The 2011 United Nations High-Level Meeting on Non- Communicable Diseases: The Africa agenda calls for a 5-by-5 approach

The High Level Meeting of the 66th Session of the United Nations General Assembly was held in September 2011. The Political Declaration issued at the meeting focused the attention of world leaders and the global health community on the prevention and control of noncommunicable diseases (NCDs). The four major NCDs (cardiovascular diseases, cancer, diabetes and chronic respiratory diseases) and their four risk factors (tobacco use, unhealthy diet, physical inactivity and harmful use of alcohol) constitute the target of the ‘4-by-4’ approach, which is also supported by national and international health organisations. We argue that while preventing these eight NCDs and risk factors is also important in Africa, it will not be enough. A ‘5-by-5’ strategy is needed, addressing neuropsychiatric disorders as the fifth NCD; and transmissible agents that underlie the neglected tropical diseases and other NCDs as the fifth risk factor. These phenomena cause substantial preventable death and disability, and must therefore be prioritised

Medical inpatient mortality at Groote Schuur Hospital, Cape Town, 2002 - 2009

Background. Despite the challenges facing healthcare in South Africa, empirical insights into the performance of healthcare services overtime are scarce.Methods. We analysed first admissions of adult medical inpatients to Groote Schuur Hospital, Cape Town, from January 2002 to July 2009.Data included age, sex, medical specialty, and date of admission and discharge. We used population group and hospital billing codes asproxy measures for socio-economic status (SES). We calculated the duration of stay in days from the date of admission to discharge, andinpatient mortality rates per 1 000 patient days. Poisson regression was used to estimate mortality rate ratios (MRR) in unadjusted analysisand after adjusting for potential confounders.Results. There were 42 582 first admissions. Patient demographics shifted towards a lower SES. Median age decreased from 52 years in 2002to 49 years in 2009, while patients aged 20 - 39 years increased in proportion from 26% to 31%. The unadjusted proportion of admissionswhich resulted in in-hospital deaths increased from 12% in 2002 to 17% in 2009. Corresponding mortality rates per 1 000 patient days were 17.0 (95% confidence interval (CI) 15.9 - 18.3) and 23.4 (95% CI 21.6 - 25.4), respectively (unadjusted MRR 1.37; 95% CI 1.23 - 1.53). Annual increases in mortality rates were highest during the first 2 days following admission (increasing from 30.1 to 50.3 deaths per 1 000), and were associated with increasing age, non-paying patient status, black population group and male sex, and were greatest in the emergency ward (adjusted MRR 1.73, comparing 2009 with 2002; 95% CI 1.49 - 2.01).Discussion. Increasing medical inpatient mortality rates at a large South African academic hospital were most marked during the first 2 days after admission and appeared greatest among emergency medical inpatients

Effect of prednisolone on inflammatory markers in pericardial tuberculosis: A pilot study

Background: Pericardial disorders are a common cause of heart disease, and the most common cause of pericarditis in developing countries is tuberculous (TB) pericarditis. It has been shown that prednisolone added to standard anti-TB therapy leads to a lower rate of constrictive pericarditis. We conducted a pilot study to evaluate the effect of adjunctive prednisolone treatment on the concentration of inflammatory markers in pericardial tuberculosis, in order to inform immunological mechanisms at the disease site. Methods: Pericardial fluid, plasma and saliva samples were collected from fourteen patients with pericardial tuberculosis, at multiple time points. Inflammatory markers were measured using multiplex luminex analysis and ELISA. Results: In samples from 14 patients we confirmed a strongly compartmentalized immune response at the disease site and found that prednisolone significantly reduced IL-6 concentrations in plasma by 8 hours of treatment, IL-1beta concentrations in saliva, as well as IL-8 concentrations in both pericardial fluid and saliva by 24 hours. Conclusion: Monitoring the early effect of adjunctive immunotherapy in plasma or saliva is a possibility in pericarditis

ANIMA: Association network integration for multiscale analysis [version 1; referees: 2 approved with reservations]

Contextual functional interpretation of -omics data derived from clinical samples is a classical and difficult problem in computational systems biology. The measurement of thousands of data points on single samples has become routine but relating ‘big data’ datasets to the complexities of human pathobiology is an area of ongoing research. Complicating this is the fact that many publically available datasets use bulk transcriptomics data from complex tissues like blood. The most prevalent analytic approaches derive molecular ‘signatures’ of disease states or apply modular analysis frameworks to the data. Here we describe ANIMA (association network integration for multiscale analysis), a network-based data integration method using clinical phenotype and microarray data as inputs. ANIMA is implemented in R and Neo4j and runs in Docker containers. In short, the build algorithm iterates over one or more transcriptomics datasets to generate a large, multipartite association network by executing multiple independent analytic steps (differential expression, deconvolution, modular analysis based on co-expression, pathway analysis) and integrating the results. Once the network is built, it can be queried directly using Cypher, or via custom functions that communicate with the graph database via language-specific APIs. We developed a web application using Shiny, which provides fully interactive, multiscale views of the data. Using our approach, we show that we can reconstruct multiple features of disease states at various scales of organization, from transcript abundance patterns of individual genes through co-expression patterns of groups of genes to patterns of cellular behaviour in whole blood samples, both in single experiments as well as in a meta-analysis of multiple datasets

A lower body mass index is associated with cardiomyopathy in people with HIV infection: Evidence from a case comparison study

The cause of cardiomyopathy in patients infected with the human immunodeficiency virus (HIV) remains largely unknown, although a number of predisposing factors have been identified. Malnutrition has been postulated to be a contributory factor, but the association of anthropometric measures of nutritional status with HIV-associated cardiomyopathy has not been established. Method. We investigated the association between anthropometric measures of nutritional status and cardiomyopathy in HIV-positive individuals in a cross-sectional case comparison study. Results. Seventeen cases of HIV-associated cardiomyopathy and a comparison group of 18 HIV-positive individuals without cardiomyopathy were studied. There was no significant difference between the two groups in age, gender, CD4 cell count, HIV RNA viral load or World Health Organization (WHO) clinical stage of HIV disease. Patients with HIV-associated cardiomyopathy had evidence of undernutrition compared with HIV-infected people without cardiomyopathy, as evidenced by a significantly lower body mass index (BMI) (20.9 kg/m2 v. 27.0 kg/m2, p=0.02), mid-upper arm circumference (26.2 cm v. 27.3 cm, p=0.02), and bone-free arm muscle area (26.7 cm2 v. 32.8 cm2, p=0.02). However, in a multivariate stepwise logistic regression model, a lower BMI was the only independent anthropometric risk factor for cardiomyopathy (odds ratio 0.76, 95% confidence interval 0.64 - 0.97, p=0.02). Conclusion. A lower BMI is associated with cardiomyopathy in people who are living with HIV

Asymptomatic rheumatic heart disease in South African schoolchildren: Implications for addressing chronic health conditions through a school health service

When new evidence comes to light, it compels us to contemplate the implications of such evidence for health policy and practice. This article examines recent research evidence on the prevalence of asymptomatic rheumatic heart disease (RHD) in  South Africa and considers the implications for the Integrated School Health  Programme (ISHP). RHD is still a major burden of disease in developing countries, and elimination of this preventable condition ranks high among World Heart  Federation goals. If left untreated, it becomes a chronic health condition that  individuals have to cope with into their adult lives. The ISHP regards the health  needs of children with chronic health conditions, which include conditions such as RHD, as a key service component. However, the chronic health component of the ISHP is still poorly developed and can benefit from good evidence to guide implementation. A recent study to ascertain the prevalence of RHD in asymptomatic schoolchildren through mass screening affords an opportunity to reflect on whether, and how, asymptomatic chronic health conditions in schoolchildren could be addressed, and what the implications would be if this were done through a school-based programme such as the ISHP

Frequency and clinical genetics of familial dilated cardiomyopathy in Cape Town: Implications for the evaluation of patients with unexplained cardiomyopathy

Background. Studies from Europe and North America suggest that 20 - 50% of patients with dilated cardiomyopathy (DCM) may have familial disease. There is little information on the frequency and clinical genetics of familial DCM in Africa. Purpose. To determine the frequency and probable mode of inheritance of familial DCM in patients referred for investigation of the cause of DCM at a tertiary centre in Cape Town. Methods. We conducted a retrospective analysis of consecutive patients diagnosed with DCM between 1 February 1996 and 31 December 2009 to determine the frequency of familial disease. Results. Of 109 unrelated patients with DCM, 29 (26.6%) had familial disease. Their mean age of onset of cardiomyopathy (28.01 (standard deviation (SD) 15.33) years) was significantly younger than that for non-familial cases (39.1 (SD 12.6) years) (p=0.001). Male predominance (N=21, 72.4%) and racial distribution (15 (48.3%) coloured patients, 10 (34.5%) black Africans, 4 (13.8%) white individuals, and 1 (3.4%) of Indian descent) of familial DCM probands were similar to the non-familial cases. Of the 29 patients with familial DCM, 2 (7%) had at least one relative diagnosed with peripartum cardiomyopathy. Pedigree analysis of the 29 families was consistent with autosomal dominant inheritance in 72.4%, autosomal recessive inheritance in 17.2% and X-linked recessive inheritance in 10.4%. Conclusions. Familial DCM affects at least a quarter of African patients with DCM, presents at a young age, is associated with peripartum cardiomyopathy, and follows an autosomal dominant pattern of inheritance in the majority of families. Family screening for familial DCM is indicated in all cases of unexplained DCM, including patients with peripartum cardiomyopathy

Clinical characteristics and outcomes of familial and idiopathic dilated cardiomyopathy in Cape Town: A comparative study of 120 cases followed up over 14 years

Background. It is not known whether there are differences in clinical characteristics and outcomes of patients with familial and idiopathic dilated cardiomyopathy (DCM) in an African setting. Purpose. To compare the clinical characteristics and outcomes of familial and idiopathic DCM. Methods. We performed a retrospective study of familial and idiopathic DCM at Groote Schuur Hospital, Cape Town, between 1 February 1996 and 31 December 2009. Clinical, electrocardiographic (ECG) and imaging characteristics were compared, in addition to treatment and survival. Results. Eighty patients with idiopathic DCM and 40 familial cases were studied. ECG T-wave inversion was significantly more frequent in familial DCM (87.5%) than in idiopathic cases (68.8%) (p=0.014), whereas idiopathic patients had a higher prevalence of pathological Q waves (32.5%) than familial cases (12.5%) (p=0.028). Cardiac chambers were significantly more dilated with poorer systolic function in idiopathic than familial cases. A mortality rate of 40% after a median follow-up of 5 years was, however, similar in both groups. The presence of New York Heart Association functional class III and IV symptoms was an independent predictor of mortality (odds ratio (OR) 3.85, 95% confidence interval (CI) 1.30 - 48.47, p<0.001), while heart transplantation was an independent predictor of survival (OR 4.72, 95% CI 1.31 - 72.60, p=0.026) in both groups. Digoxin use without serum monitoring was a significant predictor of mortality in idiopathic DCM (OR 1.62, 95% CI 1.04 - 3.98, p=0.037). Conclusion. Patients with idiopathic DCM have greater cardiac dysfunction than those with familial disease, but mortality is similarly high in both groups. Digoxin use without drug level monitoring may be associated with increased mortality in idiopathic DCM

HIV Infection Is Associated with a Lower Incidence of Constriction in Presumed Tuberculous Pericarditis: A Prospective Observational Study

The original publication is available at http:/www.plosone.orgBackground: Pericardial constriction is a serious complication of tuberculous pericardial effusion that occurs in up to a quarter of patients despite anti-tuberculosis chemotheraphy. The impact of human immunodeficiency virus (HIV) infection on the incidence of constrictive pericarditis following tuberculous pericardial effusion is unknown. Methods and Results: We conducted a prospective observational study to determine the association between HIV infection and the incidence of constrictive pericarditis among 185 patients (median age 33 years) with suspected tuberculous pericardial effusion. These patients were recruited consecutively between March and October 2004 on commencement of anti-tuberculosis treatment, from 15 hospitals in Cameroon, Nigeria and South Africa. Surviving patients (N = 119) were assessed for clinical evidence of constrictive pericarditis at 3 and 6 months of follow-up. Clinical features of HIV infection were present in 42 (35.2%) of the 119 patients at enrolment into the study.66 of the 119 (56.9%) patients consented to HIV testing at enrolment. During the 6 months of follow-up, a clinical diagnosis of constrictive pericarditis was made in 13 of the 119 patients (10.9%, 95% confidence interval [CI] 5.9-18%). Patients with clinical features of HIV infection appear less likely to develop constriction than those without (4.8% versus 14.3%; P = 0.08). None of the 33 HIV seropositive patients developed constriction, but 8 (24.2%, 95%CI 11.1-42.3%)of the 33 HIV seronegative patients did (P = 0.005). In a multivariate logistic regression model adjusting simultaneously for several baseline characteristics, only clinical signs of HIV infection were significantly associated with a lower risk of constriction (odd ratio 0.14, 95% CI 0.02-0.87, P = 0.035). Conclusions: These data suggest that HIV infection is associated with a lower incidence of pericardial constriction in patients with presumed tuberculous pericarditis. © 2008 Ntsekhe et al.This study was funded, in part, through research grants from the University of Cape Town, the Medical Scholarships for South African Blacks (MESAB), the Medical Research Council of South Africa, the National Research Foundation of South Africa.Publishers' versio