Health-related quality of life of children with attention-deficit/hyperactivity disorder versus children with diabetes and healthy controls

The impact of attention-deficit/hyperactivity disorder (ADHD) on health-related quality of life (HRQoL) is reported to be similar to that of other mental health and physical disorders. In this cross-sectional study, we hypothesized that children with ADHD and children with type 1 diabetes mellitus (T1DM) would have significantly worse HRQoL compared with healthy children, and that better clinical status in ADHD and T1DM would be associated with better HRQoL. Children were recruited from three outpatient services in Scotland. Responses to two frequently used validated HRQoL instruments, the Paediatric Quality of Life Inventory (PedsQL) and Child Health and Illness Profile-child edition (CHIP-CE), were obtained from parents/carers and children (6–16 years) with/without ADHD or T1DM. Child and parent/carer-completed HRQoL measurements were evaluated for 213 children with ADHD, 58 children with T1DM and 117 healthy children (control group). Significantly lower self and parent/carer ratings were observed across most PedsQL (P < 0.001) and CHIP-CE (P < 0.05) domains (indicating reduced HRQoL) for the ADHD group compared with the T1DM and control groups. Parent/carer and child ratings were significantly correlated for both measures of HRQoL (PedsQL total score: P < 0.001; CHIP-CE all domains: P < 0.001), but only with low-to-moderate strength. Correlation between ADHD severity and HRQoL was significant with both PedsQL and CHIP-CE for all parent/carer (P < 0.01) and most child (P < 0.05) ratings; more ADHD symptoms were associated with poorer HRQoL. These data demonstrate that ADHD has a significant impact on HRQoL (as observed in both parent/carer and child ratings), which seems to be greater than that for children with T1DM

Network meta-analysis on the log-hazard scale, combining count and hazard ratio statistics accounting for multi-arm trials: a tutorial.

BACKGROUND: Data on survival endpoints are usually summarised using either hazard ratio, cumulative number of events, or median survival statistics. Network meta-analysis, an extension of traditional pairwise meta-analysis, is typically based on a single statistic. In this case, studies which do not report the chosen statistic are excluded from the analysis which may introduce bias. METHODS: In this paper we present a tutorial illustrating how network meta-analyses of survival endpoints can combine count and hazard ratio statistics in a single analysis on the hazard ratio scale. We also describe methods for accounting for the correlations in relative treatment effects (such as hazard ratios) that arise in trials with more than two arms. Combination of count and hazard ratio data in a single analysis is achieved by estimating the cumulative hazard for each trial arm reporting count data. Correlation in relative treatment effects in multi-arm trials is preserved by converting the relative treatment effect estimates (the hazard ratios) to arm-specific outcomes (hazards). RESULTS: A worked example of an analysis of mortality data in chronic obstructive pulmonary disease (COPD) is used to illustrate the methods. The data set and WinBUGS code for fixed and random effects models are provided. CONCLUSIONS: By incorporating all data presentations in a single analysis, we avoid the potential selection bias associated with conducting an analysis for a single statistic and the potential difficulties of interpretation, misleading results and loss of available treatment comparisons associated with conducting separate analyses for different summary statistics

Psychometric properties of the quality of life scale Child Health and Illness Profile-Child Edition in a combined analysis of five atomoxetine trials

Our aim was to evaluate the psychometric properties of the generic quality of life (QoL) scale Child Health and Illness Profile-Child Edition (CHIP-CE) by means of a combined analysis of atomoxetine clinical trials in children and adolescents with attention-deficit/hyperactivity disorder (ADHD). Individual patient-level data from five clinical trials were included in the combined analysis. Psychometric properties of the CHIP-CE were explored in terms of internal consistency and structure. Patients (n = 794) aged between 6 and 15 years (mean 9.7) with mean baseline ADHD Rating Scale of 41.8 ± 8.04 were included. On average, 0.7 (SD 2.23) items were missing for the whole CHIP-CE. The internal consistency of the CHIP-CE assessed by Cronbach’s alpha was good for all sub-domains at baseline and at endpoint. Considerable ceiling effects were only observed for the “restricted activity” sub-domain. No considerable floor effects were seen. The factor analysis supported the 12-factor solution for the sub-domains, but not the 5-factor solution for the domains. Our analyses were based on a large sample of non-US patients which allowed the measurement of clear changes in QoL over time. The results support that the CHIP-CE scale is psychometrically robust over time in terms of internal consistency and structure

Cumulative subgroup analysis to reduce waste in clinical research for individualised medicine

Background: Although subgroup analyses in clinical trials may provide evidence for individualised medicine, their conduct and interpretation remain controversial. Methods: Subgroup effect can be defined as the difference in treatment effect across patient subgroups. Cumulative subgroup analysis refers to a series of repeated pooling of subgroup effects after adding data from each of related trials chronologically, to investigate the accumulating evidence for subgroup effects. We illustrated the clinical relevance of cumulative subgroup analysis in two case studies using data from published individual patient data (IPD) meta-analyses. Computer simulations were also conducted to examine the statistical properties of cumulative subgroup analysis. Results: In case study 1, an IPD meta-analysis of 10 randomised trials (RCTs) on beta blockers for heart failure reported significant interaction of treatment effects with baseline rhythm. Cumulative subgroup analysis could have detected the subgroup effect 15 years earlier, with five fewer trials and 71% less patients, than the IPD meta-analysis which first reported it. Case study 2 involved an IPD meta-analysis of 11 RCTs on treatments for pulmonary arterial hypertension that reported significant subgroup effect by aetiology. Cumulative subgroup analysis could have detected the subgroup effect 6 years earlier, with three fewer trials and 40% less patients than the IPD meta-analysis. Computer simulations have indicated that cumulative subgroup analysis increases the statistical power and is not associated with inflated false positives. Conclusions: To reduce waste of research data, subgroup analyses in clinical trials should be more widely conducted and adequately reported so that cumulative subgroup analyses could be timely performed to inform clinical practice and further research

Atomoxetine improves patient and family coping in attention deficit/hyperactivity disorder: a randomized, double-blind, placebo-controlled study in Swedish children and adolescents

This 10-week study assessed the efficacy of atomoxetine in combination with psychoeducation compared to placebo and psychoeducation in the improvement of Quality of Life in Swedish stimulant-naive children and adolescents with attention deficit/hyperactivity disorder. A total of 99 patients were treated with atomoxetine (49 patients) or placebo (50 patients) for 10 weeks and assessed regarding broader areas of functioning using the Quality of Life measures Child Health and Illness Profile-Child Edition (CHIP-CE), Family Strain Index [FSI; equivalent to the Family Burden of Illness Module used in the study], Appraisal of Stress in Child-Rearing (ASCR), Five to fifteen (FTF), “I think I am” (“Jag tycker jag är”), and Children’s Depression Rating Scale-Revised (CDRS-R) before and after the active treatment phase. Simultaneously, the patients’ parents participated in a 4-session psychoeducation program. A statistically significant difference in favor of atomoxetine was seen in the improvement from baseline to study endpoint for the CHIP-CE domains “Achievement” and “Risk avoidance”, for the FSI total score, for the ASCR section (I) domain “Child as a burden”, for all FTF domains except for “Language and Speech”, and for the CDRS-R total score. No difference between treatment groups was observed in the patient-assessed evaluation of self-esteem using the “I think I am” scale. Atomoxetine combined with psychoeducation had a positive effect on various everyday coping abilities of the patients as well as their families during 10 weeks of treatment, whereas the patients’ self-image and the parents’ image of the climate in the family were not significantly improved

Nutritional and Metabolic Requirements for the Infection of HeLa Cells by Salmonella enterica Serovar Typhimurium

Salmonella is the causative agent of a spectrum of human and animal diseases ranging from gastroenteritis to typhoid fever. It is a food - and water - borne pathogen and infects via ingestion followed by invasion of intestinal epithelial cells and phagocytic cells. In this study we employed a mutational approach to define the nutrients and metabolic pathways required by Salmonella enterica serovar Typhimurium during infection of a human epithelial cell line (HeLa). We deleted the key glycolytic genes, pfkA and pfkB to show that S. Typhimurium utilizes glycolysis for replication within HeLa cells; however, glycolysis was not absolutely essential for intracellular replication. Using S. Typhimurium strains deleted for genes encoding components of the phosphotransferase system and glucose transport, we show that glucose is a major substrate required for the intracellular replication of S. Typhimurium in HeLa cells. We also deleted genes encoding enzymes involved in the utilization of gluconeogenic substrates and the glyoxylate shunt and show that neither of these pathways were required for intracellular replication of S. Typhimurium within HeLa cells

Effects of Pre-Natal Vitamin D Supplementation with Partial Correction of Vitamin D Deficiency on Early Life Healthcare Utilisation: A Randomised Controlled Trial

Funded by Asthma UK grant number 09/ 36

Differences between children and adolescents in treatment response to atomoxetine and the correlation between health-related quality of life and Attention Deficit/Hyperactivity Disorder core symptoms: Meta-analysis of five atomoxetine trials

<p>Abstract</p> <p>Objectives</p> <p>To explore the influence of age on treatment responses to atomoxetine and to assess the relationship between core symptoms of attention deficit/hyperactivity disorder (ADHD) and health-related quality of life (HR-QoL) outcomes.</p> <p>Data Sources</p> <p>Data from five similar clinical trials of atomoxetine in the treatment of children and adolescents with ADHD were included in this meta-analysis.</p> <p>Study Selection</p> <p>Atomoxetine studies that used the ADHD Rating Scale (ADHD-RS) and the Child Health and Illness Profile Child Edition (CHIP-CE) as outcome measures were selected.</p> <p>Interventions</p> <p>Treatment with atomoxetine.</p> <p>Main Outcome Measures</p> <p>Treatment group differences (atomoxetine vs placebo) in terms of total score, domains, and subdomains of the CHIP-CE were compared across age groups, and correlations between ADHD-RS scores and CHIP-CE scores were calculated by age.</p> <p>Results</p> <p>Data of 794 subjects (611 children, 183 adolescents) were pooled. At baseline, adolescents showed significantly (p < 0.05) greater impairment compared with children in the Family Involvement, Satisfaction with Self, and Academic Performance subdomains of the CHIP-CE. Treatment effect of atomoxetine was significant in both age groups for the Risk Avoidance domain and its subdomains. There was a significant age-treatment interaction with greater efficacy seen in adolescents in both the Risk Avoidance domain and the Threats to Achievement subdomain. Correlations between ADHD-RS and CHIP-CE scores were generally low at baseline and moderate in change from baseline and were overall similar in adolescents and children.</p> <p>Conclusions</p> <p>Atomoxetine was effective in improving some aspects of HR-QoL in both age groups. Correlations between core symptoms of ADHD and HR-QoL were low to moderate.</p