DIRECT trial. Diverticulitis recurrences or continuing symptoms: Operative versus conservative Treatment. A MULTICENTER RANDOMISED CLINICAL TRIAL

Background: Persisting abdominal complaints are common after an episode of diverticulitis treated conservatively. Furthermore, some patients develop frequent recurrences. These two groups of patients suffer greatly from their disease, as shown by impaired health related quality of life and increased costs due to multiple specialist consultations, pain medication and productivity losses. Both conservative and operative management of patients with persisting abdominal complaints after an episode of diverticulitis and/or frequently recurring diverticulitis are applied. However, direct comparison by a randomised controlled trial is necessary to determine which is superior in relieving symptoms, optimising health related quality of life, minimising costs and preventing diverticulitis recurrences against acceptable morbidity and mortality associated with surgery or the occurrence of a complicated recurrence after conservative management. We, therefore, constructed a randomised clinical trial comparing these two treatment strategies. Methods/design: The DIRECT trial is a multicenter randomised clinical trial. Patients (18-75 years) presenting themselves with persisting abdominal complaints after an episode of diverticulitis and/or three or more recurrences within 2 years will be included and randomised. Patients randomised for conservative treatment are treated according to the current daily practice (antibiotics, analgetics and/or expectant management). Patients randomised for elective resection will undergo an elective resection of the affected colon segment. Preferably, a laparoscopic approach is used. The primary outcome is health related quality of life measured by the Gastro-intestinal Quality of Life Index, Short-Form 36, EQ-5D and a visual analogue scale for pain quantification. Secondary endpoints are morbidity, mortality and total costs. The total follow-u

The blameworthiness of health and safety rule violations

Man-made disasters usually lead to the tightening of safety regulations, because rule breaking is seen as a major cause of them. This reaction is based on the presumptions that the safety rules are good and that the rule-breakers are wrong. The reasons the personnel of a coke factory gave for breaking rules raise doubt about the tenability of these presumptions. It is unlikely that this result would have been achieved on the basis of a disaster evaluation or High-Reliability Theory. In both approaches, knowledge of the consequences of human conduct hinders an unprejudiced judgement about the blameworthiness of rule breaking

Alcohol consumption, alcohol dehydrogenase 3 polymorphism, and colorectal adenomas.

Alcohol is a probable risk factor with regard to colorectal neoplasm and is metabolized to the carcinogen acetaldehyde by the genetically polymorphic alcohol dehydrogenase 3 (ADH3) enzyme. We evaluated whether the association between alcohol and colorectal adenomas is modified by ADH3 polymorphism. We recruited 433 cases with adenomatous polyps and 436 polyp-free controls among Caucasians undergoing endoscopy between 1995 and 2000. Frequency and amount of habitual alcohol consumption were assessed by beverage type, using a validated self-administered food frequency questionnaire. All participants provided blood for genotyping of ADH3. Multivariate analyses adjusting for gender, age, and indication for endoscopy showed that alcohol increased the risk of colorectal adenomas among women [odds ratio (OR), 1.8; 95% confidence interval (CI), 1.0-3.2, >/=10 versus 21 drinks/week (OR, 1.8; 95% CI, 0.9-3.8, compared with men drinking < 1 drink/week). Among subjects in the highest tertile of alcohol consumption, those with the ADH3*1/*1 genotype were at higher risk (OR, 1.8; 95% CI, 1.0-3.1) than those with other ADH3 genotypes (OR, 1.2; 95% CI, 0.7-1.9) when compared with those in the lowest tertile with ADH3*1/*2 or ADH3*2/*2 genotypes. In conclusion, our findings are consistent with results of other studies, suggesting that alcohol consumption elevates the risk of adenomatous colorectal polyps. ADH3 polymorphism may modify the association between alcohol consumption and colorectal adenomas