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The National Institutes of Health requires data and safety monitoring boards (DSMBs) for all phase III clinical trials. The National Heart, Lung and Blood Institute requires DSMBs for all clinical trials involving more than one site and those involving cooperative agreements and contracts. These policies have resulted in the establishment of DSMBs for many implementation trials, with little consideration regarding the appropriateness of DSMBs and/or key adaptations needed by DSMBs to monitor data quality and participant safety. In this perspective, we review the unique features of implementation trials and reflect on key questions regarding the justification for DSMBs and their potential role and monitoring targets within implementation trials.

Background Previous cross‐sectional studies have shown conflicting results regarding the effects of television viewing and occupational sitting on cardiovascular disease (CVD) risk factors. The purpose of this study was to compare the association of both television viewing and occupational sitting with CVD events and all‐cause mortality in blacks. Methods and Results Participants included 3592 individuals enrolled in the Jackson Heart Study, a community‐based study of blacks residing in Jackson, Mississippi. Television viewing (4 h/day) and occupational sitting (never/seldom, sometimes, often/always) were self‐reported. Over a median follow‐up of 8.4 years, there were 129 CVD events and 205 deaths. The highest category of television viewing (>4 h/day) was associated with a greater risk for a composite CVD events/all‐cause mortality end point compared with the lowest category (

Introduction: Physical activity (PA) and sleep are associated with cerebrovascular disease and events like stroke. Though the interrelationships between PA, sleep, and other stroke risk factors have been studied, we are unclear about the associations of different types, frequency and duration of PA, sleep behavioral patterns (short, average and long sleep durations), within the context of stroke-related clinical, behavioral, and socio-demographic risk factors. The current study utilized Bayesian Belief Network analysis (BBN), a type of machine learning analysis, to develop profiles of physical activity (duration, intensity, and frequency) and sleep duration associated with or no history of stroke, given the influence of multiple stroke predictors and correlates. Such a model allowed us to develop a predictive classification model of stroke which can be used in post-stroke risk stratification and developing targeted stroke rehabilitation care based on an individual's profile.Method: Analysis was based on the 2004–2013 National Health Interview Survey (n = 288,888). Bayesian BBN was used to model the omnidirectional relationships of sleep duration and physical activity to history of stroke. Demographic, behavioral, health/medical, and psychosocial factors were considered as well as sleep duration [defined as short < 7 h. and long ≥ 9 h, referenced to healthy sleep (7–8 h)], and intensity (moderate and vigorous) and frequency (times/week) of physical activity.Results: Of the sample, 48.1% were ≤ 45 years; 55.7% female; 77.4% were White; 15.9%, Black/African American; and 45.3% reported an annual income < $35 K. Overall, the model had a precision index of 95.84%. We found that adults who reported 31–60 min of vigorous physical activity six times for the week and average sleep duration (7–8 h) had the lowest stroke prevalence. Of the 36 sleep (short, average, and long sleep) and physical activity profiles we tested, 30 profiles had a self-reported stroke prevalence lower than the US national average of approximately 3.07%. Women, compared to men with the same sleep and physical activity profile, appeared to have higher self-reported stroke prevalence. We also report age differences across three groups 18–45, 46–65, and 66+.Conclusion: Our findings indicate that several profiles of sleep duration and physical activity are associated with low prevalence of self-reported stroke and that there may be sex differences. Overall, our findings indicate that more than 10 min of moderate or vigorous physical activity, about 5–6 times per week and 7–8 h of sleep is associated with lower self-reported stroke prevalence. Results from the current study could lead to more tailored and personalized behavioral secondary stroke prevention strategies.

Environmental factors, such as noise exposure and air pollution, are associated with hypertension. These environmental factors also affect sleep quality. Given the growing evidence linking sleep quality with hypertension, the purpose of this review is to investigate the role of sleep as a key mediator in the association between hypertension and environmental factors. Through this narrative review of the extant literature, we highlight that poor sleep quality mediates the relationship between environmental factors and hypertension. The conceptual model proposed in this review offers opportunities to address healthcare disparities in hypertension among African Americans by highlighting the disparate impact that the predictors (environmental factors) and mediator (sleep) have on the African-American community. Understanding the impact of these factors is crucial since the main outcome variable (hypertension) severely burdens the African-American community.

Abstract Background Ibrutinib, a first-in-class inhibitor of Bruton’s tyrosine kinase, is approved for the treatment of various B-cell malignancies and chronic graft-versus-host disease. Based on encouraging preclinical data, safety and efficacy of ibrutinib combined with companion drugs for advanced renal cell carcinoma (RCC), gastric/gastroesophageal junctional adenocarcinoma (GC), and colorectal adenocarcinoma (CRC) were evaluated. Methods Ibrutinib 560 mg or 840 mg once daily was administered with standard doses of everolimus for RCC, docetaxel for GC, and cetuximab for CRC. Endpoints included determination of the recommended phase 2 dose (RP2D) of ibrutinib in phase 1b and efficacy (overall response rate [ORR] for GC and CRC; progression-free survival [PFS] for CRC) in phase 2. Results A total of 39 (RCC), 46 (GC), and 50 (RCC) patients were enrolled and received the RP2D. Safety profiles were consistent with the individual agents used in the study. Confirmed ORRs were 3% (RCC), 21% (GC), and 19% (CRC). Median (90% CI) PFS was 5.6 (3.9–7.5) months in RCC, 4.0 (2.7–4.2) months in GC, and 5.4 (4.1–5.8) months in CRC. Conclusions Clinically meaningful increases in efficacy were not observed compared to historical controls; however, the data may warrant further evaluation of ibrutinib combinations in other solid tumours. Trial registration ClinicalTrials.gov, NCT02599324.

Aim: 177Lu-Dotatate (Lu-177), a form of peptide receptor radionuclide therapy (PRRT), was approved by Food and Drug Administration (FDA) for the treatment of somatostatin-receptor-positive neuroendocrine tumors (NETs) in 2018. Clinical trials prior to the FDA approval of Lu-177 showed favorable outcomes but there is limited published real world outcomes data. This study aims to describe and analyze real world outcomes of patients with NET who received Lu-177. Methods: After obtaining institutional review board approval, retrospective evaluation was performed to analyze the efficacy of Lu-177 for somatostatin receptor-positive gastro-entero-pancreatic NETs (GEP-NETs) patients at the University of Kansas Cancer Center between June 2018 and September 2021. This study aims to determine the response rate to the treatment of the entire cohort and subgroups. Results: A total of 65 patients received Lu-177 of which 58 completed treatment. The 58 patients had a median age of 61.5 years, 24 females and 34 males, 86% Caucasian and 12% black. The origins of NETs were primarily small bowel (n = 24) and pancreatic (n = 14). Pathology showed grades 1 (n = 21), 2 (n = 25), and 3 (n = 4) and were primarily well-differentiated tumors (n = 4). Among the cohort, 52 patients had imaging to assess response with 14 (26.9%) patients with partial response (PR), 31 (59.6%) with stable disease (SD), and 7 (13.5%) with progressive disease (PD). In a subset analysis, patients with non-functional disease (n = 29) had higher rates of PR 42.3% (compared to 11.5%, P = 0.0147) and higher disease control rate of 96% (compared to 78%, P = 0.042) than patients with functional disease (n = 29). Patients with non-functional disease had a lower PD of 3.85% (compared to 23%, P = 0.0147) than those with functional disease. Conclusions: This real world outcomes analysis of NETs treated with Lu-177 shows improved PR when compared to the initial clinical trials and is promising for patients. In addition, patients with non-functional tumors were found to have a statistically significant improved response rate which has not been described in the literature before. If these study findings are validated in a larger cohort they may guide patient selection for Lu-177 therapy in the future.

Background Previous studies have established that higher baseline quality of life (QOL) scores are associated with improved survival in patients with metastatic colorectal cancer (mCRC). We examined the relationship between overall survival (OS) and baseline QOL. Patients and Methods A total of 1 247 patients with mCRC participating in N9741 (comparing bolus 5-FU/LV, irinotecan [IFL] vs infusional 5-FU/leucovorin [LV]/oxaliplatin [FOLFOX] vs. irinotecan/oxaliplatin [IROX]) provided data at baseline on overall QOL using a single-item linear analogue self-assessment (LASA) 0–100 point scale. The association of OS according to clinically deficient (defined as CD-QOL, score 0–50) vs not clinically deficient (nCD-QOL, score 51–100) baseline QOL scores was tested. A multivariable analysis using Cox proportional hazards modeling was performed to adjust for the effects of multiple baseline factors. An exploratory analysis was performed evaluating OS according to baseline QOL status among patients who did or did not receive second-line therapy. Results Baseline QOL was a strong predictor of OS for the whole cohort (CD-QOL vs nCD-QOL: 11.2 months vs 18.4 months, P < .0001), and in each arm IFL 12.4 vs 15.1 months, FOLFOX 11.1 months vs 20.6 months, and IROX 8.9 months vs 18.1 months. Baseline QOL was associated with baseline performance status (PS) ( P < .0001). After adjusting for PS and treatment arm, baseline QOL was still associated with OS ( P = .017). Conclusions Baseline QOL is an independent prognostic factor for OS in patients with mCRC. The demonstration that patient-assessed QOL and PS are independent prognostic indicators suggests that these assessments provide important complementary prognostic information.

Fluorouracil (5-FU) remains the most widely used agent for colorectal cancer. Capecitabine is a rationally designed 5-FU pro-drug developed to mimic the continuous infusion of 5-FU while avoiding complications and inconvenience of intravenous administration. Capecitabine is absorbed intact from the gastrointestinal tract, converted enzymatically to active 5-FU, and released directly into the tumor. Capecitabine’s efficacy and safety are shown in multiple phase III trials across different disease stages and therapy lines. Three randomized phase III trials demonstrated the equivalence of capecitabine plus oxaliplatin (XELOX) versus 5-FU/leucovorin (LV)/oxaliplatin (FOLFOX). The safety of capecitabine compared with 5-FU depends on the regimen of 5-FU used. The adverse event rate with oxaliplatin in combination with infusional 5-FU is similar to that of capecitabine plus oxaliplatin but is associated with more neutropenia and venous thrombotic events; capecitabine plus oxaliplatinbased regimens tend to be associated with more grade 3 diarrhea and hand-foot skin reaction. Combination therapy with capecitabine and irinotecan (CapeIRI) versus 5-FU/ LV and irinotecan (FOLFIRI) had more variable results; some former schedules resulted in excessive treatmentrelated toxicity. More recent data show that lower capecitabine and irinotecan doses, different schedules, and combination with targeted agents (e.g, bevacizumab) have resulted in more favorable outcomes.

Objective To examine the prevalence and correlates of depression in a cohort of black and Hispanic stroke survivors with uncontrolled hypertension.Setting Baseline survey data from 10 stroke centres across New York City.Participants Black and Hispanic stroke survivors with uncontrolled hypertension (n=450).Outcome measures Depressive symptoms were assessed with the 8-item Patient Reported Outcomes Measurement Information System (PROMIS) measure. Depression was defined as a PROMIS score ≥55. Other data collected included clinical factors, health-related quality of life (EuroQoL five dimensions (EQ-5D)), functional independence (Barthel Index, BI), stroke-related disability (Modified Rankin Score), physical function (PROMIS Physical Function) and executive functioning (Frontal Assessment Battery).Results The mean age was 61.7±11.1 years, 44% of participants were women and 51% were black. Poststroke depression was noted in 32% of the cohort. Examining bivariate relationships, patients with depression were observed to have poorer function and quality of life as evidenced by significantly lower PROMIS physical function scores (36.9±8.32 vs 43.4±10.19, p