Showing papers by "Cochrane Collaboration published in 2021"

Impact of COVID-19 pandemic on utilisation of healthcare services: a systematic review.

Abstract: Objectives To determine the extent and nature of changes in utilisation of healthcare services during COVID-19 pandemic. Design Systematic review. Eligibility Eligible studies compared utilisation of services during COVID-19 pandemic to at least one comparable period in prior years. Services included visits, admissions, diagnostics and therapeutics. Studies were excluded if from single centres or studied only patients with COVID-19. Data sources PubMed, Embase, Cochrane COVID-19 Study Register and preprints were searched, without language restrictions, until 10 August, using detailed searches with key concepts including COVID-19, health services and impact. Data analysis Risk of bias was assessed by adapting the Risk of Bias in Non-randomised Studies of Interventions tool, and a Cochrane Effective Practice and Organization of Care tool. Results were analysed using descriptive statistics, graphical figures and narrative synthesis. Outcome measures Primary outcome was change in service utilisation between prepandemic and pandemic periods. Secondary outcome was the change in proportions of users of healthcare services with milder or more severe illness (eg, triage scores). Results 3097 unique references were identified, and 81 studies across 20 countries included, reporting on >11 million services prepandemic and 6.9 million during pandemic. For the primary outcome, there were 143 estimates of changes, with a median 37% reduction in services overall (IQR −51% to −20%), comprising median reductions for visits of 42% (−53% to −32%), admissions 28% (−40% to −17%), diagnostics 31% (−53% to −24%) and for therapeutics 30% (−57% to −19%). Among 35 studies reporting secondary outcomes, there were 60 estimates, with 27 (45%) reporting larger reductions in utilisation among people with a milder spectrum of illness, and 33 (55%) reporting no difference. Conclusions Healthcare utilisation decreased by about a third during the pandemic, with considerable variation, and with greater reductions among people with less severe illness. While addressing unmet need remains a priority, studies of health impacts of reductions may help health systems reduce unnecessary care in the postpandemic recovery. PROSPERO registration number CRD42020203729.

Declaración PRISMA 2020: una guía actualizada para la publicación de revisiones sistemáticas

Abstract: Resumen La declaracion PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses), publicada en 2009, se diseno para ayudar a los autores de revisiones sistematicas a documentar de manera transparente el porque de la revision, que hicieron los autores y que encontraron. Durante la ultima decada, ha habido muchos avances en la metodologia y terminologia de las revisiones sistematicas, lo que ha requerido una actualizacion de esta guia. La declaracion prisma 2020 sustituye a la declaracion de 2009 e incluye una nueva guia de presentacion de las publicaciones que refleja los avances en los metodos para identificar, seleccionar, evaluar y sintetizar estudios. La estructura y la presentacion de los items ha sido modificada para facilitar su implementacion. En este articulo, presentamos la lista de verificacion PRISMA 2020 con 27 items, y una lista de verificacion ampliada que detalla las recomendaciones en la publicacion de cada item, la lista de verificacion del resumen estructurado PRISMA 2020 y el diagrama de flujo revisado para revisiones sistematicas.

Sodium-glucose cotransporter protein-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials

Abstract: Objective To evaluate sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes at varying cardiovascular and renal risk. Design Network meta-analysis. Data sources Medline, Embase, and Cochrane CENTRAL up to 11 August 2020. Eligibility criteria for selecting studies Randomised controlled trials comparing SGLT-2 inhibitors or GLP-1 receptor agonists with placebo, standard care, or other glucose lowering treatment in adults with type 2 diabetes with follow up of 24 weeks or longer. Studies were screened independently by two reviewers for eligibility, extracted data, and assessed risk of bias. Main outcome measures Frequentist random effects network meta-analysis was carried out and GRADE (grading of recommendations assessment, development, and evaluation) used to assess evidence certainty. Results included estimated absolute effects of treatment per 1000 patients treated for five years for patients at very low risk (no cardiovascular risk factors), low risk (three or more cardiovascular risk factors), moderate risk (cardiovascular disease), high risk (chronic kidney disease), and very high risk (cardiovascular disease and kidney disease). A guideline panel provided oversight of the systematic review. Results 764 trials including 421 346 patients proved eligible. All results refer to the addition of SGLT-2 inhibitors and GLP-1 receptor agonists to existing diabetes treatment. Both classes of drugs lowered all cause mortality, cardiovascular mortality, non-fatal myocardial infarction, and kidney failure (high certainty evidence). Notable differences were found between the two agents: SGLT-2 inhibitors reduced mortality and admission to hospital for heart failure more than GLP-1 receptor agonists, and GLP-1 receptor agonists reduced non-fatal stroke more than SGLT-2 inhibitors (which appeared to have no effect). SGLT-2 inhibitors caused genital infection (high certainty), whereas GLP-1 receptor agonists might cause severe gastrointestinal events (low certainty). Low certainty evidence suggested that SGLT-2 inhibitors and GLP-1 receptor agonists might lower body weight. Little or no evidence was found for the effect of SGLT-2 inhibitors or GLP-1 receptor agonists on limb amputation, blindness, eye disease, neuropathic pain, or health related quality of life. The absolute benefits of these drugs vary substantially across patients from low to very high risk of cardiovascular and renal outcomes (eg, SGLT-2 inhibitors resulted in 5 to 48 fewer deaths in 1000 patients over five years; see interactive decision support tool (https://magicevidence.org/match-it/200820dist/#!/) for all outcomes. Conclusions In patients with type 2 diabetes, SGLT-2 inhibitors and GLP-1 receptor agonists reduced cardiovascular and renal outcomes, with notable differences in benefits and harms. Absolute benefits are determined by individual risk profiles of patients, with clear implications for clinical practice, as reflected in the BMJ Rapid Recommendations directly informed by this systematic review. Systematic review registration PROSPERO CRD42019153180.

The PRISMA 2020 statement: an updated guideline for reporting systematic reviews.

Abstract: The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, published in 2009, was designed to help systematic reviewers transparently report why the review was done, what the authors did, and what they found. Over the past decade, advances in systematic review methodology and terminology have necessitated an update to the guideline. The PRISMA 2020 statement replaces the 2009 statement and includes new reporting guidance that reflects advances in methods to identify, select, appraise, and synthesise studies. The structure and presentation of the items have been modified to facilitate implementation. In this article, we present the PRISMA 2020 27-item checklist, an expanded checklist that details reporting recommendations for each item, the PRISMA 2020 abstract checklist, and the revised flow diagrams for original and updated reviews. Full English text available from:www.revespcardiol.org/en.

ERS clinical practice guidelines on treatment of sarcoidosis

Abstract: Background The major reasons to treat sarcoidosis are to lower the morbidity and mortality risk or to improve quality of life (QoL). The indication for treatment varies depending on which manifestation is the cause of symptoms: lungs, heart, brain, skin, or other manifestations. While glucocorticoids (GC) remain the first choice for initial treatment of symptomatic disease, prolonged use is associated with significant toxicity. GC-sparing alternatives are available. The presented treatment guideline aims to provide guidance to physicians treating the very heterogenous sarcoidosis manifestations. Materials and Methods A European Respiratory Society Task Force (TF) committee composed of clinicians, methodologists, and patients with experience in sarcoidosis developed recommendations based on the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) methodology. The committee developed eight PICO (Patients, Intervention, Comparison, Outcomes) questions and these were used to make specific evidence-based recommendations. Results The TF committee delivered twelve recommendations for seven PICOs. These included treatment of pulmonary, cutaneous, cardiac, and neurologic disease as well as fatigue. One PICO question regarding small fiber neuropathy had insufficient evidence to support a recommendation. In addition to the recommendations, the committee provided information on how they use alternative treatments, when there was insufficient evidence to support a recommendation. Conclusions There are many treatments available to treat sarcoidosis. Given the diverse nature of the disease, treatment decisions require an assessment of organ involvement, risk for significant morbidity, and impact on QoL of the disease and treatment. Message An evidence based guideline for treatment of sarcoidosis is presented. The panel used the GRADE approach and specific recommendations are made. A major factor in treating patients is the risk of loss of organ function or impairment of quality of life.

Mental burden and its risk and protective factors during the early phase of the SARS-CoV-2 pandemic: systematic review and meta-analyses.

Abstract: Mental burden due to the SARS-CoV-2 pandemic has been widely reported for the general public and specific risk groups like healthcare workers and different patient populations We aimed to assess its impact on mental health during the early phase by comparing pandemic with prepandemic data and to identify potential risk and protective factors For this systematic review and meta-analyses, we systematically searched PubMed, PsycINFO, and Web of Science from January 1, 2019 to May 29, 2020, and screened reference lists of included studies In addition, we searched PubMed and PsycINFO for prepandemic comparative data Survey studies assessing mental burden by the SARS-CoV-2 pandemic in the general population, healthcare workers, or any patients (eg, COVID-19 patients), with a broad range of eligible mental health outcomes, and matching studies evaluating prepandemic comparative data in the same population (if available) were included We used multilevel meta-analyses for main, subgroup, and sensitivity analyses, focusing on (perceived) stress, symptoms of anxiety and depression, and sleep-related symptoms as primary outcomes Of 2429 records retrieved, 104 were included in the review (n = 208,261 participants), 43 in the meta-analysis (n = 71,613 participants) While symptoms of anxiety (standardized mean difference [SMD] 040; 95% CI 015–065) and depression (SMD 067; 95% CI 007–127) were increased in the general population during the early phase of the pandemic compared with prepandemic conditions, mental burden was not increased in patients as well as healthcare workers, irrespective of COVID-19 patient contact Specific outcome measures (eg, Patient Health Questionnaire) and older comparative data (published ≥5 years ago) were associated with increased mental burden Across the three population groups, existing mental disorders, female sex, and concerns about getting infected were repeatedly reported as risk factors, while older age, a good economic situation, and education were protective This meta-analysis paints a more differentiated picture of the mental health consequences in pandemic situations than previous reviews High-quality, representative surveys, high granular longitudinal studies, and more research on protective factors are required to better understand the psychological impacts of the SARS-CoV-2 pandemic and to help design effective preventive measures and interventions that are tailored to the needs of specific population groups

European Academy of Neurology/Peripheral Nerve Society guideline on diagnosis and treatment of chronic inflammatory demyelinating polyradiculoneuropathy: Report of a joint Task Force-Second revision.

Abstract: To revise the 2010 consensus guideline on chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Seventeen disease experts, a patient representative, and two Cochrane methodologists constructed 12 Population/Intervention/Comparison/Outcome (PICO) questions regarding diagnosis and treatment to guide the literature search. Data were extracted and summarized in GRADE summary of findings (for treatment PICOs) or evidence tables (for diagnostic PICOs). Statements were prepared according to the GRADE Evidence-to-Decision frameworks. Typical CIDP and CIDP variants were distinguished. The previous term "atypical CIDP" was replaced by "CIDP variants" because these are well characterized entities (multifocal, focal, distal, motor, or sensory CIDP). The levels of diagnostic certainty were reduced from three (definite, probable, possible CIDP) to only two (CIDP and possible CIDP), because the diagnostic accuracy of criteria for probable and definite CIDP did not significantly differ. Good Practice Points were formulated for supportive criteria and investigations to be considered to diagnose CIDP. The principal treatment recommendations were: (a) intravenous immunoglobulin (IVIg) or corticosteroids are strongly recommended as initial treatment in typical CIDP and CIDP variants; (b) plasma exchange is strongly recommended if IVIg and corticosteroids are ineffective; (c) IVIg should be considered as first-line treatment in motor CIDP (Good Practice Point); (d) for maintenance treatment, IVIg, subcutaneous immunoglobulin or corticosteroids are recommended; (e) if the maintenance dose of any of these is high, consider either combination treatments or adding an immunosuppressant or immunomodulatory drug (Good Practice Point); and (f) if pain is present, consider drugs against neuropathic pain and multidisciplinary management (Good Practice Point).

Interleukin-6 blocking agents for treating COVID-19: a living systematic review.

Abstract: BACKGROUND: Interleukin 6 (IL-6) blocking agents have been used for treating severe coronavirus disease 2019 (COVID-19). Their immunosuppressive effect might be valuable in patients with COVID-19 characterised by substantial immune system dysfunction by controlling inflammation and promoting disease tolerance. OBJECTIVES: To assess the effect of IL-6 blocking agents compared to standard care alone or with placebo on efficacy and safety outcomes in COVID-19. We will update this assessment regularly. SEARCH METHODS: We searched the World Health Organization (WHO) International Clinical Trials Registry Platform (up to 11 February 2021) and the L-OVE platform, and Cochrane COVID-19 Study Register to identify trials up to 26 February 2021. SELECTION CRITERIA: We included randomised controlled trials (RCTs) evaluating IL-6 blocking agents compared with standard care alone or with placebo for people with COVID-19, regardless of disease severity. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. The protocol was amended to reduce the number of outcomes considered. Two review authors independently collected data and assessed the risk of bias with the Cochrane Risk of Bias 2 tool. We rated the certainty of evidence with the GRADE approach for the critical outcomes such as clinical improvement (defined as hospital discharge or improvement on the scale used by trialists to evaluate clinical progression or recovery) (day (D) 28 / ≥ D60); WHO Clinical Progression Score of level 7 or above (i.e. the proportion of participants with mechanical ventilation +/- additional organ support OR death) (D28 / ≥ D60); all-cause mortality (D28 / ≥ D60); incidence of any adverse events; and incidence of serious adverse events. MAIN RESULTS: We identified 10 RCTs with available data including one platform trial comparing tocilizumab and sarilumab with standard of care. These trials evaluated tocilizumab (nine RCTs including two platform trials; seven were reported as peer-reviewed articles, two as preprints; 6428 randomised participants); and two sarilumab (one platform trial reported as peer reviewed article, one reported as preprint, 880 randomised participants). All trials included were multicentre trials. They were conducted in Brazil, China, France, Italy, UK, USA, and four were multi-country trials. The mean age range of participants ranged from 56 to 65 years; 4572 (66.3%) of trial participants were male. Disease severity ranged from mild to critical disease. The reported proportion of participants on oxygen at baseline but not intubated varied from 56% to 100% where reported. Five trials reported the inclusion of intubated patients at baseline. We identified a further 20 registered RCTs of tocilizumab compared to placebo/standard care (five completed without available results, five terminated without available results, eight ongoing, two not recruiting); 11 RCTs of sarilumab (two completed without results, three terminated without available results, six ongoing); six RCTs of clazakisumab (five ongoing, one not recruiting); two RCTs of olokizumab (one completed, one not recruiting); one of siltuximab (ongoing) and one RCT of levilimab (completed without available results). Of note, three were cancelled (2 tocilizumab, 1 clazakisumab). One multiple-arm RCT evaluated both tocilizumab and sarilumab compared to standard of care, one three-arm RCT evaluated tocilizumab and siltuximab compared to standard of care and consequently they appear in each respective comparison. Tocilizumab versus standard care alone or with placebo a. Effectiveness of tocilizumab for patients with COVID-19 Tocilizumab probably results in little or no increase in the outcome of clinical improvement at D28 (RR 1.06, 95% CI 1.00 to 1.13; I2 = 40.9%; 7 RCTs, 5585 participants; absolute effect: 31 more with clinical improvement per 1000 (from 0 fewer to 67 more); moderate-certainty evidence). However, we cannot exclude that some subgroups of patients could benefit from the treatment. We did not obtain data for longer-term follow-up (≥ D60). The effect of tocilizumab on the proportion of participants with a WHO Clinical Progression Score of level of 7 or above is uncertain at D28 (RR 0.99, 95% CI 0.56 to 1.74; I2 = 64.4%; 3 RCTs, 712 participants; low-certainty evidence). We did not obtain data for longer-term follow-up (≥ D60). Tocilizumab reduces all-cause mortality at D28 compared to standard care alone or placebo (RR 0.89, 95% CI 0.82 to 0.97; I2 = 0.0%; 8 RCTs, 6363 participants; absolute effect: 32 fewer deaths per 1000 (from 52 fewer to 9 fewer); high-certainty evidence). The evidence suggests uncertainty around the effect on mortality at ≥ D60 (RR 0.86, 95% CI 0.53 to 1.40; I2 = 0.0%; 2 RCTs, 519 participants; low-certainty evidence). b. Safety of tocilizumab for patients with COVID-19 The evidence is very uncertain about the effect of tocilizumab on adverse events (RR 1.23, 95% CI 0.87 to 1.72; I2 = 86.4%; 7 RCTs, 1534 participants; very low-certainty evidence). Nevertheless, tocilizumab probably results in slightly fewer serious adverse events than standard care alone or placebo (RR 0.89, 95% CI 0.75 to 1.06; I2 = 0.0%; 8 RCTs, 2312 participants; moderate-certainty evidence). Sarilumab versus standard care alone or with placebo The evidence is uncertain about the effect of sarilumab on all-cause mortality at D28 (RR 0.77, 95% CI 0.43 to 1.36; 2 RCTs, 880 participants; low certainty), on all-cause mortality at ≥ D60 (RR 1.00, 95% CI 0.50 to 2.0; 1 RCT, 420 participants; low certainty), and serious adverse events (RR 1.17, 95% CI 0.77 to 1.77; 2 RCTs, 880 participants; low certainty). It is unlikely that sarilumab results in an important increase of adverse events (RR 1.05, 95% CI 0.88 to 1.25; 1 RCT, 420 participants; moderate certainty). However, an increase cannot be excluded No data were available for other critical outcomes. AUTHORS' CONCLUSIONS: On average, tocilizumab reduces all-cause mortality at D28 compared to standard care alone or placebo and probably results in slightly fewer serious adverse events than standard care alone or placebo. Nevertheless, tocilizumab probably results in little or no increase in the outcome clinical improvement (defined as hospital discharge or improvement measured by trialist-defined scales) at D28. The impact of tocilizumab on other outcomes is uncertain or very uncertain. With the data available, we were not able to explore heterogeneity. Individual patient data meta-analyses are needed to be able to identify which patients are more likely to benefit from this treatment. Evidence for an effect of sarilumab is uncertain and evidence for other anti-IL6 agents is unavailable. Thirty-nine RCTs of IL-6 blocking agents with no results are currently registered, of which nine are completed and seven trials were terminated with no results available. The findings of this review will be updated as new data are made available on the COVID-NMA platform (covid-nma.com).

Coronavirus Disease 2019 and Antimicrobial Resistance: Parallel and Interacting Health Emergencies.

Abstract: The coronavirus disease 2019 (COVID-19) pandemic and antimicrobial resistance (AMR) are parallel and interacting health emergencies that provide the opportunity for mutual learning. As their measures and consequences are comparable, the COVID-19 pandemic helps to illustrate the potential long-term impact of AMR, which is less acute but not less crucial. They may also impact each other as there is a push to use existing antimicrobials to treat critically ill COVID-19 patients in the absence of specific treatments. Attempts to manage the spread of COVID-19 may also lead to a slowdown in AMR. Understanding how COVID-19 affects AMR trends and what we can expect if these trends remain the same or worsen will help us to plan the next steps for tackling AMR. Researchers should start collecting data to measure the impact of current COVID-19 policies and programs on AMR.

European Academy of Neurology/Peripheral Nerve Society guideline on diagnosis and treatment of chronic inflammatory demyelinating polyradiculoneuropathy: Report of a joint Task Force-Second revision.

Abstract: Objective To revise the 2010 consensus guideline on chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Methods Seventeen disease experts, a patient representative, and two Cochrane methodologists constructed 12 Population/Intervention/Comparison/Outcome (PICO) questions regarding diagnosis and treatment to guide the literature search. Data were extracted and summarized in GRADE summary of findings (for treatment PICOs) or evidence tables (for diagnostic PICOs). Results Statements were prepared according to the GRADE Evidence-to-Decision frameworks. Typical CIDP and CIDP variants were distinguished. The previous term "atypical CIDP" was replaced by "CIDP variants" because these are well characterized entities (multifocal, focal, distal, motor, or sensory CIDP). The levels of diagnostic certainty were reduced from three (definite, probable, possible CIDP) to only two (CIDP and possible CIDP), because the diagnostic accuracy of criteria for probable and definite CIDP did not significantly differ. Good Practice Points were formulated for supportive criteria and investigations to be considered to diagnose CIDP. The principal treatment recommendations were: (a) intravenous immunoglobulin (IVIg) or corticosteroids are strongly recommended as initial treatment in typical CIDP and CIDP variants; (b) plasma exchange is strongly recommended if IVIg and corticosteroids are ineffective; (c) IVIg should be considered as first-line treatment in motor CIDP (Good Practice Point); (d) for maintenance treatment, IVIg, subcutaneous immunoglobulin or corticosteroids are recommended; (e) if the maintenance dose of any of these is high, consider either combination treatments or adding an immunosuppressant or immunomodulatory drug (Good Practice Point); and (f) if pain is present, consider drugs against neuropathic pain and multidisciplinary management (Good Practice Point).

COVID-19-related medical research: a meta-research and critical appraisal.

Abstract: Since the start of the COVID-19 outbreak, a large number of COVID-19-related papers have been published. However, concerns about the risk of expedited science have been raised. We aimed at reviewing and categorizing COVID-19-related medical research and to critically appraise peer-reviewed original articles. The data sources were Pubmed, Cochrane COVID-19 register study, arXiv, medRxiv and bioRxiv, from 01/11/2019 to 01/05/2020. Peer-reviewed and preprints publications related to COVID-19 were included, written in English or Chinese. No limitations were placed on study design. Reviewers screened and categorized studies according to i) publication type, ii) country of publication, and iii) topics covered. Original articles were critically appraised using validated quality assessment tools. Among the 11,452 publications identified, 10,516 met the inclusion criteria, among which 7468 (71.0%) were peer-reviewed articles. Among these, 4190 publications (56.1%) did not include any data or analytics (comprising expert opinion pieces). Overall, the most represented topics were infectious disease (n = 2326, 22.1%), epidemiology (n = 1802, 17.1%), and global health (n = 1602, 15.2%). The top five publishing countries were China (25.8%), United States (22.3%), United Kingdom (8.8%), Italy (8.1%) and India (3.4%). The dynamic of publication showed that the exponential growth of COVID-19 peer-reviewed articles was mainly driven by publications without original data (mean 261.5 articles ± 51.1 per week) as compared with original articles (mean of 69.3 ± 22.3 articles per week). Original articles including patient data accounted for 713 (9.5%) of peer-reviewed studies. A total of 576 original articles (80.8%) showed intermediate to high risk of bias. Last, except for simulation studies that mainly used large-scale open data, the median number of patients enrolled was of 102 (IQR = 37–337). Since the beginning of the COVID-19 pandemic, the majority of research is composed by publications without original data. Peer-reviewed original articles with data showed a high risk of bias and included a limited number of patients. Together, these findings underscore the urgent need to strike a balance between the velocity and quality of research, and to cautiously consider medical information and clinical applicability in a pressing, pandemic context. https://osf.io/5zjyx/

Spanish COPD Guidelines (GesEPOC) 2021: Updated Pharmacological treatment of stable COPD

Abstract: The Spanish COPD Guidelines (GesEPOC) were first published in 2012, and since then have undergone a series of updates incorporating new evidence on the diagnosis and treatment of COPD. GesEPOC was drawn up in partnership with scientific societies involved in the treatment of COPD and the Spanish Patients' Forum. Their recommendations are based on an evaluation of the evidence using GRADE methodology, and a narrative description of the evidence in areas in which GRADE cannot be applied. In this article, we summarize the recommendations on the pharmacological treatment of stable COPD based on 9 PICO questions. COPD treatment is a 4-step process: 1) diagnosis, 2) determination of the risk level, 3) initial and subsequent inhaled therapy, and 4) identification and management of treatable traits. For the selection of inhaled therapy, high-risk patients are divided into 3 phenotypes: non-exacerbator, eosinophilic exacerbator, and non-eosinophilic exacerbator. Some treatable traits are general and should be investigated in all patients, such as smoking or inhalation technique, while others affect severe patients in particular, such as chronic hypoxemia and chronic bronchial infection. COPD treatment is based on long-acting bronchodilators with single agents or in combination, depending on the patient's risk level. Eosinophilic exacerbators must receive inhaled corticosteroids, while non-eosinophilic exacerbators require a more detailed evaluation to choose the best therapeutic option. The new GesEPOC also includes recommendations on the withdrawal of inhaled corticosteroids and on indications for alpha-1 antitrypsin treatment. GesEPOC offers a more individualized approach to COPD treatment tailored according to the clinical characteristics of patients and their level of complexity.

European Respiratory Society clinical practice guidelines for the diagnosis of asthma in children aged 5-16 years.

Abstract: Diagnosing asthma in children represents an important clinical challenge. There is no single gold standard test to confirm the diagnosis. Consequently, both over-, and under-diagnosis of asthma are frequent in children. A Task Force (TF) supported by the European Respiratory Society has developed these evidence-based clinical practice guidelines for the diagnosis of asthma in children aged 5–16 years using nine PICO (Population, Intervention, Comparator and Outcome) questions. The TF conducted systematic literature searches for all PICO questions and screened the outputs from these, including relevant full text articles. All TF members approved the final decision for inclusion of research papers. The TF assessed the quality of the evidence using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. The TF then developed a diagnostic algorithm based on the critical appraisal of the PICO questions, preferences expressed by lay members and test availability. Proposed cut-offs were determined based on the best available evidence. The TF formulated recommendations using the GRADE Evidence to Decision framework. Based on the critical appraisal of the evidence and the Evidence to Decision Framework the TF recommends spirometry, bronchodilator reversibility testing and FeNO as first line diagnostic tests in children under investigation for asthma. The TF recommends against diagnosing asthma in children based on clinical history alone or following a single abnormal objective test. Finally, this guideline also proposes a set of research priorities to improve asthma diagnosis in children in the future.

Adherence to Guidelines in Adult Patients with Traumatic Brain Injury: A Living Systematic Review

Abstract: Guidelines aim to improve the quality of medical care and reduce treatment variation. The extent to which guidelines are adhered to in the field of traumatic brain injury (TBI) is unknown. The objectives of this systematic review were to (1) quantify adherence to guidelines in adult patients with TBI, (2) examine factors influencing adherence, and (3) study associations of adherence to clinical guidelines and outcome. We searched EMBASE, MEDLINE, Cochrane Central, PubMed, Web of Science, PsycINFO, SCOPUS, CINAHL, and grey literature in October 2014. We included studies of evidence-based (inter)national guidelines that examined the acute treatment of adult patients with TBI. Methodological quality was assessed using the Research Triangle Institute item bank and Quality in Prognostic Studies Risk of Bias Assessment Instrument. Twenty-two retrospective and prospective observational cohort studies, reported in 25 publications, were included, describing adherence to 13 guideline recommendations. Guideline adherence varied considerably between studies (range 18-100%) and was higher in guideline recommendations based on strong evidence compared with those based on lower evidence, and lower in recommendations of relatively more invasive procedures such as craniotomy. A number of patient-related factors, including age, Glasgow Coma Scale, and intracranial pathology, were associated with greater guideline adherence. Guideline adherence to Brain Trauma Foundation guidelines seemed to be associated with lower mortality. Guideline adherence in TBI is suboptimal, and wide variation exists between studies. Guideline adherence may be improved through the development of strong evidence for guidelines. Further research specifying hospital and management characteristics that explain variation in guideline adherence is warranted.

Prophylaxis against covid-19: living systematic review and network meta-analysis.

Abstract: 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.

Efficacy and safety of treatment with biologicals for severe chronic rhinosinusitis with nasal polyps: A systematic review for the EAACI guidelines.

Abstract: This systematic review evaluates the efficacy and safety of biologicals for chronic rhinosinusitis with nasal polyps (CRSwNP) compared with the standard of care. PubMed, Embase, and Cochrane Library were searched for RCTs. Critical and important CRSwNP-related outcomes were considered. The risk of bias and the certainty of the evidence were assessed using GRADE. RCTs evaluated (dupilumab-2, omalizumab-4, mepolizumab-2, and reslizumab-1) included 1236 adults, with follow-up of 20-64 weeks. Dupilumab reduces the need for surgery (NFS) or oral corticosteroid (OCS) use (RR 0.28; 95% CI 0.20-0.39, moderate certainty) and improves with high certainty smell evaluated with UPSIT score (mean difference (MD) +10.54; 95% CI +9.24 to +11.84) and quality of life (QoL) evaluated with SNOT-22 (MD -19.14; 95% CI -22.80 to -15.47), with fewer treatment-related adverse events (TAEs) (RR 0.95; 95% CI 0.89-1.02, moderate certainty). Omalizumab reduces NFS (RR 0.85; 95% CI 0.78-0.92, high certainty), decreases OCS use (RR 0.38; 95% CI 0.10-1.38, moderate certainty), and improves high certainty smell (MD +3.84; 95% CI +3.64 to +4.04) and QoL (MD -15.65; 95% CI -16.16 to -15.13), with increased TAE (RR 1.73; 95% CI 0.60-5.03, moderate certainty). There is low certainty for mepolizumab reducing NFS (RR 0.78; 95% CI 0.64-0.94) and improving QoL (MD -13.3; 95% CI -23.93 to -2.67) and smell (MD +0.7; 95% CI -0.48 to +1.88), with increased TAEs (RR 1.64; 95% CI 0.41-6.50). The evidence for reslizumab is very uncertain.

International Consensus Document on Obstructive Sleep Apnea.

Abstract: The main aim of this international consensus document on obstructive sleep apnea is to provide guidelines based on a critical analysis of the latest literature to help health professionals make the best decisions in the care of adult patients with this disease. The expert working group was formed primarily of 17 scientific societies and 56 specialists from a wide geographical area (including the participation of 4 international societies), an expert in methodology, and a documentalist from the Iberoamerican Cochrane Center. The document consists of a main section containing the most significant innovations and a series of online manuscripts that report the systematic literature searches performed for each section of the international consensus document. This document does not discuss pediatric patients or the management of patients receiving chronic non-invasive mechanical ventilation (these topics will be addressed in separate consensus documents).

Mini‐Mental State Examination (MMSE) for the early detection of dementia in people with mild cognitive impairment (MCI)

Abstract: Background Dementia is a progressive global cognitive impairment syndrome. In 2010, more than 35 million people worldwide were estimated to be living with dementia. Some people with mild cognitive impairment (MCI) will progress to dementia but others remain stable or recover full function. There is great interest in finding good predictors of dementia in people with MCI. The Mini-Mental State Examination (MMSE) is the best-known and the most often used short screening tool for providing an overall measure of cognitive impairment in clinical, research and community settings. Objectives To determine the accuracy of the Mini Mental State Examination for the early detection of dementia in people with mild cognitive impairment SEARCH METHODS: We searched ALOIS (Cochrane Dementia and Cognitive Improvement Specialized Register of diagnostic and intervention studies (inception to May 2014); MEDLINE (OvidSP) (1946 to May 2014); EMBASE (OvidSP) (1980 to May 2014); BIOSIS (Web of Science) (inception to May 2014); Web of Science Core Collection, including the Conference Proceedings Citation Index (ISI Web of Science) (inception to May 2014); PsycINFO (OvidSP) (inception to May 2014), and LILACS (BIREME) (1982 to May 2014). We also searched specialized sources of diagnostic test accuracy studies and reviews, most recently in May 2014: MEDION (Universities of Maastricht and Leuven, www.mediondatabase.nl), DARE (Database of Abstracts of Reviews of Effects, via the Cochrane Library), HTA Database (Health Technology Assessment Database, via the Cochrane Library), and ARIF (University of Birmingham, UK, www.arif.bham.ac.uk). No language or date restrictions were applied to the electronic searches and methodological filters were not used as a method to restrict the search overall so as to maximize sensitivity. We also checked reference lists of relevant studies and reviews, tracked citations in Scopus and Science Citation Index, used searches of known relevant studies in PubMed to track related articles, and contacted research groups conducting work on MMSE for dementia diagnosis to try to locate possibly relevant but unpublished data. Selection criteria We considered longitudinal studies in which results of the MMSE administered to MCI participants at baseline were obtained and the reference standard was obtained by follow-up over time. We included participants recruited and clinically classified as individuals with MCI under Petersen and revised Petersen criteria, Matthews criteria, or a Clinical Dementia Rating = 0.5. We used acceptable and commonly used reference standards for dementia in general, Alzheimer's dementia, Lewy body dementia, vascular dementia and frontotemporal dementia. Data collection and analysis We screened all titles generated by the electronic database searches. Two review authors independently assessed the abstracts of all potentially relevant studies. We assessed the identified full papers for eligibility and extracted data to create two by two tables for dementia in general and other dementias. Two authors independently performed quality assessment using the QUADAS-2 tool. Due to high heterogeneity and scarcity of data, we derived estimates of sensitivity at fixed values of specificity from the model we fitted to produce the summary receiver operating characteristic curve. Main results In this review, we included 11 heterogeneous studies with a total number of 1569 MCI patients followed for conversion to dementia. Four studies assessed the role of baseline scores of the MMSE in conversion from MCI to all-cause dementia and eight studies assessed this test in conversion from MCI to Alzheimer´s disease dementia. Only one study provided information about the MMSE and conversion from MCI to vascular dementia. For conversion from MCI to dementia in general, the accuracy of baseline MMSE scores ranged from sensitivities of 23% to 76% and specificities from 40% to 94%. In relationship to conversion from MCI to Alzheimer's disease dementia, the accuracy of baseline MMSE scores ranged from sensitivities of 27% to 89% and specificities from 32% to 90%. Only one study provided information about conversion from MCI to vascular dementia, presenting a sensitivity of 36% and a specificity of 80% with an incidence of vascular dementia of 6.2%. Although we had planned to explore possible sources of heterogeneity, this was not undertaken due to the scarcity of studies included in our analysis. Authors' conclusions Our review did not find evidence supporting a substantial role of MMSE as a stand-alone single-administration test in the identification of MCI patients who could develop dementia. Clinicians could prefer to request additional and extensive tests to be sure about the management of these patients. An important aspect to assess in future updates is if conversion to dementia from MCI stages could be predicted better by MMSE changes over time instead of single measurements. It is also important to assess if a set of tests, rather than an isolated one, may be more successful in predicting conversion from MCI to dementia.

Milk consumption and multiple health outcomes: umbrella review of systematic reviews and meta-analyses in humans.

Abstract: In order to recapitulate the best available evidence of milk consumption and multiple health-related outcomes, we performed an umbrella review of meta-analyses and systematic reviews in humans. Totally, 41 meta-analyses with 45 unique health outcomes were included. Milk consumption was more often related to benefits than harm to a sequence of health-related outcomes. Dose–response analyses indicated that an increment of 200 ml (approximately 1 cup) milk intake per day was associated with a lower risk of cardiovascular disease, stroke, hypertension, colorectal cancer, metabolic syndrome, obesity and osteoporosis. Beneficial associations were also found for type 2 diabetes mellitus and Alzheimer's disease. Conversely, milk intake might be associated with higher risk of prostate cancer, Parkinson’s disease, acne and Fe-deficiency anaemia in infancy. Potential allergy or lactose intolerance need for caution. Milk consumption does more good than harm for human health in this umbrella review. Our results support milk consumption as part of a healthy diet. More well-designed randomized controlled trials are warranted.

Interventions for the treatment of persistent post-COVID-19 olfactory dysfunction

Abstract: Objectives: This is a protocol for a Cochrane Review (intervention) The objectives are as follows: To assess the effects (benefits and harms) of interventions that have been used, or proposed, to prevent persisting olfactory dysfunction due to COVID-19 infection A secondary objective is to maintain the currency of the evidence, using a living systematic review approach

The use and reporting of neonatal pain scales : a systematic review of randomized trials

Abstract: The burden of pain in newborn infants has been investigated in numerous studies, but little is known about the appropriateness of the use of pain scales according to the specific type of pain or infant condition. This systematic review aimed to evaluate the reporting of neonatal pain scales in randomized trials. A systematic search up to March 2019 was performed in Embase, PubMed, PsycINFO, CINAHL, Cochrane Library, Scopus, and Luxid. Randomized and quasirandomized trials reporting neonatal pain scales were included. Screening of the studies for inclusion, data extraction, and quality assessment was performed independently by 2 researchers. Of 3718 trials found, 352 with 29,137 infants and 22 published pain scales were included. Most studies (92%) concerned procedural pain, where the most frequently used pain scales were the Premature Infant Pain Profile or Premature Infant Pain Profile-Revised (48%), followed by the Neonatal Infant Pain Scale (23%). Although the Neonatal Infant Pain Scale is validated only for acute pain, it was also the second most used scale for ongoing and postoperative pain (21%). Only in a third of the trials, blinding for those performing the pain assessment was described. In 55 studies (16%), pain scales that were used lacked validation for the specific neonatal population or type of pain. Six validated pain scales were used in 90% of all trials, although not always in the correct population or type of pain. Depending on the type of pain and population of infants included in a study, appropriate scales should be selected. The inappropriate use raises serious concerns about research ethics and use of resources. (Less)

Efficacy and safety of treatment with omalizumab for chronic spontaneous urticaria: A systematic review for the EAACI Biologicals Guidelines.

Abstract: This systematic review evaluates the efficacy and safety of omalizumab for chronic spontaneous urticaria (CSU). PubMed, Embase, and Cochrane Library were searched for RCTs. Critical and important CSU-related outcomes were considered. The risk of bias and the certainty of the evidence were assessed using GRADE. Ten RCTs including 1620 subjects aged 12 to 75 years old treated with omalizumab for 16 to 40 weeks were evaluated. Omalizumab 150 mg does not result in clinically meaningful improvement (high certainty) of the urticaria activity score (UAS)7 (mean difference (MD) -5; 95%CI -7.75 to -2.25), and the itch severity score (ISS)7 (MD -2.15; 95% CI -3.2 to -1.1) does not increase (moderate certainty) quality of life (QoL) (Dermatology Life Quality Index (DLQI); MD -2.01; 95%CI -3.22 to -0.81) and decreases (moderate certainty) rescue medication use (MD -1.68; 95%CI -2.95 to -0.4). Omalizumab 300 mg results in clinically meaningful improvements (moderate certainty) of the UAS7 (MD -11.05; 95%CI -12.87 to -9.24), the ISS7 (MD -4.45; 95%CI -5.39 to -3.51), and QoL (high certainty) (DLQI; MD -4.03; 95% CI -5.56 to -2.5) and decreases (moderate certainty) rescue medication use (MD -2.04; 95%CI -3.19 to -0.88) and drug-related serious AEs (RR 0.77; 95%CI 0.20 to 2.91).

Medical cannabis or cannabinoids for chronic pain: a clinical practice guideline.

Abstract: 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.