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Preclinical contraceptive development for men and women.

ABSTRACT: This manuscript endeavors to present research considerations for the preclinical development of non-hormonal contraceptives. Topics include (1) how advances in genomics and bioinformatics impact the identification of novel targets for non-hormonal contraception, (2) the importance of target validation prior to investment in a contraceptive development campaign, (3) considerations on targeting gametogenesis vs gamete maturation/function, (4) how targets from the male reproductive system are expanding women's options for 'on demand' contraception, and (5) some emerging non-hormonal methods that are not based on a specific molecular target. Also presented are ideas for developing a pipeline of non-hypothalamic-pituitary-gonadal-acting contraceptives for men and women while balancing risk and innovation, and our perspective on the pros and cons of industry and academic environments on contraceptive development. Three product development programs are highlighted that are biologically interesting, innovative, and likely to influence the field of contraceptive development in years to come.

SUBMITTER: Johnston DS

PROVIDER: S-EPMC7496738 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Preclinical contraceptive development for men and women.

Johnston Daniel S DS Goldberg Erwin E

Biology of reproduction 20200801 2

This manuscript endeavors to present research considerations for the preclinical development of non-hormonal contraceptives. Topics include (1) how advances in genomics and bioinformatics impact the identification of novel targets for non-hormonal contraception, (2) the importance of target validation prior to investment in a contraceptive development campaign, (3) considerations on targeting gametogenesis vs gamete maturation/function, (4) how targets from the male reproductive system are expan ...[more]

PMID: 32561907

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Project description:ObjectivesDespite substantial and rapid improvements in contraceptive uptake in Uganda, many women continue to have unmet need for contraception. As factors affecting contraceptive use are dynamic and complex, this study seeks to identify current predictors and provide effect size estimates of contraceptive use among women and men in Uganda.Study designA nationally representative cross-sectional population survey, using secondary data from Uganda's 2016 Demographic and Health Survey. Stratified by sex, weighted bivariable and multivariable logistic regression models were derived from a suite of potential predictor variables. Predictive abilities were assessed via 10-fold cross-validated area under the receiver operating characteristic curves (AUCs).SettingUganda.ParticipantsAll women aged 15-49 years who were permanent residents of the selected households or stayed in the household the night before the survey were eligible to participate. In one-third of the sampled households, all men aged 15-54 years who met the same residence criteria were also eligible.Primary outcome measuresModern contraceptive use.ResultsOverall, 4914 (26.6%) women and 1897 (35.6%) men reported using a modern contraceptive method. For women and men, both demographic and proximate variables were significantly associated with contraceptive use, although notable differences in effect sizes existed between sexes-especially for age, level of education and parity. Predictively, the multivariable model was acceptable for women with AUC=0.714 (95% CI 0.704 to 0.720) but less so for men with AUC=0.654 (95% CI 0.636 to 0.666).ConclusionsContemporary significant predictors of contraceptive use among women and men were reported, thereby enabling key Ugandan subpopulations who would benefit from more targeted family planning initiatives to be identified. However, the acceptable AUC for women and modest AUC for men suggest that other important unmeasured predictors may exist. Nonetheless, these evidence-based findings remain important for informing future programmatic and policy directions for family planning in Uganda.

Project description:BackgroundResearch on contraceptive behaviour changes over time in Uganda is scarce, yet it has among the highest fertility and maternal mortality rates of any country in the East African region. Understanding temporal patterns of contraceptive use for both women and men is vital in evaluating the effectiveness of family planning interventions and strategies, and identifying those with the most unmet need. Using repeated nationally representative cross-sectional samples, this study charts the changes in Uganda's population-based contraceptive use over recent years.MethodsFive Demographic and Health Survey datasets for Uganda over 21 years, from 1995 to 2016, were sourced and interrogated. Eligible participants included all women aged 15-49 years and men aged 15-54 years. Responses to questions on modern and any (modern or traditional) contraceptive use were analysed. Stratified by gender, weighted regression analyses were employed to detect change over time. The patterns associated with key demographic variables were also investigated.ResultsOverall, 50,027 women and 14,092 men were included within the study. In 2016, 30.3% of women and 39.9% of men were using any contraceptive method, a significant non-linear increase from 13.4% of women and 20.3% of men in 1995. Furthermore, 27.3% of women and 35.9% of men were using modern contraceptive methods in 2016, an increase from 7.4% of women and 10.4% of men in 1995. All considered demographic variables were significantly associated with contraceptive use for both women and men (all P<0.001); and for women, all variables differentially changed over time (all P<0.001).ConclusionThis study showed a significant increase and dynamism across key demographic variables in contraceptive uptake by both women and men. Sustained family planning programs and interventions have successfully resulted in behaviour change across the Ugandan population. However, continued efforts are needed to further reduce Uganda's relatively high fertility and associated maternal mortality rates.

Project description:ImportanceMany early-career surgeons struggle to develop their clinical practices, leading to high rates of burnout and attrition. Furthermore, women in surgery receive fewer, less complex, and less remunerative referrals compared with men. An enhanced understanding of the social and structural barriers to optimal growth and equity in clinical practice development is fundamental to guiding interventions to support academic surgeons.ObjectiveTo identify the barriers and facilitators to clinical practice development with attention to differences related to surgeon gender.Design, setting, and participantsA multi-institutional qualitative descriptive study was performed using semistructured interviews analyzed with a grounded theory approach. Interviews were conducted at 5 academic medical centers in the US between July 12, 2022, and January 31, 2023. Surgeons with at least 1 year of independent practice experience were selected using purposeful sampling to obtain a representative sample by gender, specialty, academic rank, and years of experience.Main outcomes and measuresSurgeon perspectives on external barriers and facilitators of clinical practice development and strategies to support practice development for new academic surgeons.ResultsA total of 45 surgeons were interviewed (23 women [51%], 18 with ≤5 years of experience [40%], and 20 with ≥10 years of experience [44%]). Surgeons reported barriers and facilitators related to their colleagues, department, institution, and environment. Dominant themes for both genders were related to competition, case distribution among partners, resource allocation, and geographic market saturation. Women surgeons reported additional challenges related to gender-based discrimination (exclusion, questioning of expertise, role misidentification, salary disparities, and unequal resource allocation) and additional demands (related to appearance, self-advocacy, and nonoperative patient care). Gender concordance with patients and referring physicians was a facilitator of practice development for women. Surgeons suggested several strategies for their colleagues, department, and institution to improve practice development by amplifying facilitators and promoting objectivity and transparency in resource allocation and referrals.Conclusions and relevanceThe findings of this qualitative study suggest that a surgeon's external context has a substantial influence on their practice development. Academic institutions and departments of surgery may consider the influence of their structures and policies on early career surgeons to accelerate practice development and workplace equity.

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Preclinical contraceptive development for men and women.

Publications

Preclinical contraceptive development for men and women.

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