The burden of serious adverse drug reactions in South Africa

Background The burden of serious adverse drug reactions (ADRs) in South Africa (SA) is not well characterised, and may be influenced by the high HIV prevalence. This thesis aims to describe this burden, by reporting findings of three hospital-based surveys of (1) ADRs causing death among adult medical inpatients, (2) ADRs causing admission of adults to medical wards, and (3) serious ADRs causing admission, prolongation of existing admission, or death among paediatric medical inpatients. Survey findings are contextualised in a systematic review of studies characterising serious ADR burden in sub-Saharan Africa (SSA). Methods In each of the three surveys, folder review with the assistance of trigger tools was used to identify potential serious ADRs. Multidisciplinary teams assessed causality, preventability, and seriousness of these events using published criteria. The World Health Organization-Uppsala Monitoring Centre system for standardised case causality assessment was used. This choice was informed by a study using a sample of cases from one of our adult surveys, which demonstrated its higher interrater agreement compared with the Liverpool ADR Causality Assessment Tool. Multivariable logistic regression was used to explore associations between demographic and clinical factors and the occurrence of serious ADRs. Results Among adult medical inpatients 56 of 357 deaths (16%) and 164 of 1951 admissions (8.4%) were ADR-related, and 43% and 45% respectively of these serious ADRs were preventable. Drugs used in the management of HIV and tuberculosis were frequently implicated. Among paediatric inpatients 3.8 serious ADRs occurred per 100 drug-exposed admissions, of which 23% were preventable and 20% fatal or near-fatal. A broad range of drugs was implicated in these serious paediatric ADRs. HIV positive status was independently associated with an increased risk of ADRs in every survey. Fifteen studies contributed to the systematic review. The median proportion of admissions attributed to ADRs was 6.4% [IQR 4.0% to 8.4%] among nine active surveillance studies in adults in SSA, with antiretroviral and antituberculosis drugs often implicated in serious ADRs. Conclusions Fatal, near-fatal, and hospitalising ADRs occurred frequently in South African hospitals. Many of these serious ADRs, particularly in adults, were preventable. Serious ADRs should be addressed in patient and health worker education, and safety monitoring systems improved. In SA and SSA the high HIV prevalence appears to be a driver of serious ADRs

Manual versus instrument assisted manipulation in the treatment of thoracic facet dysfunction

Abstract: Purpose: the aim of this study was to compare manual manipulative therapy to instrument assisted manipulative therapy in the treatment of thoracic facet dysfunction. Method: Thirty symptomatic participants with thoracic facet dysfunction were selected. The participants were divided equally into two groups, each group presenting a different treatment. One group received manual spinal manipulation using the Diversified Technique and the other received instrument assisted manipulation with the use of the Activator Adjusting Instrument. The participants needed to fulfil to the inclusion and exclusion criteria to form part of this study. Each participant had to have seven consultations within a three week period. Each participant received treatment six out of the seven consultations. Procedure: Subjective data was collected using the McGill Pain Questionnaire and the Numerical Pain Scale. Objective data was collected using an algometer to measure pressure pain threshold. Completion of the questionnaire and pain scale as well as algometer readings were recorded prior to treatment on the first, fourth and seventh consultations. The data was then analysed by a statistician. Results: Clinical improvement was noted in both groups over the duration of the study with regards to pain. The manual manipulation group did show a greater improvement in algometer measurements. No statistical significance was observed. Conclusion: The results indicated that both spinal manipulative therapies are effective in the treatment of thoracic facet dysfunction. Manual manipulative therapy did prove to be slightly more effective

Managing benchmarking in a corporate environment

Most new generation organisations have management models and processes for measuring and managing organisational performance. However, the application of these models and the direction the company needs to take are not always clearly established. Benchmarking can be defined as the search for industry best practices that lead to superior performance. The emphasis is on “best” and “superior”. There are no limitations on the search; the more creative the thinking, the greater the potential reward. Unlike traditional competitive analysis that focuses on outputs, benchmarking is applied to key operational processes within the business. Processes are compared and the best process is adapted into the organisation. Benchmarking is not guaranteed to be successful though, it needs to be managed and nurtured in the organisation and allowed to grow throughout the organisation to finally become a way of life. It also needs to be integrated into key business processes in order to ensure that the benefits can be reaped into the distant future. This paper provide guidelines for creating, managing and sustaining a benchmarking capability in a corporationDie nuwe generasie van ondernemings beskik oor bestuursmodelle en –prosesse wat meting en die bestuur van ondernemingsvertoning in die hand werk. Die wyse waarop die modelle toegepas word en hoe die onderneming sy besluite moet vorm is nog nie deeglik uitgetrap nie. Praktykvergelykings ("Benchmarking") word beskryf as die soeke na beste bedryfspraktyke wat lei tot uitstekende vertoning. Die klem word geplaas op die woorde "beste" en "uitstekende". Die soektog word geensins beperk nie; hoe meer kreatief die benadering, des te beter is die potensiële beloning. Waar tradisionele mededingingsnanalise ondernemingsuitsette onder die loep neem word praktykvergelyking togepas op sleutelprosesse in die bedryf van die onderneming. Prosesse word met mekaar vergelyk om die beste praktyk te kan volg. So 'n gestruktureerde leerproses lei die onderneming langs 'n kontinue weg van verbetering tot by die "beste" praktyk. Praktykvergelyking moet bestuur en vertroetel word om pos te vat as 'n bestaanswyse van die onderneming. Dit moet veral deel vorm van die onderneming se sleutelprosesse sodat voordele daarvan in die toekoms verseker kan word. Hierdie navorsing voorsien riglyne vir die daarstelling, bestuur en handhawing van praktykvergelyking as 'n vaste komponent van die onderneming se kultuurhttp://sajie.journals.ac.z

Vaginal leiomyoma presenting as a lateral vaginal wall mass

Leiomyomas are classified as benign mesenchymal neoplasms and consist of smooth muscle cells with variable amounts of fibrous stroma. The tumours occur most frequently in the uterus, affecting 20–30% of women of reproductive age but vaginal leiomyomas are rare with only around 300 cases reported since the first case was described in 1733. These tumours are thought to arise from Müllerian smooth muscle cells in the sub-epithelium of the vagina. Vaginal leiomyomas are usually situated in the anterior vaginal wall. This article reports a case of primary leiomyoma arising from the left lateral vaginal wall, which presented with vaginal discharge and a lateral vaginal wall mass.http://www.sajgo.co.za/index.php/sajgoam2018Obstetrics and Gynaecolog

The effect of the COVID-19 lockdown on mental health care use in South Africa: an interrupted time-series analysis.

AIMS The coronavirus disease 2019 (COVID-19) pandemic and ensuing restrictions have negatively affected the mental health and well-being of the general population, and there is increasing evidence suggesting that lockdowns have led to a disruption of health services. In March 2020, South Africa introduced a lockdown in response to the COVID-19 pandemic, entailing the suspension of all non-essential activities and a complete ban of tobacco and alcohol sales. We studied the effect of the lockdown on mental health care utilisation rates in private-sector care in South Africa. METHODS We conducted an interrupted time-series analysis using insurance claims from 1 January 2017 to 1 June 2020 of beneficiaries 18 years or older from a large private sector medical insurance scheme. We calculated weekly outpatient consultation and hospital admission rates for organic mental disorders, substance use disorders, serious mental disorders, depression, anxiety, other mental disorders, any mental disorder and alcohol withdrawal syndrome. We calculated adjusted odds ratios (OR) for the effect of the lockdown on weekly outpatient consultation and hospital admission rates and the weekly change in rates during the lockdown until 1 June 2020. RESULTS 710 367 persons were followed up for a median of 153 weeks. Hospital admission rates (OR 0.38; 95% confidence interval (CI) 0.33-0.44) and outpatient consultation rates (OR 0.74; 95% CI 0.63-0.87) for any mental disorder decreased substantially after the introduction of the lockdown and did not recover to pre-lockdown levels by 1 June 2020. Health care utilisation rates for alcohol withdrawal syndrome doubled after the introduction of the lockdown, but the statistical uncertainty around the estimates was large (OR 2.24; 95% CI 0.69-7.24). CONCLUSIONS Mental health care utilisation rates for inpatient and outpatient services decreased substantially after the introduction of the lockdown. Hospital admissions and outpatient consultations for alcohol withdrawal syndrome increased after the introduction of the lockdown, but statistical uncertainty precludes strong conclusions about a potential unintended effect of the alcohol sales ban. Governments should integrate strategies for ensuring access and continuity of essential mental health services during lockdowns in pandemic preparedness planning

Adult medical emergency unit presentations due to adverse drug reactions in a setting of high HIV prevalence

South Africa has the world's largest antiretroviral treatment programme, which may contribute to the adverse drug reaction (ADR) burden. We aimed to determine the proportion of adult non-trauma emergency unit (EU) presentations attributable to ADRs and to characterise ADR-related EU presentations, stratified according to HIV status, to determine the contribution of drugs used in management of HIV and its complications to ADR-related EU presentations, and identify factors associated with ADR-related EU presentation. Methods: We conducted a retrospective folder review on a random 1.7% sample of presentations over a 12-month period in 2014/2015 to the EUs of two hospitals in Cape Town, South Africa. We identified potential ADRs with the help of a trigger tool. A multidisciplinary panel assessed potential ADRs for causality, severity, and preventability

HIV-1 drug resistance in people on dolutegravir-based antiretroviral therapy:a collaborative cohort analysis

BACKGROUND The widespread use of the integrase strand transfer inhibitor (INSTI) dolutegravir in first-line and second-line antiretroviral therapy (ART) might facilitate emerging resistance. The DTG RESIST study combined data from HIV cohorts to examine patterns of drug resistance mutations (DRMs) and identify risk factors for dolutegravir resistance. METHODS We included cohorts with INSTI resistance data from two collaborations (ART Cohort Collaboration, International epidemiology Databases to Evaluate AIDS in Southern Africa), and the UK Collaborative HIV Cohort. Eight cohorts from Canada, France, Germany, Italy, the Netherlands, Switzerland, South Africa, and the UK contributed data on individuals who were viraemic on dolutegravir-based ART and underwent genotypic resistance testing. Individuals with unknown dolutegravir initiation date were excluded. Resistance levels were categorised using the Stanford algorithm. We identified risk factors for resistance using mixed-effects ordinal logistic regression models. FINDINGS We included 599 people with genotypic resistance testing on dolutegravir-based ART between May 22, 2013, and Dec 20, 2021. Most had HIV-1 subtype B (n=351, 59%), a third had been exposed to first-generation INSTIs (n=193, 32%), 70 (12%) were on dolutegravir dual therapy, and 18 (3%) were on dolutegravir monotherapy. INSTI DRMs were detected in 86 (14%) individuals; 20 (3%) had more than one mutation. Most (n=563, 94%) were susceptible to dolutegravir, seven (1%) had potential low, six (1%) low, 17 (3%) intermediate, and six (1%) high-level dolutegravir resistance. The risk of dolutegravir resistance was higher on dolutegravir monotherapy (adjusted odds ratio [aOR] 34·1, 95% CI 9·93-117) and dolutegravir plus lamivudine dual therapy (aOR 9·21, 2·20-38·6) compared with combination ART, and in the presence of potential low or low (aOR 5·23, 1·32-20·7) or intermediate or high-level (aOR 13·4, 4·55-39·7) nucleoside reverse transcriptase inhibitor (NRTI) resistance. INTERPRETATION Among people with viraemia on dolutegravir-based ART, INSTI DRMs and dolutegravir resistance were rare. NRTI resistance substantially increased the risk of dolutegravir resistance, which is of concern, notably in resource-limited settings. Monitoring is important to prevent resistance at the individual and population level and ensure the long-term sustainability of ART. FUNDING US National Institutes of Health, Swiss National Science Foundation

Serious adverse drug reactions at two children’s hospitals in South Africa

Abstract Background The high HIV prevalence in South Africa may potentially be shaping the local adverse drug reaction (ADR) burden. We aimed to describe the prevalence and characteristics of serious ADRs at admission, and during admission, to two South African children’s hospitals. Methods We reviewed the folders of children admitted over sequential 30-day periods in 2015 to the medical wards and intensive care units of each hospital. We identified potential ADRs using a trigger tool developed for this study. A multidisciplinary team assessed ADR causality, type, seriousness, and preventability through consensus discussion. We used multivariate logistic regression to explore associations with serious ADRs. Results Among 1050 patients (median age 11 months, 56% male, 2.8% HIV-infected) with 1106 admissions we found 40 serious ADRs (3.8 per 100 drug-exposed admissions), including 9/40 (23%) preventable serious ADRs, and 8/40 (20%) fatal or near-fatal serious ADRs. Antibacterials, corticosteroids, psycholeptics, immunosuppressants, and antivirals were the most commonly implicated drug classes. Preterm neonates and children in middle childhood (6 to 11 years) were at increased risk of serious ADRs compared to infants (under 1 year) and term neonates: adjusted odds ratio (aOR) 5.97 (95% confidence interval 1.30 to 27.3) and aOR 3.63 (1.24 to 10.6) respectively. Other risk factors for serious ADRs were HIV infection (aOR 3.87 (1.14 to 13.2) versus HIV-negative) and increasing drug count (aOR 1.08 (1.04 to 1.12) per additional drug). Conclusions Serious ADR prevalence in our survey was similar to the prevalence found elsewhere. In our setting, serious ADRs were associated with HIV-infection and the antiviral drug class was one of the most commonly implicated. Similar to other sub-Saharan African studies, a large proportion of serious ADRs were fatal or near-fatal. Many serious ADRs were preventable

A cross-sectional evaluation of five warfarin anticoagulation services in Uganda and South Africa

INTRODUCTION:Warfarin is the most commonly prescribed oral anticoagulant in sub-Saharan Africa and requires ongoing monitoring. The burden of both infectious diseases and non-communicable diseases is high and medicines used to treat comorbidities may interact with warfarin. We describe service provision, patient characteristics, and anticoagulation control at selected anticoagulation clinics in Uganda and South Africa. METHODS:We evaluated two outpatient anticoagulation services in Kampala, Uganda and three in Cape Town, South Africa between 1 January and 31 July 2018. We collected information from key staff members about the clinics' service provision and extracted demographic and clinical data from a sample of patients' clinic records. We calculated time in therapeutic range (TTR) over the most recent 3-month period using the Rosendaal interpolation method. RESULTS:We included three tertiary level, one secondary level and one primary level anticoagulation service, seeing between 30 and 800 patients per month. Care was rendered by nurses, medical officers, and specialists. All healthcare facilities had on-site pharmacies; laboratory INR testing was off-site at two. Three clinics used warfarin dose-adjustment protocols; these were not validated for local use. We reviewed 229 patient clinical records. Most common indications for warfarin were venous thrombo-embolism in 112/229 (49%), atrial fibrillation in 74/229 (32%) and valvular heart disease in 30/229 (13%). Patients were generally followed up monthly. HIV prevalence was 20% and 5% at Ugandan and South African clinics respectively. Cardiovascular comorbidity predominated. Furosemide, paracetamol, enalapril, simvastatin, and tramadol were the most common concomitant drugs. Anticoagulation control was poor at all included clinics with median TTR of 41% (interquartile range 14% to 69%). CONCLUSIONS:TTR was suboptimal at all included sites, despite frequent patient follow-up. Strategies to improve INR control in sub-Saharan patients taking warfarin are needed. Locally validated warfarin dosing algorithms in Uganda and South Africa may improve INR control