Transitions in health care settings for frequent and infrequent users of emergency departments: a population-based retrospective cohort study.

BACKGROUND: Efforts to reduce emergency department (ED) volumes often target frequent users. We examined transitions in care across ED, hospital, and community settings, and in-hospital death, for high system users (HSUs) compared to controls. METHODS: Population-based databases provided ED visits and hospitalizations in Alberta and Ontario, Canada. The retrospective cohort included the top 10% of all the ED users during 2015/2016 (termed HSUs) and a random sample of controls (4 per each HSU) from the bottom 90% per province. Rates of transitions among ED, hospitalization, community settings, and in-hospital mortality were adjusted for sociodemographic and ED variables in a multistate statistical model. RESULTS: There were 2,684,924 patients and 579,230 (21.6%) were HSUs. Patient characteristics associated with shorter community to ED transition times for HSUs included Alberta residence (ratio of hazard ratio [RHR] = 1.11, 95% confidence interval [CI] 1.11,1.12), living in areas in the lower income quintile (RHR = 1.06, 95%CI 1.06,1.06), and Ontario residents without a primary health care provider (RHR = 1.13, 95%CI 1.13,1.14). Once at the ED, characteristics associated with shorter ED to hospital transition times for HSUs included higher acuity (e.g., RHR = 1.70, 95% CI 1.61, 1.81 for emergent), and for many diagnoses including chest pain (RHR = 1.71, 95%CI 1.65,1.76) and gastrointestinal (RHR = 1.66, 95%CI 1.62,1.71). Once admitted to hospital, HSUs did not necessarily have longer stays except for conditions such as chest pain (RHR = 0.90, 95% CI 0.86, 0.95). HSUs had shorter times to death in the ED if they presented for cancer (RHR = 2.51), congestive heart failure (RHR = 1.93), myocardial infarction (RHR = 1.53), and stroke (RHR = 1.84), and shorter times to death in-hospital if they presented with cancer (RHR = 1.29). CONCLUSIONS: Differences between HSUs and controls in predictors of transitions among care settings were identified. Co-morbidities and limitations in access to primary care are associated with more rapid transitions from community to ED and hospital among HSUs. Interventions targeting these challenges may better serve patients across health systems.. TRIAL REGISTRATION: Not applicable.

Evaluating Association Between Two Event Times with Observations Subject to Informative Censoring.

This article is concerned with evaluating the association between two event times without specifying the joint distribution parametrically. This is particularly challenging when the observations on the event times are subject to informative censoring due to a terminating event such as death. There are few methods suitable for assessing covariate effects on association in this context. We link the joint distribution of the two event times and the informative censoring time using a nested copula function. We use flexible functional forms to specify the covariate effects on both the marginal and joint distributions. In a semiparametric model for the bivariate event time, we estimate simultaneously the association parameters, the marginal survival functions, and the covariate effects. A byproduct of the approach is a consistent estimator for the induced marginal survival function of each event time conditional on the covariates. We develop an easy-to-implement pseudolikelihood-based inference procedure, derive the asymptotic properties of the estimators, and conduct simulation studies to examine the finite-sample performance of the proposed approach. For illustration, we apply our method to analyze data from the breast cancer survivorship study that motivated this research. Supplementary materials for this article are available online.

Comparative effectiveness of urine drug screening strategies alongside opioid agonist treatment in British Columbia, Canada: a population-based observational study protocol.

INTRODUCTION: Urine drug tests (UDTs) are commonly used for monitoring opioid agonist treatment (OAT) responses, supporting the clinical decision for take-home doses and monitoring potential diversion. However, there is limited evidence supporting the utility of mandatory UDTs-particularly the impact of UDT frequency on OAT retention. Real-world evidence can inform patient-centred approaches to OAT and improve current strategies to address the ongoing opioid public health emergency. Our objective is to determine the safety and comparative effectiveness of alternative UDT monitoring strategies as observed in clinical practice among OAT clients in British Columbia, Canada from 2010 to 2020. METHODS AND ANALYSIS: We propose a population-level retrospective cohort study of all individuals 18 years of age or older who initiated OAT from 1 January 2010 to 17 March 2020. The study will draw on eight linked health administrative databases from British Columbia. Our primary outcomes include OAT discontinuation and all-cause mortality. To determine the effectiveness of the intervention, we will emulate a 'per-protocol' target trial using a clone censoring approach to compare fixed and dynamic UDT monitoring strategies. A range of sensitivity analyses will be executed to determine the robustness of our results. ETHICS AND DISSEMINATION: The protocol, cohort creation and analysis plan have been classified and approved as a quality improvement initiative by Providence Health Care Research Ethics Board and the Simon Fraser University Office of Research Ethics. Results will be disseminated to local advocacy groups and decision-makers, national and international clinical guideline developers, presented at international conferences and published in peer-reviewed journals electronically and in print.

Multiple event times in the presence of informative censoring: modeling and analysis by copulas.

Motivated by a breast cancer research program, this paper is concerned with the joint survivor function of multiple event times when their observations are subject to informative censoring caused by a terminating event. We formulate the correlation of the multiple event times together with the time to the terminating event by an Archimedean copula to account for the informative censoring. Adapting the widely used two-stage procedure under a copula model, we propose an easy-to-implement pseudo-likelihood based procedure for estimating the model parameters. The approach yields a new estimator for the marginal distribution of a single event time with semicompeting-risks data. We conduct both asymptotics and simulation studies to examine the proposed approach in consistency, efficiency, and robustness. Data from the breast cancer program are employed to illustrate this research.

Analysis of counts with two latent classes, with application to risk assessment based on physician-visit records of cancer survivors.

Motivated by a cancer survivorship program, this paper explores event counts from two categories of individuals with unobservable membership. We formulate the counts using a latent class model and consider two likelihood-based inference procedures, the maximum likelihood estimation (MLE) and a pseudo-MLE procedure. The pseudo-MLE utilizes additional information on one of the latent classes. It yields reduced computational intensity and potentially increased estimation efficiency. We establish the consistency and asymptotic normality of the proposed pseudo-MLE, and we present an extended Huber sandwich estimator as a robust variance estimator for the pseudo-MLE. The finite-sample properties of the two-parameter estimators along with their variance estimators are examined by simulation. The proposed methodology is illustrated by physician-claim data from the cancer program.

Estimation with Right-Censored Observations Under A Semi-Markov Model.

The semi-Markov process often provides a better framework than the classical Markov process for the analysis of events with multiple states. The purpose of this paper is twofold. First, we show that in the presence of right censoring, when the right end-point of the support of the censoring time is strictly less than the right end-point of the support of the semi-Markov kernel, the transition probability of the semi-Markov process is nonidentifiable, and the estimators proposed in the literature are inconsistent in general. We derive the set of all attainable values for the transition probability based on the censored data, and we propose a nonparametric inference procedure for the transition probability using this set. Second, the conventional approach to constructing confidence bands is not applicable for the semi-Markov kernel and the sojourn time distribution. We propose new perturbation resampling methods to construct these confidence bands. Different weights and transformations are explored in the construction. We use simulation to examine our proposals and illustrate them with hospitalization data from a recent cancer survivor study.

Analysis of recurrent events with non-negligible event duration, with application to assessing hospital utilization.

In an attempt to provide tools for assessing hospital utilization, this paper extends well-known models for recurrent events to address non-negligible event duration and presents a procedure for estimating the model parameters. The model extension is natural and easy to understand. Asymptotic properties of the associated inferences are derived adapting the well-developed methods based on the counting process formulation. Several specifications of the proposed modeling are illustrated with the hospitalization records of childhood cancer survivors from a health care insurance system that motivated this research. The usefulness and robustness of the proposed approach is demonstrated numerically via simulation.

Marginal analysis of panel counts through estimating functions.

We develop nonparametric estimation procedures for the marginal mean function of a counting process based on periodic observations, using two types of self-consistent estimating equations. The first is derived from the likelihood studied in Wellner & Zhang (2000), assuming a Poisson counting process, and gives a nondecreasing estimator, which is the same as the nonparametric maximum likelihood estimator of Wellner & Zhang and thus is consistent without the Poisson assumption. Motivated by the construction of parametric generalized estimating equations, the second type is a set of data-adaptive quasi-score functions, which are likelihood estimating functions under a mixed-Poisson assumption. We evaluate the procedures via simulation, and illustrate them with the data from a bladder cancer study.

Statistical monitoring of clinical trials with multivariate response and/or multiple arms: a flexible approach.

Randomized clinical trials with a multivariate response and/or multiple treatment arms are increasingly common, in part because of their efficiency and a greater concern about balancing risks with benefits. In some trials, the specific types and magnitudes of treatment group differences that would warrant early termination cannot easily be specified prior to the onset of the trial and/or could change as the trial progresses. This underscores the need for more flexible monitoring methods than traditional approaches. This paper extends the repeated confidence bands approach for interim monitoring to more general settings where there can be a multivariate response and/or multiple treatment arms and where the metrics for comparing treatment groups can change during the conduct of the trial. We illustrate the approach using the results of a recent AIDS clinical trial and examine its efficiency and robustness via simulation.

Joint inference for nonlinear mixed-effects models and time to event at the presence of missing data.

In many longitudinal studies, the individual characteristics associated with the repeated measures may be possible covariates of the time to an event of interest, and thus, it is desirable to model the time-to-event process and the longitudinal process jointly. Statistical analyses may be further complicated in such studies with missing data such as informative dropouts. This article considers a nonlinear mixed-effects model for the longitudinal process and the Cox proportional hazards model for the time-to-event process. We provide a method for simultaneous likelihood inference on the 2 models and allow for nonignorable data missing. The approach is illustrated with a recent AIDS study by jointly modeling HIV viral dynamics and time to viral rebound.

A comparison of calorie and protein intake in hospitalized pediatric oncology patients dining with a caregiver versus patients dining alone: a randomized, prospective clinical trial.

Hospitalization and cancer therapy can contribute to decreased food intake in children and adolescents with cancer, making it a challenge to meet their nutritional needs. The affect of hospitalization and the eating environment for pediatric oncology patients has not been studied very well, and the effect of altering the social aspect of mealtime for hospitalized pediatric oncology patients has not been studied at all. The authors conducted a randomized, prospective clinical trial to determine if hospitalized pediatric oncology patients consume more protein and calories when eating with a family member or when eating alone in their room at mealtime. All food and beverage intake was recorded for 3 consecutive days, and a food service satisfaction survey was completed on Day 3. Food records were analyzed for calorie and protein intake, and surveys were analyzed for patient/parent satisfaction. The study was completed by 200 hospitalized patients and their parent/caregiver. Overall, neither calorie nor protein intake differed significantly between the two groups, but patient/parent satisfaction was significantly higher in the group of patients who dined with their caregiver. By using analysis of variance, the authors found that ideal body weight and years of sickness were significantly associated with calorie and protein intake.

Natural history of moderate aplastic anemia in children.

BACKGROUND: Moderate aplastic anemia (MAA) in children is a rare, idiopathic condition of bone marrow insufficiency that can resolve spontaneously, persist for months or years, or progress to severe aplastic anemia (SAA). We evaluated the rate of progression to SAA. METHODS: We reviewed the records of 136 children referred for evaluation of bone marrow failure from 1978 to 2002 at St. Jude Children's Research Hospital. MAA was defined by a hypocellular bone marrow (<50%) and 2 or 3 cytopenias (absolute neutrophil count <1,500/mm(3), absolute reticulocyte count <40,000/mm(3), platelet count <100,000/mm(3)) lasting at least 6 weeks. RESULTS: Twenty-four patients met the criteria for MAA. At a median follow-up of 66 months (range, 10-293), 16 patients (67%) progressed to SAA, 5 (21%) had persistent MAA, and 3 (12%) had complete resolution of MAA. No risk factors for progression could be identified. CONCLUSIONS: When childhood MAA is treated with supportive care alone, 2/3 of patients progress to SAA.

Durability of response to treatment among antiretroviral-experienced subjects: 48-week results from AIDS Clinical Trials Group Protocol 359.

The 24-week extension of AIDS Clinical Trials Group Protocol 359, a study of human immunodeficiency virus (HIV)-infected, indinavir-experienced patients, was designed to study the durability of "salvage" treatment regimens. Patients received saquinavir in combination with either ritonavir or nelfinavir and, in addition, delavirdine, adefovir, or both. Patients who demonstrated a virologic response at weeks 12-16 were eligible to continue therapy in the extension through week 48. Of the 105 eligible subjects who were enrolled in the extension, 86 (82%) completed 48 weeks, and 49 (57%) of those 86 had HIV RNA levels