Publications

BACKGROUND: Association between light to moderate alcohol consumption and colorectal cancer (CRC) incidence remains understudied, especially regarding drinking pattern, beverage type and temporal aspects.

METHODS: Hazard ratios (HRs) and 95% confidence intervals (CIs) for time to CRC diagnosis were estimated among 137,710 participants. Estimates based on remote (eg, >10 years before follow-up) and recent (eg, the preceding 10 years before follow-up) alcohol intake, using different cutoffs (eg, 8, 10, 12 years, etc) and mutual adjustment, enabled separating independent effects and investigating time lag of alcohol-CRC association.

RESULTS: 3,599 CRC cases were documented over three decades. Light to moderate drinking was associated with an increased CRC risk only in men: HR (95% CI) for 5-14.9 and 15-29.9 vs 0 g/day of alcohol intake was 1.19 (1.01, 1.41) and 1.38 (1.13, 1.67). In women, that for 0.1-4.9 and 5-14.9 vs 0 g/day of alcohol was 1.07 (0.96, 1.20) and 1.05 (0.91, 1.20). Drinkers with both high drinking frequency and daily intake had the highest CRC risk, suggesting total alcohol intake was the critical factor. We estimated the time lag between alcohol consumption and CRC occurrence to be 8 to 12 years. Former drinkers did not experience a significant reduction in CRC risk even after 10 years of quitting or reducing consumption.

CONCLUSIONS: Based on two cohorts of health professionals, our findings suggest that the increased risk of CRC associated with alcohol intake is mainly driven by total quantity and remote intake. Former drinkers did not experience an immediate reduction in CRC risk after quitting or reducing consumption.

INTRODUCTION: Time-limited trial (TLT) is a structured approach between clinicians and seriously ill patients or their surrogates to discuss patients' values and preferences, prognosis, and shared decision-making to use specific therapies for a prespecified period of time in the face of prognostic uncertainty. Some evidence exists that this approach may lead to more patient-centered care in the intensive care unit; however, it has never been evaluated in the emergency department (ED). The study protocol aims to assess the feasibility and acceptability of TLTs initiated in the ED.

METHODS AND ANALYSIS: We will conduct a parallel group, clinician-level, pilot randomized clinical trial among 40 ED clinicians. We will measure feasibility (e.g., the time it takes to conduct the TLTs by ED clinicians) and clinician and patient-reported acceptability of the TLT, and also track patients' clinical outcomes via medical record review.

DISCUSSION: This study protocol will investigate the potential of TLT initiated in the ED to lead to patient-centered intensive care utilization. By doing so, the study intends to improve palliative care integration for seriously ill older adults in the ED and intensive care unit.

TRIAL IDENTIFIER AND REGISTRY NAME: ClinicalTrials.gov ID: NCT06378151 https://clinicaltrials.gov/study/NCT06378151; Pre-results; a randomized controlled trial: Time-limited Trials in the Emergency Department.

BACKGROUND: Long-acting injectable antiretrovirals (LAI-ARVs) for HIV prevention and treatment have been demonstrated in clinical trials to be non-inferior to daily oral medications, providing an additional option to help users overcome the challenges of daily adherence. Approval and implementation of these regimens in low- and middle-income settings have been limited.

METHOD: This study describes the anticipated barriers and facilitators to implementing LAI-ARVs in Vietnam to inform future roll-out. From July to August 2022, we conducted 27 in-depth interviews with healthcare workers and public health stakeholders involved in HIV programs at national, provincial, and clinic levels across four provinces in Vietnam. The interviews followed a semi-structured questionnaire and were audio recorded. Data were analyzed using a rapid thematic analysis approach to identify facilitators and barriers to the adoption of LAI-ARVs.

RESULTS: In total, 27 participants from 4 provinces were interviewed including 14 (52%) men and 13 (48%) women. Participants median age was 48 years and they had 11.5 years of experience with HIV services and programs. Perceived user-level facilitators included the greater convenience of injectables in comparison to oral regimens, while barriers included the increased frequency of visits, fear of pain and side effects, and cost. Clinic-level facilitators included existing technical capacity to administer injections and physical storage availability in district health centers, while barriers included lack of space and equipment for administering injections for HIV-related services, concerns about cold chain maintenance for LAI-ART, and workload for healthcare workers. Health system-level facilitators included existing mechanisms for medication distribution, while barriers included regulatory approval processes and concerns about supply chain continuity.

CONCLUSION: Overall, participants were optimistic about the potential impact of LAI-ARVs but highlighted important considerations at multiple levels needed to ensure successful implementation in Vietnam.

CLINICAL TRIAL NUMBER: Not applicable.

BACKGROUND: Risk stratification for sudden cardiac death (SCD) in patients with nonischemic cardiomyopathy (NICM) remains challenging.

OBJECTIVES: This study aimed to investigate the impact of epicardial adipose tissue (EAT) on SCD in NICM patients.

METHODS: Our study cohort included 173 consecutive patients (age 53 ± 14 years, 73% men) scheduled for primary prevention implantable cardioverter-defibrillators (ICDs) implantation who underwent preimplant cardiovascular magnetic resonance. EAT volume surrounding both ventricles was manually quantified from cine left ventricular short-axis images by summation of the EAT volume of each slice using the modified Simpson rule. The primary endpoint was appropriate ICD therapy.

RESULTS: During the mean follow-up of 3.6 years, 24 patients (14%) experienced an endpoint. An inverse and proportional relationship was evident between EAT and subsequent ICD therapies (P = 0.004). Even after adjusting for left ventricular mass and ejection fraction, EAT was significantly lower in patients with ICD therapy than those without. Low EAT was independently associated with an increased risk of ICD therapy in NICM patients (HRad per 10 mL/m2 decrease, 1.65; 95% CI: 1.17-2.42; P = 0.007). EAT ≤50 mL/m2 demonstrated a 3-fold increase in SCD event risk, with an estimated likelihood of 57% at 5 years. When considered with other potential risk factors, EAT provided incremental prognostic value in predicting ICD therapy.

CONCLUSIONS: Low ventricular EAT was associated with increased SCD risk in NICM patients receiving primary prevention ICD implantation, even in the presence of other risk markers. These data suggest a potential clinical role of EAT in selecting NICM patients who would benefit most from ICD implantation.

OBJECTIVES: In observational studies, older adults with low serum vitamin D levels are at higher risk of cardiovascular disease (CVD), but randomized trials have failed to demonstrate reduction in CVD risk from vitamin D supplementation, possibly because the doses of vitamin D supplements tested were too low. Our objective was to determine if higher doses of vitamin D supplementation reduce high-sensitivity cardiac troponin (hs-cTnI) and N-terminal pro-b-type natriuretic peptide (NT-proBNP), markers of subclinical CVD.

METHODS: The Study to Understand Fall Reduction and Vitamin D in You (STURDY) was a double-blind, randomized, response-adaptive trial that tested the effects of 4 doses of vitamin D3 supplementation (200, 1000, 2000, 4000 IU/day) on fall risk among older adults with low serum 25-hydroxyvitamin D concentrations (10-29 ng/mL). Hs-cTnI and NT-proBNP levels were measured at baseline, 3-, 12-, and 24-month follow-up visits. For this ancillary study, we used data from the original trial and compared participants by treatment group: low-dose (200 IU/day) or high-dose (1000+ IU/day). The effects of vitamin D dose on biomarkers were assessed via mixed effects tobit models.

RESULTS: Among 688 participants (mean age of 76.5) hs-cTnI increased in both the low- and high-dose groups by 5.2 % and 7.0 %, respectively; likewise, NT-proBNP increased by 11.3 % and 9.3 %, respectively. Compared to the low-dose, high-dose vitamin D supplementation did not affect hs-cTnI (1.6 %-difference; 95 % CI: -5.3, 8.9) or NT-proBNP (-1.8 %-difference; 95 % CI: -9.3, 6.3).

CONCLUSIONS: Compared to low-dose vitamin D supplementation, doses ≥1,000 IU/ day did not affect markers of subclinical CVD in older adults with low serum vitamin D levels.

BACKGROUND: A healthier diet is associated with lower chronic disease burden, but the impact of neighbourhood food environments on disability and death in older adults is not known.

METHODS: In the Cardiovascular Health Study, a cohort study of adults aged 65+, we calculated study years until death (years of life (YOL)), study years without activities of daily living (ADL) difficulty (years of able life; YoAL) and percent of study years without ADL difficulty (compression of disability). Linear regression quantified associations of food establishments within 5 km of baseline home address (as a z-score) with each outcome, adjusted for sociodemographic characteristics. Sensitivity analyses considered adjustment for risk factors and comorbidities, multiple imputation, alternate neighbourhood definitions (1-km radial buffer, census tract) and restriction on residential stability.

RESULTS: We included 4298 participants followed for up to 26 years. All food retail establishments were associated with 6 months higher YoAL per SD in the main model (beta, 0.50 years; 95% CI 0.01, 0.98; p=0.046), with similar findings across sensitivity analyses except when restricting on residential stability. Supermarkets and produce markets were associated with compression of disability (beta, 2.31; 95% CI, 0.04, 4.57) and when using 1-km buffers with YOL (beta, 0.23 years; 95% CI 0.03, 0.43) and YoAL (beta, 0.21 years; 95% CI 0.01, 0.41). Non-supermarket food stores were associated with YoAL (beta, 0.67 years; 95% CI, 0.07, 1.27) and compression of disability (beta, 3.03; 95% CI 0.44, 5.62), but significance was not consistent across sensitivity analyses. Fast-food restaurants did not reach statistical significance in any model.

CONCLUSION: All food retail was associated with YOL without impairment. Neighbourhood food retail access and type may both have roles in extending YOL and years of able life among older adults, but the findings were sensitive to decisions made during measurement and modelling.

INTRODUCTION: Fear of cancer recurrence (FCR) is prevalent and distressing among survivors of cancer. Evidence-based mind-body and cognitive-behavioral skills lack integration and testing in scalable formats.

OBJECTIVE: This pilot randomized controlled trial (NCT04876599) tested a synchronous, virtual mind-body group resiliency intervention for FCR (IN FOCUS).

METHOD: Adults with elevated FCR (FCR Inventory severity ≥ 16; 16-21 = elevated, 22-36 = clinically elevated) after completing primary treatment for non-metastatic cancer were randomly assigned (1:1) to eight weekly sessions of IN FOCUS or usual care (UC; synchronous, virtual community group support referral). Feasibility metrics included ≥ 70% retention per arm (primary outcome), ≥ 75% attendance in ≥ 6 sessions, ≥ 75% adherence to relaxation skills practice ≥ 3 days per week and by delivery fidelity (% content covered in video-recorded sessions). Acceptability was assessed quantitatively via ratings of enjoyableness, convenience, helpfulness, odds of future use, and satisfaction (benchmark ≥ 80% of ratings ≥ 4 on 1-5 Likert scale) and qualitatively via individual exit interviews. Linear mixed models explicated slopes in FCR (secondary) and resiliency (exploratory; Current Experiences Scale) from baseline to 2 months (primary endpoint) and 5 months using intention-to-treat.

RESULTS: From July 2021 to March 2022, 64 survivors enrolled (25-73 years old, M = 7 years since diagnosis). IN FOCUS was feasible and acceptable (91% retention; attendance median = 7 sessions, 97% relaxation practice adherence, 95% content fully covered; 82% of acceptability ratings ≥ 4). Interviews (n = 59) revealed benefits in both arms. By 2 months, compared to UC, IN FOCUS reduced FCR to a medium-to-large effect (Mdiff = -2.4; 95% CI = -4.2, -0.7; d = 0.66). By 5 months, FCR effects had attenuated (Mdiff = -0.16, 95% CI -1.97, 1.65; d = -0.04), although levels of resiliency had increased with a medium-to-large effect (Mdiff = 10.0; 95% CI = 4.9, 15.1; d = 0.78).

CONCLUSIONS: For survivors of non-metastatic cancer, a synchronous, virtual mind-body resiliency program for FCR is feasible, acceptable, and seemingly beneficial compared to a community group referral.