Livingstone Hospital

BACKGROUND: Tuberculous pericarditis is associated with high morbidity and mortality even if antituberculosis therapy is administered. We evaluated the effects of adjunctive glucocorticoid therapy and Mycobacterium indicus pranii immunotherapy in patients with tuberculous pericarditis. METHODS: Using a 2-by-2 factorial design, we randomly assigned 1400 adults with definite or probable tuberculous pericarditis to either prednisolone or placebo for 6 weeks and to either M. indicus pranii or placebo, administered in five injections over the course of 3 months. Two thirds of the participants had concomitant human immunodeficiency virus (HIV) infection. The primary efficacy outcome was a composite of death, cardiac tamponade requiring pericardiocentesis, or constrictive pericarditis. RESULTS: There was no significant difference in the primary outcome between patients who received prednisolone and those who received placebo (23.8% and 24.5%, respectively; hazard ratio, 0.95; 95% confidence interval [CI], 0.77 to 1.18; P=0.66) or between those who received M. indicus pranii immunotherapy and those who received placebo (25.0% and 24.3%, respectively; hazard ratio, 1.03; 95% CI, 0.82 to 1.29; P=0.81). Prednisolone therapy, as compared with placebo, was associated with significant reductions in the incidence of constrictive pericarditis (4.4% vs. 7.8%; hazard ratio, 0.56; 95% CI, 0.36 to 0.87; P=0.009) and hospitalization (20.7% vs. 25.2%; hazard ratio, 0.79; 95% CI, 0.63 to 0.99; P=0.04). Both prednisolone and M. indicus pranii, each as compared with placebo, were associated with a significant increase in the incidence of cancer (1.8% vs. 0.6%; hazard ratio, 3.27; 95% CI, 1.07 to 10.03; P=0.03, and 1.8% vs. 0.5%; hazard ratio, 3.69; 95% CI, 1.03 to 13.24; P=0.03, respectively), owing mainly to an increase in HIV-associated cancer. CONCLUSIONS: In patients with tuberculous pericarditis, neither prednisolone nor M. indicus pranii had a significant effect on the composite of death, cardiac tamponade requiring pericardiocentesis, or constrictive pericarditis. (Funded by the Canadian Institutes of Health Research and others; IMPI ClinicalTrials.gov number, NCT00810849.).

BACKGROUND: The incidence of tuberculous pericarditis has increased in Africa as a result of the human immunodeficiency virus (HIV) epidemic. However, the effect of HIV co-infection on clinical features and prognosis in tuberculous pericarditis is not well characterised. We have used baseline data of the Investigation of the Management of Pericarditis in Africa (IMPI Africa) registry to assess the impact of HIV co-infection on clinical presentation, diagnostic evaluation, and treatment of patients with suspected tuberculous pericarditis in sub-Saharan Africa. METHODS: Consecutive adult patients in 15 hospitals in three countries in sub-Saharan Africa were recruited on commencement of treatment for tuberculous pericarditis, following informed consent. We recorded demographic, clinical, diagnostic and therapeutic information at baseline, and have used the chi-square test and analysis of variance to assess probabilities of significant differences (in these variables) between groups defined by HIV status. RESULTS: A total of 185 patients were enrolled from 01 March 2004 to 31 October 2004, 147 (79.5%) of whom had effusive, 28 (15.1%) effusive-constrictive, and 10 (5.4%) constrictive or acute dry pericarditis. Seventy-four (40%) had clinical features of HIV infection. Patients with clinical HIV disease were more likely to present with dyspnoea (odds ratio [OR] 3.2, 95% confidence interval [CI] 1.4 to 7.4, P = 0.005) and electrocardiographic features of myopericarditis (OR 2.8, 95% CI 1.1 to 6.9, P = 0.03). In addition to electrocardiographic features of myopericarditis, a positive HIV serological status was associated with greater cardiomegaly (OR 3.89, 95% CI 1.34 to 11.32, P = 0.01) and haemodynamic instability (OR 9.68, 95% CI 2.09 to 44.80, P = 0.0008). However, stage of pericardial disease at diagnosis and use of diagnostic tests were not related to clinical HIV status. Similar results were obtained for serological HIV status. Most patients were treated on clinical grounds, with microbiological evidence of tuberculosis obtained in only 13 (7.0%) patients. Adjunctive corticosteroids were used in 109 (58.9%) patients, with patients having clinical HIV disease less likely to be put on them (OR 0.37, 95% CI 0.20 to 0.68). Seven patients were on antiretroviral drugs. CONCLUSION: Patients with suspected tuberculous pericarditis and HIV infection in Africa have greater evidence of myopericarditis, dyspnoea, and haemodynamic instability. These findings, if confirmed in other studies, may suggest more intensive management of the cardiac disease is warranted in patients with HIV-associated pericardial disease.

Abstract Rationale Improving treatment outcomes while reducing drug toxicity and shortening the treatment duration to ∼6 months remains an aspirational goal for the treatment of multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB). Objectives To conduct a multicenter randomized controlled trial in adults with MDR/RR-TB (i.e., without resistance to fluoroquinolones or aminoglycosides). Methods Participants were randomly assigned (1:1 ratio) to a ∼6-month all-oral regimen that included levofloxacin, bedaquiline, and linezolid, or the standard-of-care (SOC) ⩾9-month World Health Organization (WHO)-approved injectable-based regimen. The primary endpoint was a favorable WHO-defined treatment outcome (which mandates that prespecified drug substitution is counted as an unfavorable outcome) 24 months after treatment initiation. The trial was stopped prematurely when bedaquiline-based therapy became the standard of care in South Africa. Measurements and Main Results In total, 93 of 111 randomized participants (44 in the comparator arm and 49 in the interventional arm) were included in the modified intention-to-treat analysis; 51 (55%) were HIV coinfected (median CD4 count, 158 cells/ml). Participants in the intervention arm were 2.2 times more likely to experience a favorable 24-month outcome than participants in the SOC arm (51% [25 of 49] vs. 22.7% [10 of 44]; risk ratio, 2.2 [1.2–4.1]; P = 0.006). Toxicity-related drug substitution occurred more frequently in the SOC arm (65.9% [29 of 44] vs. 34.7% [17 of 49]; P = 0.001)], 82.8% (24 of 29) owing to kanamycin (mainly hearing loss; replaced by bedaquiline) in the SOC arm, and 64.7% (11 of 17) owing to linezolid (mainly anemia) in the interventional arm. Adverse event–related treatment discontinuation in the safety population was more common in the SOC arm (56.4% [31 of 55] vs. 32.1% [17 of 56]; P = 0.007). However, grade 3 adverse events were more common in the interventional arm (55.4% [31 of 56] vs. 32.7 [18 of 55]; P = 0.022). Culture conversion was significantly better in the intervention arm (hazard ratio, 2.6 [1.4–4.9]; P = 0.003) after censoring those with bedaquiline replacement in the SOC arm (and this pattern remained consistent after censoring for drug replacement in both arms; P = 0.01). Conclusions Compared with traditional injectable-containing regimens, an all-oral 6-month levofloxacin, bedaquiline, and linezolid–containing MDR/RR-TB regimen was associated with a significantly improved 24-month WHO-defined treatment outcome (predominantly owing to toxicity-related drug substitution). However, drug toxicity occurred frequently in both arms. These findings inform strategies to develop future regimens for MDR/RR-TB. Clinical trial registered with www.clinicaltrials.gov (NCT 02454205).

The Southern African Journal of HIV Medicine is focused on HIV/AIDS treatment, prevention and related topics relevant to clinical and public health practice. The purpose of the journal is to disseminate original research results and support high-level learning related to HIV Medicine. It publishes original research articles, editorials, case reports/case series, reviews of state-of-the-art clinical practice and correspondence.

The Southern African Journal of HIV Medicine is focused on HIV/AIDS treatment, prevention and related topics relevant to clinical and public health practice. The purpose of the journal is to disseminate original research results and support high-level learning related to HIV Medicine. It publishes original research articles, editorials, case reports/case series, reviews of state-of-the-art clinical practice and correspondence.

OBJECTIVES: Helicobacter pylori-associated infection is common in South Africa, as in other developing countries. Antibiotic resistance is recognised as a major cause of treatment failure. We studied the susceptibility and resistance patterns of H. pylori to guide empiric treatment and prevent the emergence of resistance. METHODS: Two hundred H. pylori strains obtained from gastric biopsies of patients presenting with gastric-related morbidities attending Livingstone Hospital, Port Elizabeth, were evaluated for their susceptibility to seven antibiotics - metronidazole, clarithromycin, tetracycline, amoxicillin, gentamicin, ciprofloxacin and erythromycin. H. pylori was isolated following standard microbiology procedures, and susceptibility determined using the Kirby-Bauer disc diffusion and agar dilution methods. Comparisons of antimicrobial resistance rates with sex of the patients were determined using the chi-square test; a p-value of <0.05 was considered significant. RESULTS: Marked susceptibility was observed for ciprofloxacin (100%) and amoxicillin (97.5%), and good activity for clarithromycin (80%) and gentamicin (72.5%). However, marked resistance (95.5%) was observed for metronidazole. The minimal inhibitory concentration (MIC) ranged from 0.0625 microg/ml to 8 microg/ml. The lowest MIC, with a range of 0.0625 - 1 microg/ml, was recorded for ciprofloxacin, while the highest (5 - 8 microg/ml) was noted for gentamicin. CONCLUSION: Multidrug resistance was commonly encountered - a finding of clinical significance that calls for continuous surveillance of antibiograms to guide empiric treatment. We advocate the inclusion of ciprofloxacin in the treatment regimen of H. pylori infection in our study environment.

BACKGROUND: In 2017, 64% of children living with HIV in Zambia accessed Antiretroviral Therapy (ART). Despite expanded ART coverage, there is paucity of information on effectiveness of pediatric ART in reducing mortality. The aim of this research is to describe treatment outcomes, measure mortality rates and assess predictors of mortality among children receiving ART. METHODS: Using a retrospective cohort study design, we abstracted routinely collected clinical data from medical records of children from birth to 15 years old, who had received ART for at least 6 months at Livingstone Central Hospital in Southern Province Zambia, between January 2003 and June 2015. The primary outcome was death. Cause of death was ascertained from medical records and death certificates. Distribution of survival times according to baseline covariates were estimated using Kaplan Meier and Cox Proportional Hazards methods. RESULTS: Overall, 1039 children were commenced on ART during the study period. The median age at treatment initiation was 3.6 years (IQR: 1.3-8.6) and 520 (50%) children were female. Of these, 71 (7%) died, 164 (16%) were lost to follow-up, 210 (20%) transferred and 594 (56%) were actively on treatment. After 4450 person years, mortality rate was 1.6/100 (95% CI: 1.4-1.8). Mortality was highest during the first 3 months of treatment (11.7/100 (95% CI: 7.6-16.3). In multivariable proportional hazards regression, the adjusted hazards of death were highest among children aged < 1 year (aHR = 3.1 (95% CI: 1.3-6.4), compared to those aged 6-15 years, WHO stage 4 (aHR =4.8 (95% CI: 2.3-10), compared to WHO stage 1 and 2. In the sensitivity analysis to address bias due to loss to follow-up, mortality increased 5 times when we assumed that all the children who were lost to follow up died within 90 days of their last visit. CONCLUSION: We observed low attrition due to mortality among children on ART. Loss to follow-up was high (16%). Mortality was highest during the first 3 months of treatment. Children aged less than one year and those with advanced WHO disease stage had higher mortality. We recommend effective interventions to improve retention in care and early diagnosis of HIV in children.

Objectives. We examined Helicobacter pylori infection in patients with gastric-related morbidities at Livingstone Hospital, Port Elizabeth, to determine the prevalence and risk factors for infection according to race, endoscopic diagnosis, age and sex. Methods. Gastric biopsies were collected from 254 consecutive patients and H. pylori isolated on Columbia agar base supplemented with 7% sheep's blood and Skirrow's supplement containing trimethoprim (2.5 mg), vancomycin (5 mg) and cefsulodin (2.5 mg). Amphotericin (2.5 mg) was added to the medium. Recovered isolates were identified following standard microbiology and biochemical techniques. Presumptive isolates were further confirmed by polymerase chain reaction (PCR) targeting the glmM gene. Fisher's exact test was used to assess the univariate association between H. pylori infection and the possible risk factors. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated to measure the strength of association, using EPI INFO 3.41 software. P-values <0.05 were required for significance. Results. The overall prevalence of H. pylori was 66.1% (168/254). Of the 168 positive subjects, H. pylori prevalence was highest in patients with non-ulcer dyspepsia (NUD) (32.7%; 55/168), and lowest (0%; 0/168) in those with atypical oesophageal reflux disease and gastroduodenitis, respectively. The prevalence of infection was highest among coloureds (68.4%; 89/130) and lowest in whites (59.5%; 25/ 42). Prevalence increased with age. Conclusion. The prevalence of H. pylori is high in dyspeptic patients in Eastern Cape Province. Gender, antibiotic treatment and alcohol consumption may be risk factors for infection. These findings are of clinical and epidemiological significance.

Developed with a strong awareness of past injustices, South Africa's progressive constitution emphasises a full spectrum of human rights. While the constitution celebrates many languages and cultures, speech-language pathologists (SLPs) face challenges in translating these values into practice with a diverse clientele. Similarly, Article 19 of the Universal Declaration of Human Rights focuses on freedom of expression in one's language of choice, but is often perceived as a "Cinderella" right (i.e. one that is frequently neglected). This paper presents a literature review undertaken in association with the Health Professions Council of South Africa to produce guidelines to support SLPs in their practice with diverse linguistic and cultural groups. The aim was to identify key points for inclusion in a set of human rights-driven guidelines. Specific objectives were to critique: (1) current guidelines for SLPs working with diverse cultural and linguistic groups; and (2) equivalent guidelines for related professions. Content analysis of the datasets revealed key themes which formed the basis of an initial skeleton, to be further developed through a consultative process and discussion, ultimately aiming to provide supportive, practical guidelines to better equip South African SLPs to serve all the people of the country.

BACKGROUND: Improved tuberculosis (TB) screening is urgently needed for human immunodeficiency virus (HIV) infected patients. METHODS: An observational, multi-country, cross-sectional study of HIV-infected patients to compare a standardized diagnostic evaluation (SDE) for TB with standard of care (SOC). SOC evaluations included TB symptom review (current cough, fever, night sweats and/or weight loss), sputum Ziehl-Neelsen staining and chest radiography. SDE screening added extended clinical signs and symptoms and fluorescent microscopy (FM). All participants underwent all evaluations. Mycobacterium tuberculosis on sputum culture was the primary outcome. RESULTS: A total of 801 participants were enrolled from Botswana, Malawi, South Africa, Zimbabwe, India, Peru and Brazil. The median age was 33 years; 37% were male, and median CD4 count was 275 cells/mm(3). Thirty-one participants (4%) had a positive culture on Löwenstein-Jensen media and 54 (8%) on MGIT. All but one positive culture came from sub-Saharan Africa, where the prevalence of TB was 54/445 (12%). SOC screening had 54% sensitivity (95%CI 40-67) and 76% specificity (95%CI 72-80). Positive and negative predictive values were respectively 24% and 92%. No elements of the SDE improved the predictive values of SOC. CONCLUSIONS: Symptom-based screening with smear microscopy was insufficiently sensitive. More sensitive diagnostic testing is required for HIV-infected patients.

Higher doses of intravenous rifampicin may improve outcomes in tuberculous meningitis but are impractical in high-burden settings. We hypothesized that plasma rifampicin exposures would be similar between oral dosing of 35 mg/kg of body weight and intravenous dosing of 20 mg/kg, which has been proposed for efficacy trials in tuberculous meningitis.

Few studies from Africa have described the clinical impact of co-infections on SARS-CoV-2 infection. Here, we investigate the presentation and outcome of SARS-CoV-2 infection in an African setting of high HIV-1 and tuberculosis prevalence by an observational case cohort of SARS-CoV-2 patients. A comparator group of non SARS-CoV-2 participants is included. The study includes 104 adults with SARS-CoV-2 infection of whom 29.8% are HIV-1 co-infected. Two or more co-morbidities are present in 57.7% of participants, including HIV-1 (30%) and active tuberculosis (14%). Amongst patients dually infected by tuberculosis and SARS-CoV-2, clinical features can be typical of either SARS-CoV-2 or tuberculosis: lymphopenia is exacerbated, and some markers of inflammation (D-dimer and ferritin) are further elevated (p < 0.05). Amongst HIV-1 co-infected participants those with low CD4 percentage strata exhibit reduced total, but not neutralising, anti-SARS-CoV-2 antibodies. SARS-CoV-2 specific CD8 T cell responses are present in 35.8% participants overall but undetectable in combined HIV-1 and tuberculosis. Death occurred in 30/104 (29%) of all COVID-19 patients and in 6/15 (40%) of patients with coincident SARS-CoV-2 and tuberculosis. This shows that in a high incidence setting, tuberculosis is a common co-morbidity in patients admitted to hospital with COVID-19. The immune response to SARS-CoV-2 is adversely affected by co-existent HIV-1 and tuberculosis.

BACKGROUND: There is a marked paucity of data concerning AKI in Sub-Saharan Africa, where there is a substantial burden of trauma and HIV. METHODS: Prospective data was collected on all patients admitted to a multi-disciplinary ICU in South Africa during 2017. Development of AKI (before or during ICU admission) was recorded and renal recovery 90 days after ICU discharge was determined. RESULTS: Of 849 admissions, the mean age was 42.5 years and mean SAPS 3 score was 48.1. Comorbidities included hypertension (30.5%), HIV (32.6%), diabetes (13.3%), CKD (7.8%) and active tuberculosis (6.2%). The most common reason for admission was trauma (26%). AKI developed in 497 (58.5%). Male gender, illness severity, length of stay, vasopressor drugs and sepsis were independently associated with AKI. AKI was associated with a higher in-hospital mortality rate of 31.8% vs 7.23% in those without AKI. Age, active tuberculosis, higher SAPS 3 score, mechanical ventilation, vasopressor support and sepsis were associated with an increased adjusted odds ratio for death. HIV was not independently associated with AKI or hospital mortality. CKD developed in 14 of 110 (12.7%) patients with stage 3 AKI; none were dialysis-dependent. CONCLUSIONS: In this large prospective multidisciplinary ICU cohort of younger patients, AKI was common, often associated with trauma in addition to traditional risk factors and was associated with good functional renal recovery at 90 days in most survivors. Although the HIV prevalence was high and associated with higher mortality, this was related to the severity of illness and not to HIV status per se.

Background: Hospital-acquired infections (HAI) are a leading cause of morbidity and mortality globally. These infections are diverse, but the majority are lower respiratory tract infection (LRTI), surgical site infection (SSI), bloodstream infection (BSI), and urinary tract infection (UTI). For most sub-Saharan African countries, studies revealing the burden and impact of HAI are scarce, and few systematic reviews and meta-analysis have been attempted. We sought to fill this gap by reporting recent trends in HAI in sub-Saharan Africa (SSA) with attention to key patient populations, geographic variation, and associated mortality. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a literature search of six electronic databases (Web of Science, Pubmed, APA PsycInfo, CINAHL, Embase, and the Cochrane Library) to identify studies assessing the prevalence of HAI in SSA countries. Studies published between 01 January 2014 and 31 December 2023 were included. We applied no language or publication restrictions. Record screening and data extractions were independently conducted by teams of two or more reviewers. Using the R software (version 4.3.1) meta and metafor packages, we calculated the pooled prevalence estimates from random-effect meta-analysis, and further explored sources of heterogeneity through subgroup analyses and meta-regression. This study is registered with PROSPERO, CRD42023433271. Findings: Forty-one relevant studies were identified for analysis, consisting of 15 from West Africa (n = 2107), 12 from Southern Africa (n = 2963), 11 from East Africa (n = 2142), and 3 from Central Africa (n = 124). A total of 59.4% of the patient population were associated with paediatric admissions. The pooled prevalence of HAI was estimated at 12.9% (95% CI: 8.9-17.4; n = 7336; number of included estimates [k] = 41, p < 0.001). By subregions, the pooled current prevalence of HAI in the West Africa, Southern Africa, East Africa and Central Africa were estimated at 15.5% (95% CI: 8.3-24.4; n = 2107; k = 15), 6.5% (95% CI: 3.3-10.7; n = 2963; k = 12), 19.7% (95% CI: 10.8-30.5; n = 2142; k = 11) and 10.3% (95% CI: 1.1-27.0; n = 124; k = 3) of the patient populations respectively. We estimated mortality resulting from HAI in SSA at 22.2% (95% CI: 14.2-31.4; n = 1118; k = 9). Interpretation: Our estimates reveal a high burden of HAI in SSA with significant heterogeneity between regions. Variations in HAI distribution highlight the need for infection prevention and surveillance strategies specifically tailored to enhance prevention and management with special focus on West and East Africa, as part of the broader global control effort. Funding: No funding was received for this study.

BACKGROUND: The travel distance from home to a treatment centre, which may impact the stage at diagnosis, has not been investigated for retinoblastoma, the most common childhood eye cancer. We aimed to investigate the travel burden and its impact on clinical presentation in a large sample of patients with retinoblastoma from Africa and Europe. METHODS: A cross-sectional analysis including 518 treatment-naïve patients with retinoblastoma residing in 40 European countries and 1024 treatment-naïve patients with retinoblastoma residing in 43 African countries. RESULTS: Capture rate was 42.2% of expected patients from Africa and 108.8% from Europe. African patients were older (95% CI -12.4 to -5.4, p<0.001), had fewer cases of familial retinoblastoma (95% CI 2.0 to 5.3, p<0.001) and presented with more advanced disease (95% CI 6.0 to 9.8, p<0.001); 43.4% and 15.4% of Africans had extraocular retinoblastoma and distant metastasis at the time of diagnosis, respectively, compared to 2.9% and 1.0% of the Europeans. To reach a retinoblastoma centre, European patients travelled 421.8 km compared to Africans who travelled 185.7 km (p<0.001). On regression analysis, lower-national income level, African residence and older age (p<0.001), but not travel distance (p=0.19), were risk factors for advanced disease. CONCLUSIONS: Fewer than half the expected number of patients with retinoblastoma presented to African referral centres in 2017, suggesting poor awareness or other barriers to access. Despite the relatively shorter distance travelled by African patients, they presented with later-stage disease. Health education about retinoblastoma is needed for carers and health workers in Africa in order to increase capture rate and promote early referral.

There is a need for effective therapy for COVID-19 pneumonia. Convalescent plasma has antiviral activity and early observational studies suggested benefit in reducing COVID-19 severity. We investigated the safety and efficacy of convalescent plasma in hospitalized patients with COVID-19 in a population with a high HIV prevalence and where few therapeutic options were available. We performed a double-blinded, multicenter, randomized controlled trial in one private and three public sector hospitals in South Africa. Adult participants with COVID-19 pneumonia requiring non-invasive oxygen were randomized 1:1 to receive a single transfusion of 200 mL of either convalescent plasma or 0.9% saline solution. The primary outcome measure was hospital discharge and/or improvement of ≥ 2 points on the World Health Organisation Blueprint Ordinal Scale for Clinical Improvement by day 28 of enrolment. The trial was stopped early for futility by the Data and Safety Monitoring Board. 103 participants, including 21 HIV positive individuals, were randomized at the time of premature trial termination: 52 in the convalescent plasma and 51 in the placebo group. The primary outcome occurred in 31 participants in the convalescent plasma group and and 32 participants in the placebo group (relative risk 1.03 (95% CI 0.77 to 1.38). Two grade 1 transfusion-related adverse events occurred. Participants who improved clinically received convalescent plasma with a higher median anti-SARS-CoV-2 neutralizing antibody titre compared with those who did not (298 versus 205 AU/mL). Our study contributes additional evidence for recommendations against the use of convalescent plasma for COVID-19 pneumonia. Safety and feasibility in this population supports future investigation for other indications.

BACKGROUND: The Eastern Cape province of South Africa has one of the highest burdens of HIV in the world. Emergency Departments (EDs) can serve as optimal clinical sites for the identification of new HIV infections and entry into care. We sought to determine the current burden of HIV disease among ED patients in the Eastern Cape. METHODS: We conducted a prospective cross-sectional observational study in the EDs of three Hospitals in the Eastern Cape province of South Africa from June 2017 to July 2018. All adult, non-critical patients presenting to the ED were systematically approached and offered a Point-Of-Care (POC) HIV test in accordance with South African guidelines. All HIV-positive individuals had their blood tested for the presence of antiretroviral therapy (ART) and the presence of viral suppression (≤ 1000 copies/ml). HIV incidence was estimated using a multi-assay algorithm, validated for a subtype C epidemic. FINDINGS: Of the 2901 patients for whom HIV status was determined (either known HIV-positive or underwent POC HIV testing), 811 (28.0%) were HIV positive, of which 234 (28.9%) were newly diagnosed. HIV prevalence was higher in Mthatha [34% (388/1134) at Mthatha Regional Hospital and 28% (142/512) at Nelson Mandela Academic Hospital], compared to Port Elizabeth [22% (281/1255) at Livingstone Hospital]. HIV incidence was estimated at 4.5/100 person-years (95% CI: 2.4, 6.50) for women and 1.5 (CI 0.5, 2.5) for men. Of all HIV positive individuals tested for ART (585), 54% (316/585) tested positive for the presence of ARTs, and for all HIV positive participants with viral load data (609), 49% (299/609) were found to be virally suppressed. INTERPRETATION: Our study not only observed a high prevalence and incidence of HIV among ED patients but also highlights significant attrition along the HIV care cascade for HIV positive individuals. Furthermore, despite developing an optimal testing environment, we were only able to enrol a small sub-set of the ED population. Given the high HIV prevalence and high attrition in the ED population, HIV services in the ED should also develop strategies that can accommodate large testing volumes and ART initiation.

OBJECTIVE: To evaluate the role of the ICA (Identification, Cause, Avoidable factor) Solution method of perinatal audit in reducing perinatal mortality. DESIGN: Retrospective audit of 1,060 perinatal deaths between 1 January 1991 and 31 December 1992. SETTING: Livingstone Hospital Maternity Service. SUBJECTS: One thousand and sixty perinatal deaths, where the gestational age exceeded 28 weeks or, when gestational age was unknown, the birth weight was equal to or exceeded 1,000 g. MAIN OUTCOME MEASURES: All perinatal deaths were identified and classified by primary obstetric cause for perinatal loss. In the second year of the study avoidable factors were sought and, if found, graded and categorised. RESULTS: The major primary obstetric causes of perinatal loss identified and amenable to intervention were intrapartum trauma, intrapartum asphyxia and infection. In the second year of study potentially avoidable factors were sought and identified in almost 50% of perinatal deaths. Appropriate intervention lowered the perinatal mortality rate by 23% (P < 0.05; odds ratio 0.76; 95% confidence interval 0.67-0.86). CONCLUSION: The ICA Solution method of perinatal audit identified problems in overall obstetric care, facilitating a significant fall in perinatal mortality.

BACKGROUND: Personalized medicine tailors care based on the patient's or pathogen's genotypic and phenotypic characteristics. An automated Clinical Decision Support System (CDSS) could help translate the genotypic and phenotypic characteristics into optimal treatment and thus facilitate implementation of individualized treatment by less experienced physicians. METHODS: We developed a hybrid knowledge- and data-driven treatment recommender CDSS. Stakeholders and experts first define the knowledge base by identifying and quantifying drug and regimen features for the prototype model input. In an iterative manner, feedback from experts is harvested to generate model training datasets, machine learning methods are applied to identify complex relations and patterns in the data, and model performance is assessed by estimating the precision at one, mean reciprocal rank and mean average precision. Once the model performance no longer iteratively increases, a validation dataset is used to assess model overfitting. RESULTS: We applied the novel methodology to develop a treatment recommender CDSS for individualized treatment of drug resistant tuberculosis as a proof of concept. Using input from stakeholders and three rounds of expert feedback on a dataset of 355 patients with 129 unique drug resistance profiles, the model had a 95% precision at 1 indicating that the highest ranked treatment regimen was considered appropriate by the experts in 95% of cases. Use of a validation data set however suggested substantial model overfitting, with a reduction in precision at 1 to 78%. CONCLUSION: Our novel and flexible hybrid knowledge- and data-driven treatment recommender CDSS is a first step towards the automation of individualized treatment for personalized medicine. Further research should assess its value in fields other than drug resistant tuberculosis, develop solid statistical approaches to assess model performance, and evaluate their accuracy in real-life clinical settings.

Background The prevalence of hypertension in low‐ and middle‐income countries is rapidly increasing, with most cases undiagnosed and many poorly controlled among those diagnosed. Medication reconciliation studies from high‐income countries have demonstrated a high occurrence of antihypertensive medication errors and a strong association between medication errors and inadequate blood pressure control, but data from low‐ and middle‐income countries are lacking. Methods and Results We conducted a cross‐sectional study from April to October 2018 of adult patients on pharmacologic management for known hypertension at 7 public health facilities in Kweneng East District, Botswana. Our aims included to evaluate the frequency of uncontrolled hypertension, the frequency and type of medication errors causing discrepancies between patient‐reported and prescribed antihypertensive medications, and the association between medication errors and uncontrolled hypertension. Descriptive analyses and multivariable logistic regression were used. The prevalence of uncontrolled hypertension was 55% among 280 enrolled adult patients, and 95 (34%) had ≥1 medication error. The most common errors included patients taking medications incorrectly (11.1%; 31/280), patients omitting medications (7.9%; 22/280), and unfilled prescriptions caused by pharmacy stock outs (7.5%%; 21/280). Uncontrolled hypertension was significantly associated with having ≥1 medication error compared with no errors (adjusted odds ratio, 3.26; 95% CI, 1.75–6.06; P &lt;0.001). Conclusions Medication errors are strongly associated with poor blood pressure control in this setting. Further research is warranted to assess whether medication reconciliation and other low‐cost interventions addressing root causes of medication errors can improve the control of hypertension and other chronic conditions in low‐ and middle‐income countries.