Strategies for enhancing the representation of women in clinical trials: an evidence map.

BACKGROUND: Equitable sex- and gender-based representation in clinical trials is an essential step to ensuring evidence-based care for women. While multi-institutional actions have led to significant improvements in the inclusion of women in trials, inequity persists in areas like sex-neutral cancers and cardiovascular disease. We sought to identify strategies described or evaluated to boost the inclusion of women in clinical trials. METHODS: We used evidence mapping methodology to examine the breadth of relevant literature. We developed an a priori protocol and followed reporting guidance from the Preferred Reporting Items for Systematic Reviews and Meta-Analysis where applicable. We searched MEDLINE® (via PubMed) and EMBASE (via Elsevier) databases from inception through April 4, 2023, and used standardized procedures incorporating duplication and data verification. We included articles that described strategies to improve the recruitment and retention of women in clinical trials. RESULTS: We identified 122 articles describing recruitment and retention strategies for 136 trials (377,595 women). Only one article distinguished between the sex and gender identity of participants, and none defined their use of the terms such as "women" or "female". The majority of articles (95%) described recruitment for only women, and 64% were conducted in the USA. Ninety-two articles (75%) described strategies in the context of sex-specific conditions (e.g., gynecologic diagnosis). The majority of included articles evaluated a behavioral intervention (52%), with 23% evaluating pharmacologic interventions and 4% invasive interventions. The most common trial phase for reported strategies was during outreach to potential participants (116 articles), followed by intervention delivery (76), enrollment (40), outcomes assessment (21), analysis and interpretation (3), and dissemination (4). We describe specific types of strategies within each of these phases. CONCLUSIONS: Most of the existing literature describing strategies to improve the inclusion of women draws from trials for sex-specific conditions and is largely related to outreach to potential participants. There is little information about how and if studies have attempted to proportionally increase the inclusion of women in trials with both men and women or those focused on invasive and pharmacologic interventions. Future work in this area should focus on how to increase the participation of women in mixed-sex studies and on those areas with remaining inequities in trial participation.

Hospital Admissions and Mortality in Patients With Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis.

BACKGROUND/OBJECTIVES: Anti-neutrophil cytoplasmic antibody-associated vasculitis has reported hospital mortality rates ranging between 10% and 20% with inadequate information regarding causes and outcomes of these hospitalizations. Characterization of outcomes in anti-neutrophil cytoplasmic antibody-associated vasculitis can improve patient care and prognostication following hospitalization. METHODS: A medical records review of all hospitalizations between October 1, 2015, and December 31, 2018, of adults with granulomatosis with polyangiitis or microscopic polyangiitis at a single academic medical center was performed. Chart review confirmed diagnoses in patients identified by International Classification of Diseases, Tenth Revision code. Vasculitis activity was determined based on clinical data and treatment during the hospitalization. Differences in outcome measures were analyzed using Fisher exact test, t test, and Wilcoxon signed-rank test. RESULTS: Of the 127 hospitalizations among 54 patients, active vasculitis was identified in 43 hospitalizations (33.9%). A total of 15 patients with active disease, including 10 patients with a new diagnosis, required intensive care unit (ICU)-level care. Of 84 hospitalizations when vasculitis was inactive, infection was diagnosed in 31 admissions (36.9%), with inactive disease representing 44% of all ICU admissions. Overall mortality was 7% for hospitalized patients and 15% for those admitted to the ICU. An additional 5 patients died within 28 days of discharge, for an overall mortality rate of 17%. All 4 hospital deaths and 3 of 5 postdischarge deaths were in the setting of known infection. CONCLUSION: Most hospitalizations and patient deaths were in the context of inactive vasculitis, with infection being the most common cause. Infection and ICU admission were associated with patient death.

Location of auxilin within a clathrin cage.

The Dna J homologue, auxilin, acts as a co-chaperone for Hsc70 in the uncoating of clathrin-coated vesicles during endocytosis. Biochemical studies have aided understanding of the uncoating mechanism but until now there was no structural information on how auxilin interacts with the clathrin cage. Here we have determined the three-dimensional structure of a complex of auxilin with clathrin cages by cryo-electron microscopy and single particle analysis. We show that auxilin forms a discrete shell of density on the inside of the clathrin cage. Peptide competition assays confirm that a candidate clathrin box motif in auxilin, LLGLE, can bind to a clathrin construct containing the beta-propeller domain and also displace the well-characterised LLNLD clathrin box motif derived from the beta-adaptin hinge region. The means by which auxilin could both aid clathrin coat assembly and displace clathrin from AP2 during uncoating is discussed.