Effectiveness of the BNT162b2 vaccine in preventing morbidity and mortality associated with COVID-19 in children aged 5 to 11 years: A systematic review and meta-analysis.

A rapid systematic review, based on Cochrane rapid review methodology was conducted to assess the effectiveness of two 10µg doses of BNT162b2 vaccine in preventing morbidity and mortality associated with COVID-19 in children aged 5 to 11 years. We searched the Cochrane Library COVID-19 study register, the COVID-NMA living review database and the McMaster University Living Evidence Synthesis for pre-appraised trials and observational studies up to 7 December 2022. Records were screened independently in duplicate. Where appraisal was not available, these were done in duplicate. Meta-analysis was conducted using RevMan 5.3 presenting risk ratios/odds ratios/inverse vaccine efficacy with 95% confidence intervals (CI). GRADE for assessing the overall certainty of the evidence was done in Gradepro. We screened 403 records and assessed 52 full-text articles for eligibility. One randomised controlled trial (RCT) and 24 observational studies were included. The RCT reported that BNT162b2 was likely safe and 91% efficacious, RR 0.09 (95% CI 0.03 to 0.32) against incident COVID-19 infection (moderate certainty evidence). In absolute terms, this is 19 fewer cases per 1,000 vaccines delivered (ranging from 15 to 21 fewer cases). Observational studies reported vaccine effectiveness (VE) against incident COVID-19 infection of 65% (OR 0.35, 95% CI 0.26 to 0.47) and 76% against hospitalisation (OR 0.24, 95% CI 0.13 to 0.42) (moderate certainty evidence). The absolute effect is 167 fewer cases per 1,000 vaccines given (ranging from 130 fewer to 196 fewer cases) and 4 fewer hospitalisations per 10,000 children (from 3 fewer to 5 fewer hospitalisations). Adverse events following vaccination with BNT162b2 were mild or moderate and transient. The evidence demonstrated a reduction in incident COVID-19 cases and small absolute reduction in hospitalisation if a two-dose BNT162b2 vaccine regimen is offered to children aged 5 to 11 years, compared to placebo. PROSPERO registration: CRD42021286710.

Health Technology Assessment in Support of National Health Insurance in South Africa.

South Africa has embarked on major health policy reform to deliver universal health coverage through the establishment of National Health Insurance (NHI). The aim is to improve access, remove financial barriers to care, and enhance care quality. Health technology assessment (HTA) is explicitly identified in the proposed NHI legislation and will have a prominent role in informing decisions about adoption and access to health interventions and technologies. The specific arrangements and approach to HTA in support of this legislation are yet to be determined. Although there is currently no formal national HTA institution in South Africa, there are several processes in both the public and private healthcare sectors that use elements of HTA to varying extents to inform access and resource allocation decisions. Institutions performing HTAs or related activities in South Africa include the National and Provincial Departments of Health, National Treasury, National Health Laboratory Service, Council for Medical Schemes, medical scheme administrators, managed care organizations, academic or research institutions, clinical societies and associations, pharmaceutical and devices companies, private consultancies, and private sector hospital groups. Existing fragmented HTA processes should coordinate and conform to a standardized, fit-for-purpose process and structure that can usefully inform priority setting under NHI and for other decision makers. This transformation will require comprehensive and inclusive planning with dedicated funding and regulation, and provision of strong oversight mechanisms and leadership.

Improving intravenous fluid prescribing in the Eastern Cape in South Africa.

Intravenous fluids are an essential component of patient care, but a 2013 National Institute for Health and Care Excellence (NICE) guideline noted that inappropriate prescribing or administration may lead to actual or potential patient harm in up to 20% of patients.1 This project aimed to improve prescribing documentation and communication between nurses and doctors regarding intravenous fluid management. This was done through the introduction of a fluid chart, in combination with teaching on appropriate fluid management. It was initiated within the medical department of Cecelia Makiwane Hospital in East London, South Africa. 309 patients were included and data were analysed over a 6-month period. The outcome measures were the standards of intravenous fluid prescribing set by the NICE guidelines. The process measure was the use of the new chart. Baseline data highlighted that there was no standardised location for fluid prescriptions within the bedside notes. Following the intervention, 81% of fluid prescriptions were on a fluid chart. The percentage of fluid scripts with a 24-hour fluid prescription, a recorded indication and recorded input increased after the intervention. Seventy six per cent of patients received more than 50% of the fluids prescribed following the intervention compared with 22% at baseline. These results indicated an increase in the doctor's awareness of appropriate fluid prescribing and an improvement in the communication between doctors and nurses regarding the patient's fluid management. The engagement of local stakeholders and staff was fundamental to the success of the project and allowed for this change in practice. Fluid management is a vital part of care in many specialties; therefore, a toolkit has been created to allow similar quality improvement projects to be implemented across other hospitals around the Eastern Cape.

Improving TB infection control in a regional hospital in the Eastern Cape, South Africa.

This quality improvement (QI) work was carried out in Cecilia Makiwane Hospital (CMH), a regional public hospital in the Eastern Cape, South Africa (SA). SA has among the highest incidence of tuberculosis (TB) in the world and this is a leading cause of death in SA. Nosocomial infection is an important source of TB transmission. Adherence to TB infection prevention control (IPC) measures in the medical inpatient department was suboptimal at CMH. The overall aim of this QI project was to make sustainable improvements in TB IPC. A multidisciplinary team was formed to undertake a root cause analysis and develop a strategy for change. The main barriers to adherence to IPC measures were limited knowledge of IPC methods and stigma associated with TB. Specifically, the project aimed to increase the number of: 'airborne precaution' signs placed above patients' beds, patients correctly isolated and patients wearing surgical face masks. Four Plan-Do-Study-Act cycles were used. The strategy for change involved education and awareness-raising in different formats, including formal in-service training delivered to nurses and doctors, a hospital-wide TB awareness week with engaging activities and competitions, and a World TB Day provincial solidarity march. Data on adherence to the three IPC measures were collected over an 8-month period. Pre-intervention (October 2016), a mean of 2% of patients wore face masks, 22% were correctly isolated and 12% had an airborne precaution sign. Post-intervention (May 2017), the compliance improved to 17%, 50% and 25%, respectively. There was a large variation in compliance to each measure. Improvement was greatest in the number of patients correctly isolated. We learnt it is important to work with, not in parallel to, existing teams or structures during QI work. On-the-ground training of nurses and clinicians should be undertaken alongside engagement of senior staff members and managers. This improves the chance of change being adopted into hospital policy.

A Window Into the HIV Epidemic from a South African Emergency Department.

The aim of the study was to describe the HIV care continuum in emergency department (ED) patients in the Eastern Cape region of South Africa. This is a cross-sectional, identity-unlinked serosurvey, whereby discarded/excess samples from all patients who had blood drawn during the study period for routine care and sufficient serum remaining were tested for HIV, hepatitis B virus, and hepatitis C virus infection; HIV viral load (VL); and presence of antiretroviral (ARV) drugs. We also estimated cross-sectional incidence using the Limiting-Antigen Avidity assay and HIV VL. The study was conducted between September and November 2016 at the Frere Hospital Emergency Department in East London, South Africa. The overall HIV prevalence in our study population was 26.9% [95% confidence interval (CI): 25.0-28.8; n = 2,100]. The highest prevalence was observed among females in the 30-39 years age group [60.3% (95% CI: 53.2-67.1)]. HIV prevalence was significantly higher among females compared with males in both the 20-29 years age group and 30-39 years age group (p < .05), but nearly identical to older age groups. ARV drugs were detected in 53.5% (95% CI: 48.1-58.9) of HIV-infected subjects. The frequency of HIV viral suppression (< 1,000 copies/mL) was 48.5% (95% CI: 44.3-52.7), and was not statistically different between males and females (age-adjusted prevalence ratio = 1.15, 95% CI: 0.95-1.39). The HIV incidence rate was estimated to be 2.6% (95% CI: 1.2-3.9). The Frere Hospital ED has an extremely high burden of HIV infection. The detection of ARV drugs and prevalence of viral suppression fall short of the World Health Organization 90-90-90 goals in this population. Furthermore, there were a large number of patients with recent infection in the ED. The ED is a critical venue for testing and linkage to care of high-yield population who are likely missed by current testing and linkage-to-care programs.

Implementing emergency department-based HIV testing in a low-resource setting: The value of a structured feasibility assessment tool.

INTRODUCTION: HIV is a worldwide health problem with continuing high rates of new infections in many parts of the world. This lack of progress in decreasing overall incidence rates has sparked innovative HIV testing strategies, including expansion of testing into the emergency department (ED) setting. Emergency departments have been shown to be high-yield testing venues in the United States and other developed world settings. The feasibility of expanding public health HIV services in the ED in limited-resource countries is unclear. METHODS: We performed a cross-sectional feasibility assessment of a convenience sample of four hospitals in the Eastern Cape, South Africa. We administered three adapted interview tools from a previously field-tested survey instrument at each facility (total of 10 interviews) to gather an overview of the health facility, their HIV counselling and testing services, and their laboratory services. RESULTS: All of the health facilities had access to basic commodities such as water and electricity. Many had severe human resource limitations and provided care to wide population catchment areas. In addition, there was little integration of HIV testing into current daily ED operations. Hospital staff identified numerous barriers to future ED testing efforts. CONCLUSIONS: Although control of the HIV epidemic requires innovative testing strategies and treatment, specific assessments are warranted on how to incorporate routine HIV testing into an acute care facility like the ED, which typically has many competing priorities. The use of a prospective structured tool incorporating both barriers and benefits can provide valuable field-tested guidance for increased programme planning for HIV testing.

HIV testing in a South African Emergency Department: A missed opportunity.

BACKGROUND: South Africa has the largest HIV epidemic in the world, with 19% of the global number of people living with HIV, 15% of new infections and 11% of AIDS-related deaths. Even though HIV testing is mandated in all hospital-based facilities in South Africa (SA), it is rarely implemented in the Emergency Department (ED). The ED provides episodic care to large volumes of undifferentiated who present with unplanned injury or illness. Thus, the ED may provide an opportunity to capture patients with undiagnosed HIV infection missed by clinic-based screening programs. METHODS AND FINDINGS: In this prospective exploratory study, we implemented the National South African HIV testing guidelines (counselor initiated non-targeted universal screening with rapid point of care testing) for 24-hours a day at Frere Hospital in the Eastern Cape from September 1st to November 30th, 2016. The purpose of our study was to quantify the burden of undiagnosed HIV infection in a South African ED setting. Furthermore, we sought to evaluate the effectiveness of the nationally recommended HIV testing strategy in the ED. All patients who presented for care in the ED during the study period, and who were clinically stable and fully conscious, were eligible to be approached by HIV counseling and testing (HCT) staff to receive a rapid point-of-care HIV test. A total of 2355 of the 9583 (24.6%) patients who presented to the ED for care during the study period were approached by the HCT staff, of whom 1714 (72.8%) accepted HIV testing. There was a high uptake of HIV testing (78.6%) among a predominantly male (58%) patient group who mostly presented with traumatic injuries (70.8%). Four hundred (21.6%) patients were HIV positive, including 115 (6.2%) with newly diagnosed HIV infection. The overall prevalence of HIV infection was twice as high in females (29.8%) compared to males (15.4%). Both sexes had a similar prevalence of newly diagnosed HIV infection (6.0% for all females and 6.4% for all males) in the ED. CONCLUSIONS: Overall there was high HIV testing acceptance by ED patients. A non-targeted testing approached revealed a high HIV prevalence with a significant burden of undiagnosed HIV infection in the ED. Unfortunately, a counselor-driven HIV testing approach fell short of meeting the testing needs in this setting, with over 75% of ED patients not approached by HCT staff.

Patient and provider attitudes to emergency department-based HIV counselling and testing in South Africa.

BACKGROUND: The national South African HIV Counselling and Testing (HCT) guidelines mandate that voluntary counselling and testing (VCT) should be offered in all healthcare facilities. Emergency departments (EDs) are at the forefront of many healthcare facilities, yet VCT is not routinely implemented in this setting. METHODS: We conducted a cross-sectional study that surveyed patients and healthcare providers at a tertiary care ED in the spring and summer of 2016 to ascertain their attitudes to VCT in the ED. We also used two previously validated survey instruments to gather data on patients' HIV knowledge and providers' stigma against patients living with HIV, as we anticipated that these may have an impact on providers' and patients' attitudes to the provision of HIV testing within the ED, and may offer insights for future intervention development. RESULTS: A total of 104 patients and 26 providers were enrolled in the study. Overall, patients responded more favourably to ED-based HIV testing (92.3%) compared to providers (only 40% responded favourably). When asked about potential barriers to receiving or providing HIV testing, 16.4% of patients and 24% of providers felt that the subject of HIV was too sensitive and 58.7% of patients and 80% of providers indicated that privacy and confidentiality issues would pose major barriers to implementing ED-based HIV testing. CONCLUSION: This study shows that while ED-based HIV testing is overall highly acceptable to patients, providers seem less willing to provide this service. The survey data also suggest that future development of ED-based testing strategies should take into consideration privacy and confidentiality concerns that may arise within a busy emergency care setting. Furthermore, every effort should be made to tackle HIV stigma among providers to improve overall attitudes towards HIV-positive individuals that present for care in the ED.

Adverse Drug Reactions Causing Admission to Medical Wards: A Cross-Sectional Survey at 4 Hospitals in South Africa.

Limited data exist on the burden of serious adverse drug reactions (ADRs) in sub-Saharan Africa, which has high HIV and tuberculosis prevalence. We determined the proportion of adult admissions attributable to ADRs at 4 hospitals in South Africa. We characterized drugs implicated in, risk factors for, and the preventability of ADR-related admissions.We prospectively followed patients admitted to 4 hospitals' medical wards over sequential 30-day periods in 2013 and identified suspected ADRs with the aid of a trigger tool. A multidisciplinary team performed causality, preventability, and severity assessment using published criteria. We categorized an admission as ADR-related if the ADR was the primary reason for admission.There were 1951 admissions involving 1904 patients: median age was 50 years (interquartile range 34-65), 1057 of 1904 (56%) were female, 559 of 1904 (29%) were HIV-infected, and 183 of 1904 (10%) were on antituberculosis therapy (ATT). There were 164 of 1951 (8.4%) ADR-related admissions. After adjustment for age and ATT, ADR-related admission was independently associated (P ≤ 0.02) with female sex (adjusted odds ratio [aOR] 1.51, 95% confidence interval [95% CI] 1.06-2.14), increasing drug count (aOR 1.14 per additional drug, 95% CI 1.09-1.20), increasing comorbidity score (aOR 1.23 per additional point, 95% CI 1.07-1.41), and use of antiretroviral therapy (ART) if HIV-infected (aOR 1.92 compared with HIV-negative/unknown, 95% CI 1.17-3.14). The most common ADRs were renal impairment, hypoglycemia, liver injury, and hemorrhage. Tenofovir disoproxil fumarate, insulin, rifampicin, and warfarin were most commonly implicated, respectively, in these 4 ADRs. ART, ATT, and/or co-trimoxazole were implicated in 56 of 164 (34%) ADR-related admissions. Seventy-three of 164 (45%) ADRs were assessed as preventable.In our survey, approximately 1 in 12 admissions was because of an ADR. The range of ADRs and implicated drugs reflect South Africa's high HIV and tuberculosis burden. Identification and management of these ADRs should be considered in HIV and tuberculosis care and treatment programs and should be emphasized in health care worker training programmes.

Mortality from adverse drug reactions in adult medical inpatients at four hospitals in South Africa: a cross-sectional survey.

AIMS: Fatal adverse drug reactions (ADRs) are important causes of death, but data from resource-limited settings are scarce. We determined the proportion of deaths in South African medical inpatients attributable to ADRs, and their preventability, stratified by human immunodeficiency virus (HIV) status. METHODS: We reviewed the folders of all patients who died over a 30 day period in the medical wards of four hospitals. We identified ADR-related deaths (deaths where an ADR was 'possible', 'probable' or 'certain' using WHO-UMC criteria and where the ADR contributed to death). We determined preventability according to previously published criteria. RESULTS: ADRs contributed to the death of 2.9% of medical admissions and 56 of 357 deaths (16%) were ADR-related. Tenofovir, rifampicin and co-trimoxazole were the most commonly implicated drugs. 43% of ADRs were considered preventable. The following factors were independently associated with ADR-related death: HIV-infected patients on antiretroviral therapy (adjusted odds ratio (aOR) 4.4, 95% confidence interval (CI) 1.6, 12), exposure to more than seven drugs (aOR 2.5, 95% CI 1.3, 4.8) and increasing comorbidity score (aOR 1.3, 95% CI 1.1, 1.7). CONCLUSIONS: In our setting, where HIV and tuberculosis are highly prevalent, fatal in-hospital ADRs were more common than reported in high income settings. Most deaths were attributed to drugs used in managing HIV and tuberculosis. A large proportion of the ADRs were preventable, highlighting the need to strengthen systems for health care worker training and support.

AGREE to disagree: critical appraisal and the publication of practice guidelines.

Treatment guidelines are important in influencing public policy, promoting distributive justice and advocating better healthcare delivery for those in need. With an increased frequency in publication of clinical guidelines in South Africa, there is a heightened responsibility to ensure the application of due process throughout their development and publication. The need for consensus opinion is critical in the application of evidence-based medicine principles, and clinical guidelines contribute fundamentally towards the process of decision making and prioritisation. The SAMJ has recognised these imperatives as well as the important role that guidelines play in setting standards for clinical practice. In fulfilling this obligation, this editorial introduces the journal's readership to the AGREE II instrument as an objective appraisal mechanism against which prospective clinical guidelines will be assessed prior to their publication.

Improving clinical governance of HIV treatment programmes in resource poor settings: the role of digitising clinical notes.

Implementing clinical audit in a resource poor setting is often beset by practical issues. Out-sourcing the burden of data analysis may go a long way to facilitating regular audit in a resource poor setting. We investigated the feasibility of using an inexpensive 12-megapixel point-and-shoot digital camera to collect data from clinical notes in a format capable of being sent via secure electronic file transfer for remote analysis. We then performed a pilot audit on this data as a proof of principle.

Starch safety in resuscitation - when will we ever learn?

Recent trials have failed to demonstrate a survival benefit from the use of hydroxyethyl starches (HES) as a colloid in fluid resuscitation and have raised concerns of renal harm. In severe sepsis, there is a concerning signal of increased mortality. New high-quality systematic reviews consistently demonstrate a statistically non-significant relative risk of death of 1.08 - 1.10 and a significant 25% increased chance of requiring renal replacement therapy. The HES literature contains many industry-affiliated reviews of indifferent quality. Traditional efficacy confidence limits may warrant re-evaluation when considering these harms. Newer formulations of HES and more focused indications for use show benefit on surrogate endpoints, but these trials are currently underpowered to ensure safety.

Prevention of infective endocarditis in developing countries - justifiable caution?

The internationally accepted practice of prescribing prophylactic antibiotics to individuals at risk of infective endocarditis has come under scrutiny. There are no published high-quality randomised controlled trials of the intervention, but new insights have emerged. Bacteraemic episodes are common following simple activities such as brushing teeth. Endocarditis following procedures is extremely rare, and systematic reviews of the evidence for prophylactic antibiotics have failed to demonstrate efficacy.

Does the nose know? Amitraz poisoning and olfaction.

The initial clinical presentation of amitraz and organophosphate poisoning may be similar. Reduced serum pseudocholinesterase supports a diagnosis of organophosphate toxicity, but there is no similar laboratory test for amitraz poisoning. A 'mothball-like' odour associated with poisoned patients may have diagnostic potential. In a blinded controlled trial, 83% (95% confidence interval, 63% to 93%) of 23 healthcare workers were able to distinguish between the odours of amitraz and organophosphate. Awareness of this simple component of bedside examination may allow earlier recognition of this potentially fatal poisoning.

Mortality in patients treated for tuberculous pericarditis in sub-Saharan Africa.

OBJECTIVE: To determine the mortality rate and its predictors in patients with a presumptive diagnosis of tuberculous pericarditis in sub-Saharan Africa. DESIGN: Between 1 March 2004 and 31 October 2004, we enrolled 185 consecutive patients with presumed tuberculous pericarditis from 15 referral hospitals in Cameroon, Nigeria and South Africa, and observed them during the 6-month course of antituberculosis treatment for the major outcome of mortality. This was an observational study, with the diagnosis and management of each patient left at the discretion of the attending physician. Using Cox regression, we have assessed the effect of clinical and therapeutic characteristics (recorded at baseline) on mortality during follow-up. RESULTS: We obtained the vital status of 174 (94%) patients (median age 33; range 14 - 87 years). The overall mortality rate was 26%. Mortality was higher in patients who had clinical features of HIV infection than in those who did not (40% v. 17%, p=0.001). Independent predictors of death during followup were: (i) a proven non-tuberculosis final diagnosis (hazard ratio (HR) 5.35, 95% confidence interval (CI) 1.76 - 16.25), (ii) the presence of clinical signs of HIV infection (HR 2.28, CI 1.14 - 4.56), (iii) coexistent pulmonary tuberculosis (HR 2.33, CI 1.20 - 4.54), and (iv) older age (HR 1.02, CI 1.01 - 1.05). There was also a trend towards an increase in death rate in patients with haemodynamic instability (HR 1.80, CI 0.90 - 3.58) and a decrease in those who underwent pericardiocentesis (HR 0.34, CI 0.10 - 1.19). CONCLUSION: A presumptive diagnosis of tuberculous pericarditis is associated with a high mortality in sub-Saharan Africa. Attention to rapid aetiological diagnosis of pericardial effusion and treatment of concomitant HIV infection may reduce the high mortality associated with the disease.