Subgroup analyses in randomized trials examine whether effects of interventions differ between subgroups of study populations according to characteristics of patients or interventions. However, ...findings from subgroup analyses may be misleading, potentially resulting in suboptimal clinical and health decision making. Few studies have investigated the reporting and conduct of subgroup analyses and a number of important questions remain unanswered. The objectives of this study are: 1) to describe the reporting of subgroup analyses and claims of subgroup effects in randomized controlled trials, 2) to assess study characteristics associated with reporting of subgroup analyses and with claims of subgroup effects, and 3) to examine the analysis, and interpretation of subgroup effects for each study's primary outcome.
We will conduct a systematic review of 464 randomized controlled human trials published in 2007 in the 118 Core Clinical Journals defined by the National Library of Medicine. We will randomly select journal articles, stratified in a 1:1 ratio by higher impact versus lower impact journals. According to 2007 ISI total citations, we consider the New England Journal of Medicine, JAMA, Lancet, Annals of Internal Medicine, and BMJ as higher impact journals. Teams of two reviewers will independently screen full texts of reports for eligibility, and abstract data, using standardized, pilot-tested extraction forms. We will conduct univariable and multivariable logistic regression analyses to examine the association of pre-specified study characteristics with reporting of subgroup analyses and with claims of subgroup effects for the primary and any other outcomes.
A clear understanding of subgroup analyses, as currently conducted and reported in published randomized controlled trials, will reveal both strengths and weaknesses of this practice. Our findings will contribute to a set of recommendations to optimize the conduct and reporting of subgroup analyses, and claim and interpretation of subgroup effects in randomized trials.
Objective To investigate the impact of industry funding on reporting of subgroup analyses in randomised controlled trials.Design Systematic review.Data sources Medline.Study selection Randomised ...controlled trials published in 118 core clinical journals (defined by the National Library of Medicine) in 2007. 1140 study reports in a 1:1 ratio by high (five general medicine journals with largest number of total citations in 2007) versus lower impact journals, were randomly sampled. Two reviewers, independently and in duplicate, used standardised, piloted forms to screen study reports for eligibility and to extract data. They also used explicit criteria to determine whether a randomised controlled trial reported subgroup analyses. Logistic regression was used to examine the association of prespecified study characteristics with reporting versus not reporting of subgroup analyses.Results 469 randomised controlled trials were included, of which 207 (44%) reported subgroup analyses. High impact journals (adjusted odds ratio 2.64, 95% confidence interval 1.62 to 4.33), non-surgical (versus surgical) trials (2.10, 1.26 to 3.50), and larger sample size (3.38, 1.64 to 6.99) were associated with more frequent reporting of subgroup analyses. The strength of association between trial funding and reporting of subgroups differed in trials with and without statistically significant primary outcomes (interaction P=0.02). In trials without statistically significant results for the primary outcome, industry funded trials were more likely to report subgroup analyses (2.29, 1.30 to 4.72) than non-industry funded trials. This was not true for trials with a statistically significant primary outcome (0.79, 0.46 to 1.36). Industry funded trials were associated with less frequent prespecification of subgroup hypotheses (31.3% v 38.0%, adjusted odds ratio 0.49, 0.26 to 0.94), and less use of the interaction test for analyses of subgroup effects (41.4% v 49.1%, 0.52, 0.28 to 0.97) than non-industry funded trials.Conclusion Industry funded randomised controlled trials, in the absence of statistically significant primary outcomes, are more likely to report subgroup analyses than non-industry funded trials. Industry funded trials less frequently prespecify subgroup hypotheses and less frequently test for interaction than non-industry funded trials. Subgroup analyses from industry funded trials with negative results for the primary outcome should be viewed with caution.
Objectives: To review 13 years’ data from a unit for grown ups with congenital heart disease (GUCH) to understand the change in surgical practice. Methods: Records were reviewed of patients over 16 ...years of age undergoing surgery between 1 January 1990 and 31 December 2002 in a dedicated GUCH unit. Patients with atrial septal defects were included but not those with Marfan’s syndrome or undergoing a first procedure for bicuspid aortic valves. Three equal time periods of 52 months were analysed. Results: Of 474 operations performed, 162 (34.2%) were repeat operations. The percentage of repeat operations increased from 24.8% (41 of 165) in January 1990–April 1994 to 49.7% (74 of 149) in September 1998–December 2002. Mortality was 6.3% (n = 30). The median age decreased from 25.4 years (interquartile range 18.7) in January 1990–April 1994 to 23.9 (interquartile range 17.3) in September 1998–December 2002 (p = 0.04). The proportion of patients with a “simple” diagnosis decreased from 45.4% (74 or 165) in January 1990–April 1994 to 27.5% (41 of 149) in September 1998–December 2002 (p = 0.013). Pulmonary valve replacements in operated tetralogy of Fallot increased from one case in January 1990–April 1994 to 23 cases in September 1998–December 2002 and conduit replacement increased from five cases to 17. However, secundum atrial septal defect closures decreased from 35 cases to 14 (p < 0.0001). The estimated cost (not including salaries and prosthetics) incurred by an adult patient with congenital heart disease was £2290 compared with £2641 for a patient undergoing coronary artery bypass grafting. Conclusion: Despite the impact of interventional cardiology, the total number of surgical procedures remained unchanged. The complexity of the cases increased particularly with repeat surgery. Nevertheless, the patients do well with low mortality and the inpatient costs remain comparable with costs of surgery for acquired disease.
To test the hypothesis that increased airway strain resulting from lung denervation initiates a fibroproliferative response in the airways, we compared the transcriptional expressions of ...alpha1(I)-procollagen and tropoelastin in the lungs of rats subjected to unilateral vagal denervation, unilateral vagal denervation combined with ipsilateral phrenectomy, or thoracotomy without denervation (controls). We found increases in alpha1(I)-procollagen messenger ribonucleic acids (mRNAs) in the submucosa of the airways and the adventitia of airways and pulmonary vessels of the denervated lungs in 31% of the rats subjected to unilateral denervation (with and without phrenectomy), and in none of the controls. The increased transcripts were associated with collagen deposition in the peribronchial and perivascular tissue, and occasionally with cell proliferation leading to occlusion of the airway and vascular lumina. Unilateral phrenectomy did not decrease the frequency with which production of Type I procollagen was upregulated, suggesting that the upregulation was not entirely dependent on airway strain. Tropoelastin expression was not influenced by denervation. Our results indicate that the autonomic nervous system has a previously unsuspected trophic influence on collagen synthesis in the airways and pulmonary vessels. Abolition of this influence by denervation may lead to structural changes analogous to those observed in bronchiolitis obliterans after lung transplantation.
Although jejunal atresia occasionally may occur with a familial pattern, an association with renal disease has not been described. The authors report on three family members treated over two ...generations, all of whom had both proximal jejunal atresia and renal dysplasia. This association was most likely inherited as an autosomal dominant trait.
Several investigators have reported good results after a one-stage Soave procedure without a stoma for infants with Hirschsprung's disease. The authors reviewed their concurrent experience with the ...one- and two-stage approaches, comparing the two groups with respect to rate of complications and clinical outcome. Over a 3-year period, 36 infants with colonic Hirschsprung's disease presenting in the first year of life were treated with a Soave pull-through. Thirteen had a one-stage pull-through, and 23 had a two-stage procedure using an initial stoma. There was no difference with respect to median age at time of diagnosis, median follow-up period, length of aganglionosis, or male:female ratio between the groups. The incidences of major complications such as small bowel obstruction, segmental or acquired aganglionosis, anastomotic leak, and malabsorption were equal between the two groups. However, 13% of the two-stage patients required revision of the stoma. All major complications in the one-stage group were in those who weighed less than 4 kg at the time of surgery. Minor complications such as wound infection, perianal excoriation, and need for repeated dilatation were similar between the groups, but minor stoma-related complications (prolapse or retraction) occurred in 26% of the two-stage infants. When complications were stratified using a more sophisticated scale of severity, no significant difference was found between the groups. The overall complication rate was 1.5 events per patient in the one-stage group and 2.0 events per patient in the two-stage group. This small difference was related to the presence of a stoma in the two-stage group. Overall, 10 of 12 survivors in the one-stage group and 22 of 23 in the two-stage group were doing well, with normal bowel function noted on long-term follow-up (mean period, of 14 and 19 months, respectively). Both one- and two-stage approaches were associated with a significant complication rate, although long-term outcome was excellent in both groups. The higher complication rate in the two-stage group was attributable to the presence of a stoma. For small infants, it may be beneficial to delay the one-stage pull-through until weight exceeds 4 kg.
Gastroschisis is a congenital anomaly in which exposure of the intestines to amniotic fluid throughout fetal life results in nutrient malabsorption. To begin to understand the molecular basis ...underlying epithelial changes in this condition, we investigated enterocytic gene expression during fetal development. Gastroschisis was surgically created at 24 days gestation (term = 31 days) in fetal rabbits; sham-operated and unoperated fetuses served as controls. Bowel was harvested at 28 and 31 days gestation. Cellular lactase expression was detected using immunohistochemistry, and apolipoprotein A-I and cellular retinol binding protein II (CRBPII) mRNA levels were quantitated using Northern blot analysis. Despite absence of gross histological changes in the mucosa, lactase protein expression and apolipoprotein A-I and CRBPII mRNA expression were decreased in intestine from gastroschisis compared to sham-operated animals. Expression of GAPDH (a housekeeping gene) increased over the same period, suggesting that the changes in enterocytic absorptive gene expression associated with gastroschisis were relatively specific. In conclusion, a decrease in expression of a variety of genes involved in nutrient absorption and trafficking within the enterocyte may contribute to the absorptive defects seen in this gastroschisis.
The objective of this study was to describe recent trends in the management of mild-to-moderate gallstone pancreatitis and assess patient outcomes. Acute gallstone pancreatitis has traditionally been ...managed with open cholecystectomy and intraoperative cholangiography during the initial hospitalization. The popularization of endoscopic retrograde cholangiopancreatography (ERCP) and laparoscopic cholecystectomy has made a reassessment necessary. Two consecutive time periods were retrospectively analyzed: prior to laparoscopic cholecystectomy (prelaparoscopic era PLE) and after the diffusion of laparoscopic cholecystectomy (laparoscopic cholectomy era LCE). There were 35 patients in the PLE group and 58 in the LCE group. LCE patients waited 37.1 ± 63 days from admission until cholecystectomy, compared to 9.8 ± 14.8 days in the PLE group (
P = 0.04). Biliary-pancreatic complications occurred in 24% of LCE patients and only 6% of PLE patients (
P = 0.05),nearly always while they were awaiting cholecystectomy (
P = 0.009). Patients in either time period who underwent cholecystectomy with intraoperative cholangiography developed less pancreatic-biliary complications than those who underwent ERCP prior to cholecystectomy, with or without sphincterotomy. Delaying the interval from pancreatitis to laparoscopic cholecystectomy beyond historical values is associated with a greater risk of recurrent biliary-pancreatic complications, which are not prevented by the use of ERCP. Early cholecystectomy with intraoperative ductal evaluation is still the approach of choice.
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