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Objectives: To describe divergence between actionable statements issued by coronavirus disease 2019 (COVID-19) guideline developers cataloged on the “COVID-19 Recommendations and Gateway to Contextualization” platform. Study Design and Setting: We defined divergence as at least two comparable actionable statements with different explicit judgments of strength, direction, or subgroup consideration of the population or intervention. We applied a content analysis to compare guideline development methods for a sample of diverging statements and to evaluate factors associated with divergence. Results: Of the 138 guidelines evaluated, 85 (62%) contained at least one statement that diverged from another guideline. We identified 223 diverging statements in these 85 guidelines. We grouped statements into 66 clusters. Each cluster addressed the same population, intervention, and comparator group or just similar interventions. Clinical practice statements were more likely to diverge in an explicit judgment of strength or direction compared to public health statements. Statements were more likely to diverge in strength than direction. The date of publication, used evidence, interpretation of evidence, and contextualization considerations were associated with divergence. Conclusion: More than half of the assessed guidelines issued at least one diverging statement. This study helps in understanding the types of differences between guidelines issuing comparable statements and factors associated with their divergence. © 2022

Background Limited number of studies have focused on the impact of pollen exposure on asthma. As a part of the EAACI Guidelines on Environment Science, this first systematic review on the relationship of pollen exposure to asthma exacerbations aimed to bridge this knowledge gap in view of implementing recommendations of prevention. Methods We searched electronic iPubMed, Embase, and Web of Science databases using a set of MeSH terms and related synonyms and identified 73 eligible studies that were included for systemic review. When possible, meta-analyses were conducted. Results Overall meta-analysis suggests that outdoor pollen exposure may have an effect on asthma exacerbation but caution is needed due to the low number of studies and their heterogeneity. The strongest associations were found between asthma attacks, asthma-related ED admissions or hospitalizations and an increase of grass pollen concentration in the previous 2 days overall in children aged less than 18 years of age. Tree pollen may increase asthma-related ED visits or admissions lagged up to 7 days overall in individuals younger than 18 years. Rare data show that among subjects under 18 years of age an exposure to grass pollen lagged up to 3 days may lower lung function. Conclusions Further research considering effect modifiers of pollen sensitization, hay fever, asthma, air pollution, green spaces and pre-existing medications is urgently warranted to better evaluate the impacts of pollen on asthma exacerbation. Preventive measures in relation to pollen exposure should be integrated in asthma control as pollen increase continues due to climate change.

In the context of a pandemic, the rapid development of clinical practice guidelines (CPGs) is critical. The guideline development process includes prioritization of the guideline topic, questions and health outcomes. This case study describes the application of a new methodology to prioritize questions and rate the importance of health outcomes for a COVID-19 dental guideline.Panel members rated the topic and the questions' overall importance, using a 9-point scale (1 = least important; 9 = most important). In addition, they rated six criteria if multiple questions received the same overall importance rating: common in practice, uncertainty in practice, variation in practice, new evidence available, cost consequences, not previously addressed. Panellists also rated the importance of each outcome, defined with health outcome descriptors, using a 9-point scale and the utility of health outcomes on a visual analogue scale. The correlation between each criterion and overall question importance was tested by Spearman correlation coefficient.Of seven topics, four were rated as high priority and three were rated as important, but not of high priority. Thirty-six percent of the questions (18/50) were rated as high priority to address in the guideline and 64% (32/50) were rated as an important question but not of high priority. Of the 11 outcomes, 72.7% were rated as critical for decision making. The mean utility rating was 0.57 (SD 0.32), with a minimum mean rating of 0.16 and a maximum of 0.76 (SD 0.23).This case study demonstrated that this approach provides a rigorous and transparent methodology to conduct the prioritizations of guideline topics, questions and health outcomes.

Background Diagnostic mammography projections (DxMM) have been traditionally used in the assessment of women recalled after a suspicious screening mammogram. Digital breast tomosynthesis (DBT) reduces the tissue overlap effect, thus improving image assessment. Some studies have suggested DBT might replace DxMM with at least equivalent performance. Objective To evaluate the replacement of DxMM with DBT in women recalled at screening. Methods We searched PubMed, EMBASE, and the Cochrane Library databases to identify diagnostic paired cohort studies or RCTs comparing DBT vs DxMM, published in English that: reported accuracy outcomes, recruited women recalled for assessment at mammography screening, and included a reference standard. Subgroup analysis was performed over lesion characteristics. We provided pooled accuracy estimates and differences between tests using a quadrivariate model. We assessed the certainty of the evidence using the GRADE approach. Results We included ten studies that reported specificity and sensitivity. One study included 7060 women while the remaining included between 52 and 738 women. DBT compared with DxMM showed a pooled difference for the sensitivity of 2% (95% CI 1%–3%) and a pooled difference for the specificity of 6% (95%CI 2%–11%). Restricting the analysis to the six studies that included women with microcalcification lesions gave similar results. In the context of a prevalence of 21% of breast cancer (BC) in recalled women, DBT probably detects 4 (95% CI 2–6) more BC cases and has 47 (95%CI 16–87) fewer false‐positive results per 1000 assessments. The certainty of the evidence was moderate due to risk of bias. Conclusion The evidence in the assessment of screen‐recalled findings with DBT is sparse and of moderate certainty. DBT probably has higher sensitivity and specificity than DxMM. Women, health care providers and policymakers might value as relevant the reduction of false‐positive results and related fewer invasive diagnostic procedures with DBT, without missing BC cases., This systematic review found that in women of average risk of breast cancer with suspicious lesions at mammography screening, DBT probably has higher specificity difference (6%) than diagnostic views of 2D mammography in women recalled for assessment (moderate certainty evidence). The sensitivity is also probably higher with DBT; however, the difference was not so large (2%). The clinical impact of these results in a screening program is a probable reduction of 47 false positive results, including related invasive procedures, and most likely a small increase of 4 additional true BC lesions per 1000 women recalled for assessment. Our results were consistent in women with calcified lesions, but with a larger imprecision in the sensitivity differences. These results were taken into account by the GDG, together with other considerations (ie, feasibility) to issue a conditional recommendation in favor of DBT which is available on the ECIBC website (https://healthcare‐quality.jrc.ec.europa.eu/european‐breast‐cancer‐guidelines/diagnosis/DBT).

Purpose Clinical guidelines' (CGs) adherence supports high-quality care. However, healthcare providers do not always comply with CGs recommendations. This systematic literature review aims to assess the extent of healthcare providers' adherence to breast cancer CGs in Europe and to identify the factors that impact on healthcare providers' adherence. Methods We searched for systematic reviews and quantitative or qualitative primary studies in MEDLINE and Embase up to May 2019. The eligibility assessment, data extraction, and risk of bias assessment were conducted by one author and cross-checked by a second author. We conducted a narrative synthesis attending to the modality of the healthcare process, methods to measure adherence, the scope of the CGs, and population characteristics. Results Out of 8137 references, we included 41 primary studies conducted in eight European countries. Most followed a retrospective cohort design (19/41; 46%) and were at low or moderate risk of bias. Adherence for overall breast cancer care process (from diagnosis to follow-up) ranged from 54 to 69%; for overall treatment process [including surgery, chemotherapy (CT), endocrine therapy (ET), and radiotherapy (RT)] the median adherence was 57.5% (interquartile range (IQR) 38.8-67.3%), while for systemic therapy (CT and ET) it was 76% (IQR 68-77%). The median adherence for the processes assessed individually was higher, ranging from 74% (IQR 10-80%), for the follow-up, to 90% (IQR 87-92.5%) for ET. Internal factors that potentially impact on healthcare providers' adherence were their perceptions, preferences, lack of knowledge, or intentional decisions. Conclusions A substantial proportion of breast cancer patients are not receiving CGs-recommended care. Healthcare providers' adherence to breast cancer CGs in Europe has room for improvement in almost all care processes. CGs development and implementation processes should address the main factors that influence healthcare providers' adherence, especially patient-related ones. Registration: PROSPERO (CRD42018092884)., The systematic review was carried out by the Iberoamerican Cochrane Center under Framework Contract 443094 for procurement of services between European Commission Joint Research Centre and Asociacion Colaboracion Cochrane Iberoamericana. YS is funded by China Scholarship Council (No. 201707040103). MR is funded by Sara Borrell contract (CD16/00157). AVM received a training Grant D43 TW007393 Fogarty International Centre of the US National Institutes of Health for the Emerging Diseases and Climate Change Research Unit of the School and Public Health Administration at Universidad Peruana Cayetano Heredia.

Five biologicals have been approved for severe eosinophilic asthma, a well-recognized phenotype. Systematic reviews (SR) evaluated the efficacy and safety of benralizumab, dupilumab, mepolizumab, omalizumab and reslizumab (alphabetical order) compared to standard of care for severe eosinophilic asthma. PubMed, Embase and Cochrane Library were searched to identify RCTs and health economic evaluations, published in English. Critical and important asthma-related outcomes were evaluated for each of the biologicals. The risk of bias and the certainty of the evidence were assessed using GRADE. 19 RCTs (three RCTs for benralizumab, three RCTs for dupilumab, three RCTs for mepolizumab, five RCTs for omalizumab and five RCTs for reslizumab), including subjects 12 to 75 years old (except for omalizumab including also subjects 6-11 years old), ranging from 12 to 56 weeks were evaluated. All biologicals reduce exacerbation rates with high certainty of evidence: benralizumab incidence rate ratio (IRR) 0.53 (95% CI 0.39 to 0.72), dupilumab (IRR) 0.43 (95% CI 0.32 to 0.59), mepolizumab IRR 0.49 (95% CI 0.38 to 0.66), omalizumab (IRR) 0.56 (95% CI 0.40 to 0.77) and reslizumab (IRR) 0.46 (95% CI 0.37 to 0.58). Benralizumab, dupilumab and mepolizumab reduce the daily dose of oral corticosteroids (OCS) with high certainty of evidence. All evaluated biologicals probably improve asthma control, QoL and FEV1 , without reaching the minimal important difference (moderate certainty). Benralizumab, mepolizumab and reslizumab slightly increase drug-related adverse events (AE) and drug-related serious AE (low to very low certainty of evidence). The incremental cost-effectiveness ratio per quality-adjusted life year value is above the willingness to pay threshold for all biologicals (moderate certainty). Potential savings are driven by decrease in hospitalizations, emergency and primary care visits. There is high certainty that all approved biologicals reduce the rate of severe asthma exacerbations and for benralizumab, dupilumab and mepolizumab for reducing OCS. There is moderate certainty for improving asthma control, QoL, FEV1 . More data on long-term safety are needed together with more efficacy data in the paediatric population.

Self-management interventions (SMIs) may improve outcomes in Chronic Obstructive Pulmonary Disease (COPD). However, accurate comparisons of their relative effectiveness are challenging, partly due to a lack of clarity and detail regarding the intervention content being evaluated. This study systematically describes intervention components and characteristics in randomized controlled trials (RCTs) related to COPD self-management using the COMPAR-EU taxonomy as a framework, identifying components that are insufficiently incorporated into the design of the intervention or insufficiently reported. Overall, 235 RCTs published between 2010 and 2018, from a systematic review were coded using the taxonomy, which includes 132 components across four domains: intervention characteristics, expected patient (or caregiver) self-management behaviours, patient relevant outcomes, and target population characteristics. Risk of bias was also assessed. Interventions mainly focused on physical activity (67.4%), and condition-specific behaviours like breathing exercise (63.5%), self-monitoring (50.8%), and medication use (33.9%). Support techniques like education and skills-training, self-monitoring, and goal setting (over 35% of the RCTs) were mostly used for this. Emotional-based techniques, problem-solving, and shared decision-making were less frequently reported (less than 15% of the studies). Numerous SMIs components were insufficiently incorporated into the design of COPD SMIs or insufficiently reported. Characteristics like mode of delivery, intensity, location, and providers involved were often not described. Only 8% of the interventions were tailored to the target population’s characteristics. Outcomes that are considered important by patients were hardly taken into account. There is still a lot to improve in both the design and description of SMIs for COPD. Using a framework such as the COMPAR-EU SMI taxonomy may contribute to better reporting and to better informing of replication efforts. In addition, prospective use of the taxonomy for developing and reporting intervention content would further aid in building a cumulative science of effective SMIs in COPD.

Background Although mammography screening is recommended in most European countries, the balance between the benefits and harms of different screening intervals is still a matter of debate. This review informed the European Commission Initiative on Breast Cancer (BC) recommendations. Methods We searched PubMed, EMBASE, and the Cochrane Library to identify RCTs, observational or modelling studies, comparing desirable (BC deaths averted, QALYs, BC stage, interval cancer) and undesirable (overdiagnosis, false positive related, radiation related) effects from annual, biennial, or triennial mammography screening in women of average risk for BC. We assessed the certainty of the evidence using the GRADE approach. Results We included one RCT, 13 observational, and 11 modelling studies. In women 50–69, annual compared to biennial screening may have small additional benefits but an important increase in false positive results; triennial compared to biennial screening may have smaller benefits while avoiding some harms. In younger women (aged 45–49), annual compared to biennial screening had a smaller gain in benefits and larger harms, showing a less favourable balance in this age group than in women 50–69. In women 70–74, there were fewer additional harms and similar benefits with shorter screening intervals. The overall certainty of the evidence for each of these comparisons was very low. Conclusions In women of average BC risk, screening intervals have different trade-offs for each age group. The balance probably favours biennial screening in women 50–69. In younger women, annual screening may have a less favourable balance, while in women aged 70–74 years longer screening intervals may be more favourable.

Aims: Nurse-led case management (CM) may improve quality of life (QoL) for advanced heart failure (HF) patients. No systematic review (SR), however, has summarized its effectiveness/cost-effectiveness. We aimed to evaluate the effect of such programs in primary care settings in advanced HF patients. We examined and summarized evidence on QoL, mortality, hospitalization, self-care, and cost-effectiveness. Methods and results: The MEDLINE, CINAHL, Embase, Clinical Trials, WHO, Registry of International Clinical Trials, and Central Cochrane were searched up to March 2022. The Consensus Health Economic Criteria instrument to assess risk-of-bias in economic evaluations, Cochrane risk-of-bias 2 for clinical trials, and an adaptation of Robins-I for quasi-experimental and cohort studies were employed. Results from nurse-led CM programs did not reduce mortality (RR 0.78, 95% CI 0.53 to 1.15; participants = 1345; studies = 6; I2 = 47%). They decreased HF hospitalizations (HR 0.79, 95% CI 0.68 to 0.91; participants = 1989; studies = 8; I2 = 0%) and all-cause ones (HR 0.73, 95% CI 0.60 to 0.89; participants = 1012; studies = 5; I2 = 36%). QoL improved in medium-term follow-up (SMD 0.18, 95% CI 0.05 to 0.32; participants = 1228; studies = 8; I2 = 28%), and self-care was not statistically significant improved (SMD 0.66, 95% CI −0.84 to 2.17; participants = 450; studies = 3; I2 = 97%). A wide variety of costs ranging from USD 4975 to EUR 27,538 was observed. The intervention was cost-effective at ≤EUR 60,000/QALY. Conclusions: Nurse-led CM reduces all-cause hospital admissions and HF hospitalizations but not all-cause mortality. QoL improved at medium-term follow-up. Such programs could be cost-effective in high-income countries.

Background: Prognostic models combine several prognostic factors to provide an estimate of the likelihood (or risk) of future events in individual patients, conditional on their prognostic factor values. A fundamental part of evaluating prognostic models is undertaking studies to determine whether their predictive performance, such as calibration and discrimination, is reproduced across settings. Systematic reviews and meta-analyses of studies evaluating prognostic models’ performance are a necessary step for selection of models for clinical practice and for testing the underlying assumption that their use will improve outcomes, including patient's reassurance and optimal future planning. Methods: In this paper, we highlight key concepts in evaluating the certainty of evidence regarding the calibration of prognostic models. Results and Conclusion: Four concepts are key to evaluating the certainty of evidence on prognostic models’ performance regarding calibration. The first concept is that the inference regarding calibration may take one of two forms: deciding whether one is rating certainty that a model's performance is satisfactory or, instead, unsatisfactory, in either case defining the threshold for satisfactory (or unsatisfactory) model performance. Second, inconsistency is the critical GRADE domain to deciding whether we are rating certainty in the model performance being satisfactory or unsatisfactory. Third, depending on whether one is rating certainty in satisfactory or unsatisfactory performance, different patterns of inconsistency of results across studies will inform ratings of certainty of evidence. Fourth, exploring the distribution of point estimates of observed to expected ratio across individual studies, and its determinants, will bear on the need for and direction of future research. © 2021

Background Vitamin D has been widely promoted for bone health through supplementation and fortification of the general adult population. However, there is growing evidence that does not support these strategies. Our aim is to review the quality and recommendations on vitamin D nutritional and clinical practice guidelines and explore predictive factors for their direction and strength. Methods We searched three databases and two guideline repositories from 2010 onwards. We performed a descriptive analysis, a quality appraisal using AGREE II scores (Appraisal of Guidelines Research and Evaluation) and a bivariate analysis evaluating the association between direction and strength of recommendations, AGREE II domains' scores and pre-specified characteristics. Results We included 34 guidelines, 44.1% recommended, 26.5% suggested, and 29.4% did not recommend vitamin D supplementation. Guidelines that scored higher for "editorial independence" and "overall quality score" were less likely to recommend or suggest vitamin D supplementation (median 68.8 vs. 35.4; p=0.001), and median 58.3 vs. 37.5; p=0.02). Guidance produced by government organizations and those that reported source of funding were associated with higher AGREE II scores. Unclear role of source of funding was associated with recommending or suggesting vitamin D supplementation (p=0.034). Editorial independence was an independent predictor for recommending or suggesting vitamin D supplementation (OR 1.09; CI95% 1.02 to 1.16; p=0.006). Conclusions Policymakers, clinicians and patients should be aware that lower quality guidelines, and those reporting conflicts of interest are more likely to promote vitamin D supplementation. Guideline organizations should improve the quality of their recommendations' development and the management of conflicts of interest. Users and editors should be aware of these findings when using and appraising guidelines.

Despite early control measures, SARS-CoV-2 reached all regions of Peru during the first wave of the pandemic, including native communities of the Peruvian Amazon. Here, we aimed to describe the epidemiological situation of COVID-19 in the Amazonas region of Peru using an open database of 11,124 COVID-19 cases reported from 19 March to 29 July 2020, including 3278 cases from native communities. A high-incidence area in northern Amazonas (Condorcanqui) reported a cumulative incidence of 63.84/1000 inhabitants with a much lower death rate (0.95%) than the national average. Our results showed at least eight significant factors for mortality, and the Native Amazonian ethnicity as a protective factor. Molecular confirmatory tests are necessary to better explain the high incidence of antibody response reported in these communities.

Salut dels nens; Pensament crític; Educació per a la salut Salud de los niños; Pensamiento crítico; Educación para la salud Children’s health; Critical thinking; Health education Introduction The Informed Health Choices (IHC) project developed learning resources to teach primary school children (10 to 12-year-olds) to assess treatment claims and make informed health choices. The aim of our study is to explore the educational context for teaching and learning critical thinking about health in Spanish primary schools. Methods During the 2020-2021 school year, we will conduct 1) a systematic assessment of educational documents and resources, and 2) semi-structured interviews with key education and health stakeholders. In the systematic assessment of educational documents and resources, we will include state and autonomous communities’ curriculums, school educational projects, and commonly used textbooks and other health teaching materials. In the semi-structured interviews, we will involve education and health policy makers, developers of learning resources, developers of health promotion and educational interventions, head teachers, teachers, families, and paediatric primary care providers. We will design and pilot a data extraction form and a semi-structured interview guide to collect the data. We will perform a quantitative and a qualitative analysis of the data to explore how critical thinking about health is being taught and learned in Spanish primary schools. Conclusion We will identify opportunities for and barriers to teaching and learning critical thinking about health in Spanish primary schools. We will formulate recommendations—for both practice and research purposes—on how to use, adapt (if needed), and implement the IHC resources in this context. This study will be funded by Institute of Health Carlos III through the project 'PI19/00068' (co-funded by the European Regional Development Fund/European Social Fund, 'Investing in your future'). LMG has a Miguel Servet research contract from the Institute of Health Carlos III [CP18/00007] (co-funded by the European Regional Development Fund/European Social Fund, 'Investing in your future').

This systematic review evaluates the efficacy and safety of biologicals for chronic rhinosinusitis with nasal polyps (CRSwNP) compared to 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, reslizumab-1) included 1236 adults, with follow-up 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 to 0.92, high certainty), decreases OCS use (RR 0.38; 95%CI 0.10-1.38, moderate certainty), improves with 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 to 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.

Background: Opportunistic prostate-specific antigen (PSA) screening may reduce prostate cancer mortality risk but is associated with false positive results, biopsy complications and overdiagnosis. Although different organisations have emphasised the importance of shared decision making (SDM) to assist men in deciding whether to undergo prostate cancer screening, recent evaluations show that the available decision aids fail to facilitate SDM, mainly because they do not consider the patients’ perspective in their design. We aim to systematically develop and test a patient decision aid to promote SDM in prostate cancer screening, following the Knowledge to Action framework. Methods: (1) Feasibility study: a quantitative survey evaluating the population and clinician (urologists and general practitioners) knowledge of the benefits and risks derived from PSA determination and the awareness of the available recommendations. Focus groups to explore the challenges patients and clinicians face when discussing prostate cancer screening, the relevance of a decision aid and how best to integrate it into practice. (2) Patient decision aid development: Based on this data, an evidence-based multicomponent SDM patient decision aid will be developed. (3) User-testing: an assessment of the prototype of the initial patient decision aid through a user-testing design based on mix-methods (questionnaire and semi-structured review). The decision aid will be refined through several iterative cycles of feedback and redesign. (4) Validation: an evaluation of the patient decision aid through a cluster-randomised controlled trial. Discussion: The designed patient decision aid will provide balanced information on screening benefits and risks and should help patients to consider their personal preferences and to take a more active role in decision making. Conclusions: The well-designed patient decision aid (PDA) will provide balanced information on screening benefits and risks and help patients consider their personal preferences. Article funded by the Instituto de Salud Carlos III, Ministry of Science and Innovation of the Government of Spain (Group 26 of the Centro de Investigación Biomédica en Red Epidemiología y Salud Pública, CIBERESP). Research funded by the research project of the Instituto de Salud Carlos III, code PI20/01334, Principal Investigator Dr. Blanca Lumbreras Lacarra, co-financed with FEDER funds from the European Union “A way of doing Europe”.

Objective To explore and characterize published evidence on the ways decision analysis has been used to inform shared decision-making. Study design and setting For this scoping review, we searched five bibliographic databases (from inception until February 2021), reference lists of included studies, trial registries, a thesis database and websites of relevant interest groups. Studies were eligible if they evaluated the application of decision analysis in a shared decision-making encounter. Pairs of reviewers independently screened and selected studies for inclusion, extracted study information using a data extraction form developed by the research team and assessed risk of bias for all studies with an experimental or quasi-experimental design. Data were narratively synthesized. Results We identified 27 studies that varied greatly with regard to their patient population, design, content and delivery. A range of outcomes were evaluated to explore the effectiveness and acceptability of decision analytic interventions, with little information about the implementation process. Most studies found that decision analysis was broadly beneficial. Conclusion Despite the compelling rationale on the potential for decision analysis to support shared decision-making, rigorous randomized controlled trials are needed to confirm these interventions' effectiveness, while qualitative studies should seek to understand their potential implementation.

Background In Latin America, the prevalence of end-stage kidney disease (ESKD) has risen tremendously during the last decade. Previous studies have suggested that receiving dialysis at high altitude confers mortality benefits; however, this effect has not been demonstrated at >2000 m above sea level (masl) or in developing countries. Methods This historical cohort study analyzed medical records from six Peruvian hemodialysis (HD) centers located at altitudes ranging from 44 to 3827 masl. Adult ESKD patients who started maintenance HD between 2000 and 2010 were included. Patients were classified into two strata based on the elevation above sea level of their city of residence: low altitude ( Results A total of 720 patients were enrolled and 163 (22.6%) resided at high altitude. The low-altitude group was significantly younger, more likely to have diabetes or glomerulonephritis as the cause of ESKD and higher hemoglobin. The all-cause mortality rate was 84.3 per 1000 person-years. In the unadjusted Cox model, no mortality difference was found between the high- and low-altitude groups {hazard ratio [HR] 1.20 [95% confidence interval (CI) 0.89–1.62]}. After multivariable adjustment, receiving HD at high altitude was not significantly associated with higher mortality, but those with diabetes as the cause of ESKD had significantly higher mortality [HR 2.50 (95% CI 1.36–4.59)]. Conclusions In Peru, patients receiving HD at high altitudes do not have mortality benefits.

Objectives Mammography screening is generally accepted in women aged 50–69, but the balance between benefits and harms remains controversial in other age groups. This study systematically reviews these effects to inform the European Breast Cancer Guidelines. Methods We searched PubMed, EMBASE and Cochrane Library for randomised clinical trials (RCTs) or systematic reviews of observational studies in the absence of RCTs comparing invitation to mammography screening to no invitation in women at average breast cancer (BC) risk. We extracted data for mortality, BC stage, mastectomy rate, chemotherapy provision, overdiagnosis and false-positive-related adverse effects. We performed a pooled analysis of relative risks, applying an inverse-variance random-effects model for three age groups (Results We identified 10 RCTs including 616,641 women aged 38–75. Mammography reduced BC mortality in women aged 50–69 (relative risk (RR) 0.77, 95%CI (confidence interval) 0.66–0.90, high certainty) and 70–74 (RR 0.77, 95%CI 0.54–1.09, high certainty), with smaller reductions in under 50s (RR 0.88, 95%CI 0.76–1.02, moderate certainty). Mammography reduced stage IIA+ in women 50–69 (RR 0.80, 95%CI 0.64–1.00, very low certainty) but resulted in an overdiagnosis probability of 23% (95%CI 18–27%) and 17% (95%CI 15–20%) in under 50s and 50–69, respectively ( moderate certainty). Mammography was associated with 2.9% increased risk of invasive procedures with benign outcomes ( low certainty). Conclusions For women 50–69, high certainty evidence that mammography screening reduces BC mortality risk would support policymakers formulating strong recommendations. In other age groups, where the net balance of effects is less clear, conditional recommendations will be more likely, together with shared decision-making.

Objective To evaluate the impact of preoperative MRI in the management of Ductal carcinoma in situ (DCIS). Methods We searched the PubMed, EMBASE and Cochrane Library databases to identify randomised clinical trials (RCTs) or cohort studies assessing the impact of preoperative breast MRI in surgical outcomes, treatment change or loco-regional recurrence. We provided pooled estimates for odds ratios (OR), relative risks (RR) and proportions and assessed the certainty of the evidence using the GRADE approach. Results We included 3 RCTs and 23 observational cohorts, corresponding to 20,415 patients. For initial breast-conserving surgery (BCS), the RCTs showed that MRI may result in little to no difference (RR 0.95, 95% CI 0.90 to 1.00) (low certainty); observational studies showed that MRI may have no difference in the odds of re-operation after BCS (OR 0.96; 95% CI 0.36 to 2.61) (low certainty); and uncertain evidence from RCTs suggests little to no difference with respect to total mastectomy rate (RR 0.91; 95% CI 0.65 to 1.27) (very low certainty). We also found that MRI may change the initial treatment plans in 17% (95% CI 12 to 24%) of cases, but with little to no effect on locoregional recurrence (aHR = 1.18; 95% CI 0.79 to 1.76) (very low certainty). Conclusion We found evidence of low to very low certainty which may suggest there is no improvement of surgical outcomes with pre-operative MRI assessment of women with DCIS lesions. There is a need for large rigorously conducted RCTs to evaluate the role of preoperative MRI in this population. Key Points • Evidence of low to very low certainty may suggest there is no improvement in surgical outcomes with pre-operative MRI. • There is a need for large rigorously conducted RCTs evaluating the role of preoperative MRI to improve treatment planning for DCIS.

BackgroundBreast cancer (BC) clinical guidelines offer evidence-based recommendations to improve quality of healthcare for patients with or at risk of BC. Suboptimal adherence to recommendations has the potential to negatively affect population health. However, no study has systematically reviewed the impact of BC guideline adherence -as prognosis factor- on BC healthcare processes and health outcomes. The objectives are to analyse the impact of guideline adherence on health outcomes and on healthcare costs.MethodsWe searched systematic reviews and primary studies in MEDLINE and Embase, conducted in European Union (EU) countries (inception to May 2019). Eligibility assessment, data extraction, and risk of bias assessment were conducted by one author and crosschecked by a second. We used random-effects meta-analyses to examine the impact of guideline adherence on overall survival and disease-free survival, and assessed certainty of evidence using GRADE.ResultsWe included 21 primary studies. Most were published during the last decade (90%), followed a retrospective cohort design (86%), focused on treatment guideline adherence (95%), and were at low (80%) or moderate (20%) risk of bias. Nineteen studies (95%) examined the impact of guideline adherence on health outcomes, while two (10%) on healthcare cost. Adherence to guidelines was associated with increased overall survival (HR=0.67, 95%CI 0.59-0.76) and disease-free survival (HR=0.35, 95%CI 0.15-0.82), representing 138 more survivors (96 more to 178 more) and 336 patients free of recurrence (73 more to 491 more) for every 1000 women receiving adherent CG treatment compared to those receiving non-adherent treatment at 5years follow-up (moderate certainty). Adherence to treatment guidelines was associated with higher costs, but adherence to follow-up guidelines was associated with lower costs (low certainty).ConclusionsOur review of EU studies suggests that there is moderate certainty that adherence to BC guidelines is associated with an improved survival. BC guidelines should be rigorously implemented in the clinical setting.Trial registrationPROSPERO (CRD42018092884)., The systematic review was carried out by the Iberoamerican Cochrane Center under Framework contract 443094 for procurement of services between European Commission Joint Research Centre and Asociacion Colaboracion Cochrane Iberoamericana.; AVM received a training grant D43 TW007393 Fogarty International Centre of the US National Institutes of Health for the Emerging Diseases and Climate Change Research Unit of the School and Public Health Administration at Universidad Peruana Cayetano Heredia.

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).

This systematic review evaluates the efficacy, safety and economic impact of dupilumab compared to standard of care for uncontrolled moderate-to-severe atopic dermatitis (AD). Pubmed, EMBASE and Cochrane Library were searched for RCTs and health economic evaluations. Critical and important AD-related outcomes were considered. The risk of bias and the certainty of the evidence were assessed using GRADE. Seven RCTs including 1845 subjects >12 years treated with dupilumab 16 to 52 weeks were evaluated. For adults, there is high certainty that dupilumab decreases SCORAD (MD -30,72; 95% CI -34,65% to -26,79%) and EASI-75 (RR 3.09; 95% CI 2.45 to 3.89), pruritus (RR 2.96; 95% CI 2.37 to 3.70), rescue medication (RR 3.46; 95% CI 2.79 to 4.30), sleep disturbance (MD -7.29; 95% CI -8.23 to -6.35) and anxiety/depression (MD -3.08; 95% CI -4.41 to -1.75) and improves quality of life (MD -4.80; 95% CI -5.55 to -4.06). The efficacy for adolescents is similar. Dupilumab-related adverse events (AEs) slightly increase (low certainty). The evidence for dupilumab-related serious AE is uncertain. The incremental cost-effectiveness ratio ranged from 28 500 pound (low certainty) to 124 541 US$ (moderate certainty). More data on long-term safety are needed both for children and for adults, together with more efficacy data in the paediatric population.Registration: PROSPERO (CRD42020153645).