Assessment of long-term bowel dysfunction after restorative proctectomy for neoplastic disease: A population-based cohort study.

BACKGROUND: The purpose of this study was to describe postoperative bowel dysfunction after restorative proctectomy, and to identify factors associated with its development. METHODS: Patients who underwent restorative proctectomy for rectal cancer between April 1998 and November 2018 were identified from the Hospital Episode Statistics database and linked to the Clinical Practice Research Datalink for postoperative follow-up. Bowel dysfunction was defined according to relevant symptom-based read codes and medication prescription-product codes. A Cox proportional hazards model was performed to identify factors associated with postoperative bowel dysfunction, adjusting for relevant covariates. RESULTS: In total, 2,197 patients were included. The median age was 70.0 (interquartile range: 62.0-77.0) years old, and the majority (59.2%) of patients were male. After a median follow-up of 51.6 (24.0-90.0) months, bowel dysfunction was identified in 620 (28.2%) patients. Risk factors for postoperative bowel dysfunction included extremes of age (<40 years old: adjusted hazards ratio 2.35, 95% confidence interval 1.18-4.65; 70-79 years old: adjusted hazards ratio 1.25, 95% confidence interval 1.03-1.52), radiotherapy (adjusted hazards ratio 1.94, 95% confidence interval 1.56-2.42), distal tumors (adjusted hazards ratio 1.62, 95% confidence interval 1.34-1.94), history of diverting ostomy (adjusted hazards ratio 1.58, 95% confidence interval 1.33-1.89), and anastomotic leak (adjusted hazards ratio 1.48, 95% confidence interval 1.06-2.05). A minimally invasive surgical approach was protective for postoperative bowel dysfunction (adjusted hazards ratio 0.68, 95% confidence interval 0.53-0.86). CONCLUSION: Bowel dysfunction was common after restorative proctectomy, and several patient, disease, and treatment-level factors were associated with its development.

Abatacept initiation in rheumatoid arthritis and the risk of cancer: a population-based comparative cohort study.

OBJECTIVE: To assess whether abatacept as initial biological DMARD (bDMARD) in the treatment of RA, when compared with other bDMARDs, is associated with an increased risk of cancer overall and by specific cancer sites (breast, lung, lymphoma, melanoma and non-melanoma skin cancer). METHODS: We performed a population-based cohort study among patients newly treated with bDMARDs within the US-based Truven MarketScan population and Supplemental US Medicare from 2007 to 2014. Cox proportional hazards models were used to estimate hazard ratios and 95% CIs of any cancer (and specific cancers) associated with initiation of abatacept, compared with initiation of other bDMARDs, adjusted for age and deciles of the propensity score. RESULTS: The cohort included 4328 patients on abatacept and 59 860 on other bDMARDs, of whom 409 and 4197 were diagnosed with any cancer during follow-up (incidence rates 4.76 per 100 per year and 3.41 per 100 per year, respectively). Compared with other bDMARDs, the use of abatacept was associated with an increased incidence of cancer overall (hazard ratioadjusted 1.17; 95% CI 1.06, 1.30). Analyses by specific cancer sites showed a significantly increased incidence of non-melanoma skin cancer (hazard ratioadjusted 1.20; 95% CI 1.03, 1.39), but no significant difference for other specific cancer sites. CONCLUSION: The use of abatacept as first bDMARD in the treatment of RA was associated with a slight increased risk of cancer overall and particularly non-melanoma skin cancer, compared with other bDMARDs. This potential signal needs to be replicated in other settings.

Measuring persistence to hormonal therapy in patients with breast cancer: accounting for temporary treatment discontinuation.

PURPOSE: Several studies have been conducted to estimate persistence to hormonal therapy among women with breast cancer (BC). Most studies focus on first treatment discontinuation. Patients, however, can have numerous periods of treatment discontinuation or treatment exposure. Our objective is to estimate persistence to tamoxifen in patients with BC while accounting for temporary treatment discontinuations and this by using multi-state (MS) models. METHODS: A cohort of 10,806 women with BC having received at least one prescription of tamoxifen between 1998 and 2008 was constituted from the UK General Practice Research Database. We fitted a semi-Markov model with three states to estimate the probability of being off treatment over a 5-year period while accounting for temporary treatment discontinuations (transition between on treatment and off treatment) and competing risks (recurrence of BC or death). RESULTS: Non-persistence, as estimated from the MS model, ranged from 12.1% (95% confidence interval [95%CI]: 9.2-15.1) at 1 year to 14.9% (95%CI: 11.7-18.1) at 5 years. Estimations of non-persistence based on the Kaplan-Meier model were higher, i.e., 29.3% (95%CI: 28.1-30.6) at 5 years, as well as those obtained from a competing risk model, i.e., 24.0% (95%CI: 22.9-25.1). Most temporary discontinuations (94.7%) lasted less than 6 months. Temporary treatment discontinuations are frequent and should be accounted for when measuring adherence to treatment. MS models can provide a useful framework for this sort of analysis insofar as they help describe patients' complex behavior. This may help tailor interventions that improve persistence to hormonal therapy among women with BC.