Estimated Prevalence and Clinical Manifestations of UBA1 Variants Associated With VEXAS Syndrome in a Clinical Population.

Importance: VEXAS (vacuoles, E1-ubiquitin-activating enzyme, X-linked, autoinflammatory, somatic) syndrome is a disease with rheumatologic and hematologic features caused by somatic variants in UBA1. Pathogenic variants are associated with a broad spectrum of clinical manifestations. Knowledge of prevalence, penetrance, and clinical characteristics of this disease have been limited by ascertainment biases based on known phenotypes. Objective: To determine the prevalence of pathogenic variants in UBA1 and associated clinical manifestations in an unselected population using a genomic ascertainment approach. Design, Setting, and Participants: This retrospective observational study evaluated UBA1 variants in exome data from 163 096 participants within the Geisinger MyCode Community Health Initiative. Clinical phenotypes were determined from Geisinger electronic health record data from January 1, 1996, to January 1, 2022. Exposures: Exome sequencing was performed. Main Outcomes and Measures: Outcome measures included prevalence of somatic UBA1 variation; presence of rheumatologic, hematologic, pulmonary, dermatologic, and other findings in individuals with somatic UBA1 variation on review of the electronic health record; review of laboratory data; bone marrow biopsy pathology analysis; and in vitro enzymatic assays. Results: In 163 096 participants (mean age, 52.8 years; 94% White; 61% women), 11 individuals harbored likely somatic variants at known pathogenic UBA1 positions, with 11 of 11 (100%) having clinical manifestations consistent with VEXAS syndrome (9 male, 2 female). A total of 5 of 11 individuals (45%) did not meet criteria for rheumatologic and/or hematologic diagnoses previously associated with VEXAS syndrome; however, all individuals had anemia (hemoglobin: mean, 7.8 g/dL; median, 7.5 g/dL), which was mostly macrocytic (10/11 [91%]) with concomitant thrombocytopenia (10/11 [91%]). Among the 11 patients identified, there was a pathogenic variant in 1 male participant prior to onset of VEXAS-related signs or symptoms and 2 female participants had disease with heterozygous variants. A previously unreported UBA1 variant (c.1861A>T; p.Ser621Cys) was found in a symptomatic patient, with in vitro data supporting a catalytic defect and pathogenicity. Together, disease-causing UBA1 variants were found in 1 in 13 591 unrelated individuals (95% CI, 1:7775-1:23 758), 1 in 4269 men older than 50 years (95% CI, 1:2319-1:7859), and 1 in 26 238 women older than 50 years (95% CI, 1:7196-1:147 669). Conclusions and Relevance: This study provides an estimate of the prevalence and a description of the clinical manifestations of UBA1 variants associated with VEXAS syndrome within a single regional health system in the US. Additional studies are needed in unselected and genetically diverse populations to better define general population prevalence and phenotypic spectrum.

The social context of smoking: A qualitative study comparing smokers of high versus low socioeconomic position.

BACKGROUND: The reductions in smoking prevalence in a number of industrialised countries are accompanied by a strong social gap and associated health inequality. Groups such as the World Health Organisation emphasise the importance of exploring potential causal factors for smoking such as socio-economic context & position. There has been little effort to compare the social context of smoking for smokers of high versus lower socio-economic position (SEP) to consider how tobacco control efforts might reduce smoking-related health inequality. METHOD: Purposive sampling was used to recruit participants for eight focus groups. The groups were segregated by age, gender and SEP. Samples were selected from suburbs within the Sydney metropolitan area defined as either high or low SEP based on the Socio Economic Index for Areas. Emergent themes were analysed according to Poland's six dimensions of the social context of smoking. Differences according to SEP, age group and gender were explored. RESULTS: While there was commonality in social experiences for smokers across groups, some important aspects of the social context of smoking varied. Smokers of high SEP appeared to be aware of particular social pressures not to smoke on five of the six social context dimensions (power, body, identity, consumption and place). Not only were some of those pressures absent for low SEP participants, there were additional influences within the social context which were pro-smoking. CONCLUSIONS: In order to narrow the health inequality gap associated with smoking, it is important to take account of the more pro-smoking social context experienced by low SEP smokers. Suggestions are made regarding social marketing campaigns, support for quit assistance and approaches to the regulation of smoking which may assist in minimising smoking-related health inequality.

Transgender Youth in the Inpatient Psychiatric Setting: A Literature Review and Case Report.

Once considered pathological, transgenderism is now accepted as a variant of normal sexuality. As society has become more accepting of transgenderism, increasing numbers of transgender patients have begun to seek psychiatric care, and younger populations are embracing their gender differences. There is a paucity of literature on how best to serve transgender youth in psychiatric inpatient units. In this article, we share our experience and discuss the need for practical guidelines to help the inpatient psychiatrist navigate key topics related to this population. We then present a case report to illustrate several of these issues. A major goal of this report is to increase the literature base.