R. K. Khan Hospital

BACKGROUND: The STREAM stage 1 trial showed that a 9-month regimen for the treatment of rifampicin-resistant tuberculosis was non-inferior to the 20-month 2011 WHO-recommended regimen. In STREAM stage 2, we aimed to compare two bedaquiline-containing regimens with the 9-month STREAM stage 1 regimen. METHODS: We did a randomised, phase 3, non-inferiority trial in 13 hospital clinics in seven countries, in individuals aged 15 years or older with rifampicin-resistant tuberculosis without fluoroquinolone or aminoglycoside resistance. Participants were randomly assigned 1:2:2:2 to the 2011 WHO regimen (terminated early), a 9-month control regimen, a 9-month oral regimen with bedaquiline (primary comparison), or a 6-month regimen with bedaquiline and 8 weeks of second-line injectable. Randomisations were stratified by site, HIV status, and CD4 count. Participants and clinicians were aware of treatment-group assignments, but laboratory staff were masked. The primary outcome was favourable status (negative cultures for Mycobacterium tuberculosis without a preceding unfavourable outcome) at 76 weeks; any death, bacteriological failure or recurrence, and major treatment change were considered unfavourable outcomes. All comparisons used groups of participants randomly assigned concurrently. For non-inferiority to be shown, the upper boundary of the 95% CI should be less than 10% in both modified intention-to-treat (mITT) and per-protocol analyses, with prespecified tests for superiority done if non-inferiority was shown. This trial is registered with ISRCTN, ISRCTN18148631. FINDINGS: Between March 28, 2016, and Jan 28, 2020, 1436 participants were screened and 588 were randomly assigned. Of 517 participants in the mITT population, 133 (71%) of 187 on the control regimen and 162 (83%) of 196 on the oral regimen had a favourable outcome: a difference of 11·0% (95% CI 2·9-19·0), adjusted for HIV status and randomisation protocol (p<0·0001 for non-inferiority). By 76 weeks, 108 (53%) of 202 participants on the control regimen and 106 (50%) of 211 allocated to the oral regimen had an adverse event of grade 3 or 4; five (2%) participants on the control regimen and seven (3%) on the oral regimen had died. Hearing loss (Brock grade 3 or 4) was more frequent in participants on the control regimen than in those on the oral regimen (18 [9%] vs four [2%], p=0·0015). Of 134 participants in the mITT population who were allocated to the 6-month regimen, 122 (91%) had a favourable outcome compared with 87 (69%) of 127 participants randomly assigned concurrently to the control regimen (adjusted difference 22·2%, 95% CI 13·1-31·2); six (4%) of 143 participants on the 6-month regimen had grade 3 or 4 hearing loss. INTERPRETATION: Both bedaquiline-containing regimens, a 9-month oral regimen and a 6-month regimen with 8 weeks of second-line injectable, had superior efficacy compared with a 9-month injectable-containing regimen, with fewer cases of hearing loss. FUNDING: USAID and Janssen Research & Development.

We assessed the relationship of plasma glucose concentrations measured on admission to mortality during the acute phase of myocardial infarction in 143 diabetic patients and 277 patients without a previous history of diabetes. Mortality in hospital in patients not known to have diabetes increased significantly from 4 per cent in patients with admission plasma glucose below 8 mmol/l to 35 per cent in patients with admission plasma glucose above 11 mmol/l. In diabetic patients the mortality increased with increasing admission plasma glucose but the difference was not significant. In patients with diabetes mean admission plasma glucose levels of the survivors and those who died were similar, whilst in the non-diabetic group the mean plasma glucose levels of the patients who did not survive were significantly higher than those of the survivors. Stepwise logistic regression analyses identified admission plasma glucose level as an important predictor of mortality in the non-diabetic group but not in the diabetic patients. Plasma glucose level on admission is an important prognostic indicator in non-diabetic patients, in that hyperglycaemia is associated with a higher mortality. In diabetic patients a clear relationship between admission plasma glucose and mortality was not demonstrated.

BACKGROUND: Bedaquiline improves treatment outcomes in patients with rifampin-resistant (RR) tuberculosis but prolongs the QT interval and carries a black-box warning from the US Food and Drug Administration. The World Health Organization recommends that all patients with RR tuberculosis receive a regimen containing bedaquiline, yet a phase 3 clinical trial demonstrating its cardiac safety has not been published. METHODS: We conducted an observational cohort study of patients with RR tuberculosis from 3 provinces in South Africa who received regimens containing bedaquiline. We performed rigorous cardiac monitoring, which included obtaining electrocardiograms in triplicate at 4 time points during bedaquiline therapy. Participants were followed up until the end of therapy or 24 months. Outcomes included final tuberculosis treatment outcome and QT interval prolongation (QT prolongation), defined as any QT interval corrected by the Fridericia method (QTcF) >500 ms or an absolute change from baseline (ΔQTcF) >60 ms. RESULTS: We enrolled 195 eligible participants, of whom 40% had extensively drug-resistant tuberculosis. Most participants (97%) received concurrent clofazimine. Of the participants, 74% were cured or successfully completed treatment, and outcomes did not differ by human immunodeficiency virus status. QTcF continued to increase throughout bedaquiline therapy, with a mean increase (standard deviation) of 23.7 (22.7) ms from baseline to month 6. Four participants experienced a QTcF >500 ms and 19 experienced a ΔQTcF >60 ms. Older age was independently associated with QT prolongation. QT prolongation was neither more common nor more severe in participants receiving concurrent lopinavir-ritonavir. CONCLUSIONS: Severe QT prolongation was uncommon and did not require permanent discontinuation of either bedaquiline or clofazimine. Close monitoring of the QT interval may be advisable in older patients.

Significant differences in the prevalence of coronary heart disease (CHD) exist with respect to gender, age and ethnicity. The disease has been reported to be higher in Indian populations that have emigrated from the Indian subcontinent. The aim of this study was to examine differences in major cardiovascular risk factors and clinical outcome in South African Asian Indians of different age groups and gender, who presented with acute coronary syndromes (ACS). The study cohort consisted of 2 290 consecutive patients, admitted between 1996 and 2002, who were divided into three age subgroups: young ( </= 45 years; 20%), middle age (> 45 to </= 65 years; 59%), and old age (> 65 years; 21%). All three age groups were predominantly male, but this was more evident in the younger (88%) and middle age groups (71%), and became less striking as the proportion of females increased with age. Smoking was more common in young men compared with young women (p < 0.01). Diabetes mellitus (21%) and hypertension (18%) were seen less frequently in young patients but this was confined to men only. Total cholesterol was elevated in 65 to 70% of all patients while high-density lipoprotein (HDL) levels were significantly lower in men compared with women for all age subsets. Hospital mortality was extremely low in young (1%) and middle-aged patients (2%), but was expectedly higher in older patients (8%; p < 0.0001). A family history of CHD was the most common familial vascular disease seen. Young patients were more often subjected to diagnostic and therapeutic interventions. They had more aggressive disease, with 48% of those subjected to angiographic studies having triple vessel disease (TVD), and 14% undergoing coronary artery bypass grafting (CABG). Triple vessel disease was also detected most commonly in middle-aged (64%) and old patients (75%). In conclusion, significant differences in risk factor status were found in South African Indians between genders and for different age groups. Also, young Indians in this study differed markedly from other young population groups with CHD, in that they frequently had premature atherosclerosis with diffuse and aggressive disease.

While clinical disease caused by drug-sensitive Mycobacterium tuberculosis (MTB) can usually be treated successfully, clinical disease caused by drug-insensitive MTB is associated with a poorer prognosis. In December 2012, a new drug, bedaquiline, was approved by the US Food and Drug Administration. This article documents the process whereby the National Department of Health, Right to Care and Médecins Sans Frontières obtained access to this medication for South Africans who might benefit from subsequent implementation of the Clinical Access to Bedaquiline Programme.

Surgery for drug-resistant tuberculosis has been shown to be safe and effective, with similar level of mortalities associated with surgical intervention observed with that for lung cancer. While surgery has been an option to treat TB in the pre-antibiotic era, it is now increasingly used to treat complications of pulmonary TB, particularly in patients with drug-resistant TB who do not respond to medical treatment. The two most frequent indications for lung resection in drug- resistant TB, are i) failed medical treatment with persistent sputum positivity or ii) patients who have had medical treatment and are sputum negative, but with persistent localized cavitary disease or bronchiectasis. Massive hemoptysis is a potentially life-threatening complication of TB. Lung resection is potentially curative in patients with massive hemoptysis and cavitary or bronchiectatic disease. Bronchial artery embolization in these patients has a high success rate but bears also the risk of recurrence. Lung resection can be safely undertaken in selected patients with HIV co-infection and pulmonary complications of TB. Ambulatory drainage is a novel, safe, affordable and effective method of draining a chronic TB associated empyema thoracis. We review here the current surgical treatment of the complications of pulmonary TB and discuss the experience from the Durban Cardiothoracic Surgery Unit for the surgical treatment of patients with complicated pulmonary TB.

Acute infantile diarrhea is often managed by introducing lactose-free diets empirically from the time of diagnosis, in addition to conventional rehydration therapy. In order to assess the efficacy of this, a therapeutic trial was undertaken in which hospitalized gastroenteritis patients previously on milk-formula feeds were randomly fed, from the time of admission, either their original feed or a lactose-free soya preparation; patients previously on human milk with or without a supplement continued to receive this during their diarrheal illness. The results show that in nonrotaviral gastroenteritis, there is no difference in the duration of the illness irrespective of the type of feed given. In rotaviral gastroenteritis, continued breast-feeding significantly reduces the duration of acute diarrhea, while lactose-free soya feeds do not lead to a significant reduction in the duration of the illness when compared to cow's milk-formula feeds. Hence, it is concluded that (a) breast-feeding should be continued during an episode of infantile diarrhea, and that (b) empirical use of soya preparations from the time of hospital admission is not justified; however, the latter should be considered in infants whose purging rate goes up or diarrheal disease severity worsens 3 to 4 days after the onset of diarrhea or hospital stay and who are passing significant amounts of reducing sugars in their stool.

OBJECTIVE: Associations between obesity-related polymorphisms and the metabolic syndrome in 485 young ( ≤ 45 Years) Asian Indian patients with acute myocardial infarction (AMI), and 300 matched controls were assessed. METHODS: Genetic variants included the adiponectin 45T→G and 276G→T, LEPR K109R and Q223R, MC4R-associated C→T and FTO A→T polymorphisms. RESULTS: The metabolic syndrome, as defined by NCEP ATP III and IDF criteria, was diagnosed in 61 and 60% of patients, respectively. No relationship was found between the obesity-associated polymorphisms and the metabolic syndrome, or between AMI patients and controls. The MC4R-associated TT genotype occurred more frequently in patients with lower triglyceride levels (p = 0.024), while the adiponectin 45 TT genotype occurred more commonly in patients with normal fasting glucose levels (p = 0.004). The LEPR Q223R TT genotype was associated with low high-density lipoprotein (HDL) cholesterol levels (p = 0.003). CONCLUSION: The metabolic syndrome occurs commonly in young Asian Indian patients with AMI. No relationship was found between any obesity-associated polymorphism and the metabolic syndrome. Particular genotypes may exert protective or disadvantageous effects on individual components of the metabolic syndrome.

BACKGROUND: Oxidative stress and endothelial dysfunction have been introduced as a unifying pathological mechanism for early atherosclerotic disease. They are caused by a variety of stimuli including cigarette smoking (environmental) and type 2 diabetes (disease factor). However, the role of hyperinsulinemia, a marker of insulin resistance, as a risk factor for atherosclerosis remains to be clarified. STUDY OBJECTIVES: To study the relationship of smoking, hyperinsulinaemia and biochemical markers of oxidative stress and endothelial dysfunction, in patients with coronary artery disease. DESIGN: Case-control study of 5-year survivor status in smokers, former smokers and nonsmokers with angiographically documented stable coronary artery disease classified by self-reporting of smoking status together with plasma cotinine measurements. SETTING: Cardiology and cardiac surgery unit of a tertiary care referral centre. PATIENTS AND METHODS: Plasma levels of vitamins C, E and selenium, and the adhesion molecules E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were assessed in 214 patients at baseline together with the glucose and insulin response to an oral glucose challenge. Sixty known or newly diagnosed type 2 diabetic patients (28%) were identified and excluded from further analysis. RESULTS: E-selectin and ICAM-1, serving as markers of endothelial dysfunction, significantly correlated with hyperinsulinaemia (p < 0.05). Circulating immunoreactive insulin was elevated in active smokers and former smokers as compared to non-smokers after an oral glucose load (p < 0.05 for the area under the insulin time curve), despite a similar glucose response. Smoking was associated with a decrease in antioxidant vitamins C (p = 0.02) and E (p = 0.03), and an increase of E-selectin (p < 0.05) and ICAM-1 (p < 0.001). Low baseline ICAM-1 and high vitamin C levels emerged as the most significant multivariate predictors of 5-year survival (p < 0.001). CONCLUSIONS: Hyperinsulinaemia in smokers is linked with markers of endothelial dysfunction. Impaired vascular reactivity can thus be a new possible mechanism linking insulin resistance and smoking.

BACKGROUND: To investigate the association between hyperuricemia and major adverse cardiac events (MACE) in patients with acute myocardial infarction (AMI). METHODS: Consecutive patients admitted with AMI to the Coronary Care Unit at R. K. Khan Hospital (Durban, South Africa) between the years 2006 and 2014 were included. Demographic data, including clinical and biochemical information stored in an electronic database, were obtained from all patients. RESULTS: A total of 2683 patients were studied, of whom 65% were males. The mean age of the participants was 57.1 ± 11.5 years, with 79% presenting with ST elevation myocardial infarction. Sixty-one percent were smokers, 59% had diabetes mellitus, 52% had hypertension, and 58% presented with a family history of premature coronary artery disease. Twenty-six percent (n = 690) had hyperuricemia, were older (59 ± 12.1 vs. 56.5 ± 11.2 years) and more likely to present with hypertension (P < 0.001), lower ejection fraction (P < 0.001), and higher median creatinine levels (P < 0.001). A significantly greater proportion of patients with hyperuricemia experienced MACE (45% vs. 30%, P < 0.001). In both sexes, considerable heterogeneity for risk factors and clinical events was noted in individuals with hyperuricemia. Multivariable analyses for risk factors associated with mortality suggest that hyperuricemia conferred a significantly increased risk of mortality after adjustment [odds ratio (OR) 1.7 (95% confidence interval 1.0-2.8); P = 0.042]. A significant increasing risk trend for MACE was observed for increasing tertiles of serum uric acid concentrations above normal (P < 0.001), particularly for cardiac failure (P < 0.001) and death (P = 0.006). CONCLUSIONS: Hyperuricemia is significantly associated with hypertension, renal dysfunction, MACE, and independently confers a higher risk of mortality in patients with AMI. Significant heterogeneity was found by gender for risk factors and clinical events in individuals with hyperuricemia. A graded increase was demonstrated in the risk of MACE, particularly for cardiac failure and death, by increasing tertiles of hyperuricemia.

In rare cases, primary malignant lymphomas may arise in the soft tissues. Only one previous case has arisen in the context of chronic lymphedema. Because of the clinical appearance of such lesions, which resemble violaceous nodular or plaquelike tumors, they may be confused clinically with lymphedema-associated angiosarcomas occurring after radical mastectomy (Stewart-Treves syndrome). Furthermore, the histologic appearance of some lymphomas and angiosarcomas may also be similar. We studied two women with primary postmastectomy lymphedema-related malignant lymphoma in the soft tissues of the upper arm. These tumors arose 11 and 30 years, respectively, after radical removal of ductal mammary carcinomas. Histologically, one neoplasm mimicked metastatic carcinoma or epithelioid angiosarcoma; whereas the other was initially confused with a variety of pathologic entities, including vasculitis, epithelioid hemangioma, and malignant fibrous histiocytoma. The lymphoid nature of both lesions was confirmed by immunoreactivity for leukocyte common antigen in addition to the B-lymphocyte marker, L26. Conversely, vascular and epithelial determinants were absent. One patient's disease pursued an indolent course; she died of unknown causes but with no evidence of lymphoma at last follow-up. The second patient is currently in remission on chemotherapy. Awareness of the existence of lymphedema-related malignant lymphoma and familiarity with methods used for its distinction from epithelioid vascular sarcomas should prevent unnecessary surgery.

OBJECTIVE: To describe risk factors and outcomes of pregnant women infected with SARS-CoV-2 admitted to South African healthcare facilities. METHODS: A population-based cohort study was conducted utilizing an amended International Obstetric Surveillance System protocol. Data on pregnant women with SARS-CoV-2 infection, hospitalized between April 14, 2020, and November 24, 2020, were analyzed. RESULTS: A total of 36 hospitals submitted data on 673 infected hospitalized pregnant women; 217 (32.2%) were admitted for COVID-19 illness and 456 for other indications. There were 39 deaths with a case fatality rate of 6.3%: 32 (14.7%) deaths occurred in women admitted for COVID-19 illness compared to 7 (1.8%) in women admitted for other indications. Of the women, 106 (15.9%) required critical care. Maternal tuberculosis, but not HIV co-infection or other co-morbidities, was associated with admission for COVID-19 illness. Rates of cesarean delivery did not differ significantly between women admitted for COVID-19 and those admitted for other indications. There were 179 (35.4%) preterm births, 25 (4.7%) stillbirths, 12 (2.3%) neonatal deaths, and 162 (30.8%) neonatal admissions. Neonatal outcomes did not differ significantly from those of infected women admitted for other indications. CONCLUSION: The maternal mortality rate was high among women admitted with SARS-CoV-2 infection and higher in women admitted primarily for COVID-19 illness with tuberculosis being the only co-morbidity associated with admission.

BACKGROUND: Fluconazole is used in combination with amphotericin B for induction treatment of cryptococcal meningitis and as monotherapy for consolidation and maintenance treatment. More than 90% of isolates from first episodes of cryptococcal disease had a fluconazole minimum inhibitory concentration (MIC) ≤4 μg/ml in a Gauteng population-based surveillance study of Cryptococcus neoformans in 2007-2008. We assessed whether fluconazole resistance had emerged in clinical cryptococcal isolates over a decade. METHODOLOGY AND PRINCIPAL FINDINGS: We prospectively collected C. neoformans isolates from 1 January through 31 March 2017 from persons with a first episode of culture-confirmed cryptococcal disease at 37 South African hospitals. Isolates were phenotypically confirmed to C. neoformans species-complex level. We determined fluconazole MICs (range: 0.125 μg/ml to 64 μg/ml) of 229 C. neoformans isolates using custom-made broth microdilution panels prepared, inoculated and read according to Clinical and Laboratory Standards Institute M27-A3 and M60 recommendations. These MIC values were compared to MICs of 249 isolates from earlier surveillance (2007-2008). Clinical data were collected from patients during both surveillance periods. There were more males (61% vs 39%) and more participants on combination induction antifungal treatment (92% vs 32%) in 2017 compared to 2007-2008. The fluconazole MIC50, MIC90 and geometric mean MIC was 4 μg/ml, 8 μg/ml and 4.11 μg/ml in 2017 (n = 229) compared to 1 μg/ml, 2 μg/ml and 2.08 μg/ml in 2007-2008 (n = 249) respectively. Voriconazole, itraconazole and posaconazole Etests were performed on 16 of 229 (7%) C. neoformans isolates with a fluconazole MIC value of ≥16 μg/ml; only one had MIC values of >32 μg/ml for these three antifungal agents. CONCLUSIONS AND SIGNIFICANCE: Fluconazole MIC50 and MIC90 values were two-fold higher in 2017 compared to 2007-2008. Although there are no breakpoints, higher fluconazole doses may be required to maintain efficacy of standard treatment regimens for cryptococcal meningitis.

SUMMARYBackground: Oxidative stress and endothelial dysfunction have been introduced as a unifying pathological mechanism for early atherosclerotic disease. They are caused by a variety of stimuli including cigarette smoking (environmental) and type 2 diabetes (disease factor). However, the role of hyperinsulininaemia, a marker of insulin resistance, as a risk factor for atherosclerosis remains to be clarified.Study objectives: To study the relationship of smoking, hyperinsulinaemia and biochemical markers of oxidative stress and endothelial dysfunction, in patients with coronary artery disease.Design: Case-control study of 5-year survivor status in smokers, former smokers and non-smokers with angiographically documented stable coronary artery disease classified by self-reporting of smoking status together with plasma cotinine measurements.Setting: Cardiology and cardiac surgery unit of a tertiary care referral centre.Patients and methods: Plasma levels of vitamins C, E and selenium, and the adhesion molecules E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were assessed in 214 patients at baseline together with the glucose and insulin response to an oral glucose challenge. Sixty known or newly diagnosed type 2 diabetic patients (28%) were identified and excluded from further analysis.Results: E-selectin and ICAM-1, serving as markers of endothelial dysfunction, significantly correlated with hyperinsulinaemia (p < 0.05). Circulating immunoreactive insulin was elevated in active smokers and former smokers as compared to non-smokers after an oral glucose load (p < 0.05 for the area under the insulin time curve), despite a similar glucose response. Smoking was associated with a decrease in antioxidant vitamins C (p = 0.02) and E (p = 0.03), and an increase of E-selectin (p < 0.05) and ICAM-1 (p < 0.001). Low baseline ICAM-1 and high vitamin C levels emerged as the most significant multivariate predictors of 5-year survival (p < 0.001).Conclusions: Hyperinsulinaemia in smokers is linked with markers of endothelial dysfunction. Impaired vascular reactivity can thus be a new possible mechanism linking insulin resistance and smoking.

66 non-diabetic Indian patients with acute myocardial infarction were assessed prospectively for the presence of hyperglycaemia and the value of this admission hyperglycaemia and glycosylated haemoglobin (HbA1) levels in reflecting the glucose tolerance status of the patients was studied. Hyperglycaemia, defined as admission plasma glucose greater than or equal to 8 mmol/l was detected in 49% of the patients, whilst raised HbA1 values were seen in 11%. The admission plasma glucose (APG) correlated significantly with both the HbA1 levels and with the 2 hour glucose value in the oral glucose tolerance test (p less than 0.001). An oral glucose tolerance test performed 3 months after the acute episode revealed that 35 patients (53%) had abnormal glucose tolerance according to WHO criteria. Of the patients with initial hyperglycaemia, 75% had abnormal glucose tolerance tests, whilst 32% of patients with normal APG had abnormal glucose tolerance. Abnormal glucose tolerance was also detected in all patients with raised HbA1 values (greater than 8.9%) and in 48% of patients with normal levels. The sensitivity and specificity of APG greater than or equal to 8 mmol/l for abnormal glucose tolerance was 68.6% and 74.2% respectively and that of raised HbA1 values were 20% and 100%. Hence an APG greater than or equal to 8 mmol/l in patients with myocardial infarction is more likely to indicate the presence of unrecognized abnormal glucose tolerance rather than stress. HbA1 measurements do not appear to offer any further advantage in the assessment of hyperglycaemia following myocardial infarction.

The renin-angiotensin system plays an important role in cardiovascular regulation. Abnormalities in genetic components of this system, such as the angiotensin-converting enzyme (ACE) gene, angiotensin II type 1 (AT1) receptor gene and angiotensinogen (AGT) gene, may cause a variety of adverse cardiovascular effects. It was the aim of this study, therefore, to investigate the involvement of the ACE insertion/deletion (I/D), AT1 receptor 1166 A->C and AGT M235T polymorphisms as predisposing factors for myocardial infarction (MI) in 195 young South African Indians (</= 45 years). Results were compared with those obtained I n 107 unaffected siblings (18-45 years old) and 300 healthy age- and race-matched control subjects. The distribution of the ACE genotypes was the same in each of the three study groups (p-value ranged between 0.83 and 0.98). No differences were observed in the 1166 A->C AT1 receptor polymorphism with respect to both genotype and allelotype (p > 0.70), or in the genotype or allele frequency distribution of the AGT M235T polymorphism (p > 0.44). However, a significant in crease was noted for both the AT1 receptor C variant (p = 0.025) and the AGT T variant (p = 0.047) in hypertensive patients compared with those who were normotensive. In conclusion, results of this study indicate that the ACE I/D, the 1166 A->C AT1 receptor and AGT M235T polymorphisms do not confer any increased risk for MI in young South African Indians.

BACKGROUND: Myocardial infarction (MI) is a complex disease caused by interaction of a number of genetic and environmental factors. This disease has reached epidemic proportions in South African Indian descendants. The aim of this study was to survey the prevalence of coronary heart disease risk factors in a sub-group of young Indian patients (< or = 45 years) who presented to the Coronary Care Unit at the R. K. Khan Hospital in Durban, a major referral centre for patients with acute MI in the province of Natal. METHODS AND RESULTS: A total of 245 patients < or = 45 years of age were recruited from patients consecutively admitted to the Coronary Care Unit at the R. K. Khan Hospital, Durban, KwaZulu Natal, South Africa between 1996 and 1999 with a diagnosis of acute MI. All patients were of Indian origin living in the Durban area in the province of KwaZulu-Natal. Demographic and risk factor data were obtained from all patients and included anthropometric measures, family history and the traditional cardiovascular risk factor assessment (smoking, lipids, hypertension, and diabetes mellitus). Clinical data included in-hospital presentation, management and complications and angiographic classification of coronary atherosclerosis. The most prevalent risk factors were previous: smoking (74%), and hypertriglyceridaemia (54%). Only 14% of the population presenting with an acute MI were women. Smoking was more common among men (81%) than in women (35%). Abnormal high density lipoprotein (HDL) cholesterol levels were detected in 38% of the patients with a dear gender difference: 43% and 9%, in men and women, respectively. In contrast hypertension was more prevalent in young women with MI than in men: 38% and 19%, respectively. Coronary angiography was performed in 79 patients on admission; a single vessel stenosis was found in 28%, two vessel disease in 20% and triple vessel disease in 52%, respectively. On admission, 92% of patients were in Killip class I. Overt heart failure and cardiogenic shock were uncommon and were seen in 3.3% and 0.8%, respectively. Patients who received thrombolytic therapy had fewer complications (8%) compared to those who did not (11%). However, the difference towards a benefit of thrombolysis did not reach significance. Recurrent angina (6%) was the commonest complication, while ventricular arrhythmias were observed in 2% of patients. There was a strong familial link: 54% of the patients had a family background of coronary heart disease (CHD) while 42% and 41% had family members who suffered from diabetes mellitus and hypertension, respectively. CONCLUSION: Smoking and dyslipidaemia (predominantly hypertriglyceridaemia, and low HDL-cholesterol) were the most common cardiovascular risk factors of MI in young South African Indians. A strong familial link was observed not only for a history of CHD/MI, but also for hypertension and diabetes mellitus, supporting a genetic basis for the development of premature CHD. Therefore, further analysis of potential genetic factors such as variance of genes involved in vascular homeostasis, haemostatic factors, lipid metabolism and other metabolic factors seems warranted.

BACKGROUND: The objective of this study was to assess whether an association exists between the metabolic syndrome and polymorphisms in genes involved in insulin resistance in young Asian Indian patients presenting with acute myocardial infarction (AMI). METHODS: The study population comprised 467 patients who were 45 years or younger. The National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) and the International Diabetes Federation (IDF) definitions were used to assess the prevalence of metabolic syndrome. We examined the genotype and allele frequencies of the IRS-I G972R, PPAR-gamma P12A, KCNJ11 E23K, and TNF-alpha -308G/A polymorphisms in relation to the metabolic syndrome determined by both definitions. RESULTS: The metabolic syndrome as defined by the NCEP ATP III criteria was found in 282 (60.4%) patients, and in 278 (59.5%) patients according to the IDF criteria. This gave only a moderate level of agreement of 79% between the two definitions (Cohen's kappa = 0.554). No association was found between the IRS-I G972R, PPAR-gamma P12A, and KCNJ11 E23K, or TNF-alpha -308G/A polymorphic variants and the metabolic syndrome, or its components, for either definition. CONCLUSION: Although the metabolic syndrome is a common finding in young Asian Indian patients with AMI, there was only a moderate level of agreement between the NCEP ATP III and IDF definitions of the syndrome. Our findings do not support a role for any of the polymorphic variant alleles in the four insulin resistance-related genes examined in the etiology of insulin resistance and reinforces the notion of a multifactorial etiology for the metabolic syndrome.

A trauma system involves the interaction of prehospital care, emergency centre care and definitive care (including prevention and rehabilitation services), providing an organised approach to acutely injured patients within a defined geographical area, from primary care to advanced care. Trauma is, after infectious disease, the second leading cause of death and disability in Africa, and must therefore feature on the national health agendas of all African countries. The requirements for developing cost-efficient, patient-centred trauma systems relevant to South Africa are outlined (each item commencing with a P, and hence the title).

The lipoprotein(a) [Lp(a)] and apolipoprotein E (apoE) polymorphisms have been shown to be important genetic determinants of cardiovascular risk. Their effect on coronary heart disease (CHD) is less clear, particularly in Asian Indians who are at high risk for this disease. The aim of this study was to examine the association of the Lp(a) promoter pentanucleotide repeat polymorphism and the apoE codon 112 and 158 genotypes in 195 young South African Indian patients (< or = 45 years) with myocardial infarction (MI). Results were compared with 300 healthy age-matched control subjects drawn from the same community and 107 unaffected siblings (18-45 years). In addition, fasting lipograms were performed on all patients and a detailed history of conventional risk factors and family background was obtained. Of the six different Lp(a) alleles detected, the 8-repeat sequence was most frequently seen. However, no difference in frequencies existed between patient and control groups. The most frequently occurring apoE genotype in the three study groups was E3/E3 (patients 71%; siblings 70%; controls 70%). A significant difference in the E3/E4 genotype was seen between patients and controls (23% vs 14%; p = 0.018) and between siblings and controls (24% vs 14%; p = 0.027). These patients were also more likely to have significantly higher low-density lipoprotein (LDL) and lower high-density lipoprotein (HDL) levels (p = 0.005 and 0.045, respectively). No association was observed between any of the Lp(a) or apoE genotypes and conventional risk factors such as smoking, diabetes, hypertension, obesity or a family history of CHD. In conclusion, the apoE3/E4 genotype is strongly associated with the incidence of myocardial infarction in young South African Indians. This genotype also adversely affects LDL and HDL cholesterol levels, both of which contribute to premature atherosclerosis. In contrast, the Lp(a) pentanucleotide repeat polymorphism does not appear to have any aetiological role in MI in this population.