Impact of Local Tailoring on Acute Stroke Care in 21 Disparate Emergency Departments: A Prospective Stepped Wedge Type III Hybrid Effectiveness-Implementation Study.

BACKGROUND: Faster delivery of tPA (tissue-type plasminogen activator) results in better health outcomes for eligible patients with stroke. Standardization of stroke protocols in emergency departments (EDs) has been difficult, especially in nonstroke centers. We measured the effectiveness of a centrally led implementation strategy with local site tailoring to sustain adherence to an acute stroke protocol to improve door-to-needle (DTN) times across disparate EDs in a multihospital health system. METHODS: Prospective, type III hybrid effectiveness-implementation cohort study measuring performance at 21 EDs in Utah and Idaho (stroke centers [4]/nonstroke centers [17]) from January 2018 to February 2020 using a nonrandomized stepped-wedge design, monthly repeated site measures and multilevel hierarchical modeling. Each site received the implementation strategies in 1 of 6 steps providing control and intervention data. Co-primary outcomes were percentage of DTN times ≤60 minutes and median DTN time. Secondary outcomes included percentage of door-to-activation of neurological consult times ≤10 minutes and clinical effectiveness outcomes. Results were stratified between stroke and nonstroke centers. RESULTS: A total of 855 474 ED patient encounters occurred with 5325 code stroke activations (median age, 69 [IQR, 56-79] years; 51.8% female patients]. Percentage of door-to-activation times ≤10 minutes increased from 47.5% to 59.9% (adjusted odds ratio, 1.93 [95% CI, 1.40-2.67]). A total of 615 patients received tPA of ≤3 hours from symptom onset (median age, 71 [IQR, 58-80] years; 49.6% female patients). The percentage of DTN times ≤60 minutes increased from 72.5% to 86.1% (adjusted odds ratio, 3.38, [95% CI, 1.47-7.78]; stroke centers (77.4%-90.0%); nonstroke centers [59.3%-72.1%]). Median DTN time declined from 46 to 38 minutes (adjusted median difference, -9.68 [95% CI, -17.17 to -2.20]; stroke centers [41-35 minutes]; nonstroke centers [55-52 minutes]). No differences were observed in clinical effectiveness outcomes. CONCLUSIONS: A centrally led implementation strategy with local site tailoring led to faster delivery of tPA across disparate EDs in a multihospital system with no change in clinical effectiveness outcomes including rates of complication. Disparities in performance persisted between stroke and nonstroke centers.

Identifying Patients for Intensive Blood Pressure Treatment Based on Cognitive Benefit: A Secondary Analysis of the SPRINT Randomized Clinical Trial.

Importance: Intensive vs standard treatment to lower systolic blood pressure (SBP) reduces risk of mild cognitive impairment (MCI) or dementia; however, the magnitude of cognitive benefit likely varies among patients. Objective: To estimate the magnitude of cognitive benefit of intensive vs standard systolic BP (SBP) treatment. Design, Setting, and Participants: In this ad hoc secondary analysis of the Systolic Blood Pressure Intervention Trial (SPRINT), 9361 randomized clinical trial participants 50 years or older with high cardiovascular risk but without a history of diabetes, stroke, or dementia were followed up. The SPRINT trial was conducted between November 1, 2010, and August 31, 2016, and the present analysis was completed on October 31, 2022. Intervention: Systolic blood pressure treatment to an intensive (<120 mm Hg) vs standard (<140 mm Hg) target. Main Outcomes and Measures: The primary outcome was a composite of adjudicated probable dementia or amnestic MCI. Results: A total of 7918 SPRINT participants were included in the analysis; 3989 were in the intensive treatment group (mean [SD] age, 67.9 [9.2] years; 2570 [64.4%] men; 1212 [30.4%] non-Hispanic Black) and 3929 were in the standard treatment group (mean [SD] age, 67.9 [9.4] years; 2570 [65.4%] men; 1249 [31.8%] non-Hispanic Black). Over a median follow-up of 4.13 (IQR, 3.50-5.88) years, there were 765 and 828 primary outcome events in the intensive treatment group and standard treatment group, respectively. Older age (hazard ratio [HR] per 1 SD, 1.87 [95% CI, 1.78-1.96]), Medicare enrollment (HR per 1 SD, 1.42 [95% CI, 1.35-1.49]), and higher baseline serum creatinine level (HR per 1 SD, 1.24 [95% CI, 1.19-1.29]) were associated with higher risk of the primary outcome, while better baseline cognitive functioning (HR per 1 SD, 0.43 [95% CI, 0.41-0.44]) and active employment status (HR per 1 SD, 0.44 [95% CI, 0.42-0.46]) were associated with lower risk of the primary outcome. Risk of the primary outcome by treatment goal was estimated accurately based on similar projected and observed absolute risk differences (C statistic = 0.79). Higher baseline risk for the primary outcome was associated with greater benefit (ie, larger absolute reduction of probable dementia or amnestic MCI) of intensive vs standard treatment across the full range of estimated baseline risk. Conclusions and Relevance: In this secondary analysis of the SPRINT trial, participants with higher baseline projected risk of probable dementia or amnestic MCI gained greater absolute cognitive benefit from intensive vs standard SBP treatment in a monotonic fashion. Trial Registration: ClinicalTrials.gov Identifier: NCT01206062.

The Impact of Temporary Housing Assistance Expenditures on Subcategories of Health Care Cost for U.S. Veterans Facing Housing Instability.

We sought to estimate the impact of temporary financial assistance (TFA) for housing-related expenses from the U.S. Department of Veterans Affairs on costs for a variety of health care services. We conducted a retrospective cohort study of Veterans who entered the Supportive Services for Veteran Families (SSVF) program between 10/2015 and 9/2018. We assessed the effect of TFA on health care costs using a multivariable difference-in-difference approach. Outcomes were direct medical costs of health care encounters (i.e., emergency department, outpatient mental health, inpatient mental health, outpatient substance use disorder treatment, and residential behavioral health) in the VA system. Temporary financial assistance was associated with a decrease in ED (-$11, p<.003), outpatient mental health (-$28, p<.001), outpatient substance use disorder treatment (-$25, p<.001), inpatient mental health (-$258, p<.001), and residential behavioral health (-$181, p<.001) costs per quarter for Veterans in the rapid re-housing component of SSVF. These results can inform policy debates regarding proper solutions to housing instability.

An efficient approach for optimizing the cost-effective individualized treatment rule using conditional random forest.

Evidence from observational studies has become increasingly important for supporting healthcare policy making via cost-effectiveness analyses. Similar as in comparative effectiveness studies, health economic evaluations that consider subject-level heterogeneity produce individualized treatment rules that are often more cost-effective than one-size-fits-all treatment. Thus, it is of great interest to develop statistical tools for learning such a cost-effective individualized treatment rule under the causal inference framework that allows proper handling of potential confounding and can be applied to both trials and observational studies. In this paper, we use the concept of net-monetary-benefit to assess the trade-off between health benefits and related costs. We estimate cost-effective individualized treatment rule as a function of patients' characteristics that, when implemented, optimizes the allocation of limited healthcare resources by maximizing health gains while minimizing treatment-related costs. We employ the conditional random forest approach and identify the optimal cost-effective individualized treatment rule using net-monetary-benefit-based classification algorithms, where two partitioned estimators are proposed for the subject-specific weights to effectively incorporate information from censored individuals. We conduct simulation studies to evaluate the performance of our proposals. We apply our top-performing algorithm to the NIH-funded Systolic Blood Pressure Intervention Trial to illustrate the cost-effectiveness gains of assigning customized intensive blood pressure therapy.

Analysis of Therapeutic Inertia and Race and Ethnicity in the Systolic Blood Pressure Intervention Trial: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Therapeutic inertia may contribute to racial and ethnic differences in blood pressure (BP) control. Objective: To determine the association between race and ethnicity and therapeutic inertia in the Systolic Blood Pressure Intervention Trial (SPRINT). Design, Setting, and Participants: This cross-sectional study was a secondary analysis of data from SPRINT, a randomized clinical trial comparing intensive (<120 mm Hg) vs standard (<140 mm Hg) systolic BP treatment goals. Participants were enrolled between November 8, 2010, and March 15, 2013, with a median follow-up 3.26 years. Participants included adults aged 50 years or older at high risk for cardiovascular disease but without diabetes, previous stroke, or heart failure. The present analysis was restricted to participant visits with measured BP above the target goal. Analyses for the present study were performed in from October 2020 through March 2021. Exposures: Self-reported race and ethnicity, mutually exclusively categorized into groups of Hispanic, non-Hispanic Black, or non-Hispanic White participants. Main Outcomes and Measures: Therapeutic inertia, defined as no antihypertensive medication intensification at each study visit where the BP was above target goal. The association between self-reported race and ethnicity and therapeutic inertia was estimated using generalized estimating equations and stratified by treatment group. Antihypertensive medication use was assessed with pill bottle inventories at each visit. Blood pressure was measured using an automated device. Results: A total of 8556 participants, including 4141 in the standard group (22 844 participant-visits; median age, 67.0 years [IQR, 61.0-76.0 years]; 1467 women [35.4%]) and 4415 in the intensive group (35 453 participant-visits; median age, 67.0 years [IQR, 61.0-76.0 years]; 1584 women [35.9%]) with at least 1 eligible study visit were included in the present analysis. Among non-Hispanic White, non-Hispanic Black, and Hispanic participants, the overall prevalence of therapeutic inertia in the standard vs intensive groups was 59.8% (95% CI, 58.9%-60.7%) vs 56.0% (95% CI, 55.2%-56.7%), 56.8% (95% CI, 54.4%-59.2%) vs 54.5% (95% CI, 52.4%-56.6%), and 59.7% (95% CI, 56.5%-63.0%) vs 51.0% (95% CI, 47.4%-54.5%), respectively. The adjusted odds ratios in the standard and intensive groups for therapeutic inertia associated with non-Hispanic Black vs non-Hispanic White participants were 0.85 (95% CI, 0.79-0.92) and 0.94 (95% CI, 0.88-1.01), respectively. The adjusted odds ratios for therapeutic inertia comparing Hispanic vs non-Hispanic White participants were 1.00 (95% CI, 0.90-1.13) and 0.89 (95% CI, 0.79-1.00) in the standard and intensive groups, respectively. Conclusions and Relevance: Among SPRINT participants above BP target goal, this cross-sectional study found that therapeutic inertia prevalence was similar or lower for non-Hispanic Black and Hispanic participants compared with non-Hispanic White participants. These findings suggest that a standardized approach to BP management, as used in SPRINT, may help ensure equitable care and could reduce the contribution of therapeutic inertia to disparities in hypertension. Trial Registration: ClinicalTrials.gov identifier: NCT01206062.

Estimating the optimal individualized treatment rule from a cost-effectiveness perspective.

Optimal individualized treatment rules (ITRs) provide customized treatment recommendations based on subject characteristics to maximize clinical benefit in accordance with the objectives in precision medicine. As a result, there is growing interest in developing statistical tools for estimating optimal ITRs in evidence-based research. In health economic perspectives, policy makers consider the tradeoff between health gains and incremental costs of interventions to set priorities and allocate resources. However, most work on ITRs has focused on maximizing the effectiveness of treatment without considering costs. In this paper, we jointly consider the impact of effectiveness and cost on treatment decisions and define ITRs under a composite-outcome setting, so that we identify the most cost-effective ITR that accounts for individual-level heterogeneity through direct optimization. In particular, we propose a decision-tree-based statistical learning algorithm that uses a net-monetary-benefit-based reward to provide nonparametric estimations of the optimal ITR. We provide several approaches to estimating the reward underlying the ITR as a function of subject characteristics. We present the strengths and weaknesses of each approach and provide practical guidelines by comparing their performance in simulation studies. We illustrate the top-performing approach from our simulations by evaluating the projected 15-year personalized cost-effectiveness of the intensive blood pressure control of the Systolic Blood Pressure Intervention Trial (SPRINT) study.

Temporary Financial Assistance Decreased Health Care Costs For Veterans Experiencing Housing Instability.

Compared with housed people, those experiencing homelessness have longer and more expensive inpatient stays as well as more frequent emergency department visits. Efforts to provide stable housing situations for people experiencing homelessness could reduce health care costs. Through the Supportive Services for Veteran Families program, the Department of Veterans Affairs partners with community organizations to provide temporary financial assistance to veterans who are currently homeless or at imminent risk of becoming homeless. We examined the impact of temporary financial assistance on health care costs for veterans in the Supportive Services for Veteran Families program and found that, on average, people receiving the assistance incurred $352 lower health care costs per quarter than those who did not receive the assistance. These results can inform national policy debates regarding the proper solution to housing instability.

Association of Temporary Financial Assistance With Housing Stability Among US Veterans in the Supportive Services for Veteran Families Program.

Importance: Temporary financial assistance (TFA) for housing-related expenses is a key component of interventions to prevent homelessness or to quickly house those who have become homeless. Through the US Department of Veterans Affairs (VA) Supportive Services for Veteran Families (SSVF) program, the department provides TFA to veterans in need of housing assistance. Objective: To assess the association between TFA and housing stability among US veterans enrolled in the SSVF program. Design, Setting, and Participants: This retrospective cohort study analyzed data on veterans who were enrolled in the SSVF program at 1 of 203 partner organizations in 49 US states and territories. Some veterans had repeat SSVF episodes, but only the first episodes were included in this analysis. An episode was defined as the period between entry into and exit from the program occurring between October 1, 2015, and September 30, 2018. Exposures: Receipt of TFA. Main Outcomes and Measures: The main outcome was stable housing, defined as permanent, independent residence with payment by the program client or housing subsidy after exit from the SSVF program. Covariates included demographic characteristics, monthly income and source, public benefits, health insurance, use of other VA programs for homelessness, comorbidities, and geographic location. Multivariable mixed-effects logistic regression, inverse probability of treatment weighting, and instrumental variable approaches were used. Results: The overall cohort consisted of 41 969 veterans enrolled in the SSVF program, of whom 29 184 (mean [SD] age, 50.4 [12.9] years; 25 396 men [87.0%]) received TFA and 12 785 (mean [SD] age, 50.0 [13.3] years; 11 229 men [87.8%]) did not receive TFA. The mean (SD) duration of SSVF episodes was 90.5 (57.7) days. A total of 69.5% of SSVF episodes involved receipt of TFA, and the mean (SD) amount of TFA was $6070 ($7272). Stable housing was obtained in 81.4% of the episodes. Compared with those who did not receive TFA, veterans who received TFA were significantly more likely to have stable housing outcomes (risk difference, 0.253; 95% CI, 0.240-0.265). An association between the amount of TFA received and stable housing was also found, with risk differences ranging from 0.168 (95% CI, 0.149-0.188) for those who received $0 to $2000 in TFA to 0.226 (95% CI, 0.203-0.249) for those who received more than $2000 to $4000 in TFA. Conclusions and Relevance: This study found that receipt of TFA through the SSVF program was associated with increased rates of stable housing. These results may inform national policy debates regarding the optimal solutions to prevent and reduce housing instability.

Application of community - engaged dissemination and implementation science to improve health equity.

Community engagement is critical to accelerate and improve implementation of evidence-based interventions to reduce health inequities. Community-engaged dissemination and implementation research (CEDI) emphasizes engaging stakeholders (e.g., community members, practitioners, community organizations, etc.) with diverse perspectives, experience, and expertise to provide tacit community knowledge regarding the local context, priorities, needs, and assets. Importantly, CEDI can help improve health inequities through incorporating unique perspectives from communities experiencing health inequities that have historically been left out of the research process. The community-engagement process that exists in practice can be highly variable, and characteristics of the process are often underreported, making it difficult to discern how engagement of community partners was used to improve implementation. This paper describes the community-engagement process for a multilevel, pragmatic randomized trial to increase the reach and impact of evidence-based tobacco cessation treatment among Community Health Center patients; describes how engagement activities and the resulting partnership informed the development of implementation strategies and improved the research process; and presents lessons learned to inform future CEDI research.

Factors That Contribute to Cost Differences Based on ICU of Admission in Neonates Undergoing Congenital Heart Surgery: A Novel Decomposition Analysis.

OBJECTIVES: We leveraged decomposition analysis, commonly used in labor economics, to understand determinants of cost differences related to location of admission in children undergoing neonatal congenital heart surgery. DESIGN: A retrospective cohort study. SETTING: Pediatric Health Information Systems database. PATIENTS: Neonates (<30 d old) undergoing their index congenital heart surgery between 2004 and 2013. MEASUREMENTS AND MAIN RESULTS: A decomposition analysis with bootstrapping determined characteristic (explainable by differing covariate levels) and structural effects (if covariates are held constant) related to cost differences. Covariates included center volume, age at admission, prematurity, sex, race, genetic or major noncardiac abnormality, Risk Adjustment for Congenital Heart Surgery-1 score, payor, admission year, cardiac arrest, infection, and delayed sternal closure.Of 19,984 infants included (10,491 [52%] to cardiac ICU/PICU and 9,493 [48%] to neonatal ICU), admission to the neonatal ICU had overall higher average costs ($24,959 ± $3,260; p < 0.001) versus cardiac ICU/PICU admission. Characteristic effects accounted for higher costs in the neonatal ICU ($28,958 ± $2,044; p < 0.001). Differing levels of prematurity, genetic syndromes, hospital volume, age at admission, and infection contributed to higher neonatal ICU costs, with infection rate providing the most significant contribution ($13,581; p < 0.001). Aggregate structural effects were not associated with cost differences for those admitted to the neonatal ICU versus cardiac ICU/PICU (p = 0.1). Individually, prematurity and age at admission were associated with higher costs due to structural effects for infants admitted to the neonatal ICU versus cardiac ICU/PICU. CONCLUSIONS: The difference in cost between neonatal ICU and cardiac ICU/PICU admissions is largely driven by differing prevalence of risk factors between these units. Infection rate was a modifiable factor that accounted for the largest difference in costs between admitting units.

The OPTIMIZE study: protocol of a pragmatic sequential multiple assessment randomized trial of nonpharmacologic treatment for chronic, nonspecific low back pain.

BACKGROUND: Low back pain is a prevalent condition that causes a substantial health burden. Despite intensive and expensive clinical efforts, its prevalence is growing. Nonpharmacologic treatments are effective at improving pain-related outcomes; however, treatment effect sizes are often modest. Physical therapy (PT) and cognitive behavioral therapy (CBT) have the most consistent evidence of effectiveness. Growing evidence also supports mindfulness-based approaches. Discussions with providers and patients highlight the importance of discussing and trying options to find the treatment that works for them and determining what to do when initial treatment is not successful. Herein, we present the protocol for a study that will evaluate evidence-based, protocol-driven treatments using PT, CBT, or mindfulness to examine comparative effectiveness and optimal sequencing for patients with chronic low back pain. METHODS: The Optimized Multidisciplinary Treatment Programs for Nonspecific Chronic Low Back Pain (OPTIMIZE) Study will be a multisite, comparative effectiveness trial using a sequential multiple assessment randomized trial design enrolling 945 individuals with chronic low back pain. The co-primary outcomes will be disability (measured using the Oswestry Disability Index) and pain intensity (measured using the Numerical Pain Rating Scale). After baseline assessment, participants will be randomly assigned to PT or CBT. At week 10, participants who have not experienced at least 50% improvement in disability will be randomized to cross-over phase-1 treatments (e.g., PT to CBT) or to Mindfulness-Oriented Recovery Enhancement (MORE). Treatment will consist of 8 weekly sessions. Long-term outcome assessments will be performed at weeks 26 and 52. DISCUSSION: Results of this study may inform referring providers and patients about the most effective nonoperative treatment and/or sequence of nonoperative treatments to treat chronic low back pain. TRIAL REGISTRATION: This study was prospectively registered on March 1, 2019, with Clinicaltrials.gov under the registration number NCT03859713 (https://clinicaltrials.gov/ct2/show/NCT03859713).

QuitSMART Utah: an implementation study protocol for a cluster-randomized, multi-level Sequential Multiple Assignment Randomized Trial to increase Reach and Impact of tobacco cessation treatment in Community Health Centers.

BACKGROUND: Tobacco use remains the leading cause of death and disability in the USA and is disproportionately concentrated among low socioeconomic status (SES) populations. Community Health Centers (CHCs) are a key venue for reaching low SES populations with evidence-based tobacco cessation treatment such as Quitlines. Electronic health record (EHR)-based interventions at the point-of-care, text messaging (TM), and phone counseling have the potential to increase Quitline reach and are feasible to implement within CHCs. However, there is a lack of data to inform how, when, and in what combination these strategies should be implemented. The aims of this cluster-randomized trial are to evaluate multi-level implementation strategies to increase the Reach (i.e., proportion of tobacco-using patients who enroll in the Quitline) and Impact (i.e., Reach × Efficacy [efficacy is defined as the proportion of tobacco-using patients who enroll in Quitline treatment that successfully quit]) and to evaluate characteristics of healthcare system, providers, and patients that may influence tobacco-use outcomes. METHODS: This study is a multilevel, three-phase, Sequential Multiple Assignment Randomized Trial (SMART), conducted in CHCs (N = 33 clinics; N = 6000 patients). In the first phase, clinics will be randomized to two different EHR conditions. The second and third phases are patient-level randomizations based on prior treatment response. Patients who enroll in the Quitline receive no further interventions. In phase two, patients who are non-responders (i.e., patients who do not enroll in Quitline) will be randomized to receive either TM or continued-EHR. In phase three, patients in the TM condition who are non-responders will be randomized to receive either continued-TM or TM + phone coaching. DISCUSSION: This project will evaluate scalable, multi-level interventions to directly address strategic national priorities for reducing tobacco use and related disparities by increasing the Reach and Impact of evidence-based tobacco cessation interventions in low SES populations. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov (NCT03900767) on April 4th, 2019.

Propensity score weighting analysis and treatment effect discovery.

Inverse probability weighting can be used to estimate the average treatment effect in propensity score analysis. When there is lack of overlap in the propensity score distributions between the treatment groups under comparison, some weights may be excessively large, causing numerical instability and bias in point and variance estimation. We study a class of modified inverse probability weighting estimators that can be used to avoid this problem. These weights cause the estimand to deviate from the average treatment effect. We provide some justification for this deviation from the perspective of treatment effect discovery. We show that when lack of overlap occurs, the modified weights can achieve substantial gains in statistical power compared with inverse probability weighting and other propensity score methods. We develop analytical variance estimates that properly adjust for the sampling variability of the estimated propensity scores, and augment the modified inverse probability weighting estimator with outcome models for improved efficiency, a property that resembles double robustness. Results from extensive simulations and a real data application support our conclusions. The proposed methodology is implemented in R package PSW.

Clinical and Economic Outcomes of Ranolazine Versus Conventional Antianginals Users Among Veterans With Chronic Stable Angina Pectoris.

Real-world outcomes in patients with chronic stable angina treated with ranolazine and other antianginal medications as second- or third-line therapy are limited. In a historical cohort study of veterans with chronic stable angina, we compared time with coronary revascularization procedures, hospitalizations, and 1-year healthcare costs between new-users of ranolazine versus conventional antianginals (i.e., calcium channel blockers, ß blockers, or long-acting nitrates) as second- or third-line. Weighted regression models calculated adjusted hazard ratios (HR) at up to 8-year follow-up, and adjusted incremental costs in the first year. Weighted groups comprised 4,699 ranolazine users and 31,815 conventional antianginal users. Percutaneous coronary intervention (PCI) occurred more often in ranolazine users compared with conventional antianginal users (HR 1.16; 95% confidence intervals [CI] 1.08 to 1.25, p <0.001), and coronary artery bypass grafting occurred less often (HR 0.82; 95% CI 0.68 to 1.00, p <0.046). All-cause and atrial fibrillation (AF) hospitalizations were less common with ranolazine users compared with conventional users (all-cause: HR 0.94; 95% CI 0.90 to 0.99, p <0.010; AF:HR 0.74; 95% CI 0.67 to 0.82, p <0.001), and acute coronary syndrome was more common (HR 1.13; 95% CI 1.00 to 1.27, p <0.042). Adjusted 1-year costs were $24,517 in ranolazine users and $24,798 in conventional users (difference, $-280; 95% CI $-1,742 to $1,181, p = 0.71). In conclusion, ranolazine users had lower rates of coronary artery bypass grafting and all-cause and AF hospitalizations, but higher rates of percutaneous coronary intervention and hospitalizations due to acute coronary syndrome compared with conventional antianginal users. Healthcare costs were similar between ranolazine and conventional antianginal users.

Extended models for nosocomial infection: parameter estimation and model selection.

We consider extensions to previous models for patient level nosocomial infection in several ways, provide a specification of the likelihoods for these new models, specify new update steps required for stochastic integration, and provide programs that implement these methods to obtain parameter estimates and model choice statistics. Previous susceptible-infected models are extended to allow for a latent period between initial exposure to the pathogen and the patient becoming themselves infectious, and the possibility of decolonization. We allow for multiple facilities, such as acute care hospitals or long-term care facilities and nursing homes, and for multiple units or wards within a facility. Patient transfers between units and facilities are tracked and accounted for in the models so that direct importation of a colonized individual from one facility or unit to another might be inferred. We allow for constant transmission rates, rates that depend on the number of colonized individuals in a unit or facility, or rates that depend on the proportion of colonized individuals. Statistical analysis is done in a Bayesian framework using Markov chain Monte Carlo methods to obtain a sample of parameter values from their joint posterior distribution. Cross validation, deviance information criterion and widely applicable information criterion approaches to model choice fit very naturally into this framework and we have implemented all three. We illustrate our methods by considering model selection issues and parameter estimation for data on methicilin-resistant Staphylococcus aureus surveillance tests over 1 year at a Veterans Administration hospital comprising seven wards.

Blood pressure and the risk of chronic kidney disease progression using multistate marginal structural models in the CRIC Study.

In patients with chronic kidney disease (CKD), clinical interest often centers on determining treatments and exposures that are causally related to renal progression. Analyses of longitudinal clinical data in this population are often complicated by clinical competing events, such as end-stage renal disease (ESRD) and death, and time-dependent confounding, where patient factors that are predictive of later exposures and outcomes are affected by past exposures. We developed multistate marginal structural models (MS-MSMs) to assess the effect of time-varying systolic blood pressure on disease progression in subjects with CKD. The multistate nature of the model allows us to jointly model disease progression characterized by changes in the estimated glomerular filtration rate (eGFR), the onset of ESRD, and death, and thereby avoid unnatural assumptions of death and ESRD as noninformative censoring events for subsequent changes in eGFR. We model the causal effect of systolic blood pressure on the probability of transitioning into 1 of 6 disease states given the current state. We use inverse probability weights with stabilization to account for potential time-varying confounders, including past eGFR, total protein, serum creatinine, and hemoglobin. We apply the model to data from the Chronic Renal Insufficiency Cohort Study, a multisite observational study of patients with CKD.

Implementation of a Value-Driven Outcomes Program to Identify High Variability in Clinical Costs and Outcomes and Association With Reduced Cost and Improved Quality.

IMPORTANCE: Transformation of US health care from volume to value requires meaningful quantification of costs and outcomes at the level of individual patients. OBJECTIVE: To measure the association of a value-driven outcomes tool that allocates costs of care and quality measures to individual patient encounters with cost reduction and health outcome optimization. DESIGN, SETTING, AND PARTICIPANTS: Uncontrolled, pre-post, longitudinal, observational study measuring quality and outcomes relative to cost from 2012 to 2016 at University of Utah Health Care. Clinical improvement projects included total hip and knee joint replacement, hospitalist laboratory utilization, and management of sepsis. EXPOSURES: Physicians were given access to a tool with information about outcomes, costs (not charges), and variation and partnered with process improvement experts. MAIN OUTCOMES AND MEASURES: Total and component inpatient and outpatient direct costs across departments; cost variability for Medicare severity diagnosis related groups measured as coefficient of variation (CV); and care costs and composite quality indexes. RESULTS: From July 1, 2014, to June 30, 2015, there were 1.7 million total patient visits, including 34 000 inpatient discharges. Professional costs accounted for 24.3% of total costs for inpatient episodes ($114.4 million of $470.4 million) and 41.9% of total costs for outpatient visits ($231.7 million of $553.1 million). For Medicare severity diagnosis related groups with the highest total direct costs, cost variability was highest for postoperative infection (CV = 1.71) and sepsis (CV = 1.37) and among the lowest for organ transplantation (CV ≤ 0.43). For total joint replacement, a composite quality index was 54% at baseline (n = 233 encounters) and 80% 1 year into the implementation (n = 188 encounters) (absolute change, 26%; 95% CI, 18%-35%; P < .001). Compared with the baseline year, mean direct costs were 7% lower in the implementation year (95% CI, 3%-11%; P < .001) and 11% lower in the postimplementation year (95% CI, 7%-14%; P < .001). The hospitalist laboratory testing mean cost per day was $138 (median [IQR], $113 [$79-160]; n = 2034 encounters) at baseline and $123 (median [IQR], $99 [$66-147]; n = 4276 encounters) in the evaluation period (mean difference, -$15; 95% CI, -$19 to -$11; P < .001), with no significant change in mean length of stay. For a pilot sepsis intervention, the mean time to anti-infective administration following fulfillment of systemic inflammatory response syndrome criteria in patients with infection was 7.8 hours (median [IQR], 3.4 [0.8-7.8] hours; n = 29 encounters) at baseline and 3.6 hours (median [IQR], 2.2 [1.0-4.5] hours; n = 76 encounters) in the evaluation period (mean difference, -4.1 hours; 95% CI, -9.9 to -1.0 hours; P = .02). CONCLUSIONS AND RELEVANCE: Implementation of a multifaceted value-driven outcomes tool to identify high variability in costs and outcomes in a large single health care system was associated with reduced costs and improved quality for 3 selected clinical projects. There may be benefit for individual physicians to understand actual care costs (not charges) and outcomes achieved for individual patients with defined clinical conditions.

Interstate Variation in Receipt of Nephrologist Care in US Patients Approaching ESRD: Race, Age, and State Characteristics.

BACKGROUND AND OBJECTIVES: Although multiple factors influence access to nephrologist care in patients with CKD stages 4-5, the geographic determinants within the United States are incompletely understood. In this study, we examined interstate differences in nephrologist care among patients approaching ESRD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This national, population-based analysis included 373,986 adult patients from the US Renal Data System, who initiated maintenance dialysis between 2005 and 2009. Multilevel logistic regression was used to examine interstate variation in nephrologist care (≥12 months before ESRD) for overall and four race-age subpopulations (black or white and older or younger than 65 years). RESULTS: The average state-level probability of having received nephrologist care in all states combined was 28.8% (95% confidence interval, 25.2% to 32.7%) overall and was lowest (24.3%) in the younger black subpopulation. Even at these lower levels, state-level probabilities varied considerably across states in overall and subpopulations (all P<0.001). Overall, excluding the states in the upper and lower five percentiles, the remaining states had a probability of receiving care that varied from 18.5% to 41.9%. The lower probability of receiving nephrologist care for blacks than whites among younger patients noted in most states was attenuated in older patients. Geographically, all New England states and most Midwest states had higher than average probability, whereas most Middle Atlantic and Southern states had lower than average probability. After controlling for patient factors, three state-characteristic categories, including general healthcare access measured by percentage of uninsured persons and Medicaid program performance scores, preventive care measured by percentage of receiving recommended preventive care, and socioeconomic status, contributed 55%-66% of interstate variation. CONCLUSIONS: Patients living in states with better health service and socioeconomic characteristics were more likely to receive predialysis nephrologist care. The reported national black-white difference in nephrologist care was primarily driven by younger black patients being the least likely to receive care.

Reducing Time-dependent Bias in Estimates of the Attributable Cost of Health Care-associated Methicillin-resistant Staphylococcus aureus Infections: A Comparison of Three Estimation Strategies.

BACKGROUND: Previous estimates of the excess costs due to health care-associated infection (HAI) have scarcely addressed the issue of time-dependent bias. OBJECTIVE: We examined time-dependent bias by estimating the health care costs attributable to an HAI due to methicillin-resistant Staphylococcus aureus (MRSA) using a unique dataset in the Department of Veterans Affairs (VA) that makes it possible to distinguish between costs that occurred before and after an HAI. In addition, we compare our results to those from 2 other estimation strategies. METHODS: Using a historical cohort study design to estimate the excess predischarge costs attributable to MRSA HAIs, we conducted 3 analyses: (1) conventional, in which costs for the entire inpatient stay were compared between patients with and without MRSA HAIs; (2) post-HAI, which included only costs that occurred after an infection; and (3) matched, in which costs for the entire inpatient stay were compared between patients with an MRSA HAI and subset of patients without an MRSA HAI who were matched based on the time to infection. RESULTS: In our post-HAI analysis, estimates of the increase in inpatient costs due to MRSA HAI were $12,559 (P<0.0001) and $24,015 (P<0.0001) for variable and total costs, respectively. The excess variable and total cost estimates were 33.7% and 31.5% higher, respectively, when using the conventional methods and 14.6% and 11.8% higher, respectively, when using matched methods. CONCLUSIONS: This is the first study to account for time-dependent bias in the estimation of incremental per-patient health care costs attributable to HAI using a unique dataset in the VA. We found that failure to account for this bias can lead to overestimation of these costs. Matching on the timing of infection can reduce this bias substantially.

Excess Length of Stay Attributable to Clostridium difficile Infection (CDI) in the Acute Care Setting: A Multistate Model.

BACKGROUND: Standard estimates of the impact of Clostridium difficile infections (CDI) on inpatient lengths of stay (LOS) may overstate inpatient care costs attributable to CDI. In this study, we used multistate modeling (MSM) of CDI timing to reduce bias in estimates of excess LOS. METHODS: A retrospective cohort study of all hospitalizations at any of 120 acute care facilities within the US Department of Veterans Affairs (VA) between 2005 and 2012 was conducted. We estimated the excess LOS attributable to CDI using an MSM to address time-dependent bias. Bootstrapping was used to generate 95% confidence intervals (CI). These estimates were compared to unadjusted differences in mean LOS for hospitalizations with and without CDI. RESULTS: During the study period, there were 3.96 million hospitalizations and 43,540 CDIs. A comparison of unadjusted means suggested an excess LOS of 14.0 days (19.4 vs 5.4 days). In contrast, the MSM estimated an attributable LOS of only 2.27 days (95% CI, 2.14-2.40). The excess LOS for mild-to-moderate CDI was 0.75 days (95% CI, 0.59-0.89), and for severe CDI, it was 4.11 days (95% CI, 3.90-4.32). Substantial variation across the Veteran Integrated Services Networks (VISN) was observed. CONCLUSIONS: CDI significantly contributes to LOS, but the magnitude of its estimated impact is smaller when methods are used that account for the time-varying nature of infection. The greatest impact on LOS occurred among patients with severe CDI. Significant geographic variability was observed. MSM is a useful tool for obtaining more accurate estimates of the inpatient care costs of CDI.