Heart Rate Variability on 10-Second Electrocardiogram and Risk of Acute Exacerbation of COPD: A Secondary Analysis of the BLOCK COPD Trial.

Introduction: Autonomic dysfunction is common in chronic obstructive pulmonary disease (COPD), and worse autonomic function may be a marker of risk for acute exacerbations of COPD (AECOPD). Heart rate variability (HRV) is a measure of autonomic function. Our objective was to test whether lower (worse) HRV is a risk factor for AECOPD. Methods: We measured standard deviation of normal RR intervals (SDNN) and root mean square of successive RR interval differences (RMSSD) on 10-second electrocardiograms (ECGs) performed at screening and day 42 in participants in the Beta Blockers for the Prevention of Acute Exacerbations of COPD trial ( BLOCK-COPD), a placebo-controlled trial of metoprolol for prevention of AECOPD. We used Cox-proportional hazards models to test if these HRV measures were associated with risk of any AECOPD, and separately, hospitalized AECOPD. We tested associations using baseline HRV measures and incorporating HRV measures from day 42 as a time-varying covariate. We also tested for interactions with metoprolol assignment. Results: Of 532 trial participants, 529 (forced expiratory volume in 1 second [FEV1 ]41 ± 16.3 % predicted) were included in this analysis. We did not find a significant association between HRV measures and risk of AECOPD when all participants were analyzed together. There was a significant interaction between RMSSD and assignment to metoprolol on time to first hospitalized AECOPD; in the placebo group greater RMSSD was associated with a lower risk of hospitalized AECOPD (adjusted hazard ratio0.71, 95% confidence interval: 0.52 to 0.96, per 10 ms increase) but there was no association in the metoprolol group. Conclusions: Autonomic dysfunction as measured by HRV may be a risk factor for AECOPD. Future studies should analyze longer HRV recordings and their performance in broader samples of people with COPD, including those on beta-blockers.

Chronotropic index during 6-minute walk and acute respiratory events in COPDGene.

BACKGROUND: Lower heart rate (HR) increases during exercise and slower HR recovery (HRR) after exercise are markers of worse autonomic function that may be associated with risk of acute respiratory events (ARE). METHODS: Data from 6-min walk testing (6MWT) in COPDGene were used to calculate the chronotropic index (CI) [(HR immediately post 6MWT - resting HR)/((220 - age) - resting HR)] and HRR at 1 min after 6MWT completion. We used zero-inflated negative binomial regression to test associations of CI and HRR with rates of any ARE (requiring steroids and/or antibiotics) and severe ARE (requiring emergency department visit or hospitalization), among all participants and in spirometry subgroups (normal, chronic obstructive pulmonary disease [COPD], and preserved ratio with impaired spirometry). RESULTS: Among 4,484 participants, mean follow-up time was 4.1 years, and 1,966 had COPD. Among all participants, CI-6MWT was not associated with rate of any ARE [adjusted incidence rate ratio (aIRR) 0.98 (0.95-1.01)], but higher CI-6MWT was associated with lower rate of severe ARE [0.95 (0.92-0.99)]. Higher HRR was associated with a lower rate of both any ARE [0.97 (0.95-0.99)] and severe ARE [0.95 (0.92-0.98)]. Results were similar in the COPD spirometry subgroup. CONCLUSION: Heart rate measures derived from 6MWT tests may have utility in predicting risk of acute respiratory events and COPD exacerbations.

Epigenetic marker of telomeric age is associated with exacerbations and hospitalizations in chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an age-related condition that has been associated with early telomere attrition; the clinical implications of telomere shortening in COPD are not well known. In this study we aimed to determine the relationship of the epigenetic regulation of telomeric length in peripheral blood with the risk of exacerbations and hospitalization in patients with COPD. METHODS: Blood DNA methylation profiles were obtained from 292 patients with COPD enrolled in the placebo arm of the Macrolide Azithromycin to Prevent Rapid Worsening of Symptoms Associated with Chronic Obstructive Pulmonary Disease (MACRO) Study and who were followed for 1-year. We calculated telomere length based on DNA methylation markers (DNAmTL) and related this biomarker to the risk of exacerbation and hospitalization and health status (St. George Respiratory Questionnaire [SGRQ]) score over time using a Cox proportional hazards model. We also used linear models to investigate the associations of DNAmTL with the rates of exacerbation and hospitalization (adjusted for chronological age, lung function, race, sex, smoking, body mass index and cell composition). RESULTS: Participants with short DNAmTL demonstrated increased risk of exacerbation (P = 0.02) and hospitalization (P = 0.03) compared to those with longer DNAmTL. DNAmTL age acceleration was associated with higher rates of exacerbation (P = 1.35 × 10-04) and hospitalization (P = 5.21 × 10-03) and poor health status (lower SGRQ scores) independent of chronological age (P = 0.03). CONCLUSION: Telomeric age based on blood DNA methylation is associated with COPD exacerbation and hospitalization and thus a promising biomarker for poor outcomes in COPD.

Chronotropic Index and Acute Exacerbations of Chronic Obstructive Pulmonary Disease: A Secondary Analysis of BLOCK COPD.

Rationale: The chronotropic index quantifies the proportion of the expected heart rate increase that is attained during exercise. The relationship between the chronotropic index and acute exacerbations of chronic obstructive pulmonary disease (AECOPDs) has not been evaluated. Objectives: To determine whether a higher chronotropic index during a 6-minute walk (CI-6MW) is associated with lower risk of AECOPD and whether the CI-6MW is a marker of susceptibility to adverse effects of metoprolol in chronic obstructive pulmonary disease (COPD). Methods: We analyzed data from the BLOCK COPD (Beta-Blockers for the Prevention of AECOPDs) trial. We used Cox proportional hazards models to investigate the relationship between the CI-6MW and the time to AECOPDs. We also tested for interactions between study group assignment (metoprolol vs. placebo) and the CI-6MW on the time to AECOPDs. Results: Four hundred seventy-seven participants with exacerbation-prone COPD (mean forced expiratory volume in 1 second, 41% of predicted) were included in this analysis. A higher CI-6MW was independently associated with a decreased risk of AECOPDs of any severity (adjusted hazard ratio per 0.1 increase in CI-6MW of 0.88; 95% confidence interval, 0.80-0.96) but was not independently associated with AECOPDs requiring hospitalization (adjusted hazard ratio, 0.94; 95% confidence interval, 0.81-1.05). There was a significant interaction by treatment assignment, and in a stratified analysis, the protective effects of a higher CI-6MW on AECOPDs were negated by metoprolol use. Conclusions: A higher CI-6MW is associated with a decreased risk of AECOPDs and may be an indicator of susceptibility to the adverse effects of metoprolol.

Does Early Glasses Wear Improve Visual Outcome in OCA1A?

Purpose: Oculocutaneous albinism type 1A (OCA1A), with lifelong absent melanin in skin, hair, and eyes, is the most severe type of albinism with greatest ametropia and poorest vision. We evaluated the relationship between age when spectacles were begun and visual outcome, in addition to status of refraction, in OCA1A. Methods: After IRB approval, a retrospective review of 70 consecutive charts of patients with OCA1A identified 24 fitting inclusion criterion of BCVA recorded at age 10-12 years. Exclusion criteria were those with other vision-threatening diagnoses and patients seen for a single visit. We recorded sex, age at beginning glasses, and refraction and BCVA at age 10-12 and most recent visit. Data were arbitrarily grouped by those initiating glasses at ≤ age 12 months and > age 12 months. Results: Regression analysis showed a larger degree of astigmatism was weakly associated with worse vision at age 10-12 years. A weakly positive relationship was found between poorer BCVA at last visit and older age at which glasses were initiated. All receiving glasses by age 1 and only half receiving glasses when older had improved visual acuity from age 10-12 years to last follow up. Conclusion: Additional study of a larger sample of this rare disorder is needed to determine if early glasses wear improves later BCVA.

Rationale and methods of the Advanced R2Eperfusion STrategies for Refractory Cardiac Arrest (ARREST) trial.

BACKGROUND: Venoarterial extracorporeal membrane oxygenation has emerged as a prominent therapy for patients with refractory cardiac arrest. However, the optimal time of initiation remains unknown. AIM: The aim was to assess the rate of survival to hospital discharge in adult patients with refractory ventricular fibrillation/pulseless ventricular tachycardia out-of-hospital cardiac arrest treated with 1 of 2 local standards of care: (1) early venoarterial extracorporeal membrane oxygenation-facilitated resuscitation for circulatory support and percutaneous coronary intervention, when needed, or (2) standard advanced cardiac life support resuscitation. DESIGN: Phase II, single-center, partially blinded, prospective, intention-to-treat, safety and efficacy clinical trial. POPULATION: Adults (aged 18-75), initial out-of-hospital cardiac arrest rhythm of ventricular fibrillation/pulseless ventricular tachycardia, no ROSC following 3 shocks, body morphology to accommodate a Lund University Cardiac Arrest System automated cardiopulmonary resuscitation device, and transfer time of <30 minutes. SETTING: Hospital-based. OUTCOMES: Primary: survival to hospital discharge. Secondary: safety, survival, and functional assessment at hospital discharge and 3 and 6 months, and cost. SAMPLE SIZE: Assuming success rates of 12% versus 37% in the 2 arms and 90% power, a type 1 error rate of .05, and a 15% rate of withdrawal prior to hospital discharge, the required sample size is N = 174 evaluated patients. CONCLUSIONS: The ARREST trial will generate safety/effectiveness data and comparative costs associated with extracorporeal cardiopulmonary resuscitation, informing broader implementation and a definitive Phase III clinical trial.

Effect of Inhaled Cannabis for Pain in Adults With Sickle Cell Disease: A Randomized Clinical Trial.

Importance: Sickle cell disease (SCD) is characterized by chronic pain and episodic acute pain caused by vasoocclusive crises, often requiring high doses of opioids for prolonged periods. In humanized mouse models of SCD, a synthetic cannabinoid has been found to attenuate both chronic and acute hyperalgesia. The effect of cannabis on chronic pain in adults with SCD is unknown. Objective: To determine whether inhaled cannabis is more effective than inhaled placebo in relieving chronic pain in adults with SCD. Design, Setting, and Participants: This pilot randomized clinical trial included participants with SCD with chronic pain admitted to a single inpatient clinical research center for 2 separate 5-day stays from August 2014 to April 2017. Participants inhaled either vaporized cannabis (4.4% Δ-9-tetrahydrocannabinol to 4.9% cannabidiol) 3 times daily or vaporized placebo cannabis. Pain and pain interference ratings using the Brief Pain Inventory were assessed throughout each 5-day period. Participants with SCD and chronic pain on stable analgesics were eligible to enroll. A total of 90 participants were assessed for eligibility; 56 participants were deemed ineligible, and 34 participants were enrolled. Of these, 7 participants dropped out before randomization. Of 27 randomized participants, 23 completed both treatment arms of the crossover study and were included in the final per protocol analysis. Data analysis was completed in June 2019, with the sensitivity analysis conducted in April 2020. Interventions: Inhalation of vaporized cannabis plant (4.4% Δ-9-tetrahydrocannbinol to 4.9% cannabidiol) or placebo cannabis plant using a vaporizer 3 times daily for 5 days. Main Outcomes and Measures: Daily pain assessed with visual analog scale and Brief Pain Inventory. Results: A total of 23 participants (mean [SD] age, 37.6 [11.4] years; 13 [56%] women) completed the trial. The mean (SD) difference in pain rating assessment between the cannabis and placebo groups was -5.3 (8.1) for day 1, -10.9 (7.0) for day 2, -16.5 (9.2) for day 3, -8.9 (6.7) for day 4, and -8.2 (8.1) for day 5; however, none of these differences were statistically significant. There was no statistically significant mean (SD) difference in pain interference ratings between cannabis and placebo between days 1 and 5 for interference in general activities (day 1: 0.27 [0.35]; day 5: -1.0 [0.5]), walking (day 1: 0.14 [0.73]; day 5: -0.87 [0.63]), sleep (day 1: 0.59 [0.74]; day 5: -1.3 [0.8]), or enjoyment (day 1: 0.23 [0.69]; day 5: -0.91 [0.48]), but there was a statistically significant mean (SD) difference in decrease in interference with mood (day 1: 0.96 [0.59]; day 5: -1.4 [0.6]; P = .02). No differences in treatment-related adverse effects were observed. Use of concomitant opioids was similar during both treatment periods. Conclusions and Relevance: This randomized clinical trial found that, compared with vaporized placebo, vaporized cannabis did not statistically significantly reduce pain and associated symptoms, except interference in mood, in patients with SCD with chronic pain. Trial Registration: ClinicalTrials.gov Identifier: NCT01771731.

Emotional quality-of-life and patient-reported limitation in sports participation in children with uncorrected congenital and acquired heart disease in healthcare-restricted settings in low- and middle-income countries.

BACKGROUND: Little is known about emotional quality-of-life in paediatric heart disease in low- and middle-income countries where the prevalence of uncorrected lesions is high. Research on emotional quality-of-life and its predictors in these settings is key to planning interventions. METHODS: Ten-year retrospective cross-sectional study of children aged 6-17 years with uncorrected congenital or acquired heart disease in 12 low- and middle-income countries was conducted. Emotional functioning score of the PedsQL TM 4.0 generic core scale and data on patient-reported limitation in sports participation were collected via in-person interview and analysed using regression analyses. RESULTS: Ninety-four children reported mean emotional functioning scores of 71.94 (SD 25.32) [95% CI 66.75-77.13] with lower scores independently associated with having a parent with a chronic illness or who had died (p = 0.005), having less than three siblings (p = 0.007), and reporting a subjective limitation in carrying an item equivalent to a 4 lb load (p = 0.021). Patient-reported limitation in sports participation at least "sometimes" was present in 69% and was independently associated with experiencing symptoms at least once a month (p < 0.001). CONCLUSION: Some of the factors which were associated with better emotional quality-of-life were similar to those identified in previous studies in patients with corrected defects. Patient-reported limitation in sports participation is common. In addition to corrective surgery and exercise, numerous other interventions which are practicable during surgical missions might improve emotional quality-of-life.

Randomized Trial of Mindfulness-Based Stress Reduction in Cardiac Patients Eligible for Cardiac Rehabilitation.

Currently, exercise-based cardiac rehabilitation (CR) is the only recommended secondary prevention strategy for cardiac patients that attempts to tackle stress and psychosocial wellbeing, but it is under-utilized and lacks a comprehensive curriculum for this purpose; hence there is a critical gap to address psychosocial needs of cardiac patients after an event. Mindfulness-based stress reduction (MBSR) has shown benefits in the general population but its role in cardiac patients is not clear. We conducted a pilot randomized controlled trial (RCT) of MBSR in CR-eligible cardiac patients during their initial year of recovery. Patients were allocated 2:1 (intervention:control) to an 8-week MBSR group intervention or usual care. Standard measures of depression, anxiety, perceived stress, health related quality of life (HRQOL), blood pressure, biomarkers (lipids, HbA1c, CRP) and 24-hour Holter monitoring were obtained at baseline, 3- and 9-months post-randomization. Sub-group analyses were performed for participants with at least mild depression (PHQ-9 ≥ 5). 47 patients [mean age 58.6 years; 38% female; 77% white] were enrolled in 2 cohorts. 87% of MBSR patients completed the intervention; study retention was >95% at each follow-up visit. At 3 months, compared to controls, MBSR patients showed improvements in depression [p = 0.01] and anxiety [p = 0.04] with a similar trend in HRQOL [p = 0.06]. The MBSR group showed greater improvement or less worsening of most CV risk factors, with an attenuation of treatment effects at 9 months. Participants with at PHQ-9 scores ≥5 at baseline showed greater improvement in psychosocial and CV outcomes, that persisted at 9 months. MBSR is a safe and well received secondary prevention strategy. This pilot RCT provides preliminary evidence of MBSR's potential to improve short term psychosocial well-being in cardiac patients during their first year of recovery.

Metoprolol for the Prevention of Acute Exacerbations of COPD.

BACKGROUND: Observational studies suggest that beta-blockers may reduce the risk of exacerbations and death in patients with moderate or severe chronic obstructive pulmonary disease (COPD), but these findings have not been confirmed in randomized trials. METHODS: In this prospective, randomized trial, we assigned patients between the ages of 40 and 85 years who had COPD to receive either a beta-blocker (extended-release metoprolol) or placebo. All the patients had a clinical history of COPD, along with moderate airflow limitation and an increased risk of exacerbations, as evidenced by a history of exacerbations during the previous year or the prescribed use of supplemental oxygen. We excluded patients who were already taking a beta-blocker or who had an established indication for the use of such drugs. The primary end point was the time until the first exacerbation of COPD during the treatment period, which ranged from 336 to 350 days, depending on the adjusted dose of metoprolol. RESULTS: A total of 532 patients underwent randomization. The mean (±SD) age of the patients was 65.0±7.8 years; the mean forced expiratory volume in 1 second (FEV1) was 41.1±16.3% of the predicted value. The trial was stopped early because of futility with respect to the primary end point and safety concerns. There was no significant between-group difference in the median time until the first exacerbation, which was 202 days in the metoprolol group and 222 days in the placebo group (hazard ratio for metoprolol vs. placebo, 1.05; 95% confidence interval [CI], 0.84 to 1.32; P = 0.66). Metoprolol was associated with a higher risk of exacerbation leading to hospitalization (hazard ratio, 1.91; 95% CI, 1.29 to 2.83). The frequency of side effects that were possibly related to metoprolol was similar in the two groups, as was the overall rate of nonrespiratory serious adverse events. During the treatment period, there were 11 deaths in the metoprolol group and 5 in the placebo group. CONCLUSIONS: Among patients with moderate or severe COPD who did not have an established indication for beta-blocker use, the time until the first COPD exacerbation was similar in the metoprolol group and the placebo group. Hospitalization for exacerbation was more common among the patients treated with metoprolol. (Funded by the Department of Defense; BLOCK COPD ClinicalTrials.gov number, NCT02587351.).

The relationship between oral health and COPD exacerbations.

Introduction: Poor oral health has been implicated as an independent risk factor for the development of COPD, but few studies have evaluated the association between oral health and COPD exacerbations. We aimed to determine if poor oral health is associated with COPD exacerbations and/or worse respiratory health. Methods: We performed a case-control study of oral health among COPD exacerbators and non-exacerbators. Cases (exacerbators) had experienced ≥1 exacerbation in the previous 12 months, while controls (non-exacerbators) had no exacerbations in the previous 24 months. We excluded those with <4 teeth. We evaluated the global oral health assessment, Oral Health Impact Profile (OHIP-5), dental symptoms/habits, and St. George's Respiratory Questionnaire (SGRQ). In a subset, we performed blinded dental exams to measure bleeding on probing, probing depth, clinical attachment loss, periodontitis severity, plaque index, gingival index, and carries risk. We evaluated associations between oral health and COPD exacerbations using logistic regression. Linear regression was used to assess relationships between oral health and SGRQ scores. Results: Screened non-exacerbators (n=118) were significantly more likely to have <4 teeth, compared to screened exacerbators (n=100) (44% vs 30%, respectively; p=0.046). After excluding those with <4 teeth, there were 70 cases and 66 controls. Self-reported oral health and objective dental exam measures did not vary significantly between cases vs controls. However, the odds of severe COPD exacerbations requiring hospitalizations and/or emergency department visits trended higher in those with worse dental exam compared to those with better dental exam. Worse OHIP-5 was strongly associated with worse SGRQ scores. Conclusions: Oral health status was not related to COPD exacerbations, but was associated with self-reported respiratory health. Non-exacerbators were more likely to be edentate or have ≤4 teeth compared to exacerbators. Larger studies are needed to address oral health as a potential method to improve respiratory health in patients with COPD.

Relationship of Absolute Telomere Length With Quality of Life, Exacerbations, and Mortality in COPD.

BACKGROUND: COPD is an age-related disease. The role of cellular senescence in COPD has not been fully elucidated. This study examined the relationship between telomere length of peripheral blood leukocytes and clinical outcomes, including health status, rate of exacerbations, and risk of mortality in individuals with COPD. METHODS: Using quantitative polymerase chain reaction, we measured the absolute telomere length (aTL) of DNA extracted from blood samples of 576 participants with moderate-to-severe COPD treated with either azithromycin or placebo for 12 months in the Macrolide Azithromycin for Prevention of Exacerbations of COPD (MACRO) study. All participants were followed for approximately 13 months, during which time health status and exacerbations were carefully ascertained, and an additional 29 months for mortality. The rates of exacerbation and mortality were determined by dividing the aTL into two groups using the median value as the cutoff. RESULTS: Participants with shorter telomere length had worse health status defined by higher St. George's Respiratory Questionnaire scores (ß = -0.09, P = .034). In the placebo arm of the study, the rate of exacerbation (rate ratio, 1.50; 95% CI, 1.16-1.95; P = .002) and the risk of mortality (hazard ratio, 9.45; 95% CI, 2.85-31.36; P = .015) were significantly higher in the shorter telomere group than in the longer telomere group; these differences were not observed in the azithromycin arm (interaction P = .008 for exacerbation and interaction P = .017 for mortality) CONCLUSIONS: These data suggest that replicative senescence may help to predict poor outcomes in COPD. Shorter leukocyte telomere lengths may represent a clinically translatable biomarker for identifying individuals at increased risk of poor clinical outcomes in COPD.

Visual Development During the Second Decade of Life in Albinism.

PURPOSE: To evaluate change in best corrected visual acuity (BCVA) during the second decade of life and the effects of albinism type and extraocular muscle surgery on BCVA in children with albinism. METHODS: In this retrospective longitudinal study, 41 patients with albinism with clinic visits recording binocular BCVA at least once between the ages of 10 and 13 years (visit A) and again between the ages of 17 and 20 years (visit B) were included. Type of albinism, age at each visit, and interval eye muscle surgeries were recorded for each patient. RESULTS: Forty (98%) patients showed BCVA improvement or stability between visits A and B. There was no significant effect of interval extraocular muscle surgery on BCVA. Those carrying either a clinically presumed or moleculary confirmed diagnosis of oculocutaneous albinism types 1B and 2 had the best visual outcomes, consistent with previous studies. CONCLUSIONS: In the majority of patients with albinism, significant improvement in BCVA occurs during the second decade of life. Extraocular muscle surgery was not a significant factor in BCVA improvement in albinism. Overall, the assessments support the finding of improvement of visual acuity in children with albinism at earlier ages and provide new information beneficial in predicting visual outcomes in the second decade of life. [J Pediatr Ophthalmol Strabismus. 2018;55(4):254-259.].

Serum IgG subclass levels and risk of exacerbations and hospitalizations in patients with COPD.

BACKGROUND: The literature is scarce regarding the prevalence and clinical impact of IgG subclass deficiency in COPD. We investigated the prevalence of IgG subclass deficiencies and their association with exacerbations and hospitalizations using subjects from two COPD cohorts. METHODS: We measured IgG subclass levels using immunonephelometry in serum samples from participants enrolled in two previous COPD trials: Macrolide Azithromycin for Prevention of Exacerbations of COPD (MACRO; n = 976) and Simvastatin for the Prevention of Exacerbations in Moderate-to-Severe COPD (STATCOPE; n = 653). All samples were collected from clinically stable participants upon entry into both studies. IgG subclass deficiency was diagnosed when IgG subclass levels were below their respective lower limit of normal: IgG1 < 2.8 g/L; IgG2 < 1.15 g/L; IgG3 < 0.24 g/L; and IgG4 < 0.052 g/L. To investigate the impact of IgG subclass levels on time to first exacerbation or hospitalization, we log-transformed IgG levels and performed Cox regression models, with adjustments for confounders. RESULTS: One or more IgG subclass deficiencies were found in 173 (17.7%) and 133 (20.4%) participants in MACRO and STATCOPE, respectively. Lower IgG1 or IgG2 levels resulted in increased risk of exacerbations with adjusted hazard ratios (HR) of 1.30 (95% CI, 1.10-1.54, p < 0.01) and 1.19 (95% CI, 1.05-1.35, p < 0.01), respectively in the MACRO study, with STATCOPE yielding similar results. Reduced IgG1 or IgG2 levels were also associated with increased risk of hospitalizations: the adjusted HR for IgG1 and IgG2 was 1.52 (95% CI: 1.15-2.02, p < 0.01) and 1.33 (95% CI, 1.08-1.64, p < 0.01), respectively for the MACRO study; in STATCOPE, only IgG2 was an independent predictor of hospitalization. In our multivariate Cox models, IgG3 and IgG4 levels did not result in significant associations for both outcomes in either MACRO or STATCOPE cohorts. CONCLUSIONS: Approximately 1 in 5 COPD patients had one or more IgG subclass deficiencies. Reduced IgG subclass levels were independent risk factors for both COPD exacerbations (IgG1 and IgG2) and hospitalizations (IgG2) in two COPD cohorts. TRIAL REGISTRATION: This study used serum samples from participants of the MACRO ( NCT00325897 ) and STATCOPE ( NCT01061671 ) trials.

Lifestyle Intervention and Medical Management With vs Without Roux-en-Y Gastric Bypass and Control of Hemoglobin A1c, LDL Cholesterol, and Systolic Blood Pressure at 5 Years in the Diabetes Surgery Study.

Importance: The Roux-en-Y gastric bypass is effective in achieving established diabetes treatment targets, but durability is unknown. Objective: To compare durability of Roux-en-Y gastric bypass added to intensive lifestyle and medical management in achieving diabetes control targets. Design, Setting, and Participants: Observational follow-up of a randomized clinical trial at 4 sites in the United States and Taiwan, involving 120 participants who had a hemoglobin A1c (HbA1c) level of 8.0% or higher and a body mass index between 30.0 and 39.9 (enrolled between April 2008 and December 2011) were followed up for 5 years, ending in November 2016. Interventions: Lifestyle-intensive medical management intervention based on the Diabetes Prevention Program and LookAHEAD trials for 2 years, with and without (60 participants each) Roux-en-Y gastric bypass surgery followed by observation to year 5. Main Outcomes and Measures: The American Diabetes Association composite triple end point of hemoglobin A1c less than 7.0%, low-density lipoprotein cholesterol less than 100 mg/dL, and systolic blood pressure less than 130 mm Hg at 5 years. Results: Of 120 participants who were initially randomized (mean age, 49 years [SD, 8 years], 72 women [60%]), 98 (82%) completed 5 years of follow-up. Baseline characteristics were similar between groups: mean (SD) body mass index 34.4 (3.2) for the lifestyle-medical management group and 34.9 (3.0) for the gastric bypass group and had hemoglobin A1c levels of 9.6% (1.2) and 9.6% (1.0), respectively. At 5 years, 13 participants (23%) in the gastric bypass group and 2 (4%) in the lifestyle-intensive medical management group had achieved the composite triple end point (difference, 19%; 95% CI, 4%-34%; P = .01). In the fifth year, 31 patients (55%) in the gastric bypass group vs 8 (14%) in the lifestyle-medical management group achieved an HbA1c level of less than 7.0% (difference, 41%; 95% CI, 19%-63%; P = .002). Gastric bypass had more serious adverse events than did the lifestyle-medical management intervention, 66 events vs 38 events, most frequently gastrointestinal events and surgical complications such as strictures, small bowel obstructions, and leaks. Gastric bypass had more parathyroid hormone elevation but no difference in B12 deficiency. Conclusions and Relevance: In extended follow-up of obese adults with type 2 diabetes randomized to adding gastric bypass compared with lifestyle and intensive medical management alone, there remained a significantly better composite triple end point in the surgical group at 5 years. However, because the effect size diminished over 5 years, further follow-up is needed to understand the durability of the improvement. Trial Registration: clinicaltrials.gov Identifier: NCT00641251.

School Practices to Foster LGBT-Supportive Climate: Associations with Adolescent Bullying Involvement.

Lesbian, gay, bisexual, and transgender (LGBT) youth experience disproportionate rates of bullying compared to their heterosexual peers. Schools are well-positioned to address these disparities by creating supportive school climates for LGBT youth, but more research is needed to examine the variety of practices and professional development opportunities put in place to this end. The current study examines how school practices to create supportive LGBT student climate relate to student reports of bullying. Student-level data come from the 2013 Minnesota Student Survey, a state-wide survey of risk and protective factors. Ninth and eleventh grade students (N = 31,183) reported on frequency of physical and relational bullying victimization and perpetration and sexual orientation-based harassment. School administrators reported on six practices related to creating supportive LGBT school climate (N = 103 schools): having a point person for LGBT student issues, displaying sexual orientation-specific content, having a gay-straight alliance, discussing bullying based on sexual orientation, and providing professional development around LGBT inclusion and LGBT student issues. An index was created to indicate how many practices each school used (M = 2.45; SD = 1.76). Multilevel logistic regressions indicated that students attending schools with more supportive LGBT climates reported lower odds of relational bullying victimization, physical bullying perpetration, and sexual orientation-based harassment compared to students in schools with less supportive LGBT climates. Sexual orientation did not moderate these relations, indicating that LGBT-supportive practices may be protective for all students, regardless of their sexual orientation. Findings support school-wide efforts to create supportive climates for LGBQ youth as part of a larger bullying prevention strategy.