Acceptability, feasibility and cost of point of care testing for sexually transmitted infections among South African adolescents where syndromic management is standard of care.

BACKGROUND: Young people (YP) in southern Africa are at substantial risk of HIV and sexually transmitted infections (STIs). Despite the epidemiological and biological link between STIs and HIV transmission and acquisition, infections such as Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) remain widely undiagnosed. Syndromic STI management is the standard of care in low- and middle-income countries (LMICs) despite a high prevalence of asymptomatic infections. We conducted an observational study to explore the acceptability, feasibility, and cost of a STI test-and-treat service for YP in Cape Town. METHODS: YP attending a mobile clinic (MC) and a youth centre clinic (YC) were offered STI screening. Urine testing for CT and NG using a 90-min molecular point-of-care (POC) test on the GeneXpert platform was conducted and treatment provided. Data were collated on demographics, sexual behaviour, presence of symptoms, uptake of same-day treatment, prevalence of CT/NG, and service acceptability. RESULTS: Three hundred sixty six participants were enrolled (median age 20, 83% female).57% (209/366) of participants tested positive for either CT (126/366, 34%) or NG (57/366, 16%) or co-infection (26/366, 7%). Clinical symptoms were a poor predictor of GeneXpert diagnosed CT or NG, with a sensitivity of 46.8% and 54.0% for CT and NG respectively. Although half of participants initially chose to receive same day results and treatment, only a third waited for results on the day. The majority of participants (91%) rated the service highly via a post-visit acceptability questionnaire. CONCLUSION: Curable STIs are highly prevalent in this population. STI screening using POC testing was feasible and acceptability was high. The study provides further impetus for moving policy beyond syndromic management of STIs in South Africa.

Elements in muscle tissue of three dolphin species from the east coast of South Africa.

We investigated elemental concentrations in muscle tissue of three species of dolphins incidentally bycaught off the KwaZulu-Natal coastline, South Africa. Thirty-six major, minor and trace elements were analysed in Indian Ocean humpback dolphin Sousa plumbea (n = 36), Indo-Pacific bottlenose dolphin Tursiops aduncus (n = 32) and the Common dolphin Delphinus delphis (n = 8). Significant differences in concentration between the three species were observed for 11 elements (cadmium, iron, manganese, sodium, platinum, antimony, selenium, strontium, uranium, vanadium and zinc). Mercury concentrations (maximum 29 mg/kg dry mass) were generally higher than those reported for coastal dolphin species found elsewhere. Our results reflect a combination of species differences in habitat, feeding ecology, age, and possibly species physiology and exposure to pollution levels. This study confirms the high organic pollutant concentrations documented previously for these species from the same location, and provides a well-founded case for the need to reduce pollutant sources.

Clinical impact of plasma concentrations of first-line antituberculosis drugs.

BACKGROUND: The clinical significance of low antituberculosis (anti-TB) drug concentrations has not been fully elucidated. OBJECTIVES: To investigate the clinical consequences of first-line drug concentrations in adult patients with drug-susceptible pulmonary TBin South Africa (SA). METHOD: We conducted a pharmacokinetic study nested within the control arm of the Improving Treatment Success (IMPRESS) trial(NCT02114684) in Durban, SA. During the first 2 months of treatment, participants received weight-based dosing of first-line anti-TBdrugs (rifampicin, isoniazid, pyrazinamide and ethambutol), and had plasma drug concentrations measured at 2 and 6 hours after drugadministration during the 8th week of treatment. Intermediate (8 weeks), end-of-treatment (6 months) and follow-up TB outcomes wereassessed using World Health Organization criteria. RESULTS: We measured plasma drug concentrations on available samples in 43 participants. Peak drug concentrations were below thetherapeutic range in 39/43 (90.7%) for rifampicin, 32/43 (74.4%) for isoniazid, 27/42 (64.3%) for pyrazinamide and 5/41 (12.2%) forethambutol. At the end of the intensive phase of treatment (week 8), 20.9% (n=9/43) of participants remained culture positive. We did notfind a relationship between the concentrations of first-line drugs and treatment outcomes at week 8. All participants were cured at the endof treatment, and there were no relapses during the 12-month follow-up period. CONCLUSION: Treatment outcomes were favourable despite low drug concentrations as defined by current reference thresholds.

Resilience from the perspective of diagnostic radiography students.

INTRODUCTION: Resilience is a concept associated with the ability to overcome, adapt, and recover from stressors. The radiography profession is known to be stressful, and one can reason that radiographers must be resilient in order to cope with the clinical environment. Research shows there are varied understandings of resilience. However, little is known about the concept of resilience specifically as it relates to the perspectives of diagnostic radiography students within the clinical workplace. This paper reports on one aspect of a comprehensive study of resilience amongst radiography students. The objective of this paper is, therefore, to present the exploration of the concept of resilience drawing from the data gathered from first-year diagnostic radiography students. METHODS: A qualitative, explorative, descriptive and contextual approach was adopted for this study. Qualitative data was collected through focus group interviews. A purposive sampling method was employed, selecting from first-year diagnostic radiography students at a University of Technology (UoT) in the Western Cape, South Africa. Interviews were audio-recorded transcribed and thematically analysed. Data was collected until saturation was reached. RESULTS: The meaning of resilience as explained from the perspective of radiography students included three subthemes namely: (1) fundamentals of resilience; (2) external protective factors and (3) internal protective factors. CONCLUSION: This study demonstrated that radiography students associated resilience with positive attributes. Furthermore, the study identified various resilience enhancement strategies to better support diagnostic radiography students in the clinical environment like supportive radiographers and talking to peers. IMPLICATIONS FOR PRACTICE: The identification of resilience enhancement strategies is important as it will assist with the introduction of curriculum renewal initiatives tailored to support first-year diagnostic radiography students as they develop their resilience to stressors in the clinical environment.

A third-line antiretroviral therapy register to track patient clinical and virological outcomes.

In 2021, South Africa (SA) had an estimated 7.8 million people living with HIV, of whom 5.6 million were receiving antiretroviral therapy (ART),[1] with 3.4 million on first-line ART, 145 000 on second-line ART (SLART) and >700 on third-line ART (TLART).

Changing mortality amongst hospitalised children with Severe Acute Malnutrition in KwaZulu-Natal, South Africa, 2009 - 2018.

BACKGROUND: The under-five mortality rates of children in South Africa (SA) remain high despite successful HIV prevention and treatment programs. The in-hospital mortality of children with severe acute malnutrition remains a key obstacle. This study identifies and describes changes in the mortality of under-five children with severe acute malnutrition (SAM) following the implementation of HIV and malnutrition prevention and treatment programmes. METHODS: This was a retrospective review of in-hospital mortality records and databases. The study was based at a large referral hospital in KwaZulu-Natal (KZN), where HIV and malnutrition rates are high, and SAM children are managed with standard WHO guidelines. Records of children under five years old who died from 2009 to 2018 were analysed. RESULTS: Of the 698 under-five children who died in this period, 285 (40, 8% of all under-5 deaths) were classified as having SAM. The number of HIV-infected SAM deaths dropped significantly, especially those below six months of age, mirroring the expansion of HIV treatment and prevention programmes. Despite this and a significant drop in the proportion of SAM admissions identified, there was no change in SAM case fatality rates over the ten years. Septicaemia remained the most common cause of death in children with SAM. CONCLUSIONS: Despite significant decreases in HIV-related malnutrition deaths over ten years, the lack of change in SAM case fatality rates is a concern at this referral hospital. Standardised WHO inpatient management protocols, may require review, especially where underlying medical conditions may contribute to SAM deaths in HIV-negative children.

Pharmacological management of post-traumatic seizures in a South African paediatric intensive care unit.

Background: Traumatic brain injury (TBI) is a common cause of paediatric intensive care unit (PICU) admissions in South Africa. Optimal care of these patients includes the prevention and control of post-traumatic seizures (PTS) in order to minimise secondary brain injury. Objectives: To describe the demographics of children admitted to a South African PICU, to describe the characteristics of PTS, and to describe the prophylactic and therapeutic management of PTS within the unit. Methods: A 3-year retrospective chart review was conducted at the PICU of the Chris Hani Baragwanath Academic Hospital (CHBAH) in Soweto, Johannesburg, from 1 July 2015 to 30 June 2018. Results: Seventy-eight patients were admitted to the PICU, all with severe TBI. A total of 66 patient files were available for analysis. The median age of admission was 6 years (interquartile range (IQR) 4 - 9) with the majority of trauma secondary to mechanical injury (89%). Prophylactic anti-epileptic drugs (AEDs) were initiated in 44 (79%) patients. Early PTS occurred in 11 (25%) patients who received prophylaxis and 4 (33%) who did not. Three (5%) patients developed late PTS, resulting in an overall incidence of PTS of 43%. The most common seizure type was generalised tonic clonic (82%). Children diagnosed with PTS were a median of 2 years younger than those without PTS, with increased prevalence of seizures (83% v. 38%) in children below 2 years of age. Maintenance therapy was initiated in all patients consistent with recommended dosages. Of the total 167 anti-epileptic levels taken during maintenance, only 56% were within target range. Of the initial 78 patients, 8 died (10%). The median length of stay was 7 (IQR 5 - 12) and 8 (IQR 8 - 24) days longer in ICU and hospital respectively, in children with PTS. Conclusion: PTS is a frequent complication of severe TBI in children. There was considerable variation in the approach to both prophylaxis and maintenance therapy of PTS in terms of choice of agent, dosage, frequency of drug monitoring and approach to subtherapeutic levels. It is clear that more high-level studies are required in order to better inform these practices. Contributions of the study: To the best of our knowledge, this article represents the first description of incidence and management practices of paediatric post traumatic seizures.

Altered drug exposures of first-line TB drugs in a moxifloxacin-containing treatment regimen.

BACKGROUND: Pharmacokinetic variability arising from drug-drug interactions and pharmacogenetics may influence the effectiveness of treatment regimens for TB. The Improving Treatment Success Trial compared the WHO-recommended standard treatment in TB patients with an experimental regimen substituting ethambutol with moxifloxacin (MFX) in Durban, South Africa.METHODS: Non-linear mixed-effects modelling was used to investigate the population pharmacokinetics of rifampicin (RIF), isoniazid (INH) and pyrazinamide (PZA). A total of 25 single-nucleotide polymorphisms, including pregnane-X-receptor, were selected for analysis.RESULTS: TB drug concentrations were available in a subset of 101 patients: 58 in the MFX arm and 43 in the control arm. Baseline characteristics were well-balanced between study arms: median age and weight were respectively 36 years and 57.7 kg; 75.2% of the patients were living with HIV. Although weight-based drug dosing was the same in the two arms, we found that RIF exposure was increased by 19.3%, INH decreased by 19% and PZA decreased by 19.2% when administered as part of the MFX-containing regimen. Genetic variation in pregnane-X-receptor (rs2472677) was associated with a 25.3% reduction in RIF exposure.CONCLUSION: Optimised weight-based TB treatment dosing is essential when RIF, INH and PZA are co-administered with fluoroquinolones. The reduction in RIF exposure associated with pharmacogenetic variation is worrying.

Radiography lecturers' understanding of a socially responsive curriculum.

INTRODUCTION: In health professions education (HPE), focus is placed on developing clinically competent practitioners who can function within their professional scope in a broad range of health care contexts. In this study, the authors investigated diagnostic radiography lecturers' understanding of how students become socially responsive. The concept of 'critical consciousness' was explored as an intervention of being a transformer in the local environment. This places focus on learning and teaching that aims to develop radiography graduates who are critically conscious, such that they can take up the challenges of healthcare in their environment, in addition to being clinically competent in their field. The study under discussion therefore sought to find out how radiography lecturers understand a socially responsive curriculum at a University of Technology in the South African context. METHOD: A qualitative, exploratory design was used where curriculum documents were reviewed and from which stimulus points were identified for a semi-structured focus group interview with radiography lecturers followed by five individual interviews. All interviews were audio-recorded, transcribed, coded and analysed through a process of thematic analysis. RESULTS: Four dominant themes emerged from the analysis, namely i) diverse understandings of critical consciousness, ii) becoming a reflective practitioner, iii) a need for curriculum transformation and iv) emerging pedagogies. CONCLUSION: Critical reflection by both the radiography students and lecturers is key to developing social awareness and critical consciousness which could drive critical motivation and critical action to effect social change. It is recommended that the current curriculum should be reviewed and transformed to include constructive reflective practice. IMPLICATIONS FOR PRACTICE: Dedicated time should be scheduled, in the curriculum, to allow students and lecturers to engage in meaningful constructive reflection to enhance socially responsive practice.

A cross-sectional observational study of endotracheal intubation and extubation practices among doctors treating adult COVID-19 and suspected COVID-19 patients in South Africa.

BACKGROUND: Patients with severe COVID-19 may require endotracheal intubation. Unique adjustments to endotracheal intubation and extubation practices are necessary to decrease the risk of SARS-CoV-2 transmission to healthcare workers (HCWs) while avoiding complications of airway management. OBJECTIVES: To investigate the practice of endotracheal intubation and extubation, resources available and complications encountered by clinicians performing endotracheal intubation and extubation of COVID-19 and suspected COVID-19 patients in South Africa (SA). METHOD: A cross-sectional observational study was conducted during the initial surge of COVID-19 cases in SA. Data were collected by means of a self-administered questionnaire completed by clinicians in the private and public healthcare sectors after performing an endotracheal intubation and/or extubation of a patient with confirmed or suspected COVID-19. RESULTS: Data from 135 endotracheal intubations and 45 extubations were collected. Anaesthetists accounted for 87.0% (n=120) of the study participants, specialist clinicians in their respective fields for 59.4% (n=82), and public HCWs for 71.0% (n=98). Cases from Gauteng Province made up 76.8% (n=106) of the database. Haemoglobin desaturation was the most frequent complication encountered during endotracheal intubation (40.0%; n=54). Endotracheal intubations performed at private healthcare institutions were associated with a significantly lower complication rate of 17.5% (n=7) compared with 52.6% (n=50) in the public healthcare sector (p<0.001). Endotracheal intubations performed in theatre had the lowest complication rate of 10.4% (n=5; p<0.001). Propofol was used in 90 endotracheal intubations (66.7%), and its use was associated with fewer complications relative to other induction agents. Minimising the number of intubation attempts (p=0.009) and the use of checklists (p=0.013) significantly reduced the frequency of complications encountered during endotracheal intubation. Intravenous induction technique, neuromuscular blocking agent used, intubating device used and time at which intubation was performed did not affect the incidence of complications. The majority of endotracheal extubations were uncomplicated (88.9%). CONCLUSIONS: The study provides valuable insight into the resources used by clinicians and complications encountered when endotracheal intubations and/or extubations were performed. Data from this study may be used to guide future clinical practice and research, especially in resource-limited settings.

The spectrum of hearing abnormalities in patients living with diabetes mellitus.

BACKGROUND: Diabetes mellitus (DM) causes both micro- and macrovascular complications. The cochlea and auditory nerves are therefore at increased risk from DM-related complications due to microangiopathy, neuropathy or mitochondrial damage. Limited data are available from Africa detailing the association between DM and hearing impairment (HI). OBJECTIVES: To describe the prevalence and spectrum of and associations with HI in patients living with DM (PLWD) with and without HIV infection. METHODS: This was an analytical cross-sectional study conducted between 1 October and 31 December 2019 at the Edendale Hospital diabetes and audiology clinics in Pietermaritzburg, South Africa. PLWD had an audiological assessment using pure-tone audiometry together with a questionnaire enquiring about tinnitus, vertigo, dizziness and HI. RESULTS: A total of 296 PLWD (89.2% with type 2 DM) were enrolled, of whom 154 (52.0%) had HI. Type 2 PLWD had a significantly higher prevalence of reported symptoms and confirmed audiological HI, which was most often bilateral. The most frequent HI categories were mild to moderate, mild, and moderate to severe (33.8% v. 25.9% v. 23.9%, respectively). Significant associations were noted between dizziness (p=0.045), reported hearing loss (p<0.001) and objective evidence of HI (all categories except mild). HI was significantly associated with age >50 years, DM duration ≤10 years, female gender, hypertension, increased low-density lipoprotein and total cholesterol (TC), lower high-density lipoprotein cholesterol, suboptimal glycaemic control, non-proliferative retinopathy, sensory neuropathy and obesity (p<0.05). Approximately half (48.9%) of PLWD and HIV infection had HI, and they were significantly younger and had higher TC levels than PLWD without HIV (p<0.05). CONCLUSIONS: We showed that HI occurs in over half of PLWD, usually within the first 10 years after diagnosis of DM. Symptoms of HI were shown to have positive associations with all HI categories except mild. A high level of vigilance for HI must be maintained in PLWD.

Evaluating the impact of single exit pricing (SEP) on medicine product withdrawal from the private healthcare market in South Africa.

BACKGROUND: The introduction of medicine pricing policies in South Africa (SA) in the form of single exit pricing (SEP) provided a mechanism to improve medicine price transparency and reduce the medicine price and inflation. However, regulation of medicine prices may have further unforeseen effects on the availability of medicine. This research presents the impact of SEP on discontinuation of medicine products on the private healthcare market in SA. OBJECTIVES: To evaluate the impact of SEP legislation on the availability of medicines in the SA private health sector in terms of withdrawal of medicines from the market. METHODS: A descriptive, quantitative analysis of all registered medicines on the SA market by stock-keeping units (SKUs) was done to establish medicine products that were withdrawn from the market by SKUs during a 14-year period (2001 - 2014). RESULTS: A total of 152 manufacturers discontinued 3 691 SKUs between 2001 and 2014. The mean number of discontinuations per generic manufacturer was 22.34 (standard deviation (SD) 58.11), while innovator manufacturers discontinued a mean of 27.61 (41.89). The largest number of SKUs were commercially withdrawn in 2002 (n=603), followed by discontinuations in 2003 (n=463) and 2004 (n=407). There was a negative correlation between number of discontinued SKUs per year and SEP increase (Pearson's correlation coefficient r ‒0.414; p=0.14). The results showed that SEP and a transparent pricing policy may have had an impact on SKU withdrawal from the market prior to SEP implementation. CONCLUSIONS: The result of reduced product availability on the market and its impact on the cost and quality of healthcare to the patient need to be regularly monitored and evaluated to ascertain if direct price regulations achieve the intended outcomes. Other intended or unintended effects on pharmaceutical market dynamics should also be evaluated.

A nurse-led intervention to improve management of virological failure in public sector HIV clinics in Durban, South Africa: A pre- and post-implementation evaluation.

BACKGROUND: Identification of patients on antiretroviral therapy (ART) with virological failure (VF) and the response in the public health sector remain significant challenges. We previously reported improvement in routine viral load (VL) monitoring after ART commencement through a health system-strengthening, nurse-led 'VL champion' programme as part of a multidisciplinary team in three public sector clinics in Durban, South Africa. OBJECTIVES: To report on the impact of the VL champion model adapted to identify, support and co-ordinate the management of individuals with VF on first-line ART in a setting with limited electronic-based record capacity. METHODS: We evaluated the VL champion model using a controlled before-after study design. A paper-based tool, the 'high VL register', was piloted under the supervision of the VL champion to improve data management, monitoring of counselling support, and enacting of clinical decisions. We abstracted chart and electronic data (TIER.net) for eligible individuals with VF in the year before and after implementation of the programme, and compared outcomes for individuals during these periods. Our primary outcome was successful completion of the VF pathway, defined as a repeat VL <1 000 copies/mL or a change to second-line ART within 6 months of VF. In a secondary analysis, we assessed the completion of each step in the pathway. RESULTS: We identified 60 and 56 individuals in the pre-intervention and post-intervention periods, respectively, with VF who met the inclusion criteria. Sociodemographic and clinical characteristics were similar between the periods. Repeat VL testing was completed in 61.7% and 57.8% of individuals in these two groups, respectively. We found no difference in the proportion achieving our primary outcome in the pre- and post-intervention periods: 11/60 (18.3%; 95% confidence interval (CI) 9 - 28) and 15/56 (22.8%; 95% CI 15 - 38), respectively (p=0.28). In multivariable logistic regression models adjusted for potential confounding factors, individuals in the post-intervention period had a non-significant doubling of the odds of achieving the primary outcome (adjusted odds ratio 2.07; 95% CI 0.75 - 5.72). However, there was no difference in the rates of completion of each step along the first-line VF cascade of care. CONCLUSIONS: This enhanced intervention to improve VF in the public sector using a paper-based data management system failed to achieve significant improvements in first-line VF management over the standard of care. In addition to interventions that better address patient-centred factors that contribute to VF, we believe that there are substantial limitations to and staffing requirements involved in the ongoing utilisation of a paper-based tool. A prioritisation is needed to further expand and upgrade the electronic medical record system with capabilities for prompting staff regarding patients with missed visits and critical laboratory results demonstrating VF.

Distinctive clinical and histological characteristics of atrophic and hypertrophic facial photoageing.

BACKGROUND: Photoageing describes complex cutaneous changes which occur following chronic exposure to solar ultraviolet radiation (UVR). Amongst White Northern Europeans, facial photoageing appears as distinct clinical phenotypes: 'hypertrophic' photoageing (HP) and 'atrophic' photoageing (AP). Deep, coarse wrinkles predominate in individuals with HP, whereas those with AP have relatively smooth, unwrinkled skin with pronounced telangiectasia. AP individuals have an increased propensity for developing keratinocyte cancers. OBJECTIVES: To investigate whether histological differences underlie these distinct phenotypes of facial photoageing. METHODS: Facial skin biopsies were obtained from participants with AP (10 M, 10 F; mean age: 78.7 years) or HP (10 M, 10 F; mean age: 74.5 years) and were assessed histologically and by immunohistochemistry. RESULTS: Demographic characterization revealed 95% of AP subjects, as compared to 35% with HP, were Fitzpatrick skin type I/II; of these, 50% had a history of one or more keratinocyte cancers. There was no history of keratinocyte cancers in the HP cohort. Analysis of UVR-induced mitochondrial DNA damage confirmed that all volunteers had received similar lifetime cumulative doses of sun exposure. Histologically, male AP had a significantly thicker epidermis than did AP females or those of either sex with HP. HP facial skin exhibited severe solar elastosis, whereas in AP facial skin, solar elastosis was apparent only in females. Loss of papillary dermal fibrillin-rich microfibrils occurred in all HP and AP female subjects, but not in AP males. Furthermore, male AP had a significant reduction in collagen VII at the dermal-epidermal junction than did AP females or those of either sex with HP. CONCLUSIONS: This study provides further evidence that AP and HP represent distinct clinical and histological entities. Knowledge of these two phenotypes is clinically relevant due to the increased prevalence of keratinocyte cancers in those - particularly males - with the AP phenotype.

Treatment outcomes in patients with drug-resistant TB-HIV co-infection treated with bedaquiline and linezolid.

BACKGROUND: Bedaquiline (BDQ) has not been extensively studied among patients co-infected with HIV drug-resistant tuberculosis (DR-TB). We compared treatment outcomes in DR-TB patients treated with BDQ- and linezolid (LZD) containing regimens to historic controls treated with second-line injectable-containing regimens.METHODS: Retrospective cohort study of consecutive DR-TB patients initiated on BDQ- and LZD-containing regimens at a TB referral hospital in KwaZulu-Natal, South Africa. Participants were prospectively followed through 24 months for treatment outcome and adverse events. Outcomes were compared to a historic control cohort of DR-TB HIV patients enrolled at the same facility prior to BDQ introduction.RESULTS: Adult DR-TB patients initiating BDQ between January 2014 and November 2015 were enrolled (n = 151). The majority of patients were female (52%), HIV co-infected (77%) and on antiretroviral therapy (100%). End of treatment outcomes included cure (63%), TB culture conversion (83%), completion (0.7%), loss to follow-up (15%), treatment failure (5%), and death (17%). Compared to historic controls (n = 105), patients treated with BDQ experienced significantly higher TB culture conversion and cure, with significantly lower mortality. Adverse effects were common (92%), and most frequently attributed to LZD (24.1%). QT segment prolongation was common but without clinical sequelae.CONCLUSION: Treatment with BDQ- and LZD-containing regimens was associated with improved treatment outcomes and survival in DR-TB HIV patients.

A systematic review and meta-analysis of first-line tuberculosis drug concentrations and treatment outcomes.

Low serum concentrations of first-line tuberculosis (TB) drugs have been widely reported. However, the impact of low serum concentrations on treatment outcome is less well studied. A systematic search of MEDLINE/Pubmed and the Cochrane Central Register of Controlled Trials up to 31 March 2018 was conducted for articles describing drug concentrations of first-line TB drugs and treatment outcome in adult patients with drug-susceptible TB. The search identified 3073 unique publication abstracts, which were reviewed for suitability: 21 articles were acceptable for inclusion in the qualitative analysis comprising 13 prospective observational cohorts, 4 retrospective observational cohorts, 1 case-control study and 3 randomised controlled trials. Data for meta-analysis were available for 15 studies, 13 studies of rifampicin (RMP), 10 of isoniazid (INH), 8 of pyrazinamide (PZA) and 4 of ethambutol (EMB). This meta-analysis revealed that low PZA concentration appears to increase the risk of poor outcomes (8 studies, n = 2727; RR 1.73, 95%CI 1.10-2.72), low RMP concentrations may slightly increase the risk of poor outcomes (13 studies, n = 2753; RR 1.40, 95%CI 0.91-2.16), whereas low concentrations of INH (10 studies, n = 2640; RR 1.32, 95%CI 0.66-2.63) and EMB (4 studies, n = 551; RR 1.12, 95%CI 0.41-3.05) appear to make no difference to treatment outcome. There was no significant publication bias or between-study heterogeneity in any of the analyses. The potential clinical impact of low concentrations of PZA and RMP warrants further evaluation. Also, comprehensive assessments of the complex pharmacokinetic-pharmacodynamic relationships in the treatment of TB are urgently needed.

The Power of the Shared Experience: MTN-020/ASPIRE Trial Participants' Descriptions of Peer Influence on Acceptability of and Adherence to the Dapivirine Vaginal Ring for HIV Prevention.

Women are disproportionately at risk of acquiring HIV in East and Southern Africa, despite global declines in incidence. Female-initiated HIV prevention methods, like the dapivirine vaginal ring, are needed to end the HIV epidemic. In-depth interviews and focus groups retrospectively explored peer influence on acceptability of and adherence to the ring during the ASPIRE trial, a phase III placebo-controlled trial. Results were analyzed using an inductive analytic approach. Study participants (peers) of all ages and adherence groups developed important interpersonal connections and reported being more open and honest with each other than with external peers or study staff. Study peers who knew each other prior to joining appeared to have a stronger influence on each other's adherence than peers who met in the study. External peers provided primarily negative input about the ring and study, which sometimes led to ring removals. Peers' influence on each other's behavior in both prosocial and detrimental manners could have repercussions on adherence to a biomedical intervention, and consequently, individual disease risk and clinical trial outcomes. Future ring demonstration and implementation studies could use peer networks to intentionally influence uptake and adherence to the ring.

Urgent need to improve programmatic management of patients with HIV failing first-line antiretroviral therapy.

INTRODUCTION: Delayed identification and response to virologic failure in case of first-line antiretroviral therapy (ART) in resource-limited settings is a threat to the health of HIV-infected patients. There is a need for the implementation of an effective, standardized response pathway in the public sector. DISCUSSION: We evaluated published cohorts describing virologic failure on first-line ART. We focused on gaps in the detection and management of treatment failure, and posited ways to close these gaps, keeping in mind scalability and standardization. Specific shortcomings repeatedly recorded included early loss to follow-up (>20%) after recognized first-line ART virologic failure; frequent delays in confirmatory viral load testing; and excessive time between the confirmation of first-line ART failure and initiation of second-line ART, which exceeded 1 year in some cases. Strategies emphasizing patient tracing, resistance testing, drug concentration monitoring, adherence interventions, and streamlined response pathways for those failing therapy are further discussed. CONCLUSION: Comprehensive, evidence-based, clinical operational plans must be devised based on findings from existing research and further tested through implementation science research. Until this standard of evidence is available and implemented, high rates of losses from delays in appropriate switch to second-line ART will remain unacceptably common and a threat to the success of global HIV treatment programs.

Recommendation to include hydroxyethyl (meth)acrylate in the British baseline patch test series.

BACKGROUND: (Meth)acrylates are potent sensitizers and a common cause of allergic contact dermatitis (ACD). The frequency of (meth)acrylate ACD has increased with soaring demand for acrylic nails. A preliminary audit has suggested a significant rate of positive patch tests to (meth)acrylates using aimed testing in patients providing a clear history of exposure. To date, (meth)acrylates have not been routinely tested in the baseline patch test series in the U.K. and Europe. OBJECTIVES: To determine whether inclusion of 2-hydroxyethyl methacrylate (2-HEMA) 2% in petrolatum (pet.) in the baseline series detects cases of treatable (meth)acrylate ACD. METHODS: During 2016-2017, 15 U.K. dermatology centres included 2-HEMA in the extended baseline patch test series. Patients with a history of (meth)acrylate exposure, or who tested positive to 2-HEMA, were selectively tested with a short series of eight (meth)acrylate allergens. RESULTS: In total 5920 patients were consecutively patch tested with the baseline series, of whom 669 were also tested with the (meth)acrylate series. Overall, 102 of 5920 (1·7%) tested positive to 2-HEMA and 140 (2·4%) to at least one (meth)acrylate. Had 2-HEMA been excluded from the baseline series, (meth)acrylate allergy would have been missed in 36 of 5920 (0·6% of all patients). The top (meth)acrylates eliciting a positive reaction were 2-HEMA (n = 102, 1·7%), 2-hydroxypropyl methacrylate (n = 61, 1·0%) and 2-hydroxyethyl acrylate (n = 57, 1·0%). CONCLUSIONS: We recommend that 2-HEMA 2% pet. be added to the British baseline patch test series. We also suggest a standardized short (meth)acrylate series, which is likely to detect most cases of (meth)acrylate allergy.