Treatment initiation among tuberculosis patients: the role of short message service (SMS) technology and Ward-based outreach teams (WBOTs).

BACKGROUND: In South Africa, tuberculosis (TB) is a public health problem with treatment initiation failure rates varying between 14.9 and 25%. Lack of proper provider/patient communication on next steps after testing, not being aware that results are ready; and other competing priorities are some of the reasons for this failure. We aimed to assess the effectiveness of Short Message Service (SMS) technology and ward-based outreach teams (WBOTs) in improving TB treatment initiation. A 3-arm randomized controlled trial (Standard of care-SOC, SMS technology or WBOTs) was conducted between September 2018 and April 2020. Newly diagnosed TB patients randomly allocated to SMS and WBOTs groups were sent reminder messages (text message or paper slip respectively) that results were ready. Due to unforeseen challenges (financial and impact of the COVID 19 pandemic), implementation was only in two of the eight clinics planned. RESULTS: 314 TB patients were assigned to one of three groups (SOC = 104, WBOTs = 105, and SMS = 105). Chi-square tests were used to compare proportions starting treatment (primary outcome). More patients in the SMS group (92/105; 88%) initiated treatment than in the SOC group (81/104; 78%), although this difference did not reach statistical significance (P = 0.062). The time to treatment initiation was significantly shorter in the SMS group than in the SOC group (P < 0.001). The proportions of patients initiated on treatment in the WBOTs group (45/62; 73%) and in the SOC group (44/61; 72%) were similar (P = 0.956). The times to treatment initiation for these two groups were also similar. The 3 group analysis yielded similar proportions initiated on treatment (P = 0.048 for SMS/SOC comparison and P = 0.956 for WBOTs/SOC comparison) but analysis of times to treatment initiation yielded some variations. CONCLUSION: Reminder SMS messages sent to newly diagnosed TB patients improved the time to treatment initiation. Further research is required to show effect of the WBOTs intervention. TRIAL REGISTRATION: Retrospectively registered with the Pan African Clinical Trial Registry ( PACTR202101914895981 ). The trial was registered with the Pan African Clinical Trial Registry on 25 January, 2021 (ref: PACTR202101914895981 ; https://pactr.samrc.ac.za ). The registration was retrospective due to an oversight. Nevertheless, the protocol details outlined in our ethics application were strictly adhered to.

Increasing medical student numbers in resource constrained settings: Ethical and legal complexities intersecting patients' rights and responsibilities.

There is a need to increase the number of practicing medical doctors in South Africa. We examine the ethical implications of patients' rights being affected in medical education in a South African context. The South African legal framework advocates public healthcare access. Yet, the State's ethical obligations when it comes to guaranteeing public healthcare access, conflict with its utilitarian policy, that allows for medical education to help achieve the State's public healthcare commitments, at the cost of eroding patients' rights, and accepts that certain actions are imperative, in line with Ubuntu, which is tenable yet nuanced. A patient treated by a licenced doctor today, benefits because other patients have allowed themselves to be used as hands-on learning material for medical students yesterday. Healthcare institutions need to take cognisance of the numbers of medical students that patients can reasonably be expected to endure. There is a need for the Health Professions Council of South Africa and medical schools to adopt guidelines on reasonable levels of medical student-patient interaction, and medical student-to-patient ratios in healthcare delivery.

Severe Acute Respiratory Syndrome Coronavirus 2 Infection Among Healthcare Workers in South Africa: A Longitudinal Cohort Study.

From April to September 2020, we investigated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in a cohort of 396 healthcare workers (HCWs) from 5 departments at Chris Hani Baragwanath Hospital, South Africa. Overall, 34.6% of HCWs had polymerase chain reaction-confirmed SARS-CoV-2 infection (132.1 [95% confidence interval, 111.8-156.2] infections per 1000 person-months); an additional 27 infections were identified by serology. HCWs in the internal medicine department had the highest rate of infection (61.7%). Among polymerase chain reaction-confirmed cases, 10.4% remained asymptomatic, 30.4% were presymptomatic, and 59.3% were symptomatic.

Screening for invasive fungal disease using non-culture-based assays among inpatients with advanced HIV disease at a large academic hospital in South Africa.

INTRODUCTION: Despite widespread access to antiretroviral therapy (ART), the burden of advanced HIV disease in South Africa is high. This translates into an increased risk of AIDS-related opportunistic infections, including invasive mycoses. METHODS: Using a limited number of non-culture-based diagnostic assays, we aimed to determine the prevalence of invasive mycoses and tuberculosis among hospitalised adults with very advanced HIV (CD4 counts < 100 cells/µL) at a large academic hospital. We conducted interviews and prospective medical chart reviews. We performed point-of-care finger stick and serum cryptococcal antigen lateral flow assays; serum (1 → 3) ß-D-glucan assays; urine Histoplasma galactomannan antigen enzyme immunoassays and TB lipoarabinomannan assays. RESULTS: We enrolled 189 participants from 5280 screened inpatients. Fifty-eight per cent were female, with median age 37 years (IQR: 30-43) and median CD4 count 32 cells/µL (IQR: 13-63). At enrolment, 60% (109/181) were receiving ART. Twenty-one participants (11%) had a diagnosis of an invasive mycosis, of whom 53% (11/21) had cryptococcal disease. Thirteen participants (7%) had tuberculosis and a concurrent invasive mycosis. ART-experienced participants were 60% less likely to have an invasive mycosis than those ART-naïve (adjusted OR: 0.4; 95% CI 0.15-1.0; P = .03). Overall in-hospital mortality was 13% (invasive mycosis: 10% [95% CI 1.2-30.7] versus other diagnoses: 13% (95% CI 8.4-19.3)). CONCLUSIONS: One in ten participants had evidence of an invasive mycosis. Diagnosis of proven invasive fungal disease and differentiation from other opportunistic infections was challenging. More fungal-specific screening and diagnostic tests should be applied to inpatients with advanced HIV disease.

Initial loss to follow up of tuberculosis patients in South Africa: perspectives of program managers.

BACKGROUND: Tuberculosis (TB) remains a serious public health problem in South Africa. Initial loss to follow up (LTFU) rates among TB patients are high, varying between 14.9 and 22.5%. From the perspective of patients, documented reasons for this include poor communication between patient and staff after testing, not being aware that results are ready and other competing priorities such as preference to go to work as opposed to seeking healthcare. Ward-based Outreach Teams (WBOTs) routinely conduct home visits to ensure adherence to medication for various conditions including TB. We explored reasons for TB initial loss to follow up from the perspectives of TB program managers and WBOT program managers, with a focus on the WBOT's (potential) role in reducing initial LTFU, in particular. METHODS: Key informant interviews with five WBOT program managers and four TB program managers were conducted. The interviews were audio-recorded, then transcribed and exported to NVivo 11 software for coding. A hybrid analytic approach consisting of both inductive and deductive coding was used to identify themes. RESULTS: The age of the nine managers ranged between 28 and 52 years old, of which two were male. They had been in their current position for between 2 to 12 years. Prior to treatment initiation, WBOTs screen household members for TB and refer them for TB testing if need be, but integration of the two programs is emphasized only after TB treatment has been initiated. Counseling of patients testing for TB is not guaranteed due to frequent staff rotations and staff shortages. Participants reported that possible dissatisfaction with services as well as stigma associated with the TB diagnosis could explain loss to follow up prior to treatment initiation. CONCLUSION: Program managers view health system related factors such as staff rotations, poor communication with patients and lack of counseling as contributing to the problem of initial LTFU among TB patients. The integration of the WBOT and TB programs is limited to referring suspected cases for testing and patients already on treatment.

Lung outcomes and related risk factors in patients after SARS-CoV-2 infection: a hospitalised single-centre cohort from Johannesburg, South Africa.

Background: Sequelae post-SARS-CoV-2 infection, including lung and functional impairment, pose a significant challenge post-recovery. We explored the burden and risk factors for post-COVID-19 sequelae in an African population with prevalent comorbidities including tuberculosis (TB) and HIV. Methods: We conducted an observational cohort study on hospitalised adults with confirmed SARS-CoV-2 infection from 20 March to 06 October 2021 at Chris Hani Baragwanath Academic Hospital, South Africa. We collected data on comorbidities, and COVID-19 severity using the World Health Organization (WHO) clinical progression scale. Prospectively, we followed up all participants within 40-days post-discharge to assess body mass index (BMI), COVID-19 symptoms and quality of life using St George's Respiratory Questionnaire (SGRQ), 6-min walking-test (6MWT), and spirometry. A subsequent in-depth visit assessed plethysmography, diffusing capacity for the lung for carbon monoxide (DLCO), and high-resolution chest-CT. Findings: We followed up 111 participants, where 65.8% were female, median age 50.5 years, and predominantly black-African (92.8%). Relevant comorbidities included TB disease (18.9%) and HIV infection (36%). SGRQ total scores were elevated in 78.9%, median 6MWT distance was reduced at 300 m (IQR 210-400), and nearly half (49.5%) exhibited spirometry findings below the lower limit of normal (LLN). In-depth pulmonary assessment for 61 participants revealed abnormalities in total lung capacity (31.6% <80% predicted), DLCO (53.4% <80% predicted), and chest-CT (86.7% abnormal). Significant risk factors for individual abnormal outcomes, adjusted for age and sex, were TB disease, HIV with CD4 <200 cells/mm3, BMI <18.5 kg/m2 and >35 kg/m2, and initial COVID-19 severity. Interpretation: This study demonstrates substantial lung and functional morbidity within the first weeks post-COVID-19, particularly in individuals with pre-existing comorbidities including TB, HIV, and low or high BMI. Chest-CT and DLCO show best early potential at reflecting COVID-19-related pathologies. Funding: The Bavarian State Ministry of Science and Arts.

Factors influencing specialist care referral of multidrug- and extensively drug-resistant tuberculosis patients in Gauteng/South Africa: a descriptive questionnaire-based study.

BACKGROUND: Sizwe Tropical Diseases Hospital is the only specialized Hospital for the management of multidrug-resistant (MDR)-TB and extensively drug-resistant (XDR)-TB cases in Gauteng Province. In South Africa, there is a mismatch between numbers of individuals with a laboratory diagnosis of drug-resistant tuberculosis (TB) and those being referred for the initiation of specialist treatment. We determined reasons for non-referral of MDR-TB and XDR-TB cases. METHODS: We conducted a descriptive questionnaire-based study amongst provincial primary health care facilities (PHC) and hospitals providing routine care for (drug-susceptible) TB, regarding specialist care referral of patients whose TB culture and susceptibility testing confirmed MDR-TB or XDR-TB diagnoses in the first half of 2008. RESULTS: In total 148 cases were analyzed; 144/148 (97%) had MDR-TB and 4/148 (3%) had XDR-TB. The main reason for non-referral to specialist care was loss to follow up, for patients diagnosed in-hospital (74/97; 76%) as well as in PHCs (11/21; 52%). Nineteen per cent (18/97) of patients diagnosed in hospital versus 33% (7/21) of patients diagnosed in PHCs deceased before referral. CONCLUSIONS: A significant problem in the fight to control DR-TB is follow-up after diagnosis with a delay in patient tracing. TB Focal Points in hospital need to be strengthened in order to improve on patient follow-up and care, and tracer teams should assist with community follow up.

Validation of the COVID-19 IgG/IgM Rapid Test Cassette (BNCP - 402 and BNCP402) in a South African setting.

Background: Different diagnostic tools could improve early detection of coronavirus disease 2019 (COVID-19). A number of antibody-based serological point-of-care tests have been developed to supplement real-time reverse transcriptase polymerase chain reaction (RT-PCR)-based diagnosis. This study describes the validity of an antibody test, namely the immunoglobulin G (IgG)/immunoglobulin M (IgM) Rapid Test Cassette® (BNCP - 402 and BNCP402), manufactured by Spring Healthcare Services. Methods: A prospective cohort validation study was undertaken at Chris Hani Baragwanath Academic Hospital between 16 July 2020 and 12 August 2020. A total of 101 patients admitted as COVID-19 cases under investigation were included in the study. They were divided into two categories depending on time since symptom onset: testing performed within seven days (early cohort) and after seven days (late cohort). The rapid antibody test was compared to the RT-PCR. Results: Overall, the test has a sensitivity and specificity of 85.2% and 80.0%, respectively, for a combination of IgG and IgM. Sensitivity and specificity of IgG testing alone were 81.5% and 85%. Sensitivity improved for testing with increasing time from symptom onset; however, specifity was not significantly different. Conclusion: The study data adds to the body of evidence that because of relatively low sensitivity and specificity, there is a limited role for antibody-based point-of-care testing in the acute phase of COVID-19 infection, as was the case with this IgG/IgM Rapid Test Cassette (BNCP - 402 and BNCP402). There may exist a role for such testing in patients recovered from prior COVID-19 infection or in seroprevalence studies; however, additional evaluations at later timepoints from symptom onset are required.

Clinical characteristics and histopathology of COVID-19 related deaths in South African adults.

Comparisons of histopathological features and microbiological findings between decedents with respiratory symptoms due to SARS-CoV-2 infection or other causes, in settings with high prevalence of HIV and Mycobacterium tuberculosis (MTB) infections have not been reported. Deaths associated with a positive ante-mortem SARS-CoV-2 PCR test and/or respiratory disease symptoms at Chris Hani Baragwanath Academic Hospital in Soweto, South Africa from 15th April to 2nd November 2020, during the first wave of the South African COVID-19 epidemic, were investigated. Deceased adult patients had post-mortem minimally-invasive tissue sampling (MITS) performed to investigate for SARS-CoV-2 infection and molecular detection of putative pathogens on blood and lung samples, and histopathology examination of lung, liver and heart tissue. During the study period MITS were done in patients displaying symptoms of respiratory disease including 75 COVID-19-related deaths (COVID+) and 42 non-COVID-19-related deaths (COVID-). The prevalence of HIV-infection was lower in COVID+ (27%) than in the COVID- (64%), MTB detection was also less common among COVID+ (3% vs 13%). Lung histopathology findings showed differences between COVID+ and COVID- in the severity of the morphological appearance of Type-II pneumocytes, alveolar injury and repair initiated by SARS-CoV-2 infection. In the liver necrotising granulomatous inflammation was more common among COVID+. No differences were found in heart analyses. The prevalence of bacterial co-infections was higher in COVID+. Most indicators of respiratory distress syndrome were undifferentiated between COVID+ and COVID- except for Type-II pneumocytes. HIV or MTB infection does not appear in these data to have a meaningful correspondence with COVID-related deaths.

Case-fatality and sequelae following acute bacterial meningitis in South Africa, 2016 through 2020.

OBJECTIVES: Providing country-specific estimates of case fatality and sequelae from bacterial meningitis (BM) is important to evaluate and monitor progress toward the World Health Organization's roadmap to "defeating meningitis by 2030". METHODS: From 2016-2020, GERMS-SA conducted enhanced surveillance at 26 hospitals across South Africa. Episodes of laboratory-confirmed BM due to Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis were included. Risk factors for in-hospital death and sequelae at hospital discharge among survivors were analyzed. RESULTS: Of 12,717 invasive bacterial infections reported nationally, 39% (4980) were from enhanced surveillance sites, including 4159 pneumococcal, 640 H. influenzae, and 181 meningococcal infections. BM accounted for 32% (1319/4159) of pneumococcal, 21% (136/640) of H. influenzae, and 83% (151/181) of meningococcal invasive diseases. Clinical data were available for 91% (1455/1606) of BM: 26% (376/1455) were aged <5 years, 50% (726/1455) were female, and 62% (723/1171) with known HIV results, were HIV-infected. In-hospital case fatality was 37% (534/1455), and 24% (222/921) of survivors had adverse sequelae. Risk factors for death included altered mental status, HIV infection, and comorbidities. Risk factors for adverse sequelae included altered mental status and antimicrobial nonsusceptibility. CONCLUSION: BM in South Africa has a high case fatality, and adverse sequelae frequently occur among survivors. Those with comorbidities (including HIV) are at the highest risk.

Outcomes of flucytosine-containing combination treatment for cryptococcal meningitis in a South African national access programme: a cross-sectional observational study.

BACKGROUND: Although flucytosine is a key component of WHO-recommended induction treatment for HIV-associated cryptococcal meningitis, this antifungal agent is not widely available in low-income and middle-income countries due to limited production and cost. In 2018, a national flucytosine access programme was initiated in South Africa. We aimed to determine the effectiveness of flucytosine-containing induction regimens in routine care to motivate for the urgent registration of flucytosine and its inclusion in treatment guidelines. METHODS: In this cross-sectional study, we compared outcomes of adults aged 18 years and older with incident laboratory-confirmed cryptococcal meningitis treated with or without flucytosine-containing regimens at 19 sentinel hospitals in South Africa. A case of cryptococcosis was defined as illness in an adult with: (1) positive cerebrospinal fluid (CSF) India ink microscopy; (2) a positive CSF cryptococcal antigen test; or (3) culture of Cryptococcus neoformans or Cryptococcus gattii from CSF or any other specimen. We excluded patients without a case report form, those with an unknown or negative HIV serology result, those with a recurrent episode, and those who did not receive antifungal treatment in hospital. We assessed cumulative in-hospital mortality at 14 days and 30 days and calculated the overall crude in-hospital case-fatality ratio. We used random-effects logistic regression to examine the association between treatment group and in-hospital mortality. FINDINGS: From July 1, 2018, to March 31, 2020, 10 668 individuals were diagnosed with laboratory-confirmed cryptococcal meningitis, 7787 cases diagnosed at non-enhanced surveillance sites and 567 cases from eight enhanced surveillance sites with no access to flucytosine were excluded. Of 2314 adults with a first episode of cryptococcosis diagnosed at 19 facilities with access to flucytosine, 1996 had a case report form and of these, 1539 received induction antifungal treatment and were confirmed HIV-seropositive first-episode cases. Of 1539 patients who received antifungal therapy, 596 (38·7%) individuals received a flucytosine-containing regimen and 943 (61·3%) received another regimen. The median age was 36 years (IQR 32-43) and 906 (58·9%) participants were male and 633 (41·1%) were female. The crude in-hospital case-fatality ratio was 23·9% (95% CI 20·0-27·0; 143 of 596) in those treated with flucytosine-containing regimens and 37·2% (95% CI 34·0-40·0; 351 of 943) in those treated with other regimens. Patients admitted to non-academic hospitals (adjusted odds ratio [aOR] 1·95 [95% CI 1·53-2·48]; p<0·0001) and those who were antiretroviral treatment-experienced (aOR 1·30 [1·02-1·67]; p=0·033) were more likely to receive flucytosine. After adjusting for relevant confounders, flucytosine treatment was associated with a 53% reduction in mortality (aOR 0·47 [95% CI 0·35-0·64]; p<0·0001). Among survivors, the median length of hospital admission in the flucytosine group was 11 days (IQR 8-15) versus 17 days (13-21) in the comparison group (p=0·0010). INTERPRETATION: In-hospital mortality among patients treated with a flucytosine-containing regimen was comparable to reduced mortality reported in patients receiving a flucytosine-containing regimen in a recent multicentre African clinical trial. Flucytosine-based treatment can be delivered in routine care in a middle-income country with a substantial survival benefit. FUNDING: National Institute for Communicable Diseases, a Division of the National Health Laboratory Service. TRANSLATION: For the Zulu translation of the abstract see Supplementary Materials section.

Early treatment outcomes and HIV status of patients with extensively drug-resistant tuberculosis in South Africa: a retrospective cohort study.

BACKGROUND: Data from Kwazulu Natal, South Africa, suggest that almost all patients with extensively drug-resistant (XDR) tuberculosis are HIV-positive, with a fatal outcome. Since, there are few data for the treatment-related outcomes of XDR tuberculosis in settings with a high HIV prevalence, we investigated the associations of these diseases in such settings to formulate recommendations for control programmes. METHODS: In a retrospective cohort study, we analysed the case records of patients (>16 years old) with XDR tuberculosis (culture-proven at diagnosis) between August, 2002, and February, 2008, at four designated provincial treatment facilities in South Africa. We used Cox proportional hazards regression models to assess risk factors associated with the outcomes-mortality and culture conversion. FINDINGS: 195 of 227 patients were analysed. 21 died before initiation of any treatment, and 174 patients (82 with HIV infection) were treated. 62 (36%) of these patients died during follow-up. The number of deaths was not significantly different in patients with or without HIV infection: 34 (41%) of 82 versus 28 (30%) of 92 (p=0.13). Treatment with moxifloxacin (hazard ratio 0.11, 95% CI 0.01-0.82; p=0.03), previous culture-proven multidrug-resistant tuberculosis (5.21, 1.93-14.1; p=0.001), and number of drugs used in a regimen (0.59, 0.45-0.78, p<0.0001) were independent predictors of death. Fewer deaths occurred in patients with HIV infection given highly active antiretroviral therapy than in those who were not (0.38, 0.18-0.80; p=0.01). 33 (19%) of 174 patients showed culture conversion, of which 23 (70%) converted within 6 months of initiation of treatment. INTERPRETATION: In South Africa, patients with XDR tuberculosis, a substantial proportion of whom are not infected with HIV, have poor management outcomes. Nevertheless, survival in patients with HIV infection is better than previously reported. The priorities for the country are still prevention of XDR tuberculosis, and early detection and management of multidrug-resistant and XDR tuberculosis through strengthened programmes and laboratory capacity. FUNDING: South African Medical Research Council, European Union Framework 7 program, and European Developing Countries Clinical Trials Partnership.

A longitudinal study of stavudine-associated toxicities in a large cohort of South African HIV infected subjects.

BACKGROUND: There has been major improvement in the survival of HIV-1 infected individuals since the South African Government introduced highly active anti-retroviral therapy (HAART) in the public sector in 2004. This has brought new challenges which include the effects of stavudine-related toxicities. METHODS: Prospective analysis of a cohort of 9040 HIV-infected adults who were initiated on HAART at the Themba Lethu Clinic (TLC) in Johannesburg between April 1, 2004 to December 31, 2007, and followed up until June 30, 2008. RESULTS: Amongst the 9040 study subjects, 8497(94%) were on stavudine based therapy and 5962 (66%) were women. The median baseline CD4 count was 81 cells/mm3 (IQR 29-149). Median follow up on HAART was 19 months (IQR: 9.1-31.6). The proportion of HAART-related side effects for stavudine compared to non-stavudine containing regimens were, respectively: peripheral neuropathy,17.1% vs. 11.2% (p < 0.001); symptomatic hyperlactataemia, 5.7% vs. 2.2% (p < 0.0005); lactic acidosis, 2.5 vs. 1.3% (p = 0.072); lipoatrophy, 7.3% vs. 4.6% (p < 0.05). Among those on stavudine-based regimens, incidence rates for peripheral neuropathy were 12.1 cases/100 person-years (95%CI 7.0-19.5), symptomatic hyperlactataemia 3.6 cases/100 person-years (95%CI 1.2-7.5), lactic acidosis 1.6 cases/100 person-years (95%CI 0.4-5.2) and lipoatrophy 4.6 cases/100 person-years (95%CI 2.1-9.6). Females experienced more toxicity when compared to males in terms of symptomatic hyperlactataemia (p < 0.0001), lactic acidosis (p < 0.0001), lipoatrophy (p < 0.0001) and hypertension (p < 0.05). CONCLUSIONS: We demonstrate significant morbidity associated with stavudine. These data support the latest WHO guidelines, and provide additional evidence for other resource limited HAART rollout programs considering the implementation of non-stavudine based regimens as first line therapy.

Patterns and outcomes of admissions to the medical acute care unit of a tertiary teaching hospital in South Africa.

BACKGROUND: A Medical Acute Care Unit (MACU) was established at Chris Hani Baragwanath Academic Hospital (CHBAH) to provide comprehensive medical specialist care to the patients presenting with acute medical emergencies. Improved healthcare delivery systems at the MACU may result in shorter hospital stays, better outcomes, and less mortality. OBJECTIVES: The study's objective was to describe the demographics, diagnoses, disease patterns, and outcomes, including patient's mortality, admitted to the MACU at CHBAH. METHODS: Records of 200 patients admitted, between March 2015 to August 2015, to the MACU at CHBAH were reviewed. Patient demographics, diagnosis at admission, duration of stay, and outcomes were documented. Patients transferred to the medical ward, the Intensive Care Unit (ICU), or discharge. The leading causes of mortality were documented. RESULTS: Of the 200 patients, 59% were females. The patients' mean age was 46 (17.2) years, and the mean duration of stay at the MACU was 1.45 (1.25) days. Non-communicable diseases accounted for 76% of admissions. The most frequently diagnosed conditions included: diabetic ketoacidosis acidosis (DKA) and hyperosmolar non-ketotic (HONK) (17.5%), non-accidental self-poisoning (16%), hypertensive emergencies (9.5%), decompensated cardiac failure (8%) and ischemic heart disease (7%). Infectious diseases comprised 14% of the diagnoses, of which cases of pneumonia were the most common (5%). Most patients (77.5%) were transferred to medical wards, 12% to ICU, while 10% demised at the MACU. The leading causes of death included sepsis (25%), DKA/HONK (20%), non-accidental self-poisoning (10%), and cardiac failure (10%). CONCLUSION: Non-communicable diseases, particularly diabetic emergencies, were the leading causes of admission to the MACU at CHBAH. During the study period, high rates of case improvement, patient discharge, shorter hospital stay, and less mortality were observed. The leading cause of mortality was sepsis related.

Prevalence and Trajectory of COVID-19-Associated Hypercoagulability Using Serial Thromboelastography in a South African Population.

INTRODUCTION: The coagulation abnormalities resulting from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been attributed to inflammation and subsequent cytokine storm. Thromboelastography (TEG) is a point-of-care test used to assess clot formation and degradation in whole blood and is an indicator of the overall real-time coagulopathic state of the patient. METHODS: A single-centre, prospective, observational cohort study was conducted in South Africa, analysing the coagulation patterns of 41 patients with hypoxia related to SARS-CoV-2 using serial thromboelastography (TEG) on admission, after 48 hours, and at resolution of hypoxia/day 10. Results: Two-thirds (n = 26) were women. The median age was 61 (IQR 50-67), and the majority (88%) were Black patients. Almost half (22) of the patients were critically ill and ventilated, with median SOFA and SAPS2 scores of 3 and 22 (IQR2-4 and 18-30), respectively. The prevalence of hypercoagulability was 0.54 (95% CI 0.46-0.62), whilst 29/41 (0.71, CI 0.64-0.78)) met the definition of hypofibrinolysis. Differences between the hypercoagulable (HC) and non-hypercoagulable groups remained apparent at 48 hours after anticoagulation. At this time point, the K time was significantly lower (p ˂ 0,01), and the α-angle (p ˂ 0,01) and maximum amplitude (MA) (p ˂ 0,01) were significantly higher in the HC cohort. At resolution of hypoxia, or day 10, only MA was significantly higher in the hypercoagulable group compared to the non-hypercoagulable group (p = 0.01). The initial impairment in fibrinolysis (Ly30), α angle, and MA were significantly associated with mortality, with p values of 0.006, 0.031, and 0.04, respectively. CONCLUSIONS: In this South African population, hypercoagulability was a highly prevalent phenomenon in COVID-19 disease. It was typified by hypofibrinolysis and a persistently elevated MA, despite anticoagulation therapy.

Perceptions of patients and medical students towards each other in the setting of patient care-a South African perspective.

INTRODUCTION: South Africa urgently needs more doctors. We examined perceptions of patients and students to provide evidence for optimum student-patient ratios and substantiate solutions for this dilemma. METHODS: We interviewed 118 patients and invited 120 students to complete a self-administered questionnaire from four specialities in an academic hospital in Johannesburg. RESULTS: The total sample size was 238 participants. A total of 91/118 (77%) patients and 78/120 (65%) students were female. Almost all the patients had some level of education, with most patients having received at least a secondary education (71/120). More than half of the students (69/120) were final year students. A third (41/118) of the patients were unaware they were admitted to a teaching hospital. Half of the patients (60/118) thought they had the right to refuse interaction with students. Patients and students preferred smaller groups of between 1-3 and 4-8 students at a bedside tutorial (p < 0.001), although patients preferred smaller groups (1-3) compared with the students (4-8). Majority of patients said they never refused consent to students, while a third of students reported at least up to three patients refusing consent to be examined. The most frequent reason cited by students for refusal of consent by patients was the exposure to excessive numbers of students and healthcare professionals. CONCLUSION: Medical schools should consider patient safeguards while responding to the country's need for more doctors. The Medical Council and medical schools need to draw up professional guidelines on patient-student interactions, including the role of patients in this setting.

Time to embrace access programmes for medicines: lessons from the South African flucytosine access programme.

BACKGROUND: Cryptococcal meningitis (CM) is estimated to cause 181 000 deaths annually, with the majority occurring in Sub-Saharan Africa. Flucytosine is recommended by the World Health Organization as part of the treatment for CM. Widespread use of flucytosine could reduce mortality in hospital by as much as 40% compared to the standard of care, yet due to market failure, quality-assured flucytosine remains unregistered and largely inaccessible throughout Africa. METHODS: The recently established South African flucytosine clinical access programme is an attempt to address the market failure that led to a lack of public sector access to flucytosine for CM, by making the medicine freely available to tertiary hospitals in South Africa. RESULTS: Between November 2018 and September 2019, 327 CM patients received flucytosine through this programme, with efforts to support sustainable national scale-up presently ongoing. We describe why this programme was needed, its catalytic potential, what is still required to ensure widespread access to flucytosine, and observations from this experience that may have wider relevance. CONCLUSIONS: The South African flucytosine access programme illustrates how access programmes may be one part of the solution to addressing the vicious cycle of perceived low demand, limiting manufacturer interest in specific product markets.

Initial loss to follow up among tuberculosis patients: the role of Ward-Based Outreach Teams and short message service (SMS) technology (research proposal).

INTRODUCTION: Tuberculosis (TB) is a problem in South Africa. Initial loss to follow up (LTFU) among TB patients is high varying between 14.9 and 18%. Some of the reasons for this are: lack of proper communication between patient and staff on next steps after testing, not aware that results are ready; and other competing priorities. Receiving reminder messages that result is ready is an intervention that can be explored to reduce initial LTFU. This can be through either receiving a note from the Ward-Based Outreach Teams (WBOTs) or via short message service (SMS) advising the patient to collect test result at the facility. This proposal aims to assess the effectiveness of WBOTs or SMS technology in reducing TB initial LTFU. METHODS: This will be a mixed methods approach. In depth interviews with WBOT Managers and TB Program Managers will be conducted. Focus group discussions with WBOT members will also be conducted. Two interventions (enhanced WBOTs/SMS technology) will be tested using a 3 arm randomized controlled trial (standard of care, SMS technology or enhanced WBOTs). The WBOTs will deliver paper note reminders while SMS intervention will entail sending reminder SMS messages to patients as soon as TB results are ready.