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BACKGROUND: Women spend most of their reproductive years avoiding pregnancy. However, we know little about contraceptive knowledge and use among women with disabilities, or about strategies to improve contraceptive knowledge and decision-making in this population. OBJECTIVE: To systematically review published literature on women with disabilities and: 1) contraceptive knowledge; 2) attitudes and preferences regarding contraception; 3) contraceptive use; 4) barriers and facilitators to informed contraceptive use; and 5) effectiveness of interventions to improve informed contraceptive decision-making and use. METHODS: We searched MEDLINE, PsychINFO, the Cochrane Library, CINAHL, and ERIC databases from inception through December 2017. Two reviewers independently reviewed studies for eligibility, abstracted study data, and assessed risk of bias following PRISMA guidance. RESULTS: We reviewed 11,659 citations to identify 62 publications of 54 unique studies (total n of women with disabilities = 21,246). No standard definition of disability existed across studies. The majority of studies focused on women with intellectual disabilities (ID). Women with ID and those who were deaf or hard-of-hearing had lower knowledge of contraceptive methods than women without disabilities. Estimates of contraceptive use varied widely, with some evidence that women with disabilities may use a narrower range of methods. Five of six studies evaluating educational interventions to increase contraceptive knowledge or use reported post-intervention improvements. CONCLUSIONS: Women with disabilities may use a more narrow mix of contraceptive methods and are often less knowledgeable about contraceptives than women without disabilities. Interventions to improve knowledge show some promise. A lack of data exists on contraceptive preferences among women with disabilities.

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BACKGROUND: Increases in patient needs can strain hospital resources, which may worsen care quality and outcomes. This systematic literature review sought to understand whether hospital capacity strain is associated with worse health outcomes for hospitalized patients and to evaluate benefits and harms of health system interventions to improve care quality during times of hospital capacity strain. METHODS: Parallel searches were conducted in MEDLINE, CINAHL, the Cochrane Library, and reference lists from 1999-2015. Two reviewers assessed study eligibility. We included English-language studies describing the association between capacity strain (high census, acuity, turnover, or an indirect measure of strain such as delayed admission) and health outcomes or intermediate outcomes for children and adults hospitalized in highly developed countries. We also included studies of health system interventions to improve care during times of capacity strain. Two reviewers extracted data and assessed risk of bias using the Newcastle-Ottawa Score for observational studies and the Cochrane Collaboration Risk of Bias Assessment Tool for experimental studies. RESULTS: Of 5,702 potentially relevant studies, we included 44 observational and 8 experimental studies. There was marked heterogeneity in the metrics used to define capacity strain, hospital settings, and overall study quality. Mortality increased during times of capacity strain in 18 of 30 studies and in 9 of 12 studies in intensive care unit settings. No experimental studies were randomized, and none demonstrated an improvement in health outcomes after implementing the intervention. The pediatric literature is very limited; only six observational studies included children. There was insufficient study homogeneity to perform meta-analyses. DISCUSSION: In highly developed countries, hospital capacity strain is associated with increased mortality and worsened health outcomes. Evidence-based solutions to improve outcomes during times of capacity strain are needed.

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The human type 1 (placenta, breast tumors) and type 2 (gonads, adrenals) isoforms of 3beta-hydroxysteroid dehydrogenase/isomerase (3beta-HSD) are key enzymes in steroidogenic pathways leading to the production of all active steroid hormones. Kinetic analyses of purified 3beta-HSD1 show that the Michaelis-Menten constants (Km) for substrates and cofactor are decreased dramatically (three- to eight-fold) by the addition of beta-mercaptoethanol (BME), which suggest that a disulfide bond may be critical to ligand utilization. Western immunoblots and SDS-PAGE of purified 3beta-HSD1 in the presence or absence of BME showed a lack of intersubunit disulfide bonds in the dimeric enzyme. The Rossmann-fold domain of 3beta-HSD1 contains two Cys residues, Cys72 and Cys111, which are capable of forming an intrasubunit disulfide bond based on their proximity in our structural model. Our structural model also predicts that Cys83 may affect the orientation of substrate and cofactor. To test these predictions, the C72S, C72F, C111S, C111A, C83S and C83A mutants of 3beta-HSD1 were produced, expressed, and purified. BME failed to diminish the Km values of substrate and cofactor for C72S, C72F, C111S and C111A but produced a 2.5 decrease in Km values for C83A ligands similar to wild-type 3beta-HSD. Thus, our results support the presence of an intrasubunit disulfide bond between Cys72 and Cys111 that participates in the tertiary structure of the Rossmann-fold domain. Although C83S had no enzyme activity, the C83A mutant enzyme exhibited two- to five-fold higher Km values for substrate and cofactor but had similar K(cat) values compared to wild-type 3beta-HSD. These data characterize the roles of Cys residues in 3beta-HSD and validate the predictions of our structural model.

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