Factors Contributing to Vitamin D Status at Hospital Admission for Pulmonary Exacerbation in Adults With Cystic Fibrosis

BackgroundIndividuals with cystic fibrosis (CF) have difficulty maintaining optimal vitamin D status due to pancreatic insufficiency-induced malabsorption, inadequate sunlight exposure, and poor intake of vitamin D containing foods. Vitamin D deficiency may increase the risk of pulmonary exacerbations of CF. The objective of this study was to assess factors impacting vitamin D status in patients with CF recently hospitalized for a pulmonary exacerbation of CF.MethodsThis was a pre-planned analysis of vitamin D intake in patients enrolled in a multi-center, double-blind, randomized controlled study examining vitamin D therapy for pulmonary exacerbation of CF. Demographic information, responses from a habitual sun exposure questionnaire and food frequency questionnaire, and vitamin D supplement usage were queried and compared to serum 25-hydroxyvitamin D (25(OH)D) concentrations.ResultsA total of 48 subjects were included in this analysis. Subjects were taking approximately 1,200 IU of vitamin D daily. Reported vitamin D intake, age, race, employment, and education were not significantly associated with vitamin D status in this population. However, smoking status, sunlight exposure in the last 3 years, and skin type (in the bivariate model) were all significantly associated with vitamin D status (all p<0.05).ConclusionsSunlight exposure was the most predictive determinant of vitamin D status in patients with CF prior to pulmonary exacerbation. Subjects reported vitamin D intake below the recommended amounts. The role and mode of optimizing vitamin D status prior to a pulmonary exacerbation needs further investigation.     

Failure of daptomycin β-Lactam combination therapy to prevent resistance emergence in Enterococcus faecium

Daptomycin β-Lactam combination therapy offers “protection” against daptomycin non-susceptibility (DNS) development in Enterococcus faecium. We report failure of this strategy and the importance of source control. Mutations were detected in the LiaF and cls genes in DNS isolates. A single DNS isolate contained an unrecognized mutation, which requires confirmation.     

The social determinants of child health

Social determinants of health have long been recognised but their importance is often overlooked. Globally social determinants are responsible for most childhood illness and death. In the UK, conditions which constitute a large part of paediatric practice are socially patterned. Social determinants exert their influence on child health through a complex inter-relationship of more distal social factors such as income and education with more proximal factors such as health behaviours.The pathways by which the social determinants exert their influence operate over time and across generations. Socially related risk and protective factors cluster in different social groups and accumulate over time. Social determinants are profoundly influenced by social and political decisions which are beyond the control of parents and individual paediatricians. Societies can protect children against the adverse effects of social disadvantage. National paediatric societies have a key role in promoting policies which protect children. This brief review summarises the impact of social determinants on children's health in the UK and considers the role of paediatricians in reducing the health inequities generated by these determinants.     

Is the UK NICE “Reference Case” Influencing the Practice of Pediatric Quality-Adjusted Life-Year Measurement within Economic Evaluations?

ObjectivesTo report findings from a systematic review, this article sought to address two related questions. First, how has the practice of UK pediatric cost-utility analyses evolved over time, in particular how are health-related outcomes assessed and valued? Second, how do the methods compare to the limited guidance available, in particular, the National Institute for Health and Care Excellence (NICE) reference case(s)?MethodsElectronic searches of MEDLINE, Embase, and Cochrane databases were conducted for the period May 2004 to April 2012 and the Paediatric Economic Database Evaluation database for the period May 2004 to December 2010. Identified studies were screened by three independent reviewers.ResultsForty-three studies were identified, 11 of which elicit utility values through primary research. A discrepancy was identified between the methods used for outcome measurement and valuation and the methods advocated within the NICE reference case. Despite NICE recommending the use of preference-based instruments designed specifically for children, most studies that were identified had used adult measures. In fact, the measurement of quality-adjusted life-years is the aspect of economic evaluation with the greatest amount of variability and the area that most digressed from the NICE reference case.ConclusionsRecommendations stemming from the review are that all studies should specify the age range of childhood and include separate statements of perspective for costs and effects as well as the reallocation of research funding away from systematic review studies toward good quality primary research measuring utilities in children.     

Low-grade inflammation and insulin resistance independently explain substantial parts of the association between body fat and serum C3: The CODAM study

ObjectiveTo investigate the role of low-grade inflammation and insulin resistance (HOMA2-IR) in adiposity-related increases in serum complement factor 3 (C3). Although C3 has been linked to type 2 diabetes and cardiovascular diseases, and C3 levels are closely related to body fat, the underlying mechanisms explaining this association are still unknown.MethodsAdiposity measures (including BMI, waist circumference (WC), sagittal diameter and several skinfolds), HOMA2-IR and markers of inflammation (hs-CRP, IL-6, SAA, haptoglobin, ceruloplasmin, sICAM-1) were determined in 532 individuals (62% men, mean age 59 ± 6.9 yrs) from the Cohort on Diabetes and Atherosclerosis Maastricht study. Markers of inflammation were standardized and compiled into an averaged inflammation score. Cross-sectional associations between adiposity measures and C3 and the mediating role of low-grade inflammation and/or HOMA2-IR herein were analysed with multiple linear regression models.ResultsAdiposity measurements were significantly associated with C3 levels, with the strongest (adjusted) associations found for WC (β = 0.383; 95%CI 0.302–0.464) and sagittal diameter (β = 0.412; 95%CI 0.333-0.490). Further adjustment for inflammation and HOMA2-IR attenuated these associations to β = 0.115 (95%CI 0.030-0.200) and β = 0.163 (95%CI 0.082-0.244) respectively. Multiple mediation analyses showed that inflammation [β = 0.090 (95%CI 0.060–0.126)] and HOMA2-IR [β = 0.179 (95%CI 0.128–0.236)] each explained, independently of one another, a significant portion of the association between WC and C3 (23% and 47%, respectively). Similar mediation by inflammation (19-27%) and HOMA2-IR (37-56%) was found for other adiposity measures.ConclusionSystemic low-grade inflammation and insulin resistance may represent two independent pathways by which body fat leads to elevated C3 levels.