical ventilation to treat respiratory deterioration was 71% less likely for the treatment group versus controls (HR, 0.29).

The treatment group were also 65% less likely to die in hospital (HR, 0.35) than were controls.

The researchers also reported a significant difference in the number of deaths at day 14 in the treatment vs. control group, at 10 vs. 33 patients (P < .0001).
 

Glucocorticoid sufficient for many

In a sensitivity analysis excluding patients who received tocilizumab, the benefits of treatment remained statistically significant, “suggesting that a clinically relevant treatment effect can be reached by high-dose glucocorticoids alone,” the researchers noted.

This finding suggests “that the timely administration of high-dose glucocorticoids alone may provide significant benefit in more than half of the patients, and that tocilizumab is only needed in those cases that had insufficient clinical improvement on methylprednisolone alone,” they added.

“This is an important finding given the limited availability of tocilizumab in many countries and tocilizumab’s high costs.”

Complications were fairly balanced between groups. For example, bacterial infections during hospitalization were diagnosed in eight patients in the treatment group versus seven in the control group.

In addition, cardiac arrhythmias occurred in both groups, but slightly less frequently in the treatment group (P = .265), and there was a trend towards more pulmonary embolisms in the treatment group (P = .059).
 

Strengths and limitations

“A treatment with high-dose glucocorticoids is a convenient choice since glucocorticoids are safe, widely available, and inexpensive,” the researchers noted. “Longer follow-up, however, is needed to give final resolution about the safety and efficacy of the strategy.”

A strength of the study was “meticulous selection of those patients more likely to benefit from immunosuppressive treatment, namely patients with a CSS,” she added.

The study featured a prospective, observational design for the treatment group and retrospective analysis of the historic controls. “Methodologically, the main limitation of the study is not being a randomized controlled trial,” she noted.

“Ethically it has shown to be very rewarding to consciously decide against a randomized control trial, as we are talking about a disease that if only treated with supportive care can lead to mortality up to almost 50% from COVID-19-associated CSS,” Dr. Ramiro said.

Going forward, Dr. Ramiro plans to continue monitoring patients who experienced CSS to assess their outcome post-COVID-19 infection. “We want to focus on cardiorespiratory, functional, and quality of life outcomes,” she said. “We will also compare the outcomes between patients that have received immunosuppression with those that haven’t.”
 

‘Quite interesting’ results

“We desperately need better evidence to guide the management of patients hospitalized with COVID-19,” Nihar R. Desai, MD, MPH, who was not affiliated with the study, said in an interview.

“These data from the Netherlands are quite interesting and provide another signal to support the use of corticosteroids, with tocilizumab if needed, among hospitalized patients with COVID-19 to improve outcomes,” added Dr. Desai, associate professor of medicine and investigator at the Center for Outcomes Research and Evaluation, Yale University, New Haven, Conn.

“While these data are not randomized and have a relatively small sample size, we had recently seen the results of the RECOVERY trial, a UK-based randomized trial demonstrating the benefit of steroids in COVID-19,” he said.

“Taken together, these studies seem to suggest that there is a benefit with steroid therapy.” Further validation of these results is warranted, he added.
“While not a randomized clinical trial, and thus susceptible to unmeasured bias, the study adds to mounting evidence that supports targeting the excessive inflammation found in some patients with COVID-19,” Jared Radbel, MD, a pulmonologist, critical care specialist, and assistant professor of medicine at Rutgers Robert Wood Johnson Medical School, New Brunswick, N.J., said in an interview.

Dr. Radbel added that he is part of a multicenter group that has submitted a manuscript examining outcomes of critically ill patients with COVID-19 treated with tocilizumab.

Dr. Ramiro, Dr. Desai, and Dr. Radbel have disclosed no relevant financial relationships.
 

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

Treatment with high-dose methylprednisolone plus tocilizumab (Actemra, Genentech) as needed was associated with faster respiratory recovery, a lower likelihood of mechanical ventilation, and fewer in-hospital deaths compared with supportive care alone among people with COVID-19 experiencing a hyperinflammatory state known as a cytokine storm.

Compared with historic controls, participants in the treatment group were 79% more likely to achieve at least a two-stage improvement in respiratory status, for example.

“COVID-19-associated cytokine storm syndrome [CSS] is an important complication of severe acute respiratory syndrome coronavirus-2 infection in up to 25% of the patients,” lead author Sofia Ramiro, MD, PhD, said in an interview.

Furthermore, CSS often leads to death in this population, said Dr. Ramiro, a consultant rheumatologist and senior researcher at Leiden University Medical Center and Zuyderland Medical Center in Heerlen, the Netherlands.

Results of the COVID High-Intensity Immunosuppression in Cytokine Storm Syndrome (CHIC) study were published online July 20 in Annals of the Rheumatic Diseases.
 

Contrary to guidance?

The World Health Organization (WHO) cautions against administering corticosteroids to some critically ill patients with COVID-19. “WHO recommends against the routine use of systemic corticosteroids for treatment of viral pneumonia,” according to an interim guidance document on the clinical management of COVID-19 published May 27.

Dr. Ramiro and colleagues make a distinction, however, noting “the risk profile of such a short course of glucocorticoid for treatment of CSS needs to be separated from preexisting chronic use of glucocorticoid for conditions like rheumatic and musculoskeletal diseases.”

Participants in the current study tolerated immunosuppressive therapy well without evidence of impaired viral clearance or bacterial superinfection, they added.

Other experts disagree with recent recommendations to use corticosteroids to treat a hyperimmune response or suspected adrenal insufficiency in the setting of refractory shock in patients with COVID-19.

Information about immunosuppressive therapy and CSS linked to COVID-19 remains anecdotal, however, Dr. Ramiro and colleagues noted.

The researchers assessed outcomes of 86 individuals with COVID-19-associated CSS treated with high-dose methylprednisolone plus/minus tocilizumab, an anti-interleukin-6 receptor monoclonal antibody. They compared them with another 86 patients with COVID-19 treated with supportive care before initiation of the combination therapy protocol.

Participants with CSS had an oxygen saturation of 94% or lower at rest or tachypnea exceeding 30 breaths per minute.

They also had at least two of the following: C-reactive protein > 100 mg/L; serum ferritin > 900 mcg/L at one occasion or a twofold increase at admission within 48 hours; or D-dimer levels > 1,500 mcg/L.

The treatment group received methylprednisolone 250 mg intravenously on day 1, followed by 80 mg intravenously on days 2-5. Investigators permitted a 2-day extension if indicated.

Those who failed to clinically improve or experienced respiratory decline could also receive intravenous tocilizumab on day 2 or after. The agent was dosed at 8 mg/kg body weight during a single infusion from day 2-5 up to a maximum of 800 mg.

In all, 37 participants received tocilizumab, including two participants who received a second dose 5 days after initial treatment.  

Except for one patient in the treatment group, all participants also received antibiotic treatment and nearly 80% received chloroquine.
 

Mechanical ventilation and mortality

The primary outcome of at least a two-stage improvement in respiratory status on a WHO scale associated with treatment yielded a hazard ratio (HR) of 1.79. The treatment group achieved this improvement a median 7 days earlier than controls.

Mechanical ventilation to treat respiratory deterioration was 71% less likely for the treatment group versus controls (HR, 0.29).

The treatment group were also 65% less likely to die in hospital (HR, 0.35) than were controls.

The researchers also reported a significant difference in the number of deaths at day 14 in the treatment vs. control group, at 10 vs. 33 patients (P < .0001).
 

Glucocorticoid sufficient for many

In a sensitivity analysis excluding patients who received tocilizumab, the benefits of treatment remained statistically significant, “suggesting that a clinically relevant treatment effect can be reached by high-dose glucocorticoids alone,” the researchers noted.

This finding suggests “that the timely administration of high-dose glucocorticoids alone may provide significant benefit in more than half of the patients, and that tocilizumab is only needed in those cases that had insufficient clinical improvement on methylprednisolone alone,” they added.

“This is an important finding given the limited availability of tocilizumab in many countries and tocilizumab’s high costs.”

Complications were fairly balanced between groups. For example, bacterial infections during hospitalization were diagnosed in eight patients in the treatment group versus seven in the control group.

In addition, cardiac arrhythmias occurred in both groups, but slightly less frequently in the treatment group (P = .265), and there was a trend towards more pulmonary embolisms in the treatment group (P = .059).
 

Strengths and limitations

“A treatment with high-dose glucocorticoids is a convenient choice since glucocorticoids are safe, widely available, and inexpensive,” the researchers noted. “Longer follow-up, however, is needed to give final resolution about the safety and efficacy of the strategy.”

A strength of the study was “meticulous selection of those patients more likely to benefit from immunosuppressive treatment, namely patients with a CSS,” she added.

The study featured a prospective, observational design for the treatment group and retrospective analysis of the historic controls. “Methodologically, the main limitation of the study is not being a randomized controlled trial,” she noted.

“Ethically it has shown to be very rewarding to consciously decide against a randomized control trial, as we are talking about a disease that if only treated with supportive care can lead to mortality up to almost 50% from COVID-19-associated CSS,” Dr. Ramiro said.

Going forward, Dr. Ramiro plans to continue monitoring patients who experienced CSS to assess their outcome post-COVID-19 infection. “We want to focus on cardiorespiratory, functional, and quality of life outcomes,” she said. “We will also compare the outcomes between patients that have received immunosuppression with those that haven’t.”
 

‘Quite interesting’ results

“We desperately need better evidence to guide the management of patients hospitalized with COVID-19,” Nihar R. Desai, MD, MPH, who was not affiliated with the study, said in an interview.

“These data from the Netherlands are quite interesting and provide another signal to support the use of corticosteroids, with tocilizumab if needed, among hospitalized patients with COVID-19 to improve outcomes,” added Dr. Desai, associate professor of medicine and investigator at the Center for Outcomes Research and Evaluation, Yale University, New Haven, Conn.

“While these data are not randomized and have a relatively small sample size, we had recently seen the results of the RECOVERY trial, a UK-based randomized trial demonstrating the benefit of steroids in COVID-19,” he said.

“Taken together, these studies seem to suggest that there is a benefit with steroid therapy.” Further validation of these results is warranted, he added.
“While not a randomized clinical trial, and thus susceptible to unmeasured bias, the study adds to mounting evidence that supports targeting the excessive inflammation found in some patients with COVID-19,” Jared Radbel, MD, a pulmonologist, critical care specialist, and assistant professor of medicine at Rutgers Robert Wood Johnson Medical School, New Brunswick, N.J., said in an interview.

Dr. Radbel added that he is part of a multicenter group that has submitted a manuscript examining outcomes of critically ill patients with COVID-19 treated with tocilizumab.

Dr. Ramiro, Dr. Desai, and Dr. Radbel have disclosed no relevant financial relationships.
 

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

COVID-19 can mean weeks’ long illness, even in young adults and those without chronic conditions who have mild disease and are treated in outpatient settings, according to survey results in Morbidity and Mortality Weekly Report from the Centers for Disease Control and Prevention.

Mark W. Tenforde, MD, PhD, for the CDC-COVID-19 Response Team, and colleagues conducted a multistate telephone survey of symptomatic adults who tested positive for SARS-CoV-2. The researchers found that 35% had not returned to their usual state of wellness when they were interviewed 2-3 weeks after testing.

Among the 270 of 274 people interviewed for whom there were data on return to health, 175 (65%) reported that they had returned to baseline health an average of 7 days from the date of testing.

Among the 274 symptomatic outpatients, the median number of symptoms was seven. Fatigue (71%), cough (61%), and headache (61%) were the most commonly reported symptoms.

Prolonged illness is well described in adults hospitalized with severe COVID-19, especially among the older adult population, but little is known about other groups.

The proportion who had not returned to health differed by age: 26% of interviewees aged 18-34 years, 32% of those aged 35-49 years, and 47% of those at least 50 years old reported not having returned to their usual health (P = .010) within 14-21 days after receiving positive test results.

Among respondents aged 18-34 years who had no chronic medical condition, 19% (9 of 48) reported not having returned to their usual state of health during that time.

Public health messaging targeting younger adults, a group who might not be expected to be sick for weeks with mild disease, is particularly important, the authors wrote.

Kyle Annen, DO, medical director of transfusion services and patient blood management at Children’s Hospital Colorado and assistant professor of pathology at the University of Colorado, Denver, said in an interview that an important message is that delayed recovery (symptoms of fatigue, cough, and shortness of breath) was evident in nearly a quarter of 18- to 34-year-olds and in a third of 35- to 49-year-olds who were not sick enough to require hospitalization.

“This should impact the perception of this being a mild illness in the young adult population and encourage them to comply with recommendations of social distancing, masking, and hand washing,” she said.

Recovery time of more than 2 weeks will affect work and school performance, especially prolonged fatigue, she noted. This was one of the prominent symptoms that were reported to be slow to dissipate.

“I think the most interesting point in this study is that of underlying conditions; psychiatric conditions were significantly correlated with prolonged recovery. I don’t think that many people think of depression and anxiety as an underlying medical condition in regards to COVID-19 risk. This could potentially have an impact, as depression and anxiety rates will likely increase as COVID-19 continues,” she said.

Buddy Creech, MD, MPH, said in an interview that it is “important to realize that the spectrum of disease with COVID is wide, including mild disease, severe disease, and prolonged disease. This report helps us understand some of the risk factors for those with prolonged symptoms and may allow us to refine even more clearly how we prioritize treatment and vaccine administration, once available.

“It also highlights the challenge of dealing with this virus. Not only do the symptoms vary widely, but so do the incubation period, the duration of symptoms, and the residual symptoms that sometimes occur. Clearly, there is much we still need to understand about this virus,” he said.

The interviews were conducted from April 15 to June 25 with a random sample of adults at least 18 years old who had received a first positive test result for SARS-CoV-2 at an outpatient visit at one of 14 US academic healthcare systems in 13 states.
 

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

COVID-19 can mean weeks’ long illness, even in young adults and those without chronic conditions who have mild disease and are treated in outpatient settings, according to survey results in Morbidity and Mortality Weekly Report from the Centers for Disease Control and Prevention.

Mark W. Tenforde, MD, PhD, for the CDC-COVID-19 Response Team, and colleagues conducted a multistate telephone survey of symptomatic adults who tested positive for SARS-CoV-2. The researchers found that 35% had not returned to their usual state of wellness when they were interviewed 2-3 weeks after testing.

Among the 270 of 274 people interviewed for whom there were data on return to health, 175 (65%) reported that they had returned to baseline health an average of 7 days from the date of testing.

Among the 274 symptomatic outpatients, the median number of symptoms was seven. Fatigue (71%), cough (61%), and headache (61%) were the most commonly reported symptoms.

Prolonged illness is well described in adults hospitalized with severe COVID-19, especially among the older adult population, but little is known about other groups.

The proportion who had not returned to health differed by age: 26% of interviewees aged 18-34 years, 32% of those aged 35-49 years, and 47% of those at least 50 years old reported not having returned to their usual health (P = .010) within 14-21 days after receiving positive test results.

Among respondents aged 18-34 years who had no chronic medical condition, 19% (9 of 48) reported not having returned to their usual state of health during that time.

Public health messaging targeting younger adults, a group who might not be expected to be sick for weeks with mild disease, is particularly important, the authors wrote.

Kyle Annen, DO, medical director of transfusion services and patient blood management at Children’s Hospital Colorado and assistant professor of pathology at the University of Colorado, Denver, said in an interview that an important message is that delayed recovery (symptoms of fatigue, cough, and shortness of breath) was evident in nearly a quarter of 18- to 34-year-olds and in a third of 35- to 49-year-olds who were not sick enough to require hospitalization.

“This should impact the perception of this being a mild illness in the young adult population and encourage them to comply with recommendations of social distancing, masking, and hand washing,” she said.

Recovery time of more than 2 weeks will affect work and school performance, especially prolonged fatigue, she noted. This was one of the prominent symptoms that were reported to be slow to dissipate.

“I think the most interesting point in this study is that of underlying conditions; psychiatric conditions were significantly correlated with prolonged recovery. I don’t think that many people think of depression and anxiety as an underlying medical condition in regards to COVID-19 risk. This could potentially have an impact, as depression and anxiety rates will likely increase as COVID-19 continues,” she said.

Buddy Creech, MD, MPH, said in an interview that it is “important to realize that the spectrum of disease with COVID is wide, including mild disease, severe disease, and prolonged disease. This report helps us understand some of the risk factors for those with prolonged symptoms and may allow us to refine even more clearly how we prioritize treatment and vaccine administration, once available.

“It also highlights the challenge of dealing with this virus. Not only do the symptoms vary widely, but so do the incubation period, the duration of symptoms, and the residual symptoms that sometimes occur. Clearly, there is much we still need to understand about this virus,” he said.

The interviews were conducted from April 15 to June 25 with a random sample of adults at least 18 years old who had received a first positive test result for SARS-CoV-2 at an outpatient visit at one of 14 US academic healthcare systems in 13 states.
 

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

COVID-19 can mean weeks’ long illness, even in young adults and those without chronic conditions who have mild disease and are treated in outpatient settings, according to survey results in Morbidity and Mortality Weekly Report from the Centers for Disease Control and Prevention.

Mark W. Tenforde, MD, PhD, for the CDC-COVID-19 Response Team, and colleagues conducted a multistate telephone survey of symptomatic adults who tested positive for SARS-CoV-2. The researchers found that 35% had not returned to their usual state of wellness when they were interviewed 2-3 weeks after testing.

Among the 270 of 274 people interviewed for whom there were data on return to health, 175 (65%) reported that they had returned to baseline health an average of 7 days from the date of testing.

Among the 274 symptomatic outpatients, the median number of symptoms was seven. Fatigue (71%), cough (61%), and headache (61%) were the most commonly reported symptoms.

Prolonged illness is well described in adults hospitalized with severe COVID-19, especially among the older adult population, but little is known about other groups.

The proportion who had not returned to health differed by age: 26% of interviewees aged 18-34 years, 32% of those aged 35-49 years, and 47% of those at least 50 years old reported not having returned to their usual health (P = .010) within 14-21 days after receiving positive test results.

Among respondents aged 18-34 years who had no chronic medical condition, 19% (9 of 48) reported not having returned to their usual state of health during that time.

Public health messaging targeting younger adults, a group who might not be expected to be sick for weeks with mild disease, is particularly important, the authors wrote.

Kyle Annen, DO, medical director of transfusion services and patient blood management at Children’s Hospital Colorado and assistant professor of pathology at the University of Colorado, Denver, said in an interview that an important message is that delayed recovery (symptoms of fatigue, cough, and shortness of breath) was evident in nearly a quarter of 18- to 34-year-olds and in a third of 35- to 49-year-olds who were not sick enough to require hospitalization.

“This should impact the perception of this being a mild illness in the young adult population and encourage them to comply with recommendations of social distancing, masking, and hand washing,” she said.

Recovery time of more than 2 weeks will affect work and school performance, especially prolonged fatigue, she noted. This was one of the prominent symptoms that were reported to be slow to dissipate.

“I think the most interesting point in this study is that of underlying conditions; psychiatric conditions were significantly correlated with prolonged recovery. I don’t think that many people think of depression and anxiety as an underlying medical condition in regards to COVID-19 risk. This could potentially have an impact, as depression and anxiety rates will likely increase as COVID-19 continues,” she said.

Buddy Creech, MD, MPH, said in an interview that it is “important to realize that the spectrum of disease with COVID is wide, including mild disease, severe disease, and prolonged disease. This report helps us understand some of the risk factors for those with prolonged symptoms and may allow us to refine even more clearly how we prioritize treatment and vaccine administration, once available.

“It also highlights the challenge of dealing with this virus. Not only do the symptoms vary widely, but so do the incubation period, the duration of symptoms, and the residual symptoms that sometimes occur. Clearly, there is much we still need to understand about this virus,” he said.

The interviews were conducted from April 15 to June 25 with a random sample of adults at least 18 years old who had received a first positive test result for SARS-CoV-2 at an outpatient visit at one of 14 US academic healthcare systems in 13 states.
 

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

All infants born to a cohort of 31 COVID-19–positive mothers tested negative for the virus during the height of the New York surge, according to a study out of New York-Presbyterian Hospital.

South_agency/Getty Images

“It is suggested in the cumulative data that the virus does not confer additional risk to the fetus during labor or during the early postnatal period in both preterm and term infants,” concluded Jeffrey Perlman, MB ChB, and colleagues in Pediatrics.

But other experts suggest substantial gaps remain in our understanding of maternal transmission of SARS-CoV-2.

“Much more needs to be known,” Munish Gupta, MD, and colleagues from Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, said in an accompanying editorial.

The prospective study is the first to describe a cohort of U.S. COVID-19–related deliveries, with the prior neonatal impact of COVID-19 “almost exclusively” reported from China, noted the authors. They included a cohort of 326 women who were tested for SARS-CoV-2 on admission to labor and delivery at New York-Presbyterian Hospital between March 22 and April 15th, 2020. Of the 31 (10%) mothers who tested positive, 15 (48%) were asymptomatic and 16 (52%) were symptomatic.

Two babies were born prematurely (one by Cesarean) and were isolated in negative pressure rooms with continuous positive airway pressure. Both were moved out of isolation after two negative test results and “have exhibited an unremarkable clinical course,” the authors reported.

The other 29 term babies were cared for in their mothers’ rooms, with breastfeeding allowed, if desired. These babies and their mothers were discharged from the hospital between 24 and 48 hours after delivery.

“Visitor restriction for mothers who were positive for COVID-19 included 14 days of no visitation from the start of symptoms,” noted the team.

They added “since the prepublication release there have been a total of 47 mothers positive for COVID-19, resulting in 47 infants; 4 have been admitted to neonatal intensive care. In addition, 32 other infants have been tested for a variety of indications within the unit. All infants test results have been negative.”

The brief report outlined the institution’s checklist for delivery preparedness in either the operating room or labor delivery room, including personal protective equipment, resuscitation, transportation to the neonatal intensive care unit, and early postresuscitation care. “Suspected or confirmed COVID-19 alone in an otherwise uncomplicated pregnancy is not an indication for the resuscitation team or the neonatal fellow,” they noted, adding delivery room preparation and management should include contact precautions. “With scrupulous attention to infectious precautions, horizontal viral transmission should be minimized,” they advised.

Dr. Perlman and associates emphasized that rapid turnaround SARSCoV-2 testing is “crucial to minimize the likelihood of a provider becoming infected and/or infecting the infant.”

Although the findings are “clearly reassuring,” Dr. Gupta and colleagues have reservations. “To what extent does this report address concerns for infection risk with a rooming-in approach to care?” they asked in their accompanying editorial. “The answer is likely some, but not much.”

Many questions remain, they said, including: “What precautions were used to minimize infection risk during the postbirth hospital course? What was the approach to skin-to-skin care and direct mother-newborn contact? Were restrictions placed on family members? Were changes made to routine interventions such as hearing screens or circumcisions? What practices were in place around environmental cleaning? Most important, how did the newborns do after discharge?”

The current uncertainty around neonatal COVID-19 infection risk has led to “disparate” variations in care recommendations, they pointed out. Whereas China’s consensus guidelines recommend a 14-day separation of COVID-19–positive mothers from their healthy infants, a practice supported by the American Academy of Pediatrics “when possible,” the Italian Society of Neonatology, the Royal College of Paediatrics and Child Health, and the Canadian Paediatric Society advise “rooming-in and breastfeeding with appropriate infection prevention measures.”

Dr. Gupta and colleagues pointed to the following as at least three “critical and time-sensitive needs for research around neonatal care and outcomes related to COVID-19”:

• Studies need to have much larger sample sizes and include diverse populations. This will allow for reliable measurement of outcomes.
• Descriptions of care practices must be in detail, especially about infection prevention; these should be presented in a way to compare the efficacy of different approaches.
• There needs to be follow-up information on outcomes of both the mother and the neonate after the birth hospitalization.

Asked to comment, Lillian Beard, MD, of George Washington University in Washington welcomed the data as “good news.”

SOURCE: Perlman J et al. Pediatrics. 2020;146(2):e20201567.

All infants born to a cohort of 31 COVID-19–positive mothers tested negative for the virus during the height of the New York surge, according to a study out of New York-Presbyterian Hospital.

South_agency/Getty Images

“It is suggested in the cumulative data that the virus does not confer additional risk to the fetus during labor or during the early postnatal period in both preterm and term infants,” concluded Jeffrey Perlman, MB ChB, and colleagues in Pediatrics.

But other experts suggest substantial gaps remain in our understanding of maternal transmission of SARS-CoV-2.

“Much more needs to be known,” Munish Gupta, MD, and colleagues from Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, said in an accompanying editorial.

The prospective study is the first to describe a cohort of U.S. COVID-19–related deliveries, with the prior neonatal impact of COVID-19 “almost exclusively” reported from China, noted the authors. They included a cohort of 326 women who were tested for SARS-CoV-2 on admission to labor and delivery at New York-Presbyterian Hospital between March 22 and April 15th, 2020. Of the 31 (10%) mothers who tested positive, 15 (48%) were asymptomatic and 16 (52%) were symptomatic.

Two babies were born prematurely (one by Cesarean) and were isolated in negative pressure rooms with continuous positive airway pressure. Both were moved out of isolation after two negative test results and “have exhibited an unremarkable clinical course,” the authors reported.

The other 29 term babies were cared for in their mothers’ rooms, with breastfeeding allowed, if desired. These babies and their mothers were discharged from the hospital between 24 and 48 hours after delivery.

“Visitor restriction for mothers who were positive for COVID-19 included 14 days of no visitation from the start of symptoms,” noted the team.

They added “since the prepublication release there have been a total of 47 mothers positive for COVID-19, resulting in 47 infants; 4 have been admitted to neonatal intensive care. In addition, 32 other infants have been tested for a variety of indications within the unit. All infants test results have been negative.”

The brief report outlined the institution’s checklist for delivery preparedness in either the operating room or labor delivery room, including personal protective equipment, resuscitation, transportation to the neonatal intensive care unit, and early postresuscitation care. “Suspected or confirmed COVID-19 alone in an otherwise uncomplicated pregnancy is not an indication for the resuscitation team or the neonatal fellow,” they noted, adding delivery room preparation and management should include contact precautions. “With scrupulous attention to infectious precautions, horizontal viral transmission should be minimized,” they advised.

Dr. Perlman and associates emphasized that rapid turnaround SARSCoV-2 testing is “crucial to minimize the likelihood of a provider becoming infected and/or infecting the infant.”

Although the findings are “clearly reassuring,” Dr. Gupta and colleagues have reservations. “To what extent does this report address concerns for infection risk with a rooming-in approach to care?” they asked in their accompanying editorial. “The answer is likely some, but not much.”

Many questions remain, they said, including: “What precautions were used to minimize infection risk during the postbirth hospital course? What was the approach to skin-to-skin care and direct mother-newborn contact? Were restrictions placed on family members? Were changes made to routine interventions such as hearing screens or circumcisions? What practices were in place around environmental cleaning? Most important, how did the newborns do after discharge?”

The current uncertainty around neonatal COVID-19 infection risk has led to “disparate” variations in care recommendations, they pointed out. Whereas China’s consensus guidelines recommend a 14-day separation of COVID-19–positive mothers from their healthy infants, a practice supported by the American Academy of Pediatrics “when possible,” the Italian Society of Neonatology, the Royal College of Paediatrics and Child Health, and the Canadian Paediatric Society advise “rooming-in and breastfeeding with appropriate infection prevention measures.”

Dr. Gupta and colleagues pointed to the following as at least three “critical and time-sensitive needs for research around neonatal care and outcomes related to COVID-19”:

• Studies need to have much larger sample sizes and include diverse populations. This will allow for reliable measurement of outcomes.
• Descriptions of care practices must be in detail, especially about infection prevention; these should be presented in a way to compare the efficacy of different approaches.
• There needs to be follow-up information on outcomes of both the mother and the neonate after the birth hospitalization.

Asked to comment, Lillian Beard, MD, of George Washington University in Washington welcomed the data as “good news.”

SOURCE: Perlman J et al. Pediatrics. 2020;146(2):e20201567.

All infants born to a cohort of 31 COVID-19–positive mothers tested negative for the virus during the height of the New York surge, according to a study out of New York-Presbyterian Hospital.

South_agency/Getty Images

“It is suggested in the cumulative data that the virus does not confer additional risk to the fetus during labor or during the early postnatal period in both preterm and term infants,” concluded Jeffrey Perlman, MB ChB, and colleagues in Pediatrics.

But other experts suggest substantial gaps remain in our understanding of maternal transmission of SARS-CoV-2.

“Much more needs to be known,” Munish Gupta, MD, and colleagues from Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, said in an accompanying editorial.

The prospective study is the first to describe a cohort of U.S. COVID-19–related deliveries, with the prior neonatal impact of COVID-19 “almost exclusively” reported from China, noted the authors. They included a cohort of 326 women who were tested for SARS-CoV-2 on admission to labor and delivery at New York-Presbyterian Hospital between March 22 and April 15th, 2020. Of the 31 (10%) mothers who tested positive, 15 (48%) were asymptomatic and 16 (52%) were symptomatic.

Two babies were born prematurely (one by Cesarean) and were isolated in negative pressure rooms with continuous positive airway pressure. Both were moved out of isolation after two negative test results and “have exhibited an unremarkable clinical course,” the authors reported.

The other 29 term babies were cared for in their mothers’ rooms, with breastfeeding allowed, if desired. These babies and their mothers were discharged from the hospital between 24 and 48 hours after delivery.

“Visitor restriction for mothers who were positive for COVID-19 included 14 days of no visitation from the start of symptoms,” noted the team.

They added “since the prepublication release there have been a total of 47 mothers positive for COVID-19, resulting in 47 infants; 4 have been admitted to neonatal intensive care. In addition, 32 other infants have been tested for a variety of indications within the unit. All infants test results have been negative.”

The brief report outlined the institution’s checklist for delivery preparedness in either the operating room or labor delivery room, including personal protective equipment, resuscitation, transportation to the neonatal intensive care unit, and early postresuscitation care. “Suspected or confirmed COVID-19 alone in an otherwise uncomplicated pregnancy is not an indication for the resuscitation team or the neonatal fellow,” they noted, adding delivery room preparation and management should include contact precautions. “With scrupulous attention to infectious precautions, horizontal viral transmission should be minimized,” they advised.

Dr. Perlman and associates emphasized that rapid turnaround SARSCoV-2 testing is “crucial to minimize the likelihood of a provider becoming infected and/or infecting the infant.”

Although the findings are “clearly reassuring,” Dr. Gupta and colleagues have reservations. “To what extent does this report address concerns for infection risk with a rooming-in approach to care?” they asked in their accompanying editorial. “The answer is likely some, but not much.”

Many questions remain, they said, including: “What precautions were used to minimize infection risk during the postbirth hospital course? What was the approach to skin-to-skin care and direct mother-newborn contact? Were restrictions placed on family members? Were changes made to routine interventions such as hearing screens or circumcisions? What practices were in place around environmental cleaning? Most important, how did the newborns do after discharge?”

The current uncertainty around neonatal COVID-19 infection risk has led to “disparate” variations in care recommendations, they pointed out. Whereas China’s consensus guidelines recommend a 14-day separation of COVID-19–positive mothers from their healthy infants, a practice supported by the American Academy of Pediatrics “when possible,” the Italian Society of Neonatology, the Royal College of Paediatrics and Child Health, and the Canadian Paediatric Society advise “rooming-in and breastfeeding with appropriate infection prevention measures.”

Dr. Gupta and colleagues pointed to the following as at least three “critical and time-sensitive needs for research around neonatal care and outcomes related to COVID-19”:

• Studies need to have much larger sample sizes and include diverse populations. This will allow for reliable measurement of outcomes.
• Descriptions of care practices must be in detail, especially about infection prevention; these should be presented in a way to compare the efficacy of different approaches.
• There needs to be follow-up information on outcomes of both the mother and the neonate after the birth hospitalization.

Asked to comment, Lillian Beard, MD, of George Washington University in Washington welcomed the data as “good news.”

SOURCE: Perlman J et al. Pediatrics. 2020;146(2):e20201567.

New data from the National Institutes of Health–funded Osteoarthritis Initiative suggest that, in some women at least, taking bisphosphonates may help to reduce the chances that there will be radiographic progression of knee osteoarthritis (OA).

decade3d/Thinkstock

In a propensity-matched cohort analysis, women who had a Kellgren and Lawrence (KL) grade of less than 2 and who used bisphosphonates were half as likely as those who did not use bisphosphonates to have radiographic OA progression at 2 years (hazard ratio, 0.53; 95% confidence interval, 0.35-0.79). Radiographic OA progression has been defined as a one-step increase in the KL grade.

While the association appeared even stronger in women with a KL grade less than 2 and who were not overweight (HR, 0.49; 95% CI, 0.26-0.92), bisphosphonate use was not associated with radiographic OA progression in women with a higher (≥2) KL grade (HR, 1.06; 95% CI, 0.83-1.35).

“In all analyses, the effect of bisphosphonates was larger in radiographic-disease-naive individuals, suggesting protection using bisphosphonates may be more profound in those who do not already have evidence of knee damage or who have mild disease, and once damage occurs, bisphosphonate use may not have much effect,” Kaleen N. Hayes, PharmD, of the University of Toronto and her coauthors reported in the Journal of Bone and Mineral Research.

“Our study was the first to our knowledge to examine bisphosphonate exposure effects in different disease severity subgroups and obesity classifications using a rigorous, propensity-matched time-to-event analysis that uniquely addresses confounding by indication,” Dr. Hayes and her team wrote.

Furthermore, they noted that extensive sensitivity analyses, which included redoing the primary analyses to look at statin use, showed that their main conclusions were unchanged and that this helped account for any potential residual confounding, healthy-user bias, or exposure misclassification.
 

Study details

The Osteoarthritis Initiative is a 10-year longitudinal cohort study conducted at four clinical sites in the United States and recruited men and women aged 45-75 years over a 2-year period starting in 2004. Dr. Hayes and her coauthors restricted their analyses to women 50 years and older. Their study population consisted of 344 bisphosphonate users and 344 bisphosphonate nonusers.

The main bisphosphonate being taken was alendronate (69%), and the average duration of bisphosphonate use was 3.3 years, but no significant effect of duration of use on radiographic progression was found.

The women were followed until the first radiographic OA progression, or the first missed visit or end of the 2-year follow-up period.

Overall, 95 (13.8%) of the 688 women included in the analysis experienced radiographic OA progression. Of those, 27 (3.9%) had a KL grade of less than 2 and 68 (9.8%) had a KL grade of 2 or greater. Ten women with KL less than 2 and 27 women with KL or 2 or greater were taking bisphosphonates at their baseline visit.

“Kaplan-Meier analysis indicated that non-users and users with a baseline KL grade of 0 or 1 had 2-year risks of progression of 10.5% and 5.9%, respectively, whereas non-users and users with a baseline KL grade of 2 or 3 had 2-year of these women risks of progression of 23.0% and 23.5%, respectively,” reported the authors.

Before propensity score matching, Dr. Hayes and her colleagues observed that women taking bisphosphonates were older, had lower body weight and a higher prevalence of any fracture or hip and vertebral fractures, and were also more likely be White, compared with non-users. “In addition, bisphosphonate-users appeared to be healthier than non-users, as suggested by a lower smoking prevalence, lower average baseline KL grade, lower diabetes prevalence, and higher multivitamin use (a healthy-user proxy),” they acknowledged.

Results in perspective

“The key thing that I’m concerned about when I see something like bisphosphonates and osteoarthritis is just how well confounding has been addressed,” commented Tuhina Neogi, MD, PhD, professor of medicine and epidemiology at Boston University and chief of rheumatology at Boston Medical Center, in an interview.

“So are there factors other than the bisphosphonates themselves that might explain the findings? It looks like they’ve taken into account a lot of important things that one would consider for trying to get the two groups to look as similar as possible,” she added. Dr. Neogi queried, however, if body mass index had been suitably been adjusted for even after propensity score matching.

“The effect estimate is quite large, so I do think there is some confounding. So I would feel comfortable saying that there’s a signal here for bisphosphonates in reducing the risk of progression among those who do not have radiographic OA at baseline,” Dr. Neogi observed.

“The context of all this is that there have been large, well-designed, randomized control trials of oral bisphosphonates from years ago that did not find any benefit of bisphosphonates in [terms of] radiographic OA progression,” Dr. Neogi explained.

In the Knee OA Structural Arthritis (KOSTAR) study, now considered “quite a large landmark study,” the efficacy of risedronate in providing symptom relief and slowing disease progression was studied in almost 2,500 patients. “They saw some improvements in signs and symptoms, but risedronate did not significantly reduce radiographic progression. [However] there were some signals on biomarkers,” Dr. Neogi said.

One of the issues is that radiographs are too insensitive to pick up early bone changes in OA, a fact not missed by Dr. Hayes et al. More recent research has thus looked to using more sensitive imaging methods, such as CT and MRI, such as a recent study published in JAMA looking at the use of intravenous zoledronic acid on bone marrow lesions and cartilage volume. The results did not show any benefit of bisphosphonate use over 2 years.

“So even though we thought the MRI might provide a better way to detect a signal, it hasn’t panned out,” Dr. Neogi said.

But that’s not to say that there isn’t still a signal. Dr. Neogi’s most recent research has been using MRI to look at bone marrow lesion volume in women who were newly starting bisphosphonate therapy versus those who were not, and this has been just been accepted for publication.

“We found no difference in bone marrow lesion volume between the two groups. But in the women who had bone marrow lesions at baseline, there was a statistically significant greater proportion of women on bisphosphonates having a decrease in bone marrow lesion volume than the non-initiators,” she said.

So is there evidence that putting more women on bisphosphonates could prevent OA? “I’m not sure that you would be able to say that this should be something that all postmenopausal women should be on,” Dr. Neogi said.

“There’s a theoretical risk that has not been formally studied that, if you diminish bone turnover and you get more and more mineralization occurring, the bone potentially may have altered mechanical properties, become stiffer and, over the long term, that might not be good for OA.”

She added that, if there is already a clear clinical indication for bisphosphonate use, however, such as older women who have had a fracture and who should be on a bisphosphonate anyway, then “a bisphosphonate has the theoretical potential additional benefit for their osteoarthritis.”

The authors and Dr. Neogi had no conflicts of interest or relationships to disclose.

SOURCE: Hayes KN et al. J Bone Miner Res. 2020 July 14. doi: 10.1002/jbmr.4133.
 

New data from the National Institutes of Health–funded Osteoarthritis Initiative suggest that, in some women at least, taking bisphosphonates may help to reduce the chances that there will be radiographic progression of knee osteoarthritis (OA).

decade3d/Thinkstock

In a propensity-matched cohort analysis, women who had a Kellgren and Lawrence (KL) grade of less than 2 and who used bisphosphonates were half as likely as those who did not use bisphosphonates to have radiographic OA progression at 2 years (hazard ratio, 0.53; 95% confidence interval, 0.35-0.79). Radiographic OA progression has been defined as a one-step increase in the KL grade.

While the association appeared even stronger in women with a KL grade less than 2 and who were not overweight (HR, 0.49; 95% CI, 0.26-0.92), bisphosphonate use was not associated with radiographic OA progression in women with a higher (≥2) KL grade (HR, 1.06; 95% CI, 0.83-1.35).

“In all analyses, the effect of bisphosphonates was larger in radiographic-disease-naive individuals, suggesting protection using bisphosphonates may be more profound in those who do not already have evidence of knee damage or who have mild disease, and once damage occurs, bisphosphonate use may not have much effect,” Kaleen N. Hayes, PharmD, of the University of Toronto and her coauthors reported in the Journal of Bone and Mineral Research.

“Our study was the first to our knowledge to examine bisphosphonate exposure effects in different disease severity subgroups and obesity classifications using a rigorous, propensity-matched time-to-event analysis that uniquely addresses confounding by indication,” Dr. Hayes and her team wrote.

Furthermore, they noted that extensive sensitivity analyses, which included redoing the primary analyses to look at statin use, showed that their main conclusions were unchanged and that this helped account for any potential residual confounding, healthy-user bias, or exposure misclassification.
 

Study details

The Osteoarthritis Initiative is a 10-year longitudinal cohort study conducted at four clinical sites in the United States and recruited men and women aged 45-75 years over a 2-year period starting in 2004. Dr. Hayes and her coauthors restricted their analyses to women 50 years and older. Their study population consisted of 344 bisphosphonate users and 344 bisphosphonate nonusers.

The main bisphosphonate being taken was alendronate (69%), and the average duration of bisphosphonate use was 3.3 years, but no significant effect of duration of use on radiographic progression was found.

The women were followed until the first radiographic OA progression, or the first missed visit or end of the 2-year follow-up period.

Overall, 95 (13.8%) of the 688 women included in the analysis experienced radiographic OA progression. Of those, 27 (3.9%) had a KL grade of less than 2 and 68 (9.8%) had a KL grade of 2 or greater. Ten women with KL less than 2 and 27 women with KL or 2 or greater were taking bisphosphonates at their baseline visit.

“Kaplan-Meier analysis indicated that non-users and users with a baseline KL grade of 0 or 1 had 2-year risks of progression of 10.5% and 5.9%, respectively, whereas non-users and users with a baseline KL grade of 2 or 3 had 2-year of these women risks of progression of 23.0% and 23.5%, respectively,” reported the authors.

Before propensity score matching, Dr. Hayes and her colleagues observed that women taking bisphosphonates were older, had lower body weight and a higher prevalence of any fracture or hip and vertebral fractures, and were also more likely be White, compared with non-users. “In addition, bisphosphonate-users appeared to be healthier than non-users, as suggested by a lower smoking prevalence, lower average baseline KL grade, lower diabetes prevalence, and higher multivitamin use (a healthy-user proxy),” they acknowledged.

Results in perspective

“The key thing that I’m concerned about when I see something like bisphosphonates and osteoarthritis is just how well confounding has been addressed,” commented Tuhina Neogi, MD, PhD, professor of medicine and epidemiology at Boston University and chief of rheumatology at Boston Medical Center, in an interview.

“So are there factors other than the bisphosphonates themselves that might explain the findings? It looks like they’ve taken into account a lot of important things that one would consider for trying to get the two groups to look as similar as possible,” she added. Dr. Neogi queried, however, if body mass index had been suitably been adjusted for even after propensity score matching.

“The effect estimate is quite large, so I do think there is some confounding. So I would feel comfortable saying that there’s a signal here for bisphosphonates in reducing the risk of progression among those who do not have radiographic OA at baseline,” Dr. Neogi observed.

“The context of all this is that there have been large, well-designed, randomized control trials of oral bisphosphonates from years ago that did not find any benefit of bisphosphonates in [terms of] radiographic OA progression,” Dr. Neogi explained.

In the Knee OA Structural Arthritis (KOSTAR) study, now considered “quite a large landmark study,” the efficacy of risedronate in providing symptom relief and slowing disease progression was studied in almost 2,500 patients. “They saw some improvements in signs and symptoms, but risedronate did not significantly reduce radiographic progression. [However] there were some signals on biomarkers,” Dr. Neogi said.

One of the issues is that radiographs are too insensitive to pick up early bone changes in OA, a fact not missed by Dr. Hayes et al. More recent research has thus looked to using more sensitive imaging methods, such as CT and MRI, such as a recent study published in JAMA looking at the use of intravenous zoledronic acid on bone marrow lesions and cartilage volume. The results did not show any benefit of bisphosphonate use over 2 years.

“So even though we thought the MRI might provide a better way to detect a signal, it hasn’t panned out,” Dr. Neogi said.

But that’s not to say that there isn’t still a signal. Dr. Neogi’s most recent research has been using MRI to look at bone marrow lesion volume in women who were newly starting bisphosphonate therapy versus those who were not, and this has been just been accepted for publication.

“We found no difference in bone marrow lesion volume between the two groups. But in the women who had bone marrow lesions at baseline, there was a statistically significant greater proportion of women on bisphosphonates having a decrease in bone marrow lesion volume than the non-initiators,” she said.

So is there evidence that putting more women on bisphosphonates could prevent OA? “I’m not sure that you would be able to say that this should be something that all postmenopausal women should be on,” Dr. Neogi said.

“There’s a theoretical risk that has not been formally studied that, if you diminish bone turnover and you get more and more mineralization occurring, the bone potentially may have altered mechanical properties, become stiffer and, over the long term, that might not be good for OA.”

She added that, if there is already a clear clinical indication for bisphosphonate use, however, such as older women who have had a fracture and who should be on a bisphosphonate anyway, then “a bisphosphonate has the theoretical potential additional benefit for their osteoarthritis.”

The authors and Dr. Neogi had no conflicts of interest or relationships to disclose.

SOURCE: Hayes KN et al. J Bone Miner Res. 2020 July 14. doi: 10.1002/jbmr.4133.
 

New data from the National Institutes of Health–funded Osteoarthritis Initiative suggest that, in some women at least, taking bisphosphonates may help to reduce the chances that there will be radiographic progression of knee osteoarthritis (OA).

decade3d/Thinkstock

In a propensity-matched cohort analysis, women who had a Kellgren and Lawrence (KL) grade of less than 2 and who used bisphosphonates were half as likely as those who did not use bisphosphonates to have radiographic OA progression at 2 years (hazard ratio, 0.53; 95% confidence interval, 0.35-0.79). Radiographic OA progression has been defined as a one-step increase in the KL grade.

While the association appeared even stronger in women with a KL grade less than 2 and who were not overweight (HR, 0.49; 95% CI, 0.26-0.92), bisphosphonate use was not associated with radiographic OA progression in women with a higher (≥2) KL grade (HR, 1.06; 95% CI, 0.83-1.35).

“In all analyses, the effect of bisphosphonates was larger in radiographic-disease-naive individuals, suggesting protection using bisphosphonates may be more profound in those who do not already have evidence of knee damage or who have mild disease, and once damage occurs, bisphosphonate use may not have much effect,” Kaleen N. Hayes, PharmD, of the University of Toronto and her coauthors reported in the Journal of Bone and Mineral Research.

“Our study was the first to our knowledge to examine bisphosphonate exposure effects in different disease severity subgroups and obesity classifications using a rigorous, propensity-matched time-to-event analysis that uniquely addresses confounding by indication,” Dr. Hayes and her team wrote.

Furthermore, they noted that extensive sensitivity analyses, which included redoing the primary analyses to look at statin use, showed that their main conclusions were unchanged and that this helped account for any potential residual confounding, healthy-user bias, or exposure misclassification.
 

Study details

The Osteoarthritis Initiative is a 10-year longitudinal cohort study conducted at four clinical sites in the United States and recruited men and women aged 45-75 years over a 2-year period starting in 2004. Dr. Hayes and her coauthors restricted their analyses to women 50 years and older. Their study population consisted of 344 bisphosphonate users and 344 bisphosphonate nonusers.

The main bisphosphonate being taken was alendronate (69%), and the average duration of bisphosphonate use was 3.3 years, but no significant effect of duration of use on radiographic progression was found.

The women were followed until the first radiographic OA progression, or the first missed visit or end of the 2-year follow-up period.

Overall, 95 (13.8%) of the 688 women included in the analysis experienced radiographic OA progression. Of those, 27 (3.9%) had a KL grade of less than 2 and 68 (9.8%) had a KL grade of 2 or greater. Ten women with KL less than 2 and 27 women with KL or 2 or greater were taking bisphosphonates at their baseline visit.

“Kaplan-Meier analysis indicated that non-users and users with a baseline KL grade of 0 or 1 had 2-year risks of progression of 10.5% and 5.9%, respectively, whereas non-users and users with a baseline KL grade of 2 or 3 had 2-year of these women risks of progression of 23.0% and 23.5%, respectively,” reported the authors.

Before propensity score matching, Dr. Hayes and her colleagues observed that women taking bisphosphonates were older, had lower body weight and a higher prevalence of any fracture or hip and vertebral fractures, and were also more likely be White, compared with non-users. “In addition, bisphosphonate-users appeared to be healthier than non-users, as suggested by a lower smoking prevalence, lower average baseline KL grade, lower diabetes prevalence, and higher multivitamin use (a healthy-user proxy),” they acknowledged.

Results in perspective

“The key thing that I’m concerned about when I see something like bisphosphonates and osteoarthritis is just how well confounding has been addressed,” commented Tuhina Neogi, MD, PhD, professor of medicine and epidemiology at Boston University and chief of rheumatology at Boston Medical Center, in an interview.

“So are there factors other than the bisphosphonates themselves that might explain the findings? It looks like they’ve taken into account a lot of important things that one would consider for trying to get the two groups to look as similar as possible,” she added. Dr. Neogi queried, however, if body mass index had been suitably been adjusted for even after propensity score matching.

“The effect estimate is quite large, so I do think there is some confounding. So I would feel comfortable saying that there’s a signal here for bisphosphonates in reducing the risk of progression among those who do not have radiographic OA at baseline,” Dr. Neogi observed.

“The context of all this is that there have been large, well-designed, randomized control trials of oral bisphosphonates from years ago that did not find any benefit of bisphosphonates in [terms of] radiographic OA progression,” Dr. Neogi explained.

In the Knee OA Structural Arthritis (KOSTAR) study, now considered “quite a large landmark study,” the efficacy of risedronate in providing symptom relief and slowing disease progression was studied in almost 2,500 patients. “They saw some improvements in signs and symptoms, but risedronate did not significantly reduce radiographic progression. [However] there were some signals on biomarkers,” Dr. Neogi said.

One of the issues is that radiographs are too insensitive to pick up early bone changes in OA, a fact not missed by Dr. Hayes et al. More recent research has thus looked to using more sensitive imaging methods, such as CT and MRI, such as a recent study published in JAMA looking at the use of intravenous zoledronic acid on bone marrow lesions and cartilage volume. The results did not show any benefit of bisphosphonate use over 2 years.

“So even though we thought the MRI might provide a better way to detect a signal, it hasn’t panned out,” Dr. Neogi said.

But that’s not to say that there isn’t still a signal. Dr. Neogi’s most recent research has been using MRI to look at bone marrow lesion volume in women who were newly starting bisphosphonate therapy versus those who were not, and this has been just been accepted for publication.

“We found no difference in bone marrow lesion volume between the two groups. But in the women who had bone marrow lesions at baseline, there was a statistically significant greater proportion of women on bisphosphonates having a decrease in bone marrow lesion volume than the non-initiators,” she said.

So is there evidence that putting more women on bisphosphonates could prevent OA? “I’m not sure that you would be able to say that this should be something that all postmenopausal women should be on,” Dr. Neogi said.

“There’s a theoretical risk that has not been formally studied that, if you diminish bone turnover and you get more and more mineralization occurring, the bone potentially may have altered mechanical properties, become stiffer and, over the long term, that might not be good for OA.”

She added that, if there is already a clear clinical indication for bisphosphonate use, however, such as older women who have had a fracture and who should be on a bisphosphonate anyway, then “a bisphosphonate has the theoretical potential additional benefit for their osteoarthritis.”

The authors and Dr. Neogi had no conflicts of interest or relationships to disclose.

SOURCE: Hayes KN et al. J Bone Miner Res. 2020 July 14. doi: 10.1002/jbmr.4133.
 

Since the early 2000s, approximately half of medical students in the United States – and in many years, more than half – have been women, but the proportion of women occupying leadership roles in medicine remains low, according to an update provided at the virtual Pediatric Hospital Medicine.

In pediatrics, a specialty in which approximately 70% of physicians are now women, there has been progress, but still less than 30% of pediatric department chairs are female, said Vincent Chiang, MD, chief medical officer of Boston Children’s Hospital, during a presentation at the virtual meeting sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.

Citing published data and a survey he personally conducted of the top children’s hospitals identified by the U.S. News and World Report, Dr. Chiang said a minority of division chiefs, chief medical officers, chief financial officers, and other leaders are female. At his institution, only 2 of 16 division chiefs are female.

“No matter how you slice it, women are underrepresented in leadership positions,” he noted.

The problem is certainly not confined to medicine. Dr. Chiang cited data showing that women and men have reached “near parity” in workforce participation in the United States even though the 20% earnings gap has changed little over time.

According to 2020 data from the World Economic Forum, the United States ranked 51 for the gender gap calculated on the basis of economic, political, educational, and health attainment. Even if this places the United States in the top third of the rankings, it is far behind Iceland and the Scandinavian countries that lead the list.

Efforts to reduce structural biases are part of the fix, but Dr. Chiang cautioned that fundamental changes might never occur if the plan is to wait for an approach based on meritocracy. He said that existing structural biases are “slanted away from women,” who are not necessarily granted the opportunities that are readily available to men.

“A meritocracy only works if the initial playing field was level. Otherwise, it just perpetuates the inequalities,” he said.

The problem is not a shortage of women with the skills to lead. In a study by Zenger/Folkman, a consulting company that works on leadership skill development, women performed better than men in 16 of 18 leadership categories, according to Dr. Chiang.

“There is certainly no shortage of capable women,” he noted.

Of the many issues, Dr. Chiang highlighted two. The first is the challenge of placing women on leadership pathways. This is likely to require proactive strategies, such as fast-track advancement programs that guide female candidates toward leadership roles.

The second is more nuanced. According to Dr. Chiang, women who want to assume a leadership role should think more actively about how and who is making decisions at their institution so they can position themselves appropriately. This is nuanced because “there is a certain amount of gamesmanship,” he said. The rise to leadership “has never been a pure meritocracy.”

Importantly, many of the key decisions in any institution involve money, according to Dr. Chiang. As a result, he advised those seeking leadership roles to join audit committees or otherwise take on responsibility for profit-and-loss management. Even in a nonprofit institution, “you need to make the numbers work,” he said, citing the common catchphrase: “No margin, no mission.”

However, Dr. Chiang acknowledged the many obstacles that prevent women from working their way into positions of leadership. For example, networking is important, but women are not necessarily attracted or invited to some of the social engagements, such as golf outings, where strong relationships are created.

In a survey of 100,000 people working at Fortune 500 companies, “82% of women say they feel excluded at work and much of that comes from that informal networking,” Dr. Chiang said. “Whereas 92% of men think they are not excluding women in their daily work.”

There is no single solution, but Dr. Chiang believes that concrete structural changes are needed. Female doctors remain grossly underrepresented in leadership roles even as they now represent more than half of the workforce for many specialties. Based on the need for proactive approaches outlined by Dr. Chiang, it appears unlikely that gender inequality will ever resolve itself.

Lisa S. Rotenstein, MD, who has written on fixing the gender imbalance in health care, including for the Harvard Business Review, said she agreed during an interview that structural changes are critical.

“In order to address current disparities, leaders should be thinking about how to remove both the formal and informal obstacles that prevent women and minorities from getting into the rooms where these decisions are being made,” said Dr. Rotenstein, who is an instructor in medicine at Brigham and Women’s Hospital, Harvard Medical School in Boston.

“This will need to involve sponsorship that gets women invited to the right committees or in positions with responsibility for profit-and-loss management,” she added.

Dr. Rotenstein spoke about improving “access to the pipeline” that leads to leadership roles. The ways in which women are excluded from opportunities is often subtle and difficult to penetrate without fundamental changes, she explained.

“Institutions need to understand the processes that lead to leadership roles and make the changes that allow women and minorities to participate,” she said. It is not enough to recognize the problem, according to Dr. Rotenstein.

Like Dr. Chiang, she noted that changes are needed in the methods that move underrepresented groups into leadership roles.

Dr. Chiang reported no potential conflicts of interest relevant to this study.

Since the early 2000s, approximately half of medical students in the United States – and in many years, more than half – have been women, but the proportion of women occupying leadership roles in medicine remains low, according to an update provided at the virtual Pediatric Hospital Medicine.

In pediatrics, a specialty in which approximately 70% of physicians are now women, there has been progress, but still less than 30% of pediatric department chairs are female, said Vincent Chiang, MD, chief medical officer of Boston Children’s Hospital, during a presentation at the virtual meeting sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.

Citing published data and a survey he personally conducted of the top children’s hospitals identified by the U.S. News and World Report, Dr. Chiang said a minority of division chiefs, chief medical officers, chief financial officers, and other leaders are female. At his institution, only 2 of 16 division chiefs are female.

“No matter how you slice it, women are underrepresented in leadership positions,” he noted.

The problem is certainly not confined to medicine. Dr. Chiang cited data showing that women and men have reached “near parity” in workforce participation in the United States even though the 20% earnings gap has changed little over time.

According to 2020 data from the World Economic Forum, the United States ranked 51 for the gender gap calculated on the basis of economic, political, educational, and health attainment. Even if this places the United States in the top third of the rankings, it is far behind Iceland and the Scandinavian countries that lead the list.

Efforts to reduce structural biases are part of the fix, but Dr. Chiang cautioned that fundamental changes might never occur if the plan is to wait for an approach based on meritocracy. He said that existing structural biases are “slanted away from women,” who are not necessarily granted the opportunities that are readily available to men.

“A meritocracy only works if the initial playing field was level. Otherwise, it just perpetuates the inequalities,” he said.

The problem is not a shortage of women with the skills to lead. In a study by Zenger/Folkman, a consulting company that works on leadership skill development, women performed better than men in 16 of 18 leadership categories, according to Dr. Chiang.

“There is certainly no shortage of capable women,” he noted.

Of the many issues, Dr. Chiang highlighted two. The first is the challenge of placing women on leadership pathways. This is likely to require proactive strategies, such as fast-track advancement programs that guide female candidates toward leadership roles.

The second is more nuanced. According to Dr. Chiang, women who want to assume a leadership role should think more actively about how and who is making decisions at their institution so they can position themselves appropriately. This is nuanced because “there is a certain amount of gamesmanship,” he said. The rise to leadership “has never been a pure meritocracy.”

Importantly, many of the key decisions in any institution involve money, according to Dr. Chiang. As a result, he advised those seeking leadership roles to join audit committees or otherwise take on responsibility for profit-and-loss management. Even in a nonprofit institution, “you need to make the numbers work,” he said, citing the common catchphrase: “No margin, no mission.”

However, Dr. Chiang acknowledged the many obstacles that prevent women from working their way into positions of leadership. For example, networking is important, but women are not necessarily attracted or invited to some of the social engagements, such as golf outings, where strong relationships are created.

In a survey of 100,000 people working at Fortune 500 companies, “82% of women say they feel excluded at work and much of that comes from that informal networking,” Dr. Chiang said. “Whereas 92% of men think they are not excluding women in their daily work.”

There is no single solution, but Dr. Chiang believes that concrete structural changes are needed. Female doctors remain grossly underrepresented in leadership roles even as they now represent more than half of the workforce for many specialties. Based on the need for proactive approaches outlined by Dr. Chiang, it appears unlikely that gender inequality will ever resolve itself.

Lisa S. Rotenstein, MD, who has written on fixing the gender imbalance in health care, including for the Harvard Business Review, said she agreed during an interview that structural changes are critical.

“In order to address current disparities, leaders should be thinking about how to remove both the formal and informal obstacles that prevent women and minorities from getting into the rooms where these decisions are being made,” said Dr. Rotenstein, who is an instructor in medicine at Brigham and Women’s Hospital, Harvard Medical School in Boston.

“This will need to involve sponsorship that gets women invited to the right committees or in positions with responsibility for profit-and-loss management,” she added.

Dr. Rotenstein spoke about improving “access to the pipeline” that leads to leadership roles. The ways in which women are excluded from opportunities is often subtle and difficult to penetrate without fundamental changes, she explained.

“Institutions need to understand the processes that lead to leadership roles and make the changes that allow women and minorities to participate,” she said. It is not enough to recognize the problem, according to Dr. Rotenstein.

Like Dr. Chiang, she noted that changes are needed in the methods that move underrepresented groups into leadership roles.

Dr. Chiang reported no potential conflicts of interest relevant to this study.

Since the early 2000s, approximately half of medical students in the United States – and in many years, more than half – have been women, but the proportion of women occupying leadership roles in medicine remains low, according to an update provided at the virtual Pediatric Hospital Medicine.

In pediatrics, a specialty in which approximately 70% of physicians are now women, there has been progress, but still less than 30% of pediatric department chairs are female, said Vincent Chiang, MD, chief medical officer of Boston Children’s Hospital, during a presentation at the virtual meeting sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.

Citing published data and a survey he personally conducted of the top children’s hospitals identified by the U.S. News and World Report, Dr. Chiang said a minority of division chiefs, chief medical officers, chief financial officers, and other leaders are female. At his institution, only 2 of 16 division chiefs are female.

“No matter how you slice it, women are underrepresented in leadership positions,” he noted.

The problem is certainly not confined to medicine. Dr. Chiang cited data showing that women and men have reached “near parity” in workforce participation in the United States even though the 20% earnings gap has changed little over time.

According to 2020 data from the World Economic Forum, the United States ranked 51 for the gender gap calculated on the basis of economic, political, educational, and health attainment. Even if this places the United States in the top third of the rankings, it is far behind Iceland and the Scandinavian countries that lead the list.

Efforts to reduce structural biases are part of the fix, but Dr. Chiang cautioned that fundamental changes might never occur if the plan is to wait for an approach based on meritocracy. He said that existing structural biases are “slanted away from women,” who are not necessarily granted the opportunities that are readily available to men.

“A meritocracy only works if the initial playing field was level. Otherwise, it just perpetuates the inequalities,” he said.

The problem is not a shortage of women with the skills to lead. In a study by Zenger/Folkman, a consulting company that works on leadership skill development, women performed better than men in 16 of 18 leadership categories, according to Dr. Chiang.

“There is certainly no shortage of capable women,” he noted.

Of the many issues, Dr. Chiang highlighted two. The first is the challenge of placing women on leadership pathways. This is likely to require proactive strategies, such as fast-track advancement programs that guide female candidates toward leadership roles.

The second is more nuanced. According to Dr. Chiang, women who want to assume a leadership role should think more actively about how and who is making decisions at their institution so they can position themselves appropriately. This is nuanced because “there is a certain amount of gamesmanship,” he said. The rise to leadership “has never been a pure meritocracy.”

Importantly, many of the key decisions in any institution involve money, according to Dr. Chiang. As a result, he advised those seeking leadership roles to join audit committees or otherwise take on responsibility for profit-and-loss management. Even in a nonprofit institution, “you need to make the numbers work,” he said, citing the common catchphrase: “No margin, no mission.”

However, Dr. Chiang acknowledged the many obstacles that prevent women from working their way into positions of leadership. For example, networking is important, but women are not necessarily attracted or invited to some of the social engagements, such as golf outings, where strong relationships are created.

In a survey of 100,000 people working at Fortune 500 companies, “82% of women say they feel excluded at work and much of that comes from that informal networking,” Dr. Chiang said. “Whereas 92% of men think they are not excluding women in their daily work.”

There is no single solution, but Dr. Chiang believes that concrete structural changes are needed. Female doctors remain grossly underrepresented in leadership roles even as they now represent more than half of the workforce for many specialties. Based on the need for proactive approaches outlined by Dr. Chiang, it appears unlikely that gender inequality will ever resolve itself.

Lisa S. Rotenstein, MD, who has written on fixing the gender imbalance in health care, including for the Harvard Business Review, said she agreed during an interview that structural changes are critical.

“In order to address current disparities, leaders should be thinking about how to remove both the formal and informal obstacles that prevent women and minorities from getting into the rooms where these decisions are being made,” said Dr. Rotenstein, who is an instructor in medicine at Brigham and Women’s Hospital, Harvard Medical School in Boston.

“This will need to involve sponsorship that gets women invited to the right committees or in positions with responsibility for profit-and-loss management,” she added.

Dr. Rotenstein spoke about improving “access to the pipeline” that leads to leadership roles. The ways in which women are excluded from opportunities is often subtle and difficult to penetrate without fundamental changes, she explained.

“Institutions need to understand the processes that lead to leadership roles and make the changes that allow women and minorities to participate,” she said. It is not enough to recognize the problem, according to Dr. Rotenstein.

Like Dr. Chiang, she noted that changes are needed in the methods that move underrepresented groups into leadership roles.

Dr. Chiang reported no potential conflicts of interest relevant to this study.

Adults who ate chocolate more than once a week or more than 3.5 times a month were significantly less likely to develop coronary artery disease than were those who ate less chocolate, according to data from a meta-analysis of more than 300,000 individuals.

Howard Shooter/Thinkstock

Consumption of chocolate has shown beneficial effects on blood pressure and endothelial function, wrote Chayakrit Krittanawong, MD, of Baylor College of Medicine, Houston, and colleagues in the European Journal of Preventive Cardiology. “However, the potential benefit of increased chocolate consumption reducing coronary artery disease (CAD) risk is not known,” they said.

The investigators reviewed data from 5 decades of research, including six studies with a total of 336,289 individuals who reported chocolate consumption. The study participants experienced 14,043 cases of CAD, 4,667 myocardial infarctions, 2,735 cerebrovascular accidents, and 332 cases of heart failure over an average follow-up period of 8.78 years.

Overall, higher chocolate consumption (defined as more than once a week or more than 3.5 times a month) was significantly associated with a decreased CAD risk (pooled risk ratio, 0.94; P < .001) compared to eating no chocolate or eating chocolate less than once a week.

The cardioprotective effects of chocolate may be linked to several nutrients, the researchers noted. Chocolate’s flavenols (epicatechin, catechin, and procyanidins) have demonstrated an ability to reduce myocardial infarct size in an animal study and to reduce platelet aggregation and improve endothelial function in humans with and without CAD. In addition, methylxanthines have demonstrated beneficial effects on cardiovascular function, polyphenols have been shown to facilitate nitric oxide synthesis, and stearic acid has been associated with reduced mean platelet volume, they wrote.

“The benefits of nutrients in chocolate appear promising and chocolate consumption at least once a week may be beneficial for CAD prevention,” the researchers suggested, although they cautioned that the effects of supplemental calories and the impact of fats, milk, and sugar in commercial chocolate must be taken into account.

The study findings were limited by several factors, including the potential dietary confounders such as total energy intake and the type of chocolate consumed (milk, dark, or white) and the relatively homogeneous study population, which included mainly individuals from Europe and the United States.

Additional long-term, double-blind, randomized trials are needed to identify the cardioprotective effects of chocolate, and “studies to determine the role of genetic potential and the beneficial effects of chocolate on CAD may be needed,” the researchers noted.

However, the current study results suggest that “consumption of chocolates at least once a week is associated with a reduction in the risk of CAD,” they concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.

SOURCE: Krittanawong C et al. Eur J Prev Cardiol. 2020 Jul 23. doi: 10.1177/2047487320936787.

Adults who ate chocolate more than once a week or more than 3.5 times a month were significantly less likely to develop coronary artery disease than were those who ate less chocolate, according to data from a meta-analysis of more than 300,000 individuals.

Howard Shooter/Thinkstock

Consumption of chocolate has shown beneficial effects on blood pressure and endothelial function, wrote Chayakrit Krittanawong, MD, of Baylor College of Medicine, Houston, and colleagues in the European Journal of Preventive Cardiology. “However, the potential benefit of increased chocolate consumption reducing coronary artery disease (CAD) risk is not known,” they said.

The investigators reviewed data from 5 decades of research, including six studies with a total of 336,289 individuals who reported chocolate consumption. The study participants experienced 14,043 cases of CAD, 4,667 myocardial infarctions, 2,735 cerebrovascular accidents, and 332 cases of heart failure over an average follow-up period of 8.78 years.

Overall, higher chocolate consumption (defined as more than once a week or more than 3.5 times a month) was significantly associated with a decreased CAD risk (pooled risk ratio, 0.94; P < .001) compared to eating no chocolate or eating chocolate less than once a week.

The cardioprotective effects of chocolate may be linked to several nutrients, the researchers noted. Chocolate’s flavenols (epicatechin, catechin, and procyanidins) have demonstrated an ability to reduce myocardial infarct size in an animal study and to reduce platelet aggregation and improve endothelial function in humans with and without CAD. In addition, methylxanthines have demonstrated beneficial effects on cardiovascular function, polyphenols have been shown to facilitate nitric oxide synthesis, and stearic acid has been associated with reduced mean platelet volume, they wrote.

“The benefits of nutrients in chocolate appear promising and chocolate consumption at least once a week may be beneficial for CAD prevention,” the researchers suggested, although they cautioned that the effects of supplemental calories and the impact of fats, milk, and sugar in commercial chocolate must be taken into account.

The study findings were limited by several factors, including the potential dietary confounders such as total energy intake and the type of chocolate consumed (milk, dark, or white) and the relatively homogeneous study population, which included mainly individuals from Europe and the United States.

Additional long-term, double-blind, randomized trials are needed to identify the cardioprotective effects of chocolate, and “studies to determine the role of genetic potential and the beneficial effects of chocolate on CAD may be needed,” the researchers noted.

However, the current study results suggest that “consumption of chocolates at least once a week is associated with a reduction in the risk of CAD,” they concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.

SOURCE: Krittanawong C et al. Eur J Prev Cardiol. 2020 Jul 23. doi: 10.1177/2047487320936787.

Adults who ate chocolate more than once a week or more than 3.5 times a month were significantly less likely to develop coronary artery disease than were those who ate less chocolate, according to data from a meta-analysis of more than 300,000 individuals.

Howard Shooter/Thinkstock

Consumption of chocolate has shown beneficial effects on blood pressure and endothelial function, wrote Chayakrit Krittanawong, MD, of Baylor College of Medicine, Houston, and colleagues in the European Journal of Preventive Cardiology. “However, the potential benefit of increased chocolate consumption reducing coronary artery disease (CAD) risk is not known,” they said.

The investigators reviewed data from 5 decades of research, including six studies with a total of 336,289 individuals who reported chocolate consumption. The study participants experienced 14,043 cases of CAD, 4,667 myocardial infarctions, 2,735 cerebrovascular accidents, and 332 cases of heart failure over an average follow-up period of 8.78 years.

Overall, higher chocolate consumption (defined as more than once a week or more than 3.5 times a month) was significantly associated with a decreased CAD risk (pooled risk ratio, 0.94; P < .001) compared to eating no chocolate or eating chocolate less than once a week.

The cardioprotective effects of chocolate may be linked to several nutrients, the researchers noted. Chocolate’s flavenols (epicatechin, catechin, and procyanidins) have demonstrated an ability to reduce myocardial infarct size in an animal study and to reduce platelet aggregation and improve endothelial function in humans with and without CAD. In addition, methylxanthines have demonstrated beneficial effects on cardiovascular function, polyphenols have been shown to facilitate nitric oxide synthesis, and stearic acid has been associated with reduced mean platelet volume, they wrote.

“The benefits of nutrients in chocolate appear promising and chocolate consumption at least once a week may be beneficial for CAD prevention,” the researchers suggested, although they cautioned that the effects of supplemental calories and the impact of fats, milk, and sugar in commercial chocolate must be taken into account.

The study findings were limited by several factors, including the potential dietary confounders such as total energy intake and the type of chocolate consumed (milk, dark, or white) and the relatively homogeneous study population, which included mainly individuals from Europe and the United States.

Additional long-term, double-blind, randomized trials are needed to identify the cardioprotective effects of chocolate, and “studies to determine the role of genetic potential and the beneficial effects of chocolate on CAD may be needed,” the researchers noted.

However, the current study results suggest that “consumption of chocolates at least once a week is associated with a reduction in the risk of CAD,” they concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.

SOURCE: Krittanawong C et al. Eur J Prev Cardiol. 2020 Jul 23. doi: 10.1177/2047487320936787.

Recommendations on use of the new dual-action anabolic agent romosozumab (Evenity, Amgen) and how to safely transition between osteoporosis agents are two of the issues addressed in the latest clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis from the American Association of Clinical Endocrinologists and American College of Endocrinology.

“This guideline is a practical tool for endocrinologists, physicians in general, regulatory bodies, health-related organizations, and interested laypersons regarding the diagnosis, evaluation, and treatment of postmenopausal osteoporosis,” the authors wrote.

The guidelines focus on 12 key clinical questions related to postmenopausal osteoporosis, with 52 specific recommendations, each graded according to the level of evidence.

They also include a treatment algorithm to help guide choice of therapy.
 

Reiterating role of FRAX in the diagnosis of patients with osteopenia

Among key updates is an emphasis on the role of the Fracture Risk Assessment Tool (FRAX) in the diagnosis of osteoporosis in patients with osteopenia.

While patients have traditionally been diagnosed with osteoporosis based on the presence of low bone mineral density (BMD) in the absence of fracture, the updated guidelines indicate that osteoporosis may be diagnosed in patients with osteopenia and an increased fracture risk using FRAX.

“The use of FRAX and osteopenia to diagnosis osteoporosis was first proposed by the National Bone Health Alliance years ago, and in the 2016 guideline, we agreed with it,” Pauline M. Camacho, MD, cochair of the guidelines task force, said in an interview.

“We reiterate in the 2020 guideline that we feel this is a valid diagnostic criteria,” said Dr. Camacho, professor of medicine and director of the Osteoporosis and Metabolic Bone Disease Center at Loyola University Chicago, Maywood, Ill. “It makes sense because when the thresholds are met by FRAX in patients with osteopenia, treatment is recommended. Therefore, why would they not fulfill treatment criteria for diagnosing osteoporosis?”

An increased risk of fracture based on a FRAX score may also be used to determine pharmacologic therapy, as can other traditional factors such as a low T score or a fragility fracture, the guidelines stated.
 

High risk vs. very high risk guides choice of first therapy

Another key update is the clarification of the risk stratification of patients who are high risk versus very high risk, which is key in determining the initial choice of agents and duration of therapy.

Specifically, patients should be considered at a very high fracture risk if they have the following criteria: a recent fracture (e.g., within the past 12 months), fractures while on approved osteoporosis therapy, multiple fractures, fractures while on drugs causing skeletal harm (e.g., long-term glucocorticoids), very low T score (e.g., less than −3.0), a high risk for falls or history of injurious falls, and a very high fracture probability by FRAX (e.g., major osteoporosis fracture >30%, hip fracture >4.5%) or other validated fracture risk algorithm.

Meanwhile, patients should be considered at high risk if they have been diagnosed with osteoporosis but do not meet the criteria for very high fracture risk.
 

Romosozumab brought into the mix

Another important update provides information on the role of one of the newest osteoporosis agents on the market, the anabolic drug romosozumab, a monoclonal antibody directed against sclerostin.

The drug’s approval by the Food and Drug Administration in 2019 for postmenopausal women at high risk of fracture was based on two large trials that showed dramatic increases in bone density through modeling as well as remodeling.

Those studies specifically showed significant reductions in radiographic vertebral fractures with romosozumab, compared with placebo and alendronate.

Dr. Camacho noted that romosozumab “will likely be for the very high risk group and those who have maxed out on teriparatide or abaloparatide.”

Romosozumab can safely be used in patients with prior radiation exposure, the guidelines noted.

Importantly, because of reports of a higher risk of serious cardiovascular events with romosozumab, compared with alendronate, romosozumab comes with a black-box warning that it should not be used in patients at high risk for cardiovascular events or who have had a recent myocardial infarction or stroke.

“Unfortunately, the very high risk group is often the older patients,” Dr. Camacho noted.

“The drug should not be given if there is a history of myocardial infarction or stroke in the past year,” she emphasized. “Clinical judgment is needed to decide who is at risk for cardiovascular complications.”

Notably, teriparatide and abaloparatide have black box warnings of their own regarding risk for osteosarcoma.

Switching therapies

Reflecting the evolving data on osteoporosis drug holidays, the guidelines also addressed the issue and the clinical challenges of switching therapies.

“In 2016, we said drug holidays are not recommended, and the treatment can be continued indefinitely, [however] in 2020, we felt that if some patients are no longer high risk, they can be transitioned off the drug,” Dr. Camacho said.

For teriparatide and abaloparatide, the FDA recommends treatment be limited to no more than 2 years, and for romosozumab, 1 year.

The updated guidelines recommend that upon discontinuation of an anabolic agent (e.g., abaloparatide, romosozumab, or teriparatide), a switch to therapy with an antiresorptive agent, such as denosumab or bisphosphonates, should be implemented to prevent loss of BMD and fracture efficacy.

Discontinuation of denosumab, however, can have notably negative effects. Clinical trials show rapid decreases in BMD when denosumab treatment is stopped after 2 or 8 years, as well as rapid loss of protection from vertebral fractures.

Therefore, if denosumab is going to be discontinued, there should be a proper transition to an antiresorptive agent for a limited time, such as one infusion of the bisphosphonate zoledronate.
 

Communicate the risks with and without treatment to patients

The authors underscored that, in addition to communicating the potential risk and expected benefits of osteoporosis treatments, clinicians should make sure patients fully appreciate the risk of fractures and their consequences, such as pain, disability, loss of independence, and death, when no treatment is given.

“It is incumbent on the clinician to provide this information to each patient in a manner that is fully understood, and it is equally important to learn from the patient about cultural beliefs, previous treatment experiences, fears, and concerns,” they wrote.

And in estimating patients’ fracture risk, T score must be combined with clinical risk factors, particularly advanced age and previous fracture, and clinicians should recognize that the absolute fracture risk is more useful than a risk ratio in developing treatment plans.

“Treatment recommendations may be quite different; an early postmenopausal woman with a T score of −2.5 has osteoporosis, although fracture risk is much lower than an 80-year-old woman with the same T score,” the authors explained.

Dr. Camacho reported financial relationships with Amgen and Shire. Disclosures for other task force members are detailed in the guidelines.

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

Recommendations on use of the new dual-action anabolic agent romosozumab (Evenity, Amgen) and how to safely transition between osteoporosis agents are two of the issues addressed in the latest clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis from the American Association of Clinical Endocrinologists and American College of Endocrinology.

“This guideline is a practical tool for endocrinologists, physicians in general, regulatory bodies, health-related organizations, and interested laypersons regarding the diagnosis, evaluation, and treatment of postmenopausal osteoporosis,” the authors wrote.

The guidelines focus on 12 key clinical questions related to postmenopausal osteoporosis, with 52 specific recommendations, each graded according to the level of evidence.

They also include a treatment algorithm to help guide choice of therapy.
 

Reiterating role of FRAX in the diagnosis of patients with osteopenia

Among key updates is an emphasis on the role of the Fracture Risk Assessment Tool (FRAX) in the diagnosis of osteoporosis in patients with osteopenia.

While patients have traditionally been diagnosed with osteoporosis based on the presence of low bone mineral density (BMD) in the absence of fracture, the updated guidelines indicate that osteoporosis may be diagnosed in patients with osteopenia and an increased fracture risk using FRAX.

“The use of FRAX and osteopenia to diagnosis osteoporosis was first proposed by the National Bone Health Alliance years ago, and in the 2016 guideline, we agreed with it,” Pauline M. Camacho, MD, cochair of the guidelines task force, said in an interview.

“We reiterate in the 2020 guideline that we feel this is a valid diagnostic criteria,” said Dr. Camacho, professor of medicine and director of the Osteoporosis and Metabolic Bone Disease Center at Loyola University Chicago, Maywood, Ill. “It makes sense because when the thresholds are met by FRAX in patients with osteopenia, treatment is recommended. Therefore, why would they not fulfill treatment criteria for diagnosing osteoporosis?”

An increased risk of fracture based on a FRAX score may also be used to determine pharmacologic therapy, as can other traditional factors such as a low T score or a fragility fracture, the guidelines stated.
 

High risk vs. very high risk guides choice of first therapy

Another key update is the clarification of the risk stratification of patients who are high risk versus very high risk, which is key in determining the initial choice of agents and duration of therapy.

Specifically, patients should be considered at a very high fracture risk if they have the following criteria: a recent fracture (e.g., within the past 12 months), fractures while on approved osteoporosis therapy, multiple fractures, fractures while on drugs causing skeletal harm (e.g., long-term glucocorticoids), very low T score (e.g., less than −3.0), a high risk for falls or history of injurious falls, and a very high fracture probability by FRAX (e.g., major osteoporosis fracture >30%, hip fracture >4.5%) or other validated fracture risk algorithm.

Meanwhile, patients should be considered at high risk if they have been diagnosed with osteoporosis but do not meet the criteria for very high fracture risk.
 

Romosozumab brought into the mix

Another important update provides information on the role of one of the newest osteoporosis agents on the market, the anabolic drug romosozumab, a monoclonal antibody directed against sclerostin.

The drug’s approval by the Food and Drug Administration in 2019 for postmenopausal women at high risk of fracture was based on two large trials that showed dramatic increases in bone density through modeling as well as remodeling.

Those studies specifically showed significant reductions in radiographic vertebral fractures with romosozumab, compared with placebo and alendronate.

Dr. Camacho noted that romosozumab “will likely be for the very high risk group and those who have maxed out on teriparatide or abaloparatide.”

Romosozumab can safely be used in patients with prior radiation exposure, the guidelines noted.

Importantly, because of reports of a higher risk of serious cardiovascular events with romosozumab, compared with alendronate, romosozumab comes with a black-box warning that it should not be used in patients at high risk for cardiovascular events or who have had a recent myocardial infarction or stroke.

“Unfortunately, the very high risk group is often the older patients,” Dr. Camacho noted.

“The drug should not be given if there is a history of myocardial infarction or stroke in the past year,” she emphasized. “Clinical judgment is needed to decide who is at risk for cardiovascular complications.”

Notably, teriparatide and abaloparatide have black box warnings of their own regarding risk for osteosarcoma.

Switching therapies

Reflecting the evolving data on osteoporosis drug holidays, the guidelines also addressed the issue and the clinical challenges of switching therapies.

“In 2016, we said drug holidays are not recommended, and the treatment can be continued indefinitely, [however] in 2020, we felt that if some patients are no longer high risk, they can be transitioned off the drug,” Dr. Camacho said.

For teriparatide and abaloparatide, the FDA recommends treatment be limited to no more than 2 years, and for romosozumab, 1 year.

The updated guidelines recommend that upon discontinuation of an anabolic agent (e.g., abaloparatide, romosozumab, or teriparatide), a switch to therapy with an antiresorptive agent, such as denosumab or bisphosphonates, should be implemented to prevent loss of BMD and fracture efficacy.

Discontinuation of denosumab, however, can have notably negative effects. Clinical trials show rapid decreases in BMD when denosumab treatment is stopped after 2 or 8 years, as well as rapid loss of protection from vertebral fractures.

Therefore, if denosumab is going to be discontinued, there should be a proper transition to an antiresorptive agent for a limited time, such as one infusion of the bisphosphonate zoledronate.
 

Communicate the risks with and without treatment to patients

The authors underscored that, in addition to communicating the potential risk and expected benefits of osteoporosis treatments, clinicians should make sure patients fully appreciate the risk of fractures and their consequences, such as pain, disability, loss of independence, and death, when no treatment is given.

“It is incumbent on the clinician to provide this information to each patient in a manner that is fully understood, and it is equally important to learn from the patient about cultural beliefs, previous treatment experiences, fears, and concerns,” they wrote.

And in estimating patients’ fracture risk, T score must be combined with clinical risk factors, particularly advanced age and previous fracture, and clinicians should recognize that the absolute fracture risk is more useful than a risk ratio in developing treatment plans.

“Treatment recommendations may be quite different; an early postmenopausal woman with a T score of −2.5 has osteoporosis, although fracture risk is much lower than an 80-year-old woman with the same T score,” the authors explained.

Dr. Camacho reported financial relationships with Amgen and Shire. Disclosures for other task force members are detailed in the guidelines.

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

Recommendations on use of the new dual-action anabolic agent romosozumab (Evenity, Amgen) and how to safely transition between osteoporosis agents are two of the issues addressed in the latest clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis from the American Association of Clinical Endocrinologists and American College of Endocrinology.

“This guideline is a practical tool for endocrinologists, physicians in general, regulatory bodies, health-related organizations, and interested laypersons regarding the diagnosis, evaluation, and treatment of postmenopausal osteoporosis,” the authors wrote.

The guidelines focus on 12 key clinical questions related to postmenopausal osteoporosis, with 52 specific recommendations, each graded according to the level of evidence.

They also include a treatment algorithm to help guide choice of therapy.
 

Reiterating role of FRAX in the diagnosis of patients with osteopenia

Among key updates is an emphasis on the role of the Fracture Risk Assessment Tool (FRAX) in the diagnosis of osteoporosis in patients with osteopenia.

While patients have traditionally been diagnosed with osteoporosis based on the presence of low bone mineral density (BMD) in the absence of fracture, the updated guidelines indicate that osteoporosis may be diagnosed in patients with osteopenia and an increased fracture risk using FRAX.

“The use of FRAX and osteopenia to diagnosis osteoporosis was first proposed by the National Bone Health Alliance years ago, and in the 2016 guideline, we agreed with it,” Pauline M. Camacho, MD, cochair of the guidelines task force, said in an interview.

“We reiterate in the 2020 guideline that we feel this is a valid diagnostic criteria,” said Dr. Camacho, professor of medicine and director of the Osteoporosis and Metabolic Bone Disease Center at Loyola University Chicago, Maywood, Ill. “It makes sense because when the thresholds are met by FRAX in patients with osteopenia, treatment is recommended. Therefore, why would they not fulfill treatment criteria for diagnosing osteoporosis?”

An increased risk of fracture based on a FRAX score may also be used to determine pharmacologic therapy, as can other traditional factors such as a low T score or a fragility fracture, the guidelines stated.
 

High risk vs. very high risk guides choice of first therapy

Another key update is the clarification of the risk stratification of patients who are high risk versus very high risk, which is key in determining the initial choice of agents and duration of therapy.

Specifically, patients should be considered at a very high fracture risk if they have the following criteria: a recent fracture (e.g., within the past 12 months), fractures while on approved osteoporosis therapy, multiple fractures, fractures while on drugs causing skeletal harm (e.g., long-term glucocorticoids), very low T score (e.g., less than −3.0), a high risk for falls or history of injurious falls, and a very high fracture probability by FRAX (e.g., major osteoporosis fracture >30%, hip fracture >4.5%) or other validated fracture risk algorithm.

Meanwhile, patients should be considered at high risk if they have been diagnosed with osteoporosis but do not meet the criteria for very high fracture risk.
 

Romosozumab brought into the mix

Another important update provides information on the role of one of the newest osteoporosis agents on the market, the anabolic drug romosozumab, a monoclonal antibody directed against sclerostin.

The drug’s approval by the Food and Drug Administration in 2019 for postmenopausal women at high risk of fracture was based on two large trials that showed dramatic increases in bone density through modeling as well as remodeling.

Those studies specifically showed significant reductions in radiographic vertebral fractures with romosozumab, compared with placebo and alendronate.

Dr. Camacho noted that romosozumab “will likely be for the very high risk group and those who have maxed out on teriparatide or abaloparatide.”

Romosozumab can safely be used in patients with prior radiation exposure, the guidelines noted.

Importantly, because of reports of a higher risk of serious cardiovascular events with romosozumab, compared with alendronate, romosozumab comes with a black-box warning that it should not be used in patients at high risk for cardiovascular events or who have had a recent myocardial infarction or stroke.

“Unfortunately, the very high risk group is often the older patients,” Dr. Camacho noted.

“The drug should not be given if there is a history of myocardial infarction or stroke in the past year,” she emphasized. “Clinical judgment is needed to decide who is at risk for cardiovascular complications.”

Notably, teriparatide and abaloparatide have black box warnings of their own regarding risk for osteosarcoma.

Switching therapies

Reflecting the evolving data on osteoporosis drug holidays, the guidelines also addressed the issue and the clinical challenges of switching therapies.

“In 2016, we said drug holidays are not recommended, and the treatment can be continued indefinitely, [however] in 2020, we felt that if some patients are no longer high risk, they can be transitioned off the drug,” Dr. Camacho said.

For teriparatide and abaloparatide, the FDA recommends treatment be limited to no more than 2 years, and for romosozumab, 1 year.

The updated guidelines recommend that upon discontinuation of an anabolic agent (e.g., abaloparatide, romosozumab, or teriparatide), a switch to therapy with an antiresorptive agent, such as denosumab or bisphosphonates, should be implemented to prevent loss of BMD and fracture efficacy.

Discontinuation of denosumab, however, can have notably negative effects. Clinical trials show rapid decreases in BMD when denosumab treatment is stopped after 2 or 8 years, as well as rapid loss of protection from vertebral fractures.

Therefore, if denosumab is going to be discontinued, there should be a proper transition to an antiresorptive agent for a limited time, such as one infusion of the bisphosphonate zoledronate.
 

Communicate the risks with and without treatment to patients

The authors underscored that, in addition to communicating the potential risk and expected benefits of osteoporosis treatments, clinicians should make sure patients fully appreciate the risk of fractures and their consequences, such as pain, disability, loss of independence, and death, when no treatment is given.

“It is incumbent on the clinician to provide this information to each patient in a manner that is fully understood, and it is equally important to learn from the patient about cultural beliefs, previous treatment experiences, fears, and concerns,” they wrote.

And in estimating patients’ fracture risk, T score must be combined with clinical risk factors, particularly advanced age and previous fracture, and clinicians should recognize that the absolute fracture risk is more useful than a risk ratio in developing treatment plans.

“Treatment recommendations may be quite different; an early postmenopausal woman with a T score of −2.5 has osteoporosis, although fracture risk is much lower than an 80-year-old woman with the same T score,” the authors explained.

Dr. Camacho reported financial relationships with Amgen and Shire. Disclosures for other task force members are detailed in the guidelines.

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

Antibody levels in patients with mild COVID-19, the level of disease most people have, appear to drop by half within 36 days, new research suggests. The research was conducted by F. Javier Ibarrondo, PhD, and colleagues and was published online on July 21 in a letter to the editor of the New England Journal of Medicine. Ibarrondo is associate researcher at the University of California, Los Angeles. (The original letter incorrectly calculated the half-life at 73 days.)

Coauthor Otto Yang, MD, professor of medicine in the division of infectious diseases at UCLA, told Medscape Medical News that the rapidity in the antibody drop at 5 weeks “is striking compared to other infections.”

The phenomenon has been suspected and has been observed before but had not been quantified.

“Our paper is the first to put firm numbers on the dropping of antibodies after early infection,” he said.

The researchers evaluated 34 people (average age, 43 years) who had recovered from mild COVID-19 and had referred themselves to UCLA for observational research.
 

Previous report also found a quick fade

As Medscape Medical News reported, a previous study from China that was published in Nature Medicine also found that the antibodies fade quickly.

Interpreting the meaning of the current research comes with a few caveats, Dr. Yang said.

“One is that we don’t know for sure that antibodies are what protect people from getting infected,” he said. Although it’s a reasonable assumption, he said, that’s not always the case.

Another caveat is that even if antibodies do protect, the tests being used to measure them – including the test that was used in this study – may not measure them the right way, and it is not yet known how many antibodies are needed for protection, he explained.

The UCLA researchers used an enzyme-linked immunosorbent assay to detect anti–SARS-CoV-2 spike receptor–binding domain immunoglobulin G concentrations.
 

“No reason for anybody to be getting an antibody test medically”

The study provides further proof that “[t]here’s no reason for anybody to be getting an antibody test medically right now,” Dr. Yang said.

Additionally, “FDA-approved tests are not approved for quantitative measures, only qualitative,” he continued. He noted that the findings may have implications with respect to herd immunity.

“Herd immunity depends on a lot of people having immunity to the infection all at the same time. If infection is followed by only brief protection from infection, the natural infection is not going to reach herd immunity,” he explained.

Buddy Creech, MD, MPH, associate professor of pediatrics and director of the Vanderbilt Vaccine Research Program in Nashville, Tenn., pointed out that antibodies “are just part of the story.”

“When we make an immune response to any germ,” he said, “we not only make an immune response for the time being but for the future. The next time we’re exposed, we can call into action B cells and T cells who have been there and done that.”

So even though the antibodies fade over time, other arms of the immune system are being trained for future action, he said.

Herd immunity does not require that populations have a huge level of antibodies that remains forever, he explained.

“It requires that in general, we’re not going to get infected as easily, and we’re not going to have disease as easily, and we’re not going to transmit the virus for as long,” he said.

Dr. Creech said he and others researching COVID-19 find that studies that show that antibodies fade quickly provide more proof “that this coronavirus is going to be here to stay unless we can take care of it through very effective treatments to take it from potentially fatal disease to one that is nothing more than a cold” or until a vaccine is developed.

He noted there are four other coronaviruses in widespread circulation every year that “amount to about 25% of the common cold.”

This study may help narrow the window as to when convalescent plasma – plasma that is taken from people who have recovered from COVID-19 and that is used to help people who are acutely ill with the disease – will be most effective, Dr. Creech explained. He said the results suggest that it is important that plasma be collected within the first couple of months after recovery so as to capture the most antibodies.

This study is important as another snapshot “so we understand the differences between severe and mild disease, so we can study it over time, so we have all the tools we need as we start these pivotal vaccine studies to make sure we’re making the right immune response for the right duration of time so we can put an end to this pandemic,” Dr. Creech concluded.

The study was supported by grants from the AIDS Healthcare Foundation, the Doris Duke Charitable Foundation, the National Institutes of Health, the James B. Pendleton Charitable Trust, and the McCarthy Family Foundation. A coauthor reports receiving grants from Gilead outside the submitted work. Dr. Creech has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Antibody levels in patients with mild COVID-19, the level of disease most people have, appear to drop by half within 36 days, new research suggests. The research was conducted by F. Javier Ibarrondo, PhD, and colleagues and was published online on July 21 in a letter to the editor of the New England Journal of Medicine. Ibarrondo is associate researcher at the University of California, Los Angeles. (The original letter incorrectly calculated the half-life at 73 days.)

Coauthor Otto Yang, MD, professor of medicine in the division of infectious diseases at UCLA, told Medscape Medical News that the rapidity in the antibody drop at 5 weeks “is striking compared to other infections.”

The phenomenon has been suspected and has been observed before but had not been quantified.

“Our paper is the first to put firm numbers on the dropping of antibodies after early infection,” he said.

The researchers evaluated 34 people (average age, 43 years) who had recovered from mild COVID-19 and had referred themselves to UCLA for observational research.
 

Previous report also found a quick fade

As Medscape Medical News reported, a previous study from China that was published in Nature Medicine also found that the antibodies fade quickly.

Interpreting the meaning of the current research comes with a few caveats, Dr. Yang said.

“One is that we don’t know for sure that antibodies are what protect people from getting infected,” he said. Although it’s a reasonable assumption, he said, that’s not always the case.

Another caveat is that even if antibodies do protect, the tests being used to measure them – including the test that was used in this study – may not measure them the right way, and it is not yet known how many antibodies are needed for protection, he explained.

The UCLA researchers used an enzyme-linked immunosorbent assay to detect anti–SARS-CoV-2 spike receptor–binding domain immunoglobulin G concentrations.
 

“No reason for anybody to be getting an antibody test medically”

The study provides further proof that “[t]here’s no reason for anybody to be getting an antibody test medically right now,” Dr. Yang said.

Additionally, “FDA-approved tests are not approved for quantitative measures, only qualitative,” he continued. He noted that the findings may have implications with respect to herd immunity.

“Herd immunity depends on a lot of people having immunity to the infection all at the same time. If infection is followed by only brief protection from infection, the natural infection is not going to reach herd immunity,” he explained.

Buddy Creech, MD, MPH, associate professor of pediatrics and director of the Vanderbilt Vaccine Research Program in Nashville, Tenn., pointed out that antibodies “are just part of the story.”

“When we make an immune response to any germ,” he said, “we not only make an immune response for the time being but for the future. The next time we’re exposed, we can call into action B cells and T cells who have been there and done that.”

So even though the antibodies fade over time, other arms of the immune system are being trained for future action, he said.

Herd immunity does not require that populations have a huge level of antibodies that remains forever, he explained.

“It requires that in general, we’re not going to get infected as easily, and we’re not going to have disease as easily, and we’re not going to transmit the virus for as long,” he said.

Dr. Creech said he and others researching COVID-19 find that studies that show that antibodies fade quickly provide more proof “that this coronavirus is going to be here to stay unless we can take care of it through very effective treatments to take it from potentially fatal disease to one that is nothing more than a cold” or until a vaccine is developed.

He noted there are four other coronaviruses in widespread circulation every year that “amount to about 25% of the common cold.”

This study may help narrow the window as to when convalescent plasma – plasma that is taken from people who have recovered from COVID-19 and that is used to help people who are acutely ill with the disease – will be most effective, Dr. Creech explained. He said the results suggest that it is important that plasma be collected within the first couple of months after recovery so as to capture the most antibodies.

This study is important as another snapshot “so we understand the differences between severe and mild disease, so we can study it over time, so we have all the tools we need as we start these pivotal vaccine studies to make sure we’re making the right immune response for the right duration of time so we can put an end to this pandemic,” Dr. Creech concluded.

The study was supported by grants from the AIDS Healthcare Foundation, the Doris Duke Charitable Foundation, the National Institutes of Health, the James B. Pendleton Charitable Trust, and the McCarthy Family Foundation. A coauthor reports receiving grants from Gilead outside the submitted work. Dr. Creech has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Antibody levels in patients with mild COVID-19, the level of disease most people have, appear to drop by half within 36 days, new research suggests. The research was conducted by F. Javier Ibarrondo, PhD, and colleagues and was published online on July 21 in a letter to the editor of the New England Journal of Medicine. Ibarrondo is associate researcher at the University of California, Los Angeles. (The original letter incorrectly calculated the half-life at 73 days.)

Coauthor Otto Yang, MD, professor of medicine in the division of infectious diseases at UCLA, told Medscape Medical News that the rapidity in the antibody drop at 5 weeks “is striking compared to other infections.”

The phenomenon has been suspected and has been observed before but had not been quantified.

“Our paper is the first to put firm numbers on the dropping of antibodies after early infection,” he said.

The researchers evaluated 34 people (average age, 43 years) who had recovered from mild COVID-19 and had referred themselves to UCLA for observational research.
 

Previous report also found a quick fade

As Medscape Medical News reported, a previous study from China that was published in Nature Medicine also found that the antibodies fade quickly.

Interpreting the meaning of the current research comes with a few caveats, Dr. Yang said.

“One is that we don’t know for sure that antibodies are what protect people from getting infected,” he said. Although it’s a reasonable assumption, he said, that’s not always the case.

Another caveat is that even if antibodies do protect, the tests being used to measure them – including the test that was used in this study – may not measure them the right way, and it is not yet known how many antibodies are needed for protection, he explained.

The UCLA researchers used an enzyme-linked immunosorbent assay to detect anti–SARS-CoV-2 spike receptor–binding domain immunoglobulin G concentrations.
 

“No reason for anybody to be getting an antibody test medically”

The study provides further proof that “[t]here’s no reason for anybody to be getting an antibody test medically right now,” Dr. Yang said.

Additionally, “FDA-approved tests are not approved for quantitative measures, only qualitative,” he continued. He noted that the findings may have implications with respect to herd immunity.

“Herd immunity depends on a lot of people having immunity to the infection all at the same time. If infection is followed by only brief protection from infection, the natural infection is not going to reach herd immunity,” he explained.

Buddy Creech, MD, MPH, associate professor of pediatrics and director of the Vanderbilt Vaccine Research Program in Nashville, Tenn., pointed out that antibodies “are just part of the story.”

“When we make an immune response to any germ,” he said, “we not only make an immune response for the time being but for the future. The next time we’re exposed, we can call into action B cells and T cells who have been there and done that.”

So even though the antibodies fade over time, other arms of the immune system are being trained for future action, he said.

Herd immunity does not require that populations have a huge level of antibodies that remains forever, he explained.

“It requires that in general, we’re not going to get infected as easily, and we’re not going to have disease as easily, and we’re not going to transmit the virus for as long,” he said.

Dr. Creech said he and others researching COVID-19 find that studies that show that antibodies fade quickly provide more proof “that this coronavirus is going to be here to stay unless we can take care of it through very effective treatments to take it from potentially fatal disease to one that is nothing more than a cold” or until a vaccine is developed.

He noted there are four other coronaviruses in widespread circulation every year that “amount to about 25% of the common cold.”

This study may help narrow the window as to when convalescent plasma – plasma that is taken from people who have recovered from COVID-19 and that is used to help people who are acutely ill with the disease – will be most effective, Dr. Creech explained. He said the results suggest that it is important that plasma be collected within the first couple of months after recovery so as to capture the most antibodies.

This study is important as another snapshot “so we understand the differences between severe and mild disease, so we can study it over time, so we have all the tools we need as we start these pivotal vaccine studies to make sure we’re making the right immune response for the right duration of time so we can put an end to this pandemic,” Dr. Creech concluded.

The study was supported by grants from the AIDS Healthcare Foundation, the Doris Duke Charitable Foundation, the National Institutes of Health, the James B. Pendleton Charitable Trust, and the McCarthy Family Foundation. A coauthor reports receiving grants from Gilead outside the submitted work. Dr. Creech has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.