BACKGROUNDThe appropriate dose of aspirin to lower the risk of death, myocardial infarction, and stroke and to minimize major bleeding in patients with established atherosclerotic cardiovascular disease is a subject of controversy. METHODSUsing an open-label, pragmatic design, we randomly assigned patients with established atherosclerotic cardiovascular disease to a strategy of 81 mg or 325 mg of aspirin per day. The primary effectiveness outcome was a composite of death from any cause, hospitalization for myocardial infarction, or hospitalization for stroke, assessed in a time-to-event analysis. The primary safety outcome was hospitalization for major bleeding, also assessed in a time-to-event analysis. RESULTSA total of 15,076 patients were followed for a median of 26.2 months (interquartile range [IQR], 19.0 to 34.9). Before randomization, 13,537 (96.0% of those with available information on previous aspirin use) were already taking aspirin, and 85.3% of these patients were previously taking 81 mg of daily aspirin. Death, hospitalization for myocardial infarction, or hospitalization for stroke occurred in 590 patients (estimated percentage, 7.28%) in the 81-mg group and 569 patients (estimated percentage, 7.51%) in the 325-mg group (hazard ratio, 1.02; 95% confidence interval [CI], 0.91 to 1.14). Hospitalization for major bleeding occurred in 53 patients (estimated percentage, 0.63%) in the 81-mg group and 44 patients (estimated percentage, 0.60%) in the 325-mg group (hazard ratio, 1.18; 95% CI, 0.79 to 1.77). Patients assigned to 325 mg had a higher incidence of dose switching than those assigned to 81 mg (41.6% vs. 7.1%) and fewer median days of exposure to the assigned dose (434 days [IQR, 139 to 737] vs. 650 days [IQR, 415 to 922]). CONCLUSIONSIn this pragmatic trial involving patients with established cardiovascular disease, there was substantial dose switching to 81 mg of daily aspirin and no significant differences in cardiovascular events or major bleeding between patients assigned to 81 mg and those assigned to 325 mg of aspirin daily. (Funded by the Patient-Centered Outcomes Research Institute; ADAPTABLE ClinicalTrials.gov number, NCT02697916.

Purpose Chronic upper extremity disability (UED) is common after breast cancer treatment but under-identified and under-treated. Although UED has been linked to quality of life (QoL), the role of UED as mediator between contemporary treatment practices and QoL has not been quantified. This investigation describes UED in a contemporary sample of breast cancer patients and examines its relationship with personal and treatment factors and QoL. Methods Eight hundred and thirty-three women diagnosed at eight medical institutions during 2013–2014 with microscopically confirmed ductal carcinoma in situ or invasive stage I–III breast cancer were surveyed an average of 22 months after diagnosis. UED was measured with a modified QuickDASH and QoL with the FACT-B. The questionnaire also collected treatments, sociodemographic information, comorbidity, body mass index, and a 3-item health literacy screener. Results Women who received post-mastectomy radiation and chemotherapy experienced significantly worse UED and QoL. Women who had lower income, lower health literacy and prior diabetes, arthritis or shoulder diagnoses had worse UED. Patients with worse UED reported significantly worse QoL. Income and health literacy were independently associated with QoL after adjustment for UED but treatment and prior conditions were not, indicating mediation by UED. UED mediated 52–79% of the effect of mastectomy-based treatments on QoL as compared with unilateral mastectomy without radiation. UED and QoL did not differ by type of axillary surgery or post-mastectomy reconstruction. Conclusions A large portion of treatment effect on QoL is mediated by UED. Rehabilitation practices that prevent and alleviate UED are likely to improve QoL for breast cancer survivors.

Background New considerations during the ethical review processes may emerge from innovative, yet unfamiliar operational methods enabled in pragmatic randomized controlled trials (RCT), potentially making institutional review board (IRB) evaluation more complex. In this manuscript, key components of the pragmatic “Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-term Effectiveness (ADAPTABLE)” randomized trial that required a reappraisal of the IRB submission, review, and approval processes are discussed. Main text ADAPTABLE is a pragmatic, multicenter, open-label RCT evaluating the comparative effectiveness of two doses of aspirin widely used for secondary prevention (81 mg and 325 mg) in 15,000 patients with an established history of atherosclerotic cardiovascular disease. The electronic informed consent form is completed online by the participants at the time of enrollment, and endpoint ascertainment is conducted through queries of electronic health records. IRB challenges encountered regarding centralized IRB evaluation, electronic informed consent, patient engagement, and risk determination in ADAPTABLE are described in this manuscript. The experience of ADAPTABLE encapsulates how pragmatic protocol components intended to facilitate the study conduct have been tempered by unexpected, yet justified concerns raised by local IRBs. How the lessons learned can be applied to future similar pragmatic trials is delineated. Conclusion Development of engaging communication channels between IRB and study personnel in pragmatic randomized trials as early as at the time of protocol design allows to reduce issues with IRB approval. Integrations of the lessons learned in ADAPTABLE regarding the IRB process for centralized IRBs, informed consent, patient engagement, and risk determination can be emulated and will be instrumental in future pragmatic studies.

In a multicenter sample of breast cancer patients, lower income was strongly associated with less receipt of neoadjuvant chemotherapy. Since patients with lower socioeconomic status are more likely to present with later-stage disease, this pattern has the potential to contribute to breast cancer outcome disparities.

IMPORTANCE Although survival for in-hospital cardiac arrest (IHCA) has improved substantially over the last 2 decades, survival rates have plateaued in recent years. A better understanding of hospital differences in IHCA incidence may provide important insights regarding best practices for prevention of IHCA. OBJECTIVETo determine the incidence of IHCA among Medicare beneficiaries, and evaluate hospital variation in incidence of IHCA. DESIGN, SETTING, AND PARTICIPANTS This observational cohort study analyzes 2014 to 2017 data from 170 hospitals participating in the Get With The Guidelines-Resuscitation registry, linked to Medicare files. Participants were adults aged 65 years and older. Statistical analysis was performed from January to December 2021. EXPOSURES Case-mix index, teaching status, and nurse-staffing. MAIN OUTCOMES AND MEASURES Hospital incidence of IHCA among Medicare beneficiaries was estimated as the number of IHCA patients divided by the total number of hospital admissions.Multivariable hierarchical regression models were used to calculate hospital incidence rates adjusted for differences in patient case-mix and evaluate the association of hospital variables with IHCA incidence. RESULTS Among a total of 4.5 million admissions at 170 hospitals, 38 630 patients experienced an IHCA during 2014 to 2017. Among the 38 630 patients with IHCAs, 7571 (19.6%) were non-Hispanic Black, 26 715 (69.2%) were non-Hispanic White, and 16 732 (43.3%) were female; the mean (SD) age at admission was 76.3 (7.8) years. The median risk-adjusted IHCA incidence was 8.5 per 1000 admissions (95% CI, 8.2-9.0 per 1000 admissions). After adjusting for differences in case-mix index, IHCA incidence varied markedly across hospitals ranging from 2.4 per 1000 admissions to 25.5 per 1000 admissions (IQR, median odds ratio, 1.51 [95% CI,). Among hospital variables, a higher case-mix index, higher nurse staffing, and teaching status were associated with a lower hospital incidence of IHCA.CONCLUSIONS AND RELEVANCE This cohort study found that the incidence of IHCA varies markedly across hospitals, and hospitals with higher nurse staffing and teaching status had lower IHCA incidence rates. Future studies are needed to better understand processes of care at hospitals with exceptionally low IHCA incidence to identify best practices for cardiac arrest prevention.