Differences in career paths and attributes of pharmacists completing a community pharmacy residency program (CPRP)

Objective: To determine any differences in career paths and career attributes of pharmacists who have completed a PGY1 community pharmacy residency program (CPRP) as compared to those that have not completed a PGY1 CPRP. Methods: A web-based survey evaluating various aspects of community pharmacists’ careers was distributed to 274 CPRP graduates in addition to a random sample of 7,376 community pharmacists. The survey contained 32 questions evaluating various career attributes. Questions that assessed level of agreement were on a 6-point Likert-type Scale (1=strongly disagree; 6=strongly agree). Results: A total of 353 participants completed the survey, with 224 indicating that they had not completed a CPRP. Pharmacists who completed a CPRP responded that they spend significantly more time on patient care services, teaching, and research, and spend less time dispensing medications compared to those that have not completed a CPRP. Compared to those that did not complete a CPRP, CPRP graduates were less likely to agree that current level of workload negatively impacts job performance, motivation to work, job satisfaction, mental/emotional health, and physical health. Conclusion: Pharmacists completing a CPRP noted significant differences in their current employment and job responsibilities. Additional expansion and education regarding the importance of CPRPs should be considered

Defining the genotypic and phenotypic spectrum of X-linked MSL3-related disorder

PURPOSE: We sought to delineate the genotypic and phenotypic spectrum of female and male individuals with X-linked, MSL3-related disorder (Basilicata-Akhtar syndrome). METHODS: Twenty-five individuals (15 males, 10 females) with causative variants in MSL3 were ascertained through exome or genome sequencing at ten different sequencing centers. RESULTS: We identified multiple variant types in MSL3 (ten nonsense, six frameshift, four splice site, three missense, one in-frame-deletion, one multi-exon deletion), most proven to be de novo, and clustering in the terminal eight exons suggesting that truncating variants in the first five exons might be compensated by an alternative MSL3 transcript. Three-dimensional modeling of missense and splice variants indicated that these have a deleterious effect. The main clinical findings comprised developmental delay and intellectual disability ranging from mild to severe. Autism spectrum disorder, muscle tone abnormalities, and macrocephaly were common as well as hearing impairment and gastrointestinal problems. Hypoplasia of the cerebellar vermis emerged as a consistent magnetic resonance image (MRI) finding. Females and males were equally affected. Using facial analysis technology, a recognizable facial gestalt was determined. CONCLUSION: Our aggregated data illustrate the genotypic and phenotypic spectrum of X-linked, MSL3-related disorder (Basilicata-Akhtar syndrome). Our cohort improves the understanding of disease related morbidity and allows us to propose detailed surveillance guidelines for affected individuals

Defining the genotypic and phenotypic spectrum of X-linked MSL3-related disorder

Purpose We sought to delineate the genotypic and phenotypic spectrum of female and male individuals with X-linked, MSL3-related disorder (Basilicata-Akhtar syndrome). Methods Twenty-five individuals (15 males, 10 females) with causative variants in MSL3 were ascertained through exome or genome sequencing at ten different sequencing centers. Results We identified multiple variant types in MSL3 (ten nonsense, six frameshift, four splice site, three missense, one in-frame-deletion, one multi-exon deletion), most proven to be de novo, and clustering in the terminal eight exons suggesting that truncating variants in the first five exons might be compensated by an alternative MSL3 transcript. Three-dimensional modeling of missense and splice variants indicated that these have a deleterious effect. The main clinical findings comprised developmental delay and intellectual disability ranging from mild to severe. Autism spectrum disorder, muscle tone abnormalities, and macrocephaly were common as well as hearing impairment and gastrointestinal problems. Hypoplasia of the cerebellar vermis emerged as a consistent magnetic resonance image (MRI) finding. Females and males were equally affected. Using facial analysis technology, a recognizable facial gestalt was determined. Conclusion Our aggregated data illustrate the genotypic and phenotypic spectrum of X-linked, MSL3-related disorder (Basilicata-Akhtar syndrome). Our cohort improves the understanding of disease related morbidity and allows us to propose detailed surveillance guidelines for affected individuals

Data-driven Testing Program Improves Detection of COVID-19 Cases and Reduces Community Transmission

COVID-19 remains a global threat in the face of emerging SARS-CoV-2 variants and gaps in vaccine administration and availability, and organizations must be prepared to detect and mitigate its risk to their people and activities. In this report we share key lessons learned from an adaptive COVID-19 testing program implemented at a mid-sized university in the Midwest. The program utilized two simple, diverse, and easily interpretable machine learning models to quickly and accurately predict which students were at elevated risk for contracting COVID-19 and should be called proactively for testing. Our adaptive testing cohorts produced positivity rates that were 26% higher than the random cohort: 0.58% positivity (95% CI 0.47% to 0.68%) from 19,171 tests, and 0.46% positivity (95% CI 0.41% to 0.51%) from 64,003 tests, respectively. Within 14 days of their selection, 2.94% of the adaptive cohort tested positive, compared to 1.27% of the random cohort. Close contacts who were predicted by the adaptive testing models received a COVID-19 test within an average of 0.94 days (95% CI 0.78 to 1.11) of the source testing positive, while those who were manually contact traced were tested in an average of 1.92 days (95% CI 1.81 to 2.02). These results suggest that machine learning strategies can improve surveillance testing effectiveness, especially in a university setting, by effectively distributing testing resources and potentially reducing community transmission

Rare germline heterozygous missense variants in BRCA1-associated protein 1, BAP1, cause a syndromic neurodevelopmental disorder

International audienceNuclear deubiquitinase BAP1 (BRCA1-associated protein 1) is a core component of multiprotein complexes that promote transcription by reversing the ubiquitination of histone 2A (H2A). BAP1 is a tumor suppressor whose germline loss-of-function variants predispose to cancer. To our knowledge, there are very rare examples of different germline variants in the same gene causing either a neurodevelopmental disorder (NDD) or a tumor predisposition syndrome. Here, we report a series of 11 de novo germline heterozygous missense BAP1 variants associated with a rare syndromic NDD. Functional analysis showed that most of the variants cannot rescue the consequences of BAP1 inactivation, suggesting a loss-of-function mechanism. In T cells isolated from two affected children, H2A deubiquitination was impaired. In matching peripheral blood mononuclear cells, histone H3 K27 acetylation ChIP-seq indicated that these BAP1 variants induced genome-wide chromatin state alterations, with enrichment for regulatory regions surrounding genes of the ubiquitin-proteasome system (UPS). Altogether, these results define a clinical syndrome caused by rare germline missense BAP1 variants that alter chromatin remodeling through abnormal histone ubiquitination and lead to transcriptional dysregulation of developmental genes