Aileen McKinley

Mercaptopurine versus placebo to prevent recurrence of Crohn's disease after surgical resection (TOPPIC): a multicentre, double-blind, randomised controlled trial

Summary Background Up to 60% of patients with Crohns disease need intestinal resection within the first 10 years of diagnosis, and postoperative recurrence is common. We investigated whether mercaptopurine can prevent or delay postoperative clinical recurrence of Crohns disease. Methods We did a randomised, placebo-controlled, double-blind trial at 29 UK secondary and tertiary hospitals of patients (aged >16 years in Scotland or >18 years in England and Wales) who had a confirmed diagnosis of Crohns disease and had undergone intestinal resection. Patients were randomly assigned (1:1) by a computer-generated web-based randomisation system to oral daily mercaptopurine at a dose of 1 mg/kg bodyweight rounded to the nearest 25 mg or placebo; patients with low thiopurine methyltransferase activity received half the normal dose. Patients and their carers and physicians were masked to the treatment allocation. Patients were followed up for 3 years. The primary endpoint was clinical recurrence of Crohns disease (Crohns Disease Activity Index >150 plus 100-point increase in score) and the need for anti-inflammatory rescue treatment or primary surgical intervention. Primary and safety analyses were by intention to treat. Subgroup analyses by smoking status, previous thiopurines, previous infliximab or methotrexate, previous surgery, duration of disease, or age at diagnosis were also done. This trial is registered with the International Standard Randomised Controlled Trial Register (ISRCTN89489788) and the European Clinical Trials Database (EudraCT number 2006-005800-15). Findings Between June 6, 2008, and April 23, 2012, 240 patients with Crohns disease were randomly assigned: 128 to mercaptopurine and 112 to placebo. All patients received at least one dose of study drug, and no randomly assigned patients were excluded from the analysis. 16 (13%) of patients in the mercaptopurine group versus 26 (23%) patients in the placebo group had a clinical recurrence of Crohns disease and needed anti-inflammatory rescue treatment or primary surgical intervention (adjusted hazard ratio [HR] 0·54, 95% CI 0·27–1·06; p=0·07; unadjusted HR 0·53, 95% CI 0·28–0·99; p=0·046). In a subgroup analysis, three (10%) of 29 smokers in the mercaptopurine group and 12 (46%) of 26 in the placebo group had a clinical recurrence that needed treatment (HR 0·13, 95% CI 0·04–0·46), compared with 13 (13%) of 99 non-smokers in the mercaptopurine group and 14 (16%) of 86 in the placebo group (0·90, 0·42–1·94; pinteraction=0·018). The effect of mercaptopurine did not significantly differ from placebo for any of the other planned subgroup analyses (previous thiopurines, previous infliximab or methotrexate, previous surgery, duration of disease, or age at diagnosis). The incidence and types of adverse events were similar in the mercaptopurine and placebo groups. One patient on placebo died of ischaemic heart disease. Adverse events caused discontinuation of treatment in 39 (30%) of 128 patients in the mercaptopurine group versus 41 (37%) of 112 in the placebo group. Interpretation Mercaptopurine is effective in preventing postoperative clinical recurrence of Crohns disease, but only in patients who are smokers. Thus, in smokers, thiopurine treatment seems to be justified in the postoperative period, although smoking cessation should be strongly encouraged given that smoking increases the risk of recurrence. Funding Medical Research Council.

A retrospective study evaluating the use of Permacol surgical implant in incisional and ventral hernia repair

BACKGROUND The outcome of incisional and ventral hernia repair depends on surgical technique, patient, and material. Permacol™ surgical implant (crosslinked porcine collagen) has been used for over a decade; however, there are few data on outcomes. This study is the largest retrospective multinational study to date to evaluate outcomes with Permacol™ surgical implant in the repair of incisional and ventral hernias. METHODS Data were collected retrospectively on 343 patients treated for 213 incisional and 130 ventral hernias. Data evaluated included patient demographics, wound classification, surgical technique, morbidity, and recurrence rates. RESULTS Median follow-up time was 649 days (max: 2857), median age 57 years (range 23-91), and BMI 32 kg/m(2) (range 17.6-77.8). Two or more comorbidities were present in 70% of patients. Open surgery was performed in 220 (64%) patients. Permacol™ surgical implant was used as an underlay (250), sublay (39), onlay (37), or inlay (17). Surgical techniques included component separation (89; 25.9%), modified Stoppa technique (197; 57.4%), and Rives-Stoppa (17; 5.0%). CDC Surgical Wound Classification was Class I (190), Class II (103), Class III (28), and Class IV (22). Complications were seen in 40.5% (139) of the patients, with seroma (19%) and wound infection (15%) as the most common. Mesh removal occurred in 1 (0.3%) patient. Kaplan-Meier analysis demonstrated that the probabilities for hernia recurrence at one, two, and three years were 5.8%, 16.6%, and 31.0%, respectively. CONCLUSIONS Permacol™ surgical implant was shown to be safe with relatively low rates of hernia recurrence. CLINICAL TRIAL REGISTRATION NUMBER NCT01214252 (http://www.clinicaltrials.gov).

Developing a community-based intervention to improve quality of life in people with colorectal cancer: a complex intervention development study

Objectives To develop and pilot a theory and evidence-based intervention to improve quality of life (QoL) in people with colorectal cancer. Design A complex intervention development study. Setting North East Scotland and Glasgow. Participants Semistructured interviews with people with colorectal cancer (n=28), cancer specialists (n=16) and primary care health professionals (n=14) and pilot testing with patients (n=12). Interventions A single, 1 h nurse home visit 6–12 weeks after diagnosis, and telephone follow-up 1 week later (with a view to ongoing follow-up in future). Primary and secondary outcome measures Qualitative assessment of intervention feasibility and acceptability. Results Modifiable predictors of QoL identified previously were symptoms (fatigue, pain, diarrhoea, shortness of breath, insomnia, anorexia/cachexia, poor psychological well-being, sexual problems) and impaired activities. To modify these symptoms and activities, an intervention based on Control Theory was developed to help participants identify personally important symptoms and activities; set appropriate goals; use action planning to progress towards goals; self-monitor progress and identify (and tackle) barriers limiting progress. Interview responses were generally favourable and included recommendations about timing and style of delivery that were incorporated into the intervention. The pilot study demonstrated the feasibility of intervention delivery. Conclusions Through multidisciplinary collaboration, a theory-based, acceptable and feasible intervention to improve QoL in colorectal cancer patients was developed, and can now be evaluated.

Using Videos to Determine the Effect of Stage of Operation and Intraoperative Events on Surgeons’ Intraoperative Leadership

Background Leadership is a key component for the successful functioning of teams and the achievement of task goals. During the intraoperative phase of surgery, the attending surgeon can be likened to a team leader with responsibility for task accomplishment by a small team. This study identified and evaluated surgeons’ leadership behaviors during operations, with particular reference to any changes that occurred following two types of events. Method Videos of live operations (n=29) from the operating rooms of three teaching hospitals in the UK were analyzed to identify and code surgeons’ intraoperative leadership behaviors using the Surgeons’ Leadership Inventory (SLI). The frequency and quality of the leadership behaviors were compared before and after the point of no return (PONR) (n=24) and before and after an unexpected intraoperative event (n=5). Results Most leadership behaviors were directed toward the resident during an operation. No significant differences were found for the overall frequency or quality of leadership behaviors pre- and post-PONR. The frequency of leadership behaviors classified as ‘training’ and ‘Supporting others’ significantly decreased after an unanticipated intraoperative event. Discussion This study provides a detailed description of surgeons’ intraoperative leadership during different types of operative situations and stages. During the intraoperative period, the attending surgeon seemed to lead the surgical trainee almost exclusively, and not other members of the operative team. Leadership was highly focused on the surgical task.

Development of a taxonomy for surgeons’ intraoperative leadership

Background: As the nominated or self –appointed leader of the surgical team, surgeons must demonstrate leadership along with technical excellence, in order to optimize performance and maximize patient safety in the operating room (OR). Method: A total of ten operating room discipline-specific focus groups from three hospitals in Scotland discussed intraoperative leadership. Surgeons’ leadership behaviors were extracted from the focus groups and used to develop a preliminary taxonomy which was independently checked by six surgeons for accuracy and face validity. It was then used to code video recordings (n = 5) of live operations, to test interrater reliability of the leadership taxonomy. Results: Eight categories of surgeons’ intraoperative leadership were identified from the focus groups. Overall interrater reliability was acceptable (kappa = .7). Discussion: The taxonomy is empirically grounded in focus group data as well as both the psychological and surgical leadership literature. The reliability of the system is acceptable. Future research should test the taxonomy to evaluate intraoperative leadership, in order to design a tool for training surgeons in intraoperative leadership.