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ObjectiveEvaluate the cost-effectiveness of laparoscopic ileocaecal resection compared with infliximab in patients with ileocaecal Crohn’s disease failing conventional therapy.DesignA multicentre randomised controlled trial was performed in 29 centres in The Netherlands and the UK. Adult patients with Crohn’s disease of the terminal ileum who failed >3 months of conventional immunomodulators or steroids without signs of critical strictures were randomised to laparoscopic ileocaecal resection or infliximab. Outcome measures included quality-adjusted life-years (QALYs) based on the EuroQol (EQ) 5D-3L Questionnaire and the Inflammatory Bowel Disease Questionnaire (IBDQ). Costs were measured from a societal perspective. Analyses were performed according to the intention-to-treat principle. Missing cost and effect data were imputed using multiple imputation. Cost-effectiveness planes and cost-effectiveness acceptability curves were estimated to show uncertainty.ResultsIn total, 143 patients were randomised. Mean Crohn’s disease total direct healthcare costs per patient at 1 year were lower in the resection group compared with the infliximab group (mean difference €−8931; 95% CI €−12 087 to €−5097). Total societal costs in the resection group were lower than in the infliximab group, however not statistically significant (mean difference €−5729, 95% CI €−10 606 to €172). The probability of resection being cost-effective compared with infliximab was 0.96 at a willingness to pay (WTP) of €0 per QALY gained and per point improvement in IBDQ Score. This probability increased to 0.98 at a WTP of €20 000/QALY gained and 0.99 at a WTP of €500/point of improvement in IBDQ Score.ConclusionLaparoscopic ileocaecal resection is a cost-effective treatment option compared with infliximab.Clinical trial registration numberDutch Trial Registry NTR1150; EudraCT number 2007-005042-20 (closed on 14 October 2015).

The risk of developing gallstones is increased in obese subjects. We have investigated whether gallbladder motility in obese subjects is different from that in lean control subjects. In 25 healthy non-diabetic obese subjects and 20 age-and sex-matched lean controls, fasting gallbladder volumes, gallbladder contraction in response to cephalic vagal cholinergic stimulation by modified sham feeding (MSF) and to hormonal stimulation with cholecystokinin (CCK) were studied. Gallbladder volumes were measured during a 30-min MSF period followed 1 h later by a 1-hour continuous i.v. infusion of 0.5 IDU/kg ideal weight of CCK-33. Fasting gallbladder volumes were significantly (p < 0.001) larger in obese (47 ± 4 cm 3 ) compared to lean subjects (24 ± 2 cm 3 ). Fasting gallbladder volume was correlated with body mass index (p < 0.01). Gallbladder contraction during MSF was significantly (p < 0.01) reduced in obese (12 ± 2%) compared to lean subjects (22 ± 3%). CCK infusion, leading to physiological post-prandial plasma CCK levels, induced a significantly (p < 0.001) greater absolute gallbladder contraction in obese (27 ± 3 cm 3 ) compared to lean subjects (15 ± 1 cm 3 ) but the percentage gallbladder contraction was in the same range (64 ± 3% vs. 67 ± 4%, respectively). In addition, residual gallbladder volumes after CCK infusion were significantly (p < 0.001) larger in obese (15 ± 2 cm 3 ) than in lean subjects (7 ± 1 cm 3 ). Two groups of obese subjects were identified: one with increased ( > 40 cm 3 ) and one with normal (≤40 cm 3 ) fasting gallbladder volumes. Only obese subjects with increased fasting volumes showed abnormal gallbladder motility.

Mark McCarthy and colleagues identify twelve new risk loci for type 2 diabetes through a large-scale genome-wide association and replication study in individuals of European ancestry. The identified loci affect both beta-cell function and insulin action and are enriched for genes involved in cell cycle regulation. By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combined P < 5 × 10 −8 . These include a second independent signal at the KCNQ1 locus; the first report, to our knowledge, of an X-chromosomal association (near DUSP9 ); and a further instance of overlap between loci implicated in monogenic and multifactorial forms of diabetes (at HNF1A ). The identified loci affect both beta-cell function and insulin action, and, overall, T2D association signals show evidence of enrichment for genes involved in cell cycle regulation. We also show that a high proportion of T2D susceptibility loci harbor independent association signals influencing apparently unrelated complex traits.

Nat. Genet. 42, 579–589 (2010); published online 27 June 2010; corrected after print 27 August 2010 In the version of this article initially published, there was an error in Table 1. Specifically, for rs5945326, the risk and non-risk alleles were reversed. The correct risk allele at rs5945326 is A, the non-risk allele is G and the risk allele frequency in HapMap CEU is 0.