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The therapeutic landscape of chronic myeloid leukemia (CML) has profoundly changed over the past 7 years. Most patients with chronic phase (CP) now have a normal life expectancy. Another goal is achieving a stable deep molecular response (DMR) and discontinuing medication for treatment-free remission (TFR). The European LeukemiaNet convened an expert panel to critically evaluate and update the evidence to achieve these goals since its previous recommendations. First-line treatment is a tyrosine kinase inhibitor (TKI; imatinib brand or generic, dasatinib, nilotinib, and bosutinib are available first-line). Generic imatinib is the cost-effective initial treatment in CP. Various contraindications and side-effects of all TKIs should be considered. Patient risk status at diagnosis should be assessed with the new EUTOS long-term survival (ELTS)-score. Monitoring of response should be done by quantitative polymerase chain reaction whenever possible. A change of treatment is recommended when intolerance cannot be ameliorated or when molecular milestones are not reached. Greater than 10% BCR-ABL1 at 3 months indicates treatment failure when confirmed. Allogeneic transplantation continues to be a therapeutic option particularly for advanced phase CML. TKI treatment should be withheld during pregnancy. Treatment discontinuation may be considered in patients with durable DMR with the goal of achieving TFR.

In 2019, the International Scientific Association for Probiotics and Prebiotics (ISAPP) convened a panel of experts specializing in nutrition, microbial physiology, gastroenterology, paediatrics, food science and microbiology to review the definition and scope of postbiotics. The term ‘postbiotics’ is increasingly found in the scientific literature and on commercial products, yet is inconsistently used and lacks a clear definition. The purpose of this panel was to consider the scientific, commercial and regulatory parameters encompassing this emerging term, propose a useful definition and thereby establish a foundation for future developments. The panel defined a postbiotic as a “preparation of inanimate microorganisms and/or their components that confers a health benefit on the host”. Effective postbiotics must contain inactivated microbial cells or cell components, with or without metabolites, that contribute to observed health benefits. The panel also discussed existing evidence of health-promoting effects of postbiotics, potential mechanisms of action, levels of evidence required to meet the stated definition, safety and implications for stakeholders. The panel determined that a definition of postbiotics is useful so that scientists, clinical triallists, industry, regulators and consumers have common ground for future activity in this area. A generally accepted definition will hopefully lead to regulatory clarity and promote innovation and the development of new postbiotic products. Postbiotics are emerging substances prepared from inactivated microorganisms, in contrast to probiotics, which must be administered alive. This Consensus Statement outlines a definition for the term ‘postbiotics’ as determined by an expert panel convened by the International Scientific Association for Probiotics and Prebiotics.

Clinical history, questionnaire data and response to antisecretory therapy are insufficient to make a conclusive diagnosis of GERD in isolation, but are of value in determining need for further investigation. Conclusive evidence for reflux on oesophageal testing include advanced grade erosive oesophagitis (LA grades C and D), long-segment Barrett’s mucosa or peptic strictures on endoscopy or distal oesophageal acid exposure time (AET) >6% on ambulatory pH or pH-impedance monitoring. A normal endoscopy does not exclude GERD, but provides supportive evidence refuting GERD in conjunction with distal AET <4% and <40 reflux episodes on pH-impedance monitoring off proton pump inhibitors. Reflux-symptom association on ambulatory reflux monitoring provides supportive evidence for reflux triggered symptoms, and may predict a better treatment outcome when present. When endoscopy and pH or pH-impedance monitoring are inconclusive, adjunctive evidence from biopsy findings (histopathology scores, dilated intercellular spaces), motor evaluation (hypotensive lower oesophageal sphincter, hiatus hernia and oesophageal body hypomotility on high-resolution manometry) and novel impedance metrics (baseline impedance, postreflux swallow-induced peristaltic wave index) can add confidence for a GERD diagnosis; however, diagnosis cannot be based on these findings alone. An assessment of anatomy, motor function, reflux burden and symptomatic phenotype will therefore help direct management. Future GERD management strategies should focus on defining individual patient phenotypes based on the level of refluxate exposure, mechanism of reflux, efficacy of clearance, underlying anatomy of the oesophagogastric junction and psychometrics defining symptomatic presentations.

Purpose For neurodevelopmental disorders (NDDs), etiological evaluation can be a diagnostic odyssey involving numerous genetic tests, underscoring the need to develop a streamlined algorithm maximizing molecular diagnostic yield for this clinical indication. Our objective was to compare the yield of exome sequencing (ES) with that of chromosomal microarray (CMA), the current first-tier test for NDDs. Methods We performed a PubMed scoping review and meta-analysis investigating the diagnostic yield of ES for NDDs as the basis of a consensus development conference. We defined NDD as global developmental delay, intellectual disability, and/or autism spectrum disorder. The consensus development conference included input from genetics professionals, pediatric neurologists, and developmental behavioral pediatricians. Results After applying strict inclusion/exclusion criteria, we identified 30 articles with data on molecular diagnostic yield in individuals with isolated NDD, or NDD plus associated conditions (such as Rett-like features). Yield of ES was 36% overall, 31% for isolated NDD, and 53% for the NDD plus associated conditions. ES yield for NDDs is markedly greater than previous studies of CMA (15–20%). Conclusion Our review demonstrates that ES consistently outperforms CMA for evaluation of unexplained NDDs. We propose a diagnostic algorithm placing ES at the beginning of the evaluation of unexplained NDDs.

ObjectiveTo update the European League Against Rheumatism (EULAR) recommendations for the pharmacological treatment of psoriatic arthritis (PsA).MethodsAccording to the EULAR standardised operating procedures, a systematic literature review was followed by a consensus meeting to develop this update involving 28 international taskforce members in May 2019. Levels of evidence and strengths of recommendations were determined.ResultsThe updated recommendations comprise 6 overarching principles and 12 recommendations. The overarching principles address the nature of PsA and diversity of both musculoskeletal and non-musculoskeletal manifestations; the need for collaborative management and shared decision-making is highlighted. The recommendations provide a treatment strategy for pharmacological therapies. Non-steroidal anti-inflammatory drugs and local glucocorticoid injections are proposed as initial therapy; for patients with arthritis and poor prognostic factors, such as polyarthritis or monoarthritis/oligoarthritis accompanied by factors such as dactylitis or joint damage, rapid initiation of conventional synthetic disease-modifying antirheumatic drugs is recommended. If the treatment target is not achieved with this strategy, a biological disease-modifying antirheumatic drugs (bDMARDs) targeting tumour necrosis factor (TNF), interleukin (IL)-17A or IL-12/23 should be initiated, taking into account skin involvement if relevant. If axial disease predominates, a TNF inhibitor or IL-17A inhibitor should be started as first-line disease-modifying antirheumatic drug. Use of Janus kinase inhibitors is addressed primarily after bDMARD failure. Phosphodiesterase-4 inhibition is proposed for patients in whom these other drugs are inappropriate, generally in the context of mild disease. Drug switches and tapering in sustained remission are addressed.ConclusionThese recommendations provide stakeholders with an updated consensus on the pharmacological management of PsA, based on a combination of evidence and expert opinion.

The CDC’s 2016 Guideline for Prescribing Opioids for Chronic Pain has largely been embraced by the medical and health policy communities. Unfortunately, some policies and practices purportedly derived from the guideline have been inconsistent with its recommendations.

Background The prominence of sedentary behavior research in health science has grown rapidly. With this growth there is increasing urgency for clear, common and accepted terminology and definitions. Such standardization is difficult to achieve, especially across multi-disciplinary researchers, practitioners, and industries. The Sedentary Behavior Research Network (SBRN) undertook a Terminology Consensus Project to address this need. Method First, a literature review was completed to identify key terms in sedentary behavior research. These key terms were then reviewed and modified by a Steering Committee formed by SBRN. Next, SBRN members were invited to contribute to this project and interested participants reviewed and provided feedback on the proposed list of terms and draft definitions through an online survey. Finally, a conceptual model and consensus definitions (including caveats and examples for all age groups and functional abilities) were finalized based on the feedback received from the 87 SBRN member participants who responded to the original invitation and survey. Results Consensus definitions for the terms physical inactivity, stationary behavior, sedentary behavior, standing, screen time, non-screen-based sedentary time, sitting, reclining, lying, sedentary behavior pattern, as well as how the terms bouts, breaks, and interruptions should be used in this context are provided. Conclusion It is hoped that the definitions resulting from this comprehensive, transparent, and broad-based participatory process will result in standardized terminology that is widely supported and adopted, thereby advancing future research, interventions, policies, and practices related to sedentary behaviors.

Core outcome sets (COS) can enhance the relevance of research by ensuring that outcomes of importance to health service users and other people making choices about health care in a particular topic area are measured routinely. Over 200 COS to date have been developed, but the clarity of these reports is suboptimal. COS studies will not achieve their goal if reports of COS are not complete and transparent. In recognition of these issues, an international group that included experienced COS developers, methodologists, journal editors, potential users of COS (clinical trialists, systematic reviewers, and clinical guideline developers), and patient representatives developed the Core Outcome Set-STAndards for Reporting (COS-STAR) Statement as a reporting guideline for COS studies. The developmental process consisted of an initial reporting item generation stage and a two-round Delphi survey involving nearly 200 participants representing key stakeholder groups, followed by a consensus meeting. The COS-STAR Statement consists of a checklist of 18 items considered essential for transparent and complete reporting in all COS studies. The checklist items focus on the introduction, methods, results, and discussion section of a manuscript describing the development of a particular COS. A limitation of the COS-STAR Statement is that it was developed without representative views of low- and middle-income countries. COS have equal relevance to studies conducted in these areas, and, subsequently, this guideline may need to evolve over time to encompass any additional challenges from developing COS in these areas. With many ongoing COS studies underway, the COS-STAR Statement should be a helpful resource to improve the reporting of COS studies for the benefit of all COS users.

[...]the universal use of the TNM classification has made it a subject of unreasonable expectation. To better define the principles of the TNM classification, a Global Consultation on Cancer Staging was held under the auspices of the Union for International Cancer Control (UICC) and The Lancet Oncology with support from the US National Cancer Institute (NCI) and the US Centers for Disease Control and Prevention (CDC). The views in this Comment are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention or of the National Cancer Institute. 1 JD Brierley, MK Gospodarowicz, C Wittekind, The TNM classification of malignant tumours, 8th edn., 2017, Wiley Blackwell, Oxford 2 MB Amin, S Edge, F Greene, AJCC cancer staging manual, 8th edn., 2017, Springer, New York 3 JD Brierley, JR Srigley, M Yurcan, The value of collecting population-based cancer stage data to support decision-making at organizational, regional and population levels, Healthc Q, Vol. 16, 2013, 27-33 4 M Piñeros, A Znaor, L Mery, F Bray, A global cancer surveillance framework within noncommunicable disease surveillance: making the case for population-based cancer registries, Epidemiol Rev, Vol. 39, 2017, 161-169 5 JD Brierley, MK Gospodarowicz,...

Dysphagia is estimated to affect ~8% of the world’s population (~590 million people). Texture-modified foods and thickened drinks are commonly used to reduce the risks of choking and aspiration. The International Dysphagia Diet Standardisation Initiative (IDDSI) was founded with the goal of developing globally standardized terminology and definitions for texture-modified foods and liquids applicable to individuals with dysphagia of all ages, in all care settings, and all cultures. A multi-professional volunteer committee developed a dysphagia diet framework through systematic review and stakeholder consultation. First, a survey of existing national terminologies and current practice was conducted, receiving 2050 responses from 33 countries. Respondents included individuals with dysphagia; their caregivers; organizations supporting individuals with dysphagia; healthcare professionals; food service providers; researchers; and industry. The results revealed common use of 3–4 levels of food texture (54 different names) and ≥3 levels of liquid thickness (27 different names). Substantial support was expressed for international standardization. Next, a systematic review regarding the impact of food texture and liquid consistency on swallowing was completed. A meeting was then convened to review data from previous phases, and develop a draft framework. A further international stakeholder survey sought feedback to guide framework refinement; 3190 responses were received from 57 countries. The IDDSI Framework (released in November, 2015) involves a continuum of 8 levels (0–7) identified by numbers, text labels, color codes, definitions, and measurement methods. The IDDSI Framework is recommended for implementation throughout the world.