Urethrocutaneous fistulas after voluntary medical male circumcision for HIV prevention-15 African Countries, 2015-2019.

BACKGROUND: Voluntary medical male circumcision (VMMC) is an HIV prevention strategy recommended to partially protect men from heterosexually acquired HIV. From 2015 to 2019, the President's Emergency Plan for AIDS Relief (PEPFAR) has supported approximately 14.9 million VMMCs in 15 African countries. Urethrocutaneous fistulas, abnormal openings between the urethra and penile skin through which urine can escape, are rare, severe adverse events (AEs) that can occur with VMMC. This analysis describes fistula cases, identifies possible risks and mechanisms of injury, and offers mitigation actions. METHODS: Demographic and clinical program data were reviewed from all reported fistula cases during 2015 to 2019, descriptive analyses were performed, and an odds ratio was calculated by patient age group. RESULTS: In total, 41 fistula cases were reported. Median patient age for fistula cases was 11 years and 40/41 (98%) occurred in patients aged < 15 years. Fistulas were more often reported among patients < 15 compared to ≥ 15 years old (0.61 vs. 0.01 fistulas per 100,000 VMMCs, odds ratio 50.9 (95% confidence interval [CI] = 8.6-2060.0)). Median time from VMMC surgery to appearance of fistula was 20 days (interquartile range (IQR) 14-27). CONCLUSIONS: Urethral fistulas were significantly more common in patients under age 15 years. Thinner tissue overlying the urethra in immature genitalia may predispose boys to injury. The delay between procedure and symptom onset of 2-3 weeks indicates partial thickness injury or suture violation of the urethral wall as more likely mechanisms of injury than intra-operative urethral transection. This analysis helped to inform PEPFAR's recent decision to change VMMC eligibility policy in 2020, raising the minimum age to 15 years.

Innovative Methods of Male Circumcision for HIV Prevention-Getting the Right Evidence.

World Health Organization recommends that countries with hyperendemic and generalized HIV epidemics implement voluntary medical male circumcision programs for HIV prevention. Innovative methods of male circumcision including devices have the potential to simplify the procedure, reduce time and cost, increase client acceptability, enhance safety, and expand the numbers of providers who may perform circumcision. We describe work led by World Health Organization and supported by global partners to define a pathway for the evaluation of efficacy and safety of male circumcision devices, to set priority criteria, and to establish a process to guide the use of devices in publicly funded voluntary medical male circumcision programs for HIV prevention. A device classification scheme, an expert Technical Advisory Group on Innovations in Male Circumcision, and a formal prequalification program have also guided considerations on safe use of devices. A rigorous approach was deemed appropriate given the intervention is for use among healthy men for public health purposes. The pathway and processes led to coordinated research, better standardization in research outcomes, and guidance that informed the research, introduction and implementation phases. The lessons learnt from this case study can inform evaluation and use of future public health innovations.

The economic impact of using alfuzosin 10 mg once daily in the management of acute urinary retention in the UK: a 6-month analysis.

OBJECTIVE: To calculate the economic consequences of using alfuzosin 10 mg once daily for managing acute urinary retention (AUR) related to benign prostatic hyperplasia (BPH). METHODS: We examined whether alfuzosin use during hospitalization for AUR and for 6 months after a successful trial without catheter (TWOC) is cost effective compared to placebo and immediate prostatectomy, from the perspective of patients managed in the National Health Service (NHS) in the UK. A decision-analysis model was developed to estimate the costs of various treatment options within the first 6 months after a first episode of AUR. Clinical data were obtained from a large randomized clinical trial comparing alfuzosin 10 mg with placebo, and from published reports. Cost data were obtained from both NHS and resource-use data gathered during the clinical trial. A Monte Carlo analysis, allowing variability in all uncertain variables of the model, was used to calculate the uncertainty surrounding the results. RESULTS: Treating patients with alfuzosin during initial hospitalization for AUR and in the first 6 months after a successful TWOC generates a cost-saving of pounds 349 relative to placebo. Savings related to immediate prostatectomy were pounds 892; both savings were significant (P < 0.05). Alfuzosin treatment was associated with a lower rate of prostatectomy after discharge from hospital after a successful TWOC. CONCLUSION: Treatment with alfuzosin 10 mg once daily before and after a successful TWOC has both clinical and economic benefits. It decreases the need for emergency surgery for BPH and reduces treatment costs in the first 6 months.

Acute urinary retention in men: the risks and outcomes with medical therapy.

This paper is restricted to the discussion of the relatively modern disorder of sudden painful inability to urinate in older men. It was not a common medical problem until the 19th century when, in developed countries, male life expectancy increased to beyond 60 years; it remains an uncommon problem in those developing countries where male life expectancy remains low, particularly in some sub-Saharan African countries where male life expectancy is only 44.8 years.

A prevalent POLG CAG microsatellite length allele in humans and African great apes.

The human nuclear gene for the catalytic subunit of mitochondrial DNA polymerase gamma ( POLG) contains within its coding region a CAG microsatellite encoding a polyglutamine repeat. Previous studies demonstrated an association between length variation at this repeat and male infertility, suggesting a mechanism whereby the prevalent (CAG)(10) allele, which occurs at a frequency of >80% in different populations, could be maintained by selection. Sequence analysis of the POLG CAG microsatellite region of more than 1000 human chromosomes reveals that virtually all allelic variation at the locus is accounted for by length variation of the CAG repeat. Analysis of POLG from African great apes shows that a prevalent length allele is present in each species, although its exact length is species-specific. In common chimpanzee ( Pan troglodytes) a number of different sequence variants contribute to the prevalent length allele, strongly supporting the idea that the length of the POLG microsatellite region, rather than its exact nucleotide or amino acid sequence, is what is maintained. Analysis of POLG in other primates indicates that the repeat has expanded from a shorter, glutamine-rich sequence, present in the common ancestor of Old and New World monkeys.