Female urinary incontinence: A review

Urinary incontinence affects approximately a quarter of a billion people worldwide. It is associated with high economic costs, psychological morbidity and adverse effects on the quality of life. Despite this, few women seek help for this condition either due to embarrassment and unwillingness to discuss the symptom with their family member or friend or, acceptance of the disorder as a natural part of aging or being unaware that treatment exists. More resources are utilised in maintaining patients with chronic incontinence rather than for diagnosis and treatment of the condition. Urinary incontinence is a complex problem resulting from many different causes and for which many different approaches to treatment exist. The commonest types of incontinence include stress urinary incontinence, urge urinary incontinence and mixed incontinence. Recently, better understanding of the pathophysiology of urinary incontinence has led to the development of numerous non-pharmacological, pharmacological and surgical interventions. South African Family Practice Vol. 49 (6) 2007: pp. 34-3

Obstetric anal sphincter injury: a systematic review of information available on the internet.

OBJECTIVE: There is no systematic evaluation of online health information pertaining to obstetric anal sphincter injury. Therefore, we evaluated the accuracy, credibility, reliability, and readability of online information concerning obstetric anal sphincter injury. MATERIALS AND METHODS: Multiple search engines were searched. The first 30 webpages were identified for each keyword and considered eligible if they provided information regarding obstetric anal sphincter injury. Eligible webpages were assessed by two independent researchers for accuracy (prioritised criteria based upon the RCOG Third and Fourth Degree Tear guideline); credibility; reliability; and readability. RESULTS: Fifty-eight webpages were included. Seventeen webpages (30%) had obtained Health On the Net certification, or Information Standard approval and performed better than those without such approvals (p = 0.039). The best overall performing website was http://www.pat.nhs.uk (score of 146.7). A single webpage (1%) fulfilled the entire criteria for accuracy with a score of 18: www.tamesidehospital.nhs.uk . Twenty-nine webpages (50%) were assessed as credible (scores ≥7). A single webpage achieved a maximum credibility score of 10: www.meht.nhs.uk . Over a third (21 out of 58) were rated as poor or very poor. The highest scoring webpage was http://www.royalsurrey.nhs.uk (score 62). No webpage met the recommended Flesch Reading Ease Score above 70. The intra-class coefficient between researchers was 0.98 (95% CI 0.96-0.99) and 0.94 (95% CI 0.89-0.96) for accuracy and reliability assessments. CONCLUSION: Online information concerning obstetric anal sphincter injury often uses language that is inappropriate for a lay audience and lacks sufficient accuracy, credibility, and reliability

Treatment outcomes of new tuberculosis patients hospitalized in Kampala, Uganda: a prospective cohort study.

BACKGROUND: In most resource limited settings, new tuberculosis (TB) patients are usually treated as outpatients. We sought to investigate the reasons for hospitalisation and the predictors of poor treatment outcomes and mortality in a cohort of hospitalized new TB patients in Kampala, Uganda. METHODS AND FINDINGS: Ninety-six new TB patients hospitalised between 2003 and 2006 were enrolled and followed for two years. Thirty two were HIV-uninfected and 64 were HIV-infected. Among the HIV-uninfected, the commonest reasons for hospitalization were low Karnofsky score (47%) and need for diagnostic evaluation (25%). HIV-infected patients were commonly hospitalized due to low Karnofsky score (72%), concurrent illness (16%) and diagnostic evaluation (14%). Eleven HIV uninfected patients died (mortality rate 19.7 per 100 person-years) while 41 deaths occurred among the HIV-infected patients (mortality rate 46.9 per 100 person years). In all patients an unsuccessful treatment outcome (treatment failure, death during the treatment period or an unknown outcome) was associated with duration of TB symptoms, with the odds of an unsuccessful outcome decreasing with increasing duration. Among HIV-infected patients, an unsuccessful treatment outcome was also associated with male sex (P = 0.004) and age (P = 0.034). Low Karnofsky score (aHR = 8.93, 95% CI 1.88 - 42.40, P = 0.001) was the only factor significantly associated with mortality among the HIV-uninfected. Mortality among the HIV-infected was associated with the composite variable of CD4 and ART use, with patients with baseline CD4 below 200 cells/µL who were not on ART at a greater risk of death than those who were on ART, and low Karnofsky score (aHR = 2.02, 95% CI 1.02 - 4.01, P = 0.045). CONCLUSION: Poor health status is a common cause of hospitalisation for new TB patients. Mortality in this study was very high and associated with advanced HIV Disease and no use of ART

Rectal Transmission of Transmitted/Founder HIV-1 Is Efficiently Prevented by Topical 1% Tenofovir in BLT Humanized Mice

Rectal microbicides are being developed to prevent new HIV infections in both men and women. We focused our in vivo preclinical efficacy study on rectally-applied tenofovir. BLT humanized mice (n = 43) were rectally inoculated with either the primary isolate HIV-1(JRCSF) or the MSM-derived transmitted/founder (T/F) virus HIV-1(THRO) within 30 minutes following treatment with topical 1% tenofovir or vehicle. Under our experimental conditions, in the absence of drug treatment we observed 50% and 60% rectal transmission by HIV-1(JRCSF) and HIV-1(THRO), respectively. Topical tenofovir reduced rectal transmission to 8% (1/12; log rank p = 0.03) for HIV-1(JRCSF) and 0% (0/6; log rank p = 0.02) for HIV-1(THRO). This is the first demonstration that any human T/F HIV-1 rectally infects humanized mice and that transmission of the T/F virus can be efficiently blocked by rectally applied 1% tenofovir. These results obtained in BLT mice, along with recent ex vivo, Phase 1 trial and non-human primate reports, provide a critically important step forward in the development of tenofovir-based rectal microbicides

Assessing the implementation effectiveness and safety of 1% tenofovir gel provision through family planning services in KwaZulu-Natal, South Africa: study protocol for an open-label randomized controlled trial.

CAPRISA, 2014.Background: The Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004 trial demonstrated a 39% reduction in HIV infection, with a 54% HIV reduction in women who used tenofovir gel consistently. A confirmatory trial is expected to report results in early 2015. In the interim, we have a unique window of opportunity to prepare for and devise effective strategies for the future policy and programmatic scale-up of tenofovir gel provision. One approach is to integrate tenofovir gel provision into family planning (FP) services. The CAPRISA 008 implementation trial provides an opportunity to provide post-trial access to tenofovir gel while generating empiric evidence to assess whether integrating tenofovir gel provision into routine FP services can achieve similar levels of adherence as the CAPRISA 004 trial. Methods/design: This is a two-arm, open-label, randomized controlled non-inferiority trial. A maximum of 700 sexually active, HIV-uninfected women aged 18 years and older who previously participated in an antiretroviral prevention study will be enrolled from an urban and rural site in KwaZulu-Natal, South Africa. The anticipated study duration is 30 months, with active accrual requiring approximately 12 months (following which an open cohort will be maintained) and follow-up continuing for approximately 18 months. At each of the two sites, eligible participants will be randomly assigned to receive tenofovir gel through either FP services (intervention arm) or through the CAPRISA research clinics (control arm). As part of the study intervention, a quality improvement approach will be used to assist the FP services to expand their current services to include tenofovir gel provision. Discussion: This protocol aims to address an important implementation question on whether FP services are able to effectively incorporate tenofovir gel provision for this at-risk group of women in South Africa. Provision of tenofovir gel to the women from the CAPRISA 004 trial meets the ethical obligation for post-trial access, and helps identify a potential avenue for future scale-up of microbicides within the public health system of South Africa. Trial registration: This trial was registered with the South Africa Department of Health (reference: DOH-27-0812-4129) and ClinicalTrials.gov (reference: NCT01691768) on 05 July 2012

Outcome of anal symptoms and anorectal function following two obstetric anal sphincter injuries (OASIS)-a nested case-controlled study.

INTRODUCTION AND HYPOTHESIS: Obstetric anal sphincter injury (OASI) is a significant risk factor for developing anal incontinence. It can therefore be hypothesised that recurrent OASI in a subsequent delivery may predispose women to further anal sphincter dysfunction. METHODS: A nested case-controlled study based on data collected prospectively between 2006 and 2019. Women matched for age and ethnicity, with a history of one OASI and no sphincter damage in a subsequent delivery (control) were compared to women sustaining a second OASI. Assessment was carried out using the St Mark's score (SMIS), anorectal manometry and endoanal ultrasound scan (findings quantified using the modified Starck score). RESULTS: Eighty-four women were included and equally distributed between the two groups, who were followed up 12 weeks postnatally. No difference in SMIS scores was found. Maximum resting pressure (MRP, mmHg) and maximum squeeze pressure (MSP, mmHg) were significantly reduced in the study group. Median (IQR) MRP in the study group was 40.0 (31.3-54.0) versus 46.0 (39.3-61.5) in the control group (p = 0.030). Median (IQR) MSP was 73.0 (58.3-93.5) in the study group versus 92.5 (70.5-110.8) (p = 0.006) in the control group. A significant difference (p = 0.002) was found in the modified Starck score between the study group (median 0.0 [IQR 0.0-6.0]) and control group (median 0.0 [IQR 0.0-0.0]). CONCLUSIONS: We have demonstrated that women with recurrent OASI do not have significant anorectal symptoms compared to those with one OASI 12 weeks after delivery, but worse anal sphincter function and integrity. Therefore, on long-term follow-up, symptoms may possibly develop. This information will be useful when counselling women in a subsequent pregnancy

HIV-positive status disclosure in patients in care in rural South Africa: implications for scaling up treatment and prevention interventions.

CAPRISA, 2015Abstract available in pdf

Efficacy, Stability, and Biosafety of Sifuvirtide Gel as a Microbicide Candidate against HIV-1

Sifuvirtide is a proven effective HIV-1 entry inhibitor and its safety profile has been established for systemic administration. The present study evaluated the potential of sifuvirtide formulated in a universal gel for topical use as a microbicide candidate for preventing sexual transmission of HIV. Our data showed that sifuvirtide formulated in HEC gel is effective against HIV-1 B, C subtypes, CRF07_BC and CRF01_AE, the latter two recombinants represents the most prevalent strains in China. In addition, we demonstrated that sifuvirtide in gel is stable for at least 8 weeks even at 40°C, and did not cause the disruption of integrity of mucosal epithelial surface, or the up-regulation of inflammatory cytokines both in vitro or in vivo. These results suggest that sifuvirtide gel is an effective, safe and stable product, and should be further tested as a vaginal or rectal microbicide in pre-clinical model or clinical trial for preventing HIV sexual transmission

Vectored immunoprophylaxis protects humanized mice from mucosal HIV transmission

The vast majority of new HIV infections result from relatively inefficient transmission of the virus across mucosal surfaces during sexual intercourse. A consequence of this inefficiency is that small numbers of transmitted founder viruses initiate most heterosexual infections. This natural bottleneck to transmission has stimulated efforts to develop interventions that are aimed at blocking this step of the infection process. Despite the promise of this strategy, clinical trials of preexposure prophylaxis have had limited degrees of success in humans, in part because of lack of adherence to the recommended preexposure treatment regimens. In contrast, a number of existing vaccines elicit systemic immunity that protects against mucosal infections, such as the vaccines for influenza and human papilloma virus. We recently demonstrated the ability of vectored immunoprophylaxis (VIP) to prevent intravenous transmission of HIV in humanized mice using broadly neutralizing antibodies. Here we demonstrate that VIP is capable of protecting humanized mice from intravenous as well as vaginal challenge with diverse HIV strains despite repeated exposures. Moreover, animals receiving VIP that expresses a modified VRC07 antibody were completely resistant to repetitive intravaginal challenge by a heterosexually transmitted founder HIV strain, suggesting that VIP may be effective in preventing vaginal transmission of HIV between humans

A Topical Microbicide Gel Formulation of CCR5 Antagonist Maraviroc Prevents HIV-1 Vaginal Transmission in Humanized RAG-hu Mice

For prevention of HIV infection many currently licensed anti-HIV drugs and new ones in the pipeline show potential as topically applied microbicides. While macaque models have been the gold standard for in vivo microbicide testing, they are expensive and sufficient numbers are not available. Therefore, a small animal model that facilitates rapid evaluation of potential candidates for their preliminary efficacy is urgently needed in the microbicide field. We previously demonstrated that RAG-hu humanized mouse model permits HIV-1 mucosal transmission via both vaginal and rectal routes and that oral pre-exposure chemo-prophylactic strategies could be tested in this system. Here in these proof-of-concept studies, we extended this system for topical microbicide testing using HIV-1 as the challenge virus. Maraviroc, a clinically approved CCR5 inhibitor drug for HIV treatment, was formulated as a microbicide gel at 5 mM concentration in 2.2% hydroxyl ethyl cellulose. Female RAG-hu mice were challenged vaginally with HIV-1 an hour after intravaginal application of the maraviroc gel. Our results showed that maraviroc gel treated mice were fully protected against vaginal HIV-1 challenge in contrast to placebo gel treated mice which all became infected. These findings highlight the utility of the humanized mouse models for microbicide testing and, together with the recent data from macaque studies, suggest that maraviroc is a promising candidate for future microbicide clinical trials in the field