Plasma-glycated CD59 as an early biomarker for gestational diabetes mellitus: prospective cohort study protocol.

INTRODUCTION: The significant maternal and neonatal outcomes of gestational diabetes mellitus (GDM) make it a major public health concern. Mothers with GDM are at greater risk of pregnancy complications and their offspring are at higher risk of diabetes and obesity. Currently, GDM is diagnosed with glucose load methods which are time-consuming and inconvenient to administer more than once during pregnancy; for this reason, there is a recognised need for a more accurate and simpler test for GDM. Previous studies indicate that plasma-glycated CD59 (pGCD59) is a novel biomarker for GDM. We present here the protocol of a prospective cohort study designed to (1) determine the accuracy of pGCD59 as an early, first trimester predictor of GDM and gestational impaired glucose tolerance and (2) assess the associations between pGCD59 levels and adverse maternal and neonatal outcomes. METHODS AND ANALYSIS: We will obtain discarded plasma samples from pregnant women at two time points: first prenatal visit (usually <14 weeks gestation) and gestational weeks 24-28. A study-specific medical record abstraction tool will be used to obtain relevant maternal and neonatal clinical data from the EPIC clinical database. The prevalence of GDM will be determined using standard of care glucose load test results. We will determine the sensitivity and specificity of pGCD59 to predict the diagnosis of GDM and gestational impaired glucose tolerance, as well as the associations between levels of pGCD59 and the prevalence of maternal and neonatal outcomes. ETHICS AND DISSEMINATION: This study has been approved by the Mass General Brigham Institutional Review Board (protocol 2011P002254). The results of this study will be presented at international meetings and disseminated in peer-reviewed journals.

Investigating the inequalities in route to diagnosis amongst patients with diffuse large B-cell or follicular lymphoma in England.

INTRODUCTION: Diagnostic delay is associated with lower chances of cancer survival. Underlying comorbidities are known to affect the timely diagnosis of cancer. Diffuse large B-cell (DLBCL) and follicular lymphomas (FL) are primarily diagnosed amongst older patients, who are more likely to have comorbidities. Characteristics of clinical commissioning groups (CCG) are also known to impact diagnostic delay. We assess the association between comorbidities and diagnostic delay amongst patients with DLBCL or FL in England during 2005-2013. METHODS: Multivariable generalised linear mixed-effect models were used to assess the main association. Empirical Bayes estimates of the random effects were used to explore between-cluster variation. The latent normal joint modelling multiple imputation approach was used to account for partially observed variables. RESULTS: We included 30,078 and 15,551 patients diagnosed with DLBCL or FL, respectively. Amongst patients from the same CCG, having multimorbidity was strongly associated with the emergency route to diagnosis (DLBCL: odds ratio 1.56, CI 1.40-1.73; FL: odds ratio 1.80, CI 1.45-2.23). Amongst DLBCL patients, the diagnostic delay was possibly correlated with CCGs that had higher population densities. CONCLUSIONS: Underlying comorbidity is associated with diagnostic delay amongst patients with DLBCL or FL. Results suggest a possible correlation between CCGs with higher population densities and diagnostic delay of aggressive lymphomas.

Early pregnancy urinary biomarkers of fatty acid and carbohydrate metabolism in pregnancies complicated by gestational diabetes.

AIMS: Alterations in organic acid biomarkers from fatty acid and carbohydrate metabolism have been documented in type 2 diabetes patients. However, their association with gestational diabetes mellitus (GDM) is largely unknown. METHODS: Participants were 25 GDM cases and 25 non-GDM controls. Biomarkers of fatty acid (adipate, suberate and ethylmalonate) and carbohydrate (pyruvate, l-lactate and ß-hydroxybutyrate) metabolism were measured in maternal urine samples collected in early pregnancy (17 weeks) using liquid chromatography-mass spectrometry methods. Logistic regression were used to calculate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: GDM cases and controls differed in median urinary concentrations of ethylmalonate (3.0 vs. 2.3µg/mg creatinine), pyruvate (7.4 vs. 2.1µg/mg creatinine), and adipate (4.6 vs. 7.3µg/mg creatinine) (all p-values <0.05). Women in the highest tertile for ethylmalonate or pyruvate concentrations had 11.4-fold (95%CI 1.10-117.48) and 3.27-fold (95%CI 0.72-14.79) increased risk of GDM compared with women in the lowest tertile for ethylmalonate and pyruvate concentrations, respectively. Women in the highest tertile for adipate concentrations, compared with women in the lowest tertile, had an 86% reduction in GDM risk (95%CI 0.02-0.97). CONCLUSIONS: These preliminary findings underscore the importance of altered fatty acid and carbohydrate metabolism in the pathogenesis of GDM.

Differences in the reproductive pattern and low birthweight by maternal country of origin in Spain, 1996-2006.

BACKGROUND: Numerous studies have highlighted poorer reproductive and perinatal health outcomes among migrant mothers in developed countries. Due to the fact that no conclusive data is currently available at national level in Spain, this study aimed to explore potential differences by comparing the prevalence of low and multiple live births and the proportion of live births by maternal age and country of origin during 1996-2006. METHODS: A cross-sectional study was conducted using data from the National Statistics Institute. Low birthweight (LBW) was compared by mothers' country of origin using a logistic regression model. Odds ratios (ORs) and their respective 95% confidence intervals (CIs) are stratified by multiplicity and maternal age. RESULTS: LBW was associated with a combination of older maternal age and multiple pregnancies in the case of women who had been born in Europe (EU15). However, this association was not found in women who originated from outside the EU15, mostly from countries who have shown significant emigration to Spain during the last decade. LBW was present among all age groups, in both singleton and multiple births, and in particular Romanian mothers showed the highest OR 2.34 (95% CI 1.20-4.80). CONCLUSION: This study confirms differences in the reproductive pattern and LBW depending on maternal country of origin. These results allow a better understanding of the reproductive pattern and the implications of mothers' country of origin in LBW. Thus, helping health decisions makers to plan future health interventions aimed at reducing the LBW prevalence in Spain.

[Incidence and risk factors for acute gastroenteritis among pilgrims following the French way to Santiago de Compostela (Spain) in 2008]. / Incidencia y factores de riesgo de gastroenteritis en los peregrinos del Camino de Santiago durante el verano de 2008 en el camino francés.

OBJECTIVES: To determine the incidence of acute gastroenteritis in pilgrims on St. James' Way, as well as associated risk factors and microbiological characteristics. METHODS: Two studies were designed simultaneously: a cross-sectional study through self-completed questionnaires among pilgrims reaching Santiago, and a case-control study of pilgrims traveling along the Way. Multivariate analysis was performed using logistic regression. RESULTS: In the cross-sectional study, the incidence rate was 23.5 episodes of acute gastroenteritis/10³ pilgrims-day (95% CI: 18.9-2.4/10³. In the case-control study, the major risk factors were age <20 years (OR=4.72; 95% CI: 2.16-10.28), traveling in groups (three or more) (OR=1.49; 95% CI: 0.98-2.28), and drinking unbottled water (OR=2.09; 95% CI: 0.91-4.82). The most frequent etiologic agent was norovirus (56%). CONCLUSIONS: Age less than 20 years, traveling in groups and drinking unbottled water were important risk factors for acute gastroenteritis.

Accuracy of MUAC in the detection of severe wasting with the new WHO growth standards.

OBJECTIVES: The objectives of this study were to estimate the accuracy of using mid-upper-arm circumference (MUAC) measurements to diagnose severe wasting by comparing the new standards from the World Health Organization (WHO) with those from the US National Center for Health Statistics (NCHS) and to analyze the age independence of the MUAC cutoff values for both curves. METHODS: We used cross-sectional anthropometric data for 34,937 children between the ages of 6 and 59 months, from 39 nutritional surveys conducted by Doctors Without Borders. Receiver operating characteristic curves were used to examine the accuracy of MUAC diagnoses. MUAC age independence was analyzed with logistic regression models. RESULTS: With the new WHO curve, the performance of MUAC measurements, in terms of sensitivity and specificity, deteriorated. With different cutoff values, however, the WHO standards significantly improved the predictive value of MUAC measurements over the NCHS standards. The sensitivity and specificity of MUAC measurements were the most age independent when the WHO curve, rather than the NCHS curve, was used. CONCLUSIONS: This study confirms the need to change the MUAC cutoff value from <110 mm to <115 mm. This increase of 5 mm produces a large change in sensitivity (from 16% to 25%) with little loss in specificity, improves the probability of diagnosing severe wasting, and reduces false-negative results by 12%. This change is needed to maintain the same diagnostic accuracy as the old curve and to identify the children at greatest risk of death resulting from severe wasting.