Primary Care-Relevant Interventions for Tobacco and Nicotine Use Prevention and Cessation in Children and Adolescents: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Interventions to discourage the use of tobacco products (including electronic nicotine delivery systems or e-cigarettes) among children and adolescents may help decrease tobacco-related illness and injury. Objective: To update the 2013 review on primary care-relevant interventions for tobacco use prevention and cessation in children and adolescents to inform the US Preventive Services Task Force. Data Sources: The Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews, MEDLINE, PsyINFO, and EMBASE (September 1, 2012, to June 25, 2019), with surveillance through February 7, 2020. Study Selection: Primary care-relevant studies; randomized clinical trials and nonrandomized controlled intervention studies of children and adolescents up to age 18 years for cessation and age 25 years for prevention. Trials comparing behavioral or pharmacological interventions with no or a minimal tobacco use intervention control group (eg, usual care, attention control, wait list) were included. Data Extraction and Synthesis: One investigator abstracted data and a second investigator checked data abstraction for accuracy. Two investigators independently assessed study quality. Studies were pooled using random-effects meta-analysis. Main Outcomes and Measures: Tobacco use initiation; tobacco use cessation; health outcomes; harms. Results: Twenty-four randomized clinical trials (N = 44 521) met inclusion criteria. Behavioral interventions were associated with decreased likelihood of cigarette smoking initiation compared with control interventions at 7 to 36 months' follow-up (13 trials, n = 21 700; 7.4% vs 9.2%; relative risk [RR], 0.82 [95% CI, 0.73-0.92]). There was no statistically significant difference between behavioral interventions and controls in smoking cessation when trials were restricted to smokers (9 trials, n = 2516; 80.7% vs 84.1% continued smoking; RR, 0.97 [95% CI, 0.93-1.01]). There were no significant benefits of medication on likelihood of smoking cessation in 2 trials of bupropion at 26 weeks (n = 523; 17% [300 mg] and 6% [150 mg] vs 10% [placebo]; 24% [150 mg] vs 28% [placebo]) and 1 trial of nicotine replacement therapy at 12 months (n = 257; 8.1% vs 8.2%). One trial each (n = 2586 and n = 1645) found no beneficial intervention effect on health outcomes or on adult smoking. No trials of prevention in young adults were identified. Few trials addressed prevention or cessation of tobacco products other than cigarettes; no trials evaluated effects of interventions on e-cigarette use. There were few trials of pharmacotherapy, and they had small sample sizes. Conclusions and Relevance: Behavioral interventions may reduce the likelihood of smoking initiation in nonsmoking children and adolescents. Research is needed to identify effective behavioral interventions for adolescents who smoke cigarettes or who use other tobacco products and to understand the effectiveness of pharmacotherapy.

Contraceptive knowledge and use among women with intellectual, physical, or sensory disabilities: A systematic review.

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.

The Association Between Hospital Capacity Strain and Inpatient Outcomes in Highly Developed Countries: A Systematic Review.

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.

Structure/function of human type 1 3beta-hydroxysteroid dehydrogenase: An intrasubunit disulfide bond in the Rossmann-fold domain and a Cys residue in the active site are critical for substrate and coenzyme utilization.

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.