Paul Rheeder

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 patients 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.

The effects of social support on health, well-being and management of diabetes mellitus: a black South African perspective

Objectives To determine the underlying dimensions of a social support measure and investigate the effects of social support on health, well-being and management of diabetes mellitus (metabolic control and blood pressure (BP) control). Design A cross-sectional, analytical design was used with a structured questionnaire, comprising demographic characteristics, the MOS Social Support Survey scale and the health perceptions and mental health sub-scales from the SF-20. Setting Two outpatient diabetes mellitus clinics in Pretoria, South Africa. Participants Over a three-month period, the questionnaire was administered to 263 black diabetes mellitus outpatients (174 women and 89 men), aged between 16 and 89 years. The majority of patients (91%) were diagnosed as type 2 diabetes mellitus. Only 22% of the patients had acceptable metabolic control (HbA1c<8.0%), in comparison with 46% who had good BP control (130/85 mmHg). There were significant differences between the clinics on BP control: participants from clinic 1 had better BP control than participants from clinic 2. Results Principal components analysis, followed by an orthogonal (VARIMAX) rotational solution, resulted in two social support factors accounting for 78.9% of the variance. The first factor was labelled socio-emotional support, due to the emphasis on close caring relationships. The second factor was concerned with the more tangible aspects of social support, such as the provision of assistance. Coefficient alpha was 0.97 (socio-emotional support), 0.95 (tangible support) and 0.97 (overall social support). Patients with lower levels of social support had poorer general health and well-being than patients with higher levels of social support. Controlling for clinic, patients with controlled BP had significantly more socio-emotional and tangible support than patients with poor BP control. Conclusions The study demonstrated that: (1) socio-emotional and tangible support were the underlying dimensions of social support; (2) socio-emotional support is an important determinant of health and well-being; and (3) social support is beneficial for one aspect of diabetes mellitus management, namely, BP control.

Glycaemic control improves fibrin network characteristics in type 2 diabetes – A purified fibrinogen model

Diabetic subjects have been shown to have altered fibrin network structures. One proposed mechanism for this is non-enzymatic glycation of fibrinogen due to high blood glucose. We investigated whether glycaemic control would result in altered fibrin network structures due to decreased fibrinogen glycation. Twenty uncontrolled type 2 diabetic subjects were treated with insulin in order to achieve glycaemic control. Twenty age- and body mass index (BMI)-matched non-diabetic subjects were included as a reference group. Purified fibrinogen, isolated from plasma samples was used for analysis. There was a significant decrease in fibrinogen glycation (6.81 to 5.02 mol glucose/mol fibrinogen) with a corresponding decrease in rate of lateral aggregation (5.86 to 4.62) and increased permeability (2.45 to 2.85 x 10(-8) cm(2)) and lysis rate (3.08 to 3.27 microm/min) in the diabetic subjects after glycaemic control. These variables correlated with markers of glycaemic control. Fibrin clots of non-diabetic subjects had a significantly higher ratio of inelastic to elastic deformation than the diabetic subjects (0.10 vs. 0.09). Although there was no difference in median fiber diameter between diabetic and non-diabetic subjects, there was a small increase in the proportion of thicker fibers in the diabetic samples after glycaemic control. Results from SDS-PAGE indicated no detectable difference in factor XIIIa-crosslinking of fibrin clots between uncontrolled and controlled diabetic samples. Diabetic subjects may have altered fibrin network formation kinetics which contributes to decreased pore size and lysis rate of fibrin clots. Achievement of glycaemic control and decreased fibrinogen glycation level improves permeability and lysis rates in a purified fibrinogen model.

Fluid management in diabetic-acidosis--Ringer's lactate versus normal saline: a randomized controlled trial.

OBJECTIVE To determine if Ringers lactate is superior to 0.9% sodium chloride solution for resolution of acidosis in the management of diabetic ketoacidosis (DKA). DESIGN Parallel double blind randomized controlled trial. METHODS Patients presenting with DKA at Kalafong and Steve Biko Academic hospitals were recruited for inclusion in this study if they were >18 years of age, had a venous pH >6.9 and ≤7.2, a blood glucose of >13 mmol/l and had urine ketones of ≥2+. All patients had to be alert enough to give informed consent and should have received <1 l of resuscitation fluid prior to enrolment. RESULTS Fifty-seven patients were randomly allocated, 29 were allocated to receive 0.9% sodium chloride solution and 28 to receive Ringers lactate (of which 27 were included in the analysis in each group). An adjusted Cox proportional hazards analysis was done to compare the time to normalization of pH between the 0.9% sodium chloride solution and Ringers lactate groups. The hazard ratio (Ringers compared with 0.9% sodium chloride solution) for time to venous pH normalization (pH = 7.32) was 1.863 (95% CI 0.937-3.705, P = 0.076). The median time to reach a pH of 7.32 for the 0.9% sodium chloride solution group was 683 min (95% CI 378-988) (IQR: 435-1095 min) and for Ringers lactate solution 540 min (95% CI 184-896, P = 0.251). The unadjusted time to lower blood glucose to 14 mmol/l was significantly longer in the Ringers lactate solution group (410 min, IQR: 240-540) than the 0.9% sodium chloride solution group (300 min, IQR: 235-420, P = 0.044). No difference could be demonstrated between the Ringers lactate and 0.9% sodium chloride solution groups in the time to resolution of DKA (based on the ADA criteria) (unadjusted: P = 0.934, adjusted: P = 0.758) CONCLUSION This study failed to indicate benefit from using Ringers lactate solution compared to 0.9% sodium chloride solution regarding time to normalization of pH in patients with DKA. The time to reach a blood glucose level of 14 mmol/l took significantly longer with the Ringers lactate solution.

Type 2 diabetes : the emerging epidemic

Abstract This article reports on the prevalence of diabetes in South Africa and gives projections for the epidemic proportions that this disease may take by the year 2030.

The effect of glycaemic control on fibrin network structure of type 2 diabetic subjects

Diabetic subjects have been shown to have altered fibrin network structures. One possible cause may be fibrinogen glycation resulting in altered structure/function properties. We investigated the effect of glucose control on fibrinogen glycation and fibrin network structure in type 2 diabetes. Blood samples were taken from twenty uncontrolled diabetic subjects at baseline to determine the levels of fibrinogen glycation and fibrin network structures. The subjects were then treated with insulin until blood glucose control was achieved before end blood samples were taken. Twenty age- and BMI-matched non-diabetic subjects were included as a reference group. The diabetic subjects had significantly higher mean fibrinogen glycation at baseline than the non-diabetic subjects (7.84 vs. 3.89 mol glucose / mol fibrinogen; p < 0.001). This was significantly reduced during the intervention (7.84 to 5.24 mol glucose / mol fibrinogen; p < 0.0002) in the diabetic group. Both groups had high mean fibrinogen concentrations (4.25 and 4.02 g/l, diabetic and non-diabetic subjects respectively). There was no difference in fibrinogen concentration, porosity, compaction and kinetics of clot formation between the diabetic subjects and non-diabetic subjects at baseline, nor were there any changes during the intervention despite the reduced fibrinogen glycation. Fibrin network characteristics correlated well with fibrinogen but not with any markers of glycaemic control. Improved glycaemic control resulted in decreased fibrinogen glycation but not fibrinogen concentration. It seems as though porosity, compaction and kinetics of clot formation are more related to fibrinogen concentration than fibrinogen glycation in this model.

Introduction of the AmpliChip CYP450 Test to a South African cohort: a platform comparative prospective cohort study.

BackgroundAdverse drug reactions and lack of therapeutic efficacy associated with currently prescribed pharmacotherapeutics may be attributed, in part, to inter-individual variability in drug metabolism. Studies on the pharmacogenetics of Cytochrome P450 (CYP) enzymes offer insight into this variability. The objective of this study was to compare the AmpliChip CYP450 Test® (AmpliChip) to alternative genotyping platforms for phenotype prediction of CYP2C19 and CYP2D6 in a representative cohort of the South African population.MethodsAmpliChip was used to screen for thirty-three CYP2D6 and three CYP2C19 alleles in two different cohorts. As a comparison cohort 2 was then genotyped using a CYP2D6 specific long range PCR with sequencing (CYP2D6 XL-PCR + Sequencing) platform and a PCR-RFLP platform for seven CYP2C19 alleles.ResultsEven though there was a low success rate for the AmpliChip, allele frequencies for both CYP2D6 and CYP2C19 were very similar between the two different cohorts. The CYP2D6 XL-PCR + Sequencing platform detected CYP2D6*5 more reliably and could correctly distinguish between CYP2D6*2 and *41 in the Black African individuals. Alleles not covered by the AmpliChip were identified and four novel CYP2D6 alleles were also detected. CYP2C19 PCR-RFLP identified CYP2C19*9,*15, *17 and *27 in the Black African individuals, with *2, *17 and *27 being relatively frequent in the cohort. Eliminating mismatches and identifying additional alleles will contribute to improving phenotype prediction for both enzymes. Phenotype prediction differed between platforms for both genes.ConclusionComprehensive genotyping of CYP2D6 and CYP2C19 with the platforms used in this study, would be more appropriate than AmpliChip for phenotypic prediction in the South African population. Pharmacogenetically important novel alleles may remain undiscovered when using assays that are designed according to Caucasian specific variation, unless alternate strategies are utilised.

Physician education programme improves quality of diabetes care

Background. Diabetes mellitus is a common chronic disease needing long-term glycaemic control to prevent complications. Guidelines are available for achievement of optimal glycaemic control, but these are seldom properly instituted. Objectives. To determine if a physician education programme and a structured consultation schedule would improve the quality of diabetes patient care in a diabetes clinic. Setting. Two tertiary care diabetes clinics at Kalafong Hospital, Pretoria. Study design. Quasi-experimental controlled before-and after study. Methods. A baseline audit of the quality of care in two comparable diabetes clinics was performed. Three hundred patients were randomly selected for an audit of their hospital records: 141 from the intervention and 159 from the control clinics. Thereafter a physician training programme and a structured consultation schedule were introduced to the intervention clinic and maintained for a 1-year period. The control clinic continued with care as usual. Process and outcome measures were determined at a post-intervention audit and compared between the two groups. Consultation time was measured for both the intervention and control groups and data were compared. Results. At baseline the intervention and control groups did not differ significantly with regard to process and outcome measures. After intervention the intervention group had significantly higher process measure scores than the control group (p < 0.01). HbA1c did not significantly differ between the two groups (p = 0.60). The average number of clinic visits reduced over time for the intervention group compared with the control group (p < 0.01), but the average consultation times were significantly longer (p < 0.01). Conclusion. The introduction of a physician education programme and a structured consultation schedule improved the quality of care delivered at a tertiary care diabetes clinic.

Global meta-analysis of the C-11377G alteration in the ADIPOQ gene indicates the presence of population-specific effects: challenge for global health initiatives

Type II diabetes mellitus is currently globally one of the fastest growing non-communicable diseases, especially in developing countries. This investigation reports on a meta-analysis undertaken of the C-11377G locus within the adiponectin gene in a black South African, a Cuban Hispanic and a German Caucasian cohort. Genotyping was performed via a real-time PCR strategy. Both fixed- and random-effects models were tested to describe the diabetes risk at both the cohort and population levels. The 2,2 genotype may only be associated with increased diabetes risk in the Cuban Hispanic cohort. Population-specific effects may have masked these associations upon meta-analytical analysis, as no significant odds ratio could be determined. Thus, to examine diabetes risk, a more global approach including the design of population-specific experimental strategies should be used, which will be crucial in developing health education and policies in a global health programme.

Use of Medical Services and Medicines Attributable to Diabetes in Sub-Saharan Africa

Background Although the large majority of persons with diabetes and other non-communicable diseases (NCDs) lives and dies in low- and middle-income countries, the prevention and treatment of diabetes and other NCDs is widely neglected in these areas. A contributing reason may be that, unlike the impacts of acute and communicable diseases, the demands on resources imposed by diabetes is not superficially obvious, and studies capable of detecting these impacts have not be done. Methods To ascertain recent use of medical services and medicines and other information about the impact of ill-health, we in 2008–2009 conducted structured, personal interviews with 1,780 persons with diagnosed diabetes (DMs) and 1,770 matched comparison subjects (MCs) without diabetes in Cameroon, Mali, Tanzania and South Africa. We sampled DMs from diabetes registries and, in Cameroon and South Africa, from attendees at outpatient diabetes clinics. To recruit MCs, we asked subjects with diabetes to identify five persons living nearest to them who were of the same sex and approximate age. We estimated diabetes impact on medical services use by calculating ratios and differences between DMs and MCs, testing for statistical significance using two-stage multivariable hurdle models. Findings DMs consumed 12.95 times more days of inpatient treatment, 7.54 times more outpatient visits, and 5.61 times more medications than MCs (all p<0.001). DMs used an estimated 3.44 inpatient days per person per year, made 10.72 outpatient visits per person per year (excluding traditional healers), and were taking an average of 2.49 prescribed medicines when interviewed. Conclusions In Sub-Saharan Africa, the relative incremental use of medical care and medicines associated with diagnosed diabetes is much greater than in industrialized countries and in China. Published calculations of the health-system impact of diabetes in Africa are dramatic underestimates. Although non-communicable diseases like diabetes are commonly thought to be minor problems for health systems and patients in Africa, our data demonstrate the opposite.