Implementation of single high-dose liposomal amphotericin B based induction therapy for treatment of HIV-associated cryptococcal meningitis in Uganda: a comparative prospective cohort study.

Background: In 2022, the World Health Organization (WHO) recommended a single 10mg/kg dose of liposomal amphotericin B in combination with 14 days of flucytosine and fluconazole (AMBITION-cm regimen) for induction therapy of HIV-associated cryptococcal meningitis, based on the results of the multisite AMBITION-cm trial. We evaluated outcomes after real-world implementation of this novel regimen in Uganda.

Methods: We enrolled Ugandan adults with cryptococcal meningitis into an observational cohort receiving the AMBITION-cm regimen with therapeutic lumbar punctures in routine care during 2022-2023.

Comparison of early fungicidal activity and mortality between daily liposomal amphotericin B and daily amphotericin B deoxycholate among patients with HIV-associated cryptococcal meningitis.

Background: Limited data exist on the antifungal activity of daily liposomal amphotericin B with flucytosine induction regimens for cryptococcal meningitis, which are recommended in high-income countries. Liposomal amphotericin B monotherapy at 3 mg/kg previously failed to meet non-inferiority criteria compared to amphotericin B deoxycholate in its registrational clinical trial. We aimed to compare the quantitative antifungal activity and mortality between daily amphotericin B deoxycholate and daily liposomal amphotericin among persons with HIV-related cryptococcal meningitis receiving adjunctive flucytosine 100 mg/kg/day.

Cross-validation approaches for penalized Cox regression.

Cross-validation is the most common way of selecting tuning parameters in penalized regression, but its use in penalized Cox regression models has received relatively little attention in the literature. Due to its partial likelihood construction, carrying out cross-validation for Cox models is not straightforward, and there are several potential approaches for implementation. Here, we propose a new approach based on cross-validating the linear predictors of the Cox model and compare it to approaches that have been proposed elsewhere.

5-Flucytosine Longitudinal Antifungal Susceptibility Testing of : A Substudy of the EnACT Trial Testing Oral Amphotericin.

Background: The EnACT trial was a phase 2 randomized clinical trial conducted in Uganda, which evaluated a novel orally delivered lipid nanocrystal (LNC) amphotericin B in combination with flucytosine for the treatment of cryptococcal meningitis. When flucytosine (5FC) is used as monotherapy in cryptococcosis, 5FC can induce resistant mutants. Oral amphotericin B uses a novel drug delivery mechanism, and we assessed whether resistance to 5FC develops during oral LNC-amphotericin B therapy.

Achieving Normoglycemia With Tirzepatide: Analysis of SURPASS 1-4 Trials.

Objective: Tirzepatide is a novel single-molecule glucose-dependent insulinotropic polypeptide/glucagon-like peptide 1 receptor agonist, which demonstrated unprecedented improvements in glycemic control and body weight reduction, in the SURPASS phase 3 program. In this exploratory analysis, we aimed to characterize tirzepatide-treated participants who achieved HbA1c <5.7% and evaluate changes in clinical markers associated with long-term cardiometabolic health.

Two-Stage Adaptive Design for Prognostic Biomarker Signatures with a Survival Endpoint.

Cancer biomarker discoveries typically involve utilizing patient specimens. In practice, there is often strong desire to preserve high quality biospecimens for studies that are most likely to yield useful information. Previously, we proposed a two-stage adaptive design for binary endpoints which terminates the biomarker study in a futility interim if the model performance is unsatisfactory.

Return-to-baseline multiple imputation for missing values in clinical trials.

Return-to-baseline is an important method to impute missing values or unobserved potential outcomes when certain hypothetical strategies are used to handle intercurrent events in clinical trials. Current return-to-baseline approaches seen in literature and in practice inflate the variability of the "complete" dataset after imputation and lead to biased mean estimators when the probability of missingness depends on the observed baseline and/or postbaseline intermediate outcomes. In this article, we first provide a set of criteria a return-to-baseline imputation method should satisfy.

Greater intraprocedural systolic blood pressure and blood pressure variability are associated with contrast-induced neurotoxicity after neurointerventional procedures.

Background: Contrast-induced neurotoxicity (CIN) is a rare complication of neurointerventional procedures and its understanding remains limited. We evaluated the association of CIN with systemic hemodynamics in patients undergoing neuroendovascular interventions.

Methods: We conducted a 1:2 matched case-control study from a prospectively collected database of 2510 neurointerventional patients.

In-House Anesthesia and Interventional Radiology Technologist Support Optimize Mechanical Thrombectomy Workflow after Hours.

Background And Purpose: Prior literature suggests after-hours delay leads to poor functional outcomes in stroke patients undergoing thrombectomy. We aimed to evaluate the impact of time of presentation on mechanical thrombectomy (MT) metrics and its association with long-term functional outcome in an Interventional Radiology (IR) suite equipped operating room (OR) setting.

Methods: Retrospective review of prospectively maintained database on all stroke patients undergoing mechanical thrombectomy between January 2015 and December 2018 at our CSC.

Patterns of Care and Clinical Outcomes in Patients with Cerebral Sinus Venous Thrombosis.

Objectives: To explore the association between rurality, transfer patterns and level of care with clinical outcomes of CVST patients in a rural Midwestern state.

Materials And Methods: CVST patients admitted to the hospitals between 2005 and 2014 were identified by inpatient diagnosis codes from statewide administrative claims dataset. Records were linked across interhospital transfers using probabilistic linkage.

Stroke mechanisms and outcomes of isolated symptomatic basilar artery stenosis.

Background: While diffuse atherosclerotic disease affecting the posterior circulation has been described extensively, the prevalence, natural history and angiographic characteristics of symptomatic basilar artery stenosis (ISBAS) remain unknown.

Methods: We reviewed our prospective institutional database to identify patients with ≥50% symptomatic basilar artery (BA) stenosis without significant atherosclerotic burden in the vertebral or posterior cerebral arteries. Stroke mechanism, collateral circulation, and degree and length of stenosis were analysed.

Association of admission clinical predictors and functional outcome in patients with Cerebral Venous and Dural Sinus Thrombosis.

Objectives: Cerebral venous sinus thrombosis (CVST) is a rare subtype of stroke that most commonly affects younger women. While most patients treated with anticoagulation therapy have good outcomes, a significant number go on to experience disability. The primary aim of this study was to identify objective, easily reproducible, clinical admission predictors of poor outcome at discharge in patients with CVST.

Computed Tomography Angiogram Derived From Computed Tomography Perfusion Done with Low Iodine Volume Protocol Preserves Diagnostic Yield for Middle Cerebral Artery-M2 Occlusions.

Background: Computed tomography angiogram (CTA) derived from computed tomography perfusion (CTP) has been proposed to avoid addition of separate CT perfusion protocol for selection of large vessel occlusion in acute stroke patients. Previous studies have validated this technique for proximal large vessel occlusions. In this study, we test reliability for identifying M2 occlusions on CTA derived from CTP.