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Abstract Background Several ovarian cancer studies have suggested that a body mass index (BMI) of 30 or higher is associated with lower compliance with National Comprehensive Cancer Network–recommended chemotherapy but primarily involved treatment before 2012, when dose capping was recommended for patients with higher body surface areas. Updated analyses in the contemporary treatment era are warranted. Methods In a retrospective cohort of patients with newly diagnosed ovarian cancer receiving curative-intent carboplatin plus paclitaxel in the Yale-Smilow Cancer Network (2012-2022), we evaluated BMI at diagnosis in relation to relative dose intensity (RDI)—the ratio of completed chemotherapy dose intensity to the National Comprehensive Cancer Network–recommended dose intensity—which reflects dose modification both before and during treatment. We also assessed starting RDI (which reflects modifications before treatment) and received RDI (which reflects modifications during treatment). Data on hospitalizations and hematological chemotoxicities were collected. We examined the association between BMI (<25, 25-30, ≥30) and chemotherapy completion, hospitalizations, and toxicities using multivariable linear and logistic regressions. Results Among 327 patients, the average RDI was 79.7%, and 44.3% had an RDI below 85%. Mean (SD) starting and received RDI were 97.9% (9.1%) and 81.8% (25.7%), respectively. Higher BMI was associated with higher RDI (Paggregate = .03) and received RDI (Paggregate = .04). Body mass index was not associated with starting RDI, dose reductions, delays, hospitalizations, or hematological toxicities. Conclusions Among patients with ovarian cancer treated since 2012, the overall RDI was low. Relative dose intensity was higher among patients with a BMI of 25 or higher compared with a BMI below 25. Most dose modifications occurred during treatment and not before initiation. Studies with body composition data and interventions that maximize chemotherapy completion during treatment are warranted.

BACKGROUND: Whether vigorous exercise increases risk of ventricular arrhythmias for individuals diagnosed and treated for congenital long QT syndrome (LQTS) remains unknown. METHODS: The National Institutes of Health–funded LIVE-LQTS study (Lifestyle and Exercise in the Long QT Syndrome) prospectively enrolled individuals 8 to 60 years of age with phenotypic and/or genotypic LQTS from 37 sites in 5 countries from May 2015 to February 2019. Participants (or parents) answered physical activity and clinical events surveys every 6 months for 3 years with follow-up completed in February 2022. Vigorous exercise was defined as ≥6 metabolic equivalents for >60 hours per year. A blinded Clinical Events Committee adjudicated the composite end point of sudden death, sudden cardiac arrest, ventricular arrhythmia treated by an implantable cardioverter defibrillator, and likely arrhythmic syncope. A National Death Index search ascertained vital status for those with incomplete follow-up. A noninferiority hypothesis (boundary of 1.5) between vigorous exercisers and others was tested with multivariable Cox regression analysis. RESULTS: Among the 1413 participants (13% <18 years of age, 35% 18–25 years of age, 67% female, 25% with implantable cardioverter defibrillators, 90% genotype positive, 49% with LQT1, 91% were treated with beta-blockers, left cardiac sympathetic denervation, and/or implantable cardioverter defibrillator), 52% participated in vigorous exercise (55% of these competitively). Thirty-seven individuals experienced the composite end point (including one sudden cardiac arrest and one sudden death in the nonvigorous group, one sudden cardiac arrest in the vigorous group) with overall event rates at 3 years of 2.6% in the vigorous and 2.7% in the nonvigorous exercise groups. The unadjusted hazard ratio for experience of events for the vigorous group compared with the nonvigorous group was 0.97 (90% CI, 0.57–1.67), with an adjusted hazard ratio of 1.17 (90% CI, 0.67–2.04). The upper 95% one-sided confidence level extended beyond the 1.5 boundary. Neither vigorous or nonvigorous exercise was found to be superior in any group or subgroup. CONCLUSIONS: Among individuals diagnosed with phenotypic and/or genotypic LQTS who were risk assessed and treated in experienced centers, LQTS-associated cardiac event rates were low and similar between those exercising vigorously and those not exercising vigorously. Consistent with the low event rate, CIs are wide, and noninferiority was not demonstrated. These data further inform shared decision-making discussions between patient and physician about exercise and competitive sports participation. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02549664.

Importance Whether vigorous intensity exercise is associated with an increase in risk of ventricular arrhythmias in individuals with hypertrophic cardiomyopathy (HCM) is unknown. Objective To determine whether engagement in vigorous exercise is associated with increased risk for ventricular arrhythmias and/or mortality in individuals with HCM. The a priori hypothesis was that participants engaging in vigorous activity were not more likely to have an arrhythmic event or die than those who reported nonvigorous activity. Design, Setting, and Participants This was an investigator-initiated, prospective cohort study. Participants were enrolled from May 18, 2015, to April 25, 2019, with completion in February 28, 2022. Participants were categorized according to self-reported levels of physical activity: sedentary, moderate, or vigorous-intensity exercise. This was a multicenter, observational registry with recruitment at 42 high-volume HCM centers in the US and internationally; patients could also self-enroll through the central site. Individuals aged 8 to 60 years diagnosed with HCM or genotype positive without left ventricular hypertrophy (phenotype negative) without conditions precluding exercise were enrolled. Exposures Amount and intensity of physical activity. Main Outcomes and Measures The primary prespecified composite end point included death, resuscitated sudden cardiac arrest, arrhythmic syncope, and appropriate shock from an implantable cardioverter defibrillator. All outcome events were adjudicated by an events committee blinded to the patient’s exercise category. Results Among the 1660 total participants (mean [SD] age, 39 [15] years; 996 male [60%]), 252 (15%) were classified as sedentary, and 709 (43%) participated in moderate exercise. Among the 699 individuals (42%) who participated in vigorous-intensity exercise, 259 (37%) participated competitively. A total of 77 individuals (4.6%) reached the composite end point. These individuals included 44 (4.6%) of those classified as nonvigorous and 33 (4.7%) of those classified as vigorous, with corresponding rates of 15.3 and 15.9 per 1000 person-years, respectively. In multivariate Cox regression analysis of the primary composite end point, individuals engaging in vigorous exercise did not experience a higher rate of events compared with the nonvigorous group with an adjusted hazard ratio of 1.01. The upper 95% 1-sided confidence level was 1.48, which was below the prespecified boundary of 1.5 for noninferiority. Conclusions and Relevance Results of this cohort study suggest that among individuals with HCM or those who are genotype positive/phenotype negative and are treated in experienced centers, those exercising vigorously did not experience a higher rate of death or life-threatening arrhythmias than those exercising moderately or those who were sedentary. These data may inform discussion between the patient and their expert clinician around exercise participation.

AbstractBackgroundOpioid overdose deaths have disproportionately impacted Black and Hispanic populations, in part due to disparities in treatment access. Emergency departments (EDs) serve as a resource for patients with opioid use disorder (OUD), many of whom have difficulty accessing outpatient addiction programs. However, inequities in ED treatment for OUD remain poorly understood.MethodsThis secondary analysis examined racial and ethnic differences in buprenorphine access using data from EMBED, a study of 21 EDs across five health care systems evaluating a clinical decision support system for initiating ED buprenorphine. The primary outcome was receipt of buprenorphine, ED administered or prescribed. Hospital type (academic vs. community) was evaluated as an effect modifier. Hierarchical models with cluster effects for site and clinician were used to assess buprenorphine receipt by race and ethnicity.ResultsBlack patients were less likely to receive buprenorphine (6.4% [51/801] vs. White patients 8.5% [268/3154], odds ratio [OR] 0.59, 95% confidence interval [CI] 0.45–0.78). This association persisted after adjusting for age, insurance, gender, clinician X‐waiver, hospital type, and urbanicity (adjusted OR [aOR] 0.64, 95% CI 0.48–0.84) but not when discharge diagnosis was included (aOR 0.75, 95% CI 0.56–1.02). Hispanic patients were more likely to receive buprenorphine (14.8% [122/822] vs. non‐Hispanic patients, 11.6% [475/4098]) in unadjusted (OR 1.57, 95% CI 1.09–1.83) and adjusted models (aOR 1.41, 95% CI 1.08–1.83) but not including discharge diagnosis (aOR 1.32, 95% CI 0.99–1.77). Odds of buprenorphine were similar in academic and community EDs by race (interaction p = 0.97) and ethnicity (interaction p = 0.64).ConclusionsBlack patients with OUD were less likely to receive buprenorphine whereas Hispanic patients were more likely to receive buprenorphine in academic and community EDs. Differences were attenuated with discharge diagnosis, as fewer Black and non‐Hispanic patients were diagnosed with opioid withdrawal. Barriers to medication treatment are heterogenous among patients with OUD; research must continue to address the multiple drivers of health inequities at the patient, clinician, and community level.

Abstract Objective To determine the effect of a user centered clinical decision support tool versus usual care on rates of initiation of buprenorphine in the routine emergency care of individuals with opioid use disorder. Design Pragmatic cluster randomized controlled trial (EMBED). Setting 18 emergency department clusters across five healthcare systems in five states representing the north east, south east, and western regions of the US, ranging from community hospitals to tertiary care centers, using either the Epic or Cerner electronic health record platform. Participants 599 attending emergency physicians caring for 5047 adult patients presenting with opioid use disorder. Intervention A user centered, physician facing clinical decision support system seamlessly integrated into user workflows in the electronic health record to support initiating buprenorphine in the emergency department by helping clinicians to diagnose opioid use disorder, assess the severity of withdrawal, motivate patients to accept treatment, and complete electronic health record tasks by automating clinical and after visit documentation, order entry, prescribing, and referral. Main outcome measures Rate of initiation of buprenorphine (administration or prescription of buprenorphine) in the emergency department among patients with opioid use disorder. Secondary implementation outcomes were measured with the RE-AIM (reach, effectiveness, adoption, implementation, and maintenance) framework. Results 1 413 693 visits to the emergency department (775 873 in the intervention arm and 637 820 in the usual care arm) from November 2019 to May 2021 were assessed for eligibility, resulting in 5047 patients with opioid use disorder (2787 intervention arm, 2260 usual care arm) under the care of 599 attending physicians (340 intervention arm, 259 usual care arm) for analysis. Buprenorphine was initiated in 347 (12.5%) patients in the intervention arm and in 271 (12.0%) patients in the usual care arm (adjusted generalized estimating equations odds ratio 1.22, 95% confidence interval 0.61 to 2.43, P=0.58). Buprenorphine was initiated at least once by 151 (44.4%) physicians in the intervention arm and by 88 (34.0%) in the usual care arm (1.83, 1.16 to 2.89, P=0.01). Conclusions User centered clinical decision support did not increase patient level rates of initiating buprenorphine in the emergency department. Although streamlining and automating electronic health record workflows can potentially increase adoption of complex, unfamiliar evidence based practices, more interventions are needed to look at other barriers to the treatment of addiction and increase the rate of initiating buprenorphine in the emergency department in patients with opioid use disorder. Trial registration ClinicalTrials.gov NCT03658642 .

Introduction: Safety of vigorous exercise for individuals with appropriately-treated HCM remains debated. Physical activity practices in this population have not been described. The objective of this report is to describe physical activity pattern in HCM patients. Long term follow up which is ongoing will determine safety of vigorous exercise. Methods: The NIH-funded LIVE-HCM study prospectively enrolled individuals age 8-60 years with clinically overt HCM or patients with a positive genetic test for sarcomeric HCM. Participants (or parents, for children) answered surveys describing activity patterns. Vigorous exercise was defined as > 6 METS for > 60 hours per year. Clinical and demographic data were derived from medical record review. Results: Among 1798 participants, 745 (41%) reported exercising vigorously, including 296 competitive athletes, with 59 at high-school or college varsity level, 770 (43%) were exercising at moderate, and 283 (16%) at low levels. Of those working, 6% described jobs more active than walking, including 16 in protective services, and 11 in sports/coaching. Clinical/demographic data including imaging characteristics and treatments, are shown in Table, and were mostly similar amongst the exercise-groups. Conclusions: Many patients with HCM are engaged in vigorous exercise including competitive athletics. Prospective follow-up of this cohort is ongoing. Comparison of arrhythmic outcomes outcomes in vigorous exercisers vs moderate/low level exercisers will help determine the safety of exercise in HCM patients.

Introduction: The safety of vigorous exercise for individuals with appropriately-treated LQTS remains unproven, and physical activity practices in this population have not been described. Methods: LIVE-LQTS prospectively enrolled individuals age 8-60 years with overt LQTS or gene mutation carriers. Participants (or parents, for children) answered surveys describing activity patterns. Vigorous exercise was defined as > 6 METS for > 60 hours per year. Clinical and demographic data were derived from medical record review. Results: Among 1554 participants, 804 (52%) reported exercising vigorously, 473 of these competitively, 577 (37%) exercising at moderate, and 173 (11%) at low levels. Seven percent of those working describe jobs more active than walking, including 10 in protective services and 19 in sports/coaching. Over 90% are genotype positive, 57% are phenotype positive at rest and an additional 16% have exercise-induced QT prolongation. Forty four percent have had documented ventricular arrhythmias or syncope. Eighty-four percent are appropriately treated with either beta-blockers, ICD, and/or sympathectomy, although among beta-blocked patients, only 60% are on the most effective agents. Among adults, BMI was significantly lower among the vigorous exercisers. Conclusion: While the high percentage of vigorous exercisers seen in this study may not represent all patients with LQTS due to self-selection for study participation, many patients with LQTS are engaged in vigorous exercise or competitive athletics. Prospective follow up of this cohort is ongoing and will determine safety of vigorous exercise through comparison of arrhythmic outcomes in vigorous exercisers vs moderate/low level exercisers.

Background: Despite safety concerns, many young patients with implantable cardioverter-defibrillators (ICDs) participate in sports. We undertook a prospective, multinational registry to determine the incidence of serious adverse events because of sports participation. The primary end points were death or resuscitated arrest during sports or injury during sports because of arrhythmia or shock. Secondary end points included system malfunction and incidence of ventricular arrhythmias requiring multiple shocks for termination. Methods: Athletes with ICDs aged ≤21 years were included in this post hoc subanalysis of the ICD Sports Registry. Data on sports and clinical outcomes were obtained by phone interview and medical records review. ICD shocks and clinical details of lead malfunction were classified by 2 electrophysiologists. Results: A total of 129 young athletes participating in competitive (n=117) or dangerous (n=12) sports were enrolled. The mean age was 16 years (range, 10–21; 40% female; 92% white). The most common diagnoses were long QT syndrome (n=49), hypertrophic cardiomyopathy (n=30), and congenital heart disease (n=16). The most common sports were basketball and soccer, including 79 varsity/junior varsity high school and college athletes. During a median follow-up of 42 months, 35 athletes (27%) received 38 shocks. There were no occurrences of death, arrest, or injury related to arrhythmia, during sports. There was 1 ventricular tachycardia/ventricular fibrillation storm during competition. Freedom from lead malfunction was 92.3% at 5 years and 79.6% at 10 years. Conclusions: Although shocks related to competition/practice are not uncommon, there were no serious adverse sequelae. Lead malfunction rates were similar to previously reported in unselected pediatric ICD populations. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00637754.