Vigorous Exercise in Patients With Congenital Long QT Syndrome: Results of the Prospective, Observational, Multinational LIVE-LQTS Study.

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.

Improving lifestyle behaviors during chemotherapy for breast cancer: The Lifestyle, Exercise, and Nutrition Early After Diagnosis (LEANer) Trial.

BACKGROUND: Little is known about improving physical activity (PA) and diet during and after chemotherapy for breast cancer. This secondary analysis examines changes in PA and diet quality during a yearlong intervention for patients with breast cancer undergoing chemotherapy and evaluates factors associated with these changes. METHODS: Newly diagnosed patients with breast cancer (N = 173) undergoing chemotherapy were randomized to a year-long nutrition and exercise intervention (n = 87) or usual care (UC, n = 86). Mixed models compared 1-year changes in PA and diet quality via the Healthy Eating Index (HEI)-2015 by study arm. Among the intervention group, baseline factors associated with change in PA and diet were assessed with multivariable linear and logistic regression. RESULTS: At 1 year, compared with UC, the intervention arm increased PA more (mean difference = 136.1 minutes/week; 95% CI, 90.2-182.0), participated in more strength training (56% vs. 15%; p < .001), and had suggestive improvements in HEI-2015 (mean difference = 2.5; 95% CI, -0.3 to 5.3; p = .08). In the intervention arm, lower fatigue was associated with improved PA (p = .04) and higher education was associated with improved HEI-2015 (p = .001) at 1 year. Higher HEI-2015 (p = .04) and married/living with someone (p = .05) were associated with higher odds of participating in strength training at 1 year. CONCLUSIONS: This year-long lifestyle intervention for patients with breast cancer undergoing chemotherapy resulted in increases in PA and suggestive improvements in diet quality. Behavior change was associated with baseline fatigue, diet quality, education, and married/living with someone. Addressing these factors in interventions may improve uptake of lifestyle behaviors in trials during and after chemotherapy.

Role of Early Psychosis Detection in the Relationship Between Personal Income and Duration of Untreated Psychosis.

OBJECTIVE: Prolonged duration of untreated psychosis (DUP) predicts poor outcomes of first-episode psychosis (FEP) and is often linked to low socioeconomic status (SES). The authors sought to determine whether patients' personal income, used as a proxy for SES, predicts length of DUP and whether personal income influences the effect of an early psychosis detection campaign-called Mindmap-on DUP reduction. METHODS: Data were drawn from a trial that compared the effectiveness of early detection in reducing DUP across the catchment area of an FEP service (N=147 participants) compared with an FEP service with no early detection (N=75 participants). Hierarchical regression was used to determine whether personal income predicted DUP when analyses controlled for effects of age, race, and exposure to early psychosis detection. A group × personal income interaction term was used to assess whether the DUP difference between the early detection and control groups differed by personal income. RESULTS: Lower personal income was significantly associated with younger age, fewer years of education, Black race, and longer DUP. Personal income predicted DUP beyond the effects of age, race, and early psychosis detection. Although Mindmap significantly reduced DUP across all income levels, this effect was smaller for participants reporting lower personal income. CONCLUSIONS: Patients' personal income may be an important indicator of disparity in access to specialty care clinics across a wide range of settings. Early detection efforts should measure and target personal income and other SES indicators to improve access for all individuals who may benefit from FEP services.

Trends and predictors of Quality of Life in lung cancer survivors.

INTRODUCTION: Health-related quality of life (HR-QoL) is often impaired in lung cancer survivors. To inform personalized survivorship care, we identified associations between HR-QoL scores and patient-, tumor-, and treatment-factors over time. MATERIALS AND METHODS: We evaluated HR-QoL scores provided at diagnosis, 6 months, 1 year, and 2 years from the Yale Lung Cancer Biorepository. HR-QoL was measured via the Functional Assessment of Cancer Therapy - Lung (FACT-L) instrument and available for a subset of patients (n = 513). Analyses were stratified by early-stage (I-II; n = 355) non-small cell lung cancer (NSCLC), advanced stage NSCLC (III-IV; n = 158), and small cell lung cancer (SCLC, n = 21). We used mixed effects modeling and multivariable analysis with covariate adjustment to examine changes in FACT-L from diagnosis to follow-up. Sensitivity analysis was performed including patients with early-stage disease and complete FACT-L scores at both baseline and year 2 (n = 91). RESULTS: The average FACT-L scores at diagnosis in early-stage NSCLC, advanced stage NSCLC, and SCLC were 121.0 (standard deviation (SD) 11.4), 109.2 (18.7), and 98.7 (20.2) respectively. At all timepoints, HR-QoL was higher in patients with early-stage NSCLC (vs advanced-stage disease). In patients with early- and advanced-stage NSCLC, HR-QoL was higher at years 1 and 2 than at diagnosis, though the changes did not meet clinical significance. At NSCLC diagnosis, higher HR-QoL was associated with older age, better performance status, participating in physical activity, adenocarcinoma histology, and (in advanced stage NSCLC) anticipated treatment with chemotherapy. At NSCLC follow-up, HR-QoL was higher in patients with higher BMI and better performance status. DISCUSSION: In patients with newly diagnosed NSCLC, HR-QoL scores are impacted by patient factors, tumor factors, and treatment factors. HR-QoL is higher in patients with early-stage disease. In patients surviving 2 years, HR-QoL was higher at follow-up, though the change did not meet clinical significance. To optimize HR-QoL, lung cancer survivorship teams should prioritize comorbidity management, physical activity, healthy weight maintenance, and treatment-related side effects.

Persistent and multiclonal malaria parasite dynamics despite extended artemether-lumefantrine treatment in children.

Standard diagnostics used in longitudinal antimalarial studies are unable to characterize the complexity of submicroscopic parasite dynamics, particularly in high transmission settings. We use molecular markers and amplicon sequencing to characterize post-treatment stage-specific malaria parasite dynamics during a 42 day randomized trial of 3- versus 5 day artemether-lumefantrine in 303 children with and without HIV (ClinicalTrials.gov number NCT03453840). The prevalence of parasite-derived 18S rRNA is >70% in children throughout follow-up, and the ring-stage marker SBP1 is detectable in over 15% of children on day 14 despite effective treatment. We find that the extended regimen significantly lowers the risk of recurrent ring-stage parasitemia compared to the standard 3 day regimen, and that higher day 7 lumefantrine concentrations decrease the probability of ring-stage parasites in the early post-treatment period. Longitudinal amplicon sequencing reveals remarkably dynamic patterns of multiclonal infections that include new and persistent clones in both the early post-treatment and later time periods. Our data indicate that post-treatment parasite dynamics are highly complex despite efficacious therapy, findings that will inform strategies to optimize regimens in the face of emerging partial artemisinin resistance in Africa.

The Anomalous Effect of COVID-19 Pandemic Restrictions on the Duration of Untreated Psychosis (DUP).

We investigated the impact of COVID-19 restrictions on the duration of untreated psychosis (DUP). First-episode psychosis admissions (n=101) to STEP Clinic in Connecticut showed DUP reduction (p=.0015) in the pandemic, with the median reducing from 208 days during the pre-pandemic to 56 days in the early pandemic period and subsequently increasing to 154 days (p=.0281). Time from psychosis onset to anti-psychotic prescription decreased significantly in the pandemic (p=.0183), with the median falling from 117 to 35 days. This cohort study demonstrates an association between greater pandemic restrictions and marked DUP reduction and provides insights for future early detection efforts.

The impact of early detection (ED) campaigns on care presentations: Beyond DUP reduction.

We examined the effects of an early detection (ED) campaign (Mindmap), that successfully shortened the duration of untreated psychosis (DUP), on patient presentation profiles at two receiving coordinated specialty care (CSC) services. Data were collected between 2015 and 2019 during a test of ED delivered at one CSC (STEP, n = 147) compared to usual detection at another CSC (PREP, n = 63). Regression models were used to test the effects of ED and DUP on presentation. Before the launch of ED, there were no differences in presentation between STEP and PREP. However, the ED changed the profile of presentations to STEP such that patients were admitted with better negative and total symptoms scores, but worse GAF current and GAF social and with a greater decline in function over the prior year (GAF-Δ). Site-by-time interaction effects were not significant. During the campaign years, STEP vs. PREP recruited patients with better negative and total symptoms, GAF role, and pre-morbid adjustment scores but with worse positive symptoms, GAF current, and GAF-Δ. Nonetheless, mediation analysis revealed that DUP reduction accounted for very little (<8 %) of these differences in presentation. Early detection campaigns while successfully reducing access delays, can have salutary effects on presentation independent of DUP reduction.

Association of Crowd-Sourced Assessment of Technical Skills and Outcomes of Robotic-assisted Radical Prostatectomy.

OBJECTIVE: To investigate if use of the Crowd-Sourced Assessment of Technical Skills (CSATS) platform and video peer review with constructive feedback is associated with improvement in technical skill and patient outcomes for robotic-assisted laparoscopic prostatectomy (RALP). METHODS: Five fellowship-trained urologists voluntarily submitted RALP cases for CSATS Global Evaluative Assessment of Robotic Skills (GEARS) scoring and expert narrative review between April 15, 2022-April 30, 2023. Surgeon-selected and randomly selected cases were reviewed. Surgeons underwent local peer review of videos with constructive feedback. Change in GEARS scores and frequency of postoperative outcomes over the 12-month periods before and during the study were analyzed in logistic regression models. Bias was assessed with sensitivity analysis comparing surgeon-selected to randomly selected cases. RESULTS: GEARS scores for randomly selected vs surgeon-selected cases did not differ significantly. Overall GEARS score correlated positively with annual surgical RALP volume (r = 0.39, P = .003) and negatively with years in practice (r = -0.34, P = .01). After adjusting for confounders, there was no significant improvement in overall GEARS Score (0.01 ± 0.02/month, P = .48); but likelihood of sepsis (Odds Ratio 0.07, 95% CI 0.01-1.00, P = .05) and pelvic fluid collection (Odds Ratio 0.09, 95% CI 0.01-0.99, P = .049) were significantly decreased during the intervention period (n = 165) compared to the prior 12months (n = 144). No outcome increased in likelihood (P > .05). CONCLUSION: Integration of CSATS and local video peer review is associated with significant improvement in patient outcomes after RALP, despite no significant change in surgeons' GEARS scores. This is the first study demonstrating improvement in patient RALP outcomes after implementation of such a paradigm in practicing surgeons.

Corrigendum to: Reducing the Duration of Untreated Psychosis (DUP) in a US Community: A Quasi-Experimental Trial.

[This corrects the article DOI: 10.1093/schizbullopen/sgab057.].