Search

The biomedical research community addresses reproducibility challenges in animal studies through standardized nomenclature, improved experimental design, transparent reporting, data sharing, and centralized repositories. The ARRIVE guidelines outline documentation standards for laboratory animals in experiments, but genetic information is often incomplete. To remedy this, we propose the Laboratory Animal Genetic Reporting (LAG-R) framework. LAG-R aims to document animals genetic makeup in scientific publications, providing essential details for replication and appropriate model use. While verifying complete genetic compositions may be impractical, better reporting and validation efforts enhance reliability of research. LAG-R standardization will bolster reproducibility, peer review, and overall scientific rigor.

Abstract Background Less than half of community pharmacies in the United States stock buprenorphine products indicated for the treatment of opioid use disorder. This lack of access to buprenorphine in community pharmacies is a significant barrier to care. To address this issue, this protocol outlines a comprehensive approach to develop a practice guideline aimed at improving access to safe and effective opioid use disorder treatment in community pharmacies. Methods The guideline development process will proceed in three phases, following a technique closely aligned with the Institute of Medicine’s guidance on guideline development. The first phase will involve conducting qualitative interviews with pharmacists in three states to identify their beliefs toward buprenorphine dispensing. As limitations on buprenorphine supply are related to constraints at all levels of the drug supply and regulatory system, the second phase, we will recruit representatives from regulatory agencies, pharmacy organizations, the Drug Enforcement Administration, pharmaceutical wholesalers as well as addiction medicine physicians and psychiatric pharmacists to develop consensus recommendations through a modified Delphi design. This will be followed by a public comment period and external expert review of the recommendations led by the National Association of Boards of Pharmacy. Finally, in the third phase, a national, mixed media dissemination campaign will be led by the National Community Pharmacists Association (NCPA) to convey recommendations to practicing pharmacists. Discussion The guideline development process aims to incorporate the perspectives of multiple stakeholders and emphasize the importance of addressing the regulatory and pharmacy-specific aspects of care in addition to clinical evidence and guidance. The development of this guideline will provide targeted, multidisciplinary guidance for pharmacists, improving access to safe and effective opioid use disorder treatment in the community setting. Preregistration This protocol was registered with the Open Science Framework in March of 2023. Registration may be found at: https://doi.org/10.17605/OSF.IO/6S9DY .

Introduction: Hypertensive disorders of pregnancy (HDP) affect up to 10% of all pregnancies annually and are associated with an increased risk of maternal and fetal morbidity and mortality. This guideline represents an update of the Society of Obstetric Medicine of Australia and New Zealand (SOMANZ) guidelines for the management of hypertensive disorders of pregnancy 2014 and has been approved by the National Health and Medical Research Council (NHMRC) under section 14A of the National Health and Medical Research Council Act 1992. In approving the guideline recommendations, NHMRC considers that the guideline meets NHMRC's standard for clinical practice guidelines. Main recommendations: A total of 39 recommendations on screening, preventing, diagnosing and managing HDP, especially preeclampsia, are presented in this guideline. Recommendations are presented as either evidence‐based recommendations or practice points. Evidence‐based recommendations are presented with the strength of recommendation and quality of evidence. Practice points were generated where there was inadequate evidence to develop specific recommendations and are based on the expertise of the working group. Changes in management resulting from the guideline: This version of the SOMANZ guideline was developed in an academically robust and rigorous manner and includes recommendations on the use of combined first trimester screening to identify women at risk of developing preeclampsia, 14 pharmacological and two non‐pharmacological preventive interventions, clinical use of angiogenic biomarkers and the long term care of women who experience HDP. The guideline also includes six multilingual patient infographics which can be accessed through the main website of the guideline. All measures were taken to ensure that this guideline is applicable and relevant to clinicians and multicultural women in regional and metropolitan settings in Australia and New Zealand. [ABSTRACT FROM AUTHOR]

Objectives: to identify content on play and interaction with children with special health care needs recommended in clinical guidelines; analyze play and interaction activities applicable to children with special health care needs and complex care requirements. Method: qualitative documentary research based on guides, protocols, or guidelines on playing and interacting with children with special and living with complex care. Search terms in English (guidelines, playing OR play, complex needs, OR chronic disease) and in Portuguese ( guia, brincar ou brincadeiras, condições crônicas ) on the first ten pages of_Google Search ® . Thematic analysis was applied to the information extracted from the documents. Results: a total of nine documents with similar content were grouped into units of analysis, keeping only the interacting and playing activities applicable to children with special health care needs and living with complex care requirements, namely stimulation of potential, stimulation of adult-child interaction, and stimulation of the senses (touch, sight, and hearing), to be carried out by health professionals and family caregivers in the different care contexts. Conclusion: interaction and play are potential promoters of adult-child interaction, with application in the stimulating and life-delivering complex care for children.

Immune-related adverse events (irAEs) associated with immune checkpoint inhibitor (ICI) therapy may vary substantially in their clinical presentation, including natural history, outcomes to treatment, and patterns. The application of clinical guidelines for irAE management can be challenging for practitioners due to a lack of common or consistently applied terminology. Furthermore, given the growing body of clinical experience and published data on irAEs, there is a greater appreciation for the heterogeneous natural histories, responses to treatment, and patterns of these toxicities, which is not currently reflected in irAE guidelines. Furthermore, there are no prospective trial data to inform the management of the distinct presentations of irAEs. Recognizing a need for uniform terminology for the natural history, response to treatment, and patterns of irAEs, the Society for Immunotherapy of Cancer (SITC) convened a consensus panel composed of leading international experts from academic medicine, industry, and regulatory agencies. Using a modified Delphi consensus process, the expert panel developed clinical definitions for irAE terminology used in the literature, encompassing terms related to irAE natural history (ie, re-emergent, chronic active, chronic inactive, delayed/late onset), response to treatment (ie, steroid unresponsive, steroid dependent), and patterns (ie, multisystem irAEs). SITC developed these definitions to support the adoption of a standardized vocabulary for irAEs, which will have implications for the uniform application of irAE clinical practice guidelines and to enable future irAE clinical trials.

ABSTRACTBackground eLearning can be an effective tool to achieve learning objectives. It facilitates asynchronous distance learning, increasing flexibility for learners and instructors. In this context, the high educational value of videos provides an invaluable primary component for longitudinal digital curricula, especially for maintaining knowledge on otherwise rarely taught subjects. Although literature concerning eLearning evaluation exists, research comprehensively describing how to design effective educational videos is lacking. In particular, studies on the requirements and design goals of educational videos need to be complemented by qualitative research using grounded theory methodology.Methods Due to the paucity of randomized controlled trials in this area, there is an urgent need to generate recommendations based on a broader fundament than a literature search alone. Thus, the authors have employed grounded theory as a guiding framework, augmented by Mayring’s qualitative content analysis and commonly used standards. An adaptive approach was conducted based on a literature search and qualitative semi-structured interviews. Drawing on these results, the authors elaborated a guide for creating effective educational videos.Results The authors identified 40 effective or presumedly effective factors fostering the success of video-based eLearning in teaching evidence-based medicine, providing a ready-to-use checklist. The information collected via the interviews supported and enriched much of the advice found in the literature.Discussion To the authors’ knowledge, this type of comprehensive guide for video-based eLearning needs has not previously been published. The interviews considerably contributed to the results. Due to the grounded theory-based approach, in particular, consensus was achieved without the presence of a formal expert panel. Although the guide was created with a focus on teaching evidence-based medicine, due to the general study selection process and research approach, the recommendations are applicable to a wide range of subjects in medical education where the teaching aim is to impart conceptual knowledge.

Introduction: Electronic cigarette (e‐cigarette) use in Australia has rapidly increased since the 2017 National Health and Medical Research Council (NHMRC) Chief Executive Officer (CEO) statement on e‐cigarettes. The type of products available and the demographic characteristics of people using these products have changed. New evidence has been published and there is growing concern among public health professionals about the increased use, particularly among young people who do not currently smoke combustible cigarettes. The combination of these issues led NHMRC to review the current evidence and provide an updated statement on e‐cigarettes. In this article, we describe the comprehensive process used to review the evidence and develop the 2022 NHMRC CEO statement on electronic cigarettes. Main recommendations: E‐cigarettes can be harmful; all e‐cigarette users are exposed to chemicals and toxins that have the potential to cause adverse health effects.There are no health benefits of using e‐cigarettes if you do not currently smoke tobacco cigarettes.Adolescents are more likely to try e‐cigarettes if they are exposed to e‐cigarettes on social media.Short term e‐cigarette use may help some smokers to quit who have been previously unsuccessful with other smoking cessation aids. There are other proven safe and effective options available to help smokers to quit. Changes in management as a result of this statement: The evidence base for the harms of e‐cigarette use has strengthened since the previous NHMRC statement. Significant gaps in the evidence base remain, especially about the longer term health harms of using e‐cigarettes and the toxicity of many chemicals in e‐cigarettes inhaled as an aerosol. [ABSTRACT FROM AUTHOR]

Introduction: Cough is the most common symptom leading to medical consultation. Chronic cough results in significant health care costs, impairs quality of life, and may indicate the presence of a serious underlying condition. Here, we present a summary of an updated position statement on cough management in the clinical consultation. Main recommendations: Assessment of children and adults requires a focused history of chronic cough to identify any red flag cough pointers that may indicate an underlying disease. Further assessment with examination should include a chest x‐ray and spirometry (when age > 6 years). Separate paediatric and adult diagnostic management algorithms should be followed. Management of the underlying condition(s) should follow specific disease guidelines, as well as address adverse environmental exposures and patient/carer concerns. First Nations adults and children should be considered a high risk group. The full statement from the Thoracic Society of Australia and New Zealand and Lung Foundation Australia for managing chronic cough is available at https://lungfoundation.com.au/resources/cicada‐full‐position‐statement. Changes in management as a result of this statement: Algorithms for assessment and diagnosis of adult and paediatric chronic cough are recommended.High quality evidence supports the use of child‐specific chronic cough management algorithms to improve clinical outcomes, but none exist in adults.Red flags that indicate serious underlying conditions requiring investigation or referral should be identified.Early and effective treatment of chronic wet/productive cough in children is critical.Culturally specific strategies for facilitating the management of chronic cough in First Nations populations should be adopted.If the chronic cough does not resolve or is unexplained, the patient should be referred to a respiratory specialist or cough clinic. [ABSTRACT FROM AUTHOR]

Objectives: To assess associations between breast cancer‐specific survival and timeliness of treatment, based on 2020 Australian guidelines for the treatment of early breast cancer. Design: Population‐based cohort study; analysis of linked Queensland Cancer Register, patient medical record, and National Death Index data, supplemented by telephone interviews. Setting, participants: Women aged 20–79 years diagnosed with invasive breast cancer during 1 March 2010 – 30 June 2013, followed to 31 December 2020. Main outcome measures: Breast cancer‐specific survival for women who received or did not receive treatment within the recommended timeframe, overall and for six treatment intervals; optimal cut‐points for each treatment interval; characteristics of women for whom treatment was not provided within the recommended timeframe. Results: Of 5426 eligible women, 4762 could be invited for interviews; complete data were available for 3044 women (56% of eligible women, 65% of invited women). Incomplete compliance with guideline interval recommendations was identified for 1375 women (45%); their risk of death from breast cancer during the follow‐up period was greater than for those for whom guideline compliance was complete (adjusted hazard ratio [aHR], 1.43; 95% confidence interval [CI], 1.04–1.96). Risk of death was greater for women for whom the diagnosis to surgery interval exceeded 29 days (aHR, 1.76; 95% CI, 1.19–2.59), the surgery to chemotherapy interval exceeded 36 days (aHR, 1.63; 95% CI, 1.13–2.36), or the chemotherapy to radiotherapy interval exceeded 31 days (aHR, 1.83; 95% CI, 1.19–2.80). Treatment intervals longer than recommended were more frequent for women for whom breast cancer was detected by public facility screening (adjusted odds ratio [aOR], 1.58; 95% CI, 1.22–2.04) or by symptoms (aOR, 1.39; 95% CI, 1.09–1.79) than when cancer had been detected in private facilities, and for women without private health insurance (aOR, 1.96; 95% CI, 1.66–2.32) or living outside major cities (aOR, 1.38; 95% CI, 1.18–1.62). Conclusions: Breast cancer‐specific survival was poorer for women for whom the diagnosis to surgery, surgery to chemotherapy, or chemotherapy to radiotherapy intervals exceeded guideline‐recommended limits. Our findings support 2020 Australian guideline recommendations regarding timely care. [ABSTRACT FROM AUTHOR]

To assess the consistency of return to sport and occupation recommendations following EHI provided in published clinical practice guidelines, consensus statements, position statements, and practice alerts. The agreement between medical policies governing the return to duty following EHI between the branches of the United States Armed Forces and published recommendations was assessed. Ovid MEDLINE, Web of Science, and CINAHL databases were searched for clinical practice guidelines and position statements published at any time that guided return to activity in individuals with EHI. Methodological quality was assessed, and the specific recommendations for clinical management were extracted. Consistency of recommendations was evaluated. Agreement between published guidelines and the policies governing return to activity in military tactical athletes with heat injury were also evaluated. Guidelines developed by two civilian sports medicine societies in the United States detailing recommendations for return to function following EHI were identified. There was consistency between guidelines regarding recommendations that addressed abstinence from activity; medical follow-up; graded resumption of activity; and return to function. Pertaining military policy, contemporary regulations published in recent years reflected the recommendations provided in the professional guidelines. The greatest incongruence was noted in older military policies. This systematic review highlights the need for consistent recommendations across all branches of the military and medical specialties pertaining to returning servicemembers to duty after EHI. [ABSTRACT FROM AUTHOR]

Introduction: First Nations Australians display remarkable strength and resilience despite the intergenerational impacts of ongoing colonisation. The continuing disadvantage is evident in the higher incidence, prevalence, morbidity and mortality of chronic kidney disease (CKD) among First Nations Australians. Nationwide community consultation (Kidney Health Australia, Yarning Kidneys, and Lowitja Institute, Catching Some Air) identified priority issues for guideline development. These guidelines uniquely prioritised the knowledge of the community, alongside relevant evidence using an adapted GRADE Evidence to Decision framework to develop specific recommendations for the management of CKD among First Nations Australians. Main recommendations: These guidelines explicitly state that health systems have to measure, monitor and evaluate institutional racism and link it to cultural safety training, as well as increase community and family involvement in clinical care and equitable transport and accommodation. The guidelines recommend earlier CKD screening criteria (age ≥ 18 years) and referral to specialists services with earlier criteria of kidney function (eg, estimated glomerular filtration rate [eGFR], ≤ 45 mL/min/1.73 m2, and a sustained decrease in eGFR, > 10 mL/min/1.73 m2 per year) compared with the general population. Changes in management as result of the guidelines: Our recommendations prioritise health care service delivery changes to address institutional racism and ensure meaningful cultural safety training. Earlier detection of CKD and referral to nephrologists for First Nations Australians has been recommended to ensure timely implementation to preserve kidney function given the excess burden of disease. Finally, the importance of community with the recognition of involvement in all aspects and stages of treatment together with increased access to care on Country, particularly in rural and remote locations, including dialysis services. [ABSTRACT FROM AUTHOR]

Human-induced salinization caused by the use of road deicing salts, agricultural practices, mining operations, and climate change is a major threat to the biodiversity and functioning of freshwater ecosystems. Yet, it is unclear if freshwater ecosystems are protected from salinization by current water quality guidelines. Leveraging an experimental network of land-based and in-lake mesocosms across North America and Europe, we tested how salinization-indicated as elevated chloride (Cl-) concentration-will affect lake food webs and if two of the lowest Cl- thresholds found globally are sufficient to protect these food webs. Our results indicated that salinization will cause substantial zooplankton mortality at the lowest Cl- thresholds established in Canada (120 mg Cl-/L) and the United States (230 mg Cl-/L) and throughout Europe where Cl- thresholds are generally higher. For instance, at 73% of our study sites, Cl- concentrations that caused a ≥50% reduction in cladoceran abundance were at or below Cl- thresholds in Canada, in the United States, and throughout Europe. Similar trends occurred for copepod and rotifer zooplankton. The loss of zooplankton triggered a cascading effect causing an increase in phytoplankton biomass at 47% of study sites. Such changes in lake food webs could alter nutrient cycling and water clarity and trigger declines in fish production. Current Cl- thresholds across North America and Europe clearly do not adequately protect lake food webs. Water quality guidelines should be developed where they do not exist, and there is an urgent need to reassess existing guidelines to protect lake ecosystems from human-induced salinization.

BackgroundPilot studies test the feasibility of methods and procedures to be used in larger-scale studies. Although numerous articles describe guidelines for the conduct of pilot studies, few have included specific feasibility indicators or strategies for evaluating multiple aspects of feasibility. In addition, using pilot studies to estimate effect sizes to plan sample sizes for subsequent randomized controlled trials has been challenged; however, there has been little consensus on alternative strategies.MethodsIn Section 1, specific indicators (recruitment, retention, intervention fidelity, acceptability, adherence, and engagement) are presented for feasibility assessment of data collection methods and intervention implementation. Section 1 also highlights the importance of examining feasibility when adapting an intervention tested in mainstream populations to a new more diverse group. In Section 2, statistical and design issues are presented, including sample sizes for pilot studies, estimates of minimally important differences, design effects, confidence intervals (CI) and nonparametric statistics. An in-depth treatment of the limits of effect size estimation as well as process variables is presented. Tables showing CI around parameters are provided. With small samples, effect size, completion and adherence rate estimates will have large CI.ConclusionThis commentary offers examples of indicators for evaluating feasibility, and of the limits of effect size estimation in pilot studies. As demonstrated, most pilot studies should not be used to estimate effect sizes, provide power calculations for statistical tests or perform exploratory analyses of efficacy. It is hoped that these guidelines will be useful to those planning pilot/feasibility studies before a larger-scale study.

The global burden of the endemic mycoses (blastomycosis, coccidioidomycosis, emergomycosis, histoplasmosis, paracoccidioidomycosis, sporotrichosis, and talaromycosis) continues to rise yearly and these infectious diseases remain a leading cause of patient morbidity and mortality worldwide. Management of the associated pathogens requires a thorough understanding of the epidemiology, risk factors, diagnostic methods and performance characteristics in different patient populations, and treatment options unique to each infection. Guidance on the management of these infections has the potential to improve prognosis. The recommendations outlined in this Review are part of the "One World, One Guideline" initiative of the European Confederation of Medical Mycology. Experts from 23 countries contributed to the development of these guidelines. The aim of this Review is to provide an up-to-date consensus and practical guidance in clinical decision making, by engaging physicians and scientists involved in various aspects of clinical management.

BackgroundPatient-level and community-level social and economic conditions impact hypertension risk and control. We examined adult hypertension management guidelines to explore whether and how existing guidelines refer to social care activities.ObjectiveThe objective of this study was to explore how hypertension guidelines reference social care activities.Research designA systematic scoping review of clinical guidelines for adult hypertension management. We employed a PubMed search strategy to identify all hypertension guidelines published in the United States between 1977 and 2019. We reviewed all titles to identify the most updated versions focused on nonpregnant adults with hypertension. We extracted instances where guidelines referred to social determinants of health (SDH) or social care activities. The primary outcome was how guidelines covered social care activities, defined using a framework adapted from the National Academies of Sciences, Engineering, and Medicine (NASEM).ResultsSearch terms yielded 126 guidelines. Thirty-six guidelines met the inclusion criteria. Of those, 72% (26/36) recommended social care activities as part of hypertension management; 58% recommended clinicians change clinical practice based on social risk information. These recommendations often lacked specific guidance around how to directly address social risk factors or reduce the impact of these risks on hypertension management. When guidelines referred to specific social factors, patient financial security was the most common. Over time, hypertension guidelines have included more references to SDH.ConclusionInformation about SDH is included in many hypertension guidelines, but few guidelines provide clear guidance for clinicians or health systems on how to identify and address social risk factors in the context of care delivery.

Objective To evaluate the most preferred style of online didactic lectures. The COVID-19 pandemic has had a significant impact on surgical resident education, instigating a major shift towards online webinar didactics as a major of resident teaching. We hypothesize that a case-based format of online didactics are the most preferred format for this style of lecture. Study Design We analyzed viewer evaluations following 82 online hour-long lectures in the Urology Collaborative Online Video Didactics Lecture Series. We categorized each lecture as case-based, guidelines-based, practice updates, or surgical technique-based and assessed viewer responses to survey questions regarding subject area relevance, lecturer knowledgeability, lecturer effectiveness, and usefulness to learning. We performed logistic regression to control for viewer level, instructor level, and lecture topic, and using surgical technique-based lectures as the baseline variable. Results 2176 evaluations were analyzed. Case-based, guidelines-based and practice updates were all scored significantly higher than surgical technique for subject area relevance. Case-based and guideline-based lectures scored significantly higher for usefulness to learning. Case-based lectures scored significantly higher for lecturer effectiveness. There was no significant difference in scoring between any lecture style when rated on lecturer knowledgeability. Conclusion When preparing online webinar based didactics for surgical resident education, case-based lecturers appear to be the most preferred and well received lecture style, followed closely by guidelines-based lectures. Practice updates and surgical technique-based lectures are less preferred formats for this teaching modality.

We are a group of archaeologists, anthropologists, curators and geneticists representing diverse global communities and 31 countries. All of us met in a virtual workshop dedicated to ethics in ancient DNA research held in November 2020. There was widespread agreement that globally applicable ethical guidelines are needed, but that recent recommendations grounded in discussion about research on human remains from North America are not always generalizable worldwide. Here we propose the following globally applicable guidelines, taking into consideration diverse contexts. These hold that: (1) researchers must ensure that all regulations were followed in the places where they work and from which the human remains derived; (2) researchers must prepare a detailed plan prior to beginning any study; (3) researchers must minimize damage to human remains; (4) researchers must ensure that data are made available following publication to allow critical re-examination of scientific findings; and (5) researchers must engage with other stakeholders from the beginning of a study and ensure respect and sensitivity to stakeholder perspectives. We commit to adhering to these guidelines and expect they will promote a high ethical standard in DNA research on human remains going forward.

ImportanceEvidence-based guidance is limited on how clinicians should screen for social risk factors and which interventions related to these risk factors improve health outcomes.ObjectiveTo describe research on screening and interventions for social risk factors to inform US Preventive Services Task Force considerations of the implications for its portfolio of recommendations.Data sourcesCochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Ovid MEDLINE, Sociological Abstracts, and Social Services Abstracts (through 2018); Social Interventions Research and Evaluation Network evidence library (January 2019 through May 2021); surveillance through May 21, 2021; interviews with 17 key informants.Study selectionIndividual-level and health care system-level interventions with a link to the health care system that addressed at least 1 of 7 social risk domains: housing instability, food insecurity, transportation difficulties, utility needs, interpersonal safety, education, and financial strain.Data extraction and synthesisOne investigator abstracted data from studies and a second investigator evaluated data abstractions for completeness and accuracy; key informant interviews were recorded, transcribed, summarized, and integrated with evidence from the literature; narrative synthesis with supporting tables and figures.Main outcomes and measuresValidity of multidomain social risk screening tools; all outcomes reported for social risk-related interventions; challenges or unintended consequences of screening and interventions.ResultsMany multidomain social risk screening tools have been developed, but they vary widely in their assessment of social risk and few have been validated. This technical brief identified 106 social risk intervention studies (N = 5 978 596). Of the interventions studied, 73 (69%; n = 127 598) addressed multiple social risk domains. The most frequently addressed domains were food insecurity (67/106 studies [63%], n = 141 797), financial strain (52/106 studies [49%], n = 111 962), and housing instability (63/106 studies [59%], n = 5 881 222). Food insecurity, housing instability, and transportation difficulties were identified by key informants as the most important social risk factors to identify in health care. Thirty-eight studies (36%, n = 5 850 669) used an observational design with no comparator, and 19 studies (18%, n = 15 205) were randomized clinical trials. Health care utilization measures were the most commonly reported outcomes in the 68 studies with a comparator (38 studies [56%], n = 111 102). The literature and key informants described many perceived or potential challenges to implementation of social risk screening and interventions in health care.Conclusions and relevanceMany interventions to address food insecurity, financial strain, and housing instability have been studied, but more randomized clinical trials that report health outcomes from social risk screening and intervention are needed to guide widespread implementation in health care.

Missing data is a persistent and unavoidable problem in even the most carefully designed traumatic brain injury (TBI) clinical research. Missing data patterns may result from participant dropout, non-compliance, technical issues, or even death. This review describes the types of missing data that are common in TBI research, and assesses the strengths and weaknesses of the statistical approaches used to draw conclusions and make clinical decisions from these data. We review recent innovations in missing values analysis (MVA), a relatively new branch of statistics, as applied to clinical TBI data. Our discussion focuses on studies from the International Traumatic Brain Injury Research (InTBIR) initiative project: Transforming Research and Clinical Knowledge in TBI (TRACK-TBI), Collaborative Research on Acute TBI in Intensive Care Medicine in Europe (CREACTIVE), and Approaches and Decisions in Acute Pediatric TBI Trial (ADAPT). In addition, using data from the TRACK-TBI pilot study (n = 586) and the completed clinical trial assessing valproate (VPA) for the treatment of post-traumatic epilepsy (n = 379) we present real-world examples of typical missing data patterns and the application of statistical techniques to mitigate the impact of missing data in order to draw sound conclusions from ongoing clinical studies.

Patients with advanced hepatocellular carcinoma (HCC) have historically had few options and faced extremely poor prognoses if their disease progressed after standard-of-care tyrosine kinase inhibitors (TKIs). Recently, the standard of care for HCC has been transformed as a combination of the immune checkpoint inhibitor (ICI) atezolizumab plus the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab was shown to offer improved overall survival in the first-line setting. Immunotherapy has demonstrated safety and efficacy in later lines of therapy as well, and ongoing trials are investigating novel combinations of ICIs and TKIs, in addition to interventions earlier in the course of disease or in combination with liver-directed therapies. Because HCC usually develops against a background of cirrhosis, immunotherapy for liver tumors is complex and oncologists need to account for both immunological and hepatological considerations when developing a treatment plan for their patients. To provide guidance to the oncology community on important concerns for the immunotherapeutic care of HCC, the Society for Immunotherapy of Cancer (SITC) convened a multidisciplinary panel of experts to develop a clinical practice guideline (CPG). The expert panel drew on the published literature as well as their clinical experience to develop recommendations for healthcare professionals on these important aspects of immunotherapeutic treatment for HCC, including diagnosis and staging, treatment planning, immune-related adverse events (irAEs), and patient quality of life (QOL) considerations. The evidence- and consensus-based recommendations in this CPG are intended to give guidance to cancer care providers treating patients with HCC.

Family engagement is a key component of high-quality critical care, with known benefits for patients, care teams, and family members themselves. The COVID-19 pandemic led to rapid enactment of prohibitions or restrictions on visitation that now persist, particularly for patients with COVID-19. Reevaluation of these policies in response to advances in knowledge and resources since the early pandemic is critical because COVID-19 will continue to be a public health threat for months to years, and future pandemics are likely. This article reviews rationales and evidence for restricting or permitting family members' physical presence and provides broad guidance for health care systems to develop and implement policies that maximize benefit and minimize risk of family visitation during COVID-19 and future similar public health crises.

Breast cancer has historically been a disease for which immunotherapy was largely unavailable. Recently, the use of immune checkpoint inhibitors (ICIs) in combination with chemotherapy for the treatment of advanced/metastatic triple-negative breast cancer (TNBC) has demonstrated efficacy, including longer progression-free survival and increased overall survival in subsets of patients. Based on clinical benefit in randomized trials, ICIs in combination with chemotherapy for the treatment of some patients with advanced/metastatic TNBC have been approved by the United States (US) Food and Drug Administration (FDA), expanding options for patients. Ongoing questions remain, however, about the optimal chemotherapy backbone for immunotherapy, appropriate biomarker-based selection of patients for treatment, the optimal strategy for immunotherapy treatment in earlier stage disease, and potential use in histological subtypes other than TNBC. To provide guidance to the oncology community on these and other important concerns, the Society for Immunotherapy of Cancer (SITC) convened a multidisciplinary panel of experts to develop a clinical practice guideline (CPG). The expert panel drew upon the published literature as well as their clinical experience to develop recommendations for healthcare professionals on these important aspects of immunotherapeutic treatment for breast cancer, including diagnostic testing, treatment planning, immune-related adverse events (irAEs), and patient quality of life (QOL) considerations. The evidence-based and consensus-based recommendations in this CPG are intended to give guidance to cancer care providers treating patients with breast cancer.

Objectives: To report stage‐specific patterns of treatment and the influence of management and treatment type on survival rates for people newly diagnosed with small cell lung cancer (SCLC). Design: Cross‐sectional patterns of care study; analysis of data prospectively collected for the Victorian Lung Cancer Registry (VLCR). Setting, participants: All people diagnosed with SCLC in Victoria during 1 April 2011 – 18 December 2019. Main outcome measures: Stage‐specific management and treatment of people with SCLC; median survival time. Results: During 2011–19, 1006 people were diagnosed with SCLC (10.5% of all lung cancer diagnoses in Victoria); their median age was 69 years (interquartile range [IQR], 62–77 years), 429 were women (43%), and 921 were current or former smokers (92%). Clinical stage was defined for 896 people (89%; TNM stages I–III, 268 [30%]; TNM stage IV, 628 [70%]) and ECOG performance status at diagnosis for 663 (66%; 0 or 1, 489 [49%]; 2–4, 174 [17%]). The cases of 552 patients had been discussed at multidisciplinary meetings (55%), 377 people had received supportive care screening (37%), and 388 had been referred for palliative care (39%). Active treatment was received by 891 people (89%): chemotherapy, 843 (84%); radiotherapy, 460 (46%); chemotherapy and radiotherapy, 419 (42%); surgery, 23 (2%). Treatment had commenced within fourteen days of diagnosis for 632 of 875 patients (72%). Overall median survival time from diagnosis was 8.9 months (IQR, 4.2–16 months; stage I–III: 16.3 [IQR, 9.3–30] months; stage IV: 7.2 [IQR, 3.3–12] months). Multidisciplinary meeting presentation (hazard ratio [HR], 0.66; 95% CI, 0.58–0.77), multimodality treatment (HR, 0.42; 95% CI, 0.36–0.49), and chemotherapy within fourteen days of diagnosis (HR, 0.68; 95% CI, 0.48–0.94) were each associated with lower mortality during follow‐up. Conclusion: Rates of supportive care screening, multidisciplinary meeting evaluation, and palliative care referral for people with SCLC could be improved. A national registry of SCLC‐specific management and outcomes data could improve the quality and safety of care. [ABSTRACT FROM AUTHOR]

Summary: This article reviews the risk equations recommended for use in international cardiovascular disease (CVD) primary prevention guidelines and assesses their suitability for use in Australia against a set of a priori defined selection criteria.The review and assessment were commissioned by the National Heart Foundation of Australia on behalf of the Australian Chronic Disease Prevention Alliance to inform recommendations on CVD risk estimation as part of the 2023 update of the Australian CVD risk assessment and management guidelines.Selected international risk equations were assessed against eight selection criteria: development using contemporary data; inclusion of established cardiovascular risk factors; inclusion of ethnicity and deprivation measures; prediction of a broad selection of fatal and non‐fatal CVD outcomes; population representativeness; model performance; external validation in an Australian dataset; and the ability to be recalibrated or modified.Of the ten risk prediction equations reviewed, the New Zealand PREDICT equation met seven of the eight selection criteria, and met additional usability criteria aimed at assessing the ability to apply the risk equation in practice in Australia. [ABSTRACT FROM AUTHOR]

Introduction: Long term opioids are commonly prescribed to manage pain. Dose reduction or discontinuation (deprescribing) can be challenging, even when the potential harms of continuation outweigh the perceived benefits. The Evidence‐based clinical practice guideline for deprescribing opioid analgesics was developed using robust guideline development processes and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology, and contains deprescribing recommendations for adults prescribed opioids for pain. Main recommendations: Eleven recommendations provide advice about when, how and for whom opioid deprescribing should be considered, while noting the need to consider each person's goals, values and preferences. The recommendations aim to achieve: implementation of a deprescribing plan at the point of opioid initiation;initiation of opioid deprescribing for persons with chronic non‐cancer or chronic cancer‐survivor pain if there is a lack of overall and clinically meaningful improvement in function, quality of life or pain, a lack of progress towards meeting agreed therapeutic goals, or the person is experiencing serious or intolerable opioid‐related adverse effects;gradual and individualised deprescribing, with regular monitoring and review;consideration of opioid deprescribing for individuals at high risk of opioid‐related harms;avoidance of opioid deprescribing for persons nearing the end of life unless clinically indicated;avoidance of opioid deprescribing for persons with a severe opioid use disorder, with the initiation of evidence‐based care, such as medication‐assisted treatment of opioid use disorder; anduse of evidence‐based co‐interventions to facilitate deprescribing, including interdisciplinary, multidisciplinary or multimodal care. Changes in management as a result of these guidelines: To our knowledge, these are the first evidence‐based guidelines for opioid deprescribing. The recommendations intend to facilitate safe and effective deprescribing to improve the quality of care for persons taking opioids for pain. [ABSTRACT FROM AUTHOR]

Building ventilation systems must get much better

Aducanumab has been approved by the US Food and Drug Administration for treatment of Alzheimer's disease (AD). Clinicians require guidance on the appropriate use of this new therapy. An Expert Panel was assembled to construct Appropriate Use Recommendations based on the participant populations, conduct of the pivotal trials of aducanumab, updated Prescribing Information, and expert consensus. Aducanumab is an amyloid-targeting monoclonal antibody delivered by monthly intravenous infusions. The pivotal trials included patients with early AD (mild cognitive impairment due to AD and mild AD dementia) who had confirmed brain amyloid using amyloid positron tomography. The Expert Panel recommends that use of aducanumab be restricted to this population in which efficacy and safety have been studied. Aducanumab is titrated to a dose of 10 mg/kg over a 6-month period. The Expert Panel recommends that the aducanumab be titrated to the highest dose to maximize the opportunity for efficacy. Aducanumab can substantially increase the incidence of amyloid-related imaging abnormalities (ARIA) with brain effusion or hemorrhage. Dose interruption or treatment discontinuation is recommended for symptomatic ARIA and for moderate-severe ARIA. The Expert Panel recommends MRIs prior to initiating therapy, during the titration of the drug, and at any time the patient has symptoms suggestive of ARIA. Recommendations are made for measures less cumbersome than those used in trials for the assessment of effectiveness in the practice setting. The Expert Panel emphasized the critical importance of engaging in a process of patient-centered informed decision-making that includes comprehensive discussions and clear communication with the patient and care partner regarding the requirements for therapy, the expected outcome of therapy, potential risks and side effects, and the required safety monitoring, as well as uncertainties regarding individual responses and benefits.

Immune effector cell (IEC) therapies offer durable and sustained remissions in significant numbers of patients with hematological cancers. While these unique immunotherapies have improved outcomes for pediatric and adult patients in a number of disease states, as 'living drugs,' their toxicity profiles, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), differ markedly from conventional cancer therapeutics. At the time of article preparation, the US Food and Drug Administration (FDA) has approved tisagenlecleucel, axicabtagene ciloleucel, and brexucabtagene autoleucel, all of which are IEC therapies based on genetically modified T cells engineered to express chimeric antigen receptors (CARs), and additional products are expected to reach marketing authorization soon and to enter clinical development in due course. As IEC therapies, especially CAR T cell therapies, enter more widespread clinical use, there is a need for clear, cohesive recommendations on toxicity management, motivating the Society for Immunotherapy of Cancer (SITC) to convene an expert panel to develop a clinical practice guideline. The panel discussed the recognition and management of common toxicities in the context of IEC treatment, including baseline laboratory parameters for monitoring, timing to onset, and pharmacological interventions, ultimately forming evidence- and consensus-based recommendations to assist medical professionals in decision-making and to improve outcomes for patients.

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has contributed to an increase in intimate partner violence (IPV), posing challenges to health care providers who must protect themselves and others during sexual assault examinations. Victims of sexual assault encountered in prehospital and emergency department (ED) settings have legal as well as medical needs. A series of procedures must be carefully followed to facilitate forensic evidence collection and law enforcement investigation. A literature review detected a paucity of published guidance on the management of sexual assault patients in the ED, and no information specific to COVID-19.ObjectiveInvestigators sought to update the San Diego County sexual assault guidelines, created in collaboration with health care professionals, forensic specialists, and law enforcement, through a consensus iterative review process. An additional objective was to create a SAFET-I Tool for use by frontline providers during the COVID-19 pandemic.DiscussionThe authors present a novel SAFET-I Tool that outlines the following five components of effective sexual assault patient care: stabilization, alert system activation, forensic evidence consideration, expedited post-assault treatment, and trauma-informed care. This framework can be used as an educational tool and template for agencies interested in developing or adapting existing sexual assault policies.ConclusionsThere is a lack of clinical guidance for ED providers that integrates the many aspects of sexual assault patient care, particularly during the COVID-19 pandemic. A SAFET-I Tool is presented to assist emergency health care providers in the treatment and advocacy of sexual assault patients during a period with increasing rates of IPV.

We must ensure that trials are scientifically, politically, and socially robust, publicly accountable, and widely transparent

This consensus document presents the suggested guidelines developed by the Laboratory Technology Committee (LTC) of the American Association of Veterinary Laboratory Diagnosticians (AAVLD) for development, validation, and modification (methods comparability) of real-time PCR (rtPCR) assays. These suggested guidelines are presented with reference to the World Organisation for Animal Health (OIE) guidelines for validation of nucleic acid detection assays used in veterinary diagnostic laboratories. Additionally, our proposed practices are compared to the guidelines from the Foods Program Regulatory Subdivision of the U.S. Food and Drug Administration (FDA) and from the American Society for Veterinary Clinical Pathology (ASVCP). The LTC suggestions are closely aligned with those from the OIE and comply with version 2021-01 of the AAVLD Requirements for an Accredited Veterinary Medical Diagnostic Laboratory, although some LTC recommendations are more stringent and extend beyond the AAVLD requirements. LTC suggested guidelines are substantially different than the guidelines recently published by the U.S. FDA for validation and modification of regulated tests used for detection of pathogens in pet food and animal-derived products, such as dairy. Veterinary diagnostic laboratories that perform assays from the FDA Bacteriological Analytical Method (BAM) manual must be aware of the different standard.

Immunotherapy is now a cornerstone for cancer treatment, and much attention has been placed on the identification of prognostic and predictive biomarkers. The success of biomarker development is dependent on accurate and timely collection of biospecimens and high-quality processing, storage and shipping. Tumors are also increasingly used as source material for the generation of therapeutic T cells. There have been few guidelines or consensus statements on how to optimally collect and manage biospecimens and source material being used for immunotherapy and related research. The Society for Immunotherapy of Cancer Surgery Committee has brought together surgical experts from multiple subspecialty disciplines to identify best practices and to provide consensus on how best to access and manage specific tissues for immuno-oncology treatments and clinical investigation. In addition, the committee recommends early integration of surgeons and other interventional physicians with expertise in biospecimen collection, especially in clinical trials, to optimize the quality of tissue and the validity of correlative clinical studies in cancer immunotherapy.

ABSTRACT This Brazilian multi-society position statement on emerging bariatric and metabolic surgical procedures was issued by the Brazilian Society of Bariatric and Metabolic Surgery (SBCBM), the Brazilian College of Digestive Surgery (CBCD), and the Brazilian College of Surgeons (CBC). This document is the result of a Brazilian Emerging Surgeries Forum aimed at evaluating the results of surgeries that are not yet listed in the Federal Council of Medicine (CFM), the regulatory agency that oversees and regulates medical practice in Brazil. The Forum integrated more than 400 specialists and academics with extensive knowledge about bariatric and metabolic surgery, representing the three surgical societies: SBCBM, CBC, and CBCD. International speakers participated online and presented their experiences with the techniques under discussion, emphasizing the regulatory policies in their countries. The indications for surgery and the subsequent procedures were carefully reviewed, including one anastomosis gastric bypass (OAGB), single anastomosis duodeno-ileal with sleeve gastrectomy (SADI-S or OADS), sleeve gastrectomy with transit bipartition (SGTB), and sleeve gastrectomy with ileal interposition (SGII). The recommendations of this document are based on an extensive literature review and discussions among bariatric surgery specialists from the three surgical societies. We concluded that patients with a body mass index over 30 kg/m2 may be candidates for metabolic surgery in the presence of comorbidities (arterial hypertension and type 2 diabetes) with no response to clinical treatment of obesity or in the control of other associated diseases. Regarding the surgical procedures, we concluded that OAGB, OADS, and SGTB are associated with low morbidity rates, satisfactory weight loss, and resolution of obesity-related comorbidities such as diabetes and arterial hypertension. SGII was considered a good and viable promising surgical alternative technique. The recommendations of this statement aim to synchronize our societies with the sentiments and understandings of most of our members and also serve as a guide for future decisions regarding bariatric surgical procedures in our country and worldwide.

There is a very large body of publications discussing the management of patients with an acute sore throat. Advocates for a restrictive antibiotic policy and advocates for a more liberal use of antibiotics emphasise different and valid arguments and to date have not been able to unite in a consensus. Contradicting guidelines based on the same body of knowledge is not logical, may cause confusion and cause unwanted variation in clinical management. In multiple video meetings and email correspondence from March to November 2022 and finally in a workshop at the annual meeting for the North American Primary Care Group in November 2022, experts from different countries representing different traditions agreed on how the current evidence should be interpreted. This critical analysis identifies that the problem can be resolved by introducing a new triage scheme considering both the acute risk for suppurative complications and sepsis as well as the long-term risk of developing rheumatic fever. The new triage scheme may solve the long-standing problem of advocating for a restrictive use of antibiotics while also satisfying concerns that critically ill patients might be missed with severe consequences. We acknowledge that the perspective of this problem is vastly different between high- and low-income countries. Furthermore, we discuss the new trend which allows nurses and pharmacists to independently manage these patients and the increased need for safety netting required for such management. [ABSTRACT FROM AUTHOR]

Background: In 2011, the Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children (CAMESA) published guidelines for the metabolic monitoring of antipsychotic-treated children and youth. Populationbased studies examining adherence to these guidelines are needed to ensure the safe use of antipsychotics in children and youth. Methods: We conducted a population-based study of all Ontario residents aged 0 to 24 who were newly dispensed an antipsychotic between April 1, 2018, and March 31, 2019. We estimated prevalence ratios (PRs) and 95% confidence intervals (CI) associating sociodemographic characteristics with the receipt of baseline and follow-up (3- and 6-month) laboratory testing using log-Poisson regression models. Results: Overall, 6,505 of 27,718 (23.5%) children and youth newly dispensed an antipsychotic received at least one guideline-recommended baseline test. Monitoring was more prevalent among individuals aged 10 to 14 years (PR 1.20; 95% CI 1.04 to 1.38), 15 to 19 years (PR 1.60; 95% CI 1.41 to 1.82), and 20 to 24 years (PR 1.71; 95% CI 1.50 to 1.94) compared to children under the age of 10. Baseline monitoring was associated with mental health-related hospitalizations or emergency department visits in the year preceding therapy (PR 1.76; 95% CI 1.65 to 1.87), a prior diagnosis of schizophrenia (PR 1.20; 95% CI 1.14 to 1.26) or diabetes (PR 1.35; 95% CI 1.19 to 1.54), benzodiazepine use (PR 1.13; 95% CI 1.04 to 1.24), and receipt of a prescription from a child and adolescent psychiatrist or developmental pediatrician versus a family physician (PR 1.41; 95% CI 1.34 to 1.48). Conversely, monitoring was less frequent in individuals co-prescribed stimulants (PR 0.83; 95% CI 0.75 to 0.91). The prevalence of any 3- and 6-month followup monitoring among children and youth receiving continuous antipsychotictherapy at these time points was 13.0% (1,179 of 9,080) and 11.4% (597 of 5,261), respectively. Correlates of follow-up testing were similar to those of baseline monitoring. Conclusion: Most children initiating antipsychotic therapy do not receive guideline-recommended metabolic laboratory monitoring. Further research is needed to understand reasons for poor guideline adherence and the role of clinician training and collaborative service models in promoting best monitoring practices. [ABSTRACT FROM AUTHOR]

Background Mathematical optimization of automated external defibrillator (AED) placement may improve AED accessibility and out-of-hospital cardiac arrest (OHCA) outcomes compared with American Heart Association (AHA) and European Resuscitation Council (ERC) placement guidelines. We conducted an in silico trial (simulated prospective cohort study) comparing mathematically optimized placements with placements derived from current AHA and ERC guidelines, which recommend placement in locations where OHCAs are usually witnessed. Methods and Results We identified all public OHCAs of presumed cardiac cause from 2008 to 2016 in Copenhagen, Denmark. For the control, we computationally simulated placing 24/7-accessible AEDs at every unique, public, witnessed OHCA location at monthly intervals over the study period. The intervention consisted of an equal number of simulated AEDs placements, deployed monthly, at mathematically optimized locations, using a model that analyzed historical OHCAs before that month. For each approach, we calculated the number of OHCAs in the study period that occurred within a 100-m route distance based on Copenhagens road network of an available AED after it was placed (OHCA coverage). Estimated impact on bystander defibrillation and 30-day survival was calculated by multivariate logistic regression. The control scenario involved 393 AEDs at historical, public, witnessed OHCA locations, covering 15.8% of the 653 public OHCAs from 2008 to 2016. The optimized locations provided significantly higher coverage (24.2%; P

The ubiquitous pollution of the environment with microplastics, a diverse suite of contaminants, is of growing concern for science and currently receives considerable public, political, and academic attention. The potential impact of microplastics in the environment has prompted a great deal of research in recent years. Many diverse methods have been developed to answer different questions about microplastic pollution, from sources, transport, and fate in the environment, and about effects on humans and wildlife. These methods are often insufficiently described, making studies neither comparable nor reproducible. The proliferation of new microplastic investigations and cross-study syntheses to answer larger scale questions are hampered. This diverse group of 23 researchers think these issues can begin to be overcome through the adoption of a set of reporting guidelines. This collaboration was created using an open science framework that we detail for future use. Here, we suggest harmonized reporting guidelines for microplastic studies in environmental and laboratory settings through all steps of a typical study, including best practices for reporting materials, quality assurance/quality control, data, field sampling, sample preparation, microplastic identification, microplastic categorization, microplastic quantification, and considerations for toxicology studies. We developed three easy to use documents, a detailed document, a checklist, and a mind map, that can be used to reference the reporting guidelines quickly. We intend that these reporting guidelines support the annotation, dissemination, interpretation, reviewing, and synthesis of microplastic research. Through open access licensing (CC BY 4.0), these documents aim to increase the validity, reproducibility, and comparability of studies in this field for the benefit of the global community.

The severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019 [COVID-19]) pandemic has challenged medical systems and clinicians globally to unforeseen levels. Rapid spread of COVID-19 has forced clinicians to care for patients with a highly contagious disease without evidence-based guidelines. Using a virtual modified nominal group technique, the Pediatric Difficult Intubation Collaborative (PeDI-C), which currently includes 35 hospitals from 6 countries, generated consensus guidelines on airway management in pediatric anesthesia based on expert opinion and early data about the disease. PeDI-C identified overarching goals during care, including minimizing aerosolized respiratory secretions, minimizing the number of clinicians in contact with a patient, and recognizing that undiagnosed asymptomatic patients may shed the virus and infect health care workers. Recommendations include administering anxiolytic medications, intravenous anesthetic inductions, tracheal intubation using video laryngoscopes and cuffed tracheal tubes, use of in-line suction catheters, and modifying workflow to recover patients from anesthesia in the operating room. Importantly, PeDI-C recommends that anesthesiologists consider using appropriate personal protective equipment when performing aerosol-generating medical procedures in asymptomatic children, in addition to known or suspected children with COVID-19. Airway procedures should be done in negative pressure rooms when available. Adequate time should be allowed for operating room cleaning and air filtration between surgical cases. Research using rigorous study designs is urgently needed to inform safe practices during the COVID-19 pandemic. Until further information is available, PeDI-C advises that clinicians consider these guidelines to enhance the safety of health care workers during airway management when performing aerosol-generating medical procedures. These guidelines have been endorsed by the Society for Pediatric Anesthesia and the Canadian Pediatric Anesthesia Society.

Outcomes in multiple myeloma (MM) have improved dramatically in the last two decades with the advent of novel therapies including immunomodulatory agents (IMiDs), proteasome inhibitors and monoclonal antibodies. In recent years, immunotherapy for the treatment of MM has advanced rapidly, with the approval of new targeted agents and monoclonal antibodies directed against myeloma cell-surface antigens, as well as maturing data from late stage trials of chimeric antigen receptor CAR T cells. Therapies that engage the immune system to treat myeloma offer significant clinical benefits with durable responses and manageable toxicity profiles, however, the appropriate use of these immunotherapy agents can present unique challenges for practicing physicians. Therefore, the Society for Immunotherapy of Cancer convened an expert panel, which met to consider the current role of approved and emerging immunotherapy agents in MM and provide guidance to the oncology community by developing consensus recommendations. As immunotherapy evolves as a therapeutic option for the treatment of MM, these guidelines will be updated.

The severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019 [COVID-19]) pandemic has challenged medical systems and clinicians globally to unforeseen levels. Rapid spread of COVID-19 has forced clinicians to care for patients with a highly contagious disease without evidence-based guidelines. Using a virtual modified nominal group technique, the Pediatric Difficult Intubation Collaborative (PeDI-C), which currently includes 35 hospitals from 6 countries, generated consensus guidelines on airway management in pediatric anesthesia based on expert opinion and early data about the disease. PeDI-C identified overarching goals during care, including minimizing aerosolized respiratory secretions, minimizing the number of clinicians in contact with a patient, and recognizing that undiagnosed asymptomatic patients may shed the virus and infect health care workers. Recommendations include administering anxiolytic medications, intravenous anesthetic inductions, tracheal intubation using video laryngoscopes and cuffed tracheal tubes, use of in-line suction catheters, and modifying workflow to recover patients from anesthesia in the operating room. Importantly, PeDI-C recommends that anesthesiologists consider using appropriate personal protective equipment when performing aerosol-generating medical procedures in asymptomatic children, in addition to known or suspected children with COVID-19. Airway procedures should be done in negative pressure rooms when available. Adequate time should be allowed for operating room cleaning and air filtration between surgical cases. Research using rigorous study designs is urgently needed to inform safe practices during the COVID-19 pandemic. Until further information is available, PeDI-C advises that clinicians consider these guidelines to enhance the safety of health care workers during airway management when performing aerosol-generating medical procedures. These guidelines have been endorsed by the Society for Pediatric Anesthesia and the Canadian Pediatric Anesthesia Society.

IntroductionMedication errors (MEs), which occur commonly in the perioperative period, have the potential to cause patient harm or death. Many published recommendations exist for preventing perioperative MEs; however, many of these recommendations conflict and are often not applicable to middle-income and low-income countries. The goal of this study is to develop and disseminate consensus-based recommendations for perioperative medication safety that are tailored to country income level.Methods and analysisThe primary site of this mixed-methods study is Massachusetts General Hospital/Harvard Medical School. Participants include a minimum of 108 international medication safety experts, 27 from each of the World Bank's four country income groups (high, upper-middle, lower-middle and low-income). Using the Delphi method, participants will rate the appropriateness of candidate medication safety recommendations by completing online surveys using RedCAP. We will use Condorcet ranking methods to prioritise the final recommendations for each country income group. We will execute a comprehensive dissemination strategy for the recommendations across each country income group. Finally, we will conduct semistructured interviews with our participants to evaluate the initial adoption and implementation of the recommendations in each country income group.Ethics and disseminationThis study was approved by the Human Research Committee/Institutional Review Board at Partners Healthcare (2019P003567). Findings will be published in peer-reviewed journals and presented at local and international conferences.Trial registration numberNCT04240301.

BackgroundPediatric Intensive Care Unit (PICU) teams provide care for critically ill children with diverse and often complex medical and surgical conditions. Researchers often lack guidance on an approach to select the best outcomes when evaluating this critically ill population. Studies would be enhanced by incorporating multi-stakeholder preferences to better evaluate clinical care. This manuscript outlines the methodology currently being used to develop a PICU Core Outcome Set (COS). This PICU COS utilizes mixed methods, an inclusive stakeholder approach, and a modified Delphi consensus process that will serve as a resource for PICU research programs.MethodsA Scoping Review of the PICU literature evaluating outcomes after pediatric critical illness, a qualitative study interviewing PICU survivors and their parents, and other relevant literature will serve to inform a modified, international Delphi consensus process. The Delphi process will derive a set of minimum domains for evaluation of outcomes of critically ill children and their families. Delphi respondents include researchers, multidisciplinary clinicians, families and former patients, research funding agencies, payors, and advocates. Consensus meetings will refine and finalize the domains of the COS, outline a battery instruments for use in future studies, and prepare for extensive dissemination for broad implementation.DiscussionThe PICU COS will be a guideline resource for investigators to assure that outcomes most important to all stakeholders are considered in PICU clinical research in addition to those deemed most important to individual scientists.Trial registrationCOMET database (http://www.comet-initiative.org/, Record ID 1131, 01/01/18).

Cells succumbing to stress via regulated cell death (RCD) can initiate an adaptive immune response associated with immunological memory, provided they display sufficient antigenicity and adjuvanticity. Moreover, multiple intracellular and microenvironmental features determine the propensity of RCD to drive adaptive immunity. Here, we provide an updated operational definition of immunogenic cell death (ICD), discuss the key factors that dictate the ability of dying cells to drive an adaptive immune response, summarize experimental assays that are currently available for the assessment of ICD in vitro and in vivo, and formulate guidelines for their interpretation.

Personalized nutrition (PN) approaches have been shown to help drive behavior change and positively influence health outcomes. This has led to an increase in the development of commercially available PN programs, which utilize various forms of individual-level information to provide services and products for consumers. The lack of a well-accepted definition of PN or an established set of guiding principles for the implementation of PN creates barriers for establishing credibility and efficacy. To address these points, the North American Branch of the International Life Sciences Institute convened a multidisciplinary panel. In this article, a definition for PN is proposed: "Personalized nutrition uses individual-specific information, founded in evidence-based science, to promote dietary behavior change that may result in measurable health benefits." In addition, 10 guiding principles for PN approaches are proposed: 1) define potential users and beneficiaries; 2) use validated diagnostic methods and measures; 3) maintain data quality and relevance; 4) derive data-driven recommendations from validated models and algorithms; 5) design PN studies around validated individual health or function needs and outcomes; 6) provide rigorous scientific evidence for an effect on health or function; 7) deliver user-friendly tools; 8) for healthy individuals, align with population-based recommendations; 9) communicate transparently about potential effects; and 10) protect individual data privacy and act responsibly. These principles are intended to establish a basis for responsible approaches to the evidence-based research and practice of PN and serve as an invitation for further public dialog. Several challenges were identified for PN to continue gaining acceptance, including defining the health-disease continuum, identification of biomarkers, changing regulatory landscapes, accessibility, and measuring success. Although PN approaches hold promise for public health in the future, further research is needed on the accuracy of dietary intake measurement, utilization and standardization of systems approaches, and application and communication of evidence.

We present a consensus-based checklist to improve and document the transparency of research reports in social and behavioural research. An accompanying online application allows users to complete the form and generate a report that they can submit with their manuscript or post to a public repository.

Ill and injured children have unique needs that can be magnified when the child's ailment is serious or life-threatening. This is especially true in the out-of-hospital environment. Providing high-quality out-of-hospital care to children requires an emergency medical services (EMS) system infrastructure designed to support the care of pediatric patients. As in the emergency department setting, it is important that all EMS agencies have the appropriate resources, including physician oversight, trained and competent staff, education, policies, medications, equipment, and supplies, to provide effective emergency care for children. Resource availability across EMS agencies is variable, making it essential that EMS medical directors, administrators, and personnel collaborate with outpatient and hospital-based pediatric experts, especially those in emergency departments, to optimize prehospital emergency care for children. The principles in the policy statement "Pediatric Readiness in Emergency Medical Services Systems" and this accompanying technical report establish a foundation on which to build optimal pediatric care within EMS systems and serve as a resource for clinical and administrative EMS leaders.

INTRODUCTION:Two developing forces have achieved prominence in medical education: the advent of competency-based assessments and a growing commitment to expand access to medicine for a broader range of learners with a wider array of preparation. Remediation is intended to support all learners to achieve sufficient competence. Therefore, it is timely to provide practical guidelines for remediation in medical education that clarify best practices, practices to avoid, and areas requiring further research, in order to guide work with both individual struggling learners and development of training program policies. METHODS:Collectively, we generated an initial list of Do's, Don'ts, and Don't Knows for remediation in medical education, which was then iteratively refined through discussions and additional evidence-gathering. The final guidelines were then graded for the strength of the evidence by consensus. RESULTS:We present 26 guidelines: two groupings of Do's (systems-level interventions and recommendations for individual learners), along with short lists of Don'ts and Don't Knows, and our interpretation of the strength of current evidence for each guideline. CONCLUSIONS:Remediation is a high-stakes, highly complex process involving learners, faculty, systems, and societal factors. Our synthesis resulted in a list of guidelines that summarize the current state of educational theory and empirical evidence that can improve remediation processes at individual and institutional levels. Important unanswered questions remain; ongoing research can further improve remediation practices to ensure the appropriate support for learners, institutions, and society.