Influence of Socioeconomic Status Trajectories on Innate Immune Responsiveness in Children

Lower socioeconomic status (SES) is consistently associated with poor health, yet little is known about the biological mechanisms underlying this inequality. In children, we examined the impact of early-life SES trajectories on the intensity of global innate immune activation, recognizing that excessive activation can be a precursor to inflammation and chronic disease.Stimulated interleukin-6 production, a measure of immune responsiveness, was analyzed ex vivo for 267 Canadian schoolchildren from a 1995 birth cohort in Manitoba, Canada. Childhood SES trajectories were determined from parent-reported housing data using a longitudinal latent-class modeling technique. Multivariate regression was conducted with adjustment for potential confounders.SES was inversely associated with innate immune responsiveness (p=0.003), with persistently low-SES children exhibiting responses more than twice as intense as their high-SES counterparts. Despite initially lower SES, responses from children experiencing increasing SES trajectories throughout childhood were indistinguishable from high-SES children. Low-SES effects were strongest among overweight children (p<0.01). Independent of SES trajectories, immune responsiveness was increased in First Nations children (p<0.05) and urban children with atopic asthma (p<0.01).These results implicate differential immune activation in the association between SES and clinical outcomes, and broadly imply that SES interventions during childhood could limit or reverse the damaging biological effects of exposure to poverty during the preschool years

Overstating the evidence - double counting in meta-analysis and related problems

Background: The problem of missing studies in meta-analysis has received much attention. Less attention has been paid to the more serious problem of double counting of evidence. Methods: Various problems in overstating the precision of results from meta-analyses are described and illustrated with examples, including papers from leading medical journals. These problems include, but are not limited to, simple double-counting of the same studies, double counting of some aspects of the studies, inappropriate imputation of results, and assigning spurious precision to individual studies. Results: Some suggestions are made as to how the quality and reliability of meta-analysis can be improved. It is proposed that the key to quality in meta-analysis lies in the results being transparent and checkable. Conclusions: Existing quality check lists for meta-analysis do little to encourage an appropriate attitude to combining evidence and to statistical analysis. Journals and other relevant organisations should encourage authors to make data available and make methods explicit. They should also act promptly to withdraw meta-analyses when mistakes are found

TLR4 Asp299Gly and Thr399Ile Polymorphisms: No Impact on Human Immune Responsiveness to LPS or Respiratory Syncytial Virus

A broad variety of natural environmental stimuli, genotypic influences and timing all contribute to expression of protective versus maladaptive immune responses and the resulting clinical outcomes in humans. The role of commonly co-segregating Toll-like receptor 4 (TLR4) non-synonymous single nucleotide polymorphisms Asp299Gly and Thr399Ile in this process remains highly controversial. Moreover, what differential impact these polymorphisms might have in at risk populations with respiratory dysfunction, such as current asthma or a history of infantile bronchiolitis, has never been examined. Here we determine the importance of these polymorphisms in modulating LPS and respiratory syncytial virus (RSV)--driven cytokine responses. We focus on both healthy children and those with clinically relevant respiratory dysfunction.To elucidate the impact of TLR4 Asp299Gly and Thr399Ile on cytokine production, we assessed multiple immune parameters in over 200 pediatric subjects aged 7-9. Genotyping was followed by quantification of pro- and anti-inflammatory cytokine responses by fresh peripheral blood mononuclear cells upon acute exposure to LPS or RSV.In contrast to early reports, neither SNP influenced immune responses evoked by LPS exposure or RSV infection, as measured by the intermediate phenotype of pro- and anti-inflammatory cytokine responses to these ubiquitous agents. There is no evidence of altered sensitivity in populations with "at risk" clinical phenotypes.Genomic medicine seeks to inform clinical practice. Determination of the TLR4 Asp299Gly/Thr399Ile haplotype is of no clinical benefit in predicting the nature or intensity of cytokine production in children whether currently healthy or among specific at-risk groups characterized by prior infantile broncholitis or current asthma

Health service utilization in IBD: comparison of self-report and administrative data

<p>Abstract</p> <p>Background</p> <p>The reliability of self-report regarding health care utilization in inflammatory bowel disease (IBD) is unknown. If proven reliable, it could help justify self-report as a means of determining health care utilization and associated costs.</p> <p>Methods</p> <p>The Manitoba IBD Cohort Study is a population-based longitudinal study of participants diagnosed within 7 years of enrollment. Health care utilization was assessed through standardized interview. Participants (n = 352) reported the total number of nights hospitalized, frequency of physician contacts in the prior 12 months and whether the medical contacts were for IBD-related reasons or not. Reports of recent antibiotic use were also recorded. Actual utilization was drawn from the administrative database of Manitoba Health, the single comprehensive provincial health insurer.</p> <p>Results</p> <p>According to the administrative data, 15% of respondents had an overnight hospitalization, while 10% had an IBD-related hospitalization. Self-report concordance was highly sensitive (92%; 82%) and specific (96%; 97%, respectively). 97% of participants had contact with a physician in the previous year, and 69% had IBD-related visits. Physician visits were significantly under-reported and there was a trend to over-report the number of nights in hospital.</p> <p>Conclusions</p> <p>Self-report data can be helpful in evaluating health service utilization, provided that the researcher is aware of the systematic sources of bias. Outpatient visits are well identified by self-report. The discordance for the type of outpatient visit may be either a weakness of self-report or a flaw in diagnosis coding of the administrative data. If administrative data are not available, self-report information may be a cost-effective alternative, particularly for hospitalizations.</p

Why do paediatricians prescribe antibiotics? Results of an Italian regional project

<p>Abstract</p> <p>Background</p> <p>To investigate determinants of antibiotic prescription in paediatric care, as a first step of a multilevel intervention to improve prescribing for common respiratory tract infections (RTIs) in a northern Italian region with high antibiotic prescription rate.</p> <p>Methods</p> <p>A two-step survey was performed: in phase I, knowledge, and attitudes were explored involving all family and hospital paediatricians of Emilia-Romagna and a sample of parents. In phase II, patient care practices were explored in a stratified random sample of visits, both in hospitals and family physician's clinics; parent expectations were investigated in a sub-sample of these visits.</p> <p>Results</p> <p>Out of overall 4352 visits for suspected RTIs, in 38% of children an antibiotic was prescribed. Diagnostic uncertainty was perceived by paediatricians as the most frequent cause of inappropriate prescription (56% of 633 interviewed paediatricians); but, rapid antigen detecting tests was used in case of pharyngitis/pharyngotonsillitis by 36% and 21% of family and hospital paediatricians only. More than 50% of paediatricians affirmed to not adopt a "wait and see strategy" in acute otitis. The perceived parental expectation of antibiotics was not indicated by paediatricians as a crucial determinant of prescription, but this perception was the second factor most strongly associated to prescription (OR = 12.8; 95% CI 10.4 - 15.8), the first being the presence of othorrea. Regarding parents, the most important identified factors, potentially associated to overprescribing, were the lack of knowledge of RTIs and antibiotics (41% of 1029 parents indicated bacteria as a possible cause of common cold), and the propensity to seek medical care for trivial infections (48% of 4352 children accessing ambulatory practice presented only symptoms of common cold).</p> <p>Conclusion</p> <p>A wide gap between perceived and real determinants of antibiotic prescription exists. This can promote antibiotic overuse. Inadequate parental knowledge can also induce inappropriate prescription. The value of this study is that it simultaneously explored determinants of antimicrobial prescribing in an entire region involving both professionals and parents.</p

Poverty, dirt, infections and non-atopic wheezing in children from a Brazilian urban center

BACKGROUND: The causation of asthma is poorly understood. Risk factors for atopic and non-atopic asthma may be different. This study aimed to analyze the associations between markers of poverty, dirt and infections and wheezing in atopic and non-atopic children. METHODS: 1445 children were recruited from a population-based cohort in Salvador, Brazil. Wheezing was assessed using the ISAAC questionnaire and atopy defined as allergen-specific IgE ≥ 0.70 kU/L. Relevant social factors, environmental exposures and serological markers for childhood infections were investigated as risk factors using multivariate multinomial logistic regression. RESULTS: Common risk factors for wheezing in atopic and non-atopic children, respectively, were parental asthma and respiratory infection in early childhood. No other factor was associated with wheezing in atopic children. Factors associated with wheezing in non-atopics were low maternal educational level (OR 1.49, 95% CI 0.98-2.38), low frequency of room cleaning (OR 2.49, 95% CI 1.27-4.90), presence of rodents in the house (OR 1.48, 95% CI 1.06-2.09), and day care attendance (OR 1.52, 95% CI 1.01-2.29). CONCLUSIONS: Non-atopic wheezing was associated with risk factors indicative of poverty, dirt and infections. Further research is required to more precisely define the mediating exposures and the mechanisms by which they may cause non-atopic wheeze

The impact of generic-only drug benefits on patients' use of inhaled corticosteroids in a Medicare population with asthma

<p>Abstract</p> <p>Background</p> <p>Patients face increasing insurance restrictions on prescription drugs, including generic-only coverage. There are no generic inhaled corticosteroids (ICS), which are a mainstay of asthma therapy, and patients pay the full price for these drugs under generic-only policies. We examined changes in ICS use following the introduction of generic-only coverage in a Medicare Advantage population from 2003–2004.</p> <p>Methods</p> <p>Subjects were age 65+, with asthma, prior ICS use, and no chronic obstructive pulmonary disorder (n = 1,802). In 2004, 74.0% switched from having a $30 brand-copayment plan to a generic-only coverage plan (restricted coverage); 26$15–25 brand copayments in 2003–2004 (unrestricted coverage). Using linear difference-in-difference models, we examined annual changes in ICS use (measured by days-of-supply dispensed). There was a lower-cost ICS available within the study setting and we also examined changes in drug choice (higher- vs. lower-cost ICS). In multivariable models we adjusted for socio-demographic, clinical, and asthma characteristics.</p> <p>Results</p> <p>In 2003 subjects had an average of 188 days of ICS supply. Restricted compared with unrestricted coverage was associated with reductions in ICS use from 2003–2004 (-15.5 days-of-supply, 95% confidence interval (CI): -25.0 to -6.0). Among patients using higher-cost ICS drugs in 2003 (n = 662), more restricted versus unrestricted coverage subjects switched to the lower-cost ICS in 2004 (39.8% vs. 10.3%). Restricted coverage was not associated with decreased ICS use (2003–2004) among patients who switched to the lower-cost ICS (18.7 days-of-supply, CI: -27.5 to 65.0), but was among patients who did not switch (-38.6 days-of-supply, CI: -57.0 to -20.3). In addition, restricted coverage was associated with decreases in ICS use among patients with both higher- and lower-risk asthma (-15.0 days-of-supply, CI: -41.4 to 11.44; and -15.6 days-of-supply, CI: -25.8 to -5.3, respectively).</p> <p>Conclusion</p> <p>In this elderly population, patients reduced their already low ICS use in response to losing drug coverage. Switching to the lower-cost ICS mitigated reductions in use among patients who previously used higher-cost drugs. Additional work is needed to assess barriers to switching ICS drugs and the clinical effects of these drug use changes.</p