Two Mechanistic Pathways for Thienopyridine-Associated Thrombotic Thrombocytopenic Purpura: A Report From the SERF-TTP Research Group and the RADAR Project

We sought to describe clinical and laboratory findings for a large cohort of patients with thienopyridine-associated thrombotic thrombocytopenic purpura (TTP)

Latent Trait Pattern-Mixture Mixed-Models for Ecological Momentary Assessment Data

Latent trait pattern-mixture mixed-models (LTPMMM) for Ecological Momentary Assessment (EMA) data are developed in which data are collected in a intermittent fashion. Initial work with intermittent data has used latent class pattern-mixture models. Using Item Response Theory (IRT) models, a latent trait is used to model the missingness mechanism and modeled jointly with a mixed-model for longitudinal outcomes. Both one- and two-parameter LTPMMMs are presented. These new pattern-mixture models offer a unique way to analyze EMA data with many unique response patterns that cannot easily formed into latent classes. Data from an EMA study involving high-school students' positive and negative affect are presented. The proposed models will estimate a latent trait that corresponds to the students' “ability" to respond to the prompting device. One-thousand simulations are performed to test the proposed models across different simulation scenarios. The models are compared to a Missing at Random (MAR) mixed-model and a latent class pattern-mixture model. The proposed models have lower bias and increased efficiency compared to standard approaches. The new models offer a viable alternative to latent class pattern-mixture models previously used with intermittent missing data

Tailoring the electronic health record to reduce inappropriate prescribing

No abstrac

Effect of sex on outcome after recurrent stroke in African Americans: results from the African American Antiplatelet Stroke Prevention Study

Background: Sex-related disparities in stroke have been previously reported. However, the influence of sex on the outcome of recurrent stroke in blacks is less clear. Our objective is to investigate the effect of sex on the outcome of recurrent non-fatal stroke in the African American Antiplatelet Stroke Prevention Study (AAASPS) Methods: The AAASPS is a double-blind, randomized, controlled trial of recurrent stroke. Participants -967 black women and 842 black men- with non-cardioembolic ischemic stroke were assigned to receive ticlopidine or aspirin and followed for up to two years. The NIH Stroke Scale (NIHSS), modified Barthel score (mBS), and the Glasgow Outcome Scale (GOS) were determined at enrollment, at pre-specified times thereafter and at the time of recurrent stroke. Survival analysis was used to test for a significant difference in the time to recurrent stroke between women and men. Results: Of the total 1,809 subjects enrolled in AAASPS, 186 subjects (89 women and 97 men) suffered recurrent non-fatal stroke. At enrollment, the NIHSS (2.87 for women and 3.00 for men; p=0.73), the mBS (18.26 for women and 18.52 for men; p=0.47) and the GOS (1.49 for women and 1.51 for men; p=0.86) were not significantly different. In follow-up and at the time of stroke recurrence, the NIHSS, mBS, and GOS were similar for both groups, except for the mBS at the 6-month visit, which was lower in women (18.49) than in men (19.37) (p=0.02). In the survival analysis, no significant difference in the time to recurrent stroke was found between women and men (p=0.69). Conclusions: Although sex-related stroke disparities have been reported, in the AAASPS cohort outcomes for recurrent non-fatal non-cardioembolic ischemic stroke for women were not significantly different than for men. Differences in study populations and methodologies may explain discrepancies in results from the various studies

Representation of Women on National Institutes of Health Study Sections

No abstrac

Assessing real-time positive subjective effects of alcohol using high-resolution ecological momentary assessment in risky versus light drinkers

Background: High-resolution ecological momentary assessment (HR-EMA) can assess acute alcohol responses during naturalistic heavy drinking episodes. The goal of this study was to use HR-EMA to examine drinking behavior and subjective responses to alcohol in risky drinkers (moderate-severe alcohol use disorder [MS-AUD], heavy social drinkers [HD]) and light drinkers (LD). We expected that risky drinkers would endorse greater alcohol stimulation and reward, with lower sedation, than LD, even when controlling for amount of alcohol consumed. Methods: Participants (N = 112; 54% male, M ± SD age = 27.2 ± 4.2 years) completed smartphone-based HR-EMA during one typical alcohol drinking occasion and one non-alcohol-drinking occasion in their natural environment. Participants were prompted to complete next-day surveys that assessed drinking-related outcomes, study acceptability, and safety. Results: HR-EMA prompt completion rates were excellent (92% and 89% for the alcohol and nonalcohol episodes, respectively). The MS-AUD group consumed the most alcohol with the highest estimated blood alcohol concentration (eBAC) by the end of the alcohol drinking episode (0.14 g/dL) versus LD (0.02 g/dL), with HD intermediate (0.10 g/dL). Relative to LD, MS-AUD and HD endorsed greater positive effects of alcohol (stimulation, liking, and wanting). Conclusions: This study is the first to use HR-EMA to measure and compare real-world acute alcohol responses across diverse drinker subgroups, including persons with MS-AUD. Results demonstrate that risky drinkers experience heightened pleasurable effects measured in real-time during natural-environment alcohol responses. Rather than drinking excessively to eventually achieve desirable subjective effects, risky drinkers show sensitivity to positive alcohol effects throughout a heavy drinking episode.</p

Treatment approach and outcomes of patients with accelerated/blast-phase myeloproliferative neoplasms in the current era

Progression of myeloproliferative neoplasms (MPNs) to accelerated or blast-phase is associated with poor survival outcomes. Since 2017 there have been several therapies approved for use in acute myeloid leukemia (AML); these therapies have been incorporated into the management of accelerated/blast-phase MPNs (MPN-AP/BP). We performed a multi-center analysis to investigate outcomes of patients diagnosed with MPN-AP/BP in 2017 or later. Two-hundred two patients were identified; median overall survival (OS) was 0.86 years. We also analyzed patients based on first-line treatment; the three most common approaches were intensive chemotherapy (IC) (n=65), DNA methyltransferase inhibitor (DNMTi)-based regimens (n=65), and DNMTi + venetoclax (VEN)-based regimens (n=54). Median OS was not significantly different by treatment type. In addition, we evaluated response by 2017 European LeukemiaNet (ELN) AML criteria and 2012 MPN-BP criteria in an effort to understand the association of response with survival outcomes. We also analyzed outcomes in 65 patients that received allogeneic hematopoietic stem cell transplant (allo-HCT); median OS was 2.30 years from time of allo-HCT. Our study demonstrates that survival amongst patients with MPN-AP/BP is limited in the absence of allo-HCT even in the current era of therapeutics and underscores the urgent need for new agents and approaches