Association between hemolysis and albuminuria in adults with sickle cell anemia.

Studies have questioned whether renal dysfunction in sickle cell disease is linked to hemolysis-associated vasculopathy. We have investigated renal function and markers of hemolysis in a cohort of 424 adult African-British patients with sickle cell disease. While significant associations were found in HbSS and HbSß(0) (sickle cell anemia) patients with and without controlling for covariates between hemolytic markers and albuminuria, the associations were not significant in patients with HbSC. Estimated glomerular filtration rate, a marker of renal function, correlated significantly with reticulocyte count and bilirubin. Alpha thalassemia, present in 34% of the sickle cell anaemia patients, had a protective effect against albuminuria in this group. Altogether, the incidence of hyperfiltration was 71% and microalbuminuria 37%, making nephropathy a common complication of sickle cell anemia.

Mid-upper arm circumference at age of routine infant vaccination to identify infants at elevated risk of death: a retrospective cohort study in the Gambia.

OBJECTIVE: To determine the predictive value for death before 12 months of age of mid-upper arm circumference (MUAC) and weight-for-length Z score (WFLz). METHODS: A retrospective cohort analysis of infants living in Keneba, in rural Gambia, was conducted. Anthropometric measures were obtained from demographic surveillance system records for infants registered between February 1974 and July 2008 who had had MUAC and WFLz recorded at 6-14 weeks of age and vital status recorded at least once more. Hazard ratios (HRs), population attributable fractions and areas under receiver operating characteristic (ROC) curves were estimated to assess the predictive value for death in infancy of MUAC and WFLz. FINDINGS: Of 2876 infants included in the analysis, 40 died before the age of 12 months. The HR for death in this group versus in well-nourished infants was 5.8 (95% confidence interval, CI: 1.6-21) for a WFLz < -3. HRs for MUACs below the thresholds of 115 mm, 110 mm and 105 mm were 4.5 (95% CI: 1.4-15), 9.5 (95% CI: 2.6-35) and 23 (95% CI: 4.2-122), respectively. The attributable fractions for a MUAC < 130 mm and a WFLz < 0 were 51% and 13%, respectively. The areas under the ROC curve for death in infancy were 0.55 (95% CI: 0.46 to 0.64) for WFLz and 0.64 (95% CI: 0.55 to 0.73) for MUAC. CONCLUSION: Among infants aged 6 to 14 weeks, unadjusted MUAC showed good performance in identifying infants at increased risk of death.

Effectiveness of an early supplementation scheme of high-dose vitamin A versus standard WHO protocol in Gambian mothers and infants: a randomised controlled trial.

BACKGROUND: Most developing countries have adopted a standard WHO dosing schedule for vitamin A supplementation. However, in 2002 the International Vitamin A Consultative Group (IVACG) Annecy Accord recommended a new high-dose regimen for mothers and infants. Our aim was to test whether the new high-dose regimen of vitamin A supplementation would increase maternal and infant plasma vitamin A, reduce infant Helicobacter pylori infection and nasopharyngeal pneumococcal carriage, and improve infant gut epithelial integrity. METHODS: In an area of moderate vitamin A deficiency in rural Gambia, 220 mother-infant pairs were enrolled in a randomised double-blind trial between September, 2001, and October, 2004, that compared the IVACG high dose with the WHO dose. The primary endpoints were levels of maternal and infant plasma vitamin A, H pylori infection, pneumococcal carriage, and gut epithelial integrity. The trial is registered as ISRCTN 98554309. FINDINGS: 197 infants completed follow-up to 12 months (99 high dose and 98 WHO dose). There were no adverse events at dosing. No differences were found in the primary outcomes for high-dose versus WHO schedule: maternal vitamin A concentration at 2 months +0.02 micromol/L (95% CI -0.10 to 0.15); infant vitamin A at 5 months +0.01 micromol/L (-0.06 to 0.08); H pylori infection at 12 months -0.3% (-14.7 to 14.2); maternal pneumococcal carriage at 12 months -2.0% (-13.7 to 9.7); infant pneumococcal carriage at 12 months -4.1% (-15.8 to 7.6); infant gut mucosal damage at 12 months 5.2% (-8.7 to 19.2). There were more clinic attendances by the high-dose group in the first 6 months of life (p=0.018). INTERPRETATION: Our results do not lend support to the proposal to increase the existing WHO standard dosing schedule for vitamin A in areas of moderate vitamin A deficiency. Caution is urged for future studies because trials have shown possible adverse effects of higher doses of vitamin A, and potential negative interactions with the expanded programme on immunisation (EPI) vaccines.

g(HbF): a genetic model of fetal hemoglobin in sickle cell disease.

Fetal hemoglobin (HbF) is a strong modifier of sickle cell disease (SCD) severity and is associated with 3 common genetic loci. Quantifying the genetic effects of the 3 loci would specifically address the benefits of HbF increases in patients. Here, we have applied statistical methods using the most representative variants: rs1427407 and rs6545816 in BCL11A, rs66650371 (3-bp deletion) and rs9376090 in HMIP-2A, rs9494142 and rs9494145 in HMIP-2B, and rs7482144 (Xmn1-HBG2 in the ß-globin locus) to create g(HbF), a genetic quantitative variable for HbF in SCD. Only patients aged ≥5 years with complete genotype and HbF data were studied. Five hundred eighty-one patients with hemoglobin SS (HbSS) or HbSß0 thalassemia formed the "discovery" cohort. Multiple linear regression modeling rationalized the 7 variants down to 4 markers (rs6545816, rs1427407, rs66650371, and rs7482144) each independently contributing HbF-boosting alleles, together accounting for 21.8% of HbF variability (r2) in the HbSS or HbSß0 patients. The model was replicated with consistent r2 in 2 different cohorts: 27.5% in HbSC patients (N = 186) and 23% in 994 Tanzanian HbSS patients. g(HbF), our 4-variant model, provides a robust approach to account for the genetic component of HbF in SCD and is of potential utility in sickle genetic and clinical studies.

Effect of moderate anaemia on later mortality in rural African children.

Severe anaemia in childhood is associated with increased mortality, although evidence relating moderate anaemia to child survival is scarce. We aimed to investigate this association. We did a case-control study of children with moderate anaemia, and compared haemoglobin concentrations measured up to a year before death for 403 children (age range 28 days to 15 years) with those from children who survived (matched for age and sex). Data were obtained from long-term health records (1950-97) of a rural Gambian research centre. Excluding an acute effect in this last week of life, no evidence was recorded of lower haemoglobin concentrations in the children who died than in survivors, or of any general or disease-specific effects of non-severe anaemia (70-110 g/L) on mortality.

Coverage and timing of children's vaccination: an evaluation of the expanded programme on immunisation in The Gambia.

OBJECTIVE: To evaluate the coverage and timeliness of the Expanded Programme on Immunisation (EPI) in The Gambia. METHODS: Vaccination data were obtained between January 2005 and December 2012 from the Farafenni Health and Demographic Surveillance System (FHDSS), the Basse Health and Demographic Surveillance System (BHDSS), the Kiang West Demographic surveillance system (KWDSS), a cluster survey in the more urban Western Health Region (WR) and a cross sectional study in four clinics in the semi-urban Greater Banjul area of WR. Kaplan-Meier survival function was used to estimate the proportion vaccinated by age and to assess timeliness to vaccination. FINDINGS: BCG vaccine uptake was over 95% in all regions. Coverage of DPT1 ranged from 93.2% in BHDSS to 99.8% in the WR. Coverage decreased with increasing number of DPT doses; DPT3 coverage ranged from 81.7% in BHDSS to 99.0% in WR. Measles vaccination coverage ranged from 83.3% in BHDSS to 97.0% in WR. DPT4 booster coverage was low and ranged from 43.9% in the WR to 82.8% in KWDSS. Across all regions, delaying on previous vaccinations increased the likelihood of being delayed for the subsequent vaccination. CONCLUSIONS: The Gambia health system achieves high vaccine coverage in the first year of life. However, there continues to be a delay to vaccination which may impact on the introduction of new vaccines. Examples of effectively functioning EPI programmes such as The Gambia one may well be important models for other low income countries struggling to achieve high routine vaccination coverage.

Gestational diabetes, comparison of women diagnosed in second and third trimester of pregnancy with non GDM women: Analysis of a cohort study.

UNLABELLED: Pregnant women are normally screened for Gestational diabetes (GDM) at week 24 of pregnancy. However some women develop the disease later on their pregnancies. No study has analyzed women developing GDM later in pregnancy. OBJECTIVE: To analyze data on a cohort study and compare women diagnosed with GDM in second and third trimester of pregnancy with women without GDM. RESULTS: GDM women diagnosed during their first two trimesters of pregnancy were older (p = 0.0008) and had higher body mass index (BMI) (p = 0.0007) than non GDM women. However, the only risk factor in women diagnosed in their third trimester of pregnancy was having first degree relatives with type 2 DM and this was independent of age and BMI (OR of 2.7, 95% CI 1.2 - 6.0). CONCLUSIONS: Women who develop GDM in their second trimester of pregnancy have known risk factors for diabetes mellitus such as age and higher BMI, however, the only recognised risk factor between non GDM women and women developing GDM late in pregnancy is family history of type 2 DM. Two populations of GDM may exist and future studies should focus on analysing short and long term complications of these women to support the need to diagnosed and treat them all.

The linear effects of alpha-thalassaemia, the UGT1A1 and HMOX1 polymorphisms on cholelithiasis in sickle cell disease.

Serum bilirubin levels and predisposition to gallstones in sickle cell disease (SCD) are influenced by genetic variation in the hepatic uridine diphosphate (UDP)-glucuronosyltransferase (UGT1A1) gene, but the association is not consistent. This study investigated whether variation in the gene encoding haem oxygenase (HMOX1), a rate-limiting enzyme upstream of UGT1A in the haem catabolic pathway, and alpha-thalassaemia could explain some of the inconsistent effects. The UGT1A1 [TA](n) and HMOX1 [GT](n) promoter polymorphisms and alpha globin genotypes were determined in 263 SCD patients (199 HbSS, 5 HbS/beta(0), 59 HbSC). Detection of gallstones was based on ultrasound of the liver/biliary tree. Regression analysis showed that serum bilirubin levels and the incidence of gallstones were strongly associated with the number of UGT1A1 [TA] repeats in all subjects (P < 0.0001 and P < 0.01, respectively). While HMOX1 genotype had no effect, co-inheritance of alpha-thalassaemia reduced serum bilirubin levels in all SCD patients independently of the number of UGT1A1 [TA] repeats. Each additional [TA] repeat is associated with an increase in mean serum bilirubin levels of 21% and cholelithiasis risk of 87% in SCD.

Gestational diabetes, comparison of women diagnosed in second and third trimester of pregnancy with non GDM women: Analysis of a cohort study / Diabetes gestational, comparación entre mujeres diagnosticadas en el segundo y tercer trimestre del embarazo con mujeres sin diabetes gestacional: Análisis de un estudio de cohorte

Pregnant women are normally screenedfor Gestational diabetes (GDM) at week 24 of pregnancy. Howeversome women develop the disease later on their pregnancies. No study has analyzed women developing GDM later in pregnancy. Objective: To analyze data on a cohort study and compare women diagnosed with GDM in second and third trimester of pregnancy with women without GDM. Results: GDM women diagnosed during their first two trimesters of pregnancy were older (p = 0.0008) and had higher body mass Índex (BMI) (p = 0.0007) than non GDM women. However, the only risk factor in women diagnosed in their third trimester of pregnancy was having first degree relatives with type 2 DM and this was independent of age and BMI (OR of2.7, 95 percent CI 1.2 - 6.0). Conclusions: Women who develop GDM in their second trimester of pregnancy have known risk factors for diabetes mellitus such as age and higher BMI, however, the only recognised risk factor between non GDM women and women developing GDM late in pregnancy is family history of type 2 DM. Two populations ofGDM may exist andfuture studies should focus on analysing short and long term complications ofthese women to support the need to diagnosed and treat them all.

La pesquisa para diabetes gestacional (DG) se realiza normalmente en la semana 24 de embarazo. Sin embargo, muchas mujeres desarrollan la enfermedad más tardíamente durante el embarazo. No hay estudios analizando DG en tercer trimestre del embarazo. Objetivo: Analizar los datos de una cohorte para comparar mujeres con DG diagnosticada en segundo y tercer trimestre del embarazo con mujeres sin DG. Resultados: Las mujeres diagnosticadas en los primeros dos trimestres del embarazo eran mayores (p = 0,0008) y tenían mayor índice de masa corporal (IMC) (p = 0,0007) que las mujeres sin DG. El único factor de riesgo en mujeres diagnosticadas en el tercer trimestre del embarazo fue tener antecedentes familiares de DM, lo cual fue independiente de la edad e IMC (OR: 2,7, 95 por ciento CI 1,2 - 6,0). Conclusiones: Mujeres con DG diagnosticada en el segundo trimestre del embarazo tienen distintos factores de riesgo que mujeres diagnosticadas más tardíamente. Es posible que existan dos poblaciones de DG según el período de diagnóstico, por lo que debiera estudiarse si las complicaciones de estos dos subgrupos justifican el diagnóstico y tratamiento de ambos.