ABSTRACT
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.
Subject(s)
Circumcision, Male/adverse effects , Cutaneous Fistula/etiology , Postoperative Complications/etiology , Urethral Diseases/etiology , Urinary Fistula/etiology , Adolescent , Africa , Child , Cutaneous Fistula/epidemiology , HIV Infections/prevention & control , Humans , Male , Postoperative Complications/epidemiology , Retrospective Studies , Time Factors , Urethral Diseases/epidemiology , Urinary Fistula/epidemiologySubject(s)
HIV Infections/drug therapy , HIV Integrase Inhibitors/adverse effects , Heterocyclic Compounds, 3-Ring/adverse effects , Neural Tube Defects/chemically induced , Pregnancy Complications, Infectious/drug therapy , Botswana/epidemiology , Female , Fetus/drug effects , HIV Integrase Inhibitors/therapeutic use , Heterocyclic Compounds, 3-Ring/therapeutic use , Humans , Infant, Newborn , Neural Tube Defects/epidemiology , Oxazines , Piperazines , Population Surveillance , Pregnancy , Prevalence , PyridonesABSTRACT
A study has been made of the effects of pigeon pea starch obtained from the plant Cajanus cajan (L) Millisp. (family Fabaceae) and plantain starch obtained from the unripe fruit of Musa paradisiaca L. (family Musaceae) on the compressional, mechanical, and disintegration properties of paracetamol tablets in comparison with official corn starch BP. Analysis of compressional properties was done by using density measurements, and the Heckel and Kawakita equations, whereas the mechanical properties of the tablets were evaluated by using tensile strength (T--a measure of bond strength) and brittle fracture index (BFI--a measure of lamination tendency). The ranking for the mean yield pressure, P(y), for the formulations containing the different starches was generally corn < pigeon pea < plantain starch while the ranking for P(k), an inverse measure of the amount of plasticity, was pigeon pea < plantain < corn starch, which indicated that formulations containing corn starch generally exhibited the fastest onset of plastic deformation, whereas those formulations containing pigeon pea starch exhibited the highest amount of plastic deformation during tableting. The tensile strength of the tablets increased with increase in concentration of the starches while the Brittle Fracture Index decreased. The ranking for T was pigeon pea > plantain > corn starch while the ranking for BFI was corn > plantain > pigeon pea starch. The bonding capacity of the formulations was in general agreement with the tensile strength results. The disintegration time (DT) of the formulation increased with concentration of plantain and corn starches but decreased with concentration of pigeon pea starch. The general ranking of DT values was plantain < pigeon pea < corn starch. Notably, formulations containing pigeon pea starch exhibited the highest bond strength and lowest brittleness, suggesting the usefulness of pigeon pea starch in producing strong tablets with minimal lamination tendency. Plantain starch, on the other hand, would be more useful where faster disintegration of tablet is desired. The results show that the starches could be useful in various formulations depending on the intended use of the tablets with the implication that the experimental starches can be developed for commercial purposes.
