Bianca Nogrady

Secondary prevention of cardiovascular disease could significantly reduce cardiac mortality among patients with schizophrenia, yet is underused, a study published Oct. 24 has found.

The retrospective study, which included a Danish nationwide cohort of 105,018 patients with myocardial infarction, including 684 patients with schizophrenia, showed that individuals with schizophrenia who did not receive secondary cardioprotective treatment had a more than eight times higher mortality, compared with people in the general population who did receive treatment (hazard ratio, 8.78; 95% confidence interval, 4.37-17.64), Pirathiv Kugathasan and his associates reported in JAMA Psychiatry.

In contrast, the investigators found, patients with schizophrenia who received cardioprotective treatment had a 97% higher mortality (HR, 1.97; 95% CI, 1.25-310), compared with the treated general population, which was not statistically different from individuals in the general population who did not receive treatment (HR, 2.95; 95% CI, 2.62-3.32) after adjustment for baseline characteristics.

“Given the increased cardiovascular risk among patients with schizophrenia, we believe that the current findings support the use of intensive cardioprotective treatments in patients with schizophrenia,” reported Mr. Kugathasan, a PhD candidate in the department of psychiatry at Aalborg University Hospital in Denmark.

However, 7.8% of patients diagnosed with schizophrenia received no prescriptions for cardioprotective medications after a myocardial infarction, compared with 3.3% of the general population. They were significantly less likely than were individuals from the general population to receive a prescription for antiplatelets (84.9% vs. 91.8%), vitamin K antagonists (15.9% vs. 24.2%), beta-blockers (74.1% vs. 84.9%), ACE inhibitors (70.9% vs. 86.6%), and statins (72.2% vs. 87.3%).

The mortality rates were not significantly different between untreated patients with schizophrenia and untreated participants from the general population.

When the researchers examined the effects of different treatment types, they found that mortality rates were still higher in treated patients with schizophrenia, compared with treated patients from the general population – with the exception of those treated with antiplatelets and statins. For ACE inhibitors, treated patients with schizophrenia had a twofold higher mortality than that of treated patients from the general population, while the mortality was more than twofold higher in the case of vitamin K antagonists.

“Previous studies have found that patients with schizophrenia have increased cardiovascular mortality and a lower prescription rate for cardioprotective treatment compared with the general population,” the authors wrote.

They noted that patients with schizophrenia might have more problems with medication adherence, and pointed to another study showing this in patients with schizophrenia and diabetes. Other studies also showed that patients with schizophrenia were less likely to talk to a cardiologist after a cardiac event.

“Together, we believe that these results could point toward a deficit in establishing an appropriate cardiac treatment plan in patients with schizophrenia that causes failure in initiation and maintenance of cardioprotective treatment,” they wrote. “This hypothesis could explain the results of a generally increased mortality rate among patients with schizophrenia, especially when the results suggest that these patients die of cardiovascular causes that might be treatable.”

They called for patients with schizophrenia to be followed up during treatment, and to increase treatment intensity after cardiac events, “because a diagnosis of schizophrenia may be associated with an increased cardiac risk, which potentially can be countered by secondary preventive cardiac treatment.”

In patients who received triple therapy, the mortality rates were similar for those with schizophrenia and the general population. However, there were much higher mortality rate differences between patients with schizophrenia and the general population for those receiving dual or monotherapy.

Significantly more patients from the general population were readmitted with myocardial infarction and more underwent percutaneous coronary intervention than from the group of patients with schizophrenia.

The prevalence of hypertension was similar between the two populations, but more patients with schizophrenia had diabetes and substance abuse, compared with the general population.

The authors noted that they did not have information on the severity of myocardial infarction or the effect of other lifestyle factors.

“Future research should attempt to assess the degree to which these factors contribute to the increased mortality in patients with schizophrenia,” they wrote.

One author declared grants, speaking fees and advisory roles with the pharmaceutical industry. No other conflicts of interest were declared.

SOURCE: Kugathasan P et al. JAMA Psychiatry 2018. Oct 24. doi: 10.1001/jamapsychiatry.2018.2742.

Secondary prevention of cardiovascular disease could significantly reduce cardiac mortality among patients with schizophrenia, yet is underused, a study published Oct. 24 has found.

The retrospective study, which included a Danish nationwide cohort of 105,018 patients with myocardial infarction, including 684 patients with schizophrenia, showed that individuals with schizophrenia who did not receive secondary cardioprotective treatment had a more than eight times higher mortality, compared with people in the general population who did receive treatment (hazard ratio, 8.78; 95% confidence interval, 4.37-17.64), Pirathiv Kugathasan and his associates reported in JAMA Psychiatry.

In contrast, the investigators found, patients with schizophrenia who received cardioprotective treatment had a 97% higher mortality (HR, 1.97; 95% CI, 1.25-310), compared with the treated general population, which was not statistically different from individuals in the general population who did not receive treatment (HR, 2.95; 95% CI, 2.62-3.32) after adjustment for baseline characteristics.

“Given the increased cardiovascular risk among patients with schizophrenia, we believe that the current findings support the use of intensive cardioprotective treatments in patients with schizophrenia,” reported Mr. Kugathasan, a PhD candidate in the department of psychiatry at Aalborg University Hospital in Denmark.

However, 7.8% of patients diagnosed with schizophrenia received no prescriptions for cardioprotective medications after a myocardial infarction, compared with 3.3% of the general population. They were significantly less likely than were individuals from the general population to receive a prescription for antiplatelets (84.9% vs. 91.8%), vitamin K antagonists (15.9% vs. 24.2%), beta-blockers (74.1% vs. 84.9%), ACE inhibitors (70.9% vs. 86.6%), and statins (72.2% vs. 87.3%).

The mortality rates were not significantly different between untreated patients with schizophrenia and untreated participants from the general population.

When the researchers examined the effects of different treatment types, they found that mortality rates were still higher in treated patients with schizophrenia, compared with treated patients from the general population – with the exception of those treated with antiplatelets and statins. For ACE inhibitors, treated patients with schizophrenia had a twofold higher mortality than that of treated patients from the general population, while the mortality was more than twofold higher in the case of vitamin K antagonists.

“Previous studies have found that patients with schizophrenia have increased cardiovascular mortality and a lower prescription rate for cardioprotective treatment compared with the general population,” the authors wrote.

They noted that patients with schizophrenia might have more problems with medication adherence, and pointed to another study showing this in patients with schizophrenia and diabetes. Other studies also showed that patients with schizophrenia were less likely to talk to a cardiologist after a cardiac event.

“Together, we believe that these results could point toward a deficit in establishing an appropriate cardiac treatment plan in patients with schizophrenia that causes failure in initiation and maintenance of cardioprotective treatment,” they wrote. “This hypothesis could explain the results of a generally increased mortality rate among patients with schizophrenia, especially when the results suggest that these patients die of cardiovascular causes that might be treatable.”

They called for patients with schizophrenia to be followed up during treatment, and to increase treatment intensity after cardiac events, “because a diagnosis of schizophrenia may be associated with an increased cardiac risk, which potentially can be countered by secondary preventive cardiac treatment.”

In patients who received triple therapy, the mortality rates were similar for those with schizophrenia and the general population. However, there were much higher mortality rate differences between patients with schizophrenia and the general population for those receiving dual or monotherapy.

Significantly more patients from the general population were readmitted with myocardial infarction and more underwent percutaneous coronary intervention than from the group of patients with schizophrenia.

The prevalence of hypertension was similar between the two populations, but more patients with schizophrenia had diabetes and substance abuse, compared with the general population.

The authors noted that they did not have information on the severity of myocardial infarction or the effect of other lifestyle factors.

“Future research should attempt to assess the degree to which these factors contribute to the increased mortality in patients with schizophrenia,” they wrote.

One author declared grants, speaking fees and advisory roles with the pharmaceutical industry. No other conflicts of interest were declared.

SOURCE: Kugathasan P et al. JAMA Psychiatry 2018. Oct 24. doi: 10.1001/jamapsychiatry.2018.2742.

Secondary prevention of cardiovascular disease could significantly reduce cardiac mortality among patients with schizophrenia, yet is underused, a study published Oct. 24 has found.

The retrospective study, which included a Danish nationwide cohort of 105,018 patients with myocardial infarction, including 684 patients with schizophrenia, showed that individuals with schizophrenia who did not receive secondary cardioprotective treatment had a more than eight times higher mortality, compared with people in the general population who did receive treatment (hazard ratio, 8.78; 95% confidence interval, 4.37-17.64), Pirathiv Kugathasan and his associates reported in JAMA Psychiatry.

In contrast, the investigators found, patients with schizophrenia who received cardioprotective treatment had a 97% higher mortality (HR, 1.97; 95% CI, 1.25-310), compared with the treated general population, which was not statistically different from individuals in the general population who did not receive treatment (HR, 2.95; 95% CI, 2.62-3.32) after adjustment for baseline characteristics.

“Given the increased cardiovascular risk among patients with schizophrenia, we believe that the current findings support the use of intensive cardioprotective treatments in patients with schizophrenia,” reported Mr. Kugathasan, a PhD candidate in the department of psychiatry at Aalborg University Hospital in Denmark.

However, 7.8% of patients diagnosed with schizophrenia received no prescriptions for cardioprotective medications after a myocardial infarction, compared with 3.3% of the general population. They were significantly less likely than were individuals from the general population to receive a prescription for antiplatelets (84.9% vs. 91.8%), vitamin K antagonists (15.9% vs. 24.2%), beta-blockers (74.1% vs. 84.9%), ACE inhibitors (70.9% vs. 86.6%), and statins (72.2% vs. 87.3%).

The mortality rates were not significantly different between untreated patients with schizophrenia and untreated participants from the general population.

When the researchers examined the effects of different treatment types, they found that mortality rates were still higher in treated patients with schizophrenia, compared with treated patients from the general population – with the exception of those treated with antiplatelets and statins. For ACE inhibitors, treated patients with schizophrenia had a twofold higher mortality than that of treated patients from the general population, while the mortality was more than twofold higher in the case of vitamin K antagonists.

“Previous studies have found that patients with schizophrenia have increased cardiovascular mortality and a lower prescription rate for cardioprotective treatment compared with the general population,” the authors wrote.

They noted that patients with schizophrenia might have more problems with medication adherence, and pointed to another study showing this in patients with schizophrenia and diabetes. Other studies also showed that patients with schizophrenia were less likely to talk to a cardiologist after a cardiac event.

“Together, we believe that these results could point toward a deficit in establishing an appropriate cardiac treatment plan in patients with schizophrenia that causes failure in initiation and maintenance of cardioprotective treatment,” they wrote. “This hypothesis could explain the results of a generally increased mortality rate among patients with schizophrenia, especially when the results suggest that these patients die of cardiovascular causes that might be treatable.”

They called for patients with schizophrenia to be followed up during treatment, and to increase treatment intensity after cardiac events, “because a diagnosis of schizophrenia may be associated with an increased cardiac risk, which potentially can be countered by secondary preventive cardiac treatment.”

In patients who received triple therapy, the mortality rates were similar for those with schizophrenia and the general population. However, there were much higher mortality rate differences between patients with schizophrenia and the general population for those receiving dual or monotherapy.

Significantly more patients from the general population were readmitted with myocardial infarction and more underwent percutaneous coronary intervention than from the group of patients with schizophrenia.

The prevalence of hypertension was similar between the two populations, but more patients with schizophrenia had diabetes and substance abuse, compared with the general population.

The authors noted that they did not have information on the severity of myocardial infarction or the effect of other lifestyle factors.

“Future research should attempt to assess the degree to which these factors contribute to the increased mortality in patients with schizophrenia,” they wrote.

One author declared grants, speaking fees and advisory roles with the pharmaceutical industry. No other conflicts of interest were declared.

SOURCE: Kugathasan P et al. JAMA Psychiatry 2018. Oct 24. doi: 10.1001/jamapsychiatry.2018.2742.

Photo from Novartis

Tisagenlecleucel has the potential to be cost-effective for pediatric B-cell acute lymphoblastic leukemia (B-ALL) patients in the United States, according to researchers.

The group found evidence to suggest the chimeric antigen receptor (CAR) T-cell therapy—which has a list price of $475,000—may prove cost-effective if long-term survival benefits are realized.

An analysis indicated that the incremental cost-effectiveness ratio for tisagenlecleucel compared to clofarabine ranged from $37,000 to $78,000 per quality-adjusted life year (QALY) gained.

Melanie D. Whittington, PhD, of the University of Colorado at Denver, Aurora, and her colleagues described this work in JAMA Pediatrics.

For this study, the researchers used a decision analytic model that extrapolated the evidence from clinical trials over a patient’s lifetime to assess life-years gained, QALYs gained, and incremental costs per life-year and QALY gained. The researchers compared tisagenlecleucel to the antineoplastic agent clofarabine.

While tisagenlecleucel has a list price of $475,000, researchers discounted the price by 3% and added several additional costs, such as hospital administration, pretreatment, and potential adverse events, to get to a total discounted cost of about $667,000.

The team estimated that 42.6% of B-ALL patients would be long-term survivors with tisagenlecleucel, 10.34 life-years would be gained, and 9.28 QALYs would be gained.

In comparison, clofarabine had a total discounted cost of approximately $337,000, which included an initial discounted price of $164,000 plus additional treatment and administrative costs.

With clofarabine, 10.8% of B-ALL patients were long-term survivors, 2.43 life-years were gained, and 2.10 QALYs were gained in the model.

Overall, the mean incremental cost-effectiveness ratio was about $46,000 per QALY gained in this base-case model.

In analyses of different scenarios, such as a deeper discount, a different treatment start, or a different calculation of future treatment costs, the cost-effectiveness ratio varied from $37,000 to $78,000 per QALY gained.

The researchers noted that clinical trial evidence for tisagenlecleucel came from single-arm trials, which made the selection of a comparator challenging. Clofarabine was chosen because it had the most similar baseline population characteristics, but the researchers acknowledged that blinatumomab is also frequently used as a treatment for these patients.

“We suspect that tisagenlecleucel would remain cost-effective compared with blinatumomab,” the researchers wrote in JAMA Pediatrics. “A study conducted by other researchers found the incremental cost-effectiveness ratio of tisagenlecleucel versus blinatumomab was similar to the incremental cost-effectiveness ratio of tisagenlecleucel versus clofarabine [i.e., $3,000 more per QALY].”

The researchers suggested that uncertainties in the evidence should be considered as payers are negotiating coverage and payment for tisagenlecleucel.

This study was funded by the Institute for Clinical and Economic Review, which receives some funding from the pharmaceutical industry. Four study authors are employees of the Institute for Clinical and Economic Review.

Photo from Novartis

Tisagenlecleucel has the potential to be cost-effective for pediatric B-cell acute lymphoblastic leukemia (B-ALL) patients in the United States, according to researchers.

The group found evidence to suggest the chimeric antigen receptor (CAR) T-cell therapy—which has a list price of $475,000—may prove cost-effective if long-term survival benefits are realized.

An analysis indicated that the incremental cost-effectiveness ratio for tisagenlecleucel compared to clofarabine ranged from $37,000 to $78,000 per quality-adjusted life year (QALY) gained.

Melanie D. Whittington, PhD, of the University of Colorado at Denver, Aurora, and her colleagues described this work in JAMA Pediatrics.

For this study, the researchers used a decision analytic model that extrapolated the evidence from clinical trials over a patient’s lifetime to assess life-years gained, QALYs gained, and incremental costs per life-year and QALY gained. The researchers compared tisagenlecleucel to the antineoplastic agent clofarabine.

While tisagenlecleucel has a list price of $475,000, researchers discounted the price by 3% and added several additional costs, such as hospital administration, pretreatment, and potential adverse events, to get to a total discounted cost of about $667,000.

The team estimated that 42.6% of B-ALL patients would be long-term survivors with tisagenlecleucel, 10.34 life-years would be gained, and 9.28 QALYs would be gained.

In comparison, clofarabine had a total discounted cost of approximately $337,000, which included an initial discounted price of $164,000 plus additional treatment and administrative costs.

With clofarabine, 10.8% of B-ALL patients were long-term survivors, 2.43 life-years were gained, and 2.10 QALYs were gained in the model.

Overall, the mean incremental cost-effectiveness ratio was about $46,000 per QALY gained in this base-case model.

In analyses of different scenarios, such as a deeper discount, a different treatment start, or a different calculation of future treatment costs, the cost-effectiveness ratio varied from $37,000 to $78,000 per QALY gained.

The researchers noted that clinical trial evidence for tisagenlecleucel came from single-arm trials, which made the selection of a comparator challenging. Clofarabine was chosen because it had the most similar baseline population characteristics, but the researchers acknowledged that blinatumomab is also frequently used as a treatment for these patients.

“We suspect that tisagenlecleucel would remain cost-effective compared with blinatumomab,” the researchers wrote in JAMA Pediatrics. “A study conducted by other researchers found the incremental cost-effectiveness ratio of tisagenlecleucel versus blinatumomab was similar to the incremental cost-effectiveness ratio of tisagenlecleucel versus clofarabine [i.e., $3,000 more per QALY].”

The researchers suggested that uncertainties in the evidence should be considered as payers are negotiating coverage and payment for tisagenlecleucel.

This study was funded by the Institute for Clinical and Economic Review, which receives some funding from the pharmaceutical industry. Four study authors are employees of the Institute for Clinical and Economic Review.

Photo from Novartis

Tisagenlecleucel has the potential to be cost-effective for pediatric B-cell acute lymphoblastic leukemia (B-ALL) patients in the United States, according to researchers.

The group found evidence to suggest the chimeric antigen receptor (CAR) T-cell therapy—which has a list price of $475,000—may prove cost-effective if long-term survival benefits are realized.

An analysis indicated that the incremental cost-effectiveness ratio for tisagenlecleucel compared to clofarabine ranged from $37,000 to $78,000 per quality-adjusted life year (QALY) gained.

Melanie D. Whittington, PhD, of the University of Colorado at Denver, Aurora, and her colleagues described this work in JAMA Pediatrics.

For this study, the researchers used a decision analytic model that extrapolated the evidence from clinical trials over a patient’s lifetime to assess life-years gained, QALYs gained, and incremental costs per life-year and QALY gained. The researchers compared tisagenlecleucel to the antineoplastic agent clofarabine.

While tisagenlecleucel has a list price of $475,000, researchers discounted the price by 3% and added several additional costs, such as hospital administration, pretreatment, and potential adverse events, to get to a total discounted cost of about $667,000.

The team estimated that 42.6% of B-ALL patients would be long-term survivors with tisagenlecleucel, 10.34 life-years would be gained, and 9.28 QALYs would be gained.

In comparison, clofarabine had a total discounted cost of approximately $337,000, which included an initial discounted price of $164,000 plus additional treatment and administrative costs.

With clofarabine, 10.8% of B-ALL patients were long-term survivors, 2.43 life-years were gained, and 2.10 QALYs were gained in the model.

Overall, the mean incremental cost-effectiveness ratio was about $46,000 per QALY gained in this base-case model.

In analyses of different scenarios, such as a deeper discount, a different treatment start, or a different calculation of future treatment costs, the cost-effectiveness ratio varied from $37,000 to $78,000 per QALY gained.

The researchers noted that clinical trial evidence for tisagenlecleucel came from single-arm trials, which made the selection of a comparator challenging. Clofarabine was chosen because it had the most similar baseline population characteristics, but the researchers acknowledged that blinatumomab is also frequently used as a treatment for these patients.

“We suspect that tisagenlecleucel would remain cost-effective compared with blinatumomab,” the researchers wrote in JAMA Pediatrics. “A study conducted by other researchers found the incremental cost-effectiveness ratio of tisagenlecleucel versus blinatumomab was similar to the incremental cost-effectiveness ratio of tisagenlecleucel versus clofarabine [i.e., $3,000 more per QALY].”

The researchers suggested that uncertainties in the evidence should be considered as payers are negotiating coverage and payment for tisagenlecleucel.

This study was funded by the Institute for Clinical and Economic Review, which receives some funding from the pharmaceutical industry. Four study authors are employees of the Institute for Clinical and Economic Review.

Cardiomyopathy induced by antimalarial treatment for systematic lupus erythematosus may not be as rare as previously thought, according to the authors of a case series published Oct. 15 in The Journal of Rheumatology.

The paper describes eight patients attending a lupus clinic, who were diagnosed with definite or possible antimalarial-induced cardiomyopathy over the course of 2 years.

Konstantinos Tselios, MD, PhD, a clinical research fellow at the University of Toronto Lupus Clinic, and his coauthors wrote that antimalarial-induced cardiomyopathy was thought to be relatively rare, with only 47 previous isolated reports, but they suggested the complication may be significantly underrecognized.

“Hypertrophic cardiomyopathy and heart failure, the most common clinical features of AM-induced cardiomyopathy (AMIC), may be falsely attributed to other causes, such as arterial hypertension or ischemic cardiomyopathy,” the authors wrote. “Consequently, nonspecific therapeutic approaches with diuretics and/or antihypertensives will exert minimum or even deleterious effects on such patients.”

All eight patients in this series were female, with a median age of 62.5 years, median disease duration of 35 years, and median antimalarial use of 22 years. They presented with conditions such as heart failure, exertional dyspnea, and pedal edema. Several patients were asymptomatic but had been found to have elevated heart biomarker levels that prompted further investigation.


All patients showed abnormal cardiac troponin I and brain natriuretic peptide levels, and seven of the eight also had chronically elevated creatine phosphokinase.

In three patients, endomyocardial biopsy showed cardiomyocyte vacuolation, intracytoplasmic myelinoid inclusions, and curvilinear bodies.

Four patients were diagnosed based on cardiac MRI, which showed features suggestive of antimalarial-induced cardiomyopathy, including ventricular hypertrophy with or without atrial enlargement and late gadolinium enhancement in a nonvascular pattern.

All patients had left ventricular hypertrophy, and four also had right ventricular hypertrophy. Only one patient showed impaired systolic function, compared with around half of patients in the literature with antimalarial-induced cardiomyopathy, but seven patients showed a restrictive filling pattern of the left ventricle.

“It seems possible that AMIC is a chronic process and systolic dysfunction will become apparent only in late stages,” the authors suggested.

One patient showed complete atrioventricular block, left ventricular and septal hypertrophy, and concomitant ocular toxicity.

After patients stopped antimalarials, the hypertrophy regressed and heart biomarkers decreased in seven patients, but one patient died from refractory heart failure.

Based on their findings, the authors proposed that heart-specific biomarkers be used as a regular screening tool for detecting myocardial injury, followed by more thorough investigations, such as cardiac MRI, in patients with positive biomarker findings.

“However, drug cessation should be prompt and probably upon suspicion of AMIC, because complete investigation may be delayed significantly.”

One author was supported by the Geoff Carr Fellowship from Lupus Ontario. The University of Toronto Lupus Research Program is supported by the University Health Network, Lou and Marissa Rocca, and the Lupus Foundation of Ontario.

SOURCE: Tselios K et al. J Rheumatol, 2018 Oct 15. doi: 10.3899/jrheum.180124.

Cardiomyopathy induced by antimalarial treatment for systematic lupus erythematosus may not be as rare as previously thought, according to the authors of a case series published Oct. 15 in The Journal of Rheumatology.

The paper describes eight patients attending a lupus clinic, who were diagnosed with definite or possible antimalarial-induced cardiomyopathy over the course of 2 years.

Konstantinos Tselios, MD, PhD, a clinical research fellow at the University of Toronto Lupus Clinic, and his coauthors wrote that antimalarial-induced cardiomyopathy was thought to be relatively rare, with only 47 previous isolated reports, but they suggested the complication may be significantly underrecognized.

“Hypertrophic cardiomyopathy and heart failure, the most common clinical features of AM-induced cardiomyopathy (AMIC), may be falsely attributed to other causes, such as arterial hypertension or ischemic cardiomyopathy,” the authors wrote. “Consequently, nonspecific therapeutic approaches with diuretics and/or antihypertensives will exert minimum or even deleterious effects on such patients.”

All eight patients in this series were female, with a median age of 62.5 years, median disease duration of 35 years, and median antimalarial use of 22 years. They presented with conditions such as heart failure, exertional dyspnea, and pedal edema. Several patients were asymptomatic but had been found to have elevated heart biomarker levels that prompted further investigation.


All patients showed abnormal cardiac troponin I and brain natriuretic peptide levels, and seven of the eight also had chronically elevated creatine phosphokinase.

In three patients, endomyocardial biopsy showed cardiomyocyte vacuolation, intracytoplasmic myelinoid inclusions, and curvilinear bodies.

Four patients were diagnosed based on cardiac MRI, which showed features suggestive of antimalarial-induced cardiomyopathy, including ventricular hypertrophy with or without atrial enlargement and late gadolinium enhancement in a nonvascular pattern.

All patients had left ventricular hypertrophy, and four also had right ventricular hypertrophy. Only one patient showed impaired systolic function, compared with around half of patients in the literature with antimalarial-induced cardiomyopathy, but seven patients showed a restrictive filling pattern of the left ventricle.

“It seems possible that AMIC is a chronic process and systolic dysfunction will become apparent only in late stages,” the authors suggested.

One patient showed complete atrioventricular block, left ventricular and septal hypertrophy, and concomitant ocular toxicity.

After patients stopped antimalarials, the hypertrophy regressed and heart biomarkers decreased in seven patients, but one patient died from refractory heart failure.

Based on their findings, the authors proposed that heart-specific biomarkers be used as a regular screening tool for detecting myocardial injury, followed by more thorough investigations, such as cardiac MRI, in patients with positive biomarker findings.

“However, drug cessation should be prompt and probably upon suspicion of AMIC, because complete investigation may be delayed significantly.”

One author was supported by the Geoff Carr Fellowship from Lupus Ontario. The University of Toronto Lupus Research Program is supported by the University Health Network, Lou and Marissa Rocca, and the Lupus Foundation of Ontario.

SOURCE: Tselios K et al. J Rheumatol, 2018 Oct 15. doi: 10.3899/jrheum.180124.

Cardiomyopathy induced by antimalarial treatment for systematic lupus erythematosus may not be as rare as previously thought, according to the authors of a case series published Oct. 15 in The Journal of Rheumatology.

The paper describes eight patients attending a lupus clinic, who were diagnosed with definite or possible antimalarial-induced cardiomyopathy over the course of 2 years.

Konstantinos Tselios, MD, PhD, a clinical research fellow at the University of Toronto Lupus Clinic, and his coauthors wrote that antimalarial-induced cardiomyopathy was thought to be relatively rare, with only 47 previous isolated reports, but they suggested the complication may be significantly underrecognized.

“Hypertrophic cardiomyopathy and heart failure, the most common clinical features of AM-induced cardiomyopathy (AMIC), may be falsely attributed to other causes, such as arterial hypertension or ischemic cardiomyopathy,” the authors wrote. “Consequently, nonspecific therapeutic approaches with diuretics and/or antihypertensives will exert minimum or even deleterious effects on such patients.”

All eight patients in this series were female, with a median age of 62.5 years, median disease duration of 35 years, and median antimalarial use of 22 years. They presented with conditions such as heart failure, exertional dyspnea, and pedal edema. Several patients were asymptomatic but had been found to have elevated heart biomarker levels that prompted further investigation.


All patients showed abnormal cardiac troponin I and brain natriuretic peptide levels, and seven of the eight also had chronically elevated creatine phosphokinase.

In three patients, endomyocardial biopsy showed cardiomyocyte vacuolation, intracytoplasmic myelinoid inclusions, and curvilinear bodies.

Four patients were diagnosed based on cardiac MRI, which showed features suggestive of antimalarial-induced cardiomyopathy, including ventricular hypertrophy with or without atrial enlargement and late gadolinium enhancement in a nonvascular pattern.

All patients had left ventricular hypertrophy, and four also had right ventricular hypertrophy. Only one patient showed impaired systolic function, compared with around half of patients in the literature with antimalarial-induced cardiomyopathy, but seven patients showed a restrictive filling pattern of the left ventricle.

“It seems possible that AMIC is a chronic process and systolic dysfunction will become apparent only in late stages,” the authors suggested.

One patient showed complete atrioventricular block, left ventricular and septal hypertrophy, and concomitant ocular toxicity.

After patients stopped antimalarials, the hypertrophy regressed and heart biomarkers decreased in seven patients, but one patient died from refractory heart failure.

Based on their findings, the authors proposed that heart-specific biomarkers be used as a regular screening tool for detecting myocardial injury, followed by more thorough investigations, such as cardiac MRI, in patients with positive biomarker findings.

“However, drug cessation should be prompt and probably upon suspicion of AMIC, because complete investigation may be delayed significantly.”

One author was supported by the Geoff Carr Fellowship from Lupus Ontario. The University of Toronto Lupus Research Program is supported by the University Health Network, Lou and Marissa Rocca, and the Lupus Foundation of Ontario.

SOURCE: Tselios K et al. J Rheumatol, 2018 Oct 15. doi: 10.3899/jrheum.180124.

Concomitant use of glucocorticoids with tofacitinib in rheumatoid arthritis may double the risk of herpes zoster, but methotrexate does not appear to increase the risk, outcomes from a cohort study of 8,030 rheumatoid arthritis patients – including 222 cases of herpes zoster – suggest.

Courtesy UAB Photo

Using information from Medicare and MarketScan, researchers found that dual therapy with tofacitinib and glucocorticoids was associated with a 96% increase in the risk of herpes zoster, compared with monotherapy with the Janus kinase inhibitor tofacitinib (95% confidence interval, 33%-188%). The crude incidence rate in those taking concomitant tofacitinib and glucocorticoids was 6 cases per 100 patient-years, compared with an incidence rate of 3.4 cases per 100 patient-years with tofacitinib monotherapy.

However, the addition of methotrexate therapy to tofacitinib was not associated with an increased risk of herpes zoster, and the incidence rate in patients on this dual therapy was 3.7 cases per 100 patient-years, Jeffrey R. Curtis, MD, MS, MPH, of the University of Alabama at Birmingham and his coauthors reported in Arthritis Care & Research.

Women – who constituted 80% of the study population – showed a significantly increased risk of herpes zoster, as did older patients.

The study also found that individuals who had received the live herpes zoster vaccine showed a trend toward a decrease in risk.

“We saw a strong trend for decreased risk related to vaccination with the live agent (Zostavax); the concern with this form of vaccination is that any live vaccination is potentially dangerous in patients receiving potent immunosuppression,” Dr. Curtis and his associates wrote.

“The risks for disease flare, and potentially problematic tolerability related to a relatively high incidence of grade 3 (severe) systemic reactogenicity, may limit enthusiasm until specific data in an RA population is available,” they wrote. However, they noted that a randomized, controlled trial of the live virus vaccine was underway in patients with rheumatoid arthritis who were being treated with tumor necrosis factor inhibitors and suggested that vaccination should be considered in at-risk patients who didn’t have contraindications.

The authors noted that the effect of glucocorticoid exposure on herpes zoster risk in patients taking tofacitinib was similar to that seen in rheumatoid arthritis patients receiving conventional synthetic disease-modifying antirheumatic drugs or biologic therapies.

The study was partly funded by the Patient-Centered Outcomes Research Institute. Two authors declared research grants and other funding from the pharmaceutical industry, but no other conflicts of interest were declared.

SOURCE: Curtis J et al. Arthritis Care Res. 2018 Oct 8. doi: 10.1002/acr.23769.

Concomitant use of glucocorticoids with tofacitinib in rheumatoid arthritis may double the risk of herpes zoster, but methotrexate does not appear to increase the risk, outcomes from a cohort study of 8,030 rheumatoid arthritis patients – including 222 cases of herpes zoster – suggest.

Courtesy UAB Photo

Using information from Medicare and MarketScan, researchers found that dual therapy with tofacitinib and glucocorticoids was associated with a 96% increase in the risk of herpes zoster, compared with monotherapy with the Janus kinase inhibitor tofacitinib (95% confidence interval, 33%-188%). The crude incidence rate in those taking concomitant tofacitinib and glucocorticoids was 6 cases per 100 patient-years, compared with an incidence rate of 3.4 cases per 100 patient-years with tofacitinib monotherapy.

However, the addition of methotrexate therapy to tofacitinib was not associated with an increased risk of herpes zoster, and the incidence rate in patients on this dual therapy was 3.7 cases per 100 patient-years, Jeffrey R. Curtis, MD, MS, MPH, of the University of Alabama at Birmingham and his coauthors reported in Arthritis Care & Research.

Women – who constituted 80% of the study population – showed a significantly increased risk of herpes zoster, as did older patients.

The study also found that individuals who had received the live herpes zoster vaccine showed a trend toward a decrease in risk.

“We saw a strong trend for decreased risk related to vaccination with the live agent (Zostavax); the concern with this form of vaccination is that any live vaccination is potentially dangerous in patients receiving potent immunosuppression,” Dr. Curtis and his associates wrote.

“The risks for disease flare, and potentially problematic tolerability related to a relatively high incidence of grade 3 (severe) systemic reactogenicity, may limit enthusiasm until specific data in an RA population is available,” they wrote. However, they noted that a randomized, controlled trial of the live virus vaccine was underway in patients with rheumatoid arthritis who were being treated with tumor necrosis factor inhibitors and suggested that vaccination should be considered in at-risk patients who didn’t have contraindications.

The authors noted that the effect of glucocorticoid exposure on herpes zoster risk in patients taking tofacitinib was similar to that seen in rheumatoid arthritis patients receiving conventional synthetic disease-modifying antirheumatic drugs or biologic therapies.

The study was partly funded by the Patient-Centered Outcomes Research Institute. Two authors declared research grants and other funding from the pharmaceutical industry, but no other conflicts of interest were declared.

SOURCE: Curtis J et al. Arthritis Care Res. 2018 Oct 8. doi: 10.1002/acr.23769.

Concomitant use of glucocorticoids with tofacitinib in rheumatoid arthritis may double the risk of herpes zoster, but methotrexate does not appear to increase the risk, outcomes from a cohort study of 8,030 rheumatoid arthritis patients – including 222 cases of herpes zoster – suggest.

Courtesy UAB Photo

Using information from Medicare and MarketScan, researchers found that dual therapy with tofacitinib and glucocorticoids was associated with a 96% increase in the risk of herpes zoster, compared with monotherapy with the Janus kinase inhibitor tofacitinib (95% confidence interval, 33%-188%). The crude incidence rate in those taking concomitant tofacitinib and glucocorticoids was 6 cases per 100 patient-years, compared with an incidence rate of 3.4 cases per 100 patient-years with tofacitinib monotherapy.

However, the addition of methotrexate therapy to tofacitinib was not associated with an increased risk of herpes zoster, and the incidence rate in patients on this dual therapy was 3.7 cases per 100 patient-years, Jeffrey R. Curtis, MD, MS, MPH, of the University of Alabama at Birmingham and his coauthors reported in Arthritis Care & Research.

Women – who constituted 80% of the study population – showed a significantly increased risk of herpes zoster, as did older patients.

The study also found that individuals who had received the live herpes zoster vaccine showed a trend toward a decrease in risk.

“We saw a strong trend for decreased risk related to vaccination with the live agent (Zostavax); the concern with this form of vaccination is that any live vaccination is potentially dangerous in patients receiving potent immunosuppression,” Dr. Curtis and his associates wrote.

“The risks for disease flare, and potentially problematic tolerability related to a relatively high incidence of grade 3 (severe) systemic reactogenicity, may limit enthusiasm until specific data in an RA population is available,” they wrote. However, they noted that a randomized, controlled trial of the live virus vaccine was underway in patients with rheumatoid arthritis who were being treated with tumor necrosis factor inhibitors and suggested that vaccination should be considered in at-risk patients who didn’t have contraindications.

The authors noted that the effect of glucocorticoid exposure on herpes zoster risk in patients taking tofacitinib was similar to that seen in rheumatoid arthritis patients receiving conventional synthetic disease-modifying antirheumatic drugs or biologic therapies.

The study was partly funded by the Patient-Centered Outcomes Research Institute. Two authors declared research grants and other funding from the pharmaceutical industry, but no other conflicts of interest were declared.

SOURCE: Curtis J et al. Arthritis Care Res. 2018 Oct 8. doi: 10.1002/acr.23769.

The high price of chimeric antigen receptor (CAR) T-cell therapy for pediatric leukemia may prove cost effective if long-term survival benefits are realized, researchers reported.

utah778/Thinkstock

A cost-effectiveness analysis of the CAR T-cell therapy tisagenlecleucel suggests that the $475,000 price tag is in alignment with the lifetime benefits of the treatment. The findings were published in JAMA Pediatrics.

Tisagenlecleucel – marketed as Kymriah – is a one-dose treatment for relapsed or refractory pediatric B-cell acute lymphoblastic leukemia (ALL) and the first CAR T-cell therapy approved by the Food and Drug Administration.

In this cost-effectiveness analysis, researchers used a decision analytic model that extrapolated the evidence from clinical trials over a patient’s lifetime to assess life-years gained, quality-adjusted life-years (QALYs) gained, and incremental costs per life-year and QALY gained. The comparator was the chemoimmunotherapeutic agent clofarabine.

While tisagenlecleucel has a list price of $475,000, researchers discounted the price by 3% and added several additional costs, such as hospital administration, pretreatment, and potential adverse events, to get to a total discounted cost of about $667,000. They estimated that 42.6% of patients were considered to be long-term survivors with tisagenlecleucel, 10.34 life-years would be gained, and 9.28 QALYs would be gained.

In comparison, clofarabine had a total discounted cost of approximately $337,000 (including an initial discounted price of $164,000 plus additional treatment and administrative costs), 10.8% of patients were long-term survivors, 2.43 life-years were gained, and 2.10 QALYs were gained in the model.

Overall, the mean incremental cost-effectiveness ratio was about $46,000 per QALY gained in this base-case model.

In analyses of different scenarios, such as a deeper discount, a different treatment start, or a different calculation of future treatment costs, the cost-effectiveness ratio varied from $37,000 to $78,000 per QALY gained.

“We acknowledge that considerable uncertainty remains around the long-term benefit of tisagenlecleucel owing to limited available evidence; however, with current evidence and assumptions, tisagenlecleucel meets commonly cited value thresholds over a patient lifetime horizon, assuming payment for treatment acquisition for responders at 1 month,” wrote Melanie D. Whittington, PhD, from the University of Colorado at Denver, Aurora, and her colleagues.

The authors noted that the clinical trial evidence for tisagenlecleucel came from single-arm trials, which made selection of a comparator challenging. Clofarabine was chosen because it had the most similar baseline population characteristics, but they acknowledged that blinatumomab was also frequently used as a treatment for these patients.

“We suspect that tisagenlecleucel would remain cost effective, compared with blinatumomab,” they wrote. “A study conducted by other researchers found the incremental cost-effectiveness ratio of tisagenlecleucel versus blinatumomab was similar to the incremental cost-effectiveness ratio of tisagenlecleucel versus clofarabine [i.e., $3,000 more per QALY].”

The authors suggested that uncertainties in the evidence should be considered as payers are negotiating coverage and payment for tisagenlecleucel.

“Novel payment models consistent with the present evidence may reduce the risk and uncertainty in long-term value and be more closely aligned with ensuring high-value care,” they wrote. “Financing cures in the United States is challenging, owing to the high up-front price, rapid uptake, and uncertainty in long-term outcomes; however, innovative payment models are an opportunity to address some of these challenges and to promote patient access to novel and promising therapies.”

The study was funded by the Institute for Clinical and Economic Review, which receives some funding from the pharmaceutical industry. Four authors are employees of the Institute for Clinical and Economic Review.

SOURCE: Whittington MD et al. JAMA Pediatr. 2018 Oct 8. doi: 10.1001/jamapediatrics.2018.2530.

The high price of chimeric antigen receptor (CAR) T-cell therapy for pediatric leukemia may prove cost effective if long-term survival benefits are realized, researchers reported.

utah778/Thinkstock

A cost-effectiveness analysis of the CAR T-cell therapy tisagenlecleucel suggests that the $475,000 price tag is in alignment with the lifetime benefits of the treatment. The findings were published in JAMA Pediatrics.

Tisagenlecleucel – marketed as Kymriah – is a one-dose treatment for relapsed or refractory pediatric B-cell acute lymphoblastic leukemia (ALL) and the first CAR T-cell therapy approved by the Food and Drug Administration.

In this cost-effectiveness analysis, researchers used a decision analytic model that extrapolated the evidence from clinical trials over a patient’s lifetime to assess life-years gained, quality-adjusted life-years (QALYs) gained, and incremental costs per life-year and QALY gained. The comparator was the chemoimmunotherapeutic agent clofarabine.

While tisagenlecleucel has a list price of $475,000, researchers discounted the price by 3% and added several additional costs, such as hospital administration, pretreatment, and potential adverse events, to get to a total discounted cost of about $667,000. They estimated that 42.6% of patients were considered to be long-term survivors with tisagenlecleucel, 10.34 life-years would be gained, and 9.28 QALYs would be gained.

In comparison, clofarabine had a total discounted cost of approximately $337,000 (including an initial discounted price of $164,000 plus additional treatment and administrative costs), 10.8% of patients were long-term survivors, 2.43 life-years were gained, and 2.10 QALYs were gained in the model.

Overall, the mean incremental cost-effectiveness ratio was about $46,000 per QALY gained in this base-case model.

In analyses of different scenarios, such as a deeper discount, a different treatment start, or a different calculation of future treatment costs, the cost-effectiveness ratio varied from $37,000 to $78,000 per QALY gained.

“We acknowledge that considerable uncertainty remains around the long-term benefit of tisagenlecleucel owing to limited available evidence; however, with current evidence and assumptions, tisagenlecleucel meets commonly cited value thresholds over a patient lifetime horizon, assuming payment for treatment acquisition for responders at 1 month,” wrote Melanie D. Whittington, PhD, from the University of Colorado at Denver, Aurora, and her colleagues.

The authors noted that the clinical trial evidence for tisagenlecleucel came from single-arm trials, which made selection of a comparator challenging. Clofarabine was chosen because it had the most similar baseline population characteristics, but they acknowledged that blinatumomab was also frequently used as a treatment for these patients.

“We suspect that tisagenlecleucel would remain cost effective, compared with blinatumomab,” they wrote. “A study conducted by other researchers found the incremental cost-effectiveness ratio of tisagenlecleucel versus blinatumomab was similar to the incremental cost-effectiveness ratio of tisagenlecleucel versus clofarabine [i.e., $3,000 more per QALY].”

The authors suggested that uncertainties in the evidence should be considered as payers are negotiating coverage and payment for tisagenlecleucel.

“Novel payment models consistent with the present evidence may reduce the risk and uncertainty in long-term value and be more closely aligned with ensuring high-value care,” they wrote. “Financing cures in the United States is challenging, owing to the high up-front price, rapid uptake, and uncertainty in long-term outcomes; however, innovative payment models are an opportunity to address some of these challenges and to promote patient access to novel and promising therapies.”

The study was funded by the Institute for Clinical and Economic Review, which receives some funding from the pharmaceutical industry. Four authors are employees of the Institute for Clinical and Economic Review.

SOURCE: Whittington MD et al. JAMA Pediatr. 2018 Oct 8. doi: 10.1001/jamapediatrics.2018.2530.

The high price of chimeric antigen receptor (CAR) T-cell therapy for pediatric leukemia may prove cost effective if long-term survival benefits are realized, researchers reported.

utah778/Thinkstock

A cost-effectiveness analysis of the CAR T-cell therapy tisagenlecleucel suggests that the $475,000 price tag is in alignment with the lifetime benefits of the treatment. The findings were published in JAMA Pediatrics.

Tisagenlecleucel – marketed as Kymriah – is a one-dose treatment for relapsed or refractory pediatric B-cell acute lymphoblastic leukemia (ALL) and the first CAR T-cell therapy approved by the Food and Drug Administration.

In this cost-effectiveness analysis, researchers used a decision analytic model that extrapolated the evidence from clinical trials over a patient’s lifetime to assess life-years gained, quality-adjusted life-years (QALYs) gained, and incremental costs per life-year and QALY gained. The comparator was the chemoimmunotherapeutic agent clofarabine.

While tisagenlecleucel has a list price of $475,000, researchers discounted the price by 3% and added several additional costs, such as hospital administration, pretreatment, and potential adverse events, to get to a total discounted cost of about $667,000. They estimated that 42.6% of patients were considered to be long-term survivors with tisagenlecleucel, 10.34 life-years would be gained, and 9.28 QALYs would be gained.

In comparison, clofarabine had a total discounted cost of approximately $337,000 (including an initial discounted price of $164,000 plus additional treatment and administrative costs), 10.8% of patients were long-term survivors, 2.43 life-years were gained, and 2.10 QALYs were gained in the model.

Overall, the mean incremental cost-effectiveness ratio was about $46,000 per QALY gained in this base-case model.

In analyses of different scenarios, such as a deeper discount, a different treatment start, or a different calculation of future treatment costs, the cost-effectiveness ratio varied from $37,000 to $78,000 per QALY gained.

“We acknowledge that considerable uncertainty remains around the long-term benefit of tisagenlecleucel owing to limited available evidence; however, with current evidence and assumptions, tisagenlecleucel meets commonly cited value thresholds over a patient lifetime horizon, assuming payment for treatment acquisition for responders at 1 month,” wrote Melanie D. Whittington, PhD, from the University of Colorado at Denver, Aurora, and her colleagues.

The authors noted that the clinical trial evidence for tisagenlecleucel came from single-arm trials, which made selection of a comparator challenging. Clofarabine was chosen because it had the most similar baseline population characteristics, but they acknowledged that blinatumomab was also frequently used as a treatment for these patients.

“We suspect that tisagenlecleucel would remain cost effective, compared with blinatumomab,” they wrote. “A study conducted by other researchers found the incremental cost-effectiveness ratio of tisagenlecleucel versus blinatumomab was similar to the incremental cost-effectiveness ratio of tisagenlecleucel versus clofarabine [i.e., $3,000 more per QALY].”

The authors suggested that uncertainties in the evidence should be considered as payers are negotiating coverage and payment for tisagenlecleucel.

“Novel payment models consistent with the present evidence may reduce the risk and uncertainty in long-term value and be more closely aligned with ensuring high-value care,” they wrote. “Financing cures in the United States is challenging, owing to the high up-front price, rapid uptake, and uncertainty in long-term outcomes; however, innovative payment models are an opportunity to address some of these challenges and to promote patient access to novel and promising therapies.”

The study was funded by the Institute for Clinical and Economic Review, which receives some funding from the pharmaceutical industry. Four authors are employees of the Institute for Clinical and Economic Review.

SOURCE: Whittington MD et al. JAMA Pediatr. 2018 Oct 8. doi: 10.1001/jamapediatrics.2018.2530.

There is little justification for the use of vitamin D supplementation for the prevention of fractures or falls or for increasing bone density, according to the authors of a meta-analysis that found no benefits from supplementation.

copyright istock/Thinkstock

A systematic review and meta-analysis, published in the Oct. 4 edition of Lancet Diabetes & Endocrinology, examined 81 randomized controlled trials – involving 53,537 participants – of the effects of vitamin D supplementation on fractures, falls, or bone mineral density.

In the pooled analyses, researchers found that vitamin D supplementation did not reduce total fracture, hip fracture, or falls, even in trials in which participants took doses greater than 800 IU/day. Their results were similar when researchers compared high doses and low doses in their trials.

Similarly, vitamin D supplementation was not associated with any clinically relevant improvements in bone mineral density at any site; lumbar spine, total hip, femoral neck, forearm, or total body.

Even a post hoc analysis of randomized, controlled trials that compared daily high doses with daily low doses, as well as trials that compared intermittent high doses with intermittent low doses found no significant interactions for any outcome.

The paper also explored whether baseline vitamin D levels might influence outcomes. Eighteen trials in the analysis reported the results of subgroup analyses using baseline serum 25-hydroxyvitamin D (25[OH]D); three found no effects of vitamin D supplements in different subgroups of baseline, five studies found no effects of subgroups or interaction with baseline serum 25[OH]D, and one found mixed effects with respect to falls.

The outcomes for bone mineral density, as related to baseline serum 25[OH]D, were slightly more mixed. One trial found a positive effect of vitamin D supplements a bone mineral density for different subgroups of baseline serum, five trials reported mixed effects, and eight trials found no effects.

“The strengths of the current analyses are that they are comprehensive, include all available data from a large number of new trials, and concomitantly assess the major clinical and surrogate endpoints for musculoskeletal health,” wrote Mark J. Bolland, MD, of the department of medicine at the University of Auckland (New Zealand), and his coauthors. “Therefore, there is little justification for the use of vitamin D supplements to maintain or improve musculoskeletal health, and clinical guidelines should reflect these findings.”

They also conducted trial sequential analyses, which is a type of cumulative meta-analysis. For each outcome, they set a relative risk reduction threshold, then progressively reduced that threshold until the optimum sample size for that threshold exceeded the actual sample size.

“The trial sequential analyses are important because they provide estimates about the reliability of current evidence and the likelihood of future trials to change current conclusions,” the authors wrote.

Using this approach, they once again found clear evidence that vitamin D supplementation did not reduce fractures or falls for any measure of relative risk reduction. For hip fracture, the trial sequential analysis even found some uncertainty as to whether vitamin D supplementation might increase the risk of hip fractures.

Given the results of the trial sequential analyses, the authors argued that further similar trials were unlikely to alter their conclusion.

“If a large future trial has markedly different results to the current trials, adding its results will substantially increase the heterogeneity of the trial results, which in turn will reduce the weighting the new large trial receives in the pooled analyses,” they wrote. “Thus, adding a positive result from a large randomized, controlled trial will have only a small effect on the pooled result and is unlikely to alter the conclusions of these meta-analyses.”

They also noted that some of the studies had methodological limitations, and smaller studies of shorter duration tended to have “inflated” effect sizes, such that “the results of small, short-duration studies should be interpreted very cautiously, since they might not be replicated in larger, longer studies.”

The study was funded by the Health Research Council of New Zealand. Two authors declared grants from the Health Research Council during the study, one author is a shareholder in a company that provides bone mineral density measurements, and one reported grants from the Scottish Government Health and Social Care Directorates during the study.

SOURCE: Bolland M et al. Lancet Diabetes Endocrinol. 2018 Oct 4. doi. org/10.1016/S2213-8587(18)30265-1.


 

There is little justification for the use of vitamin D supplementation for the prevention of fractures or falls or for increasing bone density, according to the authors of a meta-analysis that found no benefits from supplementation.

copyright istock/Thinkstock

A systematic review and meta-analysis, published in the Oct. 4 edition of Lancet Diabetes & Endocrinology, examined 81 randomized controlled trials – involving 53,537 participants – of the effects of vitamin D supplementation on fractures, falls, or bone mineral density.

In the pooled analyses, researchers found that vitamin D supplementation did not reduce total fracture, hip fracture, or falls, even in trials in which participants took doses greater than 800 IU/day. Their results were similar when researchers compared high doses and low doses in their trials.

Similarly, vitamin D supplementation was not associated with any clinically relevant improvements in bone mineral density at any site; lumbar spine, total hip, femoral neck, forearm, or total body.

Even a post hoc analysis of randomized, controlled trials that compared daily high doses with daily low doses, as well as trials that compared intermittent high doses with intermittent low doses found no significant interactions for any outcome.

The paper also explored whether baseline vitamin D levels might influence outcomes. Eighteen trials in the analysis reported the results of subgroup analyses using baseline serum 25-hydroxyvitamin D (25[OH]D); three found no effects of vitamin D supplements in different subgroups of baseline, five studies found no effects of subgroups or interaction with baseline serum 25[OH]D, and one found mixed effects with respect to falls.

The outcomes for bone mineral density, as related to baseline serum 25[OH]D, were slightly more mixed. One trial found a positive effect of vitamin D supplements a bone mineral density for different subgroups of baseline serum, five trials reported mixed effects, and eight trials found no effects.

“The strengths of the current analyses are that they are comprehensive, include all available data from a large number of new trials, and concomitantly assess the major clinical and surrogate endpoints for musculoskeletal health,” wrote Mark J. Bolland, MD, of the department of medicine at the University of Auckland (New Zealand), and his coauthors. “Therefore, there is little justification for the use of vitamin D supplements to maintain or improve musculoskeletal health, and clinical guidelines should reflect these findings.”

They also conducted trial sequential analyses, which is a type of cumulative meta-analysis. For each outcome, they set a relative risk reduction threshold, then progressively reduced that threshold until the optimum sample size for that threshold exceeded the actual sample size.

“The trial sequential analyses are important because they provide estimates about the reliability of current evidence and the likelihood of future trials to change current conclusions,” the authors wrote.

Using this approach, they once again found clear evidence that vitamin D supplementation did not reduce fractures or falls for any measure of relative risk reduction. For hip fracture, the trial sequential analysis even found some uncertainty as to whether vitamin D supplementation might increase the risk of hip fractures.

Given the results of the trial sequential analyses, the authors argued that further similar trials were unlikely to alter their conclusion.

“If a large future trial has markedly different results to the current trials, adding its results will substantially increase the heterogeneity of the trial results, which in turn will reduce the weighting the new large trial receives in the pooled analyses,” they wrote. “Thus, adding a positive result from a large randomized, controlled trial will have only a small effect on the pooled result and is unlikely to alter the conclusions of these meta-analyses.”

They also noted that some of the studies had methodological limitations, and smaller studies of shorter duration tended to have “inflated” effect sizes, such that “the results of small, short-duration studies should be interpreted very cautiously, since they might not be replicated in larger, longer studies.”

The study was funded by the Health Research Council of New Zealand. Two authors declared grants from the Health Research Council during the study, one author is a shareholder in a company that provides bone mineral density measurements, and one reported grants from the Scottish Government Health and Social Care Directorates during the study.

SOURCE: Bolland M et al. Lancet Diabetes Endocrinol. 2018 Oct 4. doi. org/10.1016/S2213-8587(18)30265-1.


 

There is little justification for the use of vitamin D supplementation for the prevention of fractures or falls or for increasing bone density, according to the authors of a meta-analysis that found no benefits from supplementation.

copyright istock/Thinkstock

A systematic review and meta-analysis, published in the Oct. 4 edition of Lancet Diabetes & Endocrinology, examined 81 randomized controlled trials – involving 53,537 participants – of the effects of vitamin D supplementation on fractures, falls, or bone mineral density.

In the pooled analyses, researchers found that vitamin D supplementation did not reduce total fracture, hip fracture, or falls, even in trials in which participants took doses greater than 800 IU/day. Their results were similar when researchers compared high doses and low doses in their trials.

Similarly, vitamin D supplementation was not associated with any clinically relevant improvements in bone mineral density at any site; lumbar spine, total hip, femoral neck, forearm, or total body.

Even a post hoc analysis of randomized, controlled trials that compared daily high doses with daily low doses, as well as trials that compared intermittent high doses with intermittent low doses found no significant interactions for any outcome.

The paper also explored whether baseline vitamin D levels might influence outcomes. Eighteen trials in the analysis reported the results of subgroup analyses using baseline serum 25-hydroxyvitamin D (25[OH]D); three found no effects of vitamin D supplements in different subgroups of baseline, five studies found no effects of subgroups or interaction with baseline serum 25[OH]D, and one found mixed effects with respect to falls.

The outcomes for bone mineral density, as related to baseline serum 25[OH]D, were slightly more mixed. One trial found a positive effect of vitamin D supplements a bone mineral density for different subgroups of baseline serum, five trials reported mixed effects, and eight trials found no effects.

“The strengths of the current analyses are that they are comprehensive, include all available data from a large number of new trials, and concomitantly assess the major clinical and surrogate endpoints for musculoskeletal health,” wrote Mark J. Bolland, MD, of the department of medicine at the University of Auckland (New Zealand), and his coauthors. “Therefore, there is little justification for the use of vitamin D supplements to maintain or improve musculoskeletal health, and clinical guidelines should reflect these findings.”

They also conducted trial sequential analyses, which is a type of cumulative meta-analysis. For each outcome, they set a relative risk reduction threshold, then progressively reduced that threshold until the optimum sample size for that threshold exceeded the actual sample size.

“The trial sequential analyses are important because they provide estimates about the reliability of current evidence and the likelihood of future trials to change current conclusions,” the authors wrote.

Using this approach, they once again found clear evidence that vitamin D supplementation did not reduce fractures or falls for any measure of relative risk reduction. For hip fracture, the trial sequential analysis even found some uncertainty as to whether vitamin D supplementation might increase the risk of hip fractures.

Given the results of the trial sequential analyses, the authors argued that further similar trials were unlikely to alter their conclusion.

“If a large future trial has markedly different results to the current trials, adding its results will substantially increase the heterogeneity of the trial results, which in turn will reduce the weighting the new large trial receives in the pooled analyses,” they wrote. “Thus, adding a positive result from a large randomized, controlled trial will have only a small effect on the pooled result and is unlikely to alter the conclusions of these meta-analyses.”

They also noted that some of the studies had methodological limitations, and smaller studies of shorter duration tended to have “inflated” effect sizes, such that “the results of small, short-duration studies should be interpreted very cautiously, since they might not be replicated in larger, longer studies.”

The study was funded by the Health Research Council of New Zealand. Two authors declared grants from the Health Research Council during the study, one author is a shareholder in a company that provides bone mineral density measurements, and one reported grants from the Scottish Government Health and Social Care Directorates during the study.

SOURCE: Bolland M et al. Lancet Diabetes Endocrinol. 2018 Oct 4. doi. org/10.1016/S2213-8587(18)30265-1.


 

Patients with pulmonary arterial hypertension as a consequence of systemic lupus erythematosus can be classified into two different subtypes, one of which shows significantly greater mortality, new research suggests.

Systemic lupus erythematosus–associated pulmonary arterial hypertension (SLE-PAH) has a poor prognosis with 3-year mortality ranging from 45% to 88%, leading the first author of the study Fangfang Sun of the School of Medicine at Shanghai (China) Jiaotong University and coauthors to seek “to further differentiate among SLE-PAH patterns to better understand the disease and optimize its management,

In a letter published online in Annals of the Rheumatic Diseases, the researchers presented data from a retrospective study of a derivation cohort of 108 Chinese patients with SLE-PAH and a validation cohort of 87 patients. Using clinical and laboratory characteristics, the researchers classified the derivation cohort into two clusters, which they labeled as the vasculitic and vasculopathic subtypes.

Patients with the vasculitic subtype of SLE-PAH had higher levels of SLE disease activity and manifestations, such as pericarditis, rash, arthritis, nephritis, and neuropsychiatric lupus, while those with the vasculopathic subtype showed “purer” PAH and lower lupus disease activity.

The researchers found that the vasculitic subtype had around a threefold higher 3-year mortality than did the vasculopathic subtype (34.5%-40.2% vs. 13.0%-18.6%; hazard ratio, 2.84-3.15; P less than .05), even after adjusting for differences in treatments.

Patients who developed PAH less than 2 years after being diagnosed with SLE were significantly more likely to have the vasculitic subtype of SLE-PAH (P less than .0001). A SLE disease activity index score greater than nine was also significantly associated with the vasculitic subtype (P = .001).

The prediction model developed based on these two factors had a sensitivity of 98.5% and a specificity of 74.4% (area under the curve = 0.94; P less than .0001), for a weighted score of two or more, in identifying patients with the vasculitic subtype of SLE-PAH.

Dr. Sun and colleagues suggested that the existence of two distinct clinical subtypes of SLE-PAH points to different underlying pathophysiologic mechanisms; one that is autoimmune mediated and one that involves noninflammatory vascular remodeling. However, the authors stressed that their findings needed confirmation in prospective studies.

“The next key question that remains unanswered is how to balance the utility of immunosuppressants and PAH-targeted drugs in patients with different phenotypes,” they wrote.

Two authors declared research funding from academic and government agencies. No conflicts of interest were declared.

SOURCE: Sun F et al. Ann Rheum Dis. 2018 Sep 19. doi: 10.1136/annrheumdis-2018-214197.

Patients with pulmonary arterial hypertension as a consequence of systemic lupus erythematosus can be classified into two different subtypes, one of which shows significantly greater mortality, new research suggests.

Systemic lupus erythematosus–associated pulmonary arterial hypertension (SLE-PAH) has a poor prognosis with 3-year mortality ranging from 45% to 88%, leading the first author of the study Fangfang Sun of the School of Medicine at Shanghai (China) Jiaotong University and coauthors to seek “to further differentiate among SLE-PAH patterns to better understand the disease and optimize its management,

In a letter published online in Annals of the Rheumatic Diseases, the researchers presented data from a retrospective study of a derivation cohort of 108 Chinese patients with SLE-PAH and a validation cohort of 87 patients. Using clinical and laboratory characteristics, the researchers classified the derivation cohort into two clusters, which they labeled as the vasculitic and vasculopathic subtypes.

Patients with the vasculitic subtype of SLE-PAH had higher levels of SLE disease activity and manifestations, such as pericarditis, rash, arthritis, nephritis, and neuropsychiatric lupus, while those with the vasculopathic subtype showed “purer” PAH and lower lupus disease activity.

The researchers found that the vasculitic subtype had around a threefold higher 3-year mortality than did the vasculopathic subtype (34.5%-40.2% vs. 13.0%-18.6%; hazard ratio, 2.84-3.15; P less than .05), even after adjusting for differences in treatments.

Patients who developed PAH less than 2 years after being diagnosed with SLE were significantly more likely to have the vasculitic subtype of SLE-PAH (P less than .0001). A SLE disease activity index score greater than nine was also significantly associated with the vasculitic subtype (P = .001).

The prediction model developed based on these two factors had a sensitivity of 98.5% and a specificity of 74.4% (area under the curve = 0.94; P less than .0001), for a weighted score of two or more, in identifying patients with the vasculitic subtype of SLE-PAH.

Dr. Sun and colleagues suggested that the existence of two distinct clinical subtypes of SLE-PAH points to different underlying pathophysiologic mechanisms; one that is autoimmune mediated and one that involves noninflammatory vascular remodeling. However, the authors stressed that their findings needed confirmation in prospective studies.

“The next key question that remains unanswered is how to balance the utility of immunosuppressants and PAH-targeted drugs in patients with different phenotypes,” they wrote.

Two authors declared research funding from academic and government agencies. No conflicts of interest were declared.

SOURCE: Sun F et al. Ann Rheum Dis. 2018 Sep 19. doi: 10.1136/annrheumdis-2018-214197.

Patients with pulmonary arterial hypertension as a consequence of systemic lupus erythematosus can be classified into two different subtypes, one of which shows significantly greater mortality, new research suggests.

Systemic lupus erythematosus–associated pulmonary arterial hypertension (SLE-PAH) has a poor prognosis with 3-year mortality ranging from 45% to 88%, leading the first author of the study Fangfang Sun of the School of Medicine at Shanghai (China) Jiaotong University and coauthors to seek “to further differentiate among SLE-PAH patterns to better understand the disease and optimize its management,

In a letter published online in Annals of the Rheumatic Diseases, the researchers presented data from a retrospective study of a derivation cohort of 108 Chinese patients with SLE-PAH and a validation cohort of 87 patients. Using clinical and laboratory characteristics, the researchers classified the derivation cohort into two clusters, which they labeled as the vasculitic and vasculopathic subtypes.

Patients with the vasculitic subtype of SLE-PAH had higher levels of SLE disease activity and manifestations, such as pericarditis, rash, arthritis, nephritis, and neuropsychiatric lupus, while those with the vasculopathic subtype showed “purer” PAH and lower lupus disease activity.

The researchers found that the vasculitic subtype had around a threefold higher 3-year mortality than did the vasculopathic subtype (34.5%-40.2% vs. 13.0%-18.6%; hazard ratio, 2.84-3.15; P less than .05), even after adjusting for differences in treatments.

Patients who developed PAH less than 2 years after being diagnosed with SLE were significantly more likely to have the vasculitic subtype of SLE-PAH (P less than .0001). A SLE disease activity index score greater than nine was also significantly associated with the vasculitic subtype (P = .001).

The prediction model developed based on these two factors had a sensitivity of 98.5% and a specificity of 74.4% (area under the curve = 0.94; P less than .0001), for a weighted score of two or more, in identifying patients with the vasculitic subtype of SLE-PAH.

Dr. Sun and colleagues suggested that the existence of two distinct clinical subtypes of SLE-PAH points to different underlying pathophysiologic mechanisms; one that is autoimmune mediated and one that involves noninflammatory vascular remodeling. However, the authors stressed that their findings needed confirmation in prospective studies.

“The next key question that remains unanswered is how to balance the utility of immunosuppressants and PAH-targeted drugs in patients with different phenotypes,” they wrote.

Two authors declared research funding from academic and government agencies. No conflicts of interest were declared.

SOURCE: Sun F et al. Ann Rheum Dis. 2018 Sep 19. doi: 10.1136/annrheumdis-2018-214197.

Sexual harassment and assault may have significant health impacts on women in midlife, including greater risk of hypertension, poor sleep, depression, and anxiety, research suggests.

thodonal/Thinkstock

In the Oct. 3 online edition of JAMA Internal Medicine, a study of 304 women aged 40-60 years showed that 19% reported a history of workplace sexual harassment, 22% reported a history of sexual assault, and 10% reported both. The report was presented simultaneously at the North American Menopause Society annual meeting in San Diego.

The researchers found that those with a history of sexual assault had an almost threefold higher odds of clinically elevated depressive symptoms (OR, 2.86, P = .003), and more than twofold greater odds of anxiety and poor sleep (OR, 2.26, P = .006 and OR, 2.15, P = .007 respectively).

Women who reported experiencing sexual harassment in the workplace – and who were not taking antihypertensive medication – were more than twice as likely to have stage 1 or 2 hypertension, compared with women who had not experienced sexual harassment (OR, 2.36, P = .03). They also had 89% higher odds of poor sleep consistent with clinical insomnia (P = .03).

These associations all persisted even after adjustment for demographic and biomedical factors such as age, ethnicity, body mass index, snoring, and the use of antihypertensive, antidepressant, and anti-anxiety medications.

“Given the high prevalence of sexual harassment and assault, addressing these prevalent and potent social exposures may be critical to promoting health and preventing disease in women,” wrote Rebecca C. Thurston, PhD, of the department of psychiatry at the University of Pittsburgh, and her coauthors.

The study was supported by the National Institutes of Health, National Heart Lung and Blood Institute, and the University of Pittsburgh Clinical and Translational Science Institute. Dr. Thurston declared consultancies for MAS Innovations, Procter & Gamble, and Pfizer, but no other conflicts of interest were declared.

SOURCE: Thurston R et al. JAMA Intern Med. 2018, Oct 3. doi: 10.1001/jamainternmed.2018.4886.

Sexual harassment and assault may have significant health impacts on women in midlife, including greater risk of hypertension, poor sleep, depression, and anxiety, research suggests.

thodonal/Thinkstock

In the Oct. 3 online edition of JAMA Internal Medicine, a study of 304 women aged 40-60 years showed that 19% reported a history of workplace sexual harassment, 22% reported a history of sexual assault, and 10% reported both. The report was presented simultaneously at the North American Menopause Society annual meeting in San Diego.

The researchers found that those with a history of sexual assault had an almost threefold higher odds of clinically elevated depressive symptoms (OR, 2.86, P = .003), and more than twofold greater odds of anxiety and poor sleep (OR, 2.26, P = .006 and OR, 2.15, P = .007 respectively).

Women who reported experiencing sexual harassment in the workplace – and who were not taking antihypertensive medication – were more than twice as likely to have stage 1 or 2 hypertension, compared with women who had not experienced sexual harassment (OR, 2.36, P = .03). They also had 89% higher odds of poor sleep consistent with clinical insomnia (P = .03).

These associations all persisted even after adjustment for demographic and biomedical factors such as age, ethnicity, body mass index, snoring, and the use of antihypertensive, antidepressant, and anti-anxiety medications.

“Given the high prevalence of sexual harassment and assault, addressing these prevalent and potent social exposures may be critical to promoting health and preventing disease in women,” wrote Rebecca C. Thurston, PhD, of the department of psychiatry at the University of Pittsburgh, and her coauthors.

The study was supported by the National Institutes of Health, National Heart Lung and Blood Institute, and the University of Pittsburgh Clinical and Translational Science Institute. Dr. Thurston declared consultancies for MAS Innovations, Procter & Gamble, and Pfizer, but no other conflicts of interest were declared.

SOURCE: Thurston R et al. JAMA Intern Med. 2018, Oct 3. doi: 10.1001/jamainternmed.2018.4886.

Sexual harassment and assault may have significant health impacts on women in midlife, including greater risk of hypertension, poor sleep, depression, and anxiety, research suggests.

thodonal/Thinkstock

In the Oct. 3 online edition of JAMA Internal Medicine, a study of 304 women aged 40-60 years showed that 19% reported a history of workplace sexual harassment, 22% reported a history of sexual assault, and 10% reported both. The report was presented simultaneously at the North American Menopause Society annual meeting in San Diego.

The researchers found that those with a history of sexual assault had an almost threefold higher odds of clinically elevated depressive symptoms (OR, 2.86, P = .003), and more than twofold greater odds of anxiety and poor sleep (OR, 2.26, P = .006 and OR, 2.15, P = .007 respectively).

Women who reported experiencing sexual harassment in the workplace – and who were not taking antihypertensive medication – were more than twice as likely to have stage 1 or 2 hypertension, compared with women who had not experienced sexual harassment (OR, 2.36, P = .03). They also had 89% higher odds of poor sleep consistent with clinical insomnia (P = .03).

These associations all persisted even after adjustment for demographic and biomedical factors such as age, ethnicity, body mass index, snoring, and the use of antihypertensive, antidepressant, and anti-anxiety medications.

“Given the high prevalence of sexual harassment and assault, addressing these prevalent and potent social exposures may be critical to promoting health and preventing disease in women,” wrote Rebecca C. Thurston, PhD, of the department of psychiatry at the University of Pittsburgh, and her coauthors.

The study was supported by the National Institutes of Health, National Heart Lung and Blood Institute, and the University of Pittsburgh Clinical and Translational Science Institute. Dr. Thurston declared consultancies for MAS Innovations, Procter & Gamble, and Pfizer, but no other conflicts of interest were declared.

SOURCE: Thurston R et al. JAMA Intern Med. 2018, Oct 3. doi: 10.1001/jamainternmed.2018.4886.

Around one-half of women and one-third of men will develop dementia, stroke, or parkinsonism during their lifetime, based on results from the population-based Rotterdam study published in the Oct. 1 online edition of the Journal of Neurology, Neurosurgery & Psychiatry.

The study involved 12,102 individuals (57.7% women) who were aged 45 years or older and free from neurologic disease at baseline who were followed for 26 years.

Silvan Licher, MD, and colleagues from the University Medical Center Rotterdam (the Netherlands) found that a 45-year-old woman had a 48.2% overall remaining lifetime risk of developing dementia, stroke, or parkinsonism, while a 45-year-old man had a 36.3% lifetime risk.

“There are currently no disease-modifying drugs available for dementia and most causes of parkinsonism, and prevention of stroke is hampered by suboptimal adherence to effective preventive strategies or unmet guideline thresholds,” the authors wrote. “Yet, a delay in onset of these common neurologic diseases by merely a few years could reduce the population burden of these diseases substantially.”

Women aged 45 years had a significantly higher lifetime risk than men of developing dementia (31.4% vs. 18.6% respectively) and stroke (21.6% vs. 19.3%), but the risk of parkinsonism was similar between the sexes.

Women also had a significantly greater lifetime risk of developing more than one neurologic disease, compared with men (4% vs. 3.1%, P less than .001), largely because of the overlap between dementia and stroke.

At age 45 women had the greatest risk of dementia, but as men and women aged, their remaining lifetime risk of dementia increased relative to other neurologic diseases. After age 85 years, 66.6% of first diagnoses in women and 55.6% in men were dementia.

By comparison, first manifestation of stroke was the greatest threat to men aged 45. Men were also at a significantly higher risk for stroke at a younger age – before age 75 years – than were women (8.4% vs. 5.8%).

In the case of parkinsonism, the lifetime risk peaked earlier than it did for dementia and stroke, and was relatively low after the age of 85 years, with no significant differences in risk between men and women.

The authors also considered what effect a delay in disease onset and occurrence might have on remaining lifetime risk for neurologic disease. They found that a 1, 2, or 3-year delay in the onset of all neurologic disease was associated with a 20% reduction in lifetime risk in individuals aged 45 years or older, and a greater than 50% reduction in risk in the very oldest.

A 3-year delay in the onset of dementia reduced the lifetime risk by 15% for both men and women aged 45 years and granted a 30% reduction in risk to those aged 45 years or older.

The Rotterdam study is supported by Erasmus MC and Erasmus University Rotterdam, The Netherlands Organization for Scientific Research, The Netherlands Organization for Health Research and Development, the Research Institute for Diseases in the Elderly, The Netherlands Genomics Initiative, the Ministry of Education, Culture and Science, the Ministry of Health, Welfare and Sports, the European Commission and the Municipality of Rotterdam, the Netherlands Consortium for Healthy Ageing, and the Dutch Heart Foundation. No conflicts of interest were declared.

SOURCE: Licher S et al. JNNP. 2018 Oct 1. doi: 10.1136/jnnp-2018-318650.

Around one-half of women and one-third of men will develop dementia, stroke, or parkinsonism during their lifetime, based on results from the population-based Rotterdam study published in the Oct. 1 online edition of the Journal of Neurology, Neurosurgery & Psychiatry.

The study involved 12,102 individuals (57.7% women) who were aged 45 years or older and free from neurologic disease at baseline who were followed for 26 years.

Silvan Licher, MD, and colleagues from the University Medical Center Rotterdam (the Netherlands) found that a 45-year-old woman had a 48.2% overall remaining lifetime risk of developing dementia, stroke, or parkinsonism, while a 45-year-old man had a 36.3% lifetime risk.

“There are currently no disease-modifying drugs available for dementia and most causes of parkinsonism, and prevention of stroke is hampered by suboptimal adherence to effective preventive strategies or unmet guideline thresholds,” the authors wrote. “Yet, a delay in onset of these common neurologic diseases by merely a few years could reduce the population burden of these diseases substantially.”

Women aged 45 years had a significantly higher lifetime risk than men of developing dementia (31.4% vs. 18.6% respectively) and stroke (21.6% vs. 19.3%), but the risk of parkinsonism was similar between the sexes.

Women also had a significantly greater lifetime risk of developing more than one neurologic disease, compared with men (4% vs. 3.1%, P less than .001), largely because of the overlap between dementia and stroke.

At age 45 women had the greatest risk of dementia, but as men and women aged, their remaining lifetime risk of dementia increased relative to other neurologic diseases. After age 85 years, 66.6% of first diagnoses in women and 55.6% in men were dementia.

By comparison, first manifestation of stroke was the greatest threat to men aged 45. Men were also at a significantly higher risk for stroke at a younger age – before age 75 years – than were women (8.4% vs. 5.8%).

In the case of parkinsonism, the lifetime risk peaked earlier than it did for dementia and stroke, and was relatively low after the age of 85 years, with no significant differences in risk between men and women.

The authors also considered what effect a delay in disease onset and occurrence might have on remaining lifetime risk for neurologic disease. They found that a 1, 2, or 3-year delay in the onset of all neurologic disease was associated with a 20% reduction in lifetime risk in individuals aged 45 years or older, and a greater than 50% reduction in risk in the very oldest.

A 3-year delay in the onset of dementia reduced the lifetime risk by 15% for both men and women aged 45 years and granted a 30% reduction in risk to those aged 45 years or older.

The Rotterdam study is supported by Erasmus MC and Erasmus University Rotterdam, The Netherlands Organization for Scientific Research, The Netherlands Organization for Health Research and Development, the Research Institute for Diseases in the Elderly, The Netherlands Genomics Initiative, the Ministry of Education, Culture and Science, the Ministry of Health, Welfare and Sports, the European Commission and the Municipality of Rotterdam, the Netherlands Consortium for Healthy Ageing, and the Dutch Heart Foundation. No conflicts of interest were declared.

SOURCE: Licher S et al. JNNP. 2018 Oct 1. doi: 10.1136/jnnp-2018-318650.

Around one-half of women and one-third of men will develop dementia, stroke, or parkinsonism during their lifetime, based on results from the population-based Rotterdam study published in the Oct. 1 online edition of the Journal of Neurology, Neurosurgery & Psychiatry.

The study involved 12,102 individuals (57.7% women) who were aged 45 years or older and free from neurologic disease at baseline who were followed for 26 years.

Silvan Licher, MD, and colleagues from the University Medical Center Rotterdam (the Netherlands) found that a 45-year-old woman had a 48.2% overall remaining lifetime risk of developing dementia, stroke, or parkinsonism, while a 45-year-old man had a 36.3% lifetime risk.

“There are currently no disease-modifying drugs available for dementia and most causes of parkinsonism, and prevention of stroke is hampered by suboptimal adherence to effective preventive strategies or unmet guideline thresholds,” the authors wrote. “Yet, a delay in onset of these common neurologic diseases by merely a few years could reduce the population burden of these diseases substantially.”

Women aged 45 years had a significantly higher lifetime risk than men of developing dementia (31.4% vs. 18.6% respectively) and stroke (21.6% vs. 19.3%), but the risk of parkinsonism was similar between the sexes.

Women also had a significantly greater lifetime risk of developing more than one neurologic disease, compared with men (4% vs. 3.1%, P less than .001), largely because of the overlap between dementia and stroke.

At age 45 women had the greatest risk of dementia, but as men and women aged, their remaining lifetime risk of dementia increased relative to other neurologic diseases. After age 85 years, 66.6% of first diagnoses in women and 55.6% in men were dementia.

By comparison, first manifestation of stroke was the greatest threat to men aged 45. Men were also at a significantly higher risk for stroke at a younger age – before age 75 years – than were women (8.4% vs. 5.8%).

In the case of parkinsonism, the lifetime risk peaked earlier than it did for dementia and stroke, and was relatively low after the age of 85 years, with no significant differences in risk between men and women.

The authors also considered what effect a delay in disease onset and occurrence might have on remaining lifetime risk for neurologic disease. They found that a 1, 2, or 3-year delay in the onset of all neurologic disease was associated with a 20% reduction in lifetime risk in individuals aged 45 years or older, and a greater than 50% reduction in risk in the very oldest.

A 3-year delay in the onset of dementia reduced the lifetime risk by 15% for both men and women aged 45 years and granted a 30% reduction in risk to those aged 45 years or older.

The Rotterdam study is supported by Erasmus MC and Erasmus University Rotterdam, The Netherlands Organization for Scientific Research, The Netherlands Organization for Health Research and Development, the Research Institute for Diseases in the Elderly, The Netherlands Genomics Initiative, the Ministry of Education, Culture and Science, the Ministry of Health, Welfare and Sports, the European Commission and the Municipality of Rotterdam, the Netherlands Consortium for Healthy Ageing, and the Dutch Heart Foundation. No conflicts of interest were declared.

SOURCE: Licher S et al. JNNP. 2018 Oct 1. doi: 10.1136/jnnp-2018-318650.

The U.S. Food and Drug Administration has approved cemiplimab-rwlc (Libtayo) for the treatment of metastatic or locally advanced cutaneous squamous cell carcinoma, the agency announced in a press release.

The U.S. Food and Drug Administration has approved cemiplimab-rwlc (Libtayo) for the treatment of metastatic or locally advanced cutaneous squamous cell carcinoma, the agency announced in a press release.

The U.S. Food and Drug Administration has approved cemiplimab-rwlc (Libtayo) for the treatment of metastatic or locally advanced cutaneous squamous cell carcinoma, the agency announced in a press release.