Some right-sided hyperplastic polyps may give rise to sporadic colorectal carcinomas with MSI. Methylation of the hMLH1 gene promoter within neoplastic cell subpopulations may be a critical step in the progression to carcinoma. The frequency with which benign lesions progress to cancer with MSI is unknown.

Off‐label prescribing is the prescription of a registered medicine for a use that is not included in the product information. The practice is common, with rates up to 40% in adults and up to 90% in paediatric patients. Off‐label prescribing is not illegal and may sometimes be clinically appropriate, but is associated with a number of clinical, safety and ethical issues. To date, no explicit guidance has been available to help clinicians assess appropriateness in off‐label prescribing. We describe the development of a guide for clinicians, policymakers and funders of health care in evaluating the appropriateness of medicines proposed for off‐label use. Three broad categories of appropriate off‐label use are identified: ➢off‐label use justified by high‐quality evidence; ➢use within the context of a formal research proposal; and ➢exceptional use, justified by individual clinical circumstances. An appropriate process for informed consent is proposed for each category. If there is no high‐quality evidence supporting off‐label use, and the medicine is not suitable for exceptional or research indications, its use is generally not recommended. This will reduce inappropriate use, enhance patient safety by reducing exposure to unnecessary risk, and may stimulate more clinically relevant medicines research.

Advances in high-throughput genomic technologies coupled with a growing number of genomic results potentially useful in clinical care have led to ground-breaking genomic medicine implementation programs in various nations. Many of these innovative programs capitalize on unique local capabilities arising from the structure of their health care systems or their cultural or political milieu, as well as from unusual burdens of disease or risk alleles. Many such programs are being conducted in relative isolation and might benefit from sharing of approaches and lessons learned in other nations. The National Human Genome Research Institute recently brought together 25 of these groups from around the world to describe and compare projects, examine the current state of implementation and desired near-term capabilities, and identify opportunities for collaboration to promote the responsible implementation of genomic medicine. The wide variety of nascent programs in diverse settings demonstrates that implementation of genomic medicine is expanding globally in varied and highly innovative ways. Opportunities for collaboration abound in the areas of evidence generation, health information technology, education, workforce development, pharmacogenomics, and policy and regulatory issues. Several international organizations that are already facilitating effective research collaborations should engage to ensure implementation proceeds collaboratively without potentially wasteful duplication. Efforts to coalesce these groups around concrete but compelling signature projects, such as global eradication of genetically-mediated drug reactions or developing a truly global genomic variant data resource across a wide number of ethnicities, would accelerate appropriate implementation of genomics to improve clinical care world-wide.

Background: The adoption of Patient Reported Outcome Measures (PROMs) in cancer care has been widely advocated, but little is known about the evidence for the implementation of PROMs in practice. Qualitative research captures the perspectives of health professionals as end-users of PROMs and can be used to inform adoption efforts. This paper presents a systematic review and synthesis of qualitative research conducted to address the question: What are the attitudes of health professionals towards PROMs in oncology, including any barriers and facilitators to the adoption of PROMS, reported in qualitative evidence? Methods: Systematic searches of qualitative evidence were undertaken in four databases and reviewed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies published in English between 1998 and 2018, which reported qualitative findings about the attitudes of health professionals working in oncology towards PROMs were eligible. Studies were assessed using the Critical Appraisal Skills Programme's Qualitative Research Checklist. A sentiment analysis was conducted on primary text to examine the polarity (neutral, positive or negative) of health professionals' views of PROMs. Qualitative meta-synthesis was conducted using a constant comparative analysis. Results: From 1227 articles after duplicates were removed, with 1014 excluded against the screening criteria, 213 full text articles remained and were assessed; 34 studies met the inclusion criteria and were included. The majority of studies were of good quality. Sentiment analysis on primary text demonstrated an overall positive polarity from the expressed opinions of health professionals. The meta-synthesis showed health professionals' attitudes in four domains: identifying patient issues and needs using PROMs; managing and addressing patient issues; the care experience; and the integration of PROMs into clinical practice.