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2.
BMJ ; 374: n2231, 2021 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-34556486

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of antiviral antibody therapies and blood products for the treatment of novel coronavirus disease 2019 (covid-19). DESIGN: Living systematic review and network meta-analysis, with pairwise meta-analysis for outcomes with insufficient data. DATA SOURCES: WHO covid-19 database, a comprehensive multilingual source of global covid-19 literature, and six Chinese databases (up to 21 July 2021). STUDY SELECTION: Trials randomising people with suspected, probable, or confirmed covid-19 to antiviral antibody therapies, blood products, or standard care or placebo. Paired reviewers determined eligibility of trials independently and in duplicate. METHODS: After duplicate data abstraction, we performed random effects bayesian meta-analysis, including network meta-analysis for outcomes with sufficient data. We assessed risk of bias using a modification of the Cochrane risk of bias 2.0 tool. The certainty of the evidence was assessed using the grading of recommendations assessment, development, and evaluation (GRADE) approach. We meta-analysed interventions with ≥100 patients randomised or ≥20 events per treatment arm. RESULTS: As of 21 July 2021, we identified 47 trials evaluating convalescent plasma (21 trials), intravenous immunoglobulin (IVIg) (5 trials), umbilical cord mesenchymal stem cells (5 trials), bamlanivimab (4 trials), casirivimab-imdevimab (4 trials), bamlanivimab-etesevimab (2 trials), control plasma (2 trials), peripheral blood non-haematopoietic enriched stem cells (2 trials), sotrovimab (1 trial), anti-SARS-CoV-2 IVIg (1 trial), therapeutic plasma exchange (1 trial), XAV-19 polyclonal antibody (1 trial), CT-P59 monoclonal antibody (1 trial) and INM005 polyclonal antibody (1 trial) for the treatment of covid-19. Patients with non-severe disease randomised to antiviral monoclonal antibodies had lower risk of hospitalisation than those who received placebo: casirivimab-imdevimab (odds ratio (OR) 0.29 (95% CI 0.17 to 0.47); risk difference (RD) -4.2%; moderate certainty), bamlanivimab (OR 0.24 (0.06 to 0.86); RD -4.1%; low certainty), bamlanivimab-etesevimab (OR 0.31 (0.11 to 0.81); RD -3.8%; low certainty), and sotrovimab (OR 0.17 (0.04 to 0.57); RD -4.8%; low certainty). They did not have an important impact on any other outcome. There was no notable difference between monoclonal antibodies. No other intervention had any meaningful effect on any outcome in patients with non-severe covid-19. No intervention, including antiviral antibodies, had an important impact on any outcome in patients with severe or critical covid-19, except casirivimab-imdevimab, which may reduce mortality in patients who are seronegative. CONCLUSION: In patients with non-severe covid-19, casirivimab-imdevimab probably reduces hospitalisation; bamlanivimab-etesevimab, bamlanivimab, and sotrovimab may reduce hospitalisation. Convalescent plasma, IVIg, and other antibody and cellular interventions may not confer any meaningful benefit. SYSTEMATIC REVIEW REGISTRATION: This review was not registered. The protocol established a priori is included as a data supplement. FUNDING: This study was supported by the Canadian Institutes of Health Research (grant CIHR- IRSC:0579001321). READERS' NOTE: This article is a living systematic review that will be updated to reflect emerging evidence. Interim updates and additional study data will be posted on our website (www.covid19lnma.com).


Assuntos
Anticorpos Antivirais/uso terapêutico , COVID-19/terapia , Terapia Baseada em Transplante de Células e Tecidos/métodos , SARS-CoV-2/imunologia , Anticorpos Monoclonais/uso terapêutico , Antivirais/uso terapêutico , Teorema de Bayes , COVID-19/imunologia , Ensaios Clínicos como Assunto , Humanos , Imunização Passiva , Metanálise em Rede , Resultado do Tratamento
3.
BMJ Open ; 11(9): e050831, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34493521

RESUMO

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.


Assuntos
Canabidiol , Cannabis , Dor Crônica , Maconha Medicinal , Dor Crônica/tratamento farmacológico , Dronabinol , Humanos , Maconha Medicinal/uso terapêutico
4.
BMJ ; 374: n1034, 2021 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-34497047

RESUMO

OBJECTIVE: To determine the benefits and harms of medical cannabis and cannabinoids for chronic pain. DESIGN: Systematic review and meta-analysis. DATA SOURCES: MEDLINE, EMBASE, AMED, PsycInfo, CENTRAL, CINAHL, PubMed, Web of Science, Cannabis-Med, Epistemonikos, and trial registries up to January 2021. STUDY SELECTION: Randomised clinical trials of medical cannabis or cannabinoids versus any non-cannabis control for chronic pain at ≥1 month follow-up. DATA EXTRACTION AND SYNTHESIS: Paired reviewers independently assessed risk of bias and extracted data. We performed random-effects models meta-analyses and used GRADE to assess the certainty of evidence. RESULTS: A total of 32 trials with 5174 adult patients were included, 29 of which compared medical cannabis or cannabinoids with placebo. Medical cannabis was administered orally (n=30) or topically (n=2). Clinical populations included chronic non-cancer pain (n=28) and cancer related pain (n=4). Length of follow-up ranged from 1 to 5.5 months. Compared with placebo, non-inhaled medical cannabis probably results in a small increase in the proportion of patients experiencing at least the minimally important difference (MID) of 1 cm (on a 10 cm visual analogue scale (VAS)) in pain relief (modelled risk difference (RD) of 10% (95% confidence interval 5% to 15%), based on a weighted mean difference (WMD) of -0.50 cm (95% CI -0.75 to -0.25 cm, moderate certainty)). Medical cannabis taken orally results in a very small improvement in physical functioning (4% modelled RD (0.1% to 8%) for achieving at least the MID of 10 points on the 100-point SF-36 physical functioning scale, WMD of 1.67 points (0.03 to 3.31, high certainty)), and a small improvement in sleep quality (6% modelled RD (2% to 9%) for achieving at least the MID of 1 cm on a 10 cm VAS, WMD of -0.35 cm (-0.55 to -0.14 cm, high certainty)). Medical cannabis taken orally does not improve emotional, role, or social functioning (high certainty). Moderate certainty evidence shows that medical cannabis taken orally probably results in a small increased risk of transient cognitive impairment (RD 2% (0.1% to 6%)), vomiting (RD 3% (0.4% to 6%)), drowsiness (RD 5% (2% to 8%)), impaired attention (RD 3% (1% to 8%)), and nausea (RD 5% (2% to 8%)), but not diarrhoea; while high certainty evidence shows greater increased risk of dizziness (RD 9% (5% to 14%)) for trials with <3 months follow-up versus RD 28% (18% to 43%) for trials with ≥3 months follow-up; interaction test P=0.003; moderate credibility of subgroup effect). CONCLUSIONS: Moderate to high certainty evidence shows that non-inhaled medical cannabis or cannabinoids results in a small to very small improvement in pain relief, physical functioning, and sleep quality among patients with chronic pain, along with several transient adverse side effects, compared with placebo. The accompanying BMJ Rapid Recommendation provides contextualised guidance based on this body of evidence. SYSTEMATIC REVIEW REGISTRATION: https://osf.io/3pwn2.


Assuntos
Dor do Câncer/tratamento farmacológico , Canabinoides/efeitos adversos , Dor Crônica/tratamento farmacológico , Maconha Medicinal/administração & dosagem , Adulto , Canabinoides/administração & dosagem , Feminino , Humanos , Masculino , Maconha Medicinal/efeitos adversos , Diferença Mínima Clinicamente Importante , Medição da Dor , Ensaios Clínicos Controlados Aleatórios como Assunto , Sono/efeitos dos fármacos
5.
BMJ ; 374: n2040, 2021 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-34497062

RESUMO

CLINICAL QUESTION: What is the role of medical cannabis or cannabinoids for people living with chronic pain due to cancer or non-cancer causes? CURRENT PRACTICE: Chronic pain is common and distressing and associated with considerable socioeconomic burden globally. Medical cannabis is increasingly used to manage chronic pain, particularly in jurisdictions that have enacted policies to reduce use of opioids; however, existing guideline recommendations are inconsistent, and cannabis remains illegal for therapeutic use in many countries. RECOMMENDATION: The guideline expert panel issued a weak recommendation to offer a trial of non-inhaled medical cannabis or cannabinoids, in addition to standard care and management (if not sufficient), for people living with chronic cancer or non-cancer pain. HOW THIS GUIDELINE WAS CREATED: An international guideline development panel including patients, clinicians with content expertise, and methodologists produced this recommendation in adherence with standards for trustworthy guidelines using the GRADE approach. The MAGIC Evidence Ecosystem Foundation (MAGIC) provided methodological support. The panel applied an individual patient perspective. THE EVIDENCE: This recommendation is informed by a linked series of four systematic reviews summarising the current body of evidence for benefits and harms, as well as patient values and preferences, regarding medical cannabis or cannabinoids for chronic pain. UNDERSTANDING THE RECOMMENDATION: The recommendation is weak because of the close balance between benefits and harms of medical cannabis for chronic pain. It reflects a high value placed on small to very small improvements in self reported pain intensity, physical functioning, and sleep quality, and willingness to accept a small to modest risk of mostly self limited and transient harms. Shared decision making is required to ensure patients make choices that reflect their values and personal context. Further research is warranted and may alter this recommendation.


Assuntos
Canabinoides/administração & dosagem , Dor Crônica/tratamento farmacológico , Maconha Medicinal/administração & dosagem , Adolescente , Adulto , Canabinoides/efeitos adversos , Criança , Humanos , Maconha Medicinal/efeitos adversos , Adulto Jovem
6.
BMJ Open ; 11(7): e047717, 2021 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-34321302

RESUMO

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.


Assuntos
Canabinoides , Dor Crônica , Maconha Medicinal , Analgésicos Opioides/uso terapêutico , Canabinoides/uso terapêutico , Dor Crônica/tratamento farmacológico , Humanos , Maconha Medicinal/uso terapêutico , Estudos Observacionais como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Vômito
7.
BMJ Open ; 11(7): e046025, 2021 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-34244262

RESUMO

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.


Assuntos
Dor Crônica , Dor Musculoesquelética , Adolescente , Adulto , Dor Crônica/terapia , Humanos , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Revisões Sistemáticas como Assunto
8.
Lancet ; 398(10295): 117-118, 2021 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-34246341
9.
J Clin Epidemiol ; 139: 68-79, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34274489

RESUMO

OBJECTIVE: To describe the characteristics of Covid-19 randomized clinical trials (RCTs) and examine the association between trial characteristics and the likelihood of finding a significant effect. STUDY DESIGN: We conducted a systematic review to identify RCTs (up to October 21, 2020) evaluating drugs or blood products to treat or prevent Covid-19. We extracted trial characteristics (number of centers, funding sources, and sample size) and assessed risk of bias (RoB) using the Cochrane RoB 2.0 tool. We performed logistic regressions to evaluate the association between RoB due to randomization, single vs. multicentre, funding source, and sample size, and finding a statistically significant effect. RESULTS: We included 91 RCTs (n = 46,802); 40 (44%) were single-center, 23 (25.3%) enrolled <50 patients, 28 (30.8%) received industry funding, and 75 (82.4%) had high or probably high RoB. Thirty-eight trials (41.8%) reported a statistically significant effect. RoB due to randomization and being a single-center trial were associated with increased odds of finding a statistically significant effect. CONCLUSIONS: There is high variability in RoB among Covid-19 trials. Researchers, funders, and knowledge-users should be cognizant of the impact of RoB due to randomization and single-center trial status in designing, evaluating, and interpreting the results of RCTs. REGISTRATION: CRD42020192095.

11.
BMC Med Inform Decis Mak ; 21(1): 202, 2021 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-34187484

RESUMO

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.


Assuntos
Tomada de Decisões , Técnicas de Apoio para a Decisão , Comunicação , Tomada de Decisão Compartilhada , Humanos , Motivação , Guias de Prática Clínica como Assunto
12.
J Psychiatr Res ; 140: 53-59, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34091347

RESUMO

OBJECTIVE: Psychiatric impact of COVID-19 is still explored and previous data suggest potential risks of anxiety, depression and PTSD related to COVID-19. We aimed to explore the predictive value of risk factors during hospitalization (T0) for COVID-19 for anxiety, depression and PTSD and at three months (T1) because they could differ over these two time points. METHODS: We performed a screening of mental suffering in hospitalized patients for COVID-19, as well as specialized care and three months longitudinal follow-up. We evaluated at T0 and at T1 the prevalence of anxiety, depression and PTSD in survivors who benefited from early detection and treatment, and assessed possible risk factors in adults surviving COVID-19 between the 30th March and the 1st of July 2020. RESULTS: 109 patients were screened at T0 and 61 of these were reassessed at T1. At T0, we found 44.9% pathological score on peritraumatic dissociation experiences questionnaire (PDEQ), 85.4% of post-traumatic stress disorder symptoms (PTSS), 14.6% of pathological rate of post-traumatic stress disorder scale 5 (PCL5) and at T1, 86.9% of PTSS, 10.6% of pathological rate of PCL5. Finally, PDEQ score at T0 during hospitalization was positively correlated to PCL-5 score at T1 (ß = 0.26, p = 0.01) and that was confirmed in multivariate analysis (ß = 0.04, p = 0.02 for the log of PCL-5 per point on the PDEQ). CONCLUSION: Screening of psychiatric symptoms during hospitalization for COVID-19 should be systematic, especially peritraumatic dissociation to offer an early treatment and prevent PTSD, which seemed frequent for hospitalized patients for COVID-19 at three months.


Assuntos
COVID-19 , Transtornos de Estresse Pós-Traumáticos , Adulto , Transtornos Dissociativos/epidemiologia , Humanos , Estudos Longitudinais , SARS-CoV-2 , Transtornos de Estresse Pós-Traumáticos/epidemiologia
13.
Respiration ; 100(8): 786-793, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34023830

RESUMO

BACKGROUND: The COVID-19 pandemic has led to shortage of intensive care unit (ICU) capacity. We developed a triage strategy including noninvasive respiratory support and admission to the intermediate care unit (IMCU). ICU admission was restricted to patients requiring invasive ventilation. OBJECTIVES: The aim of this study is to describe the characteristics and outcomes of patients admitted to the IMCU. METHOD: Retrospective cohort including consecutive patients admitted between March 28 and April 27, 2020. The primary outcome was the proportion of patients with severe hypoxemic respiratory failure avoiding ICU admission. Secondary outcomes included the rate of emergency intubation, 28-day mortality, and predictors of ICU admission. RESULTS: One hundred fifty-seven patients with COVID-19-associated pneumonia were admitted to the IMCU. Among the 85 patients admitted for worsening respiratory failure, 52/85 (61%) avoided ICU admission. In multivariate analysis, PaO2/FiO2 (OR 0.98; 95% CI: 0.96-0.99) and BMI (OR 0.88; 95% CI: 0.78-0.98) were significantly associated with ICU admission. No death or emergency intubation occurred in the IMCU. CONCLUSIONS: IMCU admission including standardized triage criteria, self-proning, and noninvasive respiratory support prevents ICU admission for a large proportion of patients with COVID-19 hypoxemic respiratory failure. In the context of the COVID-19 pandemic, IMCUs may play an important role in preserving ICU capacity by avoiding ICU admission for patients with worsening respiratory failure and allowing early discharge of ICU patients.


Assuntos
COVID-19/terapia , Ventilação não Invasiva , Unidades de Cuidados Respiratórios/estatística & dados numéricos , Insuficiência Respiratória/terapia , Idoso , COVID-19/complicações , COVID-19/mortalidade , Feminino , Pessoal de Saúde/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Respiratória/virologia , Estudos Retrospectivos , Licença Médica/estatística & dados numéricos , Suíça/epidemiologia
14.
BMJ ; 373: n1091, 2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33975892

RESUMO

CLINICAL QUESTION: What are the benefits and harms of sodium-glucose cotransporter 2 (SGLT-2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists when added to usual care (lifestyle interventions and/or other diabetes drugs) in adults with type 2 diabetes at different risk for cardiovascular and kidney outcomes? CURRENT PRACTICE: Clinical decisions about treatment of type 2 diabetes have been led by glycaemic control for decades. SGLT-2 inhibitors and GLP-1 receptor agonists are traditionally used in people with elevated glucose level after metformin treatment. This has changed through trials demonstrating atherosclerotic cardiovascular disease (CVD) and chronic kidney disease (CKD) benefits independent of medications' glucose-lowering potential. RECOMMENDATIONS: The guideline panel issued risk-stratified recommendations concerning the use of SGLT-2 inhibitors or GLP-1 receptor agonists in adults with type 2 diabetes• Three or fewer cardiovascular risk factors without established CVD or CKD: Weak recommendation against starting SGLT-2 inhibitors or GLP-1 receptor agonists.• More than three cardiovascular risk factors without established CVD or CKD: Weak recommendation for starting SGLT-2 inhibitors and weak against starting GLP-1 receptor agonists.• Established CVD or CKD: Weak recommendation for starting SGLT-2 inhibitors and GLP-1 receptor agonists.• Established CVD and CKD: Strong recommendation for starting SGLT-2 inhibitors and weak recommendation for starting GLP-1 receptor agonists.• For those committed to further reducing their risk for CVD and CKD outcomes: Weak recommendation for starting SGLT-2 inhibitors rather than GLP-1 receptor agonists. HOW THIS GUIDELINE WAS CREATED: An international panel including patients, clinicians, and methodologists created these recommendations following standards for trustworthy guidelines and using the GRADE approach. The panel applied an individual patient perspective. THE EVIDENCE: A linked systematic review and network meta-analysis (764 randomised trials included 421 346 participants) of benefits and harms found that SGLT-2 inhibitors and GLP-1 receptor agonists generally reduce overall death, and incidence of myocardial infarctions, and end-stage kidney disease or kidney failure (moderate to high certainty evidence). These medications exert different effects on stroke, hospitalisations for heart failure, and key adverse events in different subgroups. Absolute effects of benefit varied widely based on patients' individual risk (for example, from five fewer deaths in the lowest risk to 48 fewer deaths in the highest risk, for 1000 patients treated over five years). A prognosis review identified 14 eligible risk prediction models, one of which (RECODe) informed most baseline risk estimates in evidence summaries to underpin the risk-stratified recommendations. Concerning patients' values and preferences, the recommendations were supported by evidence from a systematic review of published literature, a patient focus group study, a practical issues summary, and a guideline panel survey. UNDERSTANDING THE RECOMMENDATION: We stratified the recommendations by the levels of risk for CVD and CKD and systematically considered the balance of benefits, harms, other considerations, and practical issues for each risk group. The strong recommendation for SGLT-2 inhibitors in patients with CVD and CKD reflects what the panel considered to be a clear benefit. For all other adults with type 2 diabetes, the weak recommendations reflect what the panel considered to be a finer balance between benefits, harms, and burdens of treatment options. Clinicians using the guideline can identify their patient's individual risk for cardiovascular and kidney outcomes using credible risk calculators such as RECODe. Interactive evidence summaries and decision aids may support well informed treatment choices, including shared decision making.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/uso terapêutico , Transportador 2 de Glucose-Sódio/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Humanos , Nefropatias/prevenção & controle , Guias de Prática Clínica como Assunto , Medição de Risco
15.
BMJ ; 373: n949, 2021 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-33903131

RESUMO

OBJECTIVE: To determine and compare the effects of drug prophylaxis on SARS-CoV-2 infection and covid-19. DESIGN: Living systematic review and network meta-analysis. DATA SOURCES: World Health Organization covid-19 database, a comprehensive multilingual source of global covid-19 literature to 25 March 2021, and six additional Chinese databases to 20 February 2021. STUDY SELECTION: Randomised trials of people at risk of covid-19 who were assigned to receive prophylaxis or no prophylaxis (standard care or placebo). Pairs of reviewers independently screened potentially eligible articles. METHODS: Random effects bayesian network meta-analysis was performed after duplicate data abstraction. Included studies were assessed for risk of bias using a modification of the Cochrane risk of bias 2.0 tool, and certainty of evidence was assessed using the grading of recommendations assessment, development, and evaluation (GRADE) approach. RESULTS: The first iteration of this living network meta-analysis includes nine randomised trials-six of hydroxychloroquine (n=6059 participants), one of ivermectin combined with iota-carrageenan (n=234), and two of ivermectin alone (n=540), all compared with standard care or placebo. Two trials (one of ramipril and one of bromhexine hydrochloride) did not meet the sample size requirements for network meta-analysis. Hydroxychloroquine has trivial to no effect on admission to hospital (risk difference 1 fewer per 1000 participants, 95% credible interval 3 fewer to 4 more; high certainty evidence) or mortality (1 fewer per 1000, 2 fewer to 3 more; high certainty). Hydroxychloroquine probably does not reduce the risk of laboratory confirmed SARS-CoV-2 infection (2 more per 1000, 18 fewer to 28 more; moderate certainty), probably increases adverse effects leading to drug discontinuation (19 more per 1000, 1 fewer to 70 more; moderate certainty), and may have trivial to no effect on suspected, probable, or laboratory confirmed SARS-CoV-2 infection (15 fewer per 1000, 64 fewer to 41 more; low certainty). Owing to serious risk of bias and very serious imprecision, and thus very low certainty of evidence, the effects of ivermectin combined with iota-carrageenan on laboratory confirmed covid-19 (52 fewer per 1000, 58 fewer to 37 fewer), ivermectin alone on laboratory confirmed infection (50 fewer per 1000, 59 fewer to 16 fewer) and suspected, probable, or laboratory confirmed infection (159 fewer per 1000, 165 fewer to 144 fewer) remain very uncertain. CONCLUSIONS: Hydroxychloroquine prophylaxis has trivial to no effect on hospital admission and mortality, probably increases adverse effects, and probably does not reduce the risk of SARS-CoV-2 infection. Because of serious risk of bias and very serious imprecision, it is highly uncertain whether ivermectin combined with iota-carrageenan and ivermectin alone reduce the risk of SARS-CoV-2 infection. SYSTEMATIC REVIEW REGISTRATION: This review was not registered. The protocol established a priori is included as a supplement. READERS' NOTE: This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication.


Assuntos
COVID-19 , Carragenina/farmacologia , Saúde Global/estatística & dados numéricos , Hidroxicloroquina/farmacologia , Ivermectina/farmacologia , Anti-Infecciosos/farmacologia , COVID-19/prevenção & controle , Quimioprevenção/métodos , Quimioprevenção/estatística & dados numéricos , Humanos , SARS-CoV-2 , Resultado do Tratamento , Incerteza
16.
BMJ (Online) ; 372(526): 1-5, Mar. 2, 2021. tab
Artigo em Inglês | BIGG - guias GRADE | ID: biblio-1281892

RESUMO

Clinical question What is the role of drugs in preventing covid-19? Why does this matter?There is widespread interest in whether drug interventions can be used for the prevention of covid-19, but there is uncertainty about which drugs, if any, are effective. The first version of this living guideline focuses on the evidence for hydroxychloroquine. Subsequent updates will cover other drugs being investigated for their role in the prevention of covid-19. The guideline development panel made a strong recommendation against the use of hydroxychloroquine for individuals who do not have covid-19 (high certainty). How this guideline was created This living guideline is from the World Health Organization (WHO) and provides up to date covid-19 guidance to inform policy and practice worldwide. Magic Evidence Ecosystem Foundation (MAGIC) provided methodological support. A living systematic review with network analysis informed the recommendations. An international guideline development panel of content experts, clinicians, patients, an ethicist and methodologists produced recommendations following standards for trustworthy guideline development using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Understanding the new recommendation The linked systematic review and network meta-analysis (6 trials and 6059 participants) found that hydroxychloroquine had a small or no effect on mortality and admission to hospital (high certainty evidence). There was a small or no effect on laboratory confirmed SARS-CoV-2 infection (moderate certainty evidence) but probably increased adverse events leading to discontinuation (moderate certainty evidence). The panel judged that almost all people would not consider this drug worthwhile. In addition, the panel decided that contextual factors such as resources, feasibility, acceptability, and equity for countries and healthcare systems were unlikely to alter the recommendation. The panel considers that this drug is no longer a research priority and that resources should rather be oriented to evaluate other more promising drugs to prevent covid-19. Updates This is a living guideline. New recommendations will be published in this article and signposted by update notices to this guideline.


Assuntos
Humanos , SARS-CoV-2/efeitos dos fármacos , COVID-19/tratamento farmacológico , Hidroxicloroquina/uso terapêutico
17.
CJEM ; 23(2): 214-218, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33709360

RESUMO

OBJECTIVE: To explore the impact of the implementation of eCTAS, a real-time electronic decision-support tool, on hospital admission, rate of left without being seen, and time from triage to physician initial assessment. METHODS: We conducted a cohort study using population-based administrative data from all Ontario emergency departments (EDs) that had implemented eCTAS for 9 months. We compared 6 months post-eCTAS data to the same 6 months the previous year (pre-eCTAS). We included triage encounters of adult (≥ 18 years) patients if they had one of 16 pre-specified, high-volume presenting complaints. Multivariable logistic regression and quantile regression models informed the effect of eCTAS on outcomes. RESULTS: We included data from 354,176 triage encounters from 31 EDs. There was a change in the distribution of triage scores post-eCTAS, with fewer patients classified as CTAS 2 and CTAS 3, and more patients classified as CTAS 1 and CTAS 4. Overall, hospital admission decreased post-eCTAS (adjusted OR: 0.98; 95% CI: 0.97 to 1.00), with fewer CTAS 2 and more CTAS 3 and CTAS 4 patients admitted post-eCTAS. The rate of left without being seen increased (2.8% vs. 3.0%; adjusted OR: 1.07; 95% CI: 1.03 to 1.11) post-eCTAS, while time to physician initial assessment proved similar pre and post-eCTAS. CONCLUSIONS: eCTAS implementation had little impact on admission, rate of left without being seen and time to physician initial assessment. eCTAS appears to reclassify patients from higher to lower acuity scores, resulting in higher admission rates for CTAS 3 and CTAS 4 patients. It remains unknown if this reclassification is appropriate.


Assuntos
Médicos , Triagem , Adulto , Estudos de Coortes , Eletrônica , Serviço Hospitalar de Emergência , Hospitais , Humanos
18.
BMJ ; 372: n526, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33649077

RESUMO

CLINICAL QUESTION: What is the role of drugs in preventing covid-19? WHY DOES THIS MATTER?: There is widespread interest in whether drug interventions can be used for the prevention of covid-19, but there is uncertainty about which drugs, if any, are effective. The first version of this living guideline focuses on the evidence for hydroxychloroquine. Subsequent updates will cover other drugs being investigated for their role in the prevention of covid-19. RECOMMENDATION: The guideline development panel made a strong recommendation against the use of hydroxychloroquine for individuals who do not have covid-19 (high certainty). HOW THIS GUIDELINE WAS CREATED: This living guideline is from the World Health Organization (WHO) and provides up to date covid-19 guidance to inform policy and practice worldwide. Magic Evidence Ecosystem Foundation (MAGIC) provided methodological support. A living systematic review with network analysis informed the recommendations. An international guideline development panel of content experts, clinicians, patients, an ethicist and methodologists produced recommendations following standards for trustworthy guideline development using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. UNDERSTANDING THE NEW RECOMMENDATION: The linked systematic review and network meta-analysis (6 trials and 6059 participants) found that hydroxychloroquine had a small or no effect on mortality and admission to hospital (high certainty evidence). There was a small or no effect on laboratory confirmed SARS-CoV-2 infection (moderate certainty evidence) but probably increased adverse events leading to discontinuation (moderate certainty evidence). The panel judged that almost all people would not consider this drug worthwhile. In addition, the panel decided that contextual factors such as resources, feasibility, acceptability, and equity for countries and healthcare systems were unlikely to alter the recommendation. The panel considers that this drug is no longer a research priority and that resources should rather be oriented to evaluate other more promising drugs to prevent covid-19. UPDATES: This is a living guideline. New recommendations will be published in this article and signposted by update notices to this guideline. READERS NOTE: This is the first version of the living guideline for drugs to prevent covid-19. It complements the WHO living guideline on drugs to treat covid-19. When citing this article, please consider adding the update number and date of access for clarity.


Assuntos
COVID-19/prevenção & controle , Quimioprevenção , Hidroxicloroquina/farmacologia , Medição de Risco , COVID-19/epidemiologia , Quimioprevenção/métodos , Quimioprevenção/normas , Tomada de Decisão Clínica/métodos , Humanos , Fatores Imunológicos/farmacologia , SARS-CoV-2/efeitos dos fármacos , Incerteza , Organização Mundial da Saúde
19.
Heart ; 107(16): 1289-1295, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33563630

RESUMO

The review aims to summarise evidence addressing patients' values, preferences and practical issues on deciding between transcatheter aortic valve insertion (TAVI) and surgical aortic valve replacement (SAVR) for aortic stenosis. We searched databases and grey literature until June 2020. We included studies of adults with aortic stenosis eliciting values and preferences about treatment, excluding medical management or palliative care. Qualitative findings were synthesised using thematic analysis, and quantitative findings were narratively described. Evidence certainty was assessed using CERQual (Confidence in the Evidence from Reviews of Qualitative Research) and GRADE (Grading of Recommendations Assessment, Development and Evaluation). We included eight studies. Findings ranged from low to very low certainty. Most studies only addressed TAVI. Studies addressing both TAVI and SAVR reported on factors affecting patients' decision-making along with treatment effectiveness, instead of trade-offs between procedures. Willingness to accept risk varied considerably. To improve their health status, participants were willing to accept higher mortality risk than current evidence suggests for either procedure. No study explicitly addressed valve reintervention, and one study reported variability in willingness to accept shorter duration of known effectiveness of TAVI compared with SAVR. The most common themes were desire for symptom relief and improved function. Participants preferred minimally invasive procedures with shorter hospital stay and recovery. The current body of evidence on patients' values, preferences and practical issues related to aortic stenosis management is of suboptimal rigour and reports widely disparate results regarding patients' perceptions. These findings emphasise the need for higher quality studies to inform clinical practice guidelines and the central importance of shared decision-making to individualise care fitted to each patient.

20.
Clin Microbiol Infect ; 27(4): 532-537, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33476807

RESUMO

BACKGROUND: While the landscape of vaccine and treatment candidates against the novel coronavirus disease 2019 (COVID-19) has been reviewed systematically, prophylactic candidates remain unexplored. OBJECTIVES: To map pre- and postexposure prophylactic (PrEP and PEP) candidate for COVID-19. DATA SOURCES: PubMed/Medline, Embase, International Committee of Medical Journal Editors and International Clinical Trials Registry Platform clinical trial registries and medRxiv. STUDY ELIGIBILITY CRITERIA AND PARTICIPANTS: All studies in humans or animals and randomized controlled trials (RCTs) in humans reporting primary data on prophylactic candidates against COVID-19, excluding studies focused on key populations. INTERVENTIONS: PrEP and PEP candidate for COVID-19. METHODS: Systematic review and qualitative synthesis of COVID-19 PrEP and PEP studies and RCTs complemented by search of medRxiv and PubMed and Embase for studies reporting RCT outcomes since systematic review search completion. RESULTS: We identified 13 studies (from 2119 database records) and 117 RCTs (from 5565 RCTs listed in the registries) that met the inclusion criteria. Non-RCT studies reported on cross-sectional studies using hydroxychloroquine (HCQ) in humans (n = 2) or reported on animal studies (n = 7), most of which used antibodies. All five completed RCTs focused on the use of HCQ as either PrEP or PEP, and these and the cross-sectional studies reported no prophylactic effect. The majority of ongoing RCTs evaluated HCQ or other existing candidates including non-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, anti(retro)virals or use of vitamins and supplements. CONCLUSIONS: The key message from completed studies and RCTs seems to be that HCQ does not work. There is little evidence regarding other compounds, with all RCTs using candidates other than HCQ still ongoing. It remains to be seen if the portfolio of existing molecules being evaluated in RCTs will identify successful prophylaxis against COVID-19 or if there is a need for the development of new candidates.


Assuntos
Antivirais/uso terapêutico , COVID-19/prevenção & controle , Profilaxia Pós-Exposição , Profilaxia Pré-Exposição , Animais , Anticorpos Monoclonais/uso terapêutico , Anticorpos Neutralizantes/uso terapêutico , Anticorpos Antivirais/uso terapêutico , Antimaláricos/uso terapêutico , Humanos , Hidroxicloroquina/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , SARS-CoV-2/imunologia , Vacinas
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