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Clinical course of depression is worse in older people
Older people are much more likely than younger people to experience a poorer clinical course of major depression, even after accounting for differences in social, clinical, and other health factors, new research suggests.
A longitudinal cohort study, published in the Lancet Psychiatry, examined baseline and 2-year follow-up data from 1,042 participants who had a recent diagnosis of a depressive or anxiety disorder in two previous cohort studies.
The authors adjusted initially for the number of major depressive disorder (MDD) episodes, comorbid anxiety, and antidepressant use but still found that older age was significantly associated with increased risk of a depressive diagnosis, a chronic symptom course, reduced likelihood of achieving remission, and a smaller decrease in depression severity.
They also adjusted for other factors common in old age, such as loneliness, social support, pain, other chronic disease, and higher body mass index, and again found that this only led to small reductions in the association with older age. However, the adjustment for loneliness did have the effect of dissipating the association between older age and the presence of any depression diagnosis.
“ and that are thought to worsen the course of the disease,” wrote Roxanne Schaakxs, PhD, of the Amsterdam Public Health Research Institute at VU University Medical Center, and her coauthors.
Researchers also looked for an effect of antidepressant use, in case the age differences might be related to differences in treatment response. “However, adjustment for antidepressant use at baseline did not substantially change our findings, and stratified analysis for participants who did and did not use antidepressants revealed consistent age–MDD course associations for both subsamples,” they wrote.
The authors said their findings suggested that age-tailored treatment might be needed for major depressive disorder, with a particular focus on maintenance treatment for older people.
The two cohort studies were supported by the Netherlands Organization for Health Research and Developments, NutsOhra Fonds, Stichting tot Steun VCVGZ, a NARSAD grant from the Brain & Behavior Research Foundation, and a range of universities and mental health care organizations.
One author declared research funding from Janssen Research and Boehringer Ingelheim not related to the study.
SOURCE: Schaakxs R et al. Lancet Psychiatry. 2018 Jun 7. doi: 10.1016/S2215-0366(18)30166-4.
While major depression appears to follow a worse clinical course in older people, this study is important in providing robust evidence of poorer prognostic outcomes and addresses some major methodological limitations of previous studies.
One limitation, acknowledged by the authors, is the absence of a sufficient measure of cognitive function. Cognitive impairment is associated with major depression, slows recovery from depression, and reduces treatment effectiveness. The study did exclude people with dementia or with Mini-Mental State Examination scores of 18 or lower, but this may not have excluded other variations in cognitive impairment that could have contributed to the age-related differences in outcomes.
Tze Pin Ng, MD, is with the department of psychological medicine at the National University of Singapore. These comments are taken from an accompanying editorial (Lancet Psychiatry. 2018 Jun 7. doi: 10.1016/S2215-0366[18]30186-X). No conflicts of interest were declared.
While major depression appears to follow a worse clinical course in older people, this study is important in providing robust evidence of poorer prognostic outcomes and addresses some major methodological limitations of previous studies.
One limitation, acknowledged by the authors, is the absence of a sufficient measure of cognitive function. Cognitive impairment is associated with major depression, slows recovery from depression, and reduces treatment effectiveness. The study did exclude people with dementia or with Mini-Mental State Examination scores of 18 or lower, but this may not have excluded other variations in cognitive impairment that could have contributed to the age-related differences in outcomes.
Tze Pin Ng, MD, is with the department of psychological medicine at the National University of Singapore. These comments are taken from an accompanying editorial (Lancet Psychiatry. 2018 Jun 7. doi: 10.1016/S2215-0366[18]30186-X). No conflicts of interest were declared.
While major depression appears to follow a worse clinical course in older people, this study is important in providing robust evidence of poorer prognostic outcomes and addresses some major methodological limitations of previous studies.
One limitation, acknowledged by the authors, is the absence of a sufficient measure of cognitive function. Cognitive impairment is associated with major depression, slows recovery from depression, and reduces treatment effectiveness. The study did exclude people with dementia or with Mini-Mental State Examination scores of 18 or lower, but this may not have excluded other variations in cognitive impairment that could have contributed to the age-related differences in outcomes.
Tze Pin Ng, MD, is with the department of psychological medicine at the National University of Singapore. These comments are taken from an accompanying editorial (Lancet Psychiatry. 2018 Jun 7. doi: 10.1016/S2215-0366[18]30186-X). No conflicts of interest were declared.
Older people are much more likely than younger people to experience a poorer clinical course of major depression, even after accounting for differences in social, clinical, and other health factors, new research suggests.
A longitudinal cohort study, published in the Lancet Psychiatry, examined baseline and 2-year follow-up data from 1,042 participants who had a recent diagnosis of a depressive or anxiety disorder in two previous cohort studies.
The authors adjusted initially for the number of major depressive disorder (MDD) episodes, comorbid anxiety, and antidepressant use but still found that older age was significantly associated with increased risk of a depressive diagnosis, a chronic symptom course, reduced likelihood of achieving remission, and a smaller decrease in depression severity.
They also adjusted for other factors common in old age, such as loneliness, social support, pain, other chronic disease, and higher body mass index, and again found that this only led to small reductions in the association with older age. However, the adjustment for loneliness did have the effect of dissipating the association between older age and the presence of any depression diagnosis.
“ and that are thought to worsen the course of the disease,” wrote Roxanne Schaakxs, PhD, of the Amsterdam Public Health Research Institute at VU University Medical Center, and her coauthors.
Researchers also looked for an effect of antidepressant use, in case the age differences might be related to differences in treatment response. “However, adjustment for antidepressant use at baseline did not substantially change our findings, and stratified analysis for participants who did and did not use antidepressants revealed consistent age–MDD course associations for both subsamples,” they wrote.
The authors said their findings suggested that age-tailored treatment might be needed for major depressive disorder, with a particular focus on maintenance treatment for older people.
The two cohort studies were supported by the Netherlands Organization for Health Research and Developments, NutsOhra Fonds, Stichting tot Steun VCVGZ, a NARSAD grant from the Brain & Behavior Research Foundation, and a range of universities and mental health care organizations.
One author declared research funding from Janssen Research and Boehringer Ingelheim not related to the study.
SOURCE: Schaakxs R et al. Lancet Psychiatry. 2018 Jun 7. doi: 10.1016/S2215-0366(18)30166-4.
Older people are much more likely than younger people to experience a poorer clinical course of major depression, even after accounting for differences in social, clinical, and other health factors, new research suggests.
A longitudinal cohort study, published in the Lancet Psychiatry, examined baseline and 2-year follow-up data from 1,042 participants who had a recent diagnosis of a depressive or anxiety disorder in two previous cohort studies.
The authors adjusted initially for the number of major depressive disorder (MDD) episodes, comorbid anxiety, and antidepressant use but still found that older age was significantly associated with increased risk of a depressive diagnosis, a chronic symptom course, reduced likelihood of achieving remission, and a smaller decrease in depression severity.
They also adjusted for other factors common in old age, such as loneliness, social support, pain, other chronic disease, and higher body mass index, and again found that this only led to small reductions in the association with older age. However, the adjustment for loneliness did have the effect of dissipating the association between older age and the presence of any depression diagnosis.
“ and that are thought to worsen the course of the disease,” wrote Roxanne Schaakxs, PhD, of the Amsterdam Public Health Research Institute at VU University Medical Center, and her coauthors.
Researchers also looked for an effect of antidepressant use, in case the age differences might be related to differences in treatment response. “However, adjustment for antidepressant use at baseline did not substantially change our findings, and stratified analysis for participants who did and did not use antidepressants revealed consistent age–MDD course associations for both subsamples,” they wrote.
The authors said their findings suggested that age-tailored treatment might be needed for major depressive disorder, with a particular focus on maintenance treatment for older people.
The two cohort studies were supported by the Netherlands Organization for Health Research and Developments, NutsOhra Fonds, Stichting tot Steun VCVGZ, a NARSAD grant from the Brain & Behavior Research Foundation, and a range of universities and mental health care organizations.
One author declared research funding from Janssen Research and Boehringer Ingelheim not related to the study.
SOURCE: Schaakxs R et al. Lancet Psychiatry. 2018 Jun 7. doi: 10.1016/S2215-0366(18)30166-4.
FROM THE LANCET PSYCHIATRY
Key clinical point: Older people experienced a worse clinical course of depressive disorders, compared with younger people.
Major finding: Older people with depression experienced slower remission and a higher risk of chronicity.
Study details: A longitudinal cohort study of 1,042 people with depressive or anxiety disorders.
Disclosures: The two cohort studies were supported by the Netherlands Organization for Health Research and Developments, NutsOhra Fonds, Stichting tot Steun VCVGZ, a NARSAD grant from the Brain & Behavior Research Foundation, and a range of universities and mental health care organizations. One author declared research funding from pharmaceutical companies that was not related to the study.
Source: Schaakxs R et al. Lancet Psychiatry. 2018 Jun 7. doi: 10.1016/S2215-0366(18)30166-4.
Checkpoint inhibitor shows promise in advanced squamous-cell carcinoma
An immune checkpoint inhibitor that targets the PD-1 receptor has shown “robust” efficacy among patients with advanced cutaneous squamous-cell carcinoma, according to researchers.
A combined phase 1/phase 2 study, published in the New England Journal of Medicine and presented simultaneously at the annual meeting of the American Society of Clinical Oncology, looked at the effect of monoclonal antibody cemiplimab in an expansion cohort of 26 patients with locally-advanced or metastatic cutaneous squamous-cell carcinoma who were not eligible for surgery. The phase 2 component involved 59 patients with metastatic disease.
Patients were treated with intravenous cemiplimab every 2 weeks for 48 weeks in the phase 1 study, and up to 96 weeks – or until unacceptable toxicity or disease progression – in the phase 2 study.
In the phase 1 study, researchers saw a response rate of 50% and a 65% rate of durable disease control, after a median follow-up of 11 months (1.1-17). The median time to response was 2.3 months, and more than half the patients (54%) who showed a response maintained that response past 6 months.
In the phase 2 study in patients with metastatic disease, 47% responded to the treatment – 24 patients showed a partial response and 4 showed a complete response. Of those who responded, 61% showed durable disease control after a median follow-up of 7.9 months.
The median time to response in this group of patients was 1.9 months, and 57% of those who did respond still showed a response at 6 months. However neither median progression-free survival nor median overall survival had been reached at the point of data cut-off.
The treatment showed similar effects in patients with regional and distant metastatic disease.
Advanced cutaneous squamous-cell carcinoma was thought to be an ideal target for immunotherapy because the high mutation burden in the tumor meant it would be sensitive to effector T cell attack, wrote Michael R. Migden, MD, of the University of Texas MD Anderson Cancer Center, Houston, and his coauthors.
“In addition, the dramatically increased risk of cutaneous squamous-cell carcinoma among people with immunosuppression pointed to an important role for immune surveillance with this cancer,” the authors wrote.
In the phase 2 study, 29% of patients experienced a serious adverse event – including two cases of pneumonitis – and three patients (5%) discontinued treatment. There were three deaths due to adverse events: One patient died from pneumonia complications, one died in his sleep, and one patient died following hypercalcemia and deep vein thrombosis.
Aside from these, most adverse events were grade 1 or 2. Around one-quarter of patients experienced diarrhea (27%) or fatigue (24%), while the other most common adverse events were nausea (17%), constipation (15%) and rash (15%). The authors noted that these adverse events were similar to those seen in other PD-1 inhibitors.
“Our results are consistent with an emerging theme regarding the high efficacy of immune checkpoint blockade for the treatment of hypermutated cancers, since the mutation burden of cutaneous squamous-cell carcinoma is similar to that reported for advanced solid tumors with microsatellite instability,” the authors wrote.
Cemiplimab is now being tested in a phase 2 trial in patients with advanced basal cell carcinoma.
The study was supported by Regeneron Pharmaceuticals and Sanofi. Eight authors declared funding from Regeneron to conduct the trial. Ten authors were employees of Regeneron. Fifteen authors also declared funding and payments from pharmaceutical companies outside the submitted work. Four had nothing to disclose.
SOURCE: Migden M et al. NEJM, 2018; June 4. doi: 10.1056/NEJMoa1805131.
An immune checkpoint inhibitor that targets the PD-1 receptor has shown “robust” efficacy among patients with advanced cutaneous squamous-cell carcinoma, according to researchers.
A combined phase 1/phase 2 study, published in the New England Journal of Medicine and presented simultaneously at the annual meeting of the American Society of Clinical Oncology, looked at the effect of monoclonal antibody cemiplimab in an expansion cohort of 26 patients with locally-advanced or metastatic cutaneous squamous-cell carcinoma who were not eligible for surgery. The phase 2 component involved 59 patients with metastatic disease.
Patients were treated with intravenous cemiplimab every 2 weeks for 48 weeks in the phase 1 study, and up to 96 weeks – or until unacceptable toxicity or disease progression – in the phase 2 study.
In the phase 1 study, researchers saw a response rate of 50% and a 65% rate of durable disease control, after a median follow-up of 11 months (1.1-17). The median time to response was 2.3 months, and more than half the patients (54%) who showed a response maintained that response past 6 months.
In the phase 2 study in patients with metastatic disease, 47% responded to the treatment – 24 patients showed a partial response and 4 showed a complete response. Of those who responded, 61% showed durable disease control after a median follow-up of 7.9 months.
The median time to response in this group of patients was 1.9 months, and 57% of those who did respond still showed a response at 6 months. However neither median progression-free survival nor median overall survival had been reached at the point of data cut-off.
The treatment showed similar effects in patients with regional and distant metastatic disease.
Advanced cutaneous squamous-cell carcinoma was thought to be an ideal target for immunotherapy because the high mutation burden in the tumor meant it would be sensitive to effector T cell attack, wrote Michael R. Migden, MD, of the University of Texas MD Anderson Cancer Center, Houston, and his coauthors.
“In addition, the dramatically increased risk of cutaneous squamous-cell carcinoma among people with immunosuppression pointed to an important role for immune surveillance with this cancer,” the authors wrote.
In the phase 2 study, 29% of patients experienced a serious adverse event – including two cases of pneumonitis – and three patients (5%) discontinued treatment. There were three deaths due to adverse events: One patient died from pneumonia complications, one died in his sleep, and one patient died following hypercalcemia and deep vein thrombosis.
Aside from these, most adverse events were grade 1 or 2. Around one-quarter of patients experienced diarrhea (27%) or fatigue (24%), while the other most common adverse events were nausea (17%), constipation (15%) and rash (15%). The authors noted that these adverse events were similar to those seen in other PD-1 inhibitors.
“Our results are consistent with an emerging theme regarding the high efficacy of immune checkpoint blockade for the treatment of hypermutated cancers, since the mutation burden of cutaneous squamous-cell carcinoma is similar to that reported for advanced solid tumors with microsatellite instability,” the authors wrote.
Cemiplimab is now being tested in a phase 2 trial in patients with advanced basal cell carcinoma.
The study was supported by Regeneron Pharmaceuticals and Sanofi. Eight authors declared funding from Regeneron to conduct the trial. Ten authors were employees of Regeneron. Fifteen authors also declared funding and payments from pharmaceutical companies outside the submitted work. Four had nothing to disclose.
SOURCE: Migden M et al. NEJM, 2018; June 4. doi: 10.1056/NEJMoa1805131.
An immune checkpoint inhibitor that targets the PD-1 receptor has shown “robust” efficacy among patients with advanced cutaneous squamous-cell carcinoma, according to researchers.
A combined phase 1/phase 2 study, published in the New England Journal of Medicine and presented simultaneously at the annual meeting of the American Society of Clinical Oncology, looked at the effect of monoclonal antibody cemiplimab in an expansion cohort of 26 patients with locally-advanced or metastatic cutaneous squamous-cell carcinoma who were not eligible for surgery. The phase 2 component involved 59 patients with metastatic disease.
Patients were treated with intravenous cemiplimab every 2 weeks for 48 weeks in the phase 1 study, and up to 96 weeks – or until unacceptable toxicity or disease progression – in the phase 2 study.
In the phase 1 study, researchers saw a response rate of 50% and a 65% rate of durable disease control, after a median follow-up of 11 months (1.1-17). The median time to response was 2.3 months, and more than half the patients (54%) who showed a response maintained that response past 6 months.
In the phase 2 study in patients with metastatic disease, 47% responded to the treatment – 24 patients showed a partial response and 4 showed a complete response. Of those who responded, 61% showed durable disease control after a median follow-up of 7.9 months.
The median time to response in this group of patients was 1.9 months, and 57% of those who did respond still showed a response at 6 months. However neither median progression-free survival nor median overall survival had been reached at the point of data cut-off.
The treatment showed similar effects in patients with regional and distant metastatic disease.
Advanced cutaneous squamous-cell carcinoma was thought to be an ideal target for immunotherapy because the high mutation burden in the tumor meant it would be sensitive to effector T cell attack, wrote Michael R. Migden, MD, of the University of Texas MD Anderson Cancer Center, Houston, and his coauthors.
“In addition, the dramatically increased risk of cutaneous squamous-cell carcinoma among people with immunosuppression pointed to an important role for immune surveillance with this cancer,” the authors wrote.
In the phase 2 study, 29% of patients experienced a serious adverse event – including two cases of pneumonitis – and three patients (5%) discontinued treatment. There were three deaths due to adverse events: One patient died from pneumonia complications, one died in his sleep, and one patient died following hypercalcemia and deep vein thrombosis.
Aside from these, most adverse events were grade 1 or 2. Around one-quarter of patients experienced diarrhea (27%) or fatigue (24%), while the other most common adverse events were nausea (17%), constipation (15%) and rash (15%). The authors noted that these adverse events were similar to those seen in other PD-1 inhibitors.
“Our results are consistent with an emerging theme regarding the high efficacy of immune checkpoint blockade for the treatment of hypermutated cancers, since the mutation burden of cutaneous squamous-cell carcinoma is similar to that reported for advanced solid tumors with microsatellite instability,” the authors wrote.
Cemiplimab is now being tested in a phase 2 trial in patients with advanced basal cell carcinoma.
The study was supported by Regeneron Pharmaceuticals and Sanofi. Eight authors declared funding from Regeneron to conduct the trial. Ten authors were employees of Regeneron. Fifteen authors also declared funding and payments from pharmaceutical companies outside the submitted work. Four had nothing to disclose.
SOURCE: Migden M et al. NEJM, 2018; June 4. doi: 10.1056/NEJMoa1805131.
FROM NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: PD-1 inhibitor cemiplimab shows significant response in advanced squamous-cell carcinoma.
Major finding: Around half of patients with advanced squamous-cell carcinoma responded to checkpoint inhibitor cemiplimab.
Study details: Phase 1 expanded cohort study of 26 patients with advanced cutaneous squamous-cell carcinoma and phase 2 study of 59 patients with metastatic squamous-cell carcinoma.
Disclosures: The study was supported by Regeneron Pharmaceuticals and Sanofi. Eight authors declared funding from Regeneron to conduct the trial. Ten authors were employees of Regeneron. Fifteen authors declared funding and payments from pharmaceutical companies outside the submitted work. Four had nothing to disclose.
Source: Migden M et al. N Engl J Med. 2018 June 4. doi: 10.1056/NEJMoa1805131.
Identifying insomnia in people with mental disorders
The Insomnia Severity Index might be the most effective screening tool at identifying insomnia among outpatients with mental disorders, according to a study published in Sleep Medicine.
The cross-sectional study compared six self-administered sleep measures – the Pittsburgh Sleep Quality Index, Insomnia Severity Index (ISI), Epworth Sleepiness Scale, Flinders Fatigue Scale, Functional Outcomes of Sleep Questionnaire, and Dysfunctional Beliefs and Attitudes about Sleep scale – in 400 psychiatric outpatients.
Of those, the Insomnia Severity Index was the most accurate way to discriminate between cases of insomnia and noncases according to both the DSM-5 and ICD-10 criteria. In fact, the Insomnia Severity Index was the only scale that was able to discriminate both with good accuracy.
The area under the curve for the ISI was 0.88 for the ICD definition, and 0.82 for the DSM-5 criteria. Researchers found that the best sensitivity and specificity for the ISI was achieved using cutoff scores of less than or equal to 14 for ICD-10 insomnia and less than or equal to 11 for DSM-5 insomnia.
A cutoff of 14 or above for the ISI yielded a sensitivity of 81.3%, specificity of 80.9%, positive predictive value of 66.7%, and negative predictive value of 90.2%.
The Pittsburgh Sleep Quality Index was found to have good accuracy in discriminating between cases and noncases using the ICD-10 criteria, but only had fair accuracy for the DSM-5 criteria. However, it was slightly better than the ISI at detecting insomnia cases, according to the DSM-5 criteria, in people with either bipolar affective or anxiety disorders.
The Flinders Fatigue Scale, Functional Outcomes of Sleep Questionnaire, and Dysfunctional Beliefs and Attitudes about Sleep scale all showed fair accuracy for the ICD-10 criteria but low accuracy for the DSM-5 criteria, while the Epworth Sleepiness Scale had low accuracy for the ICD-10 criteria and was nondiscriminatory for the DSM-5 criteria.
The scales were all self-administered, were designed to take 15 minutes or fewer to complete, and were chosen because they covered the six key aspects of sleep, including sleep quality, daytime sleepiness, sleep-related quality of life, and sleep-disruptive cognitions.
The investigators cited one limitation that might limit the generalizability of their findings: Only outpatients with psychiatric disorders were recruited for the study. Nevertheless, the findings have clinical implications, they wrote. “Identifying a self-report sleep measure that can detect clinically significant insomnia depending on these systems not only provides the clinicians with the ease of administration but also helps them in detecting and treating psychiatric patients whose conditions may be aggravated by the presence of comorbid insomnia,” wrote Lee Seng Esmond Seow, BA, and his colleagues at the Institute of Mental Health in Singapore.
The study was supported by the Singapore Ministry of Health’s National Medical Research Council. No conflicts of interest were declared.
SOURCE: Seow LSE et al. Sleep Med. 2018 Jan;41:86-93.
The Insomnia Severity Index might be the most effective screening tool at identifying insomnia among outpatients with mental disorders, according to a study published in Sleep Medicine.
The cross-sectional study compared six self-administered sleep measures – the Pittsburgh Sleep Quality Index, Insomnia Severity Index (ISI), Epworth Sleepiness Scale, Flinders Fatigue Scale, Functional Outcomes of Sleep Questionnaire, and Dysfunctional Beliefs and Attitudes about Sleep scale – in 400 psychiatric outpatients.
Of those, the Insomnia Severity Index was the most accurate way to discriminate between cases of insomnia and noncases according to both the DSM-5 and ICD-10 criteria. In fact, the Insomnia Severity Index was the only scale that was able to discriminate both with good accuracy.
The area under the curve for the ISI was 0.88 for the ICD definition, and 0.82 for the DSM-5 criteria. Researchers found that the best sensitivity and specificity for the ISI was achieved using cutoff scores of less than or equal to 14 for ICD-10 insomnia and less than or equal to 11 for DSM-5 insomnia.
A cutoff of 14 or above for the ISI yielded a sensitivity of 81.3%, specificity of 80.9%, positive predictive value of 66.7%, and negative predictive value of 90.2%.
The Pittsburgh Sleep Quality Index was found to have good accuracy in discriminating between cases and noncases using the ICD-10 criteria, but only had fair accuracy for the DSM-5 criteria. However, it was slightly better than the ISI at detecting insomnia cases, according to the DSM-5 criteria, in people with either bipolar affective or anxiety disorders.
The Flinders Fatigue Scale, Functional Outcomes of Sleep Questionnaire, and Dysfunctional Beliefs and Attitudes about Sleep scale all showed fair accuracy for the ICD-10 criteria but low accuracy for the DSM-5 criteria, while the Epworth Sleepiness Scale had low accuracy for the ICD-10 criteria and was nondiscriminatory for the DSM-5 criteria.
The scales were all self-administered, were designed to take 15 minutes or fewer to complete, and were chosen because they covered the six key aspects of sleep, including sleep quality, daytime sleepiness, sleep-related quality of life, and sleep-disruptive cognitions.
The investigators cited one limitation that might limit the generalizability of their findings: Only outpatients with psychiatric disorders were recruited for the study. Nevertheless, the findings have clinical implications, they wrote. “Identifying a self-report sleep measure that can detect clinically significant insomnia depending on these systems not only provides the clinicians with the ease of administration but also helps them in detecting and treating psychiatric patients whose conditions may be aggravated by the presence of comorbid insomnia,” wrote Lee Seng Esmond Seow, BA, and his colleagues at the Institute of Mental Health in Singapore.
The study was supported by the Singapore Ministry of Health’s National Medical Research Council. No conflicts of interest were declared.
SOURCE: Seow LSE et al. Sleep Med. 2018 Jan;41:86-93.
The Insomnia Severity Index might be the most effective screening tool at identifying insomnia among outpatients with mental disorders, according to a study published in Sleep Medicine.
The cross-sectional study compared six self-administered sleep measures – the Pittsburgh Sleep Quality Index, Insomnia Severity Index (ISI), Epworth Sleepiness Scale, Flinders Fatigue Scale, Functional Outcomes of Sleep Questionnaire, and Dysfunctional Beliefs and Attitudes about Sleep scale – in 400 psychiatric outpatients.
Of those, the Insomnia Severity Index was the most accurate way to discriminate between cases of insomnia and noncases according to both the DSM-5 and ICD-10 criteria. In fact, the Insomnia Severity Index was the only scale that was able to discriminate both with good accuracy.
The area under the curve for the ISI was 0.88 for the ICD definition, and 0.82 for the DSM-5 criteria. Researchers found that the best sensitivity and specificity for the ISI was achieved using cutoff scores of less than or equal to 14 for ICD-10 insomnia and less than or equal to 11 for DSM-5 insomnia.
A cutoff of 14 or above for the ISI yielded a sensitivity of 81.3%, specificity of 80.9%, positive predictive value of 66.7%, and negative predictive value of 90.2%.
The Pittsburgh Sleep Quality Index was found to have good accuracy in discriminating between cases and noncases using the ICD-10 criteria, but only had fair accuracy for the DSM-5 criteria. However, it was slightly better than the ISI at detecting insomnia cases, according to the DSM-5 criteria, in people with either bipolar affective or anxiety disorders.
The Flinders Fatigue Scale, Functional Outcomes of Sleep Questionnaire, and Dysfunctional Beliefs and Attitudes about Sleep scale all showed fair accuracy for the ICD-10 criteria but low accuracy for the DSM-5 criteria, while the Epworth Sleepiness Scale had low accuracy for the ICD-10 criteria and was nondiscriminatory for the DSM-5 criteria.
The scales were all self-administered, were designed to take 15 minutes or fewer to complete, and were chosen because they covered the six key aspects of sleep, including sleep quality, daytime sleepiness, sleep-related quality of life, and sleep-disruptive cognitions.
The investigators cited one limitation that might limit the generalizability of their findings: Only outpatients with psychiatric disorders were recruited for the study. Nevertheless, the findings have clinical implications, they wrote. “Identifying a self-report sleep measure that can detect clinically significant insomnia depending on these systems not only provides the clinicians with the ease of administration but also helps them in detecting and treating psychiatric patients whose conditions may be aggravated by the presence of comorbid insomnia,” wrote Lee Seng Esmond Seow, BA, and his colleagues at the Institute of Mental Health in Singapore.
The study was supported by the Singapore Ministry of Health’s National Medical Research Council. No conflicts of interest were declared.
SOURCE: Seow LSE et al. Sleep Med. 2018 Jan;41:86-93.
FROM SLEEP MEDICINE
Key clinical point: The Insomnia Severity Index was the most accurate screen for insomnia in patients with mental disorders.
Major finding: The Insomnia Severity Index had the greatest area under the curve for insomnia detection.
Study details: A cross-sectional study of six self-administered sleep measures tested in 400 psychiatric outpatients.
Disclosures: The study was supported by the Singapore Ministry of Health’s National Medical Research Council. No conflicts of interest were declared.
Source: Seow LSE et al. Sleep Med. 2018 Jan;41:86-93.
Esketamine nasal spray prevails in two phase 3 trials
The combination of an esketamine nasal spray and an oral antidepressant may provide additional benefits for patients with treatment-resistant major depressive disorder, new research suggested.
Two posters at a meeting of the American Society of Clinical Psychopharmacology, formerly known as the New Clinical Drug Evaluation Unit meeting, presented data from two phase 3 studies on the safety and efficacy of an esketamine nasal spray plus oral antidepressant in patients with treatment-resistant depression.
The first study – a double-blind, randomized withdrawal study – enrolled 705 patients with recurrent or single episode major depressive disorder who were either enrolled directly or after completing the double-blind phase of an acute, short-term study.
Patients began with a 16-week induction phase of esketamine nasal spray and oral antidepressant, then patients were randomized either to a placebo nasal spray or esketamine nasal spray – plus oral antidepressant – for the maintenance phase.
Researchers saw a significantly higher rate of relapse among patients randomized to the placebo nasal spray, compared with those randomized to the esketamine nasal spray. In patients classified as stable remitters at the start of the maintenance period, 26.7% of those who received the esketamine nasal spray experienced a relapse, compared with 45.3% of those who received the placebo nasal spray.
Among the stable responders, 25.8% of those who received esketamine experienced a relapse, compared with 57.6% of those who received the placebo nasal spray.
This represented a 51% lower risk of relapse with esketamine among stable remitters and a 70% lower risk of relapse among stable responders, compared with placebo. Treatment with esketamine also significantly delayed relapse, compared with placebo.
Most adverse events were mild to moderate, but six patients experienced serious adverse events that were possibly related to the study drug, including disorientation, hypothermia, lacunar stroke, sedation, and suicidal ideation, during the induction phase of the study. However on review, the study sponsor argued that the lacunar stroke and hypothermia were unlikely to be linked to the study medication.
Four patients in the esketamine group and three patients in the placebo group discontinued the nasal spray during the maintenance phase.
“The study provides support for a positive benefit-risk evaluation for treatment with esketamine plus an oral antidepressant and provides further safety data regarding longer-term, intermittent dosing frequency treatment,” wrote Ella J. Daly, MD, from Janssen Research & Development – which also funded the study – and coauthors.
The researchers also noted that, overall, cognitive performance remained stable or improved after long-term, intermittent treatment with the esketamine nasal spray plus antidepressant.
The second study – an open-label, international study – involved 802 patients with major depressive disorder who had all failed to respond to at least two oral antidepressants. They were treated with an esketamine nasal spray (28 mg, 56 mg, or 84 mg) in combination with a new oral antidepressant.
The study involved a screening phase, induction phase, and optimization/maintenance phase, but only 24.9% of patients completed the optimization/maintenance phase. However, this was enough to meet a predefined total patient exposure, and the study was terminated by the sponsor.
More than three-quarters of patients responded during the induction phase, and by the end of the induction phase, 47.2% of patients had achieved remission. By the end of the optimization/maintenance phase, 58.2% of patients who entered that phase achieved remission.
More than 90% of patients experienced at least one adverse event, although most were mild to moderate. There were two deaths during the optimization/maintenance phase – one from acute respiratory and cardiac failure and one from suicide – but neither was considered as being related to the esketamine.
Five serious adverse events – anxiety, delusion, delirium, suicidal ideation, and suicidal attempt – were judged by the investigator to be related to the esketamine.
Researchers also saw no declines in performance on multiple cognitive domains, including visual learning and memory, across the entire study.
“The adverse event profile following an up to 1 year of exposure was consistent with previous observations of esketamine in the completed short-term phase 2 and 3 studies, and no unexpected safety findings were reported,” wrote Ewa Wajs, MD, also with Janssen, and coauthors.
Both studies were funded by Janssen Research & Development. Of the authors in the first study, 12 were employees of Janssen, and 10 declared funding from the pharmaceutical industry, including Janssen. Of the authors in the second study, 11 were employees of Janssen, and four declared a range of funding from the pharmaceutical industry.
SOURCE: Daly EJ et al. ASCP 2018, Poster W68. Wajs E et al. ASCP 2018, Poster T67.
The combination of an esketamine nasal spray and an oral antidepressant may provide additional benefits for patients with treatment-resistant major depressive disorder, new research suggested.
Two posters at a meeting of the American Society of Clinical Psychopharmacology, formerly known as the New Clinical Drug Evaluation Unit meeting, presented data from two phase 3 studies on the safety and efficacy of an esketamine nasal spray plus oral antidepressant in patients with treatment-resistant depression.
The first study – a double-blind, randomized withdrawal study – enrolled 705 patients with recurrent or single episode major depressive disorder who were either enrolled directly or after completing the double-blind phase of an acute, short-term study.
Patients began with a 16-week induction phase of esketamine nasal spray and oral antidepressant, then patients were randomized either to a placebo nasal spray or esketamine nasal spray – plus oral antidepressant – for the maintenance phase.
Researchers saw a significantly higher rate of relapse among patients randomized to the placebo nasal spray, compared with those randomized to the esketamine nasal spray. In patients classified as stable remitters at the start of the maintenance period, 26.7% of those who received the esketamine nasal spray experienced a relapse, compared with 45.3% of those who received the placebo nasal spray.
Among the stable responders, 25.8% of those who received esketamine experienced a relapse, compared with 57.6% of those who received the placebo nasal spray.
This represented a 51% lower risk of relapse with esketamine among stable remitters and a 70% lower risk of relapse among stable responders, compared with placebo. Treatment with esketamine also significantly delayed relapse, compared with placebo.
Most adverse events were mild to moderate, but six patients experienced serious adverse events that were possibly related to the study drug, including disorientation, hypothermia, lacunar stroke, sedation, and suicidal ideation, during the induction phase of the study. However on review, the study sponsor argued that the lacunar stroke and hypothermia were unlikely to be linked to the study medication.
Four patients in the esketamine group and three patients in the placebo group discontinued the nasal spray during the maintenance phase.
“The study provides support for a positive benefit-risk evaluation for treatment with esketamine plus an oral antidepressant and provides further safety data regarding longer-term, intermittent dosing frequency treatment,” wrote Ella J. Daly, MD, from Janssen Research & Development – which also funded the study – and coauthors.
The researchers also noted that, overall, cognitive performance remained stable or improved after long-term, intermittent treatment with the esketamine nasal spray plus antidepressant.
The second study – an open-label, international study – involved 802 patients with major depressive disorder who had all failed to respond to at least two oral antidepressants. They were treated with an esketamine nasal spray (28 mg, 56 mg, or 84 mg) in combination with a new oral antidepressant.
The study involved a screening phase, induction phase, and optimization/maintenance phase, but only 24.9% of patients completed the optimization/maintenance phase. However, this was enough to meet a predefined total patient exposure, and the study was terminated by the sponsor.
More than three-quarters of patients responded during the induction phase, and by the end of the induction phase, 47.2% of patients had achieved remission. By the end of the optimization/maintenance phase, 58.2% of patients who entered that phase achieved remission.
More than 90% of patients experienced at least one adverse event, although most were mild to moderate. There were two deaths during the optimization/maintenance phase – one from acute respiratory and cardiac failure and one from suicide – but neither was considered as being related to the esketamine.
Five serious adverse events – anxiety, delusion, delirium, suicidal ideation, and suicidal attempt – were judged by the investigator to be related to the esketamine.
Researchers also saw no declines in performance on multiple cognitive domains, including visual learning and memory, across the entire study.
“The adverse event profile following an up to 1 year of exposure was consistent with previous observations of esketamine in the completed short-term phase 2 and 3 studies, and no unexpected safety findings were reported,” wrote Ewa Wajs, MD, also with Janssen, and coauthors.
Both studies were funded by Janssen Research & Development. Of the authors in the first study, 12 were employees of Janssen, and 10 declared funding from the pharmaceutical industry, including Janssen. Of the authors in the second study, 11 were employees of Janssen, and four declared a range of funding from the pharmaceutical industry.
SOURCE: Daly EJ et al. ASCP 2018, Poster W68. Wajs E et al. ASCP 2018, Poster T67.
The combination of an esketamine nasal spray and an oral antidepressant may provide additional benefits for patients with treatment-resistant major depressive disorder, new research suggested.
Two posters at a meeting of the American Society of Clinical Psychopharmacology, formerly known as the New Clinical Drug Evaluation Unit meeting, presented data from two phase 3 studies on the safety and efficacy of an esketamine nasal spray plus oral antidepressant in patients with treatment-resistant depression.
The first study – a double-blind, randomized withdrawal study – enrolled 705 patients with recurrent or single episode major depressive disorder who were either enrolled directly or after completing the double-blind phase of an acute, short-term study.
Patients began with a 16-week induction phase of esketamine nasal spray and oral antidepressant, then patients were randomized either to a placebo nasal spray or esketamine nasal spray – plus oral antidepressant – for the maintenance phase.
Researchers saw a significantly higher rate of relapse among patients randomized to the placebo nasal spray, compared with those randomized to the esketamine nasal spray. In patients classified as stable remitters at the start of the maintenance period, 26.7% of those who received the esketamine nasal spray experienced a relapse, compared with 45.3% of those who received the placebo nasal spray.
Among the stable responders, 25.8% of those who received esketamine experienced a relapse, compared with 57.6% of those who received the placebo nasal spray.
This represented a 51% lower risk of relapse with esketamine among stable remitters and a 70% lower risk of relapse among stable responders, compared with placebo. Treatment with esketamine also significantly delayed relapse, compared with placebo.
Most adverse events were mild to moderate, but six patients experienced serious adverse events that were possibly related to the study drug, including disorientation, hypothermia, lacunar stroke, sedation, and suicidal ideation, during the induction phase of the study. However on review, the study sponsor argued that the lacunar stroke and hypothermia were unlikely to be linked to the study medication.
Four patients in the esketamine group and three patients in the placebo group discontinued the nasal spray during the maintenance phase.
“The study provides support for a positive benefit-risk evaluation for treatment with esketamine plus an oral antidepressant and provides further safety data regarding longer-term, intermittent dosing frequency treatment,” wrote Ella J. Daly, MD, from Janssen Research & Development – which also funded the study – and coauthors.
The researchers also noted that, overall, cognitive performance remained stable or improved after long-term, intermittent treatment with the esketamine nasal spray plus antidepressant.
The second study – an open-label, international study – involved 802 patients with major depressive disorder who had all failed to respond to at least two oral antidepressants. They were treated with an esketamine nasal spray (28 mg, 56 mg, or 84 mg) in combination with a new oral antidepressant.
The study involved a screening phase, induction phase, and optimization/maintenance phase, but only 24.9% of patients completed the optimization/maintenance phase. However, this was enough to meet a predefined total patient exposure, and the study was terminated by the sponsor.
More than three-quarters of patients responded during the induction phase, and by the end of the induction phase, 47.2% of patients had achieved remission. By the end of the optimization/maintenance phase, 58.2% of patients who entered that phase achieved remission.
More than 90% of patients experienced at least one adverse event, although most were mild to moderate. There were two deaths during the optimization/maintenance phase – one from acute respiratory and cardiac failure and one from suicide – but neither was considered as being related to the esketamine.
Five serious adverse events – anxiety, delusion, delirium, suicidal ideation, and suicidal attempt – were judged by the investigator to be related to the esketamine.
Researchers also saw no declines in performance on multiple cognitive domains, including visual learning and memory, across the entire study.
“The adverse event profile following an up to 1 year of exposure was consistent with previous observations of esketamine in the completed short-term phase 2 and 3 studies, and no unexpected safety findings were reported,” wrote Ewa Wajs, MD, also with Janssen, and coauthors.
Both studies were funded by Janssen Research & Development. Of the authors in the first study, 12 were employees of Janssen, and 10 declared funding from the pharmaceutical industry, including Janssen. Of the authors in the second study, 11 were employees of Janssen, and four declared a range of funding from the pharmaceutical industry.
SOURCE: Daly EJ et al. ASCP 2018, Poster W68. Wajs E et al. ASCP 2018, Poster T67.
FROM THE ASCP ANNUAL MEETING
Atopic eczema linked to cardiovascular disease risk
according to a case-control study published online May 23 in BMJ.
In a population-based cohort study, researchers compared the electronic health records of 387,439 adults with eczema and 1,528,477 patients without eczema in the United Kingddom, matched according to age, sex, general practice, and calendar time, during 1998-2015. Patients were followed up for a median of 5.1 years
With the exception of cardiovascular death, atopic eczema was associated with all cardiovascular outcomes (MI, unstable angina, heart failure, atrial fibrillation, and stroke). The associations were stronger for severe atopic eczema, with significantly higher risks of MI, unstable angina, atrial fibrillation, stroke, cardiovascular death, and coronary revascularization among individuals with severe atopic eczema, compared with controls.
After adjustment for potential mediators such as body mass index, smoking, hyperlipidemia, diabetes, and severe alcohol use, individuals with severe eczema had a significant 37% increased risk of MI, 67% greater risk of heart failure, 35% greater risk of atrial fibrillation, 30% greater risk of cardiovascular death, and 36% greater risk of coronary revascularization, compared with controls with no eczema.
Increased cardiovascular risks also were seen in individuals whose atopic eczema was active more than half the time at follow-up. This group had a 37% greater risk of heart failure, 36% greater risk of unstable angina, and 19% greater risk of stroke, as well as significantly elevated risks of MI, atrial fibrillation, cardiovascular death, and coronary revascularization, compared with those without eczema.
Overall, atopic eczema contributed around 2.4% of the population-attributable risk for unstable angina, and 1.9% for heart failure (the highest population attributable risks). Ethnicity or high-dose corticosteroid use did not significantly impact outcomes.
Richard J. Silverwood, PhD, from the London School of Hygiene and Tropical Medicine, and his coauthors wrote that previous work examining the relationship between atopic eczema and cardiovascular disease had shown inconsistent outcomes, with some studies even pointing to a possible protective effect of mild atopic eczema.
“Mechanistic work suggests that atopic eczema may be associated with increased platelet activation and decreased fibrinolysis, which may increase the risk of clotting, though a recent study found no association with metabolite levels,” the authors wrote.
They noted that the strengths of their study were that it was largest to examine the association between atopic eczema and cardiovascular risk, and that they had access to data on body mass index, smoking, and severe alcohol use for most of the study population, which enabled them to adjust for these potential mediators.
“Consideration should be given to developing prevention strategies to reduce the risk of cardiovascular disease among patients with severe or predominantly active atopic eczema, including awareness of and screening for conventional cardiovascular risk factors by those providing clinical care,” they wrote.
The study was supported by the Wellcome Trust, and no relevant conflicts of interest were declared.
SOURCE: Silverwood R et al. BMJ 2018 May 23;361:k1786. doi: 10.1136/bmj.k1786.
The evidence in favor of a link between chronic inflammatory conditions, such as rheumatoid arthritis, and cardiovascular disease is growing. However, there are conflicting data and some of the uncertainty may be a result of a dose-response effect, where the increased cardiovascular risk is seen only in people with more severe disease.
This study and its finding of increased cardiovascular risk in patients with severe or more active eczema supports the case for targeted screening of this group for standard cardiovascular disease risk factors. It also could prompt incorporation of severe eczema as an independent cardiovascular disease risk factor in calculation of thresholds for primary prevention interventions.
The findings also may have implications for health care resources allocated to treatment of eczema, as prevention of cardiovascular disease could contribute to the argument in favor of the more expensive next-generation biologic treatments for eczema that are becoming available.
John R. Ingram, MD, is senior lecturer and consultant dermatologist, dermatology and academic wound healing in the division of infection and immunity at Cardiff (U.K.) University. These comments are taken from an accompanying editorial No conflicts of interest were declared. (BMJ. 2018 May 23. doi: 10.1136/bmj.k2064).
The evidence in favor of a link between chronic inflammatory conditions, such as rheumatoid arthritis, and cardiovascular disease is growing. However, there are conflicting data and some of the uncertainty may be a result of a dose-response effect, where the increased cardiovascular risk is seen only in people with more severe disease.
This study and its finding of increased cardiovascular risk in patients with severe or more active eczema supports the case for targeted screening of this group for standard cardiovascular disease risk factors. It also could prompt incorporation of severe eczema as an independent cardiovascular disease risk factor in calculation of thresholds for primary prevention interventions.
The findings also may have implications for health care resources allocated to treatment of eczema, as prevention of cardiovascular disease could contribute to the argument in favor of the more expensive next-generation biologic treatments for eczema that are becoming available.
John R. Ingram, MD, is senior lecturer and consultant dermatologist, dermatology and academic wound healing in the division of infection and immunity at Cardiff (U.K.) University. These comments are taken from an accompanying editorial No conflicts of interest were declared. (BMJ. 2018 May 23. doi: 10.1136/bmj.k2064).
The evidence in favor of a link between chronic inflammatory conditions, such as rheumatoid arthritis, and cardiovascular disease is growing. However, there are conflicting data and some of the uncertainty may be a result of a dose-response effect, where the increased cardiovascular risk is seen only in people with more severe disease.
This study and its finding of increased cardiovascular risk in patients with severe or more active eczema supports the case for targeted screening of this group for standard cardiovascular disease risk factors. It also could prompt incorporation of severe eczema as an independent cardiovascular disease risk factor in calculation of thresholds for primary prevention interventions.
The findings also may have implications for health care resources allocated to treatment of eczema, as prevention of cardiovascular disease could contribute to the argument in favor of the more expensive next-generation biologic treatments for eczema that are becoming available.
John R. Ingram, MD, is senior lecturer and consultant dermatologist, dermatology and academic wound healing in the division of infection and immunity at Cardiff (U.K.) University. These comments are taken from an accompanying editorial No conflicts of interest were declared. (BMJ. 2018 May 23. doi: 10.1136/bmj.k2064).
according to a case-control study published online May 23 in BMJ.
In a population-based cohort study, researchers compared the electronic health records of 387,439 adults with eczema and 1,528,477 patients without eczema in the United Kingddom, matched according to age, sex, general practice, and calendar time, during 1998-2015. Patients were followed up for a median of 5.1 years
With the exception of cardiovascular death, atopic eczema was associated with all cardiovascular outcomes (MI, unstable angina, heart failure, atrial fibrillation, and stroke). The associations were stronger for severe atopic eczema, with significantly higher risks of MI, unstable angina, atrial fibrillation, stroke, cardiovascular death, and coronary revascularization among individuals with severe atopic eczema, compared with controls.
After adjustment for potential mediators such as body mass index, smoking, hyperlipidemia, diabetes, and severe alcohol use, individuals with severe eczema had a significant 37% increased risk of MI, 67% greater risk of heart failure, 35% greater risk of atrial fibrillation, 30% greater risk of cardiovascular death, and 36% greater risk of coronary revascularization, compared with controls with no eczema.
Increased cardiovascular risks also were seen in individuals whose atopic eczema was active more than half the time at follow-up. This group had a 37% greater risk of heart failure, 36% greater risk of unstable angina, and 19% greater risk of stroke, as well as significantly elevated risks of MI, atrial fibrillation, cardiovascular death, and coronary revascularization, compared with those without eczema.
Overall, atopic eczema contributed around 2.4% of the population-attributable risk for unstable angina, and 1.9% for heart failure (the highest population attributable risks). Ethnicity or high-dose corticosteroid use did not significantly impact outcomes.
Richard J. Silverwood, PhD, from the London School of Hygiene and Tropical Medicine, and his coauthors wrote that previous work examining the relationship between atopic eczema and cardiovascular disease had shown inconsistent outcomes, with some studies even pointing to a possible protective effect of mild atopic eczema.
“Mechanistic work suggests that atopic eczema may be associated with increased platelet activation and decreased fibrinolysis, which may increase the risk of clotting, though a recent study found no association with metabolite levels,” the authors wrote.
They noted that the strengths of their study were that it was largest to examine the association between atopic eczema and cardiovascular risk, and that they had access to data on body mass index, smoking, and severe alcohol use for most of the study population, which enabled them to adjust for these potential mediators.
“Consideration should be given to developing prevention strategies to reduce the risk of cardiovascular disease among patients with severe or predominantly active atopic eczema, including awareness of and screening for conventional cardiovascular risk factors by those providing clinical care,” they wrote.
The study was supported by the Wellcome Trust, and no relevant conflicts of interest were declared.
SOURCE: Silverwood R et al. BMJ 2018 May 23;361:k1786. doi: 10.1136/bmj.k1786.
according to a case-control study published online May 23 in BMJ.
In a population-based cohort study, researchers compared the electronic health records of 387,439 adults with eczema and 1,528,477 patients without eczema in the United Kingddom, matched according to age, sex, general practice, and calendar time, during 1998-2015. Patients were followed up for a median of 5.1 years
With the exception of cardiovascular death, atopic eczema was associated with all cardiovascular outcomes (MI, unstable angina, heart failure, atrial fibrillation, and stroke). The associations were stronger for severe atopic eczema, with significantly higher risks of MI, unstable angina, atrial fibrillation, stroke, cardiovascular death, and coronary revascularization among individuals with severe atopic eczema, compared with controls.
After adjustment for potential mediators such as body mass index, smoking, hyperlipidemia, diabetes, and severe alcohol use, individuals with severe eczema had a significant 37% increased risk of MI, 67% greater risk of heart failure, 35% greater risk of atrial fibrillation, 30% greater risk of cardiovascular death, and 36% greater risk of coronary revascularization, compared with controls with no eczema.
Increased cardiovascular risks also were seen in individuals whose atopic eczema was active more than half the time at follow-up. This group had a 37% greater risk of heart failure, 36% greater risk of unstable angina, and 19% greater risk of stroke, as well as significantly elevated risks of MI, atrial fibrillation, cardiovascular death, and coronary revascularization, compared with those without eczema.
Overall, atopic eczema contributed around 2.4% of the population-attributable risk for unstable angina, and 1.9% for heart failure (the highest population attributable risks). Ethnicity or high-dose corticosteroid use did not significantly impact outcomes.
Richard J. Silverwood, PhD, from the London School of Hygiene and Tropical Medicine, and his coauthors wrote that previous work examining the relationship between atopic eczema and cardiovascular disease had shown inconsistent outcomes, with some studies even pointing to a possible protective effect of mild atopic eczema.
“Mechanistic work suggests that atopic eczema may be associated with increased platelet activation and decreased fibrinolysis, which may increase the risk of clotting, though a recent study found no association with metabolite levels,” the authors wrote.
They noted that the strengths of their study were that it was largest to examine the association between atopic eczema and cardiovascular risk, and that they had access to data on body mass index, smoking, and severe alcohol use for most of the study population, which enabled them to adjust for these potential mediators.
“Consideration should be given to developing prevention strategies to reduce the risk of cardiovascular disease among patients with severe or predominantly active atopic eczema, including awareness of and screening for conventional cardiovascular risk factors by those providing clinical care,” they wrote.
The study was supported by the Wellcome Trust, and no relevant conflicts of interest were declared.
SOURCE: Silverwood R et al. BMJ 2018 May 23;361:k1786. doi: 10.1136/bmj.k1786.
FROM THE BMJ
Key clinical point: Severe atopic eczema may be associated with a significantly increased risk of cardiovascular disease.
Major finding: Individuals with severe atopic eczema were at increased for cardiovascular disease, including a 67% greater risk of heart failure.
Study details: A population-based case-control cohort study in 387,439 patients with atopic eczema, compared with more than 1 million controls.
Disclosures: The study was supported by the Wellcome Trust, and no relevant conflicts of interest were declared.
Source: Silverwood R et al. BMJ. 2018 May 23;361:k1786.
Uvulopalatopharyngoplasty may reduce cardiac risk in sleep apnea
Surgical remodeling of the tissues of the throat using uvulopalatopharyngoplasty (UPPP) could significantly reduce the cardiac complications of obstructive sleep apnea (OSA), according to a study published in Sleep Medicine.
Researchers examined the incidence of newly diagnosed myocardial infarction, congestive heart failure, and atrial fibrillation in 192,316 patients with a new diagnosis of obstructive sleep apnea – 22,213 of whom had undergone UPPP – and 961,590 controls.
The individuals who had had UPPP had a significantly lower incidence of all three cardiovascular events, compared with those who had not undergone the procedure. The hazard ratios for myocardial infarction, congestive heart failure, and atrial fibrillation among individuals with OSA who had uvulopalatopharyngoplasty, compared with controls, were 1.002, 0.757 and 1.117, respectively. By comparison, those hazard ratios in patients with OSA who had not had UPPP, compared with controls, were 1.070, 1.165, and 1.39 for myocardial infarction, congestive heart failure, and atrial fibrillation respectively.
These figures were after accounting for confounding factors, such as age, sex, diabetes, hypertension, and dyslipidemia.
The authors wrote that the most distinctive finding of their study was that uvulopalatopharyngoplasty lowered the incidence of congestive heart failure and atrial fibrillation in patients with obstructive sleep apnea to the point that they had the same level of risk as individuals without obstructive sleep apnea.
“Prior studies have evaluated the success of UPPP based on reductions of AHI [apnea-hypopnea index], with the average success rate for the surgery being low for most patients,” wrote Heung-Man Lee, MD, PhD, then from the Guro Hospital at Korea University, Seoul, and his coauthors.
“However, the current study suggests that the effects of UPPP, regardless of the effects on AHI, can significantly reduce cardiac morbidity in patients with OSA.”
Patients without diabetes showed more benefit from UPPP in reducing the incidence of congestive heart failure, compared with those with diabetes. However, those with diabetes showed greater reductions in the risk of atrial fibrillation, compared with those without diabetes.
Similarly, the incidence of atrial fibrillation was reduced after uvulopalatopharyngoplasty but only in patients with hypertension or dyslipidemia and not in those with normal blood pressure or lipid levels.
“These differences in outcomes after UPPP are probably due to the different etiologies of cardiovascular disease,” the authors wrote. “OSA increases free fatty acid in the blood because intermittent hypoxia associated with OSA induces adipose tissue lipolysis.”
One limitation of the study was the absence of polysomnography information. The researchers relied on diagnostic codes for confirmation of OSA. They also did not have information on other sleep apnea therapies, such as CPAP or a mandibular advancing device, which may have been used in the patients who did not undergo uvulopalatopharyngoplasty.
The study was supported by the Korean Society of Otorhinolaryngology Head and Neck Surgery. No conflicts of interest were declared.
SOURCE: Lee HM et al. Sleep Med. 2018 May;45:11-16.
Surgical remodeling of the tissues of the throat using uvulopalatopharyngoplasty (UPPP) could significantly reduce the cardiac complications of obstructive sleep apnea (OSA), according to a study published in Sleep Medicine.
Researchers examined the incidence of newly diagnosed myocardial infarction, congestive heart failure, and atrial fibrillation in 192,316 patients with a new diagnosis of obstructive sleep apnea – 22,213 of whom had undergone UPPP – and 961,590 controls.
The individuals who had had UPPP had a significantly lower incidence of all three cardiovascular events, compared with those who had not undergone the procedure. The hazard ratios for myocardial infarction, congestive heart failure, and atrial fibrillation among individuals with OSA who had uvulopalatopharyngoplasty, compared with controls, were 1.002, 0.757 and 1.117, respectively. By comparison, those hazard ratios in patients with OSA who had not had UPPP, compared with controls, were 1.070, 1.165, and 1.39 for myocardial infarction, congestive heart failure, and atrial fibrillation respectively.
These figures were after accounting for confounding factors, such as age, sex, diabetes, hypertension, and dyslipidemia.
The authors wrote that the most distinctive finding of their study was that uvulopalatopharyngoplasty lowered the incidence of congestive heart failure and atrial fibrillation in patients with obstructive sleep apnea to the point that they had the same level of risk as individuals without obstructive sleep apnea.
“Prior studies have evaluated the success of UPPP based on reductions of AHI [apnea-hypopnea index], with the average success rate for the surgery being low for most patients,” wrote Heung-Man Lee, MD, PhD, then from the Guro Hospital at Korea University, Seoul, and his coauthors.
“However, the current study suggests that the effects of UPPP, regardless of the effects on AHI, can significantly reduce cardiac morbidity in patients with OSA.”
Patients without diabetes showed more benefit from UPPP in reducing the incidence of congestive heart failure, compared with those with diabetes. However, those with diabetes showed greater reductions in the risk of atrial fibrillation, compared with those without diabetes.
Similarly, the incidence of atrial fibrillation was reduced after uvulopalatopharyngoplasty but only in patients with hypertension or dyslipidemia and not in those with normal blood pressure or lipid levels.
“These differences in outcomes after UPPP are probably due to the different etiologies of cardiovascular disease,” the authors wrote. “OSA increases free fatty acid in the blood because intermittent hypoxia associated with OSA induces adipose tissue lipolysis.”
One limitation of the study was the absence of polysomnography information. The researchers relied on diagnostic codes for confirmation of OSA. They also did not have information on other sleep apnea therapies, such as CPAP or a mandibular advancing device, which may have been used in the patients who did not undergo uvulopalatopharyngoplasty.
The study was supported by the Korean Society of Otorhinolaryngology Head and Neck Surgery. No conflicts of interest were declared.
SOURCE: Lee HM et al. Sleep Med. 2018 May;45:11-16.
Surgical remodeling of the tissues of the throat using uvulopalatopharyngoplasty (UPPP) could significantly reduce the cardiac complications of obstructive sleep apnea (OSA), according to a study published in Sleep Medicine.
Researchers examined the incidence of newly diagnosed myocardial infarction, congestive heart failure, and atrial fibrillation in 192,316 patients with a new diagnosis of obstructive sleep apnea – 22,213 of whom had undergone UPPP – and 961,590 controls.
The individuals who had had UPPP had a significantly lower incidence of all three cardiovascular events, compared with those who had not undergone the procedure. The hazard ratios for myocardial infarction, congestive heart failure, and atrial fibrillation among individuals with OSA who had uvulopalatopharyngoplasty, compared with controls, were 1.002, 0.757 and 1.117, respectively. By comparison, those hazard ratios in patients with OSA who had not had UPPP, compared with controls, were 1.070, 1.165, and 1.39 for myocardial infarction, congestive heart failure, and atrial fibrillation respectively.
These figures were after accounting for confounding factors, such as age, sex, diabetes, hypertension, and dyslipidemia.
The authors wrote that the most distinctive finding of their study was that uvulopalatopharyngoplasty lowered the incidence of congestive heart failure and atrial fibrillation in patients with obstructive sleep apnea to the point that they had the same level of risk as individuals without obstructive sleep apnea.
“Prior studies have evaluated the success of UPPP based on reductions of AHI [apnea-hypopnea index], with the average success rate for the surgery being low for most patients,” wrote Heung-Man Lee, MD, PhD, then from the Guro Hospital at Korea University, Seoul, and his coauthors.
“However, the current study suggests that the effects of UPPP, regardless of the effects on AHI, can significantly reduce cardiac morbidity in patients with OSA.”
Patients without diabetes showed more benefit from UPPP in reducing the incidence of congestive heart failure, compared with those with diabetes. However, those with diabetes showed greater reductions in the risk of atrial fibrillation, compared with those without diabetes.
Similarly, the incidence of atrial fibrillation was reduced after uvulopalatopharyngoplasty but only in patients with hypertension or dyslipidemia and not in those with normal blood pressure or lipid levels.
“These differences in outcomes after UPPP are probably due to the different etiologies of cardiovascular disease,” the authors wrote. “OSA increases free fatty acid in the blood because intermittent hypoxia associated with OSA induces adipose tissue lipolysis.”
One limitation of the study was the absence of polysomnography information. The researchers relied on diagnostic codes for confirmation of OSA. They also did not have information on other sleep apnea therapies, such as CPAP or a mandibular advancing device, which may have been used in the patients who did not undergo uvulopalatopharyngoplasty.
The study was supported by the Korean Society of Otorhinolaryngology Head and Neck Surgery. No conflicts of interest were declared.
SOURCE: Lee HM et al. Sleep Med. 2018 May;45:11-16.
FROM SLEEP MEDICINE
Key clinical point: Uvulopalatopharyngoplasty might avert cardiac complications caused by obstructive sleep apnea.
Major finding: Compared with controls, the hazard ratios for MI, congestive heart failure, and atrial fibrillation 1.002, 0.757, and 1.117, respectively, among individuals with OSA who had had UPPP and 1.070, 1.165, and 1.39 among those who had not had UPPP.
Study details: Study of 192,316 patients with obstructive sleep apnea and 961,590 controls.
Disclosures: The study was supported by the Korean Society of Otorhinolaryngology–Head and Neck Surgery. No conflicts of interest were declared.
Source: Lee HM et al. Sleep Med. 2018 May;45:11-16.
Breath test may detect esophagogastric cancer
A breath test that analyzes volatile organic compounds to detect esophagogastric cancer showed similar diagnostic accuracy to an existing test for endoscopy referral based on clinical parameters, based on a study in 335 patients – 163 with esophagogastric cancer and 172 controls.
The resulting test, which examined the concentrations of volatile organic compounds including butyric acid, hexanoic acid, butanal, and decanal, had a sensitivity of 80%, a specificity of 81%, and an area under the curve of 0.85. However, all of the patients had T3-stage esophagogastric cancer, so there is no indication about whether the breath test would be effective at picking up earlier T1-stage cancers, the authors wrote in the study, published online May 17 in JAMA Oncology.
By comparison, the clinical parameters test based on the NICE guidelines for endoscopy referral has a sensitivity of 59%, a specificity of 81% and an area under the curve of 0.72. These guidelines use age thresholds and symptom criteria such as dyspepsia, but the authors commented that there still remains a huge degree of variability in referral patterns for endoscopy.
“The breath test for esophagogastric cancer aims to provide clinicians with an objective assessment of need for endoscopic referral,” wrote Sheraz R. Markar, PhD, of the department of surgery & cancer at Imperial College London and his coauthors.
The authors said the diagnostic accuracy of the breath test also compared favorably with other cancer diagnostic technologies such as the fecal occult blood test – for which the sensitivity ranges from 30% to 70% – and the Cytosponge test for Barrett esophagus, which has a sensitivity of 73%.
Because all five volatile organic compounds showed an association with esophagogastric cancer, the authors suggested that there could be the possibility of calculating a more stratified risk of cancer for individual patients.
The study found no significant differences in the concentration of the five volatile organic compounds used in the test between patients with esophageal or those with gastric cancer.
The authors noted that with fecal occult blood testing and the Cytosponge test, multiple episodes of testing were known to increase the sensitivity, so this could be another area for future research in breath testing.
The breath test was seen as something that could be used in primary care to identify patients with nonspecific symptoms who should be referred for endoscopy.
“This view has been endorsed by our recent finding that the diagnostic model for OGC [oesophagogastric cancer] is different from that for colorectal cancer, providing the concept for a single breath test for multiple gastrointestinal cancers,” the authors wrote.
“If a clinician is presented with a patient with gastrointestinal symptoms that do not prompt referral based on NICE [National Institute for Health and Care Excellence] criteria, he/she would not need to watch and wait to see if symptoms worsen but could offer the exhaled breath test immediately.”
This approach could help avoid unnecessary endoscopies, which are expensive and have a low diagnostic yield. The breath test could also be administered by a nurse.
One author declared support from the National Institute of Health Research, and the study was supported by the National Institute for Health Research, the Rosetrees Trust and Stoneygate Trust. No conflicts of interest were declared.
SOURCE: Markar SR et al. JAMA Oncol. 2018 May 17. doi: 10.1001/jamaoncol.2018.0991.
A breath test that analyzes volatile organic compounds to detect esophagogastric cancer showed similar diagnostic accuracy to an existing test for endoscopy referral based on clinical parameters, based on a study in 335 patients – 163 with esophagogastric cancer and 172 controls.
The resulting test, which examined the concentrations of volatile organic compounds including butyric acid, hexanoic acid, butanal, and decanal, had a sensitivity of 80%, a specificity of 81%, and an area under the curve of 0.85. However, all of the patients had T3-stage esophagogastric cancer, so there is no indication about whether the breath test would be effective at picking up earlier T1-stage cancers, the authors wrote in the study, published online May 17 in JAMA Oncology.
By comparison, the clinical parameters test based on the NICE guidelines for endoscopy referral has a sensitivity of 59%, a specificity of 81% and an area under the curve of 0.72. These guidelines use age thresholds and symptom criteria such as dyspepsia, but the authors commented that there still remains a huge degree of variability in referral patterns for endoscopy.
“The breath test for esophagogastric cancer aims to provide clinicians with an objective assessment of need for endoscopic referral,” wrote Sheraz R. Markar, PhD, of the department of surgery & cancer at Imperial College London and his coauthors.
The authors said the diagnostic accuracy of the breath test also compared favorably with other cancer diagnostic technologies such as the fecal occult blood test – for which the sensitivity ranges from 30% to 70% – and the Cytosponge test for Barrett esophagus, which has a sensitivity of 73%.
Because all five volatile organic compounds showed an association with esophagogastric cancer, the authors suggested that there could be the possibility of calculating a more stratified risk of cancer for individual patients.
The study found no significant differences in the concentration of the five volatile organic compounds used in the test between patients with esophageal or those with gastric cancer.
The authors noted that with fecal occult blood testing and the Cytosponge test, multiple episodes of testing were known to increase the sensitivity, so this could be another area for future research in breath testing.
The breath test was seen as something that could be used in primary care to identify patients with nonspecific symptoms who should be referred for endoscopy.
“This view has been endorsed by our recent finding that the diagnostic model for OGC [oesophagogastric cancer] is different from that for colorectal cancer, providing the concept for a single breath test for multiple gastrointestinal cancers,” the authors wrote.
“If a clinician is presented with a patient with gastrointestinal symptoms that do not prompt referral based on NICE [National Institute for Health and Care Excellence] criteria, he/she would not need to watch and wait to see if symptoms worsen but could offer the exhaled breath test immediately.”
This approach could help avoid unnecessary endoscopies, which are expensive and have a low diagnostic yield. The breath test could also be administered by a nurse.
One author declared support from the National Institute of Health Research, and the study was supported by the National Institute for Health Research, the Rosetrees Trust and Stoneygate Trust. No conflicts of interest were declared.
SOURCE: Markar SR et al. JAMA Oncol. 2018 May 17. doi: 10.1001/jamaoncol.2018.0991.
A breath test that analyzes volatile organic compounds to detect esophagogastric cancer showed similar diagnostic accuracy to an existing test for endoscopy referral based on clinical parameters, based on a study in 335 patients – 163 with esophagogastric cancer and 172 controls.
The resulting test, which examined the concentrations of volatile organic compounds including butyric acid, hexanoic acid, butanal, and decanal, had a sensitivity of 80%, a specificity of 81%, and an area under the curve of 0.85. However, all of the patients had T3-stage esophagogastric cancer, so there is no indication about whether the breath test would be effective at picking up earlier T1-stage cancers, the authors wrote in the study, published online May 17 in JAMA Oncology.
By comparison, the clinical parameters test based on the NICE guidelines for endoscopy referral has a sensitivity of 59%, a specificity of 81% and an area under the curve of 0.72. These guidelines use age thresholds and symptom criteria such as dyspepsia, but the authors commented that there still remains a huge degree of variability in referral patterns for endoscopy.
“The breath test for esophagogastric cancer aims to provide clinicians with an objective assessment of need for endoscopic referral,” wrote Sheraz R. Markar, PhD, of the department of surgery & cancer at Imperial College London and his coauthors.
The authors said the diagnostic accuracy of the breath test also compared favorably with other cancer diagnostic technologies such as the fecal occult blood test – for which the sensitivity ranges from 30% to 70% – and the Cytosponge test for Barrett esophagus, which has a sensitivity of 73%.
Because all five volatile organic compounds showed an association with esophagogastric cancer, the authors suggested that there could be the possibility of calculating a more stratified risk of cancer for individual patients.
The study found no significant differences in the concentration of the five volatile organic compounds used in the test between patients with esophageal or those with gastric cancer.
The authors noted that with fecal occult blood testing and the Cytosponge test, multiple episodes of testing were known to increase the sensitivity, so this could be another area for future research in breath testing.
The breath test was seen as something that could be used in primary care to identify patients with nonspecific symptoms who should be referred for endoscopy.
“This view has been endorsed by our recent finding that the diagnostic model for OGC [oesophagogastric cancer] is different from that for colorectal cancer, providing the concept for a single breath test for multiple gastrointestinal cancers,” the authors wrote.
“If a clinician is presented with a patient with gastrointestinal symptoms that do not prompt referral based on NICE [National Institute for Health and Care Excellence] criteria, he/she would not need to watch and wait to see if symptoms worsen but could offer the exhaled breath test immediately.”
This approach could help avoid unnecessary endoscopies, which are expensive and have a low diagnostic yield. The breath test could also be administered by a nurse.
One author declared support from the National Institute of Health Research, and the study was supported by the National Institute for Health Research, the Rosetrees Trust and Stoneygate Trust. No conflicts of interest were declared.
SOURCE: Markar SR et al. JAMA Oncol. 2018 May 17. doi: 10.1001/jamaoncol.2018.0991.
FROM JAMA ONCOLOGY
Key clinical point: A breath test could help detect esophagogastric cancer.
Major finding:
Study details: Study in 163 with esophagogastric cancer and 172 controls.
Disclosures: One author declared support from the National Institute of Health Research, and the study was supported by the National Institute for Health Research, the Rosetrees Trust and Stoneygate Trust. No conflicts of interest were declared.
Source: Markar SR et al. JAMA Oncol. 2018 May 17. doi:10.1001/jamaoncol.2018.0991.
Physical inactivity linked to lymphoma risk
A lifetime of physical inactivity could significantly increase the risk of developing both Hodgkin and non-Hodgkin lymphoma, according to a case-control study.
Researchers examined self-reported lifetime physical activity in 87 patients with Hodgkin lymphoma and 236 patients with non-Hodgkin lymphoma, as well as 1,300 cancer-free controls.
Researchers also found a nearly threefold higher risk of Hodgkin lymphoma among overweight and obese individuals who were physically inactive, compared with those who were active (odds ratio, 2.79; P = .01). Similarly, physically inactive individuals who had never smoked had a greater than threefold increase in risk, compared with never-smokers who were active (OR, 3.30; P less than .001). But despite these significant associations for smoking and weight, the small samples sizes meant they were not significant in multivariable-adjusted models, the researchers noted. For non-Hodgkin lymphoma, the associations between obesity/overweight and smoking status were also not statistically significant in multivariable-adjusted models.
Previous studies looking at the role of physical activity in Hodgkin and non-Hodgkin lymphoma had yielded mixed and inconclusive results. Since then, researchers have begun to specifically consider the role of physical inactivity, rather than physical activity, as the exposure of interest.
“An additional advantage of identifying inactivity as the exposure of interest is that a body of literature suggests that those who are at the lower end of the physical activity continuum are less likely to overreport physical activity than those who engage in greater levels of physical activity,” the researchers wrote.
They acknowledged that relying on self-reported levels of physical activity was a limitation of their study. However, they also pointed out that previous research suggested that simplified physical activity questionnaires that took a dichotomous approach to activity/inactivity were effective at identifying the most physically inactivity individuals in a population.
“Continued evidence for adverse associations between physical inactivity and cancer endpoints substantiate a powerful public health message that any amount of regular activity appears to associate with decreased cancer risk,” they wrote.
One researcher was supported by the New York State Department of Health. No conflicts of interest were reported.
SOURCE: Etter JL et al. Leuk Res. 2018 Mar 27;69:7-11.
A lifetime of physical inactivity could significantly increase the risk of developing both Hodgkin and non-Hodgkin lymphoma, according to a case-control study.
Researchers examined self-reported lifetime physical activity in 87 patients with Hodgkin lymphoma and 236 patients with non-Hodgkin lymphoma, as well as 1,300 cancer-free controls.
Researchers also found a nearly threefold higher risk of Hodgkin lymphoma among overweight and obese individuals who were physically inactive, compared with those who were active (odds ratio, 2.79; P = .01). Similarly, physically inactive individuals who had never smoked had a greater than threefold increase in risk, compared with never-smokers who were active (OR, 3.30; P less than .001). But despite these significant associations for smoking and weight, the small samples sizes meant they were not significant in multivariable-adjusted models, the researchers noted. For non-Hodgkin lymphoma, the associations between obesity/overweight and smoking status were also not statistically significant in multivariable-adjusted models.
Previous studies looking at the role of physical activity in Hodgkin and non-Hodgkin lymphoma had yielded mixed and inconclusive results. Since then, researchers have begun to specifically consider the role of physical inactivity, rather than physical activity, as the exposure of interest.
“An additional advantage of identifying inactivity as the exposure of interest is that a body of literature suggests that those who are at the lower end of the physical activity continuum are less likely to overreport physical activity than those who engage in greater levels of physical activity,” the researchers wrote.
They acknowledged that relying on self-reported levels of physical activity was a limitation of their study. However, they also pointed out that previous research suggested that simplified physical activity questionnaires that took a dichotomous approach to activity/inactivity were effective at identifying the most physically inactivity individuals in a population.
“Continued evidence for adverse associations between physical inactivity and cancer endpoints substantiate a powerful public health message that any amount of regular activity appears to associate with decreased cancer risk,” they wrote.
One researcher was supported by the New York State Department of Health. No conflicts of interest were reported.
SOURCE: Etter JL et al. Leuk Res. 2018 Mar 27;69:7-11.
A lifetime of physical inactivity could significantly increase the risk of developing both Hodgkin and non-Hodgkin lymphoma, according to a case-control study.
Researchers examined self-reported lifetime physical activity in 87 patients with Hodgkin lymphoma and 236 patients with non-Hodgkin lymphoma, as well as 1,300 cancer-free controls.
Researchers also found a nearly threefold higher risk of Hodgkin lymphoma among overweight and obese individuals who were physically inactive, compared with those who were active (odds ratio, 2.79; P = .01). Similarly, physically inactive individuals who had never smoked had a greater than threefold increase in risk, compared with never-smokers who were active (OR, 3.30; P less than .001). But despite these significant associations for smoking and weight, the small samples sizes meant they were not significant in multivariable-adjusted models, the researchers noted. For non-Hodgkin lymphoma, the associations between obesity/overweight and smoking status were also not statistically significant in multivariable-adjusted models.
Previous studies looking at the role of physical activity in Hodgkin and non-Hodgkin lymphoma had yielded mixed and inconclusive results. Since then, researchers have begun to specifically consider the role of physical inactivity, rather than physical activity, as the exposure of interest.
“An additional advantage of identifying inactivity as the exposure of interest is that a body of literature suggests that those who are at the lower end of the physical activity continuum are less likely to overreport physical activity than those who engage in greater levels of physical activity,” the researchers wrote.
They acknowledged that relying on self-reported levels of physical activity was a limitation of their study. However, they also pointed out that previous research suggested that simplified physical activity questionnaires that took a dichotomous approach to activity/inactivity were effective at identifying the most physically inactivity individuals in a population.
“Continued evidence for adverse associations between physical inactivity and cancer endpoints substantiate a powerful public health message that any amount of regular activity appears to associate with decreased cancer risk,” they wrote.
One researcher was supported by the New York State Department of Health. No conflicts of interest were reported.
SOURCE: Etter JL et al. Leuk Res. 2018 Mar 27;69:7-11.
FROM LEUKEMIA RESEARCH
Key clinical point:
Major finding: A lifetime of physical inactivity is associated with a 90% increased risk of Hodgkin lymphoma and a 35% increased risk of non-Hodgkin lymphoma.Study details: A case-control study in 323 patients with Hodgkin or non-Hodgkin lymphoma and 1,300 cancer-free controls.
Disclosures: One researcher was supported by the New York State Department of Health. No conflicts of interest were declared.
Source: Etter JL et al. Leuk Res. 2018 Mar 27;69:7-11.
Guidelines-based intervention improves pediatrician management of acne
A guidelines-based educational program on treating acne in teenagers has led to significant improvements in pediatricians’ management of the condition and decreased referrals to dermatologists, new research suggests.
A research letter published online May in the Journal of the American Academy of Dermatology described the results of a study involving 116 pediatricians, who participated in an educational program, including brief live sessions, on how to manage acne in teenagers.
After 4 months, researchers saw that acne-coded visits to pediatricians increased by 18% (P less than .001), but this did not translate to more work for the physicians involved; instead, three-quarters of those involved said the treatment process involved “minimal to no work.”
At the same time, the intervention was associated with a 26% decrease in the percentage of acne referrals to dermatologists, reported Jenna Borok of the Rady Children’s Hospital in San Diego, and her coauthors.
The researchers saw a fivefold increase in the likelihood of pediatricians prescribing retinoids (P = .003), after controlling for confounding factors such as sex and insurance status, and significantly less topical clindamycin being prescribed.
The study was initiated to address what the authors described as a “practice gap” between pediatricians treating acne, compared with dermatologists treating acne, which included significantly lower prescribing rates of topical retinoids among pediatricians.
Ms. Borok and her coauthors wrote that their educational program and prescribing tool aimed to address this practice gap without increasing the workload for pediatricians or dermatologists. “Adherence to guidelines by pediatricians has the potential to improve treatment provided in the primary care setting, better patient satisfaction, and allow greater access to dermatologists and pediatric dermatologists for patients with more severe acne and other conditions.”
Acknowledging that the study took place over a relatively short period of time, the authors said future research would examine the impact of the educational program and ordering tool on patient acne outcomes.
No funding or conflicts of interest were declared.
SOURCE: Borok J et al. J Am Acad Dermatol. 2018 May 9. doi: 10.1016/j.jaad.2018.04.055.
A guidelines-based educational program on treating acne in teenagers has led to significant improvements in pediatricians’ management of the condition and decreased referrals to dermatologists, new research suggests.
A research letter published online May in the Journal of the American Academy of Dermatology described the results of a study involving 116 pediatricians, who participated in an educational program, including brief live sessions, on how to manage acne in teenagers.
After 4 months, researchers saw that acne-coded visits to pediatricians increased by 18% (P less than .001), but this did not translate to more work for the physicians involved; instead, three-quarters of those involved said the treatment process involved “minimal to no work.”
At the same time, the intervention was associated with a 26% decrease in the percentage of acne referrals to dermatologists, reported Jenna Borok of the Rady Children’s Hospital in San Diego, and her coauthors.
The researchers saw a fivefold increase in the likelihood of pediatricians prescribing retinoids (P = .003), after controlling for confounding factors such as sex and insurance status, and significantly less topical clindamycin being prescribed.
The study was initiated to address what the authors described as a “practice gap” between pediatricians treating acne, compared with dermatologists treating acne, which included significantly lower prescribing rates of topical retinoids among pediatricians.
Ms. Borok and her coauthors wrote that their educational program and prescribing tool aimed to address this practice gap without increasing the workload for pediatricians or dermatologists. “Adherence to guidelines by pediatricians has the potential to improve treatment provided in the primary care setting, better patient satisfaction, and allow greater access to dermatologists and pediatric dermatologists for patients with more severe acne and other conditions.”
Acknowledging that the study took place over a relatively short period of time, the authors said future research would examine the impact of the educational program and ordering tool on patient acne outcomes.
No funding or conflicts of interest were declared.
SOURCE: Borok J et al. J Am Acad Dermatol. 2018 May 9. doi: 10.1016/j.jaad.2018.04.055.
A guidelines-based educational program on treating acne in teenagers has led to significant improvements in pediatricians’ management of the condition and decreased referrals to dermatologists, new research suggests.
A research letter published online May in the Journal of the American Academy of Dermatology described the results of a study involving 116 pediatricians, who participated in an educational program, including brief live sessions, on how to manage acne in teenagers.
After 4 months, researchers saw that acne-coded visits to pediatricians increased by 18% (P less than .001), but this did not translate to more work for the physicians involved; instead, three-quarters of those involved said the treatment process involved “minimal to no work.”
At the same time, the intervention was associated with a 26% decrease in the percentage of acne referrals to dermatologists, reported Jenna Borok of the Rady Children’s Hospital in San Diego, and her coauthors.
The researchers saw a fivefold increase in the likelihood of pediatricians prescribing retinoids (P = .003), after controlling for confounding factors such as sex and insurance status, and significantly less topical clindamycin being prescribed.
The study was initiated to address what the authors described as a “practice gap” between pediatricians treating acne, compared with dermatologists treating acne, which included significantly lower prescribing rates of topical retinoids among pediatricians.
Ms. Borok and her coauthors wrote that their educational program and prescribing tool aimed to address this practice gap without increasing the workload for pediatricians or dermatologists. “Adherence to guidelines by pediatricians has the potential to improve treatment provided in the primary care setting, better patient satisfaction, and allow greater access to dermatologists and pediatric dermatologists for patients with more severe acne and other conditions.”
Acknowledging that the study took place over a relatively short period of time, the authors said future research would examine the impact of the educational program and ordering tool on patient acne outcomes.
No funding or conflicts of interest were declared.
SOURCE: Borok J et al. J Am Acad Dermatol. 2018 May 9. doi: 10.1016/j.jaad.2018.04.055.
FROM THE JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
Key clinical point:
Major finding: An education program for pediatricians on acne treatment increased retinoid prescribing but decreased referrals to dermatologists.
Study details: Interventional study in 116 pediatricians.
Disclosures: No funding or conflicts of interest were declared.
Source: Borok J et al. J Am Acad Dermatol. 2018 May 9. doi: 10.1016/j.jaad.2018.04.055.
Is cancer immunotherapy more effective in men than women?
Cancer immunotherapy using checkpoint inhibitors may achieve greater mortality reductions in men than they do in women, new research has suggested.
In a meta-analysis and systematic review published in Lancet Oncology, researchers analyzed 20 randomized, controlled trials of immune checkpoint inhibitors that included detail on overall survival and patients’ sex; altogether, these studies involved 11,351 patients with advanced or metastatic cancers.
They found that while men treated with checkpoint inhibitors had a significant 28% reduced risk of death, compared with male controls, the survival benefit in women was smaller (14% reduced risk of death, compared with female controls).
Fabio Conforti, MD, from the European Institute of Oncology, Milan, and coauthors commented that the magnitude of the difference between the effect seen men and that in women was clinically significant.
“The pooled reduction of risk of death was double the size for male patients than for female patients – a difference that is similar to the size of the difference in survival benefit observed between patients with non–small cell lung cancer with PD-L1 positive (greater than 1%) tumors versus negative tumors, who were treated with anti-PD-1,” they wrote.
This difference between the benefit seen men and that in women was evident across all the subgroups in the study, which included subgroups based on cancer histotype, line of treatment, drugs used, and type of control.
However there was greater heterogeneity in the magnitude of the effect of checkpoint inhibitors on mortality in men than there was in women. The authors suggested this could be explained by the fact that the drugs have lower efficacy in women and this may therefore reduce the variability of results when compared with those in men.
The authors also looked at whether the studies that compared immunotherapies with nonimmunological therapies might show a different effect, but they still found a significantly higher benefit in men, compared with women.
The overall study population was two-thirds male and one-third female. The checkpoint inhibitors used were ipilimumab, tremelimumab, nivolumab, and pembrolizumab, and the trials were conducted in patients with melanoma, non–small cell lung cancer, head and neck cancer, renal cell carcinoma, urothelial tumors, gastric tumors, and mesothelioma.
Men have almost double the risk of mortality from cancer than do women, the authors said, with the greatest differences seen in melanoma, lung cancer, larynx cancer, esophagus cancer, and bladder cancer.
“This male-biased mortality is hypothesized to reflect differences not only in behavioral and biological factors, including causes of cancer and hormonal regulation, but also in the immune system.”
Despite this, sex is rarely taken into account when new therapeutic approaches are tested, the authors said.
They also commented on the fact that there was a relatively low number of women included in each trial, an issue that was recognized as far back as the 1990s as a major problem in medical trials.
“Our results further highlight this problem, showing clinically relevant differences in the efficacy of two important classes of immunological drugs, namely anti–CTLA-4 and anti–PD-1 antibodies, when compared with controls in male and female patients with advanced solid tumors,” they wrote.
They noted that they couldn’t exclude the possibility that the effect may be the result of other variables that were distributed differently between the sexes. However, they also qualified this by saying that variables known to affect the efficacy of immune checkpoint inhibitors, such as PD-L1 expression and mutation status, were not likely to explain the results.
Given their findings, the authors said a patient’s sex should be taken into account when weighing the risks and benefits of checkpoint inhibitors given the magnitude of benefit was sex-dependent. They also called for future immunotherapy studies to include more women.
No funding or conflicts of interest were declared.
SOURCE: Conforti F et al. Lancet Oncol. 2018 May 16. doi: 10.1016/S1470-2045(18)30261-4.
While cancer immunotherapy represents one of the most significant clinical advances in cancer treatment in the past decade, the basic but important clinical question about different effects between men and woman has not been addressed until now. The authors of this study are to be congratulated on such a comprehensive and well-conducted analysis, but the data does not completely support their final conclusion that checkpoint inhibitors benefit men more than women.
There are a large number of baseline characteristics of solid tumors that might differ between men and women and that have also been reported to impact the outcomes of patients treated with checkpoint inhibitors. Some of these may be lifestyle or behavioral characteristics – such as different smoking habits between men and women with non–small cell lung cancer – or differences in the distribution of oncogenic driver mutations between men and women.
We should therefore be cautious in jumping to conclusions and changing the current standard of care with respect to checkpoint inhibitors. In particular, we should not be denying treatment to women who are otherwise indicated for checkpoint inhibitors, based on these findings.
Omar Abdel-Rahman, MD, is from the clinical oncology department of the faculty of medicine at Ain Shams University in Cairo and from the Tom Baker Cancer Centre in Calgary. These comments are taken from an accompanying editorial (Lancet Oncol. 2018 May 16. doi: 10.1016/S1470-2045[18]30270-5.) No conflicts of interest were declared.
While cancer immunotherapy represents one of the most significant clinical advances in cancer treatment in the past decade, the basic but important clinical question about different effects between men and woman has not been addressed until now. The authors of this study are to be congratulated on such a comprehensive and well-conducted analysis, but the data does not completely support their final conclusion that checkpoint inhibitors benefit men more than women.
There are a large number of baseline characteristics of solid tumors that might differ between men and women and that have also been reported to impact the outcomes of patients treated with checkpoint inhibitors. Some of these may be lifestyle or behavioral characteristics – such as different smoking habits between men and women with non–small cell lung cancer – or differences in the distribution of oncogenic driver mutations between men and women.
We should therefore be cautious in jumping to conclusions and changing the current standard of care with respect to checkpoint inhibitors. In particular, we should not be denying treatment to women who are otherwise indicated for checkpoint inhibitors, based on these findings.
Omar Abdel-Rahman, MD, is from the clinical oncology department of the faculty of medicine at Ain Shams University in Cairo and from the Tom Baker Cancer Centre in Calgary. These comments are taken from an accompanying editorial (Lancet Oncol. 2018 May 16. doi: 10.1016/S1470-2045[18]30270-5.) No conflicts of interest were declared.
While cancer immunotherapy represents one of the most significant clinical advances in cancer treatment in the past decade, the basic but important clinical question about different effects between men and woman has not been addressed until now. The authors of this study are to be congratulated on such a comprehensive and well-conducted analysis, but the data does not completely support their final conclusion that checkpoint inhibitors benefit men more than women.
There are a large number of baseline characteristics of solid tumors that might differ between men and women and that have also been reported to impact the outcomes of patients treated with checkpoint inhibitors. Some of these may be lifestyle or behavioral characteristics – such as different smoking habits between men and women with non–small cell lung cancer – or differences in the distribution of oncogenic driver mutations between men and women.
We should therefore be cautious in jumping to conclusions and changing the current standard of care with respect to checkpoint inhibitors. In particular, we should not be denying treatment to women who are otherwise indicated for checkpoint inhibitors, based on these findings.
Omar Abdel-Rahman, MD, is from the clinical oncology department of the faculty of medicine at Ain Shams University in Cairo and from the Tom Baker Cancer Centre in Calgary. These comments are taken from an accompanying editorial (Lancet Oncol. 2018 May 16. doi: 10.1016/S1470-2045[18]30270-5.) No conflicts of interest were declared.
Cancer immunotherapy using checkpoint inhibitors may achieve greater mortality reductions in men than they do in women, new research has suggested.
In a meta-analysis and systematic review published in Lancet Oncology, researchers analyzed 20 randomized, controlled trials of immune checkpoint inhibitors that included detail on overall survival and patients’ sex; altogether, these studies involved 11,351 patients with advanced or metastatic cancers.
They found that while men treated with checkpoint inhibitors had a significant 28% reduced risk of death, compared with male controls, the survival benefit in women was smaller (14% reduced risk of death, compared with female controls).
Fabio Conforti, MD, from the European Institute of Oncology, Milan, and coauthors commented that the magnitude of the difference between the effect seen men and that in women was clinically significant.
“The pooled reduction of risk of death was double the size for male patients than for female patients – a difference that is similar to the size of the difference in survival benefit observed between patients with non–small cell lung cancer with PD-L1 positive (greater than 1%) tumors versus negative tumors, who were treated with anti-PD-1,” they wrote.
This difference between the benefit seen men and that in women was evident across all the subgroups in the study, which included subgroups based on cancer histotype, line of treatment, drugs used, and type of control.
However there was greater heterogeneity in the magnitude of the effect of checkpoint inhibitors on mortality in men than there was in women. The authors suggested this could be explained by the fact that the drugs have lower efficacy in women and this may therefore reduce the variability of results when compared with those in men.
The authors also looked at whether the studies that compared immunotherapies with nonimmunological therapies might show a different effect, but they still found a significantly higher benefit in men, compared with women.
The overall study population was two-thirds male and one-third female. The checkpoint inhibitors used were ipilimumab, tremelimumab, nivolumab, and pembrolizumab, and the trials were conducted in patients with melanoma, non–small cell lung cancer, head and neck cancer, renal cell carcinoma, urothelial tumors, gastric tumors, and mesothelioma.
Men have almost double the risk of mortality from cancer than do women, the authors said, with the greatest differences seen in melanoma, lung cancer, larynx cancer, esophagus cancer, and bladder cancer.
“This male-biased mortality is hypothesized to reflect differences not only in behavioral and biological factors, including causes of cancer and hormonal regulation, but also in the immune system.”
Despite this, sex is rarely taken into account when new therapeutic approaches are tested, the authors said.
They also commented on the fact that there was a relatively low number of women included in each trial, an issue that was recognized as far back as the 1990s as a major problem in medical trials.
“Our results further highlight this problem, showing clinically relevant differences in the efficacy of two important classes of immunological drugs, namely anti–CTLA-4 and anti–PD-1 antibodies, when compared with controls in male and female patients with advanced solid tumors,” they wrote.
They noted that they couldn’t exclude the possibility that the effect may be the result of other variables that were distributed differently between the sexes. However, they also qualified this by saying that variables known to affect the efficacy of immune checkpoint inhibitors, such as PD-L1 expression and mutation status, were not likely to explain the results.
Given their findings, the authors said a patient’s sex should be taken into account when weighing the risks and benefits of checkpoint inhibitors given the magnitude of benefit was sex-dependent. They also called for future immunotherapy studies to include more women.
No funding or conflicts of interest were declared.
SOURCE: Conforti F et al. Lancet Oncol. 2018 May 16. doi: 10.1016/S1470-2045(18)30261-4.
Cancer immunotherapy using checkpoint inhibitors may achieve greater mortality reductions in men than they do in women, new research has suggested.
In a meta-analysis and systematic review published in Lancet Oncology, researchers analyzed 20 randomized, controlled trials of immune checkpoint inhibitors that included detail on overall survival and patients’ sex; altogether, these studies involved 11,351 patients with advanced or metastatic cancers.
They found that while men treated with checkpoint inhibitors had a significant 28% reduced risk of death, compared with male controls, the survival benefit in women was smaller (14% reduced risk of death, compared with female controls).
Fabio Conforti, MD, from the European Institute of Oncology, Milan, and coauthors commented that the magnitude of the difference between the effect seen men and that in women was clinically significant.
“The pooled reduction of risk of death was double the size for male patients than for female patients – a difference that is similar to the size of the difference in survival benefit observed between patients with non–small cell lung cancer with PD-L1 positive (greater than 1%) tumors versus negative tumors, who were treated with anti-PD-1,” they wrote.
This difference between the benefit seen men and that in women was evident across all the subgroups in the study, which included subgroups based on cancer histotype, line of treatment, drugs used, and type of control.
However there was greater heterogeneity in the magnitude of the effect of checkpoint inhibitors on mortality in men than there was in women. The authors suggested this could be explained by the fact that the drugs have lower efficacy in women and this may therefore reduce the variability of results when compared with those in men.
The authors also looked at whether the studies that compared immunotherapies with nonimmunological therapies might show a different effect, but they still found a significantly higher benefit in men, compared with women.
The overall study population was two-thirds male and one-third female. The checkpoint inhibitors used were ipilimumab, tremelimumab, nivolumab, and pembrolizumab, and the trials were conducted in patients with melanoma, non–small cell lung cancer, head and neck cancer, renal cell carcinoma, urothelial tumors, gastric tumors, and mesothelioma.
Men have almost double the risk of mortality from cancer than do women, the authors said, with the greatest differences seen in melanoma, lung cancer, larynx cancer, esophagus cancer, and bladder cancer.
“This male-biased mortality is hypothesized to reflect differences not only in behavioral and biological factors, including causes of cancer and hormonal regulation, but also in the immune system.”
Despite this, sex is rarely taken into account when new therapeutic approaches are tested, the authors said.
They also commented on the fact that there was a relatively low number of women included in each trial, an issue that was recognized as far back as the 1990s as a major problem in medical trials.
“Our results further highlight this problem, showing clinically relevant differences in the efficacy of two important classes of immunological drugs, namely anti–CTLA-4 and anti–PD-1 antibodies, when compared with controls in male and female patients with advanced solid tumors,” they wrote.
They noted that they couldn’t exclude the possibility that the effect may be the result of other variables that were distributed differently between the sexes. However, they also qualified this by saying that variables known to affect the efficacy of immune checkpoint inhibitors, such as PD-L1 expression and mutation status, were not likely to explain the results.
Given their findings, the authors said a patient’s sex should be taken into account when weighing the risks and benefits of checkpoint inhibitors given the magnitude of benefit was sex-dependent. They also called for future immunotherapy studies to include more women.
No funding or conflicts of interest were declared.
SOURCE: Conforti F et al. Lancet Oncol. 2018 May 16. doi: 10.1016/S1470-2045(18)30261-4.
FROM LANCET ONCOLOGY
Key clinical point: Checkpoint inhibitors are linked with greater mortality reductions in men than in women.
Major finding: Checkpoint inhibitors are associated with a 28% reduction in cancer mortality in men and 14% in women.
Study details: Systematic review and meta-analysis of 20 randomized, controlled trials involving 11,351 patients.
Disclosures: No funding or conflicts of interest were declared.
Source: Conforti F et al. Lancet Oncol. 2018 May 16. doi: 10.1016/S1470-2045(18)30261-4.