Statin use is associated with a reduced incidence of colorectal cancer expressing SMAD4.

BACKGROUND: Long-term use of statins is associated with a small reduced risk of colorectal cancer but their mechanism of action is not well understood. While they are generally believed to act on KRAS, we have previously proposed that they act via influencing the BMP pathway. The objective of this study was to look for associations between statin use and the risk of developing colorectal cancer of a particular molecular subtype. METHODS: By linking two registries unique to the Netherlands, 69,272 statin users and 94,753 controls were identified and, if they developed colorectal cancer, their specimens traced. Colorectal cancers were molecularly subtyped according to the expression of SMAD4 and the mutation status of KRAS and BRAF. RESULTS: Statin use was associated with a reduction in the risk of developing colorectal cancer regardless of molecular subtype (HR 0.77; 95% CI 0.66-0.89) and a larger reduction in the risk of developing SMAD4-positive colorectal cancer (OR 0.64; 95% CI 0.42-0.82). There was no relationship between statin use and the risk of developing colorectal cancer with a mutation in KRAS and/or BRAF. CONCLUSIONS: Statin use is associated with a reduced risk of developing colorectal cancer with intact SMAD4 expression.

Reduction of routine radiographs in the follow-up of distal radius and ankle fractures: Barriers and facilitators perceived by orthopaedic trauma surgeons.

RATIONALE, AIMS, AND OBJECTIVES: Studies suggest that routine radiographs during follow-up of distal radius and ankle fractures result in increased radiation exposure and health care costs, without influencing treatment strategies. Encouraging clinicians to omit these routine radiographs is challenging, and little is known about barriers and facilitators that influence this omission. Therefore, this study aims to identify barriers and facilitators among orthopaedic trauma surgeons that might prove valuable towards the design of a deimplementation strategy. METHODS: A mixed-method approach was used. First, interviews were conducted with orthopaedic trauma surgeons and patients (n = 16). Subsequently, a questionnaire was developed. This questionnaire was presented to 228 orthopaedic trauma surgeons in the Netherlands. Regression analyses were performed in order to identify which variables were independently associated to the decision to stop performing routine radiographs 6 and 12 weeks after trauma if proven not effective in a large randomized controlled trial. RESULTS: In total, 130 (57%) respondents completed the questionnaire. Of these, 71% indicated they would stop ordering routine radiographs if they were proven not effective. Three facilitators were independent predictors for the intention to omit routine radiographs: This will "lead to lower health care costs" (Odds Ratio [OR]: 5.38 and 4.38), the need for "incorporation in the regional protocol" (OR: 3.66 and 2.66), and this will "result in time savings for the patient" (OR: 4.84). CONCLUSIONS: We identified three facilitators that could provide backing for a deimplementation strategy aimed at a reduction of routine radiographs for patients with distal radius and ankle fractures.

Routine Follow-Up Radiographs for Ankle Fractures Seldom Add Value to Clinical Decision-Making: A Retrospective, Observational Study.

Currently, the routine use of radiographs for uncomplicated ankle fractures represents good clinical practice. However, radiographs are associated with waiting time, radiation exposure, and costs. Studies have suggested that radiographs seldom alter the treatment strategy if no clinical indication for the imaging study was present. The objective of the present study was to evaluate the effect of routine radiographs on the treatment strategy during the follow-up period of ankle fractures. All patients aged ≥18 years, who had visited 1 of the participating clinics with an eligible ankle fracture in 2012 and with complete follow-up data were included. The data were retrospectively analyzed. The sociodemographic and clinical characteristics and the number of, and indications for, the radiographs taken were collected from the medical records of the participating clinics. We assessed the changes in treatment strategy according to the radiographic findings. In 528 patients with an ankle fracture, 1174 radiographs were performed during the follow-up period. Of these radiographs, 936 (79.7%) were considered routine. Of the routine radiographs taken during the follow-up period, only 11 (1.2 %) resulted in changes to the treatment strategy. Although it is common practice to take radiographs routinely during the follow-up period for ankle fractures, the results from the present study suggest that routine radiographs seldom alter the treatment strategy. This limited clinical relevance should be weighed against the health care costs and radiation exposure associated with the use of routine radiographs. For a definitive recommendation, however, the results of our study should be confirmed by a prospective trial, which we are currently conducting.

WARRIOR-trial - is routine radiography following the 2-week initial follow-up in trauma patients with wrist and ankle fractures necessary: study protocol for a randomized controlled trial.

BACKGROUND: Extremity fractures such as wrist and ankle fractures are a common and costly healthcare problem. The management of these fractures depends on fracture type and loss of congruity of the joint, resulting in cast immobilization or operative treatment. Loss of congruity or displacement leading to uneven joint loading, osteoarthritis and an increased probability of a poor functional outcome should be identified within the first 2 weeks post-trauma, based upon radiographs to determine optimal treatment. After this period, routine radiographs are scheduled for monitoring the bone-healing process. Current protocols describe imaging at 1, 2, 6 and 12 weeks post-trauma. However, it is questionable whether routine radiography following the initial follow-up ( 2-weeks post-trauma) is cost effective. The aim of this study is to determine whether a modification of the radiographic follow-up protocol can be conducted with no worse outcome and less cost than the current standard of care for patients with a wrist or ankle fracture. METHODS/DESIGN: In a multicenter randomized controlled trial, 697 patients aged 18 years or older will be included: 385 wrist fracture- and 312 ankle fracture patients. Patients will be randomized into two groups: Group 1 receives usual care, consisting of radiographs 1, 2, 6 and 12 weeks post-trauma; Group 2 receives radiographs beyond the initial follow-up only when clinically indicated. The primary outcome is the overall extremity-specific function. For wrist fractures, this includes the Disabilities of the Arm, Shoulder and Hand Score; for the ankle fractures, this includes the Olerud and Molander ankle score. Secondary outcomes include: healthcare cost, the specific function measured with the Patient Rated Wrist and Hand Evaluation for wrist fractures and American Academy of Orthopaedic Surgeons foot and ankle questionnaire for ankle fractures, pain-intensity, health-related quality of life, self-perceived recovery, and complications. Both groups will be monitored at 1, 2, and 6 weeks and 3, 6, and 12 months. DISCUSSION: This study will provide data on (cost) effectiveness of routine radiography in the follow-up of wrist and ankle fractures, and could pave the way for a change in (inter)national protocols. TRIAL REGISTRATION: Netherlands Trial Register NTR4610 , registration date 22 June 2014.