Confidence Interval Estimation for Continuous Outcomes in Cluster Randomization Trials

Cluster randomization trials are experiments where intact social units (e.g. hospitals, schools, communities, and families) are randomized to the arms of the trial rather than individuals. The popularity of this design among health researchers is partially due to reduced contamination of treatment effects and convenience. However, the advantages of cluster randomization trials come with a price. Due to the dependence of individuals within a cluster, cluster randomization trials suffer reduced statistical efficiency and often require a complex analysis of study outcomes. The primary purpose of this thesis is to propose new confidence intervals for effect measures commonly of interest for continuous outcomes arising from cluster randomization trials. Specifically, we construct new confidence intervals for the difference between two normal means, the difference between two lognormal means, and the exceedance probability. The proposed confidence intervals, which use the method of variance estimates recovery (MOVER), do not make certain assumptions that existing procedures make on the data. For instance, symmetry is not forced when the sampling distribution of the parameter estimate is skewed and the assumption of homoscedasticity is not made. Furthermore, the MOVER results in simple confidence interval procedures rather than complex simulation-based methods which currently exist. Simulation studies are used to investigate the small sample properties of the MOVER as compared with existing procedures. Unbalanced cluster sizes are simulated, with an average range of 50 to 200 individuals per cluster and 6 to 24 clusters per arm. The effects of various degrees of dependence between individuals within the same cluster are also investigated. When comparing the empirical coverage, tail errors, and median widths of confidence interval procedures, the MOVER has coverage close to the nominal, relatively balanced tail errors, and narrow widths as compared to existing procedure for the majority of the parameter combinations investigated. Existing data from cluster randomization trials are then used to illustrate each of the methods

Effect of conjugated linoleic acid and vitamin E on glycemic control, body composition, and inflammatory markers in overweight type2 diabetics

BACKGROUND: The healthy properties of conjugated linoleic acid (CLA) such as weight loss, reducing cardiovascular risk factors and inflammation have been reported. The trans-10, cis-12 CLA isomer is related to increasing insulin resistance, but the effects of cis-9, trans-11 isomer is not clear. The aim of this study was to investigate the effects of CLA with and without Vitamin E on body weight, body composition, glycemic index, inflammatory and coagulation factors, lipid profile, serum leptin and adiponectin, malondialdehyde (MDA), and blood pressure in type2 diabetes. METHODS: 56 patients with type2 diabetes were included in 8 week double-blind control trial that used metformin. They randomly divided into three groups: CLA + VitE, CLA + VitE placebo, CLA placebo + VitE placebo. All variables, anthropometric measurements, and body composition were evaluated at the beginning and the end of study. Statistical analysis and analysis of dietary data were performed using SPSS and nutritionist IV software, respectively. RESULTS: There were not any significant differences in variable changes among three groups. However, there was a trend to increase in MDA and decrease in apoB100 among CLA consumers. CONCLUSION: The results of this study showed that administration of CLA supplementation for 8 weeks does not affect any indicators of metabolic control in overweight type2 diabetic patients

Inadequate reporting of research ethics review and informed consent in cluster randomized trials : review of random sample of published trials

Peer reviewedPublisher PD

Impact of CONSORT extension for cluster randomised trials on quality of reporting and study methodology : review of random sample of 300 trials, 2000-8

Peer reviewedPublisher PD

Mis-sizing of Adenomatous Polyps is Common among Endoscopists and Impacts Colorectal Cancer Screening Recommendations

Background/Aims To determine the accuracy of identifying ≥6-mm adenomatous polyps during colonoscopy and define its impact on subsequent interval screening. Methods We conducted a retrospective study of patients who underwent colonoscopies at Banner University Medical Center, Tucson from 2011 to 2015. All patients with ≥6-mm adenomatous polyps based on their colonoscopy report were included. Adenomatous polyps were excluded if they did not meet the criteria. Discrepancies in the polyp size were determined by calculating the percentage of size variation (SV). Clinical mis-sizing was defined as SV >33%. Results The polyps analyzed were predominantly <10 mm in size. Approximately 13% of the examined polyps met the inclusion criteria, and 40.7% of the adenomas were ≥10 mm. A total of 189 ≥6-mm adenomatous polyps were collected from 10 different gastroenterologists and a colorectal surgeon. Adenomatous polyps were clinically mis-sized in 56.6% of cases and overestimated in 71.4%. Among the adenomas reviewed, 22% of mis-sized polyps and 11% of non-mis-sized polyps resulted in an inappropriate surveillance interval. Conclusions We found that more than half of ≥6-mm adenomatous polyps are mis-sized and that there is a tendency to overestimate adenoma size among endoscopists. This frequently leads to inappropriate intervals of surveillance colonoscopy

Placental infl ammation is not increased in infl ammatory bowel disease

Abstract Background Women with infl ammatory bowel disease (IBD) are at increased risk for adverse birth outcomes such as preterm delivery and small for gestational age (SGA) infants. Most recognized cases of fetal growth restriction in singleton pregnancies have underlying placental causes. However, studies in IBD examining poor birth outcomes have focused on maternal factors. We examined whether women with IBD have a higher rate of placental infl ammation than non-IBD controls

Clinical Activity and Quality of Life Indices Are Valid Across Ulcerative Colitis But Not Crohn’s Disease Phenotypes

Background Clinical activity and quality of life (QOL) indices assess disease activity in Crohn’s disease (CD) and ulcerative colitis (UC). However, a paucity of data exists on the validity of these indices according to disease characteristics. Aims To examine the correlation between QOL and clinical activity indices and endoscopic disease activity according to disease characteristics. Methods We used a prospective registry to identify CD and UC patients ≥18 years old with available information on Short Inflammatory Bowel Disease Questionnaire scores (SIBDQ), Harvey–Bradshaw Index (HBI) and simple endoscopic scores for CD (SES-CD), and Simple Clinical Colitis Activity Index (SCCAI) and Mayo endoscopic score for UC. We used Spearman rank correlations to calculate correlations between indices and Fisher transformation to compare correlations across disease characteristics. Results Among 282 CD patients, we observed poor correlation between clinical activity and QOL indices to SES-CD with no differences in correlation according to disease characteristics. Conversely, among 226 UC patients, clinical activity and QOL had good correlation to Mayo endoscopic score (r = 0.55 and −0.56, respectively) with better correlations observed with left-sided versus extensive colitis (r = 0.73 vs. 0.45, p = 0.005) and shorter duration of disease (r = 0.61 vs. 0.37, p = 0.04). Conclusions Our data suggest good correlation between SCCAI and endoscopic disease activity in UC, particularly in left-sided disease. Poor correlations between HBI or SIBDQ and SES-CD appear to be consistent across different disease phenotypes.American Gastroenterological Associatio

Evaluation of GJB2 and GJB6 Mutations in Patients Afflicted with Non-syndromic Hearing Loss

Background Non-syndromic hearing loss (NSHL) is assumed as one of the highly prevalent congenital defects in the world. In this regard, gap junction protein beta 2(GJB2), and gap junction protein beta 6(GJB6) mutations are considered as the leading congenital causes of deafness. The present study aimed to assess the prevalence of GJB2 and GJB6 mutations in NSHL cases. Materials and Methods This cross-sectional study was implemented from Jan. 2015 to Sep. 2017 at Alzahra Hospital (Isfahan, Iran).46 patients afflicted with NSHL were recognized and recruited by physicians. Heparinized blood was collected and DNA of each participant was extracted. Genetic analysis of GJB2 and GJB6 genes was performed using PCR and GAP-PCR methods respectively. Results: 35delG mutation had the highest prevalence with allelic frequency of 6.12%. The allelic frequencies of 35delG, and delE120 were 6(6.12%), and 3(3.06%), respectively. Allelic frequency of W77R, Y65H, G160, and R127H was 2(2.04%) for each of them. In addition, 2 patients were heterozygous for p.V153I rare polymorphism (2.04%). Conclusion Overall, the present study indicated that 35delG mutation could be considered as the foremost causative factor of NHCL.  GJB2 mutations were highly prevalent among NSHL cases (23.9%). As a result, the mutation analysis of this gene could be appropriately used for prevention and early diagnosis of NSHL

Fibre intake and the development of inflammatory bowel disease – a European prospective multi-centre cohort study (EPIC-IBD)

Background and Aims: Population-based prospective cohort studies investigating fibre intake and development of inflammatory bowel disease (IBD) are lacking. Our aim was to investigate the association between fibre intake and the development of Crohn’s disease (CD) and ulcerative colitis (UC) in a large European population. Methods: 401 326 participants, aged 20–80 years, were recruited in 8 countries in Europe between 1991 and 1998. At baseline, fibre intake (total fibres, fibres from fruit, vegetables and cereals) was recorded using food frequency questionnaires. The cohort was monitored for the development of IBD. Each case was matched with four controls and odds ratios (ORs) for the exposures were calculated using conditional logistic regression. Sensitivity analyses according to smoking status were computed. Results: In total, 104 and 221 participants developed incident CD and UC, respectively. For both CD and UC, there were no statistically significant associations with either quartiles, or trends across quartiles, for total fibre, or any of the individual sources. The associations were not affected by adjusting for smoking and energy intake. Stratification according to smoking status showed null findings apart from an inverse association with cereal fibre and CD in non-smokers (Quartile 4 vs 1 OR=0.12, 95% CI=0.02–0.75, P=0.023, OR trend across quartiles=0.50, 95% CI=0.29–0.86, P=0.017). Conclusion: The results do not support the hypothesis that dietary fibre is involved in the aetiology of UC, although future work should investigate whether there may be a protective effect of specific types of fibre according to smoking status in CD