Search

Background Increasing evidence has emerged for traditional, complementary and integrative medicine (TCIM) to treat COVID-19 which requires systematic summaries of the net benefits of interventions against standard care and one another. The study aims to conduct a systematic review and network meta-analysis (NMA) regarding TCIM therapies for treating mild/moderate acute COVID-19, potentially informing the WHO guideline development and clinical decision-making.Methods and analysis We will search Embase, MEDLINE, Virtual Health Library on Traditional Complementary and Integrative Medicine, Cochrane Central Register of Controlled Trials, WHO’s International Clinical Trials Registry Platform with additional searches of Chinese and Korean literature sources for randomised controlled trials comparing TCIM with placebo, standard care, no treatment or with an alternate type of TCIM to treat COVID-19. We will limit the search dates from 2020 to 28 March 2024. Reviewers will, in duplicate, screen eligible articles, extract data and evaluate the risk of bias. We will conduct frequentist network meta-analyses for network comparisons and each outcome. We will assess the certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation approach and classify interventions from most to least effective or harmful.Ethics and dissemination This NMA is based on the existing trials and data which is not subject to ethical approval. We will publish the NMA in a peer-reviewed journal. This may provide methodological reference and clinical evidence for TCIM on future epidemic-prone diseases.PROSPERO registration number CRD42024517321.

Objective To examine cardiovascular and kidney benefits and harms of sodium-glucose co-transporter-2 (SGLT-2) inhibitors stratified by risk in adults with chronic kidney disease regardless of diabetes status.Design Systematic review and meta-analysis.Data sources Ovid Medline, Embase, and Cochrane Central from database inception to 15 June 2024.Eligibility criteria for selecting studies Randomised controlled trials that compared SGLT-2 inhibitors with placebo or standard care with no SGLT-2 inhibitors in adults with chronic kidney disease with a follow-up duration of ≥12 weeks were eligible. Secondary analyses based on subpopulations from randomised controlled trials and publications not in English language were excluded.Data synthesis Random effects meta-analyses were conducted, with effect estimates presented as risk ratios with 95% confidence intervals (CIs). Absolute treatment effects were estimated over a five year duration for individuals with varied risks of cardiovascular and kidney complications based on the Kidney Disease Improving Global Outcomes (KDIGO) risk stratification system. Certainty of evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach.Results Evidence from 13 randomised controlled trials (29 614 patients) informed treatment effect estimates. In relative terms, SGLT-2 inhibitors reduced all cause death (risk ratio 0.85 (95% CI 0.74 to 0.98)), cardiovascular death (0.84 (0.74 to 0.96)), kidney failure (0.68 (0.60 to 0.77)), non-fatal stroke (0.73 (0.57 to 0.94)), non-fatal myocardial infarction (0.75 (0.60 to 0.93)), and admission to hospital for heart failure (0.68 (0.60 to 0.78)). No credible subgroup effects were found from diabetes status, heart failure status, estimated glomerular filtration rate, urinary albumin-to-creatinine ratio, and follow-up duration. Absolute effect estimates across these outcomes over a five year period varied across risk groups based on baseline risks of cardiovascular and kidney events. Effects of SGLT-2 inhibitors in the group at low risk included seven fewer all- cause deaths, four fewer admissions to hospital for heart failure per 1000 individuals, and no effects on kidney failure. Effects in the higher risk group included 48 fewer all cause deaths, 58 fewer kidney failures, and 25 fewer admissions to hospital for heart failure per 1000 individuals. Although SGLT-2 inhibitor use was associated with a relative increase in the risk of harms, including genital infection (2.66 (95% CI 2.07 to 3.42)), ketoacidosis (2.27 (1.30 to 3.95)), and symptomatic hypovolaemia (1.29 (1.15 to 1.44)), absolute differences for all harm outcomes were small.Conclusions Among people who have chronic kidney disease either with type 2 diabetes or not, SGLT-2 inhibitors improved cardiovascular and kidney outcomes with varying degrees of absolute benefit depending on an individual's baseline risks of cardiovascular and kidney-related sequelae. Absolute benefits and harms stratified by risk and associated with SGLT-2 inhibitors should inform individual decision making at the patient level.Systematic review registration PROSPERO CRD42022325483.

Abstract Background Arthroplasty registries are rarely used to inform encounters between clinician and patient. This study is part of a larger one which aimed to develop an information tool allowing both to benefit from previous patients’ experience after total hip arthroplasty (THA). This study focuses on generating the information tool specifically for pain outcomes. Methods Data from the Geneva Arthroplasty Registry (GAR) about patients receiving a primary elective THA between 1996 and 2019 was used. Selected outcomes were identified from patient and surgeon surveys: pain walking, climbing stairs, night pain, pain interference, and pain medication. Clusters of patients with homogeneous outcomes at 1, 5, and 10 years postoperatively were generated based on selected predictors evaluated preoperatively using conditional inference trees (CITs). Results Data from 6,836 THAs were analysed and 14 CITs generated with 17 predictors found significant (p

Introduction Large language model (LLM)-linked chatbots are being increasingly applied in healthcare due to their impressive functionality and public availability. Studies have assessed the ability of LLM-linked chatbots to provide accurate clinical advice. However, the methods applied in these Chatbot Assessment Studies are inconsistent due to the lack of reporting standards available, which obscures the interpretation of their study findings. This protocol outlines the development of the Chatbot Assessment Reporting Tool (CHART) reporting guideline.Methods and analysis The development of the CHART reporting guideline will consist of three phases, led by the Steering Committee. During phase one, the team will identify relevant reporting guidelines with artificial intelligence extensions that are published or in development by searching preprint servers, protocol databases, and the Enhancing the Quality and Transparency of health research Network. During phase two, we will conduct a scoping review to identify studies that have addressed the performance of LLM-linked chatbots in summarising evidence and providing clinical advice. The Steering Committee will identify methodology used in previous Chatbot Assessment Studies. Finally, the study team will use checklist items from prior reporting guidelines and findings from the scoping review to develop a draft reporting checklist. We will then perform a Delphi consensus and host two synchronous consensus meetings with an international, multidisciplinary group of stakeholders to refine reporting checklist items and develop a flow diagram.Ethics and dissemination We will publish the final CHART reporting guideline in peer-reviewed journals and will present findings at peer-reviewed meetings. Ethical approval was submitted to the Hamilton Integrated Research Ethics Board and deemed “not required” in accordance with the Tri-Council Policy Statement (TCPS2) for the development of the CHART reporting guideline (#17025).Registration This study protocol is preregistered with Open Science Framework: https://doi.org/10.17605/OSF.IO/59E2Q.

Abstract Background Encounter decision aids (EDAs) are tools that can support shared decision making (SDM), up to the clinical encounter. However, adoption of these tools has been limited, as they are hard to produce, to keep up-to-date, and are not available for many decisions. The MAGIC Evidence Ecosystem Foundation has created a new generation of decision aids that are generically produced along digitally structured guidelines and evidence summaries, in an electronic authoring and publication platform (MAGICapp). We explored general practitioners’ (GPs) and patients' experiences with five selected decision aids linked to BMJ Rapid Recommendations in primary care. Methods We applied a qualitative user testing design to evaluate user experiences for both GPs and patients. We translated five EDAs relevant to primary care, and observed the clinical encounters of 11 GPs when they used the EDA with their patients. We conducted a semi-structured interview with each patient after the consultation and a think-aloud interview with each GPs after multiple consultations. We used the Qualitative Analysis Guide (QUAGOL) for data analysis. Results Direct observations and user testing analysis of 31 clinical encounters showed an overall positive experience. The EDAs created better involvement in decision making and resulted in meaningful insights for patients and clinicians. The design and its interactive, multilayered structure made the tool enjoyable and well-organized. Difficult terminology, scales and numbers hindered understanding of certain information, which was sometimes perceived as too specialized or even intimidating. GPs thought the EDA was not suitable for every patient. They perceived a learning curve was required and the need for time investment was a concern. The EDAs were considered trustworthy as they were provided by a credible source. Conclusions This study showed that EDAs can be useful tools in primary care by supporting actual shared decision making and enhancing patient involvement. The graphical approach and clear representation help patients better understand their options. To overcome barriers such as health literacy and GPs attitudes, effort is still needed to make the EDAs as accessible, intuitive and inclusive as possible through use of plain language, uniform design, rapid access and training. Trial registration The study protocol was approved by the The Research Ethics Committee UZ/KU Leuven (Belgium) on 31–10-2019 with reference number MP011977.

Objectives Infographics have the potential to enhance knowledge translation and implementation of clinical practice guidelines at the point of care. They can provide a synoptic view of recommendations, their rationale and supporting evidence. They should be understandable and easy to use. Little evaluation of these infographics regarding user experience has taken place. We explored general practitioners’ experiences with five selected BMJ Rapid Recommendation infographics suited for primary care.Methods An iterative, qualitative user testing design was applied on two consecutive groups of 10 general practitioners for five selected infographics. The physicians used the infographics before clinical encounters and we performed hybrid think-aloud interviews afterwards. 20 interviews were analysed using the Qualitative Analysis Guide of Leuven.Results Many clinicians reported that the infographics were simple and rewarding to use, time-efficient and easy to understand. They were perceived as innovative and their knowledge basis as trustworthy and supportive for decision-making. The interactive, expandable format was preferred over a static version as general practitioners focused mainly on the core message. Rapid access through the electronic health record was highly desirable. The main issues were about the use of complex scales and terminology. Understanding terminology related to evidence appraisal as well as the interpretation of statistics and unfamiliar scales remained difficult, despite the infographics.Conclusions General practitioners perceive infographics as useful tools for guideline translation and implementation in primary care. They offer information in an enjoyable and user friendly format and are used mainly for rapid, tailored and just in time information retrieval. We recommend future infographic producers to provide information as concise as possible, carefully define the core message and explore ways to enhance the understandability of statistics and difficult concepts related to evidence appraisal.Trial registration number MP011977.

Objective To compare the effects of interleukin 6 receptor blockers, tocilizumab and sarilumab, with or without corticosteroids, on mortality in patients with covid-19.Design Systematic review and network meta-analysis.Data sources World Health Organization covid-19 database, a comprehensive multilingual source of global covid-19 literature, and two prospective meta-analyses (up to 9 June 2021).Review methods Trials in which people with suspected, probable, or confirmed covid-19 were randomised to interleukin 6 receptor blockers (with or without corticosteroids), corticosteroids, placebo, or standard care. The analysis used a bayesian framework and assessed the certainty of evidence using the GRADE approach. Results from the fixed effect meta-analysis were used for the primary analysis.Results Of 45 eligible trials (20 650 patients) identified, 36 (19 350 patients) could be included in the network meta-analysis. Of 36 trials, 27 were at high risk of bias, primarily due to lack of blinding. Tocilizumab, in combination with corticosteroids, suggested a reduction in the risk of death compared with corticosteroids alone (odds ratio 0.79, 95% credible interval 0.70 to 0.88; 35 fewer deaths per 1000 people, 95% credible interval 52 fewer to 18 fewer per 1000; moderate certainty of evidence), as did sarilumab in combination with corticosteroids, compared with corticosteroids alone (0.73, 0.58 to 0.92; 43 fewer per 1000, 73 fewer to 12 fewer; low certainty). Tocilizumab and sarilumab, each in combination with corticosteroids, appeared to have similar effects on mortality when compared with each other (1.07, 0.86 to 1.34; eight more per 1000, 20 fewer to 35 more; low certainty). The effects of tocilizumab (1.12, 0.91 to 1.38; 20 more per 1000, 16 fewer to 59 more; low certainty) and sarilumab (1.07, 0.81 to 1.40; 11 more per 1000, 38 fewer to 55 more; low certainty), when used alone, suggested an increase in the risk of death.Conclusion These findings suggest that in patients with severe or critical covid-19, tocilizumab, in combination with corticosteroids, probably reduces mortality, and that sarilumab, in combination with corticosteroids, might also reduce mortality. Tocilizumab and sarilumab, in combination with corticosteroids, could have similar effectiveness. Tocilizumab and sarilumab, when used alone, might not be beneficial.

High-flow nasal oxygen (HFNO) is a type of non-invasive advanced respiratory support that allows the delivery of high-flow and humidified air through a nasal cannula. It can deliver a higher inspired oxygen fraction than conventional oxygen therapy (COT), improves secretion clearance, has a small positive end-expiratory pressure, and exhibits a washout effect on the upper air space that diminishes dead space ventilation. HFNO has been shown to reduce the work of breathing in acute hypoxemic respiratory failure (AHRF) and has become an interesting option for non-invasive respiratory support. Evidence published before the COVID-19 pandemic suggested a possible reduction of the need for invasive mechanical ventilation compared to COT. The COVID-19 pandemic has resulted in a substantial increase in AHRF worldwide, overwhelming both acute and intensive care unit capacity in most countries. This triggered new trials, adding to the body of evidence on HFNO in AHRF and its possible benefits compared to COT or non-invasive ventilation. We have summarized and discussed this recent evidence to inform the best supportive strategy in AHRF both related and unrelated to COVID-19.

Healthcare workers have potentially been among the most exposed to SARS-CoV-2 infection as well as the deleterious toll of the pandemic. This study has the objective to differentiate the pandemic toll from post-acute sequelae of SARS-CoV-2 infection in healthcare workers compared to the general population.The study was conducted between April and July 2021 at the Geneva University Hospitals, Switzerland. Eligible participants were all tested staff, and outpatient individuals tested for SARS-CoV-2 at the same hospital. The primary outcome was the prevalence of symptoms in healthcare workers compared to the general population, with measures of COVID-related symptoms and functional impairment, using prevalence estimates and multivariable logistic regression models.Healthcare workers (n = 3083) suffered mostly from fatigue (25.5 %), headache (10.0 %), difficulty concentrating (7.9 %), exhaustion/burnout (7.1 %), insomnia (6.2 %), myalgia (6.7 %) and arthralgia (6.3 %). Regardless of SARS-CoV-2 infection, all symptoms were significantly higher in healthcare workers than the general population (n = 3556). SARS-CoV-2 infection in healthcare workers was associated with loss or change in smell, loss or change in taste, palpitations, dyspnea, difficulty concentrating, fatigue, and headache. Functional impairment was more significant in healthcare workers compared to the general population (aOR 2.28; 1.76–2.96), with a positive association with SARS-CoV-2 infection (aOR 3.81; 2.59–5.60).Symptoms and functional impairment in healthcare workers were increased compared to the general population, and potentially related to the pandemic toll as well as post-acute sequelae of SARS-CoV-2 infection. These findings are of concern, considering the essential role of healthcare workers in caring for all patients including and beyond COVID-19.

Abstract Background Tools for shared decision-making (e.g. decision aids) are intended to support health care professionals and patients engaged in clinical encounters involving shared decision-making. However, decision aids are hard to produce, and onerous to update. Consequently, they often do not reflect best current evidence, and show limited uptake in practice. In response, we initiated the Sharing Evidence to Inform Treatment decisions (SHARE-IT) project. Our goal was to develop and refine a new generation of decision aids that are generically produced along digitally structured guidelines and evidence summaries. Methods Applying principles of human-centred design and following the International Patient Decision Aid Standards (IPDAS) and GRADE methods for trustworthy evidence summaries we developed a decision aid prototype in collaboration with the Developing and Evaluating Communication strategies to support Informed Decisions and practice based on Evidence project (DECIDE). We iteratively user-tested the prototype in clinical consultations between clinicians and patients. Semi-structured interviews of participating clinicians and patients were conducted. Qualitative content analysis of both user-testing sessions and interviews was performed and results categorized according to a revised Morville’s framework of user-experience. We made it possible to produce, publish and use these decision aids in an electronic guideline authoring and publication platform (MAGICapp). Results Direct observations and analysis of user-testing of 28 clinical consultations between physicians and patients informed four major iterations that addressed readability, understandability, usability and ways to cope with information overload. Participants reported that the tool supported natural flow of the conversation and induced a positive shift in consultation habits towards shared decision-making. We integrated the functionality of SHARE-IT decision aids in MAGICapp, which has since generated numerous decision aids. Conclusion Our study provides a proof of concept that encounter decision aids can be generically produced from GRADE evidence summaries and clinical guidelines. Online authoring and publication platforms can help scale up production including continuous updating of electronic encounter decision aids, fully integrated with evidence summaries and clinical practice guidelines.

Objective To establish the prevalence of long-term and serious harms of medical cannabis for chronic pain.Design Systematic review and meta-analysis.Data sources MEDLINE, EMBASE, PsycINFO and CENTRAL from inception to 1 April 2020.Study selection Non-randomised studies reporting on harms of medical cannabis or cannabinoids in adults or children living with chronic pain with ≥4 weeks of follow-up.Data extraction and synthesis A parallel guideline panel provided input on the design and interpretation of the systematic review, including selection of adverse events for consideration. Two reviewers, working independently and in duplicate, screened the search results, extracted data and assessed risk of bias. We used random-effects models for all meta-analyses and the Grades of Recommendations, Assessment, Development and Evaluation approach to evaluate the certainty of evidence.Results We identified 39 eligible studies that enrolled 12 143 adult patients with chronic pain. Very low certainty evidence suggests that adverse events are common (prevalence: 26.0%; 95% CI 13.2% to 41.2%) among users of medical cannabis for chronic pain, particularly any psychiatric adverse events (prevalence: 13.5%; 95% CI 2.6% to 30.6%). Very low certainty evidence, however, indicates serious adverse events, adverse events leading to discontinuation, cognitive adverse events, accidents and injuries, and dependence and withdrawal syndrome are less common and each typically occur in fewer than 1 in 20 patients. We compared studies with

Background To summarise specific adverse effects of remdesivir, hydroxychloroquine and lopinavir/ritonavir in patients with COVID-19.Methods We searched 32 databases through 27 October 2020. We included randomised trials comparing any of the drugs of interest to placebo or standard care, or against each other. We conducted fixed-effects pairwise meta-analysis and assessed the certainty of evidence using the grading of recommendations assessment, development and evaluation approach.Results We included 16 randomised trials which enrolled 8152 patients. For most interventions and outcomes the certainty of the evidence was very low to low except for gastrointestinal adverse effects from hydroxychloroquine, which was moderate certainty. Compared with standard care or placebo, low certainty evidence suggests that remdesivir may not have an important effect on acute kidney injury (risk difference (RD) 8 fewer per 1000, 95% CI 27 fewer to 21 more) or cognitive dysfunction/delirium (RD 3 more per 1000, 95% CI 12 fewer to 19 more). Low certainty evidence suggests that hydroxychloroquine may increase the risk of cardiac toxicity (RD 10 more per 1000, 95% CI 0 more to 30 more) and cognitive dysfunction/delirium (RD 33 more per 1000, 95% CI 18 fewer to 84 more), whereas moderate certainty evidence suggests hydroxychloroquine probably increases the risk of diarrhoea (RD 106 more per 1000, 95% CI 48 more to 175 more) and nausea and/or vomiting (RD 62 more per 1000, 95% CI 23 more to 110 more) compared with standard care or placebo. Low certainty evidence suggests lopinavir/ritonavir may increase the risk of diarrhoea (RD 168 more per 1000, 95% CI 58 more to 330 more) and nausea and/or vomiting (RD 160 more per 1000, 95% CI 100 more to 210 more) compared with standard care or placebo.Discussion Hydroxychloroquine probably increases the risk of diarrhoea and nausea and/or vomiting and may increase the risk of cardiac toxicity and cognitive dysfunction/delirium. Lopinavir/ritonavir may increase the risk of diarrhoea and nausea and/or vomiting. Remdesivir may have no important effect on risk of acute kidney injury or cognitive dysfunction/delirium. These findings provide important information to support the development of evidence-based management strategies for patients with COVID-19.

Abstract Objective eCTAS is a real‐time electronic decision‐support tool designed to standardize the application of the Canadian Triage and Acuity Scale (CTAS). This study addresses the variability of CTAS score distributions across institutions pre‐ and post‐eCTAS implementation. Methods We used population‐based administrative data from 2016–2018 from all emergency departments (EDs) that had implemented eCTAS for 9 months. Following a 3‐month stabilization period, we compared 6 months post‐eCTAS data to the same 6 months the previous year (pre‐eCTAS). We included triage encounters of adult (≥17 years) patients who presented with 1 of 16 pre‐specified, high‐volume complaints. For each ED, consistency was calculated as the absolute difference in CTAS distribution compared to the average of all included EDs for each presenting complaint. Pre‐eCTAS and post‐eCTAS change scores were compared using a paired‐samples t‐test. We also assessed if eCTAS modifiers were associated with triage consistency. Results There were 363,214 (183,231 pre‐eCTAS, 179,983 post‐eCTAS) triage encounters included from 35 EDs. Triage scores were more consistent (P

Objective To explore values and preferences towards medical cannabis among people living with chronic pain.Design Mixed-methods systematic review.Data sources We searched MEDLINE, EMBASE and PsycINFO from inception to 17 March 2020.Study selection Pairs of reviewers independently screened search results and included quantitative, qualitative and mixed-methods studies reporting values and preferences towards medical cannabis among people living with chronic pain.Review methods We analysed data using meta-narrative synthesis (quantitative findings were qualitised) and tabulated review findings according to identified themes. We used the Grading of Recommendations Assessment, Development and Evaluation approach to assess certainty of evidence.Results Of 1838 initial records, 15 studies proved eligible for review. High to moderate certainty evidence showed that patient’s use of medical cannabis for chronic pain was influenced by both positive (eg, support from friends and family) and negative social factors (eg, stigma surrounding cannabis use). Most patients using medical cannabis favoured products with balanced ratios of tetrahydrocannabinol (THC) and cannabidiol (CBD), or high levels of CBD, but not high THC preparations. Many valued the effectiveness of medical cannabis for symptom management even when experiencing adverse events related to concentration, memory or fatigue. Reducing use of prescription medication was a motivating factor for use of medical cannabis, and concerns regarding addiction, losing control or acting strangely were disincentives. Out-of-pocket costs were a barrier, whereas legalisation of medical cannabis improved access and incentivised use.Low to very low certainty evidence suggested highly variable values towards medical cannabis among people living with chronic pain. Individuals with pain related to life-limiting disease were more willing to use medical cannabis, and preferred oral over inhaled administration.Conclusions Our findings highlight factors that clinicians should consider when discussing medical cannabis. The variability of patients’ values and preferences emphasise the need for shared decision making when considering medical cannabis for chronic pain.

Introduction Chronic, non-cancer, axial or radicular spinal pain is a common condition associated with considerable socioeconomic burden. Clinicians frequently offer patients various interventional procedures for the treatment of chronic spine pain; however, the comparative effectiveness and safety of available procedures remains uncertain.Methods We will conduct a systematic review of randomised controlled trials that explores the effectiveness and harms of interventional procedures for the management of axial or radicular, chronic, non-cancer, spine pain. We will identify eligible studies through a systematic search of Medline, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials and Web of Science from inception without language restrictions. Eligible trials will: (1) enrol primarily adult patients (≥18 years old) with axial or radicular, chronic, non-cancer, spine pain, (2) randomise patients to different, currently available, interventional procedures or to an interventional procedure and a placebo/sham procedure or usual care, and (3) measure outcomes at least 1 month after randomisation.Pairs of reviewers will independently screen articles identified through searches and extract information and assess risk of bias of eligible trials. We will use a modified Cochrane instrument to evaluate risk of bias. We will use frequentist random-effects network meta-analyses to assess the relative effects of interventional procedures, and five a priori hypotheses to explore between studies subgroup effects. We will use the Grading of Recommendations Assessment, Development and Evaluation approach to assess the certainty in evidence for each outcome, including direct, indirect and network estimates.Ethics and dissemination No research ethics approval is required for this systematic review, as no confidential patient data will be used. We will disseminate our findings through publication in a peer-reviewed journal and conference presentations, and our review will support development of a BMJ Rapid Recommendations providing contextualised clinical guidance based on this body of evidence.PROSPERO registration number CRD42020170667.

Objective To assess the efficacy and harms of adding medical cannabis to prescription opioids among people living with chronic pain.Design Systematic review.Data sources CENTRAL, EMBASE and MEDLINE.Main outcomes and measures Opioid dose reduction, pain relief, sleep disturbance, physical and emotional functioning and adverse events.Study selection criteria and methods We included studies that enrolled patients with chronic pain receiving prescription opioids and explored the impact of adding medical cannabis. We used Grading of Recommendations Assessment, Development and Evaluation to assess the certainty of evidence for each outcome.Results Eligible studies included five randomised trials (all enrolling chronic cancer-pain patients) and 12 observational studies. All randomised trials instructed participants to maintain their opioid dose, which resulted in a very low certainty evidence that adding cannabis has little or no impact on opioid use (weighted mean difference (WMD) −3.4 milligram morphine equivalent (MME); 95% CI (CI) −12.7 to 5.8). Randomised trials provided high certainty evidence that cannabis addition had little or no effect on pain relief (WMD −0.18 cm; 95% CI −0.38 to 0.02; on a 10 cm Visual Analogue Scale (VAS) for pain) or sleep disturbance (WMD −0.22 cm; 95% CI −0.4 to −0.06; on a 10 cm VAS for sleep disturbance; minimally important difference is 1 cm) among chronic cancer pain patients. Addition of cannabis likely increases nausea (relative risk (RR) 1.43; 95% CI 1.04 to 1.96; risk difference (RD) 4%, 95% CI 0% to 7%) and vomiting (RR 1.5; 95% CI 1.01 to 2.24; RD 3%; 95% CI 0% to 6%) (both moderate certainty) and may have no effect on constipation (RR 0.85; 95% CI 0.54 to 1.35; RD −1%; 95% CI −4% to 2%) (low certainty). Eight observational studies provided very low certainty evidence that adding cannabis reduced opioid use (WMD −22.5 MME; 95% CI −43.06 to −1.97).Conclusion Opioid-sparing effects of medical cannabis for chronic pain remain uncertain due to very low certainty evidence.PROSPERO registration numberCRD42018091098.

AIMS OF THE STUDY Hydroxychloroquine and lopinavir/ritonavir have been used as experimental therapies to treat COVID-19 during the first wave of the pandemic. Randomised controlled trials have recently shown that there are no meaningful benefits of these two therapies in hospitalised patients. Uncertainty remains regarding the potential harmful impact of these therapies as very early treatments and their burden to the health care system. The present study investigated the length of hospital stay (LOS), mortality, and costs of hydroxychloroquine, lopinavir/ritonavir or their combination in comparison with standard of care among patients hospitalised for coronavirus disease 2019 (COVID-19). METHODS This retrospective observational cohort study took place in the Geneva University Hospitals, Geneva, Switzerland (n = 840) between 26 February and 31 May 2020. Demographics, treatment regimens, comorbidities, the modified National Early Warning Score (mNEWS) on admission, and contraindications to COVID-19 treatment options were assessed. Outcomes included LOS, in-hospital mortality, and drug and LOS costs. RESULTS After successful propensity score matching, patients treated with (1) hydroxychloroquine, (2) lopinavir/ritonavir or (3) their combination had on average 3.75 additional hospitalisation days (95% confidence interval [CI] 1.37–6.12, p = 0.002), 1.23 additional hospitalisation days (95% CI −1.24 – 3.51, p = 0.319), and 4.19 additional hospitalisation days (95% CI 1.52–5.31, p

Context and objective Standards for clinical practice guidelines require explicit statements regarding how values and preferences influence recommendations. However, no cancer screening guideline has addressed the key question of what magnitude of benefit people require to undergo screening, given its harms and burdens. This article describes the development of a new method for guideline developers to address this key question in the absence of high-quality evidence from published literature.Summary of method The new method was developed and applied in the context of a recent BMJ Rapid Recommendation clinical practice guideline for colorectal cancer (CRC) screening. First, we presented the guideline panel with harms and burdens (derived from a systematic review) associated with the CRC screening tests under consideration. Second, each panel member completed surveys documenting their views of expected benefits on CRC incidence and mortality that people would require to accept the harms and burdens of screening. Third, the panel discussed results of the surveys and agreed on thresholds for benefits at which the majority of people would choose screening. During these three steps, the panel had no access to the actual benefits of the screening tests. In step four, the panel was presented with screening test benefits derived from a systematic review of clinical trials and microsimulation modelling. The thresholds derived through steps one to three were applied to these benefits, and directly informed the panel’s recommendations.Conclusion We present the development and application of a new, four-step method enabling incorporation of explicit and transparent judgements of values and preferences in a screening guideline. Guideline panels should establish their view regarding the magnitude of required benefit, given burdens and harms, before they review screening benefits and make their recommendations accordingly. Making informed screening decisions requires transparency in values and preferences judgements that our new method greatly facilitates.

BackgroundLow-molecular-weight heparin (LMWH) is usually recommended for the treatment of cancer-associated thrombosis (CAT) but this treatment requires burdensome daily injections. We did a systematic review to compare the efficacy and safety of direct oral anticoagulants (DOAC), vitamin K antagonists (VKA) and LMWH in patients with CAT.MethodsWe searched Pubmed, Embase and CENTRAL for randomised controlled trials comparing DOAC, VKA and LMWH in patients with CAT. Pairwise and network meta-analyses were computed for venous thromboembolism (VTE) recurrence and bleeding complications.ResultsWe identified 14 studies, including 4,661 patients. In pairwise comparison, DOAC were superior to LMWH to prevent VTE recurrence (HR 0.63; 95% CI 0.42-0.96) and LMWH was superior to VKA (HR 0.53; 95% CI 0.40-0.70). The rate of major bleeding was higher with DOAC compared to LMWH (HR 1.78; 95% CI 1.11-2.87). In the network meta-analysis, DOAC had a lower, but non-significant, rate of VTE recurrence compared to LMWH (HR 0.74; 95% CI 0.54-1.01). Both DOAC (HR 0.42; 95% CI 0.29-0.61) and LMWH (HR 0.57; 95% CI 0.44-0.75) were associated with lower rates of recurrence compared to VKA. No significant difference in major bleeding rate was observed in the network meta-analysis. Inconsistency was observed between pairwise and network meta-analysis comparisons for major bleeding.ConclusionsDOAC are effective to prevent VTE recurrence in patients with CAT but are associated with an increased risk of bleeding compared to LMWH. The choice of anticoagulant should be personalised, taking into account the patient's bleeding risk, including cancer site, and patient's values and preferences.

Abstract Background There is currently no guidance for selecting a specific difference to be detected in a superiority trial. We explored 3 factors that in our opinion should influence the difference to be detected (type of outcome, patient age group, and presence of treatment side-effects), and 3 that should not (baseline level of risk, logistical difficulties, and cost of treatment). Methods We conducted an experimental survey using a factorial design among 380 corresponding authors of randomized controlled trials indexed in Medline. Two hypothetical vignettes were submitted to participants: one described a trial of a new analgesic in mild trauma injuries, the other described a trial of a new chemotherapy among cancer patients. The first vignette tested the baseline level of risk, patient age-group, patient recruitment difficulties, and treatment side-effects. The second tested the baseline level of risk, patient age-group, type of outcome, and cost of treatment. The respondents were asked to select the smallest gain of effectiveness that should be detected by the trial. Results In vignette 1, respondents selected a median difference to be detected corresponding to an improvement of 7.0 % in pain control with the new treatment. In vignette 2, they selected a median difference to be detected corresponding to a reduction of 5.0 % in mortality or cancer recurrence with the new chemotherapy. In both vignettes, the difference to be detected decreased significantly with the baseline risk. The other factor influencing difference to be detected was the age group, but the impact of this factor was smaller. Cost, side-effects, outcome severity, or mention of logistical difficulties did not significantly impact the difference to be detected selected by participants. Conclusions Three of the anticipated effects conformed to our expectations (the effect of patient age, and absence of effect of the cost of treatment and of patient recruitment difficulties) and the other three did not. These findings can guide future research in determining differences to be detected in trials that can translate to meaningful clinical decision-making.

Abstract Background Many medical research projects encounter difficulties. The objective of this study was to assess the self-reported frequency of difficulties encountered by medical researchers while conducting research and to identify factors associated with their occurrence. Methods The authors conducted a cross-sectional survey in 2010 among principal investigators of 996 study protocols approved by the Research Ethics Committee in Geneva, Switzerland, between 2001 and 2005. The authors asked principal investigators to rate the level of difficulty (1: none, to 5: very great) encountered across the research process. Results 588 questionnaires were sent back (participation rate 59.0 %). 391 (66.5 %) studies were completed at the time of the survey. Investigators reported that the most frequent difficulties were related to patient enrollment (44.3 %), data collection (26.7 %), data analysis and interpretation (21.5 %), collaboration with caregivers (21.0 %), study design (20.4 %), publication in peer-reviewed journal (20.2 %), hiring of competent study personnel (20.2 %), and getting funding (19.2 %). On average, investigators reported 2.8 difficulties per project (SD 2.8, range 0 to 12). In multivariable analysis, the number of difficulties was higher for studies initiated by public sponsors (vs. private), single center studies (vs. multicenter), and studies about treatment, diagnosis or prognosis (i.e., clinical vs. other studies). Conclusions Medical researchers reported substantial logistical difficulties in conducting clinical research.

Moral distress – such as feeling strong regret over difficult patient situations – is common among nurses and physicians. Regret intensity, as well as the coping strategies used to manage regrets, may also influence the health and sickness absence of healthcare professionals. The objective of this study was to determine if the experience of regret related to difficult care-related situations is associated with poor health and sick leave and if coping strategies mediate these associations. Two cross-sectional surveys were conducted in Switzerland (Geneva, 2011 and Zurich, 2014). Outcomes were self-rated health (SRH) and sick leave in the last 6 months. We examined the associations of regret intensity with the most important care-related regret, number of recent care-related regrets, and coping strategies, using regressions models. Among 775 respondents, most reported very good SRH and 9.7% indicated absence from work during four working days or more. Intensity of the most important regret was associated with poor SRH among nurses and physicians, and with higher sick leave among nurses. Maladaptive emotion-focused strategies were associated with poor SRH among nurses, whereas adaptive emotion-focused strategies were positively associated with higher SRH and lower sick leave among physicians. Because care-related regret is an integral part of clinical practice in acute care hospitals, helping physicians and, especially, nurses to learn how to deal with negative events may yield beneficial consequences at the individual, patient care, and institutional level.

To examine the association between healthcare-related regrets and sleep difficulties among nurses and physicians, we surveyed 240 nurses and 220 physicians at the University Hospitals of Geneva. Regret intensity and regret coping were measured using validated scales. Sleep difficulties were measured using the Insomnia Severity Index (ISI), and an additional question assessed the frequency of sleeping pill use. After controlling for sex, profession, years of experience, rate of employment, and depression as well as for all other regret-related variables, the following variables remained significantly associated with self-rated severity of insomnia: regret intensity (slope = 1.32, p = 0.007, 95%CI: [0.36; 2.29], std. coefficient = 0.16) and maladaptive (e.g., rumination) emotion-focused coping (slope = 1.57, p = 0.002, 95%CI: [0.60; 2.55], std. coefficient = 0.17) remained significant predictors of self-rated insomnia severity. If these cross-sectional associations represent causal effects, the development of regret-management programs may represent a promising approach to mitigating sleep difficulties of healthcare professionals.

Activity-based funding (ABF) of hospitals is a policy intervention intended to re-shape incentives across health systems through the use of diagnosis-related groups. Many countries are adopting or actively promoting ABF. We assessed the effect of ABF on key measures potentially affecting patients and health care systems: mortality (acute and post-acute care); readmission rates; discharge rate to post-acute care following hospitalization; severity of illness; volume of care.We undertook a systematic review and meta-analysis of the worldwide evidence produced since 1980. We included all studies reporting original quantitative data comparing the impact of ABF versus alternative funding systems in acute care settings, regardless of language. We searched 9 electronic databases (OVID MEDLINE, EMBASE, OVID Healthstar, CINAHL, Cochrane CENTRAL, Health Technology Assessment, NHS Economic Evaluation Database, Cochrane Database of Systematic Reviews, and Business Source), hand-searched reference lists, and consulted with experts. Paired reviewers independently screened for eligibility, abstracted data, and assessed study credibility according to a pre-defined scoring system, resolving conflicts by discussion or adjudication.Of 16,565 unique citations, 50 US studies and 15 studies from 9 other countries proved eligible (i.e. Australia, Austria, England, Germany, Israel, Italy, Scotland, Sweden, Switzerland). We found consistent and robust differences between ABF and no-ABF in discharge to post-acute care, showing a 24% increase with ABF (pooled relative risk = 1.24, 95% CI 1.18-1.31). Results also suggested a possible increase in readmission with ABF, and an apparent increase in severity of illness, perhaps reflecting differences in diagnostic coding. Although we found no consistent, systematic differences in mortality rates and volume of care, results varied widely across studies, some suggesting appreciable benefits from ABF, and others suggesting deleterious consequences.Transitioning to ABF is associated with important policy- and clinically-relevant changes. Evidence suggests substantial increases in admissions to post-acute care following hospitalization, with implications for system capacity and equitable access to care. High variability in results of other outcomes leaves the impact in particular settings uncertain, and may not allow a jurisdiction to predict if ABF would be harmless. Decision-makers considering ABF should plan for likely increases in post-acute care admissions, and be aware of the large uncertainty around impacts on other critical outcomes.

BackgroundA common weakness of patient satisfaction surveys is a suboptimal participation rate. Some patients may be unable to participate, because of language barriers, physical limitations, or mental problems. As the role of these barriers is poorly understood, we aimed to identify patient characteristics that are associated with non-participation in a patient satisfaction survey.MethodologyAt the University Hospitals of Geneva, Switzerland, a patient satisfaction survey is regularly conducted among all adult patients hospitalized for >24 hours on a one-month period in the departments of internal medicine, geriatrics, surgery, neurosciences, psychiatry, and gynaecology-obstetrics. In order to assess the factors associated with non-participation to the patient satisfaction survey, a case-control study was conducted among patients selected for the 2005 survey. Cases (non respondents, n = 195) and controls (respondents, n = 205) were randomly selected from the satisfaction survey, and information about potential barriers to participation was abstracted in a blinded fashion from the patients' medical and nursing charts.Principal findingsNon-participation in the satisfaction survey was independently associated with the presence of a language barrier (odds ratio [OR] 4.53, 95% confidence interval [CI95%]: 2.14-9.59), substance abuse (OR 3.75, CI95%: 1.97-7.14), cognitive limitations (OR 3.72, CI95%: 1.64-8.42), a psychiatric diagnosis (OR 1.99, CI95%: 1.23-3.23) and a sight deficiency (OR 2.07, CI95%: 0.98-4.36). The odds ratio for non-participation increased gradually with the number of predictors.ConclusionsFive barriers to non-participation in a mail survey were identified. Gathering patient feedback through mailed surveys may lead to an under-representation of some patient subgroups.

BACKGROUND: Regret is an unavoidable corollary of clinical practice. Physicians and nurses perform countless clinical decisions and actions, in a context characterised by time pressure, information overload, complexity and uncertainty. OBJECTIVE: To explore feelings associated with regretted clinical decisions or interventions of hospital-based physicians and nurses and to examine how these regrets are coped with. METHOD: Qualitative study of a volunteer sample of 12 physicians and 13 nurses from Swiss University Hospitals using semi-structured interviews and thematic analysis RESULTS: All interviewees reported at least one intense regret, which sometimes led to sleep problems, or taking sickness leave. Respondents also reported an accumulation effect of small and large regrets, which sometimes led to quitting one's unit or choosing another specialty. Respondents used diverse ways of coping with regrets, including changing their practices and seeking support from peers and family but also suppression of thoughts related to the situation and ruminations on the situation. Another coping strategy was acceptance of one's limits and of medicine's limits. Physicians reported that they avoided sharing with close colleagues because they felt they could lose their credibility. CONCLUSIONS: Since regret seems related to both positive and negative consequences, it is important to learn more about regret coping among healthcare providers and to determine whether training in coping strategies could help reduce negative consequences such as sleep problems, absenteeism, or turnover.