The aim of this study was to determine the extent to which adherence to individual vascular medications, assessed by different methods, influences the absolute and relative risks (RRs) of ...cardiovascular disease (CVD) and all-cause mortality.
We performed a systematic review and meta-analysis of prospective epidemiological studies (cohort, nested case-control, or clinical trial) identified through electronic searches using MEDLINE, Web of Science, EMBASE, and Cochrane databases, involving adult populations (≥ 18 years old) and reporting risk estimates of cardiovascular medication adherence with any CVD (defined as any fatal or non-fatal coronary heart disease, stroke or sudden cardiac death) and/or all-cause mortality (defined as mortality from any cause) outcomes. Relative risks were combined using random-effects models. Forty-four unique prospective studies comprising 1 978 919 non-overlapping participants, with 135 627 CVD events and 94 126 cases of all-cause mortality. Overall, 60% (95% CI: 52-68%) of included participants had good adherence (adherence ≥ 80%) to cardiovascular medications. The RRs (95% CI) of development of CVD in those with good vs. poor (<80%) adherence were 0.85 (0.81-0.89) and 0.81 (0.76-0.86) for statins and antihypertensive medications, respectively. Corresponding RRs of all-cause mortality were 0.55 (0.46-0.67) and 0.71 (0.64-0.78) for good adherence to statins and antihypertensive agents. These associations remained consistent across subgroups representing different study characteristics. Estimated absolute risk differences for any CVD associated with poor medication adherence were 13 cases for any vascular medication, 9 cases for statins and 13 cases for antihypertensive agents, per 100 000 individuals per year.
A substantial proportion of people do not adhere adequately to cardiovascular medications, and the prevalence of suboptimal adherence is similar across all individual CVD medications. Absolute and relative risk assessments demonstrate that a considerable proportion of all CVD events (~9% in Europe) could be attributed to poor adherence to vascular medications alone, and that the level of optimal adherence confers a significant inverse association with subsequent adverse outcomes. Measures to enhance adherence to help maximize the potentials of effective cardiac therapies in the clinical setting are urgently required.
Experience with delamanid (Dlm) is limited, particularly among HIV-positive individuals. We describe early efficacy and safety data from a programmatic setting in South Africa.This was a ...retrospective cohort study of patients receiving Dlm-containing treatment regimens between November 2015 and August 2017. We report 12-month interim outcomes, sputum culture conversion (SCC) by months 2 and 6, serious adverse events (SAEs) and QT intervals corrected using the Frederica formula (QTcF).Overall, 103 patients were initiated on Dlm; 79 (77%) were HIV positive. The main indication for Dlm was intolerance to second-line anti-tuberculosis (TB) drugs (n=58, 56%). There were 12 months of follow-up for 46 patients; 28 (61%) had a favourable outcome (cure, treatment completion or culture negativity). Positive cultures were found for 57 patients at Dlm initiation; 16 out of 31 (52%) had SCC within 2 months and 25 out of 31 (81%) within 6 months. There were 67 SAEs reported in 29 patients (28%). There were four instances of QTcF prolongation >500 ms in two patients (2%), leading to permanent discontinuation in one case; however, no cardiac arrhythmias occurred.This large cohort of difficult-to-treat patients receiving Dlm for rifampicin-resistant TB treatment in a programmatic setting with high HIV prevalence had favourable early treatment response and tolerated treatment well. Dlm should remain available, particularly for those who cannot be treated with conventional regimens or with limited treatment options.
HIV and TB programs have rapidly scaled-up over the past decade in Sub-Saharan Africa and uninterrupted supplies of those medicines are critical to their success. However, estimates of stock-outs are ...largely unknown. This survey aimed to estimate the extent of stock-outs of antiretroviral and TB medicines in public health facilities across South Africa, which has the world's largest antiretroviral treatment (ART) program and a rising multidrug-resistant TB epidemic.
We conducted a cross-sectional telephonic survey (October-December 2015) of public health facilities. Facilities were asked about the prevalence of stock-outs on the day of the survey and in the preceding three months, their duration and impact.
Nationwide, of 3547 eligible health facilities, 79% (2804) could be reached telephonically. 88% (2463) participated and 4% (93) were excluded as they did not provide ART or TB treatment. Of the 2370 included facilities, 20% (485) reported a stock-out of at least 1 ARV and/or TB-related medicine on the day of contact and 36% (864) during the three months prior to contact, ranging from 74% (163/220) of health facilities in Mpumalanga to 12% (32/261) in the Western Cape province. These 864 facilities reported 1475 individual stock-outs, with one to fourteen different medicines out of stock per facility. Information on impact was provided in 98% (1449/1475) of stock-outs: 25% (366) resulted in a high impact outcome, where patients left the facility without medicine or were provided with an incomplete regimen. Of the 757 stock-outs that were resolved 70% (527) lasted longer than one month.
There was a high prevalence of stock-outs nationwide. Large interprovincial differences in stock-out occurrence, duration, and impact suggest differences in provincial ability to prevent, mitigate and cope within the same framework. End-user monitoring of the supply chain by patients and civil society has the potential to increase transparency and complement public sector monitoring systems.
There is a paucity of Neisseria gonorrhoeae antimicrobial resistance data from resource-constrained settings because of the lack of diagnostic testing and limited scale of surveillance programs. This ...study aimed to determine the antimicrobial resistance profile of N. gonorrhoeae in the rural Eastern Cape province of South Africa.
Specimens for N. gonorrhoeae culture were obtained from men with urethral discharge and women with vaginal discharge attending primary health care facilities. Direct inoculation of the agar plates was performed followed by culture and drug susceptibility testing using the Etest at the laboratory. Whole-genome sequencing of the isolates was performed to identify resistance-determining variants.
One hundred N. gonorrhoeae isolates were obtained. Most strains were nonsusceptible to ciprofloxacin (76%), tetracycline (75%), and penicillin G (72%). The gyrA S91F mutation was present in 68 of 72 ciprofloxacin-resistant isolates (94%), with concurrent parC mutations in 47 of 68 (69%); gyrA I250M was the only mutation in 4 other resistant strains. One azithromycin-resistant isolate was identified with a minimal inhibitory concentration (MIC) of 8.0 mg/L and the 23S rDNA gene mutation C2597T. The median MIC of cefixime was 0.016 mg/L (range, 0.016-0.064 mg/L), and that of ceftriaxone was 0.016 mg/L (range, 0.016 mg/L). Whole-genome sequencing showed 58 sequence types as revealed in N. gonorrhoeae sequence typing for antimicrobial resistance and 70 sequence types in N. gonorrhoeae multiantigen sequence typing.
This study confirmed high rates of N. gonorrhoeae antimicrobial resistance to ciprofloxacin, penicillin G, and tetracycline in our setting. The MICs of cephalosporins are reassuring for ceftriaxone use in syndromic treatment regimens, but the identification of azithromycin resistance warrants further attention.
Reaching universal HIV-status awareness is crucial to ensure all HIV-infected patients access antiretroviral treatment (ART) and achieve virological suppression. Opportunities for HIV testing could ...be enhanced by offering self-testing in populations that fear stigma and discrimination when accessing conventional HIV Counselling and Testing (HCT) in health care facilities. This qualitative research aims to examine the feasibility and acceptability of unsupervised oral self-testing for home use in an informal settlement of South Africa. Eleven in-depth interviews, two couple interviews, and two focus group discussions were conducted with seven healthcare workers and thirteen community members. Thematic analysis was done concurrently with data collection. Acceptability to offer home self-testing was demonstrated in this research. Home self-testing might help this population overcome barriers to accepting HCT; this was particularly expressed in the male and youth groups. Nevertheless, pilot interventions must provide evidence of potential harm related to home self-testing, intensify efforts to offer quality counselling, and ensure linkage to HIV/ART-care following a positive self-test result.
Estimates for the prevalence of rape and other forms of sexual violence (SV) vary in South Africa. This survey aimed to provide clarity by quantifying the prevalence of SV (forced sex or sexual acts) ...by 1) sexual partners, and 2) non-partners, and to describe factors associated with these outcomes among women (18-49 years) living in Rustenburg Municipality.
We conducted a cluster-randomized household survey (November-December 2015). Women were asked about their experiences of SV, associated attitudes and behaviours, and access to services. Logistic regression was used to determine factors associated with partner and non-partner SV.
Of eligible households, 83·1% (1700/2044) participated. Of 966 women invited, 836 participated (86·5%). Average age of participants was 31.6 years (95%CI: 30·9, 32·4) with 45% having completed at least secondary school, and 60% unemployed or looking for work. Lifetime prevalence of SV was 24.9% (95%CI: 21·7-28·5), reaching 9.0% (95% CI: 6·6-12·1) by age 15. Almost one third told no one of their SV experiences. Factors related to financial dependence were associated with SV by a partner. History of termination of pregnancy increased the likelihood of SV by a non-partner as an adult. Women who experienced SV in childhood or as an adult were more likely to experience SV from a different type of perpetrator than those who did not.
We found a high prevalence of SV, including during childhood, in this setting, with limited access to care. This and the high morbidity attributed to SV calls for increased service provision.
Mother-to-Mother (M2M) or "Mentor Mother" programmes utilise HIV positive mothers to provide support and advice to HIV positive pregnant women and mothers of HIV exposed babies. Médecins Sans ...Frontières (MSF) supported a Mentor Mother programme in Bulawayo, Zimbabwe from 2009 to 2012; with programme beneficiaries observed to have far higher retention at 6-8 weeks (99% vs 50%, p<0.0005) and to have higher adherence to Prevention of Mother to Child Transmission (PMTCT) guidelines, compared to those not opting in. In this study we explore how the M2M progamme may have contributed to these findings.
In this qualitative study we used thematic analysis of in-depth interviews (n = 79). This study was conducted in 2 urban districts of Bulawayo, Zimbabwe's second largest city.
Interviews were completed by 14 mentor mothers, 10 mentor mother family members, 30 beneficiaries (women enrolled both in PMTCT and M2M), 10 beneficiary family members, 5 women enrolled in PMTCT but who had declined to take part in the M2M programme and 10 health care staff members. All beneficiaries and health care staff reported that the programme had improved retention and provided rich information on how this was achieved. Additionally respondents described how the programme had helped bring about beneficial behaviour change.
M2M programmes offer great potential to empower communities affected by HIV to catalyse positive behaviour change. Our results illustrate how M2M involvement may increase retention in PMTCT programmes. Non-disclosure to one's partner, as well as some cultural practices prevalent in Zimbabwe appear to be major barriers to participation in M2M programmes.
HIV self-testing (HIVST) offers a useful addition to HIV testing services and enables individuals to test privately. Despite recommendations to the contrary, repeat HIV testing is frequent among ...people already on anti-retroviral treatment (ART) and there are concerns that oral self-testing might lead to false negative results. A study was conducted in Khayelitsha, South Africa, to assess feasibility and uptake of HIVST and linkage-to-care following HIVST.
Participants were recruited at two health facilities from 1 March 2016 to 31 March 2017. People under 18 years, or with self-reported previously-diagnosed HIV infection, were excluded. Participants received an OraQuick Rapid HIV-1/2 Antibody kit, and reported their HIVST results by pre-paid text message (SMS) or by returning to the facility. Those not reporting within 7 days were contacted by phone. Electronic and paper-based clinical and laboratory records were retrospectively examined for all participants to identify known HIV outcomes, after matching for name, date of birth, and sex. These findings were compared with self-reported HIVST results where available.
Of 639 participants, 401 (62.8%) self-reported a negative HIVST result, 27 (4.2%) a positive result, and 211 (33.0%) did not report. The record search identified that of the 401 participants self-reporting a negative HIVST result, 19 (4.7%) were already known to be HIV positive; of the 27 self-reporting positive, 12 (44%) were known HIV positive. Overall, records showed 57/639 (8.9%) were HIV positive of whom 39/57 (68.4%) had previously-diagnosed infection and 18/57 (31.6%) newly-diagnosed infection. Of the 428 participants who self-reported a result, 366 (85.5%) reported by SMS.
HIVST can improve HIV testing uptake and linkage to care. SMS is acceptable for reporting HIVST results but negative self-reports by participants may be unreliable. Use of HIVST by individuals on ART is frequent despite recommendations to the contrary and its implications need further consideration.
Cryptococcal meningitis is one of the leading causes of death among people with HIV in Africa, primarily due to delayed presentation, poor availability and high cost of treatment. Routine ...cryptococcal antigen (CrAg) screening of patients with a CD4 count less than 100 cells/mm3, followed by pre-emptive therapy if positive, might reduce mortality in high prevalence settings. Using the cryptococcal antigen (CrAg) lateral flow assay (LFA), screening is possible at the point of care (POC). However, critical shortages of health staff may limit adoption. This study investigates the feasibility of lay counsellors conducting CrAg LFA screening in rural primary care clinics in Lesotho.
From May 2014 to June 2015, individuals who tested positive for HIV were tested for CD4 count and those with CD4 <100 cells/mm3 were screened with CrAg LFA. All tests were performed by lay counsellors. CrAg-positive asymptomatic patients received fluconazole, while symptomatic patients were referred to hospital. Lay counsellors were trained and supervised by a laboratory technician and counsellor activity supervisor. Additionally, nurses and doctors were trained on CrAg screening and appropriate treatment.
During the study period, 1,388 people were newly diagnosed with HIV, of whom 129 (9%) presented with a CD4 count <100 cells/mm3. Of these, 128 (99%) were screened with CrAg LFA and 14/128 (11%) tested positive. Twelve of the 14 (86%) were asymptomatic, and received outpatient fluconazole. All commenced ART with a median time to initiation of 15.5 days IQR: 14-22. Of the asymptomatic patients, nine (75%) remained asymptomatic after a median time of 5 months IQR; 3-6 of follow up. One (8%) became co-infected with tuberculosis and died and two were transferred out. The two patients with symptomatic cryptococcal meningitis (CM) were referred to hospital, where they later died.
CrAg LFA screening by lay counsellors followed by pre-emptive fluconazole treatment for asymptomatic cases, or referral to hospital for symptomatic cases, proved feasible. However, regular follow-up to ensure proper management of cryptococcal disease was needed. These early results support the wider use of CrAg LFA screening in remote primary care settings where upper cadres of healthcare staff may be in short supply.
A community based drug resistant tuberculosis (DR-TB) program has been incrementally implemented in Khayelitsha, a high HIV and TB burden community in South Africa. We investigated loss from ...treatment (LFT), and post treatment outcomes of DR-TB patients in this setting.
LFT, defined as interruption of treatment for ≥2 consecutive months was assessed among patients initiating DR-TB treatment for the first time between January 2009 and July 2011. Patients were traced through routine data sources to identify those who subsequently restarted treatment and those who died. Additional information on patient status and survival after LTF was obtained from community DR-TB counselors and from the national death registry. Post treatment outcomes were observed until July 2013.
Among 452 patients initiating treatment for the first time within the given period, 30% (136) were LFT, with 67% retention at 18 months. Treatment was restarted in 27 (20%) patients, with additional resistance recorded in 2/25 (8%), excluding two with presumed DR-TB. Overall, 34 (25%) patients died, including 11 who restarted treatment. Males and those in the age category 15-25 years had a greater hazard of LFT; HR 1.93 (95% CI 1.35-2.75), and 2.43 (95% CI 1.52-3.88) respectively. Older age (>35 years) was associated with a greater hazard of death; HR 3.74 (1.13- 12.37) post treatment. Overall two-year survival was 62%. It was lower (45%) in older patients, and was 92% among those who received >12 months treatment.
LFT was high, occurred throughout the treatment period and was particularly high among males and those aged 15-25 years. Overall long term survival was poor. High rates of LFT should however not preclude scale up of community based care given its impact in increasing access to treatment. Further research is needed to support retention of DR-TB patients on treatment, even within community based treatment programs.
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