Adult pure red cell aplasia at Universitas Academic Hospital, Bloemfontein, South Africa: A 9-year review.

BACKGROUND: Pure red cell aplasia (PRCA) is characterised by severe normochromic, normocytic anaemia and partial or complete absence of reticulocytes from the peripheral blood. With bone marrow of normal cellularity, an almost complete absence of erythroblasts but preservation of other cell lines is observed. It may be congenital or acquired, with the latter presenting as a primary haematological disorder or secondary to various contributing factors. Management focuses on treatment of the underlying cause and supportive transfusions. Occasionally, immunosuppression or intravenous immunoglobulin (IVIG) is required. OBJECTIVES: To describe the clinical characteristics, treatment and outcomes of adult patients diagnosed with PRCA at Universitas Academic Hospital (UAH) in Bloemfontein, South Africa, from 2010 to 2018. METHODS: A retrospective descriptive file review was performed. All adult patients diagnosed with PRCA and treated in the Division of Clinical Haematology at UAH during the study period were included. Variables recorded included demographic information, clinical details of the PRCA diagnosis, classification of the PRCA, HIV and parvovirus B19 test results, results of special investigations, medical and drug history, treatment and response to treatment. RESULTS: Twenty-seven patients' files were included, with a female predominance (n=22; 81.5%). The median age at diagnosis was 35 years (range 20 - 62). The median number of days from onset of symptoms to date of diagnosis was 61 days (range 27 - 114). Approximately half (n=13; 48.2%) of the patients presented with a haemoglobin concentration of 1 - 3 g/dL. Most patients (n=26; 96.3%) were infected with HIV, with 76.9% (n=20) having a suppressed viral load. Parvovirus B19 infection accounted for 44.4% of cases (n=12), and all these patients were HIV positive. Lamivudine was a probable cause of PRCA in 18.5% of cases, although the true causal relationship was uncertain. Corticosteroids and IVIG were first-line therapy in 44.4% (n=12) and 37.0% (n=10) of cases, respectively. Thirteen patients (48.2%) achieved a complete response and 7 (25.9%) a partial response, while 2 (7.4%) showed no response, with continued transfusion dependence. CONCLUSION: In this population, women were disproportionately affected by PRCA. HIV was the single most important cause of acquired PRCA, which was independent of virological control. Parvovirus B19 and drugs were also important causes of acquired PRCA and played a critical part in the evaluation and work-up of PRCA. Nearly half of the patients achieved a complete response to therapy, which was sustained over 24 months.

Undiagnosed comorbidities among individuals hospitalised with COVID-19 in South African public hospitals.

BACKGROUND: Previous studies have reported comorbid disease, including hypertension, diabetes mellitus, chronic cardiac and renal disease, malignancy, HIV, tuberculosis (TB) and obesity, to be associated with COVID­19 mortality. National demographic surveys have reported a high proportion of undiagnosed and untreated comorbid disease in South Africa (SA). OBJECTIVES: To determine the number of individuals with previously undiagnosed HIV, TB and non-communicable diseases (NCDs) among patients hospitalised with COVID­19, and the level of medical control of these chronic diseases. METHODS: We conducted a sentinel surveillance study to collect enhanced data on HIV, TB and NCDs among individuals with COVID­19 admitted to 16 secondary-level public hospitals in six of the nine provinces of SA. Trained surveillance officers approached all patients who met the surveillance case definition for inclusion in the study, and consenting patients were enrolled. The data collection instrument included questions on past medical history to determine the self-reported presence of comorbidities. The results of clinical and laboratory testing introduced as part of routine clinical care for hospitalised COVID­19 patients were collected for the study, to objectively determine the presence of hypertension, diabetes, HIV and TB and the levels of control of diabetes and HIV. RESULTS: On self-reported history, the most prevalent comorbidities were hypertension (n=1 658; 51.5%), diabetes (n=855; 26.6%) and HIV (n=603; 18.7%). The prevalence of self-reported active TB was 3.1%, and that of previous TB 5.5%. There were 1 254 patients admitted with COVID­19 (39.0%) who met the body mass index criteria for obesity. On clinical and laboratory testing, 87 patients were newly diagnosed with HIV, 29 with TB, 215 with diabetes and 40 with hypertension during their COVID­19 admission. There were 151/521 patients living with HIV (29.0%) with a viral load >1 000 copies/mL and 309/570 (54.2%) with a CD4 count <200 cells/µL. Among 901 patients classified as having diabetes, 777 (86.2%) had a glycated haemoglobin (HbA1c) level ≥6.5%. CONCLUSION: The study revealed a high prevalence of comorbid conditions among individuals with COVID­19 admitted to public hospitals in SA. In addition, a significant number of patients had previously undiagnosed hypertension, diabetes, HIV and active TB, and many and poorly controlled chronic disease, as evidenced by high HbA1c levels in patients with diabetes, and high viral loads and low CD4 levels in patients with HIV. The findings highlight the importance of strengthening health systems and care cascades for chronic disease management, which include prevention, screening for and effectively treating comorbidities, and ensuring secure and innovative supplies of medicines in primary healthcare during the COVID­19 pandemic.

Introducing an Ethics Framework for health priority-setting in South Africa on the path to universal health coverage.

BACKGROUND: South Africa (SA) has embarked on a process to implement universal health coverage (UHC) funded by National Health Insurance (NHI). The 2019 NHI Bill proposes creation of a health technology assessment (HTA) body to inform decisions about which interventions NHI funds will cover under UHC. In practice, HTA often relies mainly on economic evaluations of cost-effectiveness and budget impact, with less attention to the systematic, specific consideration of important social, organisational and ethical impacts of the health technology in question. In this context, the South African Values and Ethics for Universal Health Coverage (SAVE-UHC) research project recognised an opportunity to help shape the health priority-setting process by providing a way to take account of multiple, ethically relevant considerations that reflect SA values. The SAVE-UHC Research Team developed and tested an SA-specific Ethics Framework for HTA assessment and analysis. OBJECTIVES: To develop and test an Ethics Framework for use in the SA context for health priority-setting. METHODS: The Framework was developed iteratively by the authors and a multidisciplinary panel (18 participants) over a period of 18 months, using the principles outlined in the 2015 NHI White Paper as a starting point. The provisional Ethics Framework was then tested with multi-stakeholder simulated appraisal committees (SACs) in three provinces. The membership of each SAC roughly reflected the composition of a potential SA HTA committee. The deliberations and dedicated focus group discussions after each SAC meeting were recorded, analysed and used to refine the Framework, which was presented to the Working Group for review, comment and final approval. RESULTS: This article describes the 12 domains of the Framework. The first four (Burden of the Health Condition, Expected Health Benefits and Harms, Cost-Effectiveness Analysis, and Budget Impact) are commonly used in HTA assessments, and a further eight cover the other ethical domains. These are Equity, Respect and Dignity, Impacts on Personal Financial Situation, Forming and Maintaining Important Personal Relationships, Ease of Suffering, Impact on Safety and Security, Solidarity and Social Cohesion, and Systems Factors and Constraints. In each domain are questions and prompts to enable use of the Framework by both analysts and assessors. Issues that arose, such as weighting of the domains and the availability of SA evidence, were discussed by the SACs. CONCLUSIONS: The Ethics Framework is intended for use in priority-setting within an HTA process. The Framework was well accepted by a diverse group of stakeholders. The final version will be a useful tool not only for HTA and other priority-setting processes in SA, but also for future efforts to create HTA methods in SA and elsewhere.

Treatment outcomes of Acinetobacter baumannii -associated pneumonia and/or bacteraemia at the intensive care unit of Universitas Academic Hospital, Bloemfontein, South Africa.

BACKGROUND: Nosocomial infection with multidrug-resistant (MDR) Acinetobacter baumannii is associated with high mortality rates and the optimal treatment regimen is uncertain. OBJECTIVES: To compare outcomes, as well as ICU and in-hospital survival rates of patients with A. baumannii pneumonia and/or bacteraemia who were treated with colistin monotherapy v. colistin/tigecycline combination therapy. METHODS: This was a retrospective cross-sectional study of patients admitted to the multidisciplinary ICU of Universitas Academic Hospital, Bloemfontein, South Africa, between 1 January 2018 and 31 December 2019. RESULTS: Sixteen patients were included in the study. Nine patients were treated with a combination of colistin and tigecycline, while 7 patients were treated with colistin only. Seven out of 9 (77.8%) patients in the colistin/tigecycline combination therapy group were treated successfully and survived until discharge from ICU, as opposed to 2 out of 7 (28.6%) in the colistin monotherapy group (relative risk (RR) 2.7; 95% CI 0.80 - 9.24). Five out of 9 (55.6%) in the colistin/tigecycline combination therapy group v. 2 out of 7 (28.6%) in the colistin monotherapy group survived until discharge from hospital (RR 1.94; 95% CI 0.53 - 7.20). CONCLUSION: Although ICU survival in patients with A. baumannii infection was better when treated with colistin/tigecycline combination therapy compared with colistin monotherapy, a statistically significant difference could not be detected. Adequately powered prospective clinical trials are required to detect statistically significant differences in treatment outcomes.

Directionality of corticomuscular coupling in essential tremor and cortical myoclonic tremor.

OBJECTIVE: A role of the motor cortex in tremor generation in essential tremor (ET) is assumed, yet the directionality of corticomuscular coupling is unknown. Our aim is to clarify the role of the motor cortex. To this end we also study 'familial cortical myoclonic tremor with epilepsy' (FCMTE) and slow repetitive voluntary movements with a known cortical drive. METHODS: Directionality of corticomuscular coupling (EEG-EMG) was studied with renormalized partial directed coherence (rPDC) during tremor in 25 ET patients, 25 healthy controls (mimicked) and in seven FCMTE patients; and during a self-paced 2 Hz task in eight ET patients and seven healthy controls. RESULTS: Efferent coupling around tremor frequency was seen in 33% of ET patients, 45.5% of healthy controls, all FCMTE patients, and, around 2 Hz, in all ET patients and all healthy controls. Ascending coupling, seen in the majority of all participants, was weaker in ET than in healthy controls around 5-6 Hz. CONCLUSIONS: Possible explanations are that tremor in ET results from faulty subcortical output bypassing the motor cortex; rate-dependent transmission similar to generation of rhythmic movements; and/or faulty feedforward mechanism resulting from decreased afferent (sensory) coupling. SIGNIFICANCE: A linear cortical drive is lacking in the majority of ET patients.

Prevalence of isoniazid resistance-conferring mutations associated with multidrug-resistant tuberculosis in Free State Province, South Africa.

BACKGROUND: Multidrug- and extensively drug-resistant tuberculosis (MDR-TB and XDR- TB) threaten local and global control of the disease. The molecular line-probe assay (LPA) provides rapid diagnosis and early management of MDR-TB. The LPA detects mutations of katG and inhA genes associated with isoniazid (INH) resistance in Mycobacterium tuberculosis isolates. The katG and inhA genes are associated with high- and low-level INH resistance, respectively, as well as cross-resistance to ethionamide in the case of inhA gene mutations. Patients with MDR-TB due to an inhA mutation could benefit from the use of high-dose INH - instead of ethionamide - in their MDR-TB regimen. OBJECTIVES: To determine the frequencies of katG and inhA mutations that conferred INH resistance among MDR-TB isolates during 2014 - 2016 in Free State (FS) Province of South Africa. METHODS: We retrospectively reviewed MDR-TB isolates assayed with GenoType MTBDRplus (Hain Lifescience, Germany) (LPA) at the central TB laboratory of Universitas Academic Hospital, Bloemfontein, FS, and calculated the frequencies of katG and inhA mutations. RESULTS: Among 918 MDR-TB isolates, the prevalence of katG, inhA and katG plus inhA mutations was 63.9%, 13.4% and 22.7%, respectively. Approximately 60% (n=536; 58.4%) of the isolates were obtained from male patients. The patients' ages ranged from 1 to 89 (median 37) years. The Xhariep district had the highest incidence of INH resistance-conferring mutations in the province. CONCLUSIONS: katG-associated mutations are the predominant INH resistance-conferring mechanism among MDR-TB isolates in the FS. Patients infected with isolates that harbour the katG mutation are unlikely to benefit from high-dose INH therapy in the bedaquiline (BDQ)-containing modified short MDR-TB regimen. They may, however, benefit from the inclusion of ethionamide in the regimen. Dual katG and inhA gene mutations make these patients unlikely to respond to either high-dose INH or ethionamide and should now be considered for either the BDQ-containing long MDR-TB regimen or an individualised treatment regimen, depending on fluoroquinolone susceptibility. Clinicians should familiarise themselves with interpreting various INH resistance-conferring mutation results and their implications for management of MDR-TB treatment.

Event related potentials during attention tasks in VLBW children with and without attention deficit disorder.

OBJECTIVE: Children born prematurely have a higher incidence of attention deficit disorder with or without hyperactivity. We have used visual event related potentials to study possible brain dysfunctions that could explain this higher incidence. METHODS: Very low birth weight (VLBW) children with and without AD/HD and term born children with and without AD/HD, were matched for IQ, age and socio-economic status (n=41, mean age 104 months). A visual oddball paradigm, consisting of target and non-target stimuli, was used with analysis of response times, error scores, N200, P300 and a P500 component. RESULTS: AD/HD children responded slower (F (1,38)=11.20, p<0.002); more varied (F (1,38)=21.77, p<0.000) and made more commission and omission errors (Kruskal-Wallis p<0.000). Non-target N200 was increased in amplitude (F (1.39)=4.01, p=0.05) with a wide anterior topography in children with AD/HD. The late positivity (P500) was decreased over central leads in children with AD/HD during the non-target stimuli (F (3,75)=3.00, p<0.036). No differences could be found in latency, amplitude or topography between VLBW children with AD/HD and term born children with AD/HD. CONCLUSIONS: Prematurity does not induce specific attentional brain dysfunction or maturation delays in stimulus processing during cognitive tasks. Other factors should be investigated to explain the higher incidence of AD/HD in VLBW children.

The neurobiology of autism.

Although the primary cause of autism has not yet been unravelled, a number of genetic conditions have been strongly associated with the behavioural triad of autism. We briefly review the underlying neuropathological, biological and genetic evidence of the possible mechanisms involved in autism. This knowledge should guide accurate investigation of the autistic individual and genetic counselling of parents and family members.

Mosaic normal/15q11-q13 duplication associated with developmental delay but normal phenotype.

We report a proximal duplication in the long arm of chromosome 15 (15q11-15q13) in mosaic with a normal cell line in a 4-year-old boy presenting developmental delay and history of seizures, but normal phenotype.

[A model for handling grievances in nursing services]. / 'n Model vir griewehantering in verpleegdienste.

A model for management of grievances in a nursing service is described, in terms of the guidelines for model generation, based on a qualitative, exploratory, descriptive and theory generating research strategy and design. Potgieter's (1992) research served as the conceptual framework for the description of a model case. The statements derived from this description was used as basis for the description of the model. The central concepts were identified, defined and classified. The model was implemented in practice and was evaluated by means of a retrospective case study. Guidelines for the implementation of the model were consequently described and the model was positively evaluated by a panel of experts. The testing of hypothesis is recommended to validate the model.

[Grievances in South African hospitals: from a nursing service management perspective]. / Griewe in Suid-Afrikaanse hospitale: 'n Geskiedkundig-verpleegkundige perspektief.

The nursing service manager is accountable for adequate and efficient personnel management in the nursing service and the management of grievances is an important aspect of the personnel management function. The question arises, however, how and when grievances in nursing services arose and developed? The purpose of this article is to give a historical description of the development and management of grievances in nursing services for the time frame 1652-1990. An historical analysis was undertaken by means of news paper analysis, as well as other written resources. The results show that the development of grievances are related to the development of hospitals in South Africa and that grievances were poorly managed. The following conclusions are made: grievances in nursing are related to the establishment of hospitals; the first official grievance was lodged in 1824 by a surgeon; grievance are mainly related to the working conditions, remuneration and management; complaints with salaries and food were lodged by nurses as early as 1869; it appears as if nursing service managers are not adequately skilled in the management of grievances experienced by nursing staff--the same mistakes are made leading to strike action by nurses/midwives; unhappiness with the inappropriate manner in which grievances are managed lead to industrial action by nursing staff since 1889. Continuous empowerment of nursing services managers in the management of grievances is important and therefore the development of a model for grievance management in nursing services is also recommended.

Prevalence of isoniazid resistance-conferring mutations associated with multidrug-resistant tuberculosis in Free State Province, South Africa

Background. Multidrug- and extensively drug-resistant tuberculosis (MDR-TB and XDR- TB) threaten local and global control of the disease. The molecular line-probe assay (LPA) provides rapid diagnosis and early management of MDR-TB. The LPA detects mutations of katG and inhA genes associated with isoniazid (INH) resistance in Mycobacterium tuberculosis isolates. The katG and inhA genes are associated with high- and low-level INH resistance, respectively, as well as cross-resistance to ethionamide in the case of inhA gene mutations. Patients with MDR-TB due to an inhA mutation could benefit from the use of high-dose INH ­ instead of ethionamide ­ in their MDR-TB regimen.Objectives. To determine the frequencies of katG and inhA mutations that conferred INH resistance among MDR-TB isolates during 2014 - 2016 in Free State (FS) Province of South Africa.Methods. We retrospectively reviewed MDR-TB isolates assayed with GenoType MTBDRplus (Hain Lifescience, Germany) (LPA) at the central TB laboratory of Universitas AcademicHospital, Bloemfontein, FS, and calculated the frequencies of katG andinhAmutations.Results. Among 918 MDR-TB isolates, the prevalence of katG, inhA and katG plus inhA mutations was 63.9%, 13.4% and 22.7%,respectively.Approximately 60% (n=536; 58.4%) of the isolates were obtained from male patients. The patients' ages ranged from 1 to 89 (median 37) years. The Xhariep district had the highest incidence of INH resistance-conferring mutations in the province.Conclusions. katG-associated mutations are the predominant INH resistance-conferring mechanism among MDR-TB isolates in the FS. Patients infected with isolates that harbour the katG mutation are unlikely to benefit from high-dose INH therapy in the bedaquiline (BDQ)-containing modified short MDR-TB regimen. They may, however, benefit from the inclusion of ethionamide in the regimen. Dual katG and inhA gene mutations make these patients unlikely to respond to either high-dose INH or ethionamide and should now be considered for either the BDQ-containing long MDR-TB regimen or an individualised treatment regimen, depending on fluoroquinolone susceptibility. Clinicians should familiarise themselves with interpreting various INH resistance-conferring mutation results and their implications for management of MDR-TB treatment

History of medicine. Medicine in Bloemfontein--anecdotes from the turn of the century.

During the first year of the 1899-1902 Anglo-Boer War many doctors and patients arrived in Bloemfontein. One of these, Lord Denman, a grateful patient, donated an instrument cupboard to the Volks Hospital which survives to this day. In the later years of the war, Dr George Pratt Yule founded the Orange River Colony Medical Society, which eventually led, by a very roundabout route, to the founding of the Medical Association of South Africa, while Ella Scarlett became the first woman medical practitioner in the Free State.

Sleeping positions of infants in the Cape Peninsula.

The prone position is thought to be an important factor in the sudden infant death syndrome (SIDS). The sleep positions of unselected infants aged 6 months and younger attending clinics in the Cape Peninsula were studied; 62.4% slept prone with the face to the side. This position differs between the ethnic groups (whites 50.0%; blacks 58.7%; coloureds 69.8%) and the respondents' social class (higher classes 54.1%; lower classes 69.2%). The sex of the baby, the sleeping place and the educational level of the mother did not influence the position used. Ninety-four per cent of black infants slept with their mothers compared with 71% of coloured and 4% of white babies. The study confirmed that there are cultural differences in sleeping positions adopted by infants. The role this plays in SIDS among different ethnic groupings still needs to be clarified.

Information processing in very-low-birth-weight children with and without attention deficit disorder.

Very-low-birth-weight children (16 with and 45 without attention deficit/hyperactivity disorder) were matched to term-born controls (27 with attention deficit/hyperactivity disorder and 30 without) according to age, intelligence, and social class of their parents. The children were screened for motor, visual, and mental disabilities. The general aim of the study was to evaluate information processing stages using the additive factor method of Sternberg. The tasks consisted of computerized visual-motor letter recognition and arrow detection tasks. The tasks elicited similar prolongations of response times, increases in standard deviation of the response times, and increased error rates in the four groups. We conclude that very-low-birth-weight and control children do not differ in their information processing stages.

Immunological manifestations of HIV-infected children.

This cross-sectional study of stable HIV-infected children was designed to document the immunological manifestations of paediatric HIV infection and to determine whether inexpensive markers of immunosuppression could be identified. Investigations included lymphocyte count and subset analysis, levels of total protein, albumin, immunoglobulins, beta-2 microglobulin and neopterin. The median age of the 74 children studied was 16.5 months and 76% and 39% had subnormal percentage CD4+ counts and absolute CD4+ counts, respectively. According to the Centers for Disease Control (CDC) guidelines, 85% were moderately or severely immunosuppressed. The majority had elevated neopterin, beta-2 microglobulin, IgG, IgM and IgA concentrations. The IgG concentration correlated positively with total globulin, IgG1 and IgG3 concentrations. On bivariate analysis, the absolute CD4+ count correlated positively with total lymphocyte count (r = 0.28 < 0.48 < 0.64) and negatively with total IgG concentration (r = -0.47 < -0.27 < -0.04), IgG1 concentration (r = -0.51 < -0.31 < -0.08), and neopterin concentration (r = -0.49 < -0.28 < -0.04). There was no correlation between CD4+ count, total globulin or beta-2 microglobulin concentration. On multiple linear regression analysis only the total lymphocyte count correlated with CD4+ count. Furthermore, on bivariate analysis total lymphocyte count correlated positively with absolute CD8+ count (r = 0.82 < 0.88 < 0.92). In conclusion, although there was a positive correlation between absolute CD4+ count and total lymphocyte count, the clinical significance is questionable as the total lymphocyte count correlated more strongly with the absolute CD8+ count.