Publications

The noniterative conditional expectation (NICE) parametric g-formula can be used to estimate the causal effect of sustained treatment strategies. In addition to identifiability conditions, the validity of the NICE parametric g-formula generally requires the correct specification of models for time-varying outcomes, treatments, and confounders at each follow-up time point. An informal approach for evaluating model specification is to compare the observed distributions of the outcome, treatments, and confounders with their parametric g-formula estimates under the "natural course." In the presence of loss to follow-up, however, the observed and natural-course risks can differ even if the identifiability conditions of the parametric g-formula hold and there is no model misspecification. Here, we describe 2 approaches for evaluating model specification when using the parametric g-formula in the presence of censoring: 1) comparing factual risks estimated by the g-formula with nonparametric Kaplan-Meier estimates and 2) comparing natural-course risks estimated by inverse probability weighting with those estimated by the g-formula. We also describe how to correctly compute natural-course estimates of time-varying covariate means when using a computationally efficient g-formula algorithm. We evaluate the proposed methods via simulation and implement them to estimate the effects of dietary interventions in 2 cohort studies.

IMPORTANCE: Long-term acute care hospitals (LTCHs) are common sites of postacute care for patients recovering from severe respiratory failure requiring mechanical ventilation (MV). However, federal payment reform led to the closure of many LTCHs in the US, and it is unclear how closure of LTCHs may have affected upstream care patterns at short-stay hospitals and overall patient outcomes.

OBJECTIVE: To estimate the association between LTCH closures and short-stay hospital care patterns and patient outcomes.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective, national, matched cohort study used difference-in-differences analysis to compare outcomes at short-stay hospitals reliant on LTCHs that closed during 2012 to 2018 with outcomes at control hospitals. Data were obtained from the Medicare Provider Analysis and Review File, 2011 to 2019. Participants included Medicare fee-for-service beneficiaries aged 66 years and older receiving MV for at least 96 hours in an intensive care unit (ie, patients at-risk for prolonged MV) and the subgroup also receiving a tracheostomy (ie, receiving prolonged MV). Data were analyzed from October 2022 to June 2023.

EXPOSURE: Admission to closure-affected hospitals, defined as those discharging at least 60% of patients receiving a tracheostomy to LTCHs that subsequently closed, vs control hospitals.

MAIN OUTCOMES AND MEASURES: Upstream hospital care pattern outcomes were short-stay hospital do-not-resuscitate orders, palliative care delivery, tracheostomy placement, and discharge disposition. Patient outcomes included hospital length of stay, days alive and institution free within 90 days, spending per days alive within 90 days, and 90-day mortality.

RESULTS: Between 2011 and 2019, 99 454 patients receiving MV for at least 96 hours at 1261 hospitals were discharged to 459 LTCHs; 84 LTCHs closed. Difference-in-differences analysis included 8404 patients (mean age, 76.2 [7.2] years; 4419 [52.6%] men) admitted to 45 closure-affected hospitals and 45 matched-control hospitals. LTCH closure was associated with decreased LTCH transfer rates (difference, -5.1 [95% CI -8.2 to -2.0] percentage points) and decreased spending-per-days-alive (difference, -$8701.58 [95% CI, -$13 323.56 to -$4079.60]). In the subgroup of patients receiving a tracheostomy, there was additionally an increase in do-not-resuscitate rates (difference, 10.3 [95% CI, 4.2 to 16.3] percentage points) and transfer to skilled nursing facilities (difference, 10.0 [95% CI, 4.2 to 15.8] percentage points). There was no significant association of closure with 90-day mortality.

CONCLUSIONS AND RELEVANCE: In this cohort study, LTCH closure was associated with changes in discharge patterns in patients receiving mechanical ventilation for at least 96 hours and advanced directive decisions in the subgroup receiving a tracheostomy, without change in mortality. Further studies are needed to understand how LTCH availability may be associated with other important outcomes, including functional outcomes and patient and family satisfaction.

PURPOSE OF REVIEW: Peripheral artery disease (PAD) is an increasingly prevalent but frequently underdiagnosed condition that can be associated with high rates of morbidity and mortality. While an initial noninvasive approach is the cornerstone of management, revascularization is often pursued for patients with treatment-refractory claudication or chronic limb-threatening ischemia (CLTI). In this review, we discuss the current state of endovascular interventions for PAD and explore the many new emerging technologies.

RECENT FINDINGS: The last decade has resulted in numerous advances in PAD interventions including the ongoing evolution of drug-coated devices, novel approaches to complex lesions, and contemporary evidence from large clinical trials for CLTI. Advances in endovascular management have allowed for increasingly complex lesions to be tackled percutaneously. Future directions for the field include the continued evolution in device technology, continued development of state-of-the-art techniques to revascularization of complex lesions, and increased collaboration between a largely multidisciplinary field.

Registry Assessment of Peripheral Interventional Devices (RAPID) initiated the Pathways Program to provide a transparent, collaborative forum in which to pursue insights into multiple unresolved questions on benefit-risk of paclitaxel-coated devices, including understanding the basis of the mortality signal, without a demonstrable potential biological mechanism, and whether the late mortality signal could be artifact intrinsic to multiple independent prospective randomized data sources that did not prespecify death as a long-term end point. In response to the directive, the LEAN-Case Report Form working group focused on enhancements to the RAPID Phase I Minimum Core Data set through the addition of key clinical modifiers that would be more strongly linked to longer-term mortality outcomes after peripheral arterial disease intervention in the drug-eluting device era, with the goal to have future mortality signals more accurately examined.

BACKGROUND: Federal programs measuring hospital quality of care for acute cardiovascular conditions are based solely on Medicare fee-for-service (FFS) beneficiaries, and exclude Medicare Advantage (MA) beneficiaries. In this study we characterize the proportion of Medicare beneficiaries enrolled in MA at the time of acute myocardial infarction (AMI), heart failure (HF), and ischemic stroke hospitalization.

METHODS: Retrospective cross-sectional study of short-term acute care hospitals using Medicare claims in 2009 and 2019.

RESULTS: There were 2,653 hospitals in 2009 and 2,732 hospitals in 2019. Across hospitals, the proportion of Medicare beneficiaries hospitalized for AMI who were enrolled in MA increased between 2009 (hospital-level median 14.4% [IQR 5.1%-26.0%]) and 2019 (33.3% [IQR 20.6%-45.2%]), with substantial variation across hospitals. Similar patterns were observed for HF (13.0% [IQR 5.3%-24.3%] to 31.0% [IQR 20.2%-42.3%]) and ischemic stroke (14.6% [IQR 5.3%-26.7%] to 33.3% [IQR 20.9%-46.0%]). Within each hospital referral region, hospital size (large 36.3% vs small 24.5%; adjusted difference 6.7%, 95% CI, 4.5%-8.8%), teaching status (teaching 34.5% vs nonteaching 28.2%; 2.8%, 1.4%-4.1%), and ownership status (private nonprofit 32.3% vs public 24.5%; 5.2%, 3.5%-6.9%) were each associated with a higher hospital MA proportion.

CONCLUSIONS: The proportion of Medicare beneficiaries hospitalized for AMI, HF, and ischemic stroke enrolled in MA doubled between 2009 and 2019, with substantial variation across hospitals. These findings have implications for federal efforts to measure and improve quality, which currently focus only on FFS beneficiaries.

IMPORTANCE: Long-term acute care hospitals (LTCHs) are common sites of postacute care for patients recovering from severe respiratory failure requiring mechanical ventilation (MV). However, federal payment reform led to the closure of many LTCHs in the US, and it is unclear how closure of LTCHs may have affected upstream care patterns at short-stay hospitals and overall patient outcomes.

OBJECTIVE: To estimate the association between LTCH closures and short-stay hospital care patterns and patient outcomes.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective, national, matched cohort study used difference-in-differences analysis to compare outcomes at short-stay hospitals reliant on LTCHs that closed during 2012 to 2018 with outcomes at control hospitals. Data were obtained from the Medicare Provider Analysis and Review File, 2011 to 2019. Participants included Medicare fee-for-service beneficiaries aged 66 years and older receiving MV for at least 96 hours in an intensive care unit (ie, patients at-risk for prolonged MV) and the subgroup also receiving a tracheostomy (ie, receiving prolonged MV). Data were analyzed from October 2022 to June 2023.

EXPOSURE: Admission to closure-affected hospitals, defined as those discharging at least 60% of patients receiving a tracheostomy to LTCHs that subsequently closed, vs control hospitals.

MAIN OUTCOMES AND MEASURES: Upstream hospital care pattern outcomes were short-stay hospital do-not-resuscitate orders, palliative care delivery, tracheostomy placement, and discharge disposition. Patient outcomes included hospital length of stay, days alive and institution free within 90 days, spending per days alive within 90 days, and 90-day mortality.

RESULTS: Between 2011 and 2019, 99 454 patients receiving MV for at least 96 hours at 1261 hospitals were discharged to 459 LTCHs; 84 LTCHs closed. Difference-in-differences analysis included 8404 patients (mean age, 76.2 [7.2] years; 4419 [52.6%] men) admitted to 45 closure-affected hospitals and 45 matched-control hospitals. LTCH closure was associated with decreased LTCH transfer rates (difference, -5.1 [95% CI -8.2 to -2.0] percentage points) and decreased spending-per-days-alive (difference, -$8701.58 [95% CI, -$13 323.56 to -$4079.60]). In the subgroup of patients receiving a tracheostomy, there was additionally an increase in do-not-resuscitate rates (difference, 10.3 [95% CI, 4.2 to 16.3] percentage points) and transfer to skilled nursing facilities (difference, 10.0 [95% CI, 4.2 to 15.8] percentage points). There was no significant association of closure with 90-day mortality.

CONCLUSIONS AND RELEVANCE: In this cohort study, LTCH closure was associated with changes in discharge patterns in patients receiving mechanical ventilation for at least 96 hours and advanced directive decisions in the subgroup receiving a tracheostomy, without change in mortality. Further studies are needed to understand how LTCH availability may be associated with other important outcomes, including functional outcomes and patient and family satisfaction.

The noniterative conditional expectation (NICE) parametric g-formula can be used to estimate the causal effect of sustained treatment strategies. In addition to identifiability conditions, the validity of the NICE parametric g-formula generally requires the correct specification of models for time-varying outcomes, treatments, and confounders at each follow-up time point. An informal approach for evaluating model specification is to compare the observed distributions of the outcome, treatments, and confounders with their parametric g-formula estimates under the "natural course." In the presence of loss to follow-up, however, the observed and natural-course risks can differ even if the identifiability conditions of the parametric g-formula hold and there is no model misspecification. Here, we describe 2 approaches for evaluating model specification when using the parametric g-formula in the presence of censoring: 1) comparing factual risks estimated by the g-formula with nonparametric Kaplan-Meier estimates and 2) comparing natural-course risks estimated by inverse probability weighting with those estimated by the g-formula. We also describe how to correctly compute natural-course estimates of time-varying covariate means when using a computationally efficient g-formula algorithm. We evaluate the proposed methods via simulation and implement them to estimate the effects of dietary interventions in 2 cohort studies.

BACKGROUND: Female sex is frequently cited as a risk factor for anthracycline cardiotoxicity based on pediatric data, but the role of sex in the development of cardiotoxicity has not been clearly established in adults.

OBJECTIVES: To assess the effect of female sex on the development of incident heart failure (HF) in adult patients treated with anthracyclines.

METHODS: This was a retrospective cohort study of 1525 adult patients with no prior history of HF or cardiomyopathy who were treated with anthracyclines between 1992 and 2019. The primary outcome was new HF within 5 years of the first dose of anthracyclines. The effect of sex was assessed using Cox proportional hazards and competing risk models.

RESULTS: Over a median (IQR) follow-up of 1.02 (0.30-3.01) years, 4.78% of patients developed HF (44 men and 29 women). Female sex was not associated with the primary outcome in a multivariable Cox proportional hazards model (HR 0.87; 95% CI 0.53-1.43; P = 0.58). Similar results were observed in a multivariable model accounting for the competing risk of death (HR 0.94; 95% CI 0.39-2.25; P = 0.88). Age, coronary artery disease and hematopoietic stem cell transplant were associated with the primary outcome in a multivariable Cox proportional hazards model. Age and body mass index were associated with the primary outcome in a multivariable competing risk model.

CONCLUSIONS: In this large, single-center, retrospective cohort study, female sex was not associated with incident HF in adult patients treated with anthracyclines.

CONDENSED ABSTRACT: Female sex is frequently cited as a risk factor for anthracycline cardiotoxicity based on pediatric data, but the role of sex in the development of cardiotoxicity has not been clearly established in adults. In this retrospective cohort study, we assessed the effect of female sex on the development of incident heart failure in adult patients treated with anthracyclines. Using Cox proportional hazards and competing risk regression models, we found that there was no association between female sex and heart failure after treatment with anthracyclines.

BACKGROUND AND AIMS: Declines in cardiovascular mortality have stagnated in the United States since 2011. There is growing concern that these patterns reflect worsening cardiovascular health in younger adults. However, little is known about how the burden of acute cardiovascular hospitalizations and mortality have changed in this population. Changes in cardiovascular hospitalizations and mortality among adults aged 25-64 years were evaluated, overall and by community-level income.

METHODS: Using the National Inpatient Sample, age-standardized annual hospitalization and inhospital mortality rates for acute myocardial infarction (AMI), heart failure, and ischemic stroke were determined among adults aged 25-64 years. Quasi-Poisson and quasi-binominal regression models were fitted to compare outcomes between individuals residing in low- and higher-income communities.

RESULTS: Between 2008 and 2019, age-standardized hospitalization rates for AMI increased among younger adults from 155.0 (95% CI 154.6, 155.4) per 100,000 to 160.7 (160.3, 161.1) per 100,000 (absolute change +5.7 [5.0, 6.3], p<0.001). Heart failure hospitalizations also increased (165.3 [164.8, 165.7] to 225.3 [224.8, 225.8], absolute change +60.0 (59.3, 60.6), p<0.001), as ischemic stroke hospitalizations (76.3 [76.1, 76.7] to 108.1 [107.8, 108.5], absolute change +31.7 (31.2, 32.2), p<0.001). Across all conditions, hospitalizations rates were significantly higher among younger adults residing in low-income compared with higher-income communities, and disparities did not narrow between groups. In-hospital mortality decreased for all conditions over the study period.

CONCLUSIONS: There was an alarming increase in cardiovascular hospitalizations among younger adults in the US from 2008 to 2019, and disparities between those residing in low- and higher-income communities did not narrow.