Humans

Meta-Analysis Evaluating the Effects of Renin-Angiotensin-Aldosterone System Blockade on Outcomes of Heart Failure With Preserved Ejection Fraction

Author/s: 
Kuno, T, Ueyama, H, Fujisaki, T, Briasouli, A, Takagi, H, Briasoulis, A

Clinical trials of renin-angiotensin-aldosterone system (RAAS) antagonists in heart failure with preserved ejection fraction (HFpEF) have suggested neutral results and treatment is focused on associated symptoms and comorbidities. MEDLINE and EMBASE were searched through October 2019 for randomized controlled studies investigating the effects of different RAAS antagonists in patients with HFpEF. The main outcomes were all-cause mortality, trial defined cardiovascular mortality, and heart failure (HF) hospitalizations. To compare different RAAS antagonists, a random-effects restricted-maximum-likelihood network meta-analysis based on a frequentist framework for indirect and mixed comparisons was used. We used p scores to rank best treatments per outcome. Our search identified 5 eligible clinical trials (PEP-CHF, perindopril; CHARM-preserved, candesartan; I-PRESERVE, irbesartan; TOPCAT, spironolactone; PARAGON-HF, sacubitril-valsartan and valsartan) enrolling a total 10,523 on RAAS antagonists and 6,259 controls. We did not identify any statistical difference in all-cause and cardiovascular mortality among RAAS antagonists and placebo. The combination of sacubitril-valsartan was associated with significantly decreased HF hospitalization risk compared with controls (odds ratio 0.73, 95% confidence interval 0.61 to 0.87) and angiotensin II receptor blockers (odds ratio 0.80, 95% confidence interval 0.71 to 0.91), without heterogeneity among studies (I2 = 0). Angiotensin receptor neprilysin inhibitor (ARNI) ranked better than other RAAS antagonists for HF hospitalizations (p value 0.9). In conclusion, RAAS antagonists do not affect mortality but the combination of sacubitril-valsartan is associated with lower HF hospitalizations in HFpEF patients.

Mental Health Conditions Among Patients Seeking and Undergoing Bariatric Surgery: A Meta-analysis

Author/s: 
Dawes, AJ, Maggard-Gibbons, M, Maher, AR, Booth, MJ, Miake-Lye, I, Shekelle, PG

IMPORTANCE:

Bariatric surgery is associated with sustained weight loss and improved physical health status for severely obese individuals. Mental health conditions may be common among patients seeking bariatric surgery; however, the prevalence of these conditions and whether they are associated with postoperative outcomes remains unknown.

OBJECTIVE:

To determine the prevalence of mental health conditions among bariatric surgery candidates and recipients, to evaluate the association between preoperative mental health conditions and health outcomes following bariatric surgery, and to evaluate the association between surgery and the clinical course of mental health conditions.

DATA SOURCES:

We searched PubMed, MEDLINE on OVID, and PsycINFO for studies published between January 1988 and November 2015. Study quality was assessed using an adapted tool for risk of bias; quality of evidence was rated based on GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria.

FINDINGS:

We identified 68 publications meeting inclusion criteria: 59 reporting the prevalence of preoperative mental health conditions (65,363 patients) and 27 reporting associations between preoperative mental health conditions and postoperative outcomes (50,182 patients). Among patients seeking and undergoing bariatric surgery, the most common mental health conditions, based on random-effects estimates of prevalence, were depression (19% [95% CI, 14%-25%]) and binge eating disorder (17% [95% CI, 13%-21%]). There was conflicting evidence regarding the association between preoperative mental health conditions and postoperative weight loss. Neither depression nor binge eating disorder was consistently associated with differences in weight outcomes. Bariatric surgery was, however, consistently associated with postoperative decreases in the prevalence of depression (7 studies; 8%-74% decrease) and the severity of depressive symptoms (6 studies; 40%-70% decrease).

CONCLUSIONS AND RELEVANCE:

Mental health conditions are common among bariatric surgery patients-in particular, depression and binge eating disorder. There is inconsistent evidence regarding the association between preoperative mental health conditions and postoperative weight loss. Moderate-quality evidence supports an association between bariatric surgery and lower rates of depression postoperatively.

Outcomes Associated With Oral Anticoagulants Plus Antiplatelets in Patients With Newly Diagnosed Atrial Fibrillation

Author/s: 
Fox, KAA, Velentgas, P, Camm, AJ, Bassand, JP, Fitzmaurice, DA, Gersh, BJ, Goldhaber, SZ, Goto, S, Haas, S, Misselwitz, F, Pieper, KS, Turpie, AGG, Verhegut, FWA, Dabrowski, E, Luo, K, Gibbs, L, Kakkar, AK, GARFIELD-AF Investigators

IMPORTANCE:

Patients with nonvalvular atrial fibrillation at risk of stroke should receive oral anticoagulants (OAC). However, approximately 1 in 8 patients in the Global Anticoagulant Registry in the Field (GARFIELD-AF) registry are treated with antiplatelet (AP) drugs in addition to OAC, with or without documented vascular disease or other indications for AP therapy.

OBJECTIVE:

To investigate baseline characteristics and outcomes of patients who were prescribed OAC plus AP therapy vs OAC alone.

DESIGN, SETTING, AND PARTICIPANTS:

Prospective cohort study of the GARFIELD-AF registry, an international, multicenter, observational study of adults aged 18 years and older with recently diagnosed nonvalvular atrial fibrillation and at least 1 risk factor for stroke enrolled between March 2010 and August 2016. Data were extracted for analysis in October 2017 and analyzed from April 2018 to June 2019.

EXPOSURE:

Participants received either OAC plus AP or OAC alone.

MAIN OUTCOMES AND MEASURES:

Clinical outcomes were measured over 3 and 12 months. Outcomes were adjusted for 40 covariates, including baseline conditions and medications.

RESULTS:

A total of 24 436 patients (13 438 [55.0%] male; median [interquartile range] age, 71 [64-78] years) were analyzed. Among eligible patients, those receiving OAC plus AP therapy had a greater prevalence of cardiovascular indications for AP, including acute coronary syndromes (22.0% vs 4.3%), coronary artery disease (39.1% vs 9.8%), and carotid occlusive disease (4.8% vs 2.0%). Over 1 year, patients treated with OAC plus AP had significantly higher incidence rates of stroke (adjusted hazard ratio [aHR], 1.49; 95% CI, 1.01-2.20) and any bleeding event (aHR, 1.41; 95% CI, 1.17-1.70) than those treated with OAC alone. These patients did not show evidence of reduced all-cause mortality (aHR, 1.22; 95% CI, 0.98-1.51). Risk of acute coronary syndrome was not reduced in patients taking OAC plus AP compared with OAC alone (aHR, 1.16; 95% CI, 0.70-1.94). Patients treated with OAC plus AP also had higher rates of all clinical outcomes than those treated with OAC alone over the short term (3 months).

CONCLUSIONS AND RELEVANCE:

This study challenges the practice of coprescribing OAC plus AP unless there is a clear indication for adding AP to OAC therapy in newly diagnosed atrial fibrillation.

Preoperative Cardiac Risk Assessment

Author/s: 
Raslau, D, Bierle, DM, Stephenson, CR, Mikhail, MA, Kebede, EB, Mauck, KF

Major adverse cardiac events are common causes of perioperative mortality and major morbidity. Preventing these complications requires thorough preoperative risk assessment and postoperative monitoring of at-risk patients. Major guidelines recommend assessment based on a validated risk calculator that incorporates patient- and procedure-specific factors. American and European guidelines define when stress testing is needed on the basis of functional capacity assessment. Favoring cost-effectiveness, Canadian guidelines instead recommend obtaining brain natriuretic peptide or N-terminal prohormone of brain natriuretic peptide levels to guide postoperative screening for myocardial injury or infarction. When conditions such as acute coronary syndrome, severe pulmonary hypertension, and decompensated heart failure are identified, nonemergent surgery should be postponed until the condition is appropriately managed. There is an evolving role of biomarkers and myocardial injury after noncardiac surgery to enhance risk stratification, but the effect of interventions guided by these strategies is unclear.

Clinical diagnosis of benign paroxysmal positional vertigo and vestibular neuritis

Author/s: 
Johns, P, Quinn, J

KEY POINTS

• Assess patients with vertigo for focal neurologic signs and symptoms, sustained substantial headache or neck pain, inability to stand and spontaneous vertical nystagmus.

• Perform the Dix–Hallpike test only for patients with episodes of vertigo less than 2 minutes and no nystagmus at rest.

• Perform the head impulse, nystagmus and test of skew (HINTS) plus (plus refers to a test of recent hearing loss) examination only for patients with hours or days of constant, ongoing vertigo and nystagmus at rest

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

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

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.

Twenty-Four-Hour Movement Guidelines and Body Weight in Youth

Author/s: 
Zhu, X, Healy, S, Haegele, JA, Patterson, F

Objective

To examine the prevalence of youth meeting the 24-hour healthy movement guidelines (ie, ≥60 minutes of moderate-to-vigorous physical activity, ≤2 hours of screen time, age-appropriate sleep duration), and which combination of meeting these guidelines was most associated with bodyweight status, in a nationally representative US sample.

Study design

Cross-sectional data from the 2016-2017 National Survey of Children's Health were used. A multinomial regression model of body weight status was generated (underweight, overweight, obese vs healthy weight) and then stratified by sex. Analyses were adjusted for potential confounders.

Results

The sample (n = 30 478) was 50.4% female, 52.4% white, and the mean age was 13.85 ± 2.28 years; 15% percent were obese and 15.2% were overweight. Overall, 9.4% met all 3 of the 24-hour healthy movement guidelines, 43.6% met 2, 37.9% met 1, and 9.1% met none. Meeting zero guidelines (vs 3) was associated with the greatest likelihood of overweight (aOR, 1.85; 95% CI, 1.31-2.61), and obesity (aOR, 4.25; 95% CI, 2.87-6.31). Females (aOR, 4.97; 95% CI, 2.59-9.53) had higher odds of obesity than males (aOR, 3.99; 95% CI, 2.49-6.40) when zero (vs 3) guidelines were met. Meeting the moderate-to-vigorous physical activity guideline, either alone or in combination with screen time or sleep duration (vs all 3), was associated with the lowest odds for overweight and obesity in the full sample.

Conclusion

Meeting all movement guidelines was associated with the lowest risk for obesity, particularly in females. Meeting the moderate-to-vigorous physical activity guideline may be a priority to prevent overweight and obesity in youth.

Immunization Strategies to Span the Spectrum of Immunocompromised Adults

Author/s: 
Whitaker, JA

The Advisory Committee on Immunization Practices to the US Centers for Disease Control and Prevention provides annual recommendations for routine adult immunizations. Many recommendations consider patient factors such as age, medical conditions, and medications that increase an individual’s risk for infection with a vaccine-preventable disease. These factors, particularly those that lead to immunocompromise, may also alter the risk-benefit ratio for live vaccines, and/or lead to decreased vaccine immunogenicity and effectiveness. The provider may need to consider alternative vaccination strategies, including higher antigen dose vaccines, adjuvanted vaccines, avoidance of live vaccines, and careful timing of vaccination to optimize safety and effectiveness in immunocompromised populations. This thematic review discusses general principles regarding immunization of adults across the spectrum of immunocompromise, examines current guidelines and studies that support them, and outlines future research needs.

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