The time course of cardiovascular disease (CVD) risk after smoking cessation is unclear. Risk calculators consider former smokers to be at risk for only 5 years.
To evaluate the association between ...years since quitting smoking and incident CVD.
Retrospective analysis of prospectively collected data from Framingham Heart Study participants without baseline CVD (original cohort: attending their fourth examination in 1954-1958; offspring cohort: attending their first examination in 1971-1975) who were followed up through December 2015.
Time-updated self-reported smoking status, years since quitting, and cumulative pack-years.
Incident CVD (myocardial infarction, stroke, heart failure, or cardiovascular death). Primary analyses included both cohorts (pooled) and were restricted to heavy ever smokers (≥20 pack-years).
The study population included 8770 individuals (original cohort: n = 3805; offspring cohort: n = 4965) with a mean age of 42.2 (SD, 11.8) years and 45% male. There were 5308 ever smokers with a median 17.2 (interquartile range, 7-30) baseline pack-years, including 2371 heavy ever smokers (406 17% former and 1965 83% current). Over 26.4 median follow-up years, 2435 first CVD events occurred (original cohort: n = 1612 n = 665 among heavy smokers; offspring cohort: n = 823 n = 430 among heavy smokers). In the pooled cohort, compared with current smoking, quitting within 5 years was associated with significantly lower rates of incident CVD (incidence rates per 1000 person-years: current smoking, 11.56 95% CI, 10.30-12.98; quitting within 5 years, 6.94 95% CI, 5.61-8.59; difference, -4.51 95% CI, -5.90 to -2.77) and lower risk of incident CVD (hazard ratio, 0.61; 95% CI, 0.49-0.76). Compared with never smoking, quitting smoking ceased to be significantly associated with greater CVD risk between 10 and 15 years after cessation in the pooled cohort (incidence rates per 1000 person-years: never smoking, 5.09 95% CI, 4.52-5.74; quitting within 10 to <15 years, 6.31 95% CI, 4.93-8.09; difference, 1.27 95% CI, -0.10 to 3.05; hazard ratio, 1.25 95% CI, 0.98-1.60).
Among heavy smokers, smoking cessation was associated with significantly lower risk of CVD within 5 years relative to current smokers. However, relative to never smokers, former smokers' CVD risk remained significantly elevated beyond 5 years after smoking cessation.
Verifying that a statistically significant result is scientifically meaningful is not only good scientific practice, it is a natural way to control the Type I error rate. Here we introduce a novel ...extension of the p-value-a second-generation p-value (pδ)-that formally accounts for scientific relevance and leverages this natural Type I Error control. The approach relies on a pre-specified interval null hypothesis that represents the collection of effect sizes that are scientifically uninteresting or are practically null. The second-generation p-value is the proportion of data-supported hypotheses that are also null hypotheses. As such, second-generation p-values indicate when the data are compatible with null hypotheses (pδ = 1), or with alternative hypotheses (pδ = 0), or when the data are inconclusive (0 < pδ < 1). Moreover, second-generation p-values provide a proper scientific adjustment for multiple comparisons and reduce false discovery rates. This is an advance for environments rich in data, where traditional p-value adjustments are needlessly punitive. Second-generation p-values promote transparency, rigor and reproducibility of scientific results by a priori specifying which candidate hypotheses are practically meaningful and by providing a more reliable statistical summary of when the data are compatible with alternative or null hypotheses.
To evaluate whether early initiation of prophylactic anticoagulation compared with no anticoagulation was associated with decreased risk of death among patients admitted to hospital with coronavirus ...disease 2019 (covid-19) in the United States.
Observational cohort study.
Nationwide cohort of patients receiving care in the Department of Veterans Affairs, a large integrated national healthcare system.
All 4297 patients admitted to hospital from 1 March to 31 July 2020 with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and without a history of anticoagulation.
The main outcome was 30 day mortality. Secondary outcomes were inpatient mortality, initiating therapeutic anticoagulation (a proxy for clinical deterioration, including thromboembolic events), and bleeding that required transfusion.
Of 4297 patients admitted to hospital with covid-19, 3627 (84.4%) received prophylactic anticoagulation within 24 hours of admission. More than 99% (n=3600) of treated patients received subcutaneous heparin or enoxaparin. 622 deaths occurred within 30 days of hospital admission, 513 among those who received prophylactic anticoagulation. Most deaths (510/622, 82%) occurred during hospital stay. Using inverse probability of treatment weighted analyses, the cumulative incidence of mortality at 30 days was 14.3% (95% confidence interval 13.1% to 15.5%) among those who received prophylactic anticoagulation and 18.7% (15.1% to 22.9%) among those who did not. Compared with patients who did not receive prophylactic anticoagulation, those who did had a 27% decreased risk for 30 day mortality (hazard ratio 0.73, 95% confidence interval 0.66 to 0.81). Similar associations were found for inpatient mortality and initiation of therapeutic anticoagulation. Receipt of prophylactic anticoagulation was not associated with increased risk of bleeding that required transfusion (hazard ratio 0.87, 0.71 to 1.05). Quantitative bias analysis showed that results were robust to unmeasured confounding (e-value lower 95% confidence interval 1.77 for 30 day mortality). Results persisted in several sensitivity analyses.
Early initiation of prophylactic anticoagulation compared with no anticoagulation among patients admitted to hospital with covid-19 was associated with a decreased risk of 30 day mortality and no increased risk of serious bleeding events. These findings provide strong real world evidence to support guidelines recommending the use of prophylactic anticoagulation as initial treatment for patients with covid-19 on hospital admission.
Acute kidney injury is a common complication in patients hospitalized with SARSCoV-2 (COVID-19), with prior studies implicating multiple potential mechanisms of injury. Although COVID-19 is often ...compared to other respiratory viral illnesses, few formal comparisons of these viruses on kidney health exist. In this retrospective cohort study, we compared the incidence, features, and outcomes of acute kidney injury among Veterans hospitalized with COVID-19 or influenza and adjusted for baseline conditions using weighted comparisons. A total of 3402 hospitalizations for COVID-19 and 3680 hospitalizations for influenza admitted between October 1, 2019 and May 31, 2020 across 127 Veterans Administration hospitals nationally were studied using the electronic medical record. Acute kidney injury occurred more frequently among those with COVID-19 compared to those with influenza (40.9% versus 29.4%, weighted analysis) and was more severe. Patients with COVID-19 were more likely to require mechanical ventilation and vasopressors and experienced higher mortality. Proteinuria and hematuria were frequent in both groups but more common in COVID-19. Recovery of kidney function was less common in patients with COVID-19 and acute kidney injury but was similar among survivors. Thus, findings from this study confirm that acute kidney injury is more common and severe among patients hospitalized with COVID-19 compared to influenza, a finding that may be driven largely by illness severity. Hence, the combined impact of these two illnesses on kidney health may be significant and have important implications for resource allocation.
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Family/friend involvement and diabetes distress are associated with outcomes for persons with type 2 diabetes (PWDs), but little is known about how they relate to each other. We aim to (1) describe ...associations between PWD and support person (SP) distress; (2) describe associations between involvement and diabetes distress for PWDs, for SPs, and across the dyad; and (3) explore whether associations differ by PWD-SP cohabitation.
PWDs and SPs co-enrolled in a study evaluating the effects of a self-care support intervention and completed self-report measures at baseline.
PWDs and SPs (N = 297 dyads) were, on average, in their mid-50s and around one-third identified as racial or ethnic minorities. The association between PWD and SP diabetes distress was small (Spearman’s ρ = 0.25, p < 0.01). For PWDs, experienced harmful involvement from family/friends was associated with more diabetes distress (standardized β = 0.23, p < 0.001) independent of helpful involvement in adjusted models. Separately, SPs’ self-reported harmful involvement was associated with their own diabetes distress (standardized β = 0.35, p < 0.001) and with PWDs’ diabetes distress (standardized β = 0.25, p = 0.002), independent of SPs’ self-reported helpful involvement.
Findings suggest dyadic interventions may need to address both SP harmful involvement and SP diabetes distress, in addition to PWD distress.
•For people with diabetes, harmful involvement was associated with higher distress.•Family may engage harmfully when they are distressed about the patients’ diabetes.•Family engaging harmfully may lead to their own distress.•This is the first study, known to us, to demonstrate associations across the dyad.•Harmful has greater impact than lack of helpful involvement for diabetes distress.
Covariate‐adjusted randomization (CAR) can reduce the risk of covariate imbalance and, when accounted for in analysis, increase the power of a trial. Despite CAR advances, stratified randomization ...remains the most common CAR method. Matched randomization (MR) randomizes treatment assignment within optimally identified matched pairs based on covariates and a distance matrix. When participants enroll sequentially, sequentially matched randomization (SMR) randomizes within matches found “on‐the‐fly” to meet a pre‐specified matching threshold. However, pre‐specifying the ideal threshold can be challenging and SMR yields less‐optimal matches than MR. We extend SMR to allow multiple participants to be randomized simultaneously, to use a dynamic threshold, and to allow matches to break and rematch if a better match later enrolls (sequential rematched randomization; SRR). In simplified settings and a real‐world application, we assess whether these extensions improve covariate balance, estimator/study efficiency, and optimality of matches. We investigate whether adjusting for more covariates can be detrimental upon covariate balance and efficiency as is the case of traditional stratified randomization. As secondary objectives, we use the case study to assess how SMR schemes compare side‐by‐side with common and related CAR schemes and whether adjusting for covariates in the design can be as powerful as adjusting for covariates in a parametric model. We find each SMR extension, individually and collectively, to improve covariate balance, estimator efficiency, study power, and quality of matches. We provide a case‐study where CAR schemes with randomization‐based inference can be as and more powerful than non‐CAR schemes with parametric adjustment for covariates.
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•A framework to detect calibration drift and inform updating of prediction models.•Incorporates generalizable, customizable methods for diverse models and use cases.•Provides ...data-driven guidance on the timing of and data to be used for model updates.•Evaluations highlight accuracy of detected drift and relevancy of returned data.
Model calibration, critical to the success and safety of clinical prediction models, deteriorates over time in response to the dynamic nature of clinical environments. To support informed, data-driven model updating strategies, we present and evaluate a calibration drift detection system. Methods are developed for maintaining dynamic calibration curves with optimized online stochastic gradient descent and for detecting increasing miscalibration with adaptive sliding windows. These methods are generalizable to support diverse prediction models developed using a variety of learning algorithms and customizable to address the unique needs of clinical use cases. In both simulation and case studies, our system accurately detected calibration drift. When drift is detected, our system further provides actionable alerts by including information on a window of recent data that may be appropriate for model updating. Simulations showed these windows were primarily composed of data accruing after drift onset, supporting the potential utility of the windows for model updating. By promoting model updating as calibration deteriorates rather than on pre-determined schedules, implementations of our drift detection system may minimize interim periods of insufficient model accuracy and focus analytic resources on those models most in need of attention.
•Supportive social environments theoretically improve diabetes self-management.•Measures relevant to adults needed to assess helpful & harmful social involvement.•We developed a measure applicable to ...diverse adults agnostic to living situation.•Helpful & harmful scores were independently divergently associated with self-management.•Harmful involvement was independently associated with worsening HbA1c over 3 months.
Objective: Develop and evaluate a measure assessing helpful and harmful family/friends’ involvement in adults’ type 2 diabetes (T2D) self-management.
Methods: Prior mixed-methods research, cognitive interviews, and expert input informed measure development. We administered the measure in two studies (N = 392 and N = 512) to evaluate its factor structure, internal consistency reliability, test-retest reliability, and construct, criterion and predictive validity.
Results: Analyses supported a two-factor solution: helpful and harmful involvement with internal consistency reliability α = .86 and .72, respectively. Three-month test-retest reliability was rho = 0.64 for helpful and rho = 0.61 for harmful (both p < 0.001). Over 90% reported at least one instance of family/friend involvement in the past month. Associations with other measures of diabetes involvement were as anticipated (all p < .01). Helpful and harmful involvement were independently associated with diabetes self-efficacy, diet, blood glucose testing and medication adherence cross-sectionally βs 0.13–0.39 helpful, −0.12–−0.33 harmful; all p < .05. Harmful involvement independently predicted worse HbA1c (β = 0.08), and worsening HbA1c over three months (β = 0.12, both p < 0.05).
Conclusion: The Family and Friend Involvement in Adults’ Diabetes (FIAD) is a reliable and valid measure assessing family/friend involvement in adults’ T2D.
Practice implications: FIAD use can inform interventions to improve social contexts in which adults manage diabetes.
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