Women's access to family planning and experiences of reproductive coercion during the COVID-19 lockdown in two districts of Uganda.

Background: In March 2020, Uganda enforced country-wide restrictions to control the spread of SARS-CoV-2, categorizing some health services, including family planning (FP), as non-essential. Globally, similar COVID-19 restrictions have been associated with increased vulnerability to reproductive coercion (RC) among women, due to changes in FP service availability and restricted access by partners. This study aims to investigate these dynamics in Uganda, specifically examining the impact of the COVID-19 lockdown on women's access to FP, their experiences of RC, and the relationship between RC and intimate partner violence (IPV). Methods: We conducted a cross-sectional analysis of data from 960 women participating in the AMBSO Population Health Surveillance Study (APHS) between August 2020 and March 2021 across Wakiso (N = 164) and Hoima (N = 796) districts in Uganda. Our analysis focused on women who were sexually active in the past month, using bivariate analyses to explore the associations between RC and recent experiences of sexual, physical, and verbal IPV. Findings: The most commonly reported FP methods were injectables (36.8 %) and implants (16 %). Despite the COVID-19 lockdown, less than one percent of participants reported an inability to access their preferred FP method. Notably, 3 % of the women experienced RC in the past 12 months. There was a significant association between RC and sexual IPV (p < 0.0001), as well as physical IPV (p < 0.0001). Instances of verbal IPV were observed to have tripled during the lockdown period. Interpretation: An increase in verbal IPV was found among women during the COVID-19 lockdown. Additionally, a notable association emerged between other forms of IPV and an increased risk of RC. Despite the lockdown, access to FP remained high, which could be attributed to the prevalent use of long-acting FP methods.

Prevalence and predictors of use of long-term and short-acting reversible contraceptives among women of reproductive age in Wakiso and Hoima districts, Uganda: A cross-sectional study.

Modern contraceptive use has increased globally, but unmet needs persist in low- and middle-income countries. This study in Uganda aimed to examine the prevalence and factors influencing the use of short-acting reversible contraceptives (SARC) like pills and long-term methods such as intrauterine devices. Limited evidence exists on the use of SARC and long-term methods in Uganda. Data from the Africa Medical and Behavioural Sciences Organization (AMBSO) Population Health Surveillance (APHS) in Hoima and Wakiso districts were analysed. Among the 1642 women aged 15-49 years, the prevalence of modern contraceptive use was 30% for SARC, and 18% for long-term method. Women with formal education were three times more likely to use long-term methods than those without formal education, relative risk ratios (RRR), 3.1-3.4, (95%CI 1.2-8.2). Joint decision-making for contraceptive use increased SARC usage, RRR 1.4 (95%CI 1.1-1.8). Urbanization played a role, with women in more urbanized Wakiso district less likely to use any modern contraception, RRR 0.6-0.7 (95%CI 0.5-0.9) compared to those living in the less urbanized Hoima. About half of the women in the study used modern contraceptives and the use of SARC was almost twice that of long-term methods. Increased access to contraception education for all women of reproductive age could significantly improve the use of long-term methods which offer more reliable protection against unintended pregnancies. The findings shed light on the need to strengthen both general and sexuality education to girls and women and to tailor contraception access for all in need, for mobile semi-urban as well as rural women. Well-informed strategies that engage young men and male partners in informed decision-making for contraceptive use could enhance progress.

Polygenic Risk Score Modifies Prostate Cancer Risk of Pathogenic Variants in Men of African Ancestry.

Prostate cancer risk is influenced by rare and common germline variants. We examined the aggregate association of rare germline pathogenic/likely pathogenic/deleterious (P/LP/D) variants in ATM, BRCA2, PALB2, and NBN with a polygenic risk score (PRS) on prostate cancer risk among 1,796 prostate cancer cases (222 metastatic) and 1,424 controls of African ancestry. Relative to P/LP/D non-carriers at average genetic risk (33%-66% of PRS), men with low (0%-33%) and high (66%-100%) PRS had Odds Ratios (ORs) for overall prostate cancer of 2.08 [95% confidence interval (CI) = 0.58-7.49] and 18.06 (95% CI = 4.24-76.84) among P/LP/D carriers and 0.57 (95% CI = 0.46-0.71) and 3.02 (95% CI = 2.53-3.60) among non-carriers, respectively. The OR for metastatic prostate cancer was 2.73 (95% CI = 0.24-30.54) and 28.99 (95% CI = 4.39-191.43) among P/LP/D carriers and 0.54 (95% CI = 0.31-0.95) and 3.22 (95% CI = 2.20-4.73) among non-carriers, for men with low and high PRS, respectively. Lifetime absolute risks of overall prostate cancer increased with PRS (low to high) from 9.8% to 51.5% in P/LP/D carriers and 5.5% to 23.9% in non-carriers. Lifetime absolute risks of metastatic prostate cancer increased with PRS from 1.9% to 18.1% in P/LP/D carriers and 0.3% to 2.2% in non-carriers These findings suggest that assessment of prostate cancer risk for rare variant carriers should include PRS status. SIGNIFICANCE: These findings highlight the importance of considering rare and common variants to comprehensively assess prostate cancer risk in men of African ancestry.

Heterogeneous genetic architectures and evolutionary genomics of prostate cancer in Sub-Saharan Africa.

Men of African descent have the highest prostate cancer (CaP) incidence and mortality rates, yet the genetic basis of CaP in African men has been understudied. We used genomic data from 3,963 CaP cases and 3,509 controls recruited in Ghana, Nigeria, Senegal, South Africa, and Uganda, to infer ancestry-specific genetic architectures and fine-mapped disease associations. Fifteen independent associations at 8q24.21, 6q22.1, and 11q13.3 reached genome-wide significance, including four novel associations. Intriguingly, multiple lead SNPs are private alleles, a pattern arising from recent mutations and the out-of-Africa bottleneck. These African-specific alleles contribute to haplotypes with odds ratios above 2.4. We found that the genetic architecture of CaP differs across Africa, with effect size differences contributing more to this heterogeneity than allele frequency differences. Population genetic analyses reveal that African CaP associations are largely governed by neutral evolution. Collectively, our findings emphasize the utility of conducting genetic studies that use diverse populations.

Timing for maximum anaesthetic effect of topical cream during early infant circumcision (EIC) in Rakai, Uganda.

Objectives: The objective of this study is to determine the optimal timing for device-based infant circumcision under topical anaesthesia. Subjects/patients: We include infants aged 1-60 days who were enrolled in a field study of the no-flip ShangRing device at four hospitals in the Rakai region of south-central Uganda, between 5 February 2020 and 27 October 2020. Methods: Two hundred infants, aged 0-60 days, were enrolled, and EMLA cream was applied on the foreskin and entire penile shaft. The anaesthetic effect was assessed every 5 min by gentle application of artery forceps at the tip of the foreskin, starting at 10 min post-application until 60 min, the recommended time to start circumcision. The response was measured using the Neonatal Infant Pain Scale (NIPS). We determined the onset and duration of anaesthesia (defined as <20% of infants with NIPS score >4) and maximum anaesthesia (defined as <20% of infants with NIPS score >2). Results: Overall, NIPS scores decreased to a minimum and reversed before the recommended 60 min. Baseline response varied with age, with minimal response among infants aged 40 days. Overall, anaesthesia was achieved after at least 25 min and lasted 20-30 min. Maximum anaesthesia was achieved after at least 30 min (except among those aged >45 days where it was not achieved) and lasted up to 10 min. Conclusion: The optimal timing for maximum topical anaesthesia occurred before the recommended 60 min of waiting time. A shorter waiting time and speed may be efficient for mass device-based circumcision.

Exploring the impact of COVID-19 on women's alcohol use, mental health, and experiences of intimate partner violence in Wakiso, Uganda.

INTRODUCTION: Uganda confirmed its first COVID-19 case in March 2020, leading to country-wide closures and a stay-at-home order. Infectious disease pandemics can overwhelm adaptive coping capacity (e.g., general self-efficacy and resilience) and increase the risk for mental distress. For individuals experiencing intimate partner violence (IPV) and cohabitating with a perpetrator, stay-at-home orders can also increase risk of violence, which can further exacerbate mental distress. The present study explores women's perceived self-efficacy and resilient coping, mental health outcomes (depression and COVID-19 related anxiety), hazardous alcohol use and IPV in the context of Uganda's national 2020 lockdown. METHODS: A phone-based survey was undertaken from June-August of 2020 in Wakiso District, Uganda. The study sample consisted of Africa Medical and Behavioral Sciences Organization (AMBSO) Population Health Surveillance (APHS) study participants who agreed to be contacted for future research. The analytic sample was restricted to women aged 13-80 years. Bivariate analysis and multivariable models explored associations between experiences of IPV and measures of adaptive coping, mental health and alcohol use. RESULTS: A total of 556 women aged 13-79 years (mean age of 33.4 years) participated. Over half (55%) were currently married. The majority (60%) reported a decrease in alcohol use during the lockdown. Nearly half of the sample were experiencing physical or verbal IPV and reported an increase in violence during the lockdown. In adjusted analysis, alcohol use was associated with four times greater odds of recent physical IPV (aOR 4.06, 95% CI = 1.65-10.02, p = 0.0024), while participants had lower odds of experiencing any form of IPV as general self-efficacy increased (aOR 0.95, 95% CI = 0.91-0.99, p = 0.0308). CONCLUSION: Lockdown measures in Uganda may have mitigated increased alcohol consumption. IPV was exacerbated during lockdown; more than 2 in 5 IPV victims experienced increased physical or verbal violence. Development of programming and policies aimed at mitigating women's risk of IPV during future lockdowns are needed.

Prostate cancer risk stratification improvement across multiple ancestries with new polygenic hazard score.

BACKGROUND: Prostate cancer risk stratification using single-nucleotide polymorphisms (SNPs) demonstrates considerable promise in men of European, Asian, and African genetic ancestries, but there is still need for increased accuracy. We evaluated whether including additional SNPs in a prostate cancer polygenic hazard score (PHS) would improve associations with clinically significant prostate cancer in multi-ancestry datasets. METHODS: In total, 299 SNPs previously associated with prostate cancer were evaluated for inclusion in a new PHS, using a LASSO-regularized Cox proportional hazards model in a training dataset of 72,181 men from the PRACTICAL Consortium. The PHS model was evaluated in four testing datasets: African ancestry, Asian ancestry, and two of European Ancestry-the Cohort of Swedish Men (COSM) and the ProtecT study. Hazard ratios (HRs) were estimated to compare men with high versus low PHS for association with clinically significant, with any, and with fatal prostate cancer. The impact of genetic risk stratification on the positive predictive value (PPV) of PSA testing for clinically significant prostate cancer was also measured. RESULTS: The final model (PHS290) had 290 SNPs with non-zero coefficients. Comparing, for example, the highest and lowest quintiles of PHS290, the hazard ratios (HRs) for clinically significant prostate cancer were 13.73 [95% CI: 12.43-15.16] in ProtecT, 7.07 [6.58-7.60] in African ancestry, 10.31 [9.58-11.11] in Asian ancestry, and 11.18 [10.34-12.09] in COSM. Similar results were seen for association with any and fatal prostate cancer. Without PHS stratification, the PPV of PSA testing for clinically significant prostate cancer in ProtecT was 0.12 (0.11-0.14). For the top 20% and top 5% of PHS290, the PPV of PSA testing was 0.19 (0.15-0.22) and 0.26 (0.19-0.33), respectively. CONCLUSIONS: We demonstrate better genetic risk stratification for clinically significant prostate cancer than prior versions of PHS in multi-ancestry datasets. This is promising for implementing precision-medicine approaches to prostate cancer screening decisions in diverse populations.

Household food insecurity and its association with self-reported male perpetration of intimate partner violence: a survey of two districts in central and western Uganda.

OBJECTIVES: This study aimed to determine the lifetime prevalence of male-perpetrated intimate partner violence (IPV), and to assess the association with food insecurity, sociodemographic factors and health risk behaviours in Uganda in the year preceding COVID-19-associated lockdowns. DESIGN: Population-based, cross-sectional household survey. SETTING: Urban, semiurban and rural communities of the Wakiso and Hoima districts in Uganda. PARTICIPANTS: A total of N=2014 males aged 13-80 years participated in the survey. The current study included males who reported having ever been in a sexual union and responded to the IPV questions (N=1314). MEASURES: Data were collected face-to-face from May 2018 to July 2019 using an interviewer-mediated questionnaire. Lifetime IPV perpetration was measured as 'no physical and/or sexual IPV', 'physical' versus 'sexual violence only', and 'physical and sexual violence'. Past-year food insecurity was measured through the Food Insecurity Experience Scale and categorised into 'none', 'low' and 'high'. Multinomial logistic regression was used to determine the crude and adjusted relative risk ratios (aRRRs) of IPV perpetration in relation to self-reported food insecurity, adjusting for sociodemographic and health risk behaviours. RESULTS: The prevalence of self-reported lifetime IPV perpetration was 14.6% for physical and 6.5% for sexual violence, while 5.3% reported to have perpetrated both physical and sexual IPV. Most (75.7%) males reported no food insecurity, followed by low (20.7%) and high (3.6%) food insecurity. In adjusted models, food insecurity was associated with increased risk of having perpetrated both physical and sexual violence (aRRR=2.57, 95% CI 1.52 to 4.32). IPV perpetration was also independently associated with having had more than one lifetime sexual partner and drinking alcohol, but not with education level or religion. CONCLUSION: This study suggests that food insecurity is associated with male IPV perpetration, and more efforts are needed to prevent and mitigate the expected worsening of this situation as a result of the COVID-19 pandemic.

Polygenic hazard score is associated with prostate cancer in multi-ethnic populations.

Genetic models for cancer have been evaluated using almost exclusively European data, which could exacerbate health disparities. A polygenic hazard score (PHS1) is associated with age at prostate cancer diagnosis and improves screening accuracy in Europeans. Here, we evaluate performance of PHS2 (PHS1, adapted for OncoArray) in a multi-ethnic dataset of 80,491 men (49,916 cases, 30,575 controls). PHS2 is associated with age at diagnosis of any and aggressive (Gleason score ≥ 7, stage T3-T4, PSA ≥ 10 ng/mL, or nodal/distant metastasis) cancer and prostate-cancer-specific death. Associations with cancer are significant within European (n = 71,856), Asian (n = 2,382), and African (n = 6,253) genetic ancestries (p < 10-180). Comparing the 80th/20th PHS2 percentiles, hazard ratios for prostate cancer, aggressive cancer, and prostate-cancer-specific death are 5.32, 5.88, and 5.68, respectively. Within European, Asian, and African ancestries, hazard ratios for prostate cancer are: 5.54, 4.49, and 2.54, respectively. PHS2 risk-stratifies men for any, aggressive, and fatal prostate cancer in a multi-ethnic dataset.

Not Enough Money and Too Many Thoughts: Exploring Perceptions of Mental Health in Two Ugandan Districts Through the Mental Health Literacy Framework.

Mental health disorders account for a heavy disease burden in Uganda. In order to provide culturally appropriate mental health prevention and treatment approaches, it is necessary to understand how mental health is conceptualized in the population. Three focus group discussions (FGDs) and 31 in-depth interviews (IDIs) were conducted with men and women aged 14 to 62 years residing in rural, urban, and semi-urban low-income communities in central and western Uganda to explore perceptions and knowledge of mental health. Interpretive thematic analysis was undertaken; results were organized through the lens of the mental health literacy framework. Environmental and societal stressors were identified as primary underlying causes of poor mental health. While participants recognized symptoms of poor mental health, gaps in mental health literacy also emerged. Mental health resources are needed in this setting and additional qualitative work assessing knowledge and attitudes toward mental health care seeking behavior can inform the development of acceptable integrated services.

Construct validity and internal consistency of the Patient Health Questionnaire-9 (PHQ-9) depression screening measure translated into two Ugandan languages.

BACKGROUND: In Uganda, depression is a major public health issue because of its direct disease burden and as a risk factor and co-morbidity for other pervasive health issues. Psychometric assessment of translated depression measures is critical to public health planning to ensure proper screening, surveillance, and treatment of depression and related outcomes. We examined aspects of the validity and reliability of the Patient Health Questionnaire-9 (PHQ-9) translated into Luganda and Runyoro in a large population-based cohort of Ugandan adolescents and adults. METHODS: Data from the ongoing open cohort AMBSO Population Health Surveillance study were analyzed from the Wakiso and Hoima districts in Uganda. Descriptive statistics were calculated for the overall sample and stratified by translated language. Construct validity was assessed for each translated scale using confirmatory factor analysis for ordinal data. The internal consistency of each translated scale was assessed using Cronbach's alpha, McDonald's omega total and omega hierarchical. RESULTS: Compared to the Runyoro-speaking subsample from Hoima (n=2297), participants in the Luganda-speaking subsample from Wakiso (n=672) were older (27 vs 21 years, p < 0.01) and a greater proportion were female (62% vs. 55%, p < 0.01). The Luganda-translated PHQ-9 had a sample mean of 3.46 (SD=3.26), supported a single-factor structure (RMSEA=0.05, CFI=0.96, TLI=0.94), and demonstrated satisfactory internal consistency (Cronbach's alpha=0.73, McDonald's omega total=0.76, McDonald's omega hierarchical=0.53). The Runyoro-translated PHQ-9 had a comparable sample mean of 3.58 (SD=3.00), also supported a one-factor structure (RMSEA=0.08, CFI=0.92, TLI=0.90), and demonstrated satisfactory internal consistency (Cronbach's alpha=0.72, McDonald's omega total=0.76, McDonald's omega hierarchical=0.57). CONCLUSIONS: Our preliminary findings indicate that the Luganda and Runyoro translations of the PHQ-9 had satisfactory construct validity and internal consistency in our sample of Ugandan adolescents and adults. Future studies should expand on this promising work by assessing additional psychometric characteristics of these translated measures in other communities in Uganda.

Pathogenic Variants in Cancer Predisposition Genes and Prostate Cancer Risk in Men of African Ancestry.

PURPOSE: In studies of men of European ancestry, rare pathogenic variants in DNA repair pathway genes have been shown to be associated with risk of aggressive prostate cancer. The contribution of rare coding variation to prostate cancer risk in men of African ancestry has not been established. METHODS: We sequenced a panel of 19 DNA repair and cancer predisposition genes in 2,453 African American and 1,151 Ugandan prostate cancer cases and controls. Rare variants were classified as pathogenic or putatively functionally disruptive and examined in association with prostate cancer risk and disease aggressiveness in gene and pathway-level association analyses. RESULTS: Pathogenic variants were found in 75 out of 2,098 cases (3.6%) and 31 out of 1,481 controls (2.1%) (OR=1.82, 95% CI=1.19 to 2.79, P=0.0044) with the association being stronger for more aggressive disease phenotypes (OR=3.10, 95% CI=1.54 to 6.23, P=0.0022). The highest risks for aggressive disease were observed with pathogenic variants in the ATM, BRCA2, PALB2 and NBN genes, with odds ratios ranging from ~4 to 15 in the combined study sample of African American and Ugandan men. Rare, non-pathogenic, non-synonymous variants did not have a major impact on risk of overall prostate cancer or disease aggressiveness. CONCLUSIONS: Rare pathogenic variants in DNA repair genes have appreciable effects on risk of aggressive prostate cancer in men of African ancestry. These findings have potential implications for panel testing and risk stratification in this high-risk population.

Determinants of occupational injuries among building construction workers in Kampala City, Uganda.

BACKGROUND: Globally, about 1000 people die and close to 860,000 people sustain injury at work daily. Injury prevention and control require contextual evidence, although most studies in Uganda have focused on general causes. Factors associated with occupational injuries among building construction workers were assessed in this study. METHODS: A cross-sectional study among building construction workers was conducted in Kampala, Uganda. A standardized semi-structured questionnaire was used to collect data. Three hundred nineteen (319) participants were randomly and proportionately selected from 57 construction sites. Descriptive statistics were used to describe the variables while generalized linear modeling was used to estimate the crude/adjusted prevalence ratios. RESULTS: The prevalence of occupational injuries was 32.4%. Most injuries, approximately 70% occurred among nightshift workers. Age of ≤24 years (APR: 2.09 CI: 1.20-3.65, P = 0.009); daily income in or above the second quartile-USD ≥3.2 (APR: 1.72, CI: 1.06-2.80, P = 0.028); job dissatisfaction (APR: 1.63, CI: 1.17-2.27, P = 0.004); job stress (APR: 1.72, CI: 1.22-2.41, P = 0.004); poor safety environment (APR: 1.51, CI: 1.10-2.05, P = 0.009); PPE provision (APR: 1.47, CI: 1.05-2.05, P = 0.02) and routine use of PPE (APR: 0.57, CI: 0.34-0.95, P = 0.03) were significantly associated with occupational injuries. CONCLUSION: There was a relatively high prevalence of injuries mostly resulting from cuts and mostly suffered on night duty. Upper and lower extremities were the most hurt parts of the body during injury leading to loss of a substantial number of productive days. This could affect the health and wellbeing of construction workers. Most of the factors significantly associated with occupational injuries are modifiable thus an opportunity to address the problem. Efforts towards integrating education for behaviour change, advocacy and training workers to demand for their rights to safe and protection at work and legislation enforcement can help reduce occupational injury occurrence.

Genetic risk of prostate cancer in Ugandan men.

BACKGROUND: Men of African-ancestry have elevated prostate cancer (PCa) incidence and mortality compared to men of other racial groups. There is support for a genetic contribution to this disparity, with evidence of genetic heterogeneity in the underlying risk alleles between populations. Studies of PCa among African men may inform the contribution of genetic risk factors to the elevated disease burden in this population. METHODS: We conducted an association study of >100 previously reported PCa risk alleles among 571 incidence cases and 485 controls among Uganda men. Unconditional logistic regression was used to test genetic associations and a polygenic risk score (PRS) was derived to assess the cumulative effect of the known risk alleles in association with PCa risk. In an exploratory analysis, we also tested associations of 17 125 421 genotyped and imputed markers genome-wide in association with PCa risk. RESULTS: Of the 111 known risk loci with a frequency >1%, 75 (68%) had effects that were directionally consistent with the initial discovery population,14 (13%) of which were nominally significantly associated with PCa risk at P < 0.05. Compared to men with average risk (25th -75th percentile in PRS distribution), Ugandan men in the top 10% of the PRS, constructed of alleles outside of 8q24, had a 2.9-fold (95%CI: 1.75, 4.97) risk of developing PCa; risk for the top 10% increased to 4.86 (95%CI: 2.70, 8.76) with the inclusion of risk alleles at 8q24. In genome-wide association testing, the strongest associations were noted with known risk alleles located in the 8q24 region, including rs72725854 (OR = 3.37, P = 2.14 × 10-11 ) that is limited to populations of African ancestry (6% frequency). CONCLUSIONS: The ∼100 known PCa risk variants were shown to effectively stratify PCa risk in Ugandan men, with 10% of men having a >4-fold increase in risk. The 8q24 risk region was also found to be a major contributor to PCa risk in Ugandan men, with the African ancestry-specific risk variant rs72725854 estimated to account for 12% of PCa in this population.

Prevalence of protective tetanus antibodies and immunological response following tetanus toxoid vaccination among men seeking medical circumcision services in Uganda.

INTRODUCTION: Tetanus infection associated with men who had male circumcision has been reported in East Africa, suggesting a need for tetanus toxoid-containing vaccines (TTCV). OBJECTIVE: To determine the prevalence of tetanus toxoid antibodies following vaccination among men seeking circumcision. METHODS: We enrolled 620 consenting men who completed a questionnaire and received TTCV at enrollment (day 0) prior to circumcision on day 28. Blood samples were obtained at day 0 from all enrollees and on days 14, 28 and 42 from a random sample of 237 participants. Tetanus toxoid (TT) IgG antibody levels were assayed using EUROIMMUN. Analyses included prevalence of TT antibodies at enrollment and used a mixed effects model to determine the immunological response. RESULTS: Mean age was 21.4 years, 65.2% had knowledge of tetanus, 56.6% knew how tetanus was contracted, 22.8% reported ever receipt of TTCV, and 16.8% had current/recently healed wounds. Insufficient tetanus immunity was 57.1% at enrollment, 7.2% at day 14, 3.8% at day 28, and 0% at day 42. Antibody concentration was 0.44IU/ml (CI 0.35-0.53) on day 0, 3.86IU/ml (CI 3.60-4.11) on day 14, 4.05IU/ml (CI 3.81-4.29) on day 28, and 4.48IU/ml (CI 4.28-4.68) on day 42. TT antibodies increased by 0.24IU/ml (CI 0.23, 0.26) between days 0 and 14 and by 0.023IU/ml (CI 0.015, 0.031) between days 14 and 42 days. Immunological response was poorer in HIV-infected clients and men aged 35+ years. CONCLUSION: Insufficient immunity was common prior to TTCV, and a protective immunological response was achieved by day 14. Circumcision may safely be provided 14 days after vaccination in HIV-uninfected men aged less than 35 years.

Efficacy of knowledge and competence-based training of non-physicians in the provision of early infant male circumcision using the Mogen clamp in Rakai, Uganda.

OBJECTIVE: To assess acquisition of knowledge and competence in performing Early Infant Male Circumcision (EIMC) by non-physicians trained using a structured curriculum. SUBJECTS AND METHODS: Training in provision of EIMC using the Mogen clamp was conducted for 10 Clinical Officers (COs) and 10 Registered Nurse Midwives (RNMWs), in Rakai, Uganda. Healthy infants whose mothers consented to study participation were assigned to the trainees, each of whom performed at least 10 EIMCs. Ongoing assessment and feedback for competency were done, and safety assessed by adverse events. RESULTS: Despite similar baseline knowledge, COs acquired more didactic knowledge than RNMWs (P = 0.043). In all, 100 EIMCs were assessed for gain in competency. The greatest improvement in competency was between the first and third procedures, and all trainees achieved 80% competency and retention of skills by the seventh procedure. The median (interquartile range) time to complete a procedure was 14.5 (10-47) min for the COs, and 15 (10-50) min for the RNMWs (P = 0.180). The procedure times declined by 2.2 min for each subsequent EIMC (P = 0.005), and rates of improvement were similar for COs and RNMWs. Adverse events were comparable between providers (3.5%), of which 1% were of moderate severity. CONCLUSION: Competence-based training of non-physicians improved knowledge and competency in EIMC performed by COs and RNMWs in Uganda.

Randomised trial of early infant circumcision performed by clinical officers and registered nurse midwives using the Mogen clamp in Rakai, Uganda.

OBJECTIVES: To assess the safety and acceptability of early infant circumcision (EIC) provided by trained clinical officers (COs) and registered nurse midwives (RNMWs) in rural Uganda. SUBJECTS AND METHODS: We conducted a randomised trial of EIC using the Mogen clamp provided by newly trained COs and RNMWs in four health centres in rural Rakai, Uganda. The trial was registered with clinicaltrials.gov # NCT02596282. In all, 501 healthy neonates aged 1-28 days with normal birth weight and gestational age were randomised to COs (n = 256) and RNMWs (n = 245) for EIC, and were followed-up at 1, 7 and 28 days. RESULTS: In all, 701 mothers were directly invited to participate in the trial, 525 consented to circumcision (74.9%) and 23 were found ineligible on screening (4.4%). The procedure took an average of 10.5 min. Adherence to follow-up was >90% at all scheduled visits. The rates of moderate/severe adverse events were 2.4% for COs and 1.6% for RNMWs (P = 0.9). All wounds were healed by 28 days after circumcision. Maternal satisfaction with the procedure was 99.6% for infants circumcised by COs and 100% among infants circumcised by RNMWs. CONCLUSIONS: EIC was acceptable in this rural Ugandan population and can be safely performed by RNMWs who have direct contact with the mothers during pregnancy and delivery. EIC services should be made available to parents who are interested in the service.

Postcoital penile washing and the risk of HIV acquisition in uncircumcised men.

BACKGROUND: Postcoital genital washing by uncircumcised men may affect the risk of male HIV acquisition. METHOD: We assessed the association between self-reported washing after sex in 2976 initially HIV-negative, uncircumcised men enrolled in a prospective cohort study in Rakai, Uganda. RESULTS: Data from the 2976 participants who reported sexual intercourse in the past 12 months contributed 4290 visits, with 7316.6 person-years of observation during the 2-year follow-up. The overall HIV-incidence was 1.28/100 person-years 95%CI (1.04-1.57). About 91.0% of men reported washing their penis after sex, and their HIV incidence was 1.34/100 person-years (95%CI 1.08-1.66), compared with an incidence of 0.62/100 person-years (95%CI 0.17-1.60) in men who did not wash their penis after intercourse. Using Poisson multivariable regression, the adjusted incidence rate ratio of HIV acquisition associated with postcoital washing was 1.94 (95%CI 0.71-5.29). CONCLUSION: Postcoital penile washing, as practiced in this rural African population does not afford protection from HIV acquisition among uncircumcised men, and may increase risk.

Whole-exome sequencing of over 4100 men of African ancestry and prostate cancer risk.

Prostate cancer is the most common non-skin cancer in males, with a ∼1.5-2-fold higher incidence in African American men when compared with whites. Epidemiologic evidence supports a large heritable contribution to prostate cancer, with over 100 susceptibility loci identified to date that can explain ∼33% of the familial risk. To explore the contribution of both rare and common variation in coding regions to prostate cancer risk, we sequenced the exomes of 2165 prostate cancer cases and 2034 controls of African ancestry at a mean coverage of 10.1×. We identified 395 220 coding variants down to 0.05% frequency [57% non-synonymous (NS), 42% synonymous and 1% gain or loss of stop codon or splice site variant] in 16 751 genes with the strongest associations observed in SPARCL1 on 4q22.1 (rs13051, Ala49Asp, OR = 0.78, P = 1.8 × 10(-6)) and PTPRR on 12q15 (rs73341069, Val239Ile, OR = 1.62, P = 2.5 × 10(-5)). In gene-level testing, the two most significant genes were C1orf100 (P = 2.2 × 10(-4)) and GORAB (P = 2.3 × 10(-4)). We did not observe exome-wide significant associations (after correcting for multiple hypothesis testing) in single variant or gene-level testing in the overall case-control or case-case analyses of disease aggressiveness. In this first whole-exome sequencing study of prostate cancer, our findings do not provide strong support for the hypothesis that NS coding variants down to 0.5-1.0% frequency have large effects on prostate cancer risk in men of African ancestry. Higher-coverage sequencing efforts in larger samples will be needed to study rarer variants with smaller effect sizes associated with prostate cancer risk.