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Purpose To assess the methodological quality of all relevant and recent European clinical practice guidelines (CPGs) for advanced oesophageal and gastric cancers, and to synthesise their recommendations on the use of chemotherapy. Methods We searched PubMed, EMBASE, guidelines repositories, and other sources from 2010 onwards. We appraised quality using AGREE-II and AGREE-REX. Results 11 CPGs were included (five high, five low, and one moderate quality). Most guidelines showed deficiencies in the domain "applicability", with only three scoring above 60%. Nine did not report having sought the views and preferences of the target population. The lowest scores for AGREE-REX were item Values and Preferences of Target Users (1.6; SD 1.3), and item Values and Preferences of Policy/Decision-Makers (1.8; SD 1.7). The domain Clinical Applicability got the highest score and the domain Implementability got the lowest. Conclusions An urgent area of research is how to develop credible and implementable recommendations on the clinical use of CT for advanced oesophageal and gastric cancer. Systematic review registration: PROSPERO (CRD42021236753).

Purpose To conduct a systematic review to analyse the performance of the sentinel lymph-node biopsy (SLNB) in women with node-positive breast cancer at diagnosis and node-negative tumour after neoadjuvant therapy, compared to axillary lymph-node dissection. Methods The more relevant databases were searched. Main outcomes were false-negative rate (FNR), sentinel lymph-node identification rate (SLNIR), negative predictive value (NPV), and accuracy. We conducted meta-analyses when appropriate. Results Twenty studies were included. The pooled FNR was 0.14 (95% CI 0.11-0.17), the pooled SLNIR was 0.89 (95% CI 0.86-0.92), NPV was 0.83 (95% CI 0.79-0.87), and summary accuracy was 0.92 (95% CI 0.90-0.94). SLNB performed better when more than one node was removed and double mapping was used. Conclusions SLNB can be performed in women with a node-negative tumour after neoadjuvant therapy. It has a better performance when used with previous marking of the affected node and with double tracer.

Background: Patients with advanced pancreatic cancer (PC) have a high risk of dying in the short or medium-term. This overview aimed to assess the evidence regarding systemic oncological treatments (SOT) versus supportive care for advanced PC. Methods: We searched for systematic reviews (SRs) in MEDLINE, Embase, The CochraneLibrary, Epistemonikos, and PROSPERO. Two authors assessed eligibility independently. Data extraction and methodological quality assessment were conducted by one author and cross-checked by another one. We evaluated the overlap of primary studies, performed a de novo meta-analysis, and assessed the certainty of evidence. Primary outcomes were overall survival (OS), quality of life (QoL), functional status (FS), and toxicity. Results: We identified three SRs that assessed SOT versus supportive care in patients with advanced PC. All SRs had critically low methodological quality. At 12 months, OS improved with chemotherapy, radiotherapy followed by chemotherapy, and immunotherapy, but the certainty of the evidence supporting these findings is very low. The evidence on chemotherapy is very uncertain about its effects on QoL; it suggests a slight increase in toxicity and little to no difference in FS. The evidence on immunotherapy is very uncertain about its effects in toxicity. Conclusions: The identified evidence is very uncertain about the benefits of oncological treatments on OS and QoL in patients with advanced PC with a high risk of dying in the short or medium-term, so its use should be proposed only to selected patients. Further studies that include a thorough assessment of patient-centred outcomes are needed. (C) 2021 Published by Elsevier Ltd.

Background: The number of randomized clinical trials (RCTs) for manual therapy (MT) has increased exponentially in recent years but the quality of reporting is heterogeneous. Objective: To assess the quality of the reporting of results in RCTs manual therapy, both in the text and in the graphs. Study design: Methodological review. Methods: We reviewed a random sample of 120 RCTs in MT published between 2000 and 2020 in indexed journals. We identified the primary outcome for each trial, and evaluated the completeness and correctness of reporting of results in the text and in the graphs. Results: Forty per cent of the RCTs explicitly identified the primary outcome and 47.5% reported a sample size calculation. In 46.7% of the trials, the reporting of between groups comparisons was complete (including effect size and precision). Only 29.2% used the confidence interval as a measure of precision. Fifty-eight per cent of the trials reported significant differences in the results, and 30.8% reported a value of clinical relevance for at least one variable of the study. Forty-seven per cent reported the primary outcome graphically but only 19.6% of the graphs were self explanatory and 66.1% had problems of visual clarity. Conclusions: Our findings suggest that the reporting of the results in MT trials is generally incomplete and graphics are often poor. These shortcomings could affect the interpretation of the results and their application in clinical practice. Improvements are needed in the reporting of results in order to advance clinical practice and research in manual therapy. © 2021 Elsevier Ltd

Background: Esophageal and gastric cancers are a significant public health problem worldwide, with most patients presenting with advanced-stage disease and, consequently, poor prognosis. Systemic oncological treatments (SOT) have been widely used over more conservative approaches, such as supportive care. Nevertheless, its effectiveness in this scenario is not sufficiently clear. This paper provides an overview of systematic reviews that assessed the effectiveness of SOT compared with the best supportive care (BSC) or placebo in patients with advanced esophageal or gastric cancers in an end-of-life context. Methods: We searched MEDLINE, EMBASE, The Cochrane Library, Epistemonikos, and PROSPERO for eligible systematic reviews (SRs) published from 2008 onwards. The primary outcomes were overall survival (OS), progression-free survival (PFS), functional status, and toxicity. Two authors assessed eligibility and extracted data independently. We evaluated the methodological quality of included SRs using the AMSTAR-2 tool and the overlap of primary studies (corrected covered area, CCA). Also, we performed a de novo meta-analysis with data reported for each primary study when it was possible. We assessed the certainty of evidence using the GRADE approach. Results: We identified 16 SRs (19 included trials) for inclusion within this overview. Most reviews had a critically low methodological quality, and there was a very high overlap of primary studies. It is uncertain whether SOT improves OS and PFS over more conservative approaches due to the very low certainty of evidence. Conclusions: The evidence is very uncertain about the effectiveness of SOT for advanced esophageal or gastric cancers. High-quality SRs and further randomized clinical trials that include a thorough assessment of patient-centered outcomes are needed.

Objectives: The aim of this study was to quantify and analyze the presence and type of self-acknowledged limitations (SALs) in a sample of manual therapy (MT) randomized controlled trials. Study Design and Setting: We randomly selected 120 MT trials. We extracted data related to SALs from the original reports and classified them into 12 categories. After data extraction, specific limitations within each category were identified. A descriptive analysis was performed using frequencies and percentages for qualitative variables. Results: The number of SALs per trial article ranged from 0 to 8, and more than two-thirds of trials acknowledged at least two different limitations. Despite its small proportion, 9% of trials did not report SALs. The most common limitation declared, in almost half of our sample, related to sample size (47.5%) followed by limitations related to study length and follow-up (33.3%) and inadequate controls (32.5%). Conclusion: Our results indicate that at least two different limitations are consistently acknowledged in MT trial reports, the most common being those related to sample size, study length, follow-up, and inadequate controls. Analysis of the reasons behind the SALs gives some insights about the main difficulties in conducting research in this field and may help develop strategies to improve future research. (C) 2020 Elsevier Inc. All rights reserved.

Inhaled corticosteroids (ICSs) are indicated for the prevention of exacerbations in COPD; however, a significant proportion of patients at low risk of exacerbations are treated with ICSs. We conducted a systematic review including a diversity of types of study designs and safety outcomes with the objective of describing the risk of adverse effects associated with the long-term use of ICSs in patients with COPD. A total of 90 references corresponding to 83 studies were included, including 26 randomised clinical trials (RCTs), 33 cohort studies, and 24 nested case-control (NCC) studies. Analysis of 19 RCTs showed that exposure to ICSs for >= 1 year increased the risk of pneumonia by 41% (risk ratio 1.41, 95% CI 1.23-1.61). Additionally, cohort and NCC studies showed an association between ICSs and risk of tuberculosis and mycobacterial disease. There was a strong association between ICS use and local disorders such as oral candidiasis and dysphonia. The association between ICSs and the risk of diabetes and fractures was less clear and appeared significant only at high doses of ICSs. Since most patients with COPD are elderly and with frequent comorbidities, an adequate risk-benefit balance is crucial for the indication of ICSs.

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. (C) 2021 Sociedad Espanola de Cardiologia. Published by Elsevier Espana, S.L.U.

Objective: The aim of this review was to evaluate a selection of major reporting aspects in manual therapy (MT) trials, before and after the publication of the CONSORT extension for nonpharmacological trials (CONSORTnpt) Study Design and Setting: We randomly selected 100 MT trials published between 2000 and 2015 and divided them into a preCONSORTnpt (n 5 50) and a post-CONSORTnpt (n 5 50) group. We extracted data on relevant issues of internal validity, reliability, and description of interventions. Two authors extracted data independently. Percentages were used for descriptive analyses, and Fisher's exact test and the chi-square test were used for group comparisons. Results: Six different types of MT interventions with up to 20 controls were analyzed. The most common populations/conditions studied were healthy subjects and subjects with lower back or neck pain. Over 70% of studies included multi-session interventions, and 42% of studies reported long-term followup. The only significant differences between groups were the inclusion of a flowchart diagram, the estimated effect size, precision descriptions, and the description of intervention procedures. Conclusion: Our findings suggest that trials in MT show poor reporting even after the availability of standardized guidelines. (C) 2020 Elsevier Inc. All rights reserved.

Objective: To assess the effectiveness of Extracorporeal Shock Wave Therapy (ESWT) to reduce lower limb spasticity in adult stroke survivors.Data Sources: A systematic review of Medline/Pubmed, CENTRAL, CINAHL, PEDro database, REHABDATA, Scielo, Scopus, Web of Science, Trip Database, and Epistemonikos from 1980 to December 2018 was carried out.Review Methods: The bibliography was screened to identify clinical trials (controlled and before-after) that used ESWT to reduce spasticity in stroke survivors. Two reviewers independently screened references, selected relevant studies, extracted data, and assessed risk of bias by PEDro scale. The primary outcome was spasticity.Results: A total of 12 studies (278 participants) were included (5 randomized controlled trials, 1 controlled trial, and 6 before-after studies). A meta-analysis was performed by randomized controlled trials. A beneficial effect on spasticity was found. The mean difference (MD) was 0.58; 95% confidence interval (CI) 0.30 to 0.86 and also in subgroup analysis (short, medium, and long term). The MD for range of motion was 1.81; CI -0.20 to 3.82 and for lower limb function the standard mean difference (SMD) was 0.34; 95% CI -0.09 to 0.77. Sensitivity analysis demonstrated a better beneficial effect for myotendinous junction. MD was 1.5; 95% CI -2.44 to 5.44 at long-term (9 weeks).Conclusion: The ESWT (radial/focused) would be a good non-invasive rehabilitation strategy in chronic stroke survivors to reduce lower limb spasticity, increase ankle range of motion, and improve lower limb function. It does not show any adverse events and it is a safe and effective method.

Background: Venous thromboembolism (VTE) is a serious, sometimes life-threatening complication that can occur following spine surgery. The incidence of VTE, and the optimal type and timing of thromboprophylaxis for this complication in elective spine surgery is a matter of debate. Objective: To perform a systematic review with the aim of clarifying the efficacy and adverse effects of mechanical and chemical prophylaxis for preventing thromboembolic complications in elective spine surgery for conditions other than trauma and malignant disease. Methods/design: A search strategy of related articles up to March 2018 was designed and executed in Medline and Embase. Patients: adolescents (>10 years) and adults undergoing elective surgery for spinal deformity or degenerative disease (from C1 to S1). Intervention: Perioperative mechanical and chemical thromboprophylaxis. Studies could be randomized controlled trials or observational studies that reported data on any relevant clinical outcomes. Results: In total, 2451 uniquecitations were identified and 35 studies were ultimately included in the systematic review. The overall mean incidence of complications was 3.7% for deep venous thrombosis, 0.0% for pulmonary embolism, and 3.7% for bleeding in chemoprophylaxis group; 2.9% for deep venous thrombosis, 0.4% for pulmonary embolism and 0.0% for bleeding in mechanoprophylaxis; and 0.7% for deep venous thrombosis, 0.1% for pulmonary embolism and 0.2% for bleeding in mixed prophylaxis group with no specific data on these rates for the type of patient and type and location of surgery. None of the articles retrieved provided information on the adolescent population. Discussion and Conclusions: The poor design and high variability among the studies regarding characteristics of study population, details of interventions, and definitions of outcomes, determines a low quality of the available evidence and limits the interpretation of the results. We were unable to identify a clear advantage of one type of thromboprophylaxis over the other, although there was an increased risk of bleeding with chemoprophylaxis, which could favor the use of mechanoprophylaxis in this scenario.

Introduction Sepsis is a leading cause of mortality in critically ill patients. Recently, it has been recognised that sex may contribute to a differential risk for developing sepsis and it remains uncertain if the prognosis of sepsis varies between the sexes. The aim of this systematic review is to summarise the available evidence to assess the role of sex as a prognostic factor in patients with sepsis managed in the intensive care unit (ICU). Methods and analysis This is a systematic review protocol of prognostic studies of sex in patients with sepsis managed in the ICU. The primary outcomes include all-cause hospital mortality and all-cause hospital mortality during the first 28 days. The secondary outcomes include all-cause hospital mortality during the first 7 days and all-cause mortality at 1 year. We will conduct a search strategy based on the population (sepsis), the prognostic factor (sex), the outcome of interest (mortality) and prognostic study methods. We will search in the following databases up to December 2019: MEDLINE Ovid (from 1976), Embase Elsevier (from 1974), Web of Science and two trial registries. We will impose no language restrictions. Two authors will independently screen titles, abstracts and full-text articles for eligibility of studies, and subsequently extract data. Two authors will independently assess the risk of bias of each study using the Quality in Prognostic Studies (QUIPS) tool. If possible, we will carry out a meta-analysis to provide a pooled prognostic effect estimate for each outcome. We will use the Grading of Recommendations Assessment, Development and Evaluation system to assess the quality of evidence. Ethics and dissemination Ethical approval will not be required. Findings from this review will be reported in a peer-reviewed scientific journal. Additionally, the results will be disseminated at conferences and in the mass media. PROSPERO registration number CRD42019145054. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Introduction We assessed the efficacy of fibrin sealant (FS) and tranexamic acid (TXA) administered topically in patients with a hip fracture treated with prosthetic replacement. Materials and methods Parallel, multicentre, open label, randomised, clinical trial. We compared three interventions to reduce blood loss: (1) 10ml of FS, (2) 1g of topical TXA, both administered at the end of the surgery, and (3) usual haemostasis (control group). The main outcome was blood loss collected in drains. Other secondary variables were total blood loss, hidden blood loss, transfusion rate, average hospital stay, complications, adverse events, and mortality. Results A total of 158 patients were included, 56 in the FS group, 52 in the TXA group, and 50 in the control group. The total amount of blood collected in drains was lower in the TXA group (148.6ml, SD 122.7 in TXA; 168.2ml, SD 137.4 in FS; and 201.5ml, SD 166.5 in control group) without achieving statistical significance (p=0.178). The transfusion rate was lower in the TXA group (32.7%), compared with FS group (42.9%) and control group (44.0%), without statistical significance (p=0.341). There were no complications or adverse effects related to the evaluated interventions. Conclusions The use of TXA and FS administered topically prior to surgical closure in patients with a sub-capital femoral fracture undergoing arthroplasty did not significantly reduce either postoperative blood loss or transfusion rate, compared with a group that only received usual haemostasis.

Background Early enteral nutrition support (within 48 hours of admission or injury) is frequently recommended for the management of patients in intensive care units (ICU). Early enteral nutrition is recommended in many clinical practice guidelines, although there appears to be a lack of evidence for its use and benefit. Objectives To evaluate the efficacy and safety of early enteral nutrition (initiated within 48 hours of initial injury or ICU admission) versus delayed enteral nutrition (initiated later than 48 hours after initial injury or ICU admission), with or without supplemental parenteral nutrition, in critically ill adults. Search methods We searched CENTRAL (2019, lssue4), MEDLINE Ovid (1946 to April 2019), Embase Ovid SP (1974 to April 2019), CINAHL EBSCO (1982 to April 2019), and ISI Web of Science (1945 to April 2019). We also searched Turning Research Into Practice (TRIP), trial registers (ClinicatTrials.gov, ISRCTN registry), and scientific conference reports, including the American Society for Parenteral and Enteral Nutrition and the European Society for Clinical Nutrition and Metabolism. We applied no restrictions by language or publication status. Selection criteria We included all randomized controlled trials (RCTs) that compared early versus delayed enteral nutrition, with or without supplemental parenteral nutrition, in adults who were in the ICU for longer than 72 hours. This included individuals admitted for medical, surgical, and trauma diagnoses, and who required any type of enteral nutrition. Data collection and analysis Two review authors extracted study data and assessed the risk of bias in the included studies, We expressed results as risk ratios (RR) for dichotomous data, and as mean differences (MD) for continuous data, both with 95% confidence intervals (CI). We assessed the certainty of the evidence using GRADE. Main results We included seven RCTs with a total of 345 participants. Outcome data were limited, and we judged many trials to have an unclear risk of bias in several domains. Early versus delayed enterat nutrition Six trials (318 participants) assessed early versus delayed enteral nutrition in general, medical, and trauma ICUs in the USA, Australia, Greece, India, and Russia. Primary outcomes Five studies (259 participants) measured mortality. It is uncertain whether early enteral nutrition affects the risk of mortality within 30 days (RR 1.00, 95% CI 0.16 to 6.38; 1 study, 38 participants; very low-quality evidence). Four studies (221 participants) reported mortality without describing the timeframe; we did not pool these results. None of the studies reported a clear difference in mortality between groups. Three studies (156 participants) reported infectious complications. We were unable to pool the results due to unreported data and sub-stantiat clinical heterogeneity. The results were inconsistent across studies. One trial measured feed intolerance or gastrointestinal complications; it is uncertain whether early enteral nutrition affects this outcome (RR 0.84, 95% CI 0.35 to 2.01; 59 participants; very low quality evidence). Secondary outcomes One trial assessed hospital length of stay and reported a longer stay in the early enteral group (median 15 days (interquartile range (IQR) 9.5 to 20) versus 12 days (IQR 7.5 to15); P = 0.05; 59 participants; very low-quality evidence). Three studies (125 participants) reported the duration of mechanical ventilation. We did not pool the results due to clinical and statistical heterogeneity. The results were inconsistent across studies. It is uncertain whether early enteral nutrition affects the risk of pneumonia (RR 0.77, 95% CI 0.55 to 1.06; 4 studies, 192 participants; very low-quality evidence). Early enteral nutrition with supplemental parenterat nutrition versus delayed enteral nutrition with supplemental parenterat nutrition We identified one trial in a burn ICU in the USA (27 participants). Primary outcomes It is uncertain whether early enteral nutrition with supplemental parenteral nutrition affects the risk of mortality (RR 0.74, 95% CI 0.25 to 2.18; very low-quality evidence), or infectious complications (MD 0.00,95% CI -1.94 to 1.94; very low-quality evidence). There were no data available for feed intolerance or gastrointestinal complications. Secondary outcomes It is uncertain whether early enteral nutrition with supplemental parenteral nutrition reduces the duration of mechanical ventilation (MD 9.00, 95% CI 10.99 to 28.99; very low quality evidence). There were no data available for hospital length of stay or pneumonia. Authors' conclusions Due to very low-quality evidence, we are uncertain whether early enteral nutrition, compared with delayed enteral nutrition, affects the risk of mortality within 30 days, feed intolerance or gastrointestinal complications, or pneumonia. Due to very low-quality evidence, we are uncertain if early enteral nutrition with supplemental parenteral nutrition compared with delayed enteral nutrition with supplemental parenteral nutrition reduces mortality, infectious complications, or duration of mechanical ventilation. There is currently insufficient evidence; there is a need for large, multicentred studies with rigorous methodology, which measure important clinical outcomes.

Background. Leukocytes contained in the allogeneic packed red blood cell (PRBC) are the cause of certain adverse reactions associated with blood transfusion. Leukoreduction consists of eliminating leukocytes in all blood products below the established safety levels for any patient type. In this systematic review, we appraise the clinical effectiveness of allogeneic leukodepleted (LD) PRBC transfusion for preventing infections and death in patients undergoing major cardiovascular surgical procedures. Methods. We searched randomized controlled trials (RCT), enrolling patients undergoing a major cardiovascular surgical procedure and transfused with LD-PRBC. Data were extracted, and risk of bias was assessed according to Cochrane guidelines. In addition, trial sequential analysis (TSA) was used to assess the need of conducting additional trials. Quality of the evidence was assessed using the GRADE approach. Results. Seven studies met the eligibility criteria. Quality of the evidence was rated as moderate for both outcomes. The risk ratio for death from any cause comparing the LD-PRBC versus non-LD-PRBC group was 0.69 (CI 95% = 0.53 to 0.90; I2 = 0%). The risk ratio for infection in the same comparison groups was 0.77 (CI 95% = 0.66 to 0.91; I2 = 0%). TSA showed a conclusive result in this outcome. Conclusions. We found evidence that supports the routine use of leukodepletion in patients undergoing a major cardiovascular surgical procedure requiring PRBC transfusion to prevent death and infection. In the case of infection, the evidence should be considered sufficient and conclusive and hence indicated that further trials would not be required.

Introduction and objectives Heart transplantation (HT) is the treatment for patients with end-stage heart disease. Despite contradictory reports, survival seems to be worse when donor/recipient sex is mismatched. This systematic review and meta-analysis aims to synthesize the evidence on the effect of donor/recipient sex mismatch after HT. Methods We searched PubMed and EMBASE until November 2017. Comparative cohort and registry studies were included. Published articles were systematically selected and, when possible, pooled in a meta-analysis. The primary endpoint was one-year mortality. Results After retrieving 556 articles, ten studies (76 175 patients) were included in the quantitative meta-analysis. Significant differences were found in one-year survival between sex-matched and mismatched recipients (odds ratio (OR) 1.30, 95% confidence interval (CI) 1.25-1.35, P < .001). In female recipients, we found that sex mismatch was not a risk factor for one-year mortality (OR = 0.93, 95% CI = 0.85-1.00, P = .06). However, in male recipients, we found that it was a risk factor for one-year mortality (OR = 1.38, 95% CI = 1.31-1.44, P < .001). Conclusions Sex mismatch increases one-year mortality after HT in male recipients. Its influence in long-term survival should be further explored with high-quality studies.

Background Safely reducing red blood cell transfusions can prevent transfusion-related adverse effects, conserve the blood supply, and reduce health care costs. Both anemia and red blood cell transfusion are independently associated with AKI, but observational data are insufficient to determine whether a restrictive approach to transfusion can be used without increasing AKI risk. Methods In a prespecified kidney substudy of a randomized noninferiority trial, we compared a restrictive threshold for red blood cell transfusion (transfuse if hemoglobin= 0.3 mg/dl within 48 hours of surgery, or >= 50% within 7 days of surgery. Results Patients in the restrictive-threshold group received significantly fewer transfusions than patients in the liberal-threshold group (1.8 versus 2.9 on average, or 38% fewer transfusions in the restricted threshold group compared with the liberal-threshold group; P

Background: Long-acting bronchodilators are the cornerstone of pharmacologic treatment of COPD. The new combination of long-acting muscarinic antagonist (LAMA) tiotropium (TIO) and long acting beta-agonists (LABA) olodaterol (OLO) has been introduced as fist line therapy for COPD. This article analyses the evidence of efficacy and safety of the TIO/OLO combination. Methods: A systematic review and metaanalysis of randomized controlled trials (RCT) with a period of treatment of at least 6 weeks, in patients with COPD confirmed by spirometry, comparing combined treatment with TIO/OLO (approved doses only), with any of the mono-components or any other active comparator administered as an inhalator. Results: A total of 10 Randomized controlled trials (RCT) were identified (N = 10,918). TIO/OLO significantly improved trough FEV1 from baseline to week 12 versus TIO, OLO and LABA/ICS (0.06 L, 0.09 L and between 0.04 and 0.05 L, respectively). TIO/OLO improved transitional dyspnea index (TDI) and St. George's Respiratory Questionnaire (SGRQ) compared with mono-components, with patients more likely to achieve clinically important improvements in TDI (risk ratio [RR]: 1.17, 95% confidence interval [CI]: [1.07, 1.28] versus TIO and RR: 1.14, 95% CI: [1.01, 1.28] versus OLO) and in SGRQ (RR: 1.21, 95% CI: [1.12, 1.30] versus TIO and RR: 1.28, 95% CI: [1.18, 1.40] versus OLO). Patients treated with TIO/OLO showed a significant reduction in the use of rescue medication and no significant differences in frequency of general and serious adverse events were observed between TIO/OLO and mono-components. Conclusions: Treatment with TIO/OLO provided significant improvements in lung function versus mono-components and LABA/ICS with more patients achieving significant improvements in dyspnea and health status. No differences in adverse events were observed compared with other active treatments.

Background: Gastrointestinal Stromal Tumours (GISTs) are the most common mesenchymal tumours. Currently, different pharmacological and surgical options are used to treat localised and metastatic GISTs, although this research field is broad and the body of evidence is scattered and expanding. Our objectives are to identify, describe and organise the current available evidence for GIST through an evidence mapping approach. Methods: We followed the methodology of Global Evidence Mapping (GEM). We searched Pubmed, EMBASE, The Cochrane Library and Epistemonikos in order to identify systematic reviews (SRs) with or without meta-analyses published between 1990 and March 2016. Two authors assessed eligibility and extracted data. Methodological quality of the included systematic reviews was assessed using AMSTAR. We organised the results according to identified PICO questions and presented the evidence map in tables and a bubble plot. Results: A total of 17 SRs met eligibility criteria. These reviews included 66 individual studies, of which three quarters were either observational or uncontrolled clinical trials. Overall, the quality of the included SRs was moderate or high. In total, we extracted 14 PICO questions from them and the corresponding results mostly favoured the intervention arm. Conclusions: The most common type of study used to evaluate therapeutic interventions in GIST sarcomas has been non-experimental studies. However, the majority of the interventions are reported as beneficial or probably beneficial by the respective authors of SRs. The evidence mapping is a useful and reliable methodology to identify and present the existing evidence about therapeutic interventions.

Background. The goals of the treatment of muscle injuries are to shorten the time of healing and to avoid relapses. The aim of this study was to assess the efficacy of autologous platelet-rich plasma (PRP) in the healing of muscle injuries. Materials and methods. A multicentre, randomised, double-blind, parallel, controlled clinical trial was conducted in 71 patients (81.8% males) aged 45.6 (SD=10.0) years with muscle tears in the legs and haematoma. The haematoma was evacuated in all patients. Thirty-three patients were randomised to a single dose of autologous PRP and 38 patients to simulation of PRP administration. The primary end-point was time to complete recovery of muscle injury. Secondary end-points were pain, relapses, ultrasound parameters, and adverse events. The total follow-up per patient was 12 months. Results. Time to complete recovery after the treatment was 31.63 days (SD=15.38) in the PRP group, and 38.43 days (SD=18.58) in the control group (p=0.261). Pain decreased over time in both groups without statistical differences between them. Eight patients relapsed (seven in the control group, and one in the PRP group). There were no adverse effects related to the interventions. Discussion. Autologous PRP did not significantly improve the time to healing compared to that in the control group.

Background Inadvertent perioperative hypothermia is a phenomenon that can occur as a result of the suppression of the central mechanisms of temperature regulation due to anaesthesia, and of prolonged exposure of large surfaces of skin to cold temperatures in operating rooms. Inadvertent perioperative hypothermia has been associated with clinical complications such as surgical site infection and wound-healing delay, increased bleeding or cardiovascular events. One of the most frequently used techniques to prevent inadvertent perioperative hypothermia is active body surface warming systems (ABSW), which generate heat mechanically (heating of air, water or gels) that is transferred to the patient via skin contact. Objectives To assess the effectiveness of pre- or intraoperative active body surface warming systems (ABSW), or both, to prevent perioperative complications from unintended hypothermia during surgery in adults. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL; Issue 9, 2015); MEDLINE (PubMed) (1964 to October 2015), EMBASE (Ovid) (1980 to October 2015), and CINAHL (Ovid) (1982 to October 2015). Selection criteria We included randomized controlled trials (RCTs) that compared an ABSW system aimed at maintaining normothermia perioperatively against a control or against any other ABSW system. Eligible studies also had to include relevant clinical outcomes other than measuring temperature alone. Data collection and analysis Several authors, by pairs, screened references and determined eligibility, extracted data, and assessed risks of bias. We resolved disagreements by discussion and consensus, with the collaboration of a third author. Main results We included 67 trials with 5438 participants that comprised 79 comparisons. Forty-five RCTs compared ABSW versus control, whereas 18 compared two different types of ABSW, and 10 compared two different techniques to administer the same type of ABSW. Forced-air warming (FAW) was by far the most studied intervention. Trials varied widely regarding whether the interventions were applied alone or in combination with other active (based on a different mechanism of heat transfer) and/or passive methods of maintaining normothermia. The type of participants and surgical interventions, as well as anaesthesia management, co-interventions and the timing of outcome measurement, also varied widely. The risk of bias of included studies was largely unclear due to limitations in the reports. Most studies were open-label, due to the nature of the intervention and the fact that temperature was usually the principal outcome. Nevertheless, given that outcome measurement could have been conducted in a blinded manner, we rated the risk of detection and performance bias as high. The comparison of ABSW versus control showed a reduction in the rate of surgical site infection (risk ratio (RR) 0.36, 95% confidence interval (CI) 0.20 to 0.66; 3 RCTs, 589 participants, low-quality evidence). Only one study at low risk of bias observed a beneficial effect with forced-air warming on major cardiovascular complications (RR 0.22, 95% CI 0.05 to 1.00; 1 RCT with 12 events, 300 participants, low-quality evidence) in people at high cardiovascular risk. We found no beneficial effect for mortality. ABSW also reduced blood loss during surgery but the magnitude of this effect seems to be irrelevant (MD -46.17 mL, 95% CI -82.74 to -9.59; I-2 = 78%; 20 studies, 1372 participants). The same conclusion applies to total fluids infused during surgery (MD -144.49 mL, 95% CI -221.57 to -67.40; I-2 = 73%; 24 studies, 1491 participants). These effects did not translate into a significant reduction in the number of participants being transfused or the average amount of blood transfused. ABSW was associated with a reduction in shivering (RR 0.39, 95% CI 0.28 to 0.54; 29 studies, 1922 participants) and in thermal comfort (standardized mean difference (SMD) 0.76, 95% CI 0.29 to 1.24; I-2 = 77%, 4 trials, 364 participants). For the comparison between different types of ABSW system or modes of administration of a particular type of ABSW, we found no evidence for the superiority of any system in terms of clinical outcomes, except for extending systemic warming to the preoperative period in participants undergoing major abdominal surgery (one study at low risk of bias). There were limited data on adverse effects (the most relevant being thermal burns). While some trials included a narrative report mentioning that no adverse effects were observed, the majority made no reference to it. Nothing so far suggests that ABSW involves a significant risk to patients. Authors' conclusions Forced-air warming seems to have a beneficial effect in terms of a lower rate of surgical site infection and complications, at least in those undergoing abdominal surgery, compared to not applying any active warming system. It also has a beneficial effect on major cardiovascular complications in people with substantial cardiovascular disease, although the evidence is limited to one study. It also improves patient's comfort, although we found high heterogeneity among trials. While the effect on blood loss is statistically significant, this difference does not translate to a significant reduction in transfusions. Again, we noted high heterogeneity among trials for this outcome. The clinical relevance of blood loss reduction is therefore questionable. The evidence for other types of ABSW is scant, although there is some evidence of a beneficial effect in the same direction on chills/shivering with electric or resistive-based heating systems. Some evidence suggests that extending systemic warming to the preoperative period could be more beneficial than limiting it only to during surgery. Nothing suggests that ABSW systems pose a significant risk to patients. The difficulty in observing a clinically-relevant beneficial effect with ABSW in outcomes other than temperature may be

Objective: The objective of the present study was to determine the publication rate of cancer randomized controlled trial (RCTs) and to analyze the determinants of the publication, as well as to estimate the possible existence of a location and time lag bias. We also described the bibliometric characteristics of the publications. Study design and Setting: We conducted an observational study that identified publications resulting from RCTs involving cancer-related drug products. These studies were authorized and registered by the Spanish Agency of Medicines and Medical Devices between 1999 and 2003. Results: We identified 168 publications of 303 RCTs, resulting in a publication rate of 55.4% after a mean follow-up of 12 years. The only factor associated to the likelihood of nonpublication was the study setting favoring only national RCTs (odds ratio 2.7;95% confidence interval 1.5-4.8). Type of sponsor did not seem to be associated, although the largest volume of nonpublished trials is international, industry-sponsored. Positive results seemed to be associated to a publication in a higher impact factor journal and a shorter time-to-publication. Conclusions: About half of the cancer RCTs during the target period have not been published. The national setting is a factor associated to nonpublication, whereas the direction of results determines its dissemination (impact factor and timely publication). (C) 2016 Elsevier Inc. All rights reserved.

BACKGROUND: There is substantial variability in the perioperative administration of aspirin in patients undergoing noncardiac surgery, both among patients who are already on an aspirin regimen and among those who are not. METHODS: Using a 2-by-2 factorial trial design, we randomly assigned 10,010 patients who were preparing to undergo noncardiac surgery and were at risk for vascular complications to receive aspirin or placebo and clonidine or placebo. The results of the aspirin trial are reported here. The patients were stratified according to whether they had not been taking aspirin before the study (initiation stratum, with 5628 patients) or they were already on an aspirin regimen (continuation stratum, with 4382 patients). Patients started taking aspirin (at a dose of 200 mg) or placebo just before surgery and continued it daily (at a dose of 100 mg) for 30 days in the initiation stratum and for 7 days in the continuation stratum, after which patients resumed their regular aspirin regimen. The primary outcome was a composite of death or nonfatal myocardial infarction at 30 days. RESULTS: The primary outcome occurred in 351 of 4998 patients (7.0%) in the aspirin group and in 355 of 5012 patients (7.1%) in the placebo group (hazard ratio in the aspirin group, 0.99; 95% confidence interval [CI], 0.86 to 1.15; P = 0.92). Major bleeding was more common in the aspirin group than in the placebo group (230 patients [4.6%] vs. 188 patients [3.8%]; hazard ratio, 1.23; 95% CI, 1.01, to 1.49; P = 0.04). The primary and secondary outcome results were similar in the two aspirin strata. CONCLUSIONS: Administration of aspirin before surgery and throughout the early postsurgical period had no significant effect on the rate of a composite of death or nonfatal myocardial infarction but increased the risk of major bleeding. (Funded by the Canadian Institutes of Health Research and others; POISE-2 ClinicalTrials.gov number, NCT01082874.) Copyright © 2014 Massachusetts Medical Society.

Background: Marked activation of the sympathetic nervous system occurs during and after noncardiac surgery. Low-dose clonidine, which blunts central sympathetic outflow, may prevent perioperative myocardial infarction and death without inducing hemodynamic instability. Methods: We performed a blinded, randomized trial with a 2-by-2 factorial design to allow separate evaluation of low-dose clonidine versus placebo and low-dose aspirin versus placebo in patients with, or at risk for, atherosclerotic disease who were undergoing noncardiac surgery. A total of 10,010 patients at 135 centers in 23 countries were enrolled. For the comparison of clonidine with placebo, patients were randomly assigned to receive clonidine (0.2 mg per day) or placebo just before surgery, with the study drug continued until 72 hours after surgery. The primary outcome was a composite of death or nonfatal myocardial infarction at 30 days. Results: Clonidine, as compared with placebo, did not reduce the number of primary-outcome events (367 and 339, respectively; hazard ratio with clonidine, 1.08; 95% confidence interval [CI], 0.93 to 1.26; P=0.29). Myocardial infarction occurred in 329 patients (6.6%) assigned to clonidine and in 295 patients (5.9%) assigned to placebo (hazard ratio, 1.11; 95% CI, 0.95 to 1.30; P=0.18). Significantly more patients in the clonidine group than in the placebo group had clinically important hypotension (2385 patients [47.6%] vs. 1854 patients [37.1%]; hazard ratio 1.32; 95% CI, 1.24 to 1.40; P

Background: Postoperative blood loss in patients after total knee arthroplasty may cause local and systemic complications and influence clinical outcome. The aim of this study was to assess whether fibrin glue or tranexamic acid reduced blood loss compared with routine hemostasis in patients undergoing total knee arthroplasty. Methods: A randomized, single-center, parallel, open clinical trial was performed in adult patients undergoing primary total knee arthroplasty. Patients were divided into four groups. Group 1 received fibrin glue manufactured by the Blood and Tissue Bank of Catalonia, Group 2 received Tissucol (fibrinogen and thrombin), Group 3 received intravenous tranexamic acid, and Group 4 (control) had no treatment other than routine hemostasis. The primary outcome was total blood loss collected in drains after surgery. Secondary outcomes were the calculated hidden blood loss, transfusion rate, preoperative and postoperative hemoglobin, number of blood units transfused, adverse events, and mortality. Results: One hundred and seventy-two patients were included. The mean total blood loss (and standard deviation) collected in drains was 553.9+/-321.5 mL for Group 1,567.8+/-299.3 mL for Group 2, 244.1+/-223.4 mL for Group 3, and 563.5+/-269.7 mL for Group 4. In comparison with the control group, Group 3 had significantly lower total blood loss (p < 0.001), but it was not significantly lover in Groups 1 and 2. The overall rate of patients who had a blood transfusion was 21.1% (thirty-five of 166 patients analyzed per protocol). Two patients required transfusion in Group 3 compared with twelve patients in Group 4 (p = 0.015). No significant difference was observed between the two fibrin glue groups and the control group with regard to the need for transfusion. There was no difference between groups with regard to the percentage of adverse events. Conclusions: Neither type of fibrin glue was more effective than routine hemostasis in reducing postoperative bleeding and transfusion requirements, and we no longer use them. However, this trial supports findings from previous studies showing that intravenous tranexamic acid can decrease postoperative blood loss.

El presente documento constituye el informe Final del proyecto Estudio biológico pesquero de anguila en la Región de Magallanes, cuyo objetivo general fue determinar antecedentes biológicos y pesqueros del recurso anguila babosa en la región y proponer medidas de ordenamiento para su explotación. This document constitutes the Final Report draft biological study of eel fishing in Magallanes region, whose main objective was determine life history and fishery slimy eel resource in the region and suggest measures order to exploit them. Unpublished

BACKGROUND CONTEXT: Shock wave and especially ultrasound are commonly used to treat low back pain (LBP) in routine practice. PURPOSE: To assess the evidence on the efficacy, effectiveness, cost-effectiveness, and safety of ultrasound and shock wave to treat LBP. STUDY DESIGN: Systematic review. METHODS: An electronic search was performed in MEDLINE, EMBASE, and the Cochrane Library databases up to July 2009 to identify randomized controlled trials (RCTs) comparing vibrotherapy with placebo or with other treatments for LBP. No language restrictions were applied. Additional data were requested from the authors of the original studies. The risk of bias of each study was assessed following the criteria recommended by the Cochrane Back Review Group. RESULTS: Thirteen studies were identified. The four RCTs complying with the inclusion criteria included 252 patients. Two of the three RCTs on ultrasound had a high risk of bias. For acute patients with LBP and leg pain attributed to disc herniation, ultrasound, traction, and low-power laser obtained similar results. For chronic LBP patients without leg pain, ultrasound was less effective than spinal manipulation, whereas a shock wave device and transcutaneous electrical nerve stimulation led to similar results. Results from the only study comparing ultrasound versus a sham procedure are unreliable because of the inappropriateness of the sham procedure, low sample size, and lack of adjustment for potential confounders. No study assessed cost-effectiveness. No adverse events were reported. CONCLUSION: The available evidence does not support the effectiveness of ultrasound or shock wave for treating LBP. High-quality RCTs are needed to assess their efficacy versus appropriate sham procedures, and their effectiveness and cost-effectiveness versus other procedures shown to be effective for LBP. In the absence of such evidence, the clinical use of these forms of treatment is not justified and should be discouraged. (C) 2011 Elsevier Inc. All rights reserved.

Context Theory and simulation suggest that randomized controlled trials (RCTs) stopped early for benefit (truncated RCTs) systematically overestimate treatment effects for the outcome that precipitated early stopping. Objective To compare the treatment effect from truncated RCTs with that from meta-analyses of RCTs addressing the same question but not stopped early (nontruncated RCTs) and to explore factors associated with overestimates of effect. Data Sources Search of MEDLINE, EMBASE, Current Contents, and full-text journal content databases to identify truncated RCTs up to January 2007; search of MEDLINE, Cochrane Database of Systematic Reviews, and Database of Abstracts of Reviews of Effects to identify systematic reviews from which individual RCTs were extracted up to January 2008. Study Selection Selected studies were RCTs reported as having stopped early for benefit and matching nontruncated RCTs from systematic reviews. Independent reviewers with medical content expertise, working blinded to trial results, judged the eligibility of the nontruncated RCTs based on their similarity to the truncated RCTs. Data Extraction Reviewers with methodological expertise conducted data extraction independently. Results The analysis included 91 truncated RCTs asking 63 different questions and 424 matching nontruncated RCTs. The pooled ratio of relative risks in truncated RCTs vs matching nontruncated RCTs was 0.71 (95% confidence interval, 0.65-0.77). This difference was independent of the presence of a statistical stopping rule and the methodological quality of the studies as assessed by allocation concealment and blinding. Large differences in treatment effect size between truncated and nontruncated RCTs (ratio of relative risks

El objetivo de esta investigación es conocer las pesquerías de pez espada que se configuran en aguas internacionales del pacífico Sur Oriental, frente a las costas de Chile, precisando su localización y estacionalidad, niveles de captura, esfuerzo de pesca, rendimientos y composición de tamaños. The objective of this research is to understand the swordfish fisheries that are set in international waters of eastern South Pacific, off the coast of Chile, indicating their location and seasonality, catch levels, fishing effort, yield and size composition. Unpublished

Objetivo: Determinar la incidencia del cáncer de vejiga en la comarca del Vallès Occidental (Barcelona), describir sus características histopatológicas y comparar su incidencia con la de otras áreas españolas y europeas. Método: Se incluyeron los casos nuevos de cáncer de vejiga diagnosticados entre 1992 y 1994 en el Vallès Occidental, área muy industrializada de Cataluña (España). Se ajustaron por edad las tasas de incidencia y se compararon con las de los datos publicados en los registros de otras áreas españolas y europeas. Resultados: Se identificaron 485 casos de cáncer de vejiga, el 95,5% de los cuales eran carcinomas de células transicionales. La mayoría de los tumores (75,9%) eran superficiales y tenían un grado de diferenciacón I o II (62,6%). El cáncer de vejiga fue más frecuente en los varones. Las mujeres presentaron tumores de peor pronóstico y una edad media en el momento del diagnóstico significativamente superior a la de los varones (71 frente a 66 años; p = 0,03). La tasa de incidencia ajustada para los varones (52,2 casos/100.000) fue de las más altas, mientras que en las mujeres (5,4 casos/100.000) fue relativamente baja. Conclusiones: La incidencia de cáncer de vejiga en la población del Vallès Occidental se encuentra para los varones entre las más altas de Europa, y en cambio para las mujeres ocupa un lugar bajo. La elevada razón varón/mujer observada podría ser debida a que las mujeres españolas han estado menos expuestas a los factores de riesgo, o bien lo han hecho más recientemente. Aim: To identify all incident cases of bladder cancer in the county of Vallès Occidental (Spain), describe their histopathological characteristics, and make comparisons with other Spanish and European areas. Method: The study was carried out from the Corporació Parc Taulí (Sabadell). All new cases of bladder cancer in residents of the county Vallès Occidental, a highly industrialised area of Catalonia (Spain), were included between 1992 and 1994. Incidence rates of bladder cancer were adjusted and were compared with adjusted incidence rates reported by registries in other Spanish and European countries. Results: 485 new cases were identified. Transitional cell carcinomas predominated (95.5%). The majority of tumours were diagnosed in their initial stages, 75.9% being superficial and 62.6% well to moderately differentiated. Bladder cancer was more common in men than in women, but women presented tumours of worse prognosis. The mean age at diagnosis was also higher in women than men (71 vs. 66 years, p = 0.03). The adjusted incidence rate in men (52.2 cases/100,000) was among the highest of the observed areas, whereas for women (5.4 cases/100,000) was relatively low. Conclusions: The incidence of bladder cancer among men in Vallès Occidental is among the highest in Europe, and intermediate for women. The high male/female ratio seen in all Spanish areas could be attributed to the fact that women in Spain have been less exposed than men to the risk factors, or their exposure occurred more recently

BACKGROUND Consensus recommendations regarding the threshold levels of cardiac troponin elevations for the definition of perioperative myocardial infarction and clinically important periprocedural myocardial injury in patients undergoing cardiac surgery range widely (from >10 times to >= 70 times the upper reference limit for the assay). Limited evidence is available to support these recommendations. METHODS We undertook an international prospective cohort study involving patients 18 years of age or older who underwent cardiac surgery. High-sensitivity cardiac troponin I measurements (upper reference limit, 26 ng per liter) were obtained 3 to 12 hours after surgery and on days 1, 2, and 3 after surgery. We performed Cox analyses using a regression spline that explored the relationship between peak troponin measurements and 30-day mortality, adjusting for scores on the European System for Cardiac Operative Risk Evaluation II (which estimates the risk of death after cardiac surgery on the basis of 18 variables, including age and sex). RESULTS Of 13,862 patients included in the study, 296 (2.1%) died within 30 days after surgery. Among patients who underwent isolated coronary-artery bypass grafting or aortic-valve replacement or repair, the threshold troponin level, measured within 1 day after surgery, that was associated with an adjusted hazard ratio of more than 1.00 for death within 30 days was 5670 ng per liter (95% confidence interval [CI], 1045 to 8260), a level 218 times the upper reference limit. Among patients who underwent other cardiac surgery, the corresponding threshold troponin level was 12,981 ng per liter (95% CI, 2673 to 16,591), a level 499 times the upper reference limit. CONCLUSIONS The levels of high-sensitivity troponin I after cardiac surgery that were associated with an increased risk of death within 30 days were substantially higher than levels currently recommended to define clinically important periprocedural myocardial injury. (Funded by the Canadian Institutes of Health Research and others; VISION Cardiac Surgery ClinicalTrials.gov number, NCT01842568.)