Impact of nationwide enhanced implementation of best practices in pancreatic cancer care (PACAP-1): A multicenter stepped-wedge cluster randomized controlled trial

Background: Pancreatic cancer has a very poor prognosis. Best practices for the use of chemotherapy, enzyme replacement therapy, and biliary drainage have been identified but their implementation in daily clinical practice is often suboptimal. We hypothesized that a nationwide program to enhance implementation of these best practices in pancreatic cancer care would improve survival and quality of life. Methods/design: PACAP-1 is a nationwide multicenter stepped-wedge cluster randomized controlled superiority trial. In a per-center stepwise and randomized manner, best practices in pancreatic cancer care regarding the use of (neo)adjuvant and palliative chemotherapy, pancreatic enzyme replacement therapy, and metal biliary stents are implemented in all 17 Dutch pancreatic centers and their regional referral networks during a 6-week initiation period. Per pancreatic center, one multidisciplinary team functions as reference for the other centers in the network. Key best practices were identified from the literature, 3 years of data from existing nationwide registries within the Dutch Pancreatic Cancer Project (PACAP), and national expert meetings. The best practices follow the Dutch guideline on pancreatic cancer and the current state of the literature, and can be executed within daily clinical practice. The implementation process includes monitoring, return visits, and provider feedback in combination with education and reminders. Patient outcomes and compliance are monitored within the PACAP registries. Primary outcome is 1-year overall survival (for all disease stages). Secondary outcomes include quality of life, 3- and 5-year overall survival, and guideline compliance. An improvement of 10% in 1-year overall survival is considered clinically relevant. A 25-month study duration was chosen, which provides 80% statistical power for a mortality reduction of 10.0% in the 17 pancreatic cancer centers, with a required sample size of 2142 patients, corresponding to a 6.6% mortality reduction and 4769 patients nationwide. Discussion: The PACAP-1 trial is designed to evaluate whether a nationwide program for enhanced implementation of best practices in pancreatic cancer care can improve 1-year overall survival and quality of life. Trial registration: ClinicalTrials.gov, NCT03513705. Trial opened for accrual on 22th May 2018

The genetic epidemiology of joint shape and the development of osteoarthritis

Congruent, low-friction relative movement between the articulating elements of a synovial joint is an essential pre-requisite for sustained, efficient, function. Where disorders of joint formation or maintenance exist, mechanical overloading and osteoarthritis (OA) follow. The heritable component of OA accounts for ~ 50% of susceptible risk. Although almost 100 genetic risk loci for OA have now been identified, and the epidemiological relationship between joint development, joint shape and osteoarthritis is well established, we still have only a limited understanding of the contribution that genetic variation makes to joint shape and how this modulates OA risk. In this article, a brief overview of synovial joint development and its genetic regulation is followed by a review of current knowledge on the genetic epidemiology of established joint shape disorders and common shape variation. A summary of current genetic epidemiology of OA is also given, together with current evidence on the genetic overlap between shape variation and OA. Finally, the established genetic risk loci for both joint shape and osteoarthritis are discussed

Residual stresses in aluminium alloy friction stir welds

Residual stresses are detrimental to the fatigue, fracture and corrosion resistance of welds. The literature on residual stress measurements in aluminium alloy friction stir welds is reviewed. The results of a large number of longitudinal residual stress measurements performed by the slitting method on friction stir welds in 2024-T3, 6082-T6 and 5754-H111 aluminium alloys are compared and their origin discussed. From the current investigation, it can be derived that the type of machine used for welding has only little influence on the residual stress profile. The influence of alloy type and welding parameters on the magnitude of the residual stresses and the shape of their distribution across the weld is investigated. Their magnitude is far below the room temperature yield strength of the base material. A distribution with an “M-shape” is always found on age hardenable structural alloys (albeit more pronounced in 6082-T6 alloy than in 2024-T3 alloy), while a “plateau” is found in the case of the strain hardenable 5754 H111 alloy. The low magnitude and the differences in distribution of the longitudinal residual stress are attributed mainly to the microstructural changes in the weld centre and are discussed based on the hardness profiles performed across the welds. The paper also discusses the reasons why those results are in disagreement with a number of numerical simulations from the literature that do not account for the influence of the welding thermomechanical history on the material microstructure and properties

Guidance notes for the safety assessment of genetically modified crops for food and feed use

This document describes the elements needed for the safety assessment of foods and feeds derived from genetically modified crops. This document does not address environmental, ethical or socio-economical aspects of the marketing of these foods and feeds, but considers the aspects with relevance to human or animal health. This document provides guidance to notifiers and biosafety assessors as to which extent studies have to be carried out following a case-by-case approach for the evaluation of genetically modified food and feed crops. This guidance document is not a static data package, but should be considered along with newly evolving scientific knowledge and technology. The scientific aspects and the presentation of information in the dossier should fulfil the requirements of the ongoing legislations and recommendations as specified insection 4 of this chapter. This document complements these requirements by providing more detailed guidelines for the safety assessment of foods and feeds derived from genetically modified&nbsp;crops.</p