Slowing Disease Progression in Type 2 Diabetes: Latest Advances

Background: Largest head-to-head, double-blind study of metformin, glyburide and rosiglitazone (N = 4,360). Primary objective: To compare the durability of glycemic control using rosiglitazone versus metformin or glyburide as initial monotherapy in patients with recently diagnosed type 2 diabetes. Design: Double-blind, randomized, controlled trial. Inclusion criteria: Type 2 diabetes ≤ 3 years, drug-naive, male and female, aged 30–75 years, FPG 126–180 mg/dl (7–10 mmol/l). Exclusion criteria: Previous use of glucose-lowering therapy, women of child-bearing potential, significant hepatic disease, renal impairment, unstable or severe angina, known CHF (NYHA Class I–IV), uncontrolled hypertension. Treatment duration: Treatment period: 4 to 6 years. Median duration of treatment: 4 years (rosiglitazone and metformin); 3.3 years (glyburide). Interventions: Rosiglitazone, metformin, glyburide

Nephropathy in patients with recently diagnosed type 2 diabetes mellitus black Africans

Background: Albuminuria is long recognised as a sign of renal disease in diabetes. In type 1 diabetes, renal disease occurs after a longer duration of diabetic state. In type 2 diabetes, it is more variable. Objective: To determine the prevalence and any risk factors of albuminuria in short­ term (≤2 yrs) type 2 diabetes. Design: Cross sectional, descriptive study. Microalbuminuria was assessed using micro II strips. Setting: Outpatient diabetic clinic at Kenyatta National Hospital, Nairobi. Subjects: Patients who were newly diagnosed or had had type 2 diabetes for two years or less. Main outcome measures: Microalbuminuria, lipids, glycated haemoglobin, fasting blood glucose and blood pressure. Results: One hundred and thirty nine patients who had type 2 diabetes mellitus for ≤2 yrs were seen, but only 100 patients were included in the study over a six month period. Their mean (SD) age was 53.7 (9.3) years. Mean (SD) duration of diabetes was 10.3 (7.5) months. Fifty per cent of the study patients were hypertensive. Only 48% had HbAic \u3c8% while 36% had HbAic \u3e9%. The lipid profile of total, LDL - HDL­ cholesterol and triglycerides were predominantly within normal limits. Twenty six per cent were established to have albuminuria of which one patient had macroalbuminuria. Blood pressure, glycated haemoglobin and lipid parameters were not significantly different from patients without albuminuria Conclusion: Albuminuria occurred in a significant proportion of patients with short term type 2 diabetes. Comparable to studies done elsewhere on short-term type 2 diabetes, albuminuria is both a sign of nephropathy and a cardiovascular risk factor. It should be looked for in all patients with type 2 diabetes attending this clinic, even at diagnosis

Whole-genome DNA/RNA sequencing identifies truncating mutations in RBCK1 in a novel Mendelian disease with neuromuscular and cardiac involvement

Background: Whole-exome sequencing has identified the causes of several Mendelian diseases by analyzing multiple unrelated cases, but it is more challenging to resolve the cause of extremely rare and suspected Mendelian diseases from individual families. We identified a family quartet with two children, both affected with a previously unreported disease, characterized by progressive muscular weakness and cardiomyopathy, with normal intelligence. During the course of the study, we identified one additional unrelated patient with a comparable phenotype. Methods: We performed whole-genome sequencing (Complete Genomics platform), whole-exome sequencing (Agilent SureSelect exon capture and Illumina Genome Analyzer II platform), SNP genotyping (Illumina HumanHap550 SNP array) and Sanger sequencing on blood samples, as well as RNA-Seq (Illumina HiSeq platform) on transformed lymphoblastoid cell lines. Results: From whole-genome sequence data, we identified RBCK1, a gene encoding an E3 ubiquitin-protein ligase, as the most likely candidate gene, with two protein-truncating mutations in probands in the first family. However, exome data failed to nominate RBCK1 as a candidate gene, due to poor regional coverage. Sanger sequencing identified a private homozygous splice variant in RBCK1 in the proband in the second family, yet SNP genotyping revealed a 1.2Mb copy-neutral region of homozygosity covering RBCK1. RNA-Seq confirmed aberrant splicing of RBCK1 transcripts, resulting in truncated protein products. Conclusions: While the exact mechanism by which these mutations cause disease is unknown, our study represents an example of how the combined use of whole-genome DNA and RNA sequencing can identify a disease-predisposing gene for a novel and extremely rare Mendelian disease

Whole-genome sequencing in an autism multiplex family

BACKGROUND: Autism spectrum disorders (ASDs) represent a group of childhood neurodevelopmental disorders that affect 1 in 88 children in the US. Previous exome sequencing studies on family trios have implicated a role for rare, de-novo mutations in the pathogenesis of autism. METHODS: To examine the utility of whole-genome sequencing to identify inherited disease candidate variants and genes, we sequenced two probands from a large pedigree, including two parents and eight children. We evaluated multiple analytical strategies to identify a prioritized list of candidate genes. RESULTS: By assuming a recessive model of inheritance, we identified seven candidate genes shared by the two probands. We also evaluated a different analytical strategy that does not require the assumption of disease model, and identified a list of 59 candidate variants that may increase susceptibility to autism. Manual examination of this list identified ANK3 as the most likely candidate gene. Finally, we identified 33 prioritized non-coding variants such as those near SMG6 and COQ5, based on evolutionary constraint and experimental evidence from ENCODE. Although we were unable to confirm rigorously whether any of these genes indeed contribute to the disease, our analysis provides a prioritized shortlist for further validation studies. CONCLUSIONS: Our study represents one of the first whole-genome sequencing studies in autism leveraging a large family-based pedigree. These results provide for a discussion on the relative merits of finding de-novo mutations in sporadic cases versus finding inherited mutations in large pedigrees, in the context of neuropsychiatric and neurodevelopmental diseases

An intensive, active surveillance reveals continuous invasion and high diversity of rhinovirus in households

We report on infection patterns in 5 households (78 participants) delineating the natural history of human rhinovirus (HRV). Nasopharyngeal collections were obtained every 3–4 days irrespective of symptoms, over a 6-month period, with molecular screening for HRV and typing by sequencing VP4/VP2 junction. Overall, 311/3468 (8.9%) collections were HRV positive: 256 were classified into 3 species: 104 (40.6%) HRV-A; 14 (5.5%) HRV-B, and 138 (53.9%) HRV-C. Twenty-six known HRV types (13 HRV-A, 3 HRV-B, and 10 HRV-C) were identified (A75, C1, and C35 being most frequent). We observed continuous invasion and temporal clustering of HRV types in households (range 5–13 over 6 months). Intrahousehold transmission was independent of clinical status but influenced by age. Most (89.0%) of HRV infection episodes were limited to <14 days. Individual repeat infections were frequent (range 1–7 over 6 months), decreasing with age, and almost invariably heterotypic, indicative of lasting type-specific immunity and low cross-type protection

Factors Influencing Preferences and Adoption of Improved Groundnut Varieties among Farmers in Tanzania

Access and use of seed of improved varieties of groundnut among farmers can improve farmers’ livelihoods and contribute to the potential of crop production in Tanzania. This paper analyzes factors underpinning the adoption of improved groundnut varieties among farmers to pave the way for upscaling quality seed used for increased production and commodity business in farming communities. A four-stage stratified sampling was used to collect data from 300 groundnut farmers in seven agro-ecological zones through individual interviews. Secondary data were collected from the literature and the Tanzania Agricultural Research Institute at Naliendele centre (TARI–Naliendele). Descriptive statistics and Probit regression model were used for data analysis. The empirical results showed that Johari 1985, Pendo 1998, Naliendele 2009, Mnanje 2009, Mangaka 2009 and Nachi 2015, are the main six improved groundnut varieties used by farmers, with Pendo 1998 having the highest adoption rate (17.1%). In the grain market, four varieties, namely Pendo 1998, Mnanje 2009, Nachi 2015 and Johari 1985, were observed to be highly preferred by grain off-takers. Furthermore, among the adopted improved varieties, Nachi 2015, is observed to be the most consistent high yielding variety, ranging from 1100 kg/ha to 1500 kg/ha in all agro-ecological zones. A farmer’s decision to adopt new varieties is affected by age and gender, farmer group membership, availability of improved seed and seed cost. Overall, male farmers are more likely to adopt improved varieties of groundnut than female farmers. The implications of these findings are also discussed, in particular in the area of policy support

Identifying gaps in HIV policy and practice along the HIV care continuum: evidence from a national policy review and health facility surveys in urban and rural Kenya

The last decade has seen rapid evolution in guidance from the WHO concerning the provision of HIV services along the diagnosis-to-treatment continuum, but the extent to which these recommendations are adopted as national policies in Kenya, and subsequently implemented in health facilities, is not well understood. Identifying gaps in policy coverage and implementation is important for highlighting areas for improving service delivery, leading to better health outcomes. We compared WHO guidance with national policies for HIV testing and counselling, prevention of mother-to-child transmission, HIV treatment and retention in care. We then investigated implementation of these national policies in health facilities in one rural (Kisumu) and one urban (Nairobi) sites in Kenya. Implementation was documented using structured questionnaires that were administered to in-charge staff at 10 health facilities in Nairobi and 34 in Kisumu. Policies were defined as widely implemented if they were reported to occur in > 70% facilities, partially implemented if reported to occur in 30–70% facilities, and having limited implementation if reported to occur in < 30% facilities. Overall, Kenyan national HIV care and treatment policies were well aligned with WHO guidance. Policies promoting access to treatment and retention in care were widely implemented, but there was partial or limited implementation of several policies promoting access to HIV testing, and the more recent policy of Option B+ for HIV-positive pregnant women. Efforts are needed to improve implementation of policies designed to increase rates of diagnosis, thus facilitating entry into HIV care, if morbidity and mortality burdens are to be further reduced in Kenya, and as the country moves towards universal access to antiretroviral therapy

Reliability of Community Health Worker Collected Data for Planning and Policy in a Peri-Urban Area of Kisumu, Kenya

A general introduction of this article is as follows: Reliable and timely health information is an essential foundation of public health action and health systems strengthening, both nationally and internationally (Aqil et al. in Health Policy Plan 24(3): 217–228, 2009; Bradshaw et al. in initial burden of disease estimates for South Africa, 2000. South African Medical Research Council, Cape Town, 2003). The need for sound information is especially urgent in the case of emergent diseases and other acute health threats, where rapid awareness, investigation and response can save lives and prevent broader national outbreaks and even global pandemics (Aqil et al. in Health Policy Plan 24(3): 217–228, 2009). The government of Kenya, through the ministry of public health and sanitation has rolled out the community health strategy as a way of improving health care at the household level. This involves community health workers collecting health status data at the household level, which is then used for dialogue at all the levels to inform decisions and actions towards improvement in health status. A lot of health interventions have involved the community health workers in reaching out to the community, hence successfully implementing these health interventions. Large scale involvement of community health workers in government initiatives and most especially to collect health data for use in the health systems has been minimal due to the assumption that the data may not be useful to the government, because its quality is uncertain. It was therefore necessary that the validity and reliability of the data collected by community health workers be determined, and whether this kind of data can be used for planning and policy formulation for the communities from which it is collected. This would go a long way to settle speculation on whether the data collected by these workers is valid and reliable for use in determining the health status, its causes and distribution, of a community. Our general objective of this article is to investigate the validity and reliability of Community Based Information, and we deal with research question “What is the reliability of data collected at the Community level by Community health workers?”. The methods which we use to find an reliable answer to this question is “Ten percent of all households visited by CHWs for data collection were recollected by a technically trained team. Test/retest method was applied to the data to establish reliability. The Kappa score, sensitivity, specificity and positive predictive values were also used to measure reliability”. Finally our findings are as follows: Latrine availability and Antenatal care presented good correspondence between the two sets of data. This was also true for exclusive breast feeding indicator. Measles immunization coverage showed less consistency than the rest of the child health indicators. At last we conclude and recommend that CHWs can accurately and reliably collect household data which can be used for health decisions and actions especially in resource poor settings where other approaches to population based data are too expensive

Commonly cited incentives in the community implementation of the emergency maternal and newborn care study in western Kenya

Background: Mortality of mothers and newborns is an important public health problem in low-income countries. In the rural setting, implementation of community based education and mobilization are strategies that have sought to reduce these mortalities. Frequently such approaches rely on volunteers within each community. Objective: To assess the perceptions of the community volunteers in rural Kenya as they implemented the EmONC program and to identify the incentives that could result in their sustained engagement in the project. Method: A community-based cross sectional survey was administered to all volunteers involved in the study. Data were collected using a self-administered supervision tool from all the 881 volunteers. Results: 881 surveys were completed. 769 respondents requested some form of incentive; 200 (26%) were for monetary allowance, 149 (19.4%) were for a bicycle to be used for transportation, 119 (15.5%) were for uniforms for identification, 88 (11.4%) were for provision of training materials, 81(10.5%) were for training in Home based Life Saving Skills (HBLSS), 57(7.4%) were for provision of first AID kits, and 39(5%) were for provision of training more facilitators, 36(4.7%) were for provision of free medication. Conclusion: Monetary allowances, improved transportation and some sort of identification are the main incentives cited by the respondents in this context

Pattern and Outcome of Chest Injuries at Bugando Medical Centre in Northwestern Tanzania.

Chest injuries constitute a continuing challenge to the trauma or general surgeon practicing in developing countries. This study was conducted to outline the etiological spectrum, injury patterns and short term outcome of these injuries in our setting. This was a prospective study involving chest injury patients admitted to Bugando Medical Centre over a six-month period from November 2009 to April 2010 inclusive. A total of 150 chest injury patients were studied. Males outnumbered females by a ratio of 3.8:1. Their ages ranged from 1 to 80 years (mean = 32.17 years). The majority of patients (72.7%) sustained blunt injuries. Road traffic crush was the most common cause of injuries affecting 50.7% of patients. Chest wall wounds, hemothorax and rib fractures were the most common type of injuries accounting for 30.0%, 21.3% and 20.7% respectively. Associated injuries were noted in 56.0% of patients and head/neck (33.3%) and musculoskeletal regions (26.7%) were commonly affected. The majority of patients (55.3%) were treated successfully with non-operative approach. Underwater seal drainage was performed in 39 patients (19.3%). One patient (0.7%) underwent thoracotomy due to hemopericardium. Thirty nine patients (26.0%) had complications of which wound sepsis (14.7%) and complications of long bone fractures (12.0%) were the most common complications. The mean LOS was 13.17 days and mortality rate was 3.3%. Using multivariate logistic regression analysis, associated injuries, the type of injury, trauma scores (ISS, RTS and PTS) were found to be significant predictors of the LOS (P < 0.001), whereas mortality was significantly associated with pre-morbid illness, associated injuries, trauma scores (ISS, RTS and PTS), the need for ICU admission and the presence of complications (P < 0.001). Chest injuries resulting from RTCs remain a major public health problem in this part of Tanzania. Urgent preventive measures targeting at reducing the occurrence of RTCs is necessary to reduce the incidence of chest injuries in this region