Notes

B-cell severe lymphoblastic the leukemia disease in individuals using germline RUNX1 mutations.
Further research is required to disentangle the underlying pathophysiologic mechanisms, leading to the complex phenotype of
-related disorder.
This family with a novel PCYT2 variant expands the clinical spectrum of PCYT2-related disorder to include axonal motor and sensory polyneuropathy and the genetic spectrum to include the variant located in the first catalytic domain, whereas all previously reported variants are located in the second catalytic domain. Further research is required to disentangle the underlying pathophysiologic mechanisms, leading to the complex phenotype of PCYT2-related disorder.
There are few curriculum materials designed to provide training and support for peer tutors to become effective clinical skills teachers. We designed the Clinical Skills Tutoring Program (CSTP) curriculum to guide tutors to help their students reflect on clinical skills performance, create an individualized learning plan, and engage in improvement based on feedback to achieve clinical skills competencies.

Curriculum content was delivered through an in-person training session, formal curriculum written content, online resources, and longitudinal support from faculty directors. Tutors (fourth-year medical students) received surveys to evaluate the in-person training session, curriculum resources, and overall program experience. Leukadherin-1 clinical trial Student participants (medical students of any year) completed a survey to rate their satisfaction in working with their tutors.

There were 12 tutors in cohort 1 and 18 tutors in cohort 2. Survey response rates ranged from 50% to 70% among tutors. The tutors were satisfied with the in-person training session, program experience, curriculum resources, support from directors, development of learning goals with the student, and clinical skills practice with the student (mean Likert ratings greater than 4 out of 5). Student participants were satisfied with their experience creating learning goals and receiving feedback from their tutors.

The tutor curriculum fills a gap by training and supporting tutors before and during their work with students needing further resources and remediation in one or more clinical skills domains. The curriculum can be implemented and further adapted by other tutoring programs locally and nationally.
The tutor curriculum fills a gap by training and supporting tutors before and during their work with students needing further resources and remediation in one or more clinical skills domains. The curriculum can be implemented and further adapted by other tutoring programs locally and nationally.
Microvascular angina is a common cause of ischemia with non-obstructive coronary arteries (INOCA) and limited therapeutic options are available to those affected. Endothelin-1 (ET-1) is a potent vasoconstrictor implicated in the pathophysiology of microvascular angina. A large randomised, double blinded, placebo controlled crossover trial, the PRecIsion medicine with ZibotEntan in microvascular angina (PRIZE) trial is currently underway, investigating an endothelin receptor antagonist - Zibotentan, as a new drug treatment for microvascular angina. The trial uses a 'precision medicine' approach by preferential selection of those with higher ET-1 expression conferred by the PHACTR1 minor G allele single nucleotide polymorphism (SNP). The incidence of this SNP occurs in approximately one third of the population therefore a considerable number of screened patients will be ineligible for randomisation and the treatment phase of the trial.

In the PRIZE Endothelin (ET) Sub-Study, patients screened out of the PRIZE trial will be genotyped for other genetic variants in the ET-1 pathway. These will be correlated with phenotypic characteristics including exercise tolerance, angina severity and quantitative measures of microvascular function on cardiovascular MRI as well as mechanistic data on endothelin pathway signalling.

The study will provide a comprehensive genotype and phenotype bio-resource identifying novel ET-1 genotypes to inform the potential wider use of endothelin receptor antagonists for this indication.
The study will provide a comprehensive genotype and phenotype bio-resource identifying novel ET-1 genotypes to inform the potential wider use of endothelin receptor antagonists for this indication.
Intravascular lithotripsy (IVL) can be used to assist stent deployment in severe coronary artery calcifications (CAC).

Studies employing IVL for CAC lesions were included. The primary outcomes included clinical and angiographic success. The secondary outcomes, including lumen gain, maximum calcium thickness, and calcium angle at the final angiography site, minimal lumen area site, and minimal stent area site, were analyzed by the random-effects model to calculate the pooled standardized mean difference. Tertiary outcomes included safety event ratios.

Seven studies (760 patients) were included. The primary outcomes pooled clinical and angiographic success event ratio parentage of IVL was 94.4% and 94.8%, respectively. On a random effect model for standard inverse variance for secondary outcomes showed minimal lumen diameter increase with IVL was 4.68mm (p-value<0.0001, 95% CI 1.69-5.32); diameter decrease in the stenotic area after IVL session was -5.23mm (95 CI -22.6-12.8). At the minimal lumen area (MLA) and final minimal stent area (MSA) sites, mean lumen area gain was 1.42mm
(95% CI 1.06-1.63; p<0.00001) and 1.34mm
(95% CI 0.71-1.43; p<0.00001), respectively. IVL reduced calcium thickness at the MLA site (SMD -0.22; 95% CI -0.40-0.04; P=0.02); calcium angle was not affected at the MLA site. The tertiary outcomes most common complication was major adverse cardiovascular events (n=48/669), and least common complication was abrupt closure of the vessel (n=1/669).

Evidence suggests that IVL safely and effectively facilitates stent deployment with high angiographic and clinical success rates in treating severely calcified coronary lesions.
Evidence suggests that IVL safely and effectively facilitates stent deployment with high angiographic and clinical success rates in treating severely calcified coronary lesions.
Use of existing data in electronic health records (EHRs) could be used more extensively to better leverage real world data for clinical studies, but only if standard, reliable processes are developed. Numerous computable phenotypes have been validated against manual chart review, and common data models (CDMs) exist to aid implementation of such phenotypes across platforms and sites. Our objective was to measure consistency between data that had previously been manually collected for an implantable cardiac device registry and CDM-based phenotypes for the condition of heart failure (HF).

Patients enrolled in an implantable cardiac device registry at two hospitals from 2013 to 2018 contributed to this analysis wherein registry data were compared to PCORnet CDM-formatted EHR data. Seven different phenotype algorithms were used to search for the presence of HF and compare the results with the registry. Sensitivity, specificity, predictive value and congruence were calculated for each phenotype.

In the registry, 176 of 319 (55%) patients had history of HF, compared with different phenotypes estimating between 96 (30%) and 188 (59%). The least-restrictive phenotypes (any diagnosis) had high sensitivity and specificity (90%/80%), but more restrictive phenotypes had higher specificity (e.g., code present in problem list, 94%). Differences were observed using time-based criteria (e.g., days between visit diagnoses) and between participating hospitals.

Consistency between manually-collected registry data and CDM-based phenotypes for history of HF was high overall, but use of different phenotypes impacted sensitivity and specificity, and results may differ depending on the medical condition of interest.
Consistency between manually-collected registry data and CDM-based phenotypes for history of HF was high overall, but use of different phenotypes impacted sensitivity and specificity, and results may differ depending on the medical condition of interest.
Continuous outpatient inotrope infusion therapy (COIIT) can be used as palliative or interim treatment in patients with advanced heart failure (AHF). Despite widespread use, there is a relative lack of data informing best practices. This study aimed to examine whether patterns of COIIT use differed by region and to explore whether observed differences influenced clinical outcomes.

Retrospective study of AHF patients receiving COIIT from May 2009 through June 2016. The primary outcome was regional difference, the secondary outcome was persistence (duration) on therapy. Cox proportional hazards model was used to calculate hazard ratios for treatment regimens.

There were 3,286 patients, mean (SD) age 61.9 (14.4) years and 74.0% (2,433) male. Inotrope selection and beta blocker use varied by region by chi square (χ2 (21)=166.9, p<0.001). Persistence was greater on milrinone compared to dobutamine (HR (for discontinuation) 0.54, CI 0.41-0.70, p<0.001). Concurrent beta-blocker was associated with greater persistence for patients receiving milrinone (HR 0.13, CI 0.08-0.20, p<0.001) and dobutamine (HR 0.36, CI 0.18-0.71, p<0.001).

Patterns of COIIT use varied by region, and variations in use were associated with differences in clinical outcomes.
Patterns of COIIT use varied by region, and variations in use were associated with differences in clinical outcomes.Since the 1990s, there has been a striking urban-rural divergence in life expectancy within the United States, with metropolitan areas achieving strong life expectancy increases and nonmetropolitan areas experiencing stagnation or actual declines in life expectancy. While Alzheimer's disease and related dementias (ADRD) are likely to pose a particular challenge in nonmetropolitan areas, we know relatively little about the level of ADRD mortality in nonmetropolitan areas, how it has changed over time, and whether it is contributing to metropolitan/nonmetropolitan life expectancy gaps. This study finds that ADRD mortality has risen more rapidly in nonmetropolitan areas than in all other metro areas (large central metros, suburbs, and medium/small cities) between 1999 and 2019. While death rates from ADRD were nearly identical in large central metros and nonmetros in 1999, a clear metro/nonmetro gradient has emerged and widened substantially over the past two decades. Today, nonmetros now experience the highest levels of ADRD mortality, while large central metros have the lowest levels. These metro/nonmetro gaps in ADRD differ substantially by region, with the largest gaps observed in the Middle Atlantic and South Atlantic. The contribution of ADRD to metro/nonmetro differences life expectancy at age 65 is now considerable in many regions, reaching up to 30% for women and 13% for men. In several regions, ADRD's contribution to female life expectancy gaps is on par with or exceeds the contributions of other leading causes of death such as heart disease, cancer, and chronic lower respiratory diseases. The rising burden of Alzheimer's disease mortality is likely to pose a substantial challenge in rural areas of the United States which are aging rapidly, experiencing adverse mortality trends, and increasingly disadvantaged in terms of socioeconomic resources and health care infrastructure.
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