Shortfall in stroke care: A study of ischaemic stroke care practices in a South African metropole.

BACKGROUND: In recent years there have been significant advances in the management of stroke. In particular, reperfusion therapies have been shown to confer significant benefit, with the possibility of reversing ischaemic stroke or reducing disability when administered to suitable patients. However, these therapies also carry significant risk, including death. The South African (SA) and other international guidelines for stroke care provide recommendations to optimise benefit and reduce risk of these novel treatments. Failure to adhere to recommended guidelines can lead to increased preventable morbidity and mortality in such patients. OBJECTIVES: To describe the acute and post-acute ischaemic stroke services offered to patients in level 1, 2 and 3 hospitals in the Cape Metro Health District, determine levels of adherence to the SA stroke guideline, and identify barriers to optimal stroke patient care. METHODS: This study in five level 1, one level 2 and two level 3 public hospitals involved semi-structured interviewer-administered questionnaires and reviews of ischaemic stroke patient discharge summaries, hospital staffing, stroke protocols, diagnostic investigations available and stroke education for patients and their caregivers. The findings were then compared with recommendations in the national guideline. RESULTS: Twenty-eight participants (18 doctors, 10 nurses) from the general medical wards, stroke units and emergency units of eight hospitals were invited to participate in interviews. Most level 1 and 2 hospitals experienced difficulties transferring patients to higher levels of care. There was also limited access to stroke management protocols, inadequate stroke education among health professionals, pre- and in-hospital delays in patients receiving medical attention, and limited access to diagnostic investigations. As only a total of 12 stroke unit beds were available at the two level 3 hospitals, the majority of ischaemic stroke patients were admitted to the general medical wards of level 1, 2 and 3 hospitals. The level of care at all these facilities was not homogeneous. CONCLUSIONS: The two stroke units at the level 3 hospitals adhered most closely to the recommended SA stroke guideline. Elsewhere, ischaemic stroke care varied widely across general medical wards at all hospital levels. Adherence to the guideline was influenced by factors such as limited access to diagnostic investigations, patient delays in receiving medical attention, and shortages of staff. Monitoring systems for continuous evaluation of the quality of acute and post-acute stroke services are needed. The shortfall in compliance with recommended stroke treatment guidelines could lead to worse outcomes and exposure to litigation.

Registration of amiloride in South Africa: Cutting the Gordian knot.

Amiloride is an antagonist of the renal tubular epithelial sodium channel (ENaC). As such, it is a diuretic that is both potassium and magnesium sparing. It is used for the treatment of potassium depletion and hypertension, and is the specific therapy for hypertension due to overactivity of the ENaC (Liddle syndrome and several additional genetic causes of the Liddle phenotype - low renin and low aldosterone). It is listed as a World Health Organization essential drug, but has never been registered in South Africa (SA) and can therefore only be prescribed under a Section 21 application to the SA Health Products Regulatory Authority (SAHPRA) on a case-by-case basis. In SA, >50% of patients treated for hypertension are not controlled. In the USA, the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study reported that African Americans are more likely to be diagnosed with hypertension, more likely to be treated, more likely to be treated intensively, and less likely to achieve blood pressure (BP) control. Although the reasons are complex, studies show that 10 - 20% of blacks may carry the Liddle phenotype. Observational data and a controlled clinical trial done in three African countries have shown that these patients respond to amiloride and not to conventional guideline-based antihypertensive treatment. The former is likely to result in a significant reduction in cardiovascular, stroke and kidney morbidity and mortality, because of improved BP control. Amiloride is very unlikely to ever be registered in SA, as it was first developed >50 years ago, and SAHPRA regulations prevent widespread prescription of this essential drug. This is a classic Gordian knot that requires a novel approach from authorities to sever the knot and improve the health of many South Africans.

Poor anticoagulation control in patients taking warfarin at a tertiary and district-level prothrombin clinic in Cape Town, South Africa.

BACKGROUND: Warfarin is the most commonly used anticoagulant for both primary and secondary prevention of thromboembolism. For anticoagulation efficacy, the international normalised ratio (INR) needs to be within the therapeutic range for at least 65% of time on warfarin. OBJECTIVES: To describe INR control in patients on long-term warfarin and identified predictors of good INR control at two dedicated warfarin follow-up clinics in Cape Town, South Africa (SA). METHODS: We reviewed clinical records of patients in care at the INR clinics at Mitchell's Plain Community Health Centre and Groote Schuur Hospital. We included patients who had been on warfarin therapy for at least 27 months and excluded patients with <6 months of INR monitoring data or a >70-day gap between INR tests in the calculation period, and if >25% of follow-up time was at an alternative site. The time in therapeutic range (TTR) over 180 days using the Rosendaal method was calculated, and we categorised INR control as good if the TTR was ≥65%. We constructed a multivariate logistic regression model to identify associations with good INR control. RESULTS: We included 363 patients, with a median age of 55 years (interquartile range (IQR) 44 - 64), of whom 65.6% were women. The most common indications for warfarin were valvular heart disease (45.7%) and atrial fibrillation (25.1%). The mean TTR was 47%, with only 91/363 patients having good INR control. In a multivariate model adjusted for age, sex, clinic and target INR, patients aged ≥55 years were more likely to have good INR control than younger patients (adjusted odds ratio 1.69, 95% confidence interval 1.03 - 2.79). Poorly controlled patients had more frequent INR monitoring than those with good INR control, with a median of 8 INRs (IQR 6 - 10) v. 6 INRs (IQR 5 - 8) in the 180-day period (p<0.0001). CONCLUSIONS: Only 25.1% of patients in our study achieved good INR control, despite regular INR monitoring. There is an urgent need to improve anticoagulation control of patients receiving warfarin in SA. Validated dosing algorithms are required, and access to lower warfarin dosage formulations may optimise individual dose titration. Advocacy for these formulations is advised.

The hereditary ataxias: Where are we now? Four decades of local research.

The hereditary ataxias have been studied at the University of Cape Town for more than 40 years, following from initial clinical investigations by Beighton and colleagues in the early 1970s. This group of inherited disorders is characterised by progressive neurodegeneration and associated symptoms, including the inability to coordinate movement. Following initial local and international linkage studies, and the discovery of the genes responsible for the key dominant and recessive inherited ataxias in the 1990s, a local molecular testing service was established at Groote Schuur Hospital. More than 1 600 individuals have been referred through this testing service (now offered by the National Health Laboratory Service), leading to the molecular diagnosis of 253 families with spinocerebellar ataxia types 1, 2, 3, 6 or 7, and 30 families with Friedreich's ataxia. This is likely to be an under-representation of the number of South Africans affected with hereditary ataxia, and future research efforts will focus on increasing the awareness of this group of disorders, both locally and throughout the rest of Africa. Next-generation technologies will be beneficial in identifying additional genes underlying inherited ataxia in indigenous patients to enable more appropriate management and treatment of individuals with molecularly undiagnosed forms of the disease.

Acute intermittent porphyria presenting as progressive muscular atrophy in a young black man.

Acute intermittent porphyria, the most common porphyria affecting the nervous system, typically presents with neurovisceral crises followed by a motor neuropathy. We describe a 23-year-old black South African man presenting with a progressive stuttering, lower motor neuron syndrome developing over months. He had not experienced pain or neuropsychiatric symptoms. One year after symptom onset he was bed-bound with a flaccid quadriparesis. There was marked amyotrophy, but without fasciculations. Sensation was intact apart from a hypo-aesthetic patch over the thigh. Electrophysiological investigations showed an active motor axonopathy. Urinary porphyrins, delta-aminolaevulinic acid and porphobilinogen were elevated. Mutation analysis revealed the c445C>T (R149X) mutation in the porphobilinogen deaminase gene. The patient responded dramatically to haem arginate and could walk with assistance 2 weeks later. We identified the first molecularly confirmed acute intermittent porphyria in a black South African. The clinical presentation mimicked a progressive lower motor neuron syndrome.

Thrombolysis risk prediction: applying the SITS-SICH and SEDAN scores in South African patients.

At present, the only specific medical treatment for acute ischaemic stroke is intravenous administration of recombinant tissue plasminogen activator within 4.5 hours of stroke onset. In the last year, two scores for risk stratification of intracranial haemorrhage have been derived from multicentric European trial groups, the Safe Implementation of Treatment in Stroke - Symptomatic IntraCerebral Haemorrhage risk score (SITS-SICH) and the SEDAN score. The aim of this study was to pilot their use in a cohort of patients treated at a South African tertiary hospital. Prospectively collected data were used from a cohort of 41 patients who underwent thrombolysis at Groote Schuur Hospital from 2000 to 2012. Computerised tomography brain imaging was available for review in 23 of these cases. The SITS-SICH and SEDAN scores were then applied and risk prediction was compared with outcomes. Two patients suffered symptomatic intracranial haemorrhage (SICH), representing 4.9% (95% CI: 0-11.5%) of the cohort. This was comparable to the SICH rate in both the SITS-SICH (5.1%) and SEDAN (6.5%) cohorts. Patient scores in the Groote Schuur Hospital cohort appeared similar to those of the validation cohorts of both SITS-SICH and SEDAN. With increasing use of thrombolysis in a resource-constrained setting, these scores represent a potentially useful tool in patient selection of those most likely to benefit from intravenous thrombolysis, reducing risk for SICH and with the added benefit of curtailing cost.

Thrombolysis risk Prediction : Applying the SITS-SICH and SEDAN Scores in South African Patients : Cardiovascular Topic

Abstract: At present; the only specific medical treatment for acute ischaemic stroke is intravenous administration of recombinant tissue plasminogen activator within 4.5 hours of stroke onset. In the last year; two scores for risk stratification of intracranial haemorrhage have been derived from multicentric European trial groups; the Safe Implementation of Treatment in Stroke - Symptomatic IntraCerebral Haemorrhage risk score (SITS-SICH) and the SEDAN score. The aim of this study was to pilot their use in a cohort of patients treated at a South African tertiary hospital. Prospectively collected data were used from a cohort of 41 patients who underwent thrombolysis at Groote Schuur Hospital from 2000 to 2012. Computerised tomography brain imaging was available for review in 23 of these cases. The SITS-SICH and SEDAN scores were then applied and risk prediction was compared with outcomes.Two patients suffered symptomatic intracranial haemorrhage (SICH); representing 4.9 (95 CI: 0-11.5) of the cohort. This was comparable to the SICH rate in both the SITS-SICH (5.1) and SEDAN (6.5) cohorts. Patient scores in the Groote Schuur Hospital cohort appeared similar to those of the validation cohorts of both SITS-SICH and SEDAN. With increasing use of thrombolysis in a resource-constrained setting; these scores represent a potentially useful tool in patient selection of those most likely to benefit from intravenous thrombolysis; reducing risk for SICH and with the added benefit of curtailing cost. (95 CI: 0-11.5) of the cohort. This was comparable to the SICH rate in both the SITS-SICH (5.1) and SEDAN (6.5) cohorts. Patient scores in the Groote Schuur Hospital cohort appeared similar to those of the validation cohorts of both SITS-SICH and SEDAN. With increasing use of thrombolysis in a resource-constrained setting; these scores represent a potentially useful tool in patient selection of those most likely to benefit from intravenous thrombolysis; reducing risk for SICH and with the added benefit of curtailing cost

Inherited polyglutamine spinocerebellar ataxias in South Africa.

OBJECTIVE: To determine the frequency and distribution of polyglutamine spinocerebellar ataxias (SCAs) from referrals over a 24-year period to the National Health Laboratory Service (NHLS) in South Africa (SA). METHODS: Paper-based clinical reports in the University of Cape Town laboratory and the NHLS electronic patient record database spanning a 24-year period were mined for information regarding the molecular diagnosis, ethnicity and CAG repeat length for individuals referred for molecular genetic testing for the polyglutamine SCAs. RESULTS: SCA1 and 7 are the most frequent types of polyglutamine SCA in the SA patient population, followed by SCA2, 3 and 6. SCA1 is the most common type in the coloured, white and Indian populations, whereas the majority of indigenous black African patients are affected with SCA7 and 2. Of individuals tested, 22% were found to be positive for one of the polyglutamine SCAs. CONCLUSION: Although trends in the frequency and distribution of the polyglutamine SCAs in SA have not changed significantly since our previous study in 2003, they differ remarkably from those reported elsewhere, and reflect the unique genetic and demographic background of SA. The provision of accurate and complete patient information and family history is crucial to the diagnostic process, to enable comprehensive epidemiological studies and assist in developing therapeutic and patient management strategies.

The South African stroke risk in general practice study.

BACKGROUND: Incidence of stroke is increasing in sub-Saharan Africa and stroke prevention is an essential component of successful stroke management. General practitioners (GPs) are well placed to manage stroke risk factors. To design appropriate strategies for risk factor reduction we need to know the risk factor prevalence in each of the population groups attending GPs. The aim of this study was to establish the prevalence of stroke risk factors in the South African general practice population. METHOD: We conducted a multicentre, observational study of patients attending general practice in South Africa. Two hundred general practices were randomly selected from lists provided by pharmaceutical representatives. Each GP approached 50 consecutive patients aged 30 years and older. Patients completed an information sheet and the GP documented the patient's risk factors. The resulting sample is relevant if not necessarily representative in a statistical sense. RESULTS: A total of 9 731 questionnaires were returned out of a possible 10,000. The mean age of particpants was 50.7 years. Seventy-six per cent had 1 or more risk factors and 40% had 2 or more risk factors. Hypertension was the commonest risk factor in all population groups (55%) but was highest in black patients (59%). Dyslipidaemia was commonest in whites (37%) and least common in blacks (5%). Diabetes was commonest in Asians (24%) but least common in whites (8%). Risk factors other than smoking increased with age. CONCLUSION: This study provides unique data on the prevalence of stroke risk factors in a South African general practice population. Risk factors are common in all population groups, but differ in distribution among the groups. There is considerable opportunity to reduce the burden of stroke in South Africa through GP screening for and treatment of risk factors.

Renal outcome of type 2 diabetes in South Africa--a 12-year follow-up study.

AIMS: Previous studies of type 2 diabetes mellitus have indicated a benign renal outcome after long-term follow-up. The aim of this study was to determine how often renal failure due to diabetic nephropathy was a cause of death in patients with type 2 diabetes. METHODS: Prospective observational study of 59 South African patients with type 2 diabetes over a 12-year period. During the study repeated clinical evaluations were accompanied by measurements of serum creatinine, serum cholesterol, random blood sugar, and urine protein/creatinine ratios. RESULTS: The mean duration of diabetes at the end of the study was 17.8 years. There was a wide variation in the time from clinical diagnosis of diabetes to macroproteinuria (mean 9.7 years, SD 5.9, range 0 - 21) and the rate of deterioration of renal function. This rate correlated with poor control of blood pressure, a glucose level of > 14 mmol/l, heavy proteinuria, a high retinopathy score, a body mass index of < 28 and the number of pack years of smoking. At the end of the study 47 patients (79.7%) had died. Of these deaths 17 (28.8%) were due to chronic renal failure. CONCLUSIONS: In contrast to other studies we have shown that in a developing country renal failure in type 2 diabetic patients is a major cause of death. Determining the prognosis for an individual patient is difficult as there are wide ranges in the time of onset of proteinuria, the rise in serum creatinine and the time to ultimate progression to end-stage renal failure.