Multivariate GWAS analysis reveals loci associated with liver functions in continental African populations.

BACKGROUND: Liver disease is any condition that causes liver damage and inflammation and may likely affect the function of the liver. Vital biochemical screening tools that can be used to evaluate the health of the liver and help diagnose, prevent, monitor, and control the development of liver disease are known as liver function tests (LFT). LFTs are performed to estimate the level of liver biomarkers in the blood. Several factors are associated with differences in concentration levels of LFTs in individuals, such as genetic and environmental factors. The aim of our study was to identify genetic loci associated with liver biomarker levels with a shared genetic basis in continental Africans, using a multivariate genome-wide association study (GWAS) approach. METHODS: We used two distinct African populations, the Ugandan Genome Resource (UGR = 6,407) and South African Zulu cohort (SZC = 2,598). The six LFTs used in our analysis were: aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), total bilirubin, and albumin. A multivariate GWAS of LFTs was conducted using the exact linear mixed model (mvLMM) approach implemented in GEMMA and the resulting P-values were presented in Manhattan and quantile-quantile (QQ) plots. First, we attempted to replicate the findings of the UGR cohort in SZC. Secondly, given that the genetic architecture of UGR is different from that of SZC, we further undertook similar analysis in the SZC and discussed the results separately. RESULTS: A total of 59 SNPs reached genome-wide significance (P = 5x10-8) in the UGR cohort and with 13 SNPs successfully replicated in SZC. These included a novel lead SNP near the RHPN1 locus (lead SNP rs374279268, P-value = 4.79x10-9, Effect Allele Frequency (EAF) = 0.989) and a lead SNP at the RGS11 locus (lead SNP rs148110594, P-value = 2.34x10-8, EAF = 0.928). 17 SNPs were significant in the SZC, while all the SNPs fall within a signal on chromosome 2, rs1976391 mapped to UGT1A was identified as the lead SNP within this region. CONCLUSIONS: Using multivariate GWAS method improves the power to detect novel genotype-phenotype associations for liver functions not found with the standard univariate GWAS in the same dataset.

Transferability of genetic risk scores in African populations.

The poor transferability of genetic risk scores (GRSs) derived from European ancestry data in diverse populations is a cause of concern. We set out to evaluate whether GRSs derived from data of African American individuals and multiancestry data perform better in sub-Saharan Africa (SSA) compared to European ancestry-derived scores. Using summary statistics from the Million Veteran Program (MVP), we showed that GRSs derived from data of African American individuals enhance polygenic prediction of lipid traits in SSA compared to European and multiancestry scores. However, our GRS prediction varied greatly within SSA between the South African Zulu (low-density lipoprotein cholesterol (LDL-C), R2 = 8.14%) and Ugandan cohorts (LDL-C, R2 = 0.026%). We postulate that differences in the genetic and environmental factors between these population groups might lead to the poor transferability of GRSs within SSA. More effort is required to optimize polygenic prediction in Africa.

Genetic loci implicated in meta-analysis of body shape in Africans.

BACKGROUND AND AIMS: Obesity is one of the leading causes of non-communicable diseases (NCD). Thus, NCD risk varies in obese individuals based on the location of their fat depots; while subcutaneous adiposity is protective, visceral adiposity increases NCD risk. Although, previously anthropometric traits have been used to quantify body shape in low-income settings, there is no consensus on how it should be assessed. Hence, there is a growing interest to evaluate body shape derived from the principal component analysis (PCA) of anthropometric traits; however, this is yet to be explored in individuals of African ancestry whose body shape is different from those of Europeans. We set out to capture body shape in its multidimensional structure and examine the association between genetic variants and body shape in individuals of African ancestry. METHOD AND RESULTS: We performed a genome-wide association study (GWAS) for body shape derived from PCA analysis of anthropometric traits in the Ugandan General Population Cohort (GPC, n = 6407) and the South African Zulu Cohort (SZC, n = 2595), followed by a GWAS meta-analysis to assess the genetic variants associated with body shape. We identified variants in FGF12, GRM8, TLX1NB and TRAP1 to be associated with body shape. These genes were different from the genes been associated with BMI, height, weight, WC and waist-hip ration in continental Africans. Notably, we also observed that a standard deviation change in body shape was associated with an increase in blood pressure and blood lipids. CONCLUSION: Variants associated with body shape, as a composite variable might be different for those of individual anthropometric traits. Larger studies are required to further explore these phenomena.

Polygenic Prediction of Type 2 Diabetes in Africa.

OBJECTIVE: Polygenic prediction of type 2 diabetes (T2D) in continental Africans is adversely affected by the limited number of genome-wide association studies (GWAS) of T2D from Africa and the poor transferability of European-derived polygenic risk scores (PRSs) in diverse ethnicities. We set out to evaluate if African American, European, or multiethnic-derived PRSs would improve polygenic prediction in continental Africans. RESEARCH DESIGN AND METHODS: Using the PRSice software, ethnic-specific PRSs were computed with weights from the T2D GWAS multiancestry meta-analysis of 228,499 case and 1,178,783 control subjects. The South African Zulu study (n = 1,602 case and 981 control subjects) was used as the target data set. Validation and assessment of the best predictive PRS association with age at diagnosis were conducted in the Africa America Diabetes Mellitus (AADM) study (n = 2,148 case and 2,161 control subjects). RESULTS: The discriminatory ability of the African American and multiethnic PRSs was similar. However, the African American-derived PRS was more transferable in all the countries represented in the AADM cohort and predictive of T2D in the country combined analysis compared with the European and multiethnic-derived scores. Notably, participants in the 10th decile of this PRS had a 3.63-fold greater risk (odds ratio 3.63; 95% CI 2.19-4.03; P = 2.79 × 10-17) per risk allele of developing diabetes and were diagnosed 2.6 years earlier than those in the first decile. CONCLUSIONS: African American-derived PRS enhances polygenic prediction of T2D in continental Africans. Improved representation of non-European populations (including Africans) in GWAS promises to provide better tools for precision medicine interventions in T2D.

Type 2 diabetes mellitus in sub-Saharan Africa: challenges and opportunities.

Type 2 diabetes mellitus (T2DM), which was once thought to be rare in sub-Saharan Africa (SSA), is now well established in this region. The SSA region is undergoing a rapid but variable epidemiological transition fuelled by the pace of urbanization, with disease burden profiles shifting from communicable diseases to non-communicable diseases (NCDs). Information on the epidemiology of T2DM has increased, but wide variations in study methods, diagnostic biomarkers and criteria hamper analytical comparison, and data from high-quality studies are limited. The prevalence of T2DM is still low in some rural populations but moderate or high rates are reported in many countries/regions, with evidence for an increase in some. In addition, the proportion of undiagnosed T2DM is still high. The prevalence of T2DM is highest in African people living in urban areas, and the gradient between African people living in urban areas and people in the African diaspora is rapidly fading. However, data from longitudinal studies are lacking and there is limited information on chronic complications and the genetics of T2DM. The large unmet needs for T2DM care call for greater investment of resources into health systems to manage NCDs in SSA. Proposed health-system paradigms are being developed in some countries/regions. However, national NCD programmes need to be adequately funded and coordinated to stem the tide of T2DM and its complications.

HIV infection and anaemia do not affect HbA1c for the detection of diabetes in black South Africans: Evidence from the Durban Diabetes Study.

OBJECTIVE: South Africa has a high burden of HIV infection and anaemia. These conditions may cause HbA1c to over- or underestimate glycaemia; however, this has not been comprehensively investigated in African populations. We assessed the association of anaemia, HIV infection and antiretroviral therapy (ART) with HbA1c , and implications for the detection and diagnosis of diabetes, in a black South African population. RESEARCH DESIGN AND METHODS: In this population-based cross-sectional study in eThekwini municipality (Durban), South Africa, we assessed HbA1c and conducted oral glucose tolerance tests (OGTTs), HIV diagnostic tests and full blood count measurements among 1067 participants without a history of diabetes diagnosis. Linear regression was used to examine differences in HbA1c by anaemia (comparator: no anaemia), or HIV and ART (comparator: no HIV) status. HbA1c -based diabetes prevalence was compared with OGTT-based prevalence among individuals with anaemia and with untreated and ART-treated HIV. RESULTS: In adjusted analyses, normocytic and microcytic anaemia were associated with higher HbA1c compared with no anaemia, whereas macrocytic anaemia and ART-treated HIV were associated with lower HbA1c compared with no anaemia and no HIV, respectively. However, magnitudes of association were small (range: ß  = -3.4 mmol/mol or -0.31%, p < 0.001 [macrocytic anaemia] to ß = 2.1 mmol/mol or 0.19%, p < 0.001 [microcytic anaemia]). There was no significant difference in diabetes prevalence based on HbA1c or OGTT among individuals with anaemia (2.9% vs. 3.3%, p = 0.69), untreated HIV (1.6% vs. 1.6% p = 1.00) or ART-treated HIV (2.9% vs. 1.2%, p = 0.08). CONCLUSIONS: Our results suggest that anaemia and HIV status appear unlikely to materially affect the utility of HbA1c for diabetes detection and diagnosis in this population. Further studies are needed to examine these associations in sub-Saharan African populations.

Uganda Genome Resource Enables Insights into Population History and Genomic Discovery in Africa.

Genomic studies in African populations provide unique opportunities to understand disease etiology, human diversity, and population history. In the largest study of its kind, comprising genome-wide data from 6,400 individuals and whole-genome sequences from 1,978 individuals from rural Uganda, we find evidence of geographically correlated fine-scale population substructure. Historically, the ancestry of modern Ugandans was best represented by a mixture of ancient East African pastoralists. We demonstrate the value of the largest sequence panel from Africa to date as an imputation resource. Examining 34 cardiometabolic traits, we show systematic differences in trait heritability between European and African populations, probably reflecting the differential impact of genes and environment. In a multi-trait pan-African GWAS of up to 14,126 individuals, we identify novel loci associated with anthropometric, hematological, lipid, and glycemic traits. We find that several functionally important signals are driven by Africa-specific variants, highlighting the value of studying diverse populations across the region.

High frequency of hypoglycaemia in patients with type 1 diabetes mellitus attending a tertiary diabetes clinic in Durban, South Africa.

AIM: The study aimed to assess the prevalence of hypoglycaemia in subjects with type 1 diabetes (T1D) attending a public health tertiary diabetes clinic in Durban, South Africa. METHODS: Patients with T1D were enrolled at the time of clinic attendance. Data on hypoglycaemia over the previous 12 weeks were obtained from glucose meter downloads as well as diary records. Each patient completed the Hypoglycaemia Fear Survey questionnaire as well as an in-house questionnaire on hypoglycaemic episodes in the previous 12 months. RESULTS: A total of 151 subjects (58% female, 54% black African) were enrolled. "Any" hypoglycaemia occurred in 144 (95.4%) in the 12 months prior to clinic attendance. Of these, "severe" hypoglycaemia occurred in 107 (74.3%) and 22 (20.6%) had five or more severe episodes. The most frequent behavioural change in response to hypoglycaemia was insulin dose self-adjustment and the commonest worry was the possibility of becoming emotionally upset during hypoglycaemia. CONCLUSIONS: In a tertiary diabetes clinic in Durban, South Africa, there was a high frequency of hypoglycaemia in patients with T1D and in the majority, at least one severe episode occurred in the 12 months prior to clinic attendance. The results indicate a need for further study and strategies to reduce the frequency and severity of hypoglycaemia.

Genome-wide association study of type 2 diabetes in Africa.

AIMS/HYPOTHESIS: Genome-wide association studies (GWAS) for type 2 diabetes have uncovered >400 risk loci, primarily in populations of European and Asian ancestry. Here, we aimed to discover additional type 2 diabetes risk loci (including African-specific variants) and fine-map association signals by performing genetic analysis in African populations. METHODS: We conducted two type 2 diabetes genome-wide association studies in 4347 Africans from South Africa, Nigeria, Ghana and Kenya and meta-analysed both studies together. Likely causal variants were identified using fine-mapping approaches. RESULTS: The most significantly associated variants mapped to the widely replicated type 2 diabetes risk locus near TCF7L2 (p = 5.3 × 10-13). Fine-mapping of the TCF7L2 locus suggested one type 2 diabetes association signal shared between Europeans and Africans (indexed by rs7903146) and a distinct African-specific signal (indexed by rs17746147). We also detected one novel signal, rs73284431, near AGMO (p = 5.2 × 10-9, minor allele frequency [MAF] = 0.095; monomorphic in most non-African populations), distinct from previously reported signals in the region. In analyses focused on 100 published type 2 diabetes risk loci, we identified 21 with shared causal variants in African and non-African populations. CONCLUSIONS/INTERPRETATION: These results demonstrate the value of performing GWAS in Africans, provide a resource to larger consortia for further discovery and fine-mapping and indicate that additional large-scale efforts in Africa are warranted to gain further insight in to the genetic architecture of type 2 diabetes.

Non-alcoholic fatty liver disease in Africa: a hidden danger.

There is a dearth of data on the burden and spectrum of non-alcoholic fatty liver disease (NAFLD) in African populations. The limited available information suggests that the prevalence of NAFLD in the general population is lowest for the Africa region. However, this is likely to be an underestimate and also does not take into consideration the long-term impact of rising rates of obesity, type-2 diabetes mellitus (T2DM) and high human immunodeficiency virus infection burden in Africa. A racial disparity in the prevalence of NAFLD has been observed in some studies but remains unexplained. There is an absence of data from population-based studies in Africa and this highlights the need for such studies, to reliably define the health service needs for this region. Screening for NAFLD at a population-based level using ultrasound is perhaps the ideal method for resource-poor settings because of its relative cost-effectiveness. What is required as a priority from Africa, are well-designed epidemiologic studies that screen for NAFLD in the general population as well as high-risk groups such as patients with T2DM or obesity.

Diabetes management and treatment approaches outside of North America and West Europe in 2006 and 2015.

AIMS: The impact of introducing new classes of glucose-lowering medication (GLM) on diabetes management remains unclear, especially outside North America and Western Europe. Therefore, we aimed to analyse trends in glycaemic control and the usage of new and old GLMs in people with type 2 diabetes from 2006 to 2015. METHODS: Summary data from clinical services from nine countries outside North America and Western Europe were collected and pooled for statistical analysis. Each site summarized individual-level data from out-patient medical records for 2006 and 2015. Data included: demographics; HbA1c and fasting plasma glucose levels; and the proportions of patients taking GLM as monotherapy, combination therapy and/or insulin. RESULTS: Between 2006 and 2015, glycaemic control remained stable, although body mass index and duration of diabetes increased in most sites. The proportion of people on GLM increased, and the therapeutic regimens became more complex. There were increases in the use of insulin and triple therapy in most sites, while monotherapy, particularly in relation to sulphonylureas, decreased. Despite the introduction of new GLMs, such as DPP-4 inhibitors, insulin use increased over time. CONCLUSIONS: There was no clear evidence that the use of new classes of GLMs was associated with improvements in glycaemic control or reduced the reliance on insulin. These findings were consistent across a range of economic and geographic settings.

Prevalence and characteristics of celiac disease in South African patients with type 1 diabetes mellitus: Results from the Durban Diabetes and Celiac Disease Study.

BACKGROUND AND AIM: The aim of this study was to assess the prevalence and characteristics of celiac disease (CD) in all patients with type 1 diabetes mellitus attending a tertiary adult diabetes clinic in Durban, South Africa. METHODS: This was a cross-sectional observational study that screened 202 patients; of these, 56.4% were African (Black), 31.7% Asian Indian, 4.5% White, and 7.4% mixed race. Demographic data, symptoms, and anthropometry were documented. Blood tests included anti-tissue transglutaminase antibody (tTG), anti-endomysial antibody (EMA), and anti-gliadin antibody (AGA). Endoscopy and duodenal biopsy were performed in patients with celiac antibodies. Diagnosis of CD was based on the modified Marsh classification. RESULTS: Mean age and mean duration of diabetes were 26.4 ± 11.4 and 10.7 ± 9.1 years, respectively. Celiac antibodies were found in 65 (32.2%) patients: EMA 7.4%, tTG immunoglobulin A (IgA) 8.4%, tTG immunoglobulin G 1.9%, AGA IgA 18.3%, and AGA immunoglobulin G 21.8%. Histological evidence of CD was found in 5.9% (n = 12/202): 2.5% were classed as definite CD (Marsh 3) and 3.4% as potential CD (Marsh 1). None of the patients with CD were symptomatic. The sensitivity of AGA IgA, EMA, and tTG IgA antibodies for detecting histologically proven CD was 66.7%, 50.0%, and 41.7%, respectively. CONCLUSION: The prevalence of CD was similar to reports from western countries. No ethnic specific differences were noted. CD was silent in all patients in this study. The sensitivity of EMA and tTG antibodies was poor and merits further evaluation as screening tools for CD in South African patients with type 1 diabetes mellitus.

High prevalence of antithyroid peroxidase and antiparietal cell antibodies among patients with type 1 diabetes mellitus attending a tertiary diabetes centre in South Africa.

OBJECTIVE: Data on the prevalence of autoimmune thyroid disease (AITD) and gastric autoimmunity in type 1 diabetes mellitus (T1DM) in Africa are limited. The aim of this study was to assess the prevalence of antithyroid peroxidase (TPO-A) and antiparietal cell antibody (PCA) in patients with T1DM at a tertiary diabetes clinic in Durban, South Africa. RESEARCH DESIGN AND METHODS: This was a cross-sectional observational study among subjects attending the adult T1DM clinic at Inkosi Albert Luthuli Hospital. Information about history and clinical examination was collected. Blood tests included glutamic acid decarboxylase antibody (GADA), TPO-A, PCA, vitamin B12, folate, ferritin, thyroid stimulating hormone (TSH), free thyroxine, lipids and HbA1c. RESULTS: A total of 202 (M:F, 90:112) patients were recruited. The ethnic composition was African (black) (56.4%; n=114), Indian (31.7%; n=64), white (4.5%; n=9) and coloured (mixed race) (7.4%; n=15). Mean age and mean duration of diabetes were 26.4±11.4 and 10.7±9.1 years, respectively. Mean body mass index was 21.6±6.3 kg/m2. GADA was positive in 63.37% (n=128). The prevalence of TPO-A was 18.9% (n=39) and PCA 8.9% (n=17). The prevalence of overt hypothyroidism, subclinical hypothyroidism and Graves' disease was 10.9%, 2.5% and 1.5%, respectively; vitamin B12 deficiency was noted in 3.5% (n=7) and iron deficiency in 19.3% (n=39). CONCLUSIONS: Among patients with T1DM in this study, there was a high prevalence of coexistent AITD and gastric autoimmunity. Screening for hypothyroidism and thyroid autoimmunity should be undertaken in all patients at initial presentation. However, to assess the feasibility and optimal timing of subsequent testing in the African setting with limited resources, more collaborative research with longitudinal studies is required.

Characteristics and outcome of surgically treated pituitary tumours in South Africa: a single-centre experience.

AIMS: To describe the clinical, biochemical, radiological and histological features and to determine the outcome of all patients with pituitary tumours treated surgically at Inkosi Albert Luthuli Central Hospital (ILACH) in Durban over a 5-year period. RESEARCH DESIGN: Retrospective chart review from 2008 to 2012. Clinical, biochemical and radiological data were collected before and 1 year after surgery. Histopathology findings and perioperative complications were recorded. RESULTS: Seventy patients were included (age 44·8 ± 14·9 years, 55·7% female). Headache (84·1%) and visual disturbances (78·3%) were the predominant presenting symptoms (84·1% and 78·3%). Most tumours were macroadenomas (97·1%). Trans-sphenoidal surgery was employed in the majority (90%). A single procedure was required in 55·7% patients, two procedures in 30% and up to six in others. Complete resection was achieved in only nine patients (12·8%), residual tumour postsurgery was found in 48 (68·6%), and no change in tumour size was found in 13 (18·6%) patients. Additional medical therapy was used in 22 (31·4%) and radiotherapy in 13 (18·6%). On biopsy, the most common pathology was nonfunctional adenoma in 33 (47·1%); 29 (41·4%) were secretory tumours, and 8 (11·4%) were craniopharyngiomas. Overall mortality was 4·3%. The commonest surgical complication was cerebrospinal fluid (CSF) leak (10%; n = 7). New postsurgical pituitary hypofunction occurred in 50 (71·4%) patients. The outcome at 1 year was similar to that on discharge. CONCLUSIONS: Patients presenting to IALCH had large tumours, and complete resection was achieved in a minority. There was a low overall mortality but high rate of postsurgical pituitary hypofunction.

Burden of Diabetes and First Evidence for the Utility of HbA1c for Diagnosis and Detection of Diabetes in Urban Black South Africans: The Durban Diabetes Study.

OBJECTIVE: Glycated haemoglobin (HbA1c) is recommended as an additional tool to glucose-based measures (fasting plasma glucose [FPG] and 2-hour plasma glucose [2PG] during oral glucose tolerance test [OGTT]) for the diagnosis of diabetes; however, its use in sub-Saharan African populations is not established. We assessed prevalence estimates and the diagnosis and detection of diabetes based on OGTT, FPG, and HbA1c in an urban black South African population. RESEARCH DESIGN AND METHODS: We conducted a population-based cross-sectional survey using multistage cluster sampling of adults aged ≥18 years in Durban (eThekwini municipality), KwaZulu-Natal. All participants had a 75-g OGTT and HbA1c measurements. Receiver operating characteristic (ROC) analysis was used to assess the overall diagnostic accuracy of HbA1c, using OGTT as the reference, and to determine optimal HbA1c cut-offs. RESULTS: Among 1190 participants (851 women, 92.6% response rate), the age-standardised prevalence of diabetes was 12.9% based on OGTT, 11.9% based on FPG, and 13.1% based on HbA1c. In participants without a previous history of diabetes (n = 1077), using OGTT as the reference, an HbA1c ≥48 mmol/mol (6.5%) detected diabetes with 70.3% sensitivity (95%CI 52.7-87.8) and 98.7% specificity (95%CI 97.9-99.4) (AUC 0.94 [95%CI 0.89-1.00]). Additional analyses suggested the optimal HbA1c cut-off for detection of diabetes in this population was 42 mmol/mol (6.0%) (sensitivity 89.2% [95%CI 78.6-99.8], specificity 92.0% [95%CI: 90.3-93.7]). CONCLUSIONS: In an urban black South African population, we found a high prevalence of diabetes and provide the first evidence for the utility of HbA1c for the diagnosis and detection of diabetes in black Africans in sub-Saharan Africa.

The African Genome Variation Project shapes medical genetics in Africa.

Given the importance of Africa to studies of human origins and disease susceptibility, detailed characterization of African genetic diversity is needed. The African Genome Variation Project provides a resource with which to design, implement and interpret genomic studies in sub-Saharan Africa and worldwide. The African Genome Variation Project represents dense genotypes from 1,481 individuals and whole-genome sequences from 320 individuals across sub-Saharan Africa. Using this resource, we find novel evidence of complex, regionally distinct hunter-gatherer and Eurasian admixture across sub-Saharan Africa. We identify new loci under selection, including loci related to malaria susceptibility and hypertension. We show that modern imputation panels (sets of reference genotypes from which unobserved or missing genotypes in study sets can be inferred) can identify association signals at highly differentiated loci across populations in sub-Saharan Africa. Using whole-genome sequencing, we demonstrate further improvements in imputation accuracy, strengthening the case for large-scale sequencing efforts of diverse African haplotypes. Finally, we present an efficient genotype array design capturing common genetic variation in Africa.

Myocardial perfusion imaging for evaluation of suspected ischemia and its relationship with glycemic control in South African subjects with diabetes mellitus.

BACKGROUND: The relationship between myocardial perfusion imaging (MPI) abnormalities, diabetes mellitus, and glucose control in South African populations is unknown. It was hypothesized that in subjects undergoing MPI for suspected coronary artery disease (CAD), those with diabetes would have more extensive perfusion defects and that diabetes control would influence MPI abnormalities. The aim of this study was to examine the relationship between the severity of CAD diagnosed with MPI in subjects with and without diabetes and to determine the relationship between diabetes control and extent of CAD. METHODS: This study was a retrospective chart review of 340 subjects in whom MPI scans were performed over a 12-month period. RESULTS: Subjects with diabetes had a higher prevalence of abnormal MPI, with more extensive ischemia, compared with subjects without diabetes (85.6% versus 68%; odds ratio 2.81, P<0.01). Glycated hemoglobin ≥7.0% was associated with a higher risk of abnormal MPI, with more extensive ischemia, compared with subjects having diabetes and glycated hemoglobin <7.0% (odds ratio 2.46, P=0.03) and those without diabetes (odds ratio 4.55, P=0.0001). CONCLUSION: Subjects with diabetes have more extensive myocardial ischemia when compared with subjects without diabetes. Furthermore, poorer diabetes control is associated with more abnormalities on MPI scanning.

Open-source electronic data capture system offered increased accuracy and cost-effectiveness compared with paper methods in Africa.

OBJECTIVES: Existing electronic data capture options are often financially unfeasible in resource-poor settings or difficult to support technically in the field. To help facilitate large-scale multicenter studies in sub-Saharan Africa, the African Partnership for Chronic Disease Research (APCDR) has developed an open-source electronic questionnaire (EQ). STUDY DESIGN AND SETTING: To assess its relative validity, we compared the EQ against traditional pen-and-paper methods using 200 randomized interviews conducted in an ongoing type 2 diabetes case-control study in South Africa. RESULTS: During its 3-month validation, the EQ had a lower frequency of errors (EQ, 0.17 errors per 100 questions; paper, 0.73 errors per 100 questions; P-value ≤0.001), and a lower monetary cost per correctly entered question, compared with the pen-and-paper method. We found no marked difference in the average duration of the interview between methods (EQ, 5.4 minutes; paper, 5.6 minutes). CONCLUSION: This validation study suggests that the EQ may offer increased accuracy, similar interview duration, and increased cost-effectiveness compared with paper-based data collection methods. The APCDR EQ software is freely available (https://github.com/apcdr/questionnaire).

Characteristics, management and outcome of primary hyperparathyroidism in South Africa: a single-centre experience.

INTRODUCTION: Primary hyperparathyroidism (PHPT) is a common endocrine disorder characterised by hypercalcaemia and elevated parathyroid hormone (PTH) levels. However, it remains a relatively underdiagnosed disease in the developing world primarily due to a lack of routine blood chemistry screening. The aim of this analysis was to evaluate the characteristics, management and outcome of patients with PHPT at a tertiary referral clinic in South Africa. METHODS: A retrospective analysis was undertaken on all patients with a diagnosis of PHPT attending the endocrinology clinic at a tertiary referral hospital in Durban, South Africa, between January 2003 and June 2009. Information on clinical presentation, past medical history, biochemistry, radiology, histology and surgical notes were recorded. Patients with multiple endocrine neoplasia were excluded. RESULTS: A total of 28 case records of PHPT were reviewed. The mean age at presentation was 60±14.5 years with a female preponderance (78.6%). The mode of presentation included referral for investigation of an abnormal serum calcium (n: 23), referral from urologist with nephrolithiasis (n: 3) and for investigation of bone disease (n: 2). Symptomatic disease was found in 26 patients (92.9%), including bone pain (75%), fatigue (46.4%) and abdominal pain (32.1%). Mean serum calcium was 3.0+0.39 (normal 2.08-2.65) mmol/L, serum intact PTH 34.7±41.5 (normal 1.2-8.5) pmol/L and serum alkaline phosphatase 206.3±340.2 (normal 53-141) mIU/L. Sestamibi scan was performed on 24 patients and an adenoma was identified in 83.3%. Of the 19 (68%) patients who had parathyroidectomy, an adenoma was identified as the cause in all cases where histology was available (n:18). Surgery was successful in 18 patients with only one patient requiring repeat parathyroidectomy for persistent hypercalcaemia. Postoperative hypocalcaemia developed in eight patients (42.1%) including four patients who required intravenous calcium infusion for symptomatic hypocalcaemia. CONCLUSIONS: PHPT is a treatable disorder with good surgical success. Asymptomatic disease was uncommon in this group of patients. This is compatible with the symptomatic pattern of presentation reported in other developing countries.