Polar vectors as a method for evaluating the effectiveness of irritable bowel syndrome treatments: An analysis with pinaverium bromide 100 mg plus simethicone 300 mg po bid

Background: Irritable Bowel Syndrome (IBS) is a disorder characterized by abdominal pain or discomfort associated with changes in bowel habit. Currently there are no objective outcome measures for evaluating the effectiveness of treatments for this disorder. Aims: To determine the usefulness of a method of analysis that employs polar vectors to evaluate the effectiveness of IBS treatments. Methods: Data from a Phase IV clinical study with 1677 active IBS-Rome III patients who received 100 mg of pinaverium bromide + 300 mg of simethicone (PB + S) po bid for a period of four weeks were used for the analysis. Using the Bristol Stool Scale as a reference, the consistency and frequency of each type of bowel movement were recorded weekly in a Bristol Matrix (BM) and the data were expressed as polar vectors. Results: The analysis showed a differential response to the PB + S treatment among the IBS subtypes: in reference to the IBS with constipation subtype, the magnitude of the vector increased from 10.2 to 12.5, reaching maximum improvement at two weeks of treatment (p < 0.05, Scheffé). In the IBS with diarrhea and mixed IBS subtypes, the magnitude of the vector decreased from 19 to 14 (p<0.05) and from 16.5 to 13 (p < 0.05), respectively, with continuous improvement for a period of four weeks. There was no definable vectorial pattern in the unsubtyped IBS group. Conclusions: Analysis with polar vectors enables treatment response to be measured in different IBS subtypes. All the groups showed improvement with PB + S, but each one had its own characteristic response in relation to vector magnitude and direction. The proposed method can be implemented in clinical studies to evaluate the efficacy of IBS treatments

Evaluation of a quality improvement intervention to reduce anastomotic leak following right colectomy (EAGLE): pragmatic, batched stepped-wedge, cluster-randomized trial in 64 countries

Background: Anastomotic leak affects 8 per cent of patients after right colectomy with a 10-fold increased risk of postoperative death. The EAGLE study aimed to develop and test whether an international, standardized quality improvement intervention could reduce anastomotic leaks. Methods: The internationally intended protocol, iteratively co-developed by a multistage Delphi process, comprised an online educational module introducing risk stratification, an intraoperative checklist, and harmonized surgical techniques. Clusters (hospital teams) were randomized to one of three arms with varied sequences of intervention/data collection by a derived stepped-wedge batch design (at least 18 hospital teams per batch). Patients were blinded to the study allocation. Low- and middle-income country enrolment was encouraged. The primary outcome (assessed by intention to treat) was anastomotic leak rate, and subgroup analyses by module completion (at least 80 per cent of surgeons, high engagement; less than 50 per cent, low engagement) were preplanned. Results: A total 355 hospital teams registered, with 332 from 64 countries (39.2 per cent low and middle income) included in the final analysis. The online modules were completed by half of the surgeons (2143 of 4411). The primary analysis included 3039 of the 3268 patients recruited (206 patients had no anastomosis and 23 were lost to follow-up), with anastomotic leaks arising before and after the intervention in 10.1 and 9.6 per cent respectively (adjusted OR 0.87, 95 per cent c.i. 0.59 to 1.30; P = 0.498). The proportion of surgeons completing the educational modules was an influence: the leak rate decreased from 12.2 per cent (61 of 500) before intervention to 5.1 per cent (24 of 473) after intervention in high-engagement centres (adjusted OR 0.36, 0.20 to 0.64; P < 0.001), but this was not observed in low-engagement hospitals (8.3 per cent (59 of 714) and 13.8 per cent (61 of 443) respectively; adjusted OR 2.09, 1.31 to 3.31). Conclusion: Completion of globally available digital training by engaged teams can alter anastomotic leak rates. Registration number: NCT04270721 (http://www.clinicaltrials.gov)