Faculty Bibliography

INTRODUCTION:) study is to compare the effectiveness of two postdischarge interventions on healthcare utilisation, patient-reported outcomes and healthcare quality among patients with HF. METHODS AND ANALYSIS:The MIGHTy-Heart study is a pragmatic comparative effectiveness trial comparing two interventions demonstrated to improve the hospital to home transition for patients with HF: mobile integrated health (MIH) and transitions of care coordinators (TOCC). The MIH intervention bundles home visits from a community paramedic (CP) with telehealth video visits by emergency medicine physicians to support the management of acute symptoms and postdischarge care coordination. The TOCC intervention consists of follow-up phone calls from a registered nurse within 48-72 hours of discharge to assess a patient's clinical status, identify unmet clinical and social needs and reinforce patient education (eg, medication adherence and lifestyle changes). MIGHTy-Heart is enrolling and randomising (1:1) 2100 patients with HF who are discharged to home following a hospitalisation in two New York City (NY, USA) academic health systems. The coprimary study outcomes are all-cause 30-day hospital readmissions and quality of life measured with the Kansas City Cardiomyopathy Questionnaire 30 days after hospital discharge. The secondary endpoints are days at home, preventable emergency department visits, unplanned hospital admissions and patient-reported symptoms. Data sources for the study outcomes include patient surveys, electronic health records and claims submitted to Medicare and Medicaid. ETHICS AND DISSEMINATION:All participants provide written or verbal informed consent prior to randomisation in English, Spanish, French, Mandarin or Russian. Study findings are being disseminated to scientific audiences through peer-reviewed publications and presentations at national and international conferences. This study has been approved by: Biomedical Research Alliance of New York (BRANY #20-08-329-380), Weill Cornell Medicine Institutional Review Board (20-08022605) and Mt. Sinai Institutional Review Board (20-01901). TRIAL REGISTRATION NUMBER:Clinicaltrials.gov, NCT04662541.

BACKGROUND AND AIMS/OBJECTIVE:Dynamic, adaptive pharmacologic treatment for opioid use disorder (OUD) has been previously recommended over static dosing to prevent relapse, and is aligned with personalized medicine. However, there has been no quantitative evidence demonstrating its advantage. Our objective was to estimate the extent to which a hypothetical intervention that increased buprenorphine dose in response to opioid use would affect risk of relapse over 24 weeks of follow-up. DESIGN/METHODS:A secondary analysis of the buprenorphine arm of an open-label randomized controlled 24-week comparative effectiveness trial, 2014-17. SETTING/METHODS:Eight community addiction treatment programs in the United States. PARTICIPANTS/METHODS:English-speaking adults with DSM-5 OUD, recruited during inpatient admission (n = 270). Participants were mainly white (65%) and male (72%). INTERVENTION(S)/METHODS:Participants were treated with daily sublingual buprenorphine-naloxone (BUP-NX), with dose based on clinical indication, determined by the provider. We examined a hypothetical intervention of increasing dose in response to opioid use. MEASUREMENTS/METHODS:Outcome was relapse to regular opioid use during the 24 weeks of outpatient treatment, assessed in a survival framework. We estimated the relapse-free survival curves of participants under a hypothetical (i.e. counterfactual) intervention in which their BUP-NX dosage would be increased following their own subject-specific opioid use during the first 12 weeks of treatment versus a hypothetical intervention in which dose would remain constant. FINDINGS/RESULTS:We estimated that increasing BUP-NX dose in response to recent opioid use would lower risk of relapse by 19.17 percentage points [95% confidence interval (CI) = -32.17, -6.18) (additive risk)] and 32% (0.68, 95% CI = 0.49, 0.86) (relative risk). The number-needed-to-treat with this intervention to prevent a single relapse is 6. CONCLUSIONS:In people with opioid use disorder, a hypothetical intervention that increases sublingual buprenorphine-naloxone dose in response to opioid use during the first 12 weeks of treatment appears to reduce risk of relapse over 24 weeks, compared with holding the dose constant after week 2.

BACKGROUND AND OBJECTIVES:To determine the effects of dimethyl fumarate (DMF) and glatiramer acetate on iron content in chronic active lesions in patients with multiple sclerosis (MS) and in human microglia in vitro. METHODS:This was a retrospective observational study of 34 patients with relapsing-remitting MS and clinically isolated syndrome treated with DMF or glatiramer acetate. Patients had lesions with hyperintense rims on quantitative susceptibility mapping, were treated with DMF or glatiramer acetate (GA), and had a minimum of 2 on-treatment scans. Changes in susceptibility in rim lesions were compared among treatment groups in a linear mixed effects model. In a separate in vitro study, induced pluripotent stem cell-derived human microglia were treated with DMF or GA, and treatment-induced changes in iron content and activation state of microglia were compared. RESULTS:Rim lesions in patients treated with DMF had on average a 2.77-unit reduction in susceptibility per year over rim lesions in patients treated with GA (bootstrapped 95% CI -5.87 to -0.01), holding all other variables constant. Moreover, DMF but not GA reduced inflammatory activation and concomitantly iron content in human microglia in vitro. DISCUSSION:Together, our data indicate that DMF-induced reduction of susceptibility in MS lesions is associated with a decreased activation state in microglial cells. We have demonstrated that a specific disease modifying therapy, DMF, decreases glial activity in chronic active lesions. Susceptibility changes in rim lesions provide an in vivo biomarker for the effect of DMF on microglial activity. CLASSIFICATION OF EVIDENCE:This study provided Class III evidence that DMF is superior to GA in the presence of iron as a marker of inflammation as measured by MRI quantitative susceptibility mapping.

We introduce a novel Bayesian estimator for the class proportion in an unlabeled dataset, based on the targeted learning framework. The procedure requires the specification of a prior (and outputs a posterior) only for the target of inference, and yields a tightly concentrated posterior. When the scientific question can be characterized by a low-dimensional parameter functional, this focus on target prior and posterior distributions perfectly aligns with Bayesian subjectivism. We prove a Bernstein-von Mises-type result for our proposed Bayesian procedure, which guarantees that the posterior distribution converges to the distribution of an efficient, asymptotically linear estimator. In particular, the posterior is Gaussian, doubly robust, and efficient in the limit, under the only assumption that certain nuisance parameters are estimated at slower-than-parametric rates. We perform numerical studies illustrating the frequentist properties of the method. We also illustrate their use in a motivating application to estimate the proportion of embolic strokes of undetermined source arising from occult cardiac sources or large-artery atherosclerotic lesions. Though we focus on the motivating example of the proportion of cases in an unlabeled dataset, the procedure is general and can be adapted to estimate any pathwise differentiable parameter in a non-parametric model.

OBJECTIVE:Transesophageal echocardiography (TEE) is sometimes used to search for cardioembolic sources after ischemic stroke or transient ischemic attack (TIA). TEE visualizes some sources better than transthoracic echocardiography, but TEE is invasive and may cause aspiration. Few data exist on the risk of respiratory complications after TEE in patients who had stroke or TIA. Our objective was to determine whether TEE was associated with increased risk of respiratory failure in patients who had ischemic stroke or TIA. DESIGN/METHODS:This is a retrospective cohort study using administrative data from inpatient and outpatient insurance claims collected by the US federal government's Centers for Medicare and Medicaid Services. SETTING/METHODS:Hospitals and outpatient clinics throughout the USA. PARTICIPANTS/METHODS:99 081 patients ≥65 years old hospitalized for out-of-hospital ischemic stroke or TIA, defined by validated International Classification of Disease-9/10 diagnosis codes and present-on-admission codes, using claims data from 2008 to 2018 in a random 5% sample of Medicare beneficiaries. MAIN OUTCOME MEASURES/METHODS:Acute respiratory failure, defined as endotracheal intubation and/or mechanical ventilation, starting on the first day after admission through 28 days afterward. RESULTS:Of 99 081 patients included in this analysis, 73 733 (74.4%) had an ischemic stroke and 25 348 (25.6%) a TIA. TEE was performed in 4677 (4.7%) patients and intubation and/or mechanical ventilation in 1403 (1.4%) patients. The 28-day cumulative risk of respiratory failure after TEE (1.4%; 95% CI 0.8% to 2.7%) was similar to that seen in those without TEE (1.4%; 95% CI 1.4% to 1.5%) (p=0.84). After adjustment for age, sex, race, Charlson comorbidities, diagnosis of stroke versus TIA, intravenous thrombolysis, and mechanical thrombectomy, TEE was not associated with an increased risk of respiratory failure (HR, 0.9; 95% CI 0.6 to 1.2). CONCLUSIONS:In a cohort of older patients who had ischemic stroke or TIA, TEE was not associated with an increased risk of subsequent respiratory failure.