Association of Body Iron Status with the Risk of Premature Acute Myocardial Infarction in a Pakistani Population

Background

Coronary artery disease is very common in Pakistani population. Some of the studies carried out on Western populations have shown a relationship between body iron status as determined by the ratio of concentrations of serum soluble transferrin receptor (sTfR) to ferritin and the risk of acute myocardial infarction (AMI). In order to investigate whether increased body iron status has any relationship with the risk of premature AMI in Pakistani population, a case-control study was carried out.

Methodology/Principal findings

In this case-control study, 203 consecutive AMI patients [146 males and 57 females; age range 18–45 years] admitted to the National Institute for Cardiovascular Diseases, Karachi, were enrolled with informed consent. In addition, 205 healthy controls whose gender and age (within 3 years) matched the patients, and who had a similar socio-economic background were recruited. Fasting venous blood was obtained and assessed for plasma/serum folate, vitamin B12, homocysteine, total cholesterol, triglycerides, LDL-cholesterol, HDL-cholesterol, sTfR and ferritin and blood lead. It was found that serum concentration of ferritin and blood lead levels were significantly higher in AMI patients compared to their age and gender-matched healthy controls (p value <0.05), while the concentrations of vitamin B12 and HDL-cholesterol were significantly lower in AMI patients compared to controls (p value <0.01). The ratio of sTfR to ferritin was significantly lower in AMI patients compared to controls [mean±SD/median (IQR) values 84.7±295/28.9 (38.4) vs 255±836/49.4 (83.8), respectively; p value <0.001]. Compared with the highest quartile of sTfR/ferritin (low body iron status), the OR for the risk of AMI was 3.29(95% CI, 1.54–7.03) for the lowest quartile (quartile 1) when the model was adjusted for vitamin B12 and HDL-cholesterol (p value for trend <0.01).

Conclusions/Significance

This study shows a positive association between total body iron status and risk of premature AMI in a Pakistani population.     

Plasma Concentrations of Hepcidin in Anemic Zimbabwean Infants

Objective

Anemia in infancy is a global public health problem. We evaluated the relative contributions of iron deficiency and inflammation to infant anemia.

Methods

We measured plasma hepcidin, ferritin, soluble transferrin receptor (sTfR), alpha-1-acid glycoprotein and C-reactive protein (CRP) by ELISA on archived plasma from 289 HIV-unexposed anemic or non-anemic Zimbabwean infants at ages 3mo, 6mo and 12mo. Among anemic infants, we determined the proportion with iron-deficiency anemia (IDA) and anemia of inflammation (AI). We undertook regression analyses of plasma hepcidin and anemia status, adjusting for sex, age and birthweight.

Results

Anemic infants at 3mo were more stunted and had higher CRP (median 0.45 vs 0.21mg/L; P = 0.037) and hepcidin (median 14.7 vs 9.7ng/mL; P = 0.022) than non-anemic infants, but similar levels of ferritin and sTfR; 11% infants had IDA and 15% had AI. Anemic infants at 6mo had higher hepcidin (median 7.9 vs 4.5ng/mL; P = 0.016) and CRP (median 2.33 vs 0.32mg/L; P<0.001), but lower ferritin (median 13.2 vs 25.1μg/L; P<0.001) than non-anemic infants; 56% infants had IDA and 12% had AI. Anemic infants at 12mo had lower ferritin (median 3.2 vs 22.2μg/L; P<0.001) and hepcidin (median 0.9 vs 1.9ng/mL; P = 0.019), but similar CRP levels; 48% infants had IDA and 8% had AI. Comparing anemic with non-anemic infants, plasma hepcidin was 568% higher, 405% higher and 64% lower at 3mo, 6mo and 12mo, respectively, after adjusting for sex and birthweight (all p<0.01). Plasma hepcidin declined significantly with age among anemic but not non-anemic infants. Girls had 61% higher hepcidin than boys, after adjusting for age, anemia and birthweight (p<0.001).

Conclusion

Anemia is driven partly by inflammation early in infancy, and by iron deficiency later in infancy, with plasma hepcidin concentrations reflecting the relative contribution of each. However, there is need to better characterize the drivers of hepcidin during infancy in developing countries.     

The Status of Vitamin B12 and Folate among Chinese Women: A Population-Based Cross-Sectional Study in Northwest China

Objective

To assess the status of the vitamin B12 and folate of Chinese women living in northwest China.

Methods

A population-based cross-sectional study was conducted in 2008 among Chinese women aged 10–49 years living in Shaanxi province of northwest China. A stratified multistage random sampling method was adopted to obtain a sample of 1170 women. The women were interviewed for collection of their background information and their plasma vitamin B12 and folate were measured with the immunoassay method. The status of both vitamins was evaluated and the prevalence of deficiency was estimated.

Results

The median value of the women was 214.5 pg/mL for vitamin B12 and 4.6 ng/mL for folate. The urban women had a significantly higher vitamin B12 (254.1 vs. 195.9 pg/mL) but lower folate (4.4 vs. 4.7 ng/mL) than rural women. Total prevalence of deficiency was 45.5% (95% CI: 42.6%∼48.4%) for vitamin B12 and 14.7% (95% CI: 12.6%∼16.8%) for folate. About 36% of women presented vitamin B12 deficiency alone, 5.2% belonged to folate deficiency alone and 9.5% was combined deficiency in both vitamins. More than 25% of the women were in marginal vitamin B12 status (200–299 pg/mL) and 60% in marginal status of folate (3–6 ng/mL). About 75.2% of rural women with folate deficiency were deficient in vitamin B12 and 46% for urban women. Quantile regression model found decreasing coefficient of folate status across 73 different quantiles of vitamin B12, which indicated that the women with folate deficiency had lower vitamin B12 significantly compared with those with no deficiency.

Conclusions

The deficiency of vitamin B12 and folate is still prevalent among the Chinese women in northwest China. Vitamin B12 deficiency could be more serious and the improvement of poor vitamin B12 status should be invoked when practicing the supplementation of folate against the neural tube defects in northwest China.     

Micronutrient Deficiencies and Related Factors in School-Aged Children in Ethiopia: A Cross-Sectional Study in Libo Kemkem and Fogera Districts,Amhara Regional State

Introduction

The present study describes the distribution of selected micronutrients and anaemia among school-aged children living in Libo Kemkem and Fogera (Amhara State, Ethiopia), assessing differences by socio-demographic characteristics, health status and dietary habits.

Methods

A cross-sectional survey was carried out during May–December 2009. Socio-demographic characteristics, health status and dietary habits were collected. Biomarkers were determined for 764 children. Bivariate and multivariable statistical methods were employed to assess micronutrient deficiencies (MD), anaemia, and their association with different factors.

Results

More than two thirds of the school-aged children (79.5%) had at least one MD and 40.5% had two or more coexisting micronutrient deficiencies. The most prevalent deficiencies were of zinc (12.5%), folate (13.9%), vit A (29.3%) and vit D (49%). Anaemia occurred in 30.9% of the children. Children living in rural areas were more likely to have vit D insufficiency [OR: 5.9 (3.7–9.5)] but less likely to have folate deficiency [OR: 0.2 (0.1–0.4)] and anaemia [OR: 0.58 (0.35–0.97)]. Splenomegaly was positively associated with folate deficiency and anaemia [OR: 2.77 (1.19–6.48) and 4.91 (2.47–9.75)]. Meat and fish consumption were inversely correlated with zinc and ferritin deficiencies [OR: 0.2 (0.1–0.8) and 0.2 (0.1–0.9)], while oil consumption showed a negative association with anaemia and deficiencies of folate and vitamin A [0.58 (0.3–0.9), OR: 0.5 (0.3–0.9) and 0.6 (0.4–0.9)]. Serum ferritin levels were inversely correlated to the presence of anaemia (p<0.005).

Conclusion

There is a high prevalence of vitamin A deficiency and vitamin D insufficiency and a moderate prevalence of zinc and folate deficiencies in school-aged children in this area. The inverse association of anaemia and serum ferritin levels may be due to the presence of infectious diseases in the area. To effectively tackle malnutrition, strategies should target not only isolated micronutrient supplementation but also diet diversification.     

Anthropometric and Micronutrient Status of School-Children in an Urban West Africa Setting: A Cross-Sectional Study in Dakar (Senegal)

Background

Urban areas in West Africa are not immune to undernutrition with recent urbanization and high food prices being important factors. School children often have a poor nutritional status, potentially affecting their health and schooling performance. Yet, generally school children do not benefit from nutrition programs. The objective of the study was to assess the anthropometric and micronutrient status of children from state schools in the Dakar area.

Methods

School children (n = 604) aged from 5 to 17 y (52.5% girls, 47.5% ≥10 y) were selected through a two-stage random cluster sample of children attending urban primary state schools in the Dakar area (30 schools × 20 children). The prevalence of stunting (height-for-age<−2 z-scores) and thinness (BMI-for-age<−2 z-scores, WHO 2006, and three grades of thinness corresponding to BMI of 18.5, 17.0 and 16.0 kg/m2 in adults) were calculated from weight and height. Hemoglobin, plasma concentrations of ferritin (FER), transferrin receptors (TfR), retinol binding protein (RBP), and zinc, and urinary iodine concentrations were measured. Correction factors were used for FER and RBP in subjects with inflammation determined with C-reactive protein and α1-acid-glycoprotein.

Results

4.9% of children were stunted, 18.4% were thin, 5.6% had severe thinness (BMI-for-age<−3 z-scores). Only one child had a BMI-for-age>2 z-scores. Prevalence of anemia, iron deficiency and iron deficiency anemia was 14.4%, 39.1% and 10.6% respectively. 3.0% had vitamin A deficiency, 35.9% a marginal vitamin A status, and 25.9% zinc deficiency. Urinary iodine was <50 µg/L in 7.3% of children and ≥200 µg/L in 22.3%. The prevalence of marginal vitamin A, zinc deficiency, high TfR was significantly higher in boys than in girls (P<0.05). Height-for-age and retinol were significantly lower in participants ≥10 y and <10 y respectively.

Conclusion

Undernutrition, especially thinness, iron and zinc deficiencies in school children in the Dakar area requires special targeted nutrition interventions.     

CXCL9 Associated with Sustained Virological Response in Chronic Hepatitis B Patients Receiving Peginterferon Alfa-2a Therapy: A Pilot Study

Background and Aims

There is lack of a practical biomarker to predict sustained virological response (SVR) in chronic hepatitis B (CHB) patients undergoing peginterferon alfa-2a (PEG-IFN). The aim of this pilot study was to identify immunological features associated with SVR.

Methods

Consecutive 74 CHB patients receiving 24 weeks (for hepatitis B e antigen (HBeAg)-positive) or 48 weeks (for HBeAg-negative) PEG-IFN, were prospectively enrolled. Serum HBV viral loads, hepatitis B surface antigen (HBsAg), CXCL9, IFN-γ-inducible protein 10 (IP-10), interferon-gamma (IFN-γ) and transforming growth factor beta (TGF-β) were measured at baseline and week 12. SVR was defined as HBeAg seroconversion combined with viral load <2000 IU/mL in HBeAg-positive (n=36), and viral load <2000 IU/mL in HBeAg-negative patients (n=38) at 48 weeks after the end of treatment.

Results

Nineteen patients (25.7%), 7 in HBeAg-positive and 12 in HBeAg-negative, achieved SVR. There were significant declines of HBV DNA, HBsAg, IP-10 and IFN-γ levels at week 12. In multivariate analysis, pre-treatment CXCL9 >80 pg/mL, HBV DNA <2.5 x 10⁷ IU/mL and on-treatment HBV viral load, HBsAg decline >10% at week 12 were predictors of SVR. The performance of CXCL9 in predicting SVR was good in patients with HBV DNA <2.5 x 10⁷ IU/mL, particularly in HBeAg-negative CHB cases (positive predictive value, PPV= 64.3%).

Conclusions

Pre-treatment CXCL9 level has the potential to select CHB patients who can respond to PEG-IFN, especially in HBeAg-negative patients with low viral loads.     

Prevalence,Types, Risk Factors and Clinical Correlates of Anaemia in Older People in a Rural Ugandan Population

Background

Studies conducted in high income countries have shown that anaemia is a common medical condition among older people, but such data are scarce in Africa. The objectives of this study were to estimate the prevalence, types, risk factors and clinical correlates of anaemia in older people.

Methods

Participants were aged (≥ 50) years recruited from a general population cohort from January 2012 to January 2013. Blood samples were collected for assessing hemoglobin, serum ferritin, serum vitamin B12, serum folate, C-reactive protein, malaria infection and stool samples for assessment of hookworm infection. HIV status was assessed using an algorithm for HIV rapid testing. Questionnaires were used to collect data on sociodemographic characteristics and other risk factors for anaemia.

Results

In total, 1449 people participated (response rate 72.3%). The overall prevalence of anaemia was 20.3 % (95% CI 18.2-22.3%), and this was higher for males (24.1%, 95% CI=20.7-27.7%) than females (17.5%, 95% CI=15.0-20.1%). In males, the prevalence of anaemia increased rapidly with age almost doubling between 50 and 65 years (p-trend<0.001). Unexplained anaemia was responsible for more than half of all cases (59.7%). Anaemia was independently associated with infections including malaria (OR 3.49, 95% CI 1.78-6.82), HIV (OR 2.17, 1.32-3.57) heavy hookworm infection (OR 3.45, 1.73-6.91), low fruit consumption (OR 1.55, 1.05-2.29) and being unmarried (OR 1.37 , 95% CI 1.01-1.89). However, the odds of anaemia were lower among older people with elevated blood pressure (OR 0.47, 95% CI 0.29-0.77).

Conclusion

Anaemia control programmes in Uganda should target older people and should include interventions to treat and control hookworms and educational programs on diets that enhance iron absorption. Clinicians should consider screening older people with HIV or malaria for anaemia. Further studies should be done on unexplained anaemia and serum ferritin levels that predict iron deficiency anaemia in older people.     

ESA Hyporesponsiveness Is Associated with Adverse Events in Maintenance Hemodialysis (MHD) Patients,But Not with Iron Storage

Objective

It has been reported that hyporesponsiveness to erythropoiesis-stimulating agent (ESA) is associated with adverse events in patients on maintenance hemodialysis (MHD). However, it has not been determined whether higher iron storage is associated with an improved response, including better survival, to ESA.

Design and Method

We measured serum ferritin, hemoglobin (Hb), and transferrin saturation (TSAT) levels every three months for two years in 1,095 MHD patients. The weekly dose of ESA to Hb ratio was also calculated as an index of ESA responsiveness (ERI).

Results

A significant correlation (p<0.001, R = 0.89) between ferritin and Hb was only observed in the patients with ferritin levels <50 ng/mL. High-dose (≥50 mg/week) intravenous iron administration, female sex, low serum albumin, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use were significant predictors of a high ERI value (>280); however, serum ferritin and TSAT levels did not predict a higher ERI. In the time-dependent Cox hazard model, the risk for a composite event in the patients with a high ERI (≥280) and a high ferritin level (≥100 ng/mL) was significantly greater (hazard ratio [HR], 2.09, P = 0.033) than that for patients with a high ERI and a low ferritin (<100 ng/mL) level.

Conclusion

Hb was dependent upon ferritin levels in patients with ferritin levels <50 ng/mL but not in patients with ferritin levels ≥50 ng/mL. Patients with hyporesponsiveness to ESA had a greater risk of composite events, but ERI was unrelated to iron storage.     

Plasma Homocysteine,Vitamin B12 and Folate Levels in Multiple System Atrophy: A Case-Control Study

Background

Multiple system atrophy (MSA) is a neurodegenerative disease, and its pathological hallmark is the accumulation of α-synuclein proteins. Homocysteine (Hcy) is an intermediate amino acid generated during the metabolism of methionine. Hcy may contribute to the pathogenesis of neurodegenerative disorders. Vitamin B12 and folate are cofactors necessary for the methylation of homocysteine.

Methods

This study compared the levels of serum Hcy, vitamin B12 and folate in patients with MSA with those in healthy people to reveal the possible association between MSA and plasma levels of Hcy, vitamin B12 and folate. We enrolled 161 patients with MSA and 161 healthy people in this study. The association between MSA and the levels of Hcy, vitamin B12 and folate were analyzed using binary logistic regression.

Results

The mean level of Hcy in patients with MSA was significantly higher than that in healthy controls (16.23 ± 8.09 umol/l vs 14.04 ± 4.25 umol/l, p < 0.05). After adjusting for age, sex and medical history, the odds ratio for Hcy was 1.07 (95% CI = 1.01–1.13, p < 0.05) for patients with MSA. Vitamin B12 and folate levels were not significantly different between patients with MSA and controls.

Conclusion

Our data suggest that higher levels of Hcy may be associated with an increased risk for MSA.     

Low Birthweight (LBW) and Neonatal Hyperbilirubinemia (NNH) in an Indian Cohort: Association of Homocysteine,Its Metabolic Pathway Genes and Micronutrients as Risk Factors

Background & Aims

Indian subcontinent has the highest child mortality rates along with a very high frequency of low birthweight (LBW). Folate and vitamin B12 (Vit-B12) are necessary during foetal development and their deficiency prevalence in Indians is very high. The objective of the present paper is to assess whether foetal homocysteine (Hcy)/folate metabolic pathway genes, their cofactors and homocysteine level independently (or collectively) predispose children to Low birth weight.

Methods

Cord blood was collected for the study. Frequency of 5 SNPs in 4-Hcy-pathway genes, and levels of Hcy, Vit-B12 and folate were evaluated.

Results

Of the 421 newborns recruited for the study, 38% showed low birth weight (<2.5kg) and 16% were preterm babies. 101 neonates developed neonatal hyperbilirubinemia (NNH). High prevalence of Vit-B12 (65%) and folate (27%) deficiency was observed in newborns along with hyperhomocystinemia (hypHcy-25%). Preterm delivery, micronutrient deficiency, hypHcy and MTHFR 677T SNP are associated as risk factor while G allele of TCN2 C776G is protective against LBW. MTHFR 677T allele and folate deficiency are also independent risk factors for NNH.

Conclusion

We record the highest incidence of Vit-B12, folate deficiency and elevated Hcy levels, of all the studies so far reported on neonates. These together with MTHFR 677T are potential risk factors for LBW. Association of impaired folate/Hcy metabolism with NNH is reported for the first time and the possible way of interaction is discussed. It appears that proper nutritional management during pregnancy would reduce the risk of complex clinical outcomes.     

Assessment of Clinical Signs of Liver Cirrhosis Using T1 Mapping on Gd-EOB-DTPA-Enhanced 3T MRI

Objectives

To assess the differences between normal and cirrhotic livers by means of T1 mapping of liver parenchyma on gadoxetic acid (Gd-EOB-DTPA)-enhanced 3 Tesla (3T) MR imaging (MRI).

Methods

162 patients with normal (n = 96) and cirrhotic livers (n = 66; Child-Pugh class A, n = 30; B, n = 28; C, n = 8) underwent Gd-EOB-DTPA-enhanced 3T MRI. To obtain T1 maps, two TurboFLASH sequences (TI = 400 ms and 1000 ms) before and 20 min after Gd-EOB-DTPA administration were acquired. T1 relaxation times of the liver and the reduction rate between pre- and post-contrast enhancement images were measured.

Results

The T1 relaxation times for Gd-EOB-DTPA-enhanced MRI showed significant differences between patients with normal liver function and patients with Child-Pugh class A, B, and C (p < 0.001). The T1 relaxation times showed a constant significant increase from Child-Pugh class A up to class C (Child-Pugh class A, 335 ms ± 80 ms; B, 431 ms ± 75 ms; C, 557 ms ± 99 ms; Child-Pugh A to B, p < 0.001; Child-Pugh A to C, p < 0.001; Child-Pugh B to C, p < 0.001) and a constant decrease of the reduction rate of T1 relaxation times (Child-Pugh class A, 57.1% ± 8.8%; B, 44.3% ± 10.2%, C, 29.9% ± 6.9%; Child-Pugh A to B, p < 0.001; Child-Pugh A to C,p < 0.001; Child-Pugh B to C, p < 0.001).

Conclusion

Gd-EOB-DTPA-enhanced T1 mapping of the liver parenchyma may present a useful method for determining severity of liver cirrhosis.     

Psychological and Social Factors Associated with Late Pregnancy Iron Deficiency Anaemia in Rural Viet Nam: A Population-Based Prospective Study

Objectives

The aim of this study was to examine the relationships between psychological and social factors and late pregnancy IDA among pregnant women in rural Viet Nam.

Methods

Pregnant women from 50 randomly-selected communes within Ha Nam province were recruited and assessed at 12 - 20 weeks gestation (Wave 1, W1). They were followed up in the last trimester (Wave 2, W2). IDA was defined as Haemoglobin < 11 g/dL and serum ferritin < 15 ng/mL. Symptoms of Common Mental Disorders (CMD) were assessed by the Edinburgh Postnatal Depression Scale-Vietnam (EPDS-V). Persistent antenatal CMD was defined as having an EPDS-V score ≥ 4 in both W1 and W2. Hypothesis models were tested by Structural Equation Modeling analyses.

Results

A total of 378 women provided complete data at both W1 and W2. The incidence risk of IDA in the third trimester was 13.2% (95% confidence interval (CI): 9.8-16.7). Persistent CMD was found in 16.9% (95% CI: 13.1-20.7) pregnant women and predicted by intimate partner violence, fear of other family members, experience of childhood abuse, coincidental life adversity, and having a preference for the sex of the baby. There was a significant pathway from persistent CMD to IDA in late pregnancy via the length of time that iron supplements had been taken. Receiving advice to take iron supplements and higher household wealth index were indirectly related to lower risk of late pregnancy IDA. Early pregnancy IDA and being multi-parous also contributed to late pregnancy IDA.

Conclusions

Antenatal IDA and CMD are prevalent public health problems among women in Viet Nam. The link between them suggests that while direct recommendations to use iron supplements are important, the social factors associated with common mental disorders should be addressed in antenatal care in order to improve the health of pregnant women and their infants.     

Clinical Relevance of Minimal Residual Viremia during Long-Term Therapy with Nucleos(t)ide Analogues in Patients with Chronic Hepatitis B

Background

Successful therapy of chronic hepatitis B with nucleos(t)ide analogues (NUCs) has been defined by undetectable HBV-DNA determined with conventional PCR (lower limit of detection (LLD) 60–80 IU/mL) in clinical registration trials. However, current EASL guidelines recommend highly sensitive real-time PCR (LLD<10–20 IU/mL) and define treatment response by HBV-DNA<10 IU/mL.

Aim

We evaluated frequency and relevance of minimal residual viremia (MRV) during long-term NUC-treatment in a real-life setting.

Methods

Frozen serum samples (HBV-DNA negative by in-house PCR, LLD <73 IU/mL) were re-analyzed by real-time PCR (LLD<10 IU/mL, Abbott, Germany). MRV was defined by real time PCR positivity and conventional PCR negativity.

Results

237 samples of six HBsAg carriers and 27 NUC-treated CHB patients were analyzed (treatment period 28 (11–111) months, different treatment regimens with mono- or combination therapy). MRV was detected in 31/33 individuals (n = 160/237 serum samples) and more frequent in HBsAg carriers (95%) and HBeAg positive (87%) compared to HBeAg negative patients (53%) (p<0.0001, respectively). Five HBsAg carriers, five HBeAg positive, and four HBeAg negative individuals were continuously HBV-DNA positive. MRV was not significantly more often observed during NUC-monotherapies compared to combination therapies. Concomitant immunosuppressive therapy was present in nine cases and did not influence the results. Viral resistance occurred in three immunocompetent patients with adefovir or lamivudine monotherapy.

Conclusions

MRV is frequently observed during long-term NUC-therapy. Adjustment of treatment with highly potent NUCs does not seem to be necessary in case of minimal residual viremia in a real-life setting.     

Duration of HIV-1 Viral Suppression on Cessation of Antiretroviral Therapy in Primary Infection Correlates with Time on Therapy

Objective

A minority of HIV-1 positive individuals treated with antiretroviral therapy (ART) in primary HIV-1 infection (PHI) maintain viral suppression on stopping. Whether this is related to ART duration has not been explored.

Design

And Methods: Using SPARTAC trial data from individuals recruited within 6 months of seroconversion, we present an observational analysis investigating whether duration of ART was associated with post-treatment viraemic control. Kaplan-Meier estimates, logistic regression and Cox models were used.

Results

165 participants reached plasma viral loads (VL) <400 copies/ml at the time of stopping therapy (ART stop). After ART stop, 159 experienced confirmed VL ≥400 copies/ml during median (IQR) follow-up of 167 (108,199) weeks.Most participants experienced VL rebound within 12 weeks from ART stop, however, there was a suggestion of a higher probability of remaining <400 copies/ml for those on ART >12 weeks compared to ≤12 weeks (p=0.061). Cumulative probabilities of remaining <400 copies/ml at 12, 52 and 104 weeks after ART stop were 21% (95%CI=13,30), 4% (1,9), and 4% (1,9) for ≤12 weeks ART, and 32% (22,42), 14% (7,22), and 5% (2,11) for >12 weeks.In multivariable regression, ART for >12 weeks was independently associated with a lower probability of being ≥400 copies/ml within 12 weeks of ART stop (OR=0.11 (95%CI=0.03,0.34), p<0.001)). In Cox models of time to VL ≥400 after 12 weeks, we only found an association with female sex (OR=0.2, p=0.001).

Conclusion

Longer ART duration in PHI was associated with a higher probability of viral control after ART stop.

Trial Registration

Controlled-Trials.com 76742797 http://www.controlled-trials.com/ISRCTN76742797.     

Severe Painful Vaso-Occlusive Crises and Mortality in a Contemporary Adult Sickle Cell Anemia Cohort Study

Background

Frequent painful vaso-occlusive crises (VOCs) were associated with mortality in the Cooperative Study of Sickle Cell Disease (CSSCD) over twenty years ago. Modern therapies for sickle cell anemia (SCA) like hydroxyurea are believed to have improved overall patient survival. The current study sought to determine the relevance of the association between more frequent VOCs and death and its relative impact upon overall mortality compared to other known risk factors in a contemporary adult SCA cohort.

Methods

Two hundred sixty four SCA adults were assigned into two groups based on patient reported outcomes for emergency department (ED) visits or hospitalizations for painful VOC treatment during the 12 months prior to evaluation.

Results

Higher baseline hematocrit (p = 0.0008), ferritin (p = 0.005), and HDL cholesterol (p = 0.01) were independently associated with 1 or more painful VOCs requiring an ED visit or hospitalization for acute pain. During a median follow-up of 5 years, mortality was higher in the ED visit/hospitalization group (relative risk [RR] 2.68, 95% CI 1.1-6.5, p = 0.03). Higher tricuspid regurgitatant jet velocity (TRV) (RR 2.41, 95% CI 1.5-3.9, p < 0.0001), elevated ferritin (RR 4.00, 95% CI 1.8-9.0, p = 0.001) and lower glomerular filtration rate (RR=2.73, 95% CI 1.6-4.6, p < 0.0001) were also independent risk factors for mortality.

Conclusions

Severe painful VOCs remain a marker for SCA disease severity and premature mortality in a modern cohort along with other known risk factors for death including high TRV, high ferritin and lower renal function. The number of patient reported pain crises requiring healthcare utilization is an easily obtained outcome that could help to identify high risk patients for disease modifying therapies.

Trial Registration

ClinicalTrials.gov NCT00011648 http://clinicaltrials.gov/     

Lower Circulating B12 Is Associated with Higher Obesity and Insulin Resistance during Pregnancy in a Non-Diabetic White British Population

Objective

Vitamin B12 and folate are critical micronutrients needed to support the increased metabolic demands of pregnancy. Recent studies from India have suggested that low vitamin B12 and folate concentrations in pregnancy are associated with increased obesity; however differences in diet, antenatal vitamin supplementation, and socioeconomic status may limit the generalisability of these findings. We aimed to explore the cross-sectional relationship of circulating serum vitamin B12 and folate at 28 weeks’ gestation with maternal adiposity and related biochemical markers in a white non diabetic UK obstetric cohort.

Methods

Anthropometry and biochemistry data was available on 995 women recruited at 28 weeks gestation to the Exeter Family Study of Childhood Health. Associations between B12 and folate with maternal BMI and other obesity-related biochemical factors (HOMA-R, fasting glucose, triglycerides, HDL and AST) were explored using regression analysis, adjusting for potential confounders (socioeconomic status, vegetarian diet, vitamin supplementation, parity, haemodilution (haematocrit)).

Results

Higher 28 week BMI was associated with lower circulating vitamin B12 (r = -0.25; P<0.001) and folate (r = -0.15; P<0.001). In multiple regression analysis higher 28 week BMI remained an independent predictor of lower circulating B12 (β (95% CI) = -0.59 (-0.74, -0.44) i.e. for every 1% increase in BMI there was a 0.6% decrease in circulating B12). Other markers of adiposity/body fat metabolism (HOMA-R, triglycerides and AST) were also independently associated with circulating B12. In a similar multiple regression AST was the only independent obesity-related marker associated with serum folate (β (95% CI) = 0.16 (0.21, 0.51))

Conclusion

In conclusion, our study has replicated the previous Indian findings of associations between lower serum B12 and higher obesity and insulin resistance during pregnancy in a non-diabetic White British population. These findings may have important implications for fetal and maternal health in obese pregnancies.     

Serum Levels of 25-Hydroxyvitamin D and Functional Outcome among Postmenopausal Women with Hip Fracture

Objective

The main objective of the current study was to assess the distribution and its prognostic value of serum 25-hydroxyvitamin D (25[OH] D) levels assessed at admission in Chinese postmenopausal women with hip fracture.

Methods

From January 1, 2012 to December 31, 2013, all postmenopausal women with first-ever hip fracture were recruited to participate in the study. Serum 25[OH] D levels were measured at admission. The functional evaluation at the time of discharge was performed by the Barthel Index (BI). The prognostic value of 25[OH] D to predict the functional outcome within discharge was analyzed by logistic regression analysis, after adjusting for the possible confounders.

Results

In our study, 261 patients were included and assessed. In the 76 patients with an unfavorable functional outcome, serum 25(OH) D levels were lower compared with those in patients with a favorable outcome [11.8(IQR, 9.9–16.1)ng/ml; 16.8(IQR, 13.6–21.4)ng/ml, respectively; P<0.0001]. In multivariate analysis, there was an increased risk of unfavorable outcome associated with serum 25(OH) D levels ≤ 20ng/ml (OR 5.24, 95%CI: 3.11–8.15; P<0.0001) after adjusting for possible confounders.

Conclusions

Our data support an association between serum 25[OH] D levels and prognosis in Chinese postmenopausal women with hip fracture.     

Role of Breastfeeding and Complementary Food on Hemoglobin and Ferritin Levels in a Cambodian Cross-Sectional Sample of Children Aged 3 to 24 Months

Background

Iron deficiency derives from a low intake of dietary iron, poor absorption of iron, and high requirements due to growth as well as blood loss. An estimated number of about 50% of all anemia may be attributed to iron deficiency among young children in Cambodia.

Methods

A cross-sectional survey was conducted in rural Cambodia in September 2012. Villages in pre-selected communes were randomly chosen using stunting as a primary indicator of nutritional status. In total, 928 randomly selected households with children aged 3–23 months were included. Hemoglobin, ferritin, soluble transferrin receptor (sTfR), and retinol binding protein (RBP) were assessed from capillary blood samples. In addition, length/height and weight of mothers and children were taken and data on dietary diversity was collected. A child feeding index (CFI) was created. Associations between biomarkers of iron and vitamin A status and nutritional status or food intake were explored.

Results

Anemia prevalence was highest among 6- to 12-months-olds (71%). Ferritin and sTfR inversely correlated and were significantly associated with hemoglobin concentrations. The consumption of animal source foods (ASF) significantly impacts on the interaction between ferritin, sTfR and hemoglobin. Concentrations of RBP were significantly higher in children who had received a vitamin A supplement. The CFI was associated with sTfR and hemoglobin. Lower length and weight were associated with lower ferritin levels and showed an indirect effect on hemoglobin through ferritin.

Conclusion

Nutrition programs targeting children under 2 years of age need to focus on the preparation of complementary foods with high nutrient density to sustainably prevent micronutrient deficiency and generally improve nutritional status. Future assessments of the micronutrient status should include identification of hemoglobinopathies and parasitic infections to better understand all causes of anemia in Cambodian infants and young children.

Trial Registration

German Clinical Trials Register DRKS00004379