comorbidity

Objective: To assess the effective dose range, safety, and tolerability of the novel selective orexin-2 receptor antagonist seltorexant in insomnia disorder.

Design, setting, and participants: This randomized, double-blind, active- and placebo-controlled, dose-finding, polysomnography study was conducted from November 2017 to April 2019 at 55 sites in 6 countries and analyzed in August 2019. The timeline for submission of this data for publication was impacted by internal strategic decision-making. Adults (aged 18-64 years) and older adults (aged 65-85 years) with insomnia (Insomnia Severity Index score ≥15) and no psychiatric comorbidity were included.

Interventions: Participants were randomized 1:1:1:1:1 to receive nightly oral-seltorexant (5 mg, 10 mg, or 20 mg), placebo, or zolpidem (5-10 mg) for 14 days.

Main outcomes and measures: Primary and key secondary outcomes included the dose-response relationship of night 1 latency to persistent sleep (LPS) and wake after sleep onset over the first 6 hours (WASO-6). Other secondary outcomes included night 13 LPS and WASO-6. Due to asymmetrical distributions of LPS and WASO-6 at baseline, log transformation was applied and results were expressed as back-transformed least-squares mean (LSM) ratios for comparisons between groups.

Results: Overall, 364 participants (mean [SD] age, 57.8 [12.4] years; 246 [67.6%] female) received seltorexant, 5 mg (n = 71), 10 mg (n = 74), or 20 mg (n = 71); placebo (n = 75); or zolpidem (n = 73). The night 1 dose-response relationship for LPS was significant (with trend test t statistics ≥3.99 and adjusted P values <.001 for all 4 prespecified models), with greater improvements in seltorexant, 10 mg and 20 mg, vs placebo (10 mg: LSM ratio, 0.64; 90% CI, 0.51-0.81; 20 mg: LSM ratio, 0.51; 90% CI, 0.41-0.64) and in seltorexant, 20 mg, vs zolpidem (LSM ratio, 0.71; 90% CI, 0.57-0.88). The night 1 dose-response relationship for WASO-6 was also significant, with trend test t statistics ≥3.99 and adjusted P values <.001 for all 4 prespecified models (seltorexant, 10 mg: LSM ratio, 0.68; 90% CI, 0.55-0.85; seltorexant, 20 mg: LSM ratio, 0.60; 90% CI, 0.48-0.74). Night 1 LPS and WASO-6 improvements were maintained on night 13 for seltorexant, 10 mg and 20 mg, but diminished for zolpidem. On night 13, compared with zolpidem, seltorexant, 10 mg and 20 mg, improved LPS by 30% and 28%, respectively, and seltorexant, 20 mg, improved WASO-6 by 31%. Treatment-emergent adverse events (TEAEs) were lower across the combined seltorexant doses (73/216 [33.8%]) relative to placebo (37/75 [49.3%]) and zolpidem (31/73 [42.5%]). Two participants experienced serious TEAEs during the double-blind phase (1 in the seltorexant, 20 mg, group and 1 in the zolpidem group). Three participants in the seltorexant, 5 mg, and 1 in the seltorexant, 20 mg, group experienced asymptomatic electrocardiogram-related TEAEs leading to discontinuation.

Conclusions and relevance: Among participants with insomnia in this study, seltorexant, 10 mg and 20 mg, improved sleep initiation and maintenance throughout 14 days of treatment. Seltorexant was generally well tolerated.

Trial registration: ClinicalTrials.gov Identifier: NCT03375203.

Author/s:

Sofie Mesens, Andrew D Krystal, Rama Melkote, Haiyan Xu, Gahan Pandina, Jay B Saoud, Remy Luthringer, Adam Savitz, Wayne C Drevets

Diagnosis and Treatment of Chronic Spontaneous Urticaria

Alex Haga — Tue, 01 Oct 2024 17:10:47 +0000

Date Added:

October 1, 2024

Journal/Publication:

JAMA

Publication Date:

September 26, 2024

URL:

Diagnosis and Treatment of Chronic Spontaneous Urticaria

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Web Page

Keywords

Chronic Spontaneous Urticaria

MeSH

An 18-minute audiotape on the subject of chronic urticaria. James W. Mold, MD, MPH

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Chronic spontaneous urticaria affects approximately 1% of the general population worldwide, impairs patients’ quality of life, and is associated with multiple comorbidities. Pavel Kolkhir, MD, discusses the current evidence on the epidemiology, pathophysiology, diagnosis, and treatment of chronic spontaneous urticaria with JAMA Senior Editor Karen E. Lasser, MD, MPH.

Author/s:

Pavel Kolkhir, Karen E. Lasser

Standards of Medical Care in Diabetes

Brian Desmarais — Thu, 19 Nov 2020 17:37:56 +0000

Date Added:

November 19, 2020

Journal/Publication:

Diabetes Care

Publication Date:

January 1, 2020

Issue:

Volume:

URL:

Standards of Medical Care in Diabetes

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

https://doi.org/10.2337/dc20-Sint

MeSH

diabetes mellitus, type 2

diabetes mellitus, type 1

risk reduction behavior

Longitudinal Studies

This is the 2020 version of the ADA guidelines. James W. Mold, MD, MPH

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Not available.

Pharmacologic and Nonpharmacologic Treatments for Posttraumatic Stress Disorder: An Update of the PTSD-Repository Evidence Base

Brian Desmarais — Mon, 09 Nov 2020 20:14:11 +0000

Date Added:

November 9, 2020

Journal/Publication:

Agency for Healthcare Research and Quality

Publisher:

U.S Department of Health & Human Services

Publication Date:

November 4, 2020

URL:

Pharmacologic and Nonpharmacologic Treatments for Posttraumatic Stress Disorder: An Update of the PTSD-Repository Evidence Base

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.23970/AHRQEPCCER235

Keywords

PTSD

MeSH

stress disorders, post-traumatic

23-valent pneumococcal capsular polysaccharide vaccine

An AHRQ evidence report on the treatment of PTSD, both pharmacologic and non-pharmacologic. James W. Mold,. MD, MPH

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Structured Abstract

Objectives. Identify and abstract data from posttraumatic stress disorder (PTSD) treatment randomized controlled trials (RCTs) to update the PTSD Trials Standardized Data Repository (PTSD-Repository) with data on PTSD and mental health, including suicide-related outcomes and substance use.

Data sources. We searched PTSDpubs, Ovid® MEDLINE®, Cochrane CENTRAL, PsycINFO®, Embase®, CINAHL®, and Scopus® for eligible RCTs published from 1980 to May 22, 2020.

Review methods. In consultation with the National Center for PTSD (NCPTSD), we updated the PTSD-Repository by expanding inclusion criteria to RCTs targeting comorbid PTSD/substance use disorder (SUD) and adding data elements. The primary publication for each RCT was abstracted; data and citations from secondary publications (i.e., companion papers) appear in the same record. We assessed risk of bias (ROB) for all studies in the PTSD-Repository. We undertook an exploratory assessment of an expanded ROB system developed with guidance from a Technical Expert Panel and NCPTSD, which was pilot tested on a small subset of studies.

Results. We identified 47 new RCTs of interventions for PTSD and 21 RCTs for comorbid PTSD/SUD, resulting in 389 included studies published from 1988 to 2020. Psychotherapy interventions were the most common (63%), followed by pharmacologic interventions (25%). Most studies were conducted in the United States (62%) and had sample sizes ranging from 25 to 99 participants (60%). Approximately half of studies enrolled community participants (55%), and most were conducted in the outpatient setting (72%). Studies typically enrolled participants with a mix of trauma types (53%). Most RCTs (60%) were rated as having a medium ROB, and only 6 percent were rated as having a low ROB. Our pilot testing of an expanded ROB assessment tool emphasized more detailed assessment of elements, including: (1) methods for managing missing data, including both dropout from treatment and missing measurements (i.e., loss to followup); (2) differential assessment of subjective and objective outcomes; and (3) consideration of a five-category overall rating system.

Conclusions. The PTSD-Repository is a comprehensive database of data from PTSD trials. The PTSD-Repository allows clinical, research, education, and policy stakeholders to understand current research on treatment effectiveness and harms, and enable informed decisions about future research, mental health policy, and clinical care priorities. This report updates the studies and variables included in the PTSD-Repository to include recently published trials, interventions targeting comorbid PTSD/SUD, variables related to comorbidities such as suicide and SUDs, and ROB assessment.

Author/s:

Agency for Healthcare Research and Quality

Medical Care of Adults With Down Syndrome: A Clinical Guideline

Brian Desmarais — Thu, 22 Oct 2020 14:30:11 +0000

Date Added:

October 22, 2020

Journal/Publication:

Journal of the American Medical Association

Publication Date:

October 20, 2020

Issue:

Volume:

324

Pages:

1543-1556

URL:

Medical Care of Adults With Down Syndrome: A Clinical Guideline

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

https://doi.org/10.1001/jama.2020.17024

MeSH

cardiovascular diseases

Patient Advocacy

comorbidity

Abstracting and Indexing

A guideline for the medical care of adults with Down’s Syndrome (see Results section). James W. Mold,. MD, MPH

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Abstract

Importance: Down syndrome is the most common chromosomal condition, and average life expectancy has increased substantially, from 25 years in 1983 to 60 years in 2020. Despite the unique clinical comorbidities among adults with Down syndrome, there are no clinical guidelines for the care of these patients.

Objective: To develop an evidence-based clinical practice guideline for adults with Down syndrome.

Evidence review: The Global Down Syndrome Foundation Medical Care Guidelines for Adults with Down Syndrome Workgroup (n = 13) developed 10 Population/Intervention/ Comparison/Outcome (PICO) questions for adults with Down syndrome addressing multiple clinical areas including mental health (2 questions), dementia, screening or treatment of diabetes, cardiovascular disease, obesity, osteoporosis, atlantoaxial instability, thyroid disease, and celiac disease. These questions guided the literature search in MEDLINE, EMBASE, PubMed, PsychINFO, Cochrane Library, and the TRIP Database, searched from January 1, 2000, to February 26, 2018, with an updated search through August 6, 2020. Using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology and the Evidence-to-Decision framework, in January 2019, the 13-member Workgroup and 16 additional clinical and scientific experts, nurses, patient representatives, and a methodologist developed clinical recommendations. A statement of good practice was made when there was a high level of certainty that the recommendation would do more good than harm, but there was little direct evidence.

Findings: From 11 295 literature citations associated with 10 PICO questions, 20 relevant studies were identified. An updated search identified 2 additional studies, for a total of 22 included studies (3 systematic reviews, 19 primary studies), which were reviewed and synthesized. Based on this analysis, 14 recommendations and 4 statements of good practice were developed. Overall, the evidence base was limited. Only 1 strong recommendation was formulated: screening for Alzheimer-type dementia starting at age 40 years. Four recommendations (managing risk factors for cardiovascular disease and stroke prevention, screening for obesity, and evaluation for secondary causes of osteoporosis) agreed with existing guidance for individuals without Down syndrome. Two recommendations for diabetes screening recommend earlier initiation of screening and at shorter intervals given the high prevalence and earlier onset in adults with Down syndrome.

Conclusions and relevance: These evidence-based clinical guidelines provide recommendations to support primary care of adults with Down syndrome. The lack of high-quality evidence limits the strength of the recommendations and highlights the need for additional research.

Author/s:

Tsou, Amy Y., Bulova, Peter, Capone, George, Chicoine, Brian, Global Down Syndrome Foundation Medical Care Guidelines for Adults with Down Syndrome Workgroup

5-year mental health and eating pattern outcomes following bariatric surgery in adolescents: a prospective cohort study

John Bayhi — Fri, 21 Feb 2020 19:36:07 +0000

Date Added:

February 21, 2020

Journal/Publication:

The Lancet Child and Adolescent Health

Publisher:

Elsevier Ltd.

Publication Date:

January 21, 2020

Issue:

Volume:

Pages:

P210-219

URL:

5-year mental health and eating pattern outcomes following bariatric surgery in adolescents: a prospective cohort study

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1016/S2352-4642(20)30024-9

Keywords

PMID (1):

31978372

Bariatric surgery in adolescents can improve BMI but not mental health, at least not in Sweden. James W. Mold, MD, MPH

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BACKGROUND:

Mental health problems are prevalent among adolescents with severe obesity, but long-term mental health outcomes after adolescent bariatric surgery are not well known. We aimed to assess mental health outcomes over 5 years of follow-up after Roux-en-Y gastric bypass surgery in adolescents who participated in the Adolescent Morbid Obesity Surgery (AMOS) study.

METHODS:

This was a non-randomised matched-control study in adolescents aged 13-18 years who had a BMI of 40 kg/m2 or higher, or 35 kg/m2 or higher in addition to obesity-related comorbidity; who had previously undergone failed comprehensive conservative treatment; and were of pubertal Tanner stage III or higher, with height growth velocity beyond peak. A contemporary control group, matched for BMI, age, and sex, who underwent conventional obesity treatment, was obtained from the Swedish Childhood Obesity Treatment Register. Data on dispensed psychiatric drugs and specialist treatment for mental disorders were retrieved from national registers with complete coverage. In the surgical group only, questionnaires were used to assess self-esteem (Rosenberg Self-Esteem [RSE] score), mood (Mood Adjective Checklist [MACL]), and eating patterns (Binge Eating Scale [BES] and Three-Factor Eating Questionnaire-R21 [TFEQ]). This study is registered with ClinicalTrials.gov (NCT00289705).

FINDINGS:

Between April 10, 2006, and May 20, 2009, 81 adolescents (53 [65%] female) underwent Roux-en-Y gastric bypass surgery, and 80 control participants received conventional treatment. The proportion of participants prescribed psychiatric drugs did not differ between groups in the years before study inclusion (pre-baseline; absolute risk difference 5% [95% CI -7 to 16], p=0·4263) or after intervention (10% [-6 to 24], p=0·2175). Treatment for mental and behavioural disorders did not differ between groups before baseline (2% [-10 to 14], p=0·7135); however, adolescents in the surgical group had more specialised psychiatric treatment in the 5 years after obesity treatment than did the control group (15% [1 to 28], p=0·0410). There were few patients who discontinued psychiatric treatment post-surgery (three [4%] receiving psychiatric drug treatment and six [7%] receiving specialised care for a mental disorder before surgery). In the surgical group, self-esteem (RSE score) was improved after 5 years (mixed model mean 21·6 [95% CI 19·9 to 23·4]) relative to baseline (18·9 [17·4 to 20·4], p=0·0059), but overall mood (MACL score) was not (2·8 [2·7 to 2·9] at 5 years vs 2·7 [2·6 to 2·8] at baseline, p=0·0737). Binge eating was improved at 5 years (9·3 [7·4 to 11·2]) relative to baseline (15·0 [13·5 to 16·5], p<0·0001). Relative changes in BMI were not associated with the presence or absence of binge eating at baseline.

INTERPRETATION:

Mental health problems persist in adolescents 5 years after bariatric surgery despite substantial weight loss. Although bariatric surgery can improve many aspects of health, alleviation of mental health problems should not be expected, and a multidisciplinary bariatric team should offer long-term mental health support after surgery.

FUNDING:

Swedish Research Council, VINNOVA, Västra Götalandsregionen, ALF VG-region, Region Stockholm, Swedish Child Diabetes Foundation, Swedish Heart and Lung Foundation, Tore Nilsson's Foundation, SUS Foundations and Donations, Capio Research Foundation, and Mary von Sydow's Foundation.

Author/s:

Järvholm, K, Bruze, G, Peltonen, M, Marcus, C, Flodmark, CE, Henfridsson, P, Beamish, AJ, Gronowitz, E, Dahlgren, J, Karlsson, J, Olbers, T

Oseltamivir plus usual care versus usual care for influenza-like illness in primary care: an open-label, pragmatic, randomised controlled trial

John Bayhi — Thu, 02 Jan 2020 19:26:04 +0000

Date Added:

January 2, 2020

Journal/Publication:

Lancet

Publisher:

Elsevier Inc.

Publication Date:

December 12, 2019

URL:

Oseltamivir plus usual care versus usual care for influenza-like illness in primary care: an open-label, pragmatic, randomised controlled trial

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1016/S0140-6736(19)32982-4

Keywords

PMID (1):

31839279

MeSH

Polymerase Chain Reaction

Europe

Large pragmatic clinical trial from Europe documenting impacts of treatment of influenza with Tamiflu. James W. Mold, MD, MPH

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BACKGROUND:

Antivirals are infrequently prescribed in European primary care for influenza-like illness, mostly because of perceived ineffectiveness in real world primary care and because individuals who will especially benefit have not been identified in independent trials. We aimed to determine whether adding antiviral treatment to usual primary care for patients with influenza-like illness reduces time to recovery overall and in key subgroups.

METHODS:

We did an open-label, pragmatic, adaptive, randomised controlled trial of adding oseltamivir to usual care in patients aged 1 year and older presenting with influenza-like illness in primary care. The primary endpoint was time to recovery, defined as return to usual activities, with fever, headache, and muscle ache minor or absent. The trial was designed and powered to assess oseltamivir benefit overall and in 36 prespecified subgroups defined by age, comorbidity, previous symptom duration, and symptom severity, using a Bayesian piece-wise exponential primary analysis model. The trial is registered with the ISRCTN Registry, number ISRCTN 27908921.

FINDINGS:

Between Jan 15, 2016, and April 12, 2018, we recruited 3266 participants in 15 European countries during three seasonal influenza seasons, allocated 1629 to usual care plus oseltamivir and 1637 to usual care, and ascertained the primary outcome in 1533 (94%) and 1526 (93%). 1590 (52%) of 3059 participants had PCR-confirmed influenza infection. Time to recovery was shorter in participants randomly assigned to oseltamivir (hazard ratio 1·29, 95% Bayesian credible interval [BCrI] 1·20-1·39) overall and in 30 of the 36 prespecified subgroups, with estimated hazard ratios ranging from 1·13 to 1·72. The estimated absolute mean benefit from oseltamivir was 1·02 days (95% [BCrI] 0·74-1·31) overall, and in the prespecified subgroups, ranged from 0·70 (95% BCrI 0·30-1·20) in patients younger than 12 years, with less severe symptoms, no comorbidities, and shorter previous illness duration to 3·20 (95% BCrI 1·00-5·50) in patients aged 65 years or older who had more severe illness, comorbidities, and longer previous illness duration. Regarding harms, an increased burden of vomiting or nausea was observed in the oseltamivir group.

INTERPRETATION:

Primary care patients with influenza-like illness treated with oseltamivir recovered one day sooner on average than those managed by usual care alone. Older, sicker patients with comorbidities and longer previous symptom duration recovered 2-3 days sooner.

FUNDING:

European Commission's Seventh Framework Programme.

Author/s:

Butler, CC, van der Velden, AW, Bongard, E, Saville, BR, Holmes, J, Coenen, S, Cook, J, Francis, NA, Lewis, RJ, Godycki-Cwirko, M, Llor, C, Chlabicz, S, Lionis, C, Seifert, B, Sundvall, PD, Colliers, A, Aabenhus, R, Bjerrum, L, Jonassen Harbin, N, Lindbæk M, Glinz, D, Bucher, HC, Kovacs, B, Radzeviciene Jurgute, R, Touboul Lundgren, P, Little, P, Murphy, AW, De Sutter, A, Openshaw, P, de Jong, MD, Connor, JT, Matheeussen, V, Ieven, M, Goossens, H, Verheij, TJ

Assessing and Counseling the Older Driver: A Concise Review for the Generalist Clinician

John Bayhi — Fri, 02 Aug 2019 18:51:18 +0000

Date Added:

August 9, 2019

Journal/Publication:

Mayo Clinic Proceedings

Publisher:

Mayo Foundation for Medical Education and Research

Publication Date:

August 1, 2019

Issue:

Volume:

Pages:

1582–1588

URL:

Assessing and Counseling the Older Driver: A Concise Review for the Generalist Clinician

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1016/j.mayocp.2019.03.023

Keywords

MeSH

referral and consultation

A concise review of issues and counseling strategies relevant to older drivers. James W. Mold, MD, MPH

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Older drivers are putting more miles on the road during their “golden years” than generations prior. Many older adults have safe driving habits, but unique age-related changes increase the risk for crash-related morbidity and mortality. Generalists are poised to assess and guide older adults' driving fitness. Although there is no uniformly accepted tool for driving fitness, assessment of 5 key domains (cognition, vision, physical function, medical comorbidities, and medications) using valid tools can help clinicians stratify older drivers into low, intermediate, and high risk for unsafe driving. Clinicians can then make recommendations about fitness to drive and appropriate referrals for rehabilitation or alternative transportation resources to optimize mobility, independence, and quality of life for older adults.

Author/s:

Hill, Larisa J.N., Pignolo, Robert J., Tung, Ericka E.