High-Sensitivity Troponin I after Cardiac Surgery and 30-Day Mortality.

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.).

Stem cell therapy for dilated cardiomyopathy.

BACKGROUND: Stem cell therapy (SCT) has been proposed as an alternative treatment for dilated cardiomyopathy (DCM), nonetheless its effectiveness remains debatable. OBJECTIVES: To assess the effectiveness and safety of SCT in adults with non-ischaemic DCM. SEARCH METHODS: We searched CENTRAL in the Cochrane Library, MEDLINE, and Embase for relevant trials in November 2020. We also searched two clinical trials registers in May 2020. SELECTION CRITERIA: Eligible studies were randomized controlled trials (RCT) comparing stem/progenitor cells with no cells in adults with non-ischaemic DCM. We included co-interventions such as the administration of stem cell mobilizing agents. Studies were classified and analysed into three categories according to the comparison intervention, which consisted of no intervention/placebo, cell mobilization with cytokines, or a different mode of SCT. The first two comparisons (no cells in the control group) served to assess the efficacy of SCT while the third (different mode of SCT) served to complement the review with information about safety and other information of potential utility for a better understanding of the effects of SCT. DATA COLLECTION AND ANALYSIS: Two review authors independently screened all references for eligibility, assessed trial quality, and extracted data. We undertook a quantitative evaluation of data using random-effects meta-analyses. We evaluated heterogeneity using the I² statistic. We could not explore potential effect modifiers through subgroup analyses as they were deemed uninformative due to the scarce number of trials available. We assessed the certainty of the evidence using the GRADE approach. We created summary of findings tables using GRADEpro GDT. We focused our summary of findings on all-cause mortality, safety, health-related quality of life (HRQoL), performance status, and major adverse cardiovascular events. MAIN RESULTS: We included 13 RCTs involving 762 participants (452 cell therapy and 310 controls). Only one study was at low risk of bias in all domains. There were many shortcomings in the publications that did not allow a precise assessment of the risk of bias in many domains. Due to the nature of the intervention, the main source of potential bias was lack of blinding of participants (performance bias). Frequently, the format of the continuous data available was not ideal for use in the meta-analysis and forced us to seek strategies for transforming data in a usable format. We are uncertain whether SCT reduces all-cause mortality in people with DCM compared to no intervention/placebo (mean follow-up 12 months) (risk ratio (RR) 0.84, 95% confidence interval (CI) 0.54 to 1.31; I² = 0%; studies = 7, participants = 361; very low-certainty evidence). We are uncertain whether SCT increases the risk of procedural complications associated with cells injection in people with DCM (data could not be pooled; studies = 7; participants = 361; very low-certainty evidence). We are uncertain whether SCT improves HRQoL (standardized mean difference (SMD) 0.62, 95% CI 0.01 to 1.23; I² = 72%; studies = 5, participants = 272; very low-certainty evidence) and functional capacity (6-minute walk test) (mean difference (MD) 70.12 m, 95% CI -5.28 to 145.51; I² = 87%; studies = 5, participants = 230; very low-certainty evidence). SCT may result in a slight functional class (New York Heart Association) improvement (data could not be pooled; studies = 6, participants = 398; low-certainty evidence). None of the included studies reported major adverse cardiovascular events as defined in our protocol. SCT may not increase the risk of ventricular arrhythmia (data could not be pooled; studies = 8, participants = 504; low-certainty evidence). When comparing SCT to cell mobilization with granulocyte-colony stimulating factor (G-CSF), we are uncertain whether SCT reduces all-cause mortality (RR 0.46, 95% CI 0.16 to 1.31; I² = 39%; studies = 3, participants = 195; very low-certainty evidence). We are uncertain whether SCT increases the risk of procedural complications associated with cells injection (studies = 1, participants = 60; very low-certainty evidence). SCT may not improve HRQoL (MD 4.61 points, 95% CI -5.62 to 14.83; studies = 1, participants = 22; low-certainty evidence). SCT may improve functional capacity (6-minute walk test) (MD 140.14 m, 95% CI 119.51 to 160.77; I² = 0%; studies = 2, participants = 155; low-certainty evidence). None of the included studies reported MACE as defined in our protocol or ventricular arrhythmia. The most commonly reported outcomes across studies were based on physiological measures of cardiac function where there were some beneficial effects suggesting potential benefits of SCT in people with non-ischaemic DCM. However, it is unclear if this intermediate effects translates into clinical benefits for these patients. With regard to specific aspects related to the modality of cell therapy and its delivery, uncertainties remain as subgroup analyses could not be performed as planned, making it necessary to wait for the publication of several studies that are currently in progress before any firm conclusion can be reached. AUTHORS' CONCLUSIONS: We are uncertain whether SCT in people with DCM reduces the risk of all-cause mortality and procedural complications, improves HRQoL, and performance status (exercise capacity). SCT may improve functional class (NYHA), compared to usual care (no cells). Similarly, when compared to G-CSF, we are also uncertain whether SCT in people with DCM reduces the risk of all-cause mortality although some studies within this comparison observed a favourable effect that should be interpreted with caution. SCT may not improve HRQoL but may improve to some extent performance status (exercise capacity). Very low-quality evidence reflects uncertainty regarding procedural complications. These suggested beneficial effects of SCT, although uncertain due to the very low certainty of the evidence, are accompanied by favourable effects on some physiological measures of cardiac function. Presently, the most effective mode of administration of SCT and the population that could benefit the most is unclear. Therefore, it seems reasonable that use of SCT in people with DCM is limited to clinical research settings. Results of ongoing studies are likely to modify these conclusions.

Sex-mismatch influence on survival after heart transplantation: A systematic review and meta-analysis of observational studies.

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.

Early enteral nutrition (within 48 hours) versus delayed enteral nutrition (after 48 hours) with or without supplemental parenteral nutrition in critically ill adults.

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, Issue 4), 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 (ClinicalTrials.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 enteral 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 substantial 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 parenteral nutrition versus delayed enteral nutrition with supplemental parenteral 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.

Myocardial Injury After Noncardiac Surgery (MINS) in Vascular Surgical Patients: A Prospective Observational Cohort Study.

OBJECTIVE: To determine the prognostic relevance, clinical characteristics, and 30-day outcomes associated with myocardial injury after noncardiac surgery (MINS) in vascular surgical patients. BACKGROUND: MINS has been independently associated with 30-day mortality after noncardiac surgery. The characteristics and prognostic importance of MINS in vascular surgery patients are poorly described. METHODS: This was an international prospective cohort study of 15,102 noncardiac surgery patients 45 years or older, of whom 502 patients underwent vascular surgery. All patients had fourth-generation plasma troponin T (TnT) concentrations measured during the first 3 postoperative days. MINS was defined as a TnT of 0.03 ng/mL of higher secondary to ischemia. The objectives of the present study were to determine (i) if MINS is prognostically important in vascular surgical patients, (ii) the clinical characteristics of vascular surgery patients with and without MINS, (iii) the 30-day outcomes for vascular surgery patients with and without MINS, and (iv) the proportion of MINS that probably would have gone undetected without routine troponin monitoring. RESULTS: The incidence of MINS in the vascular surgery patients was 19.1% (95% confidence interval (CI), 15.7%-22.6%). 30-day all-cause mortality in the vascular cohort was 12.5% (95% CI 7.3%-20.6%) in patients with MINS compared with 1.5% (95% CI 0.7%-3.2%) in patients without MINS (P < 0.001). MINS was independently associated with 30-day mortality in vascular patients (odds ratio, 9.48; 95% CI, 3.46-25.96). The 30-day mortality was similar in MINS patients with (15.0%; 95% CI, 7.1-29.1) and without an ischemic feature (12.2%; 95% CI, 5.3-25.5, P = 0.76). The proportion of vascular surgery patients who suffered MINS without overt evidence of myocardial ischemia was 74.1% (95% CI, 63.6-82.4). CONCLUSIONS: Approximately 1 in 5 patients experienced MINS after vascular surgery. MINS was independently associated with 30-day mortality. The majority of patients with MINS were asymptomatic and would have gone undetected without routine postoperative troponin measurement.

Troponin T monitoring to detect myocardial injury after noncardiac surgery: a cost-consequence analysis.

BACKGROUND: Myocardial injury after noncardiac surgery (MINS) is a mostly asymptomatic condition that is strongly associated with 30-day mortality; however, it remains mostly undetected without systematic troponin T monitoring. We evaluated the cost and consequences of postoperative troponin T monitoring to detect MINS. METHODS: We conducted a model-based cost-consequence analysis to compare the impact of routine troponin T monitoring versus standard care (troponin T measurement triggered by ischemic symptoms) on the incidence of MINS detection. Model inputs were based on Canadian patients enrolled in the Vascular Events in Noncardiac Surgery Patients Cohort Evaluation (VISION) study, which enrolled patients aged 45 years or older undergoing inpatient noncardiac surgery. We conducted probability analyses with 10 000 iterations and extensive sensitivity analyses. RESULTS: The data were based on 6021 patients (48% men, mean age 65 [standard deviation 12] yr). The 30-day mortality rate for MINS was 9.6%. We determined the incremental cost to avoid missing a MINS event as $1632 (2015 Canadian dollars). The cost-effectiveness of troponin monitoring was higher in patient subgroups at higher risk for MINS, e.g., those aged 65 years or more, or with a history of atherosclerosis or diabetes ($1309). CONCLUSION: The costs associated with a troponin T monitoring program to detect MINS were moderate. Based on the estimated incremental cost per health gain, implementation of postoperative troponin T monitoring seems appealing, particularly in patients at high risk for MINS.

CONTEXTE: Les lésions myocardiques après chirurgie non cardiaque (CNC) sont majoritairement asymptomatiques et fortement associées au risque de mortalité dans les 30 jours; toutefois, dans la plupart des cas, elles ne sont pas détectées en l'absence d'une surveillance systématique de la troponine T. Nous avons évalué les coûts et les conséquences d'une telle surveillance pour détecter les lésions myocardiques après CNC. MÉTHODES: Nous avons mené une analyse coût-conséquence modélisée pour comparer la surveillance systématique de la troponine T aux soins habituels seuls (mesure de la troponine T seulement s'il y a présence de symptômes d'ischémie) sur la fréquence de détection de lésions myocardiques après CNC. Les données ayant servi à l'analyse provenaient des patients canadiens ayant participé à l'étude de cohorte VISION, qui visait à évaluer les complications vasculaires chez les patients de 45 ans et plus ayant subi une CNC. Nous avons mené des analyses de probabilité avec 10  000 itérations et des analyses de sensibilité approfondies. RÉSULTATS: Les données portaient sur 6021 patients (48 % du sexe masculin; âge moyen de 65 ans [écart-type de 12 ans]). Le taux de mortalité dans les 30 jours associé à une lésion myocardique après CNC était de 9,6 %. Nous avons déterminé que le coût marginal de la détection de la présence d'une lésion par surveillance de la troponine T était de 1632 $ (dollars canadiens en 2015). Le rapport coût-efficacité était plus bas pour les sous-groupes de patients à risque élevé de lésion myocardique après CNC, comme les patients de 65 ans et plus ou ceux ayant des antécédents d'athérosclérose ou de diabète (1309 $), que pour leurs pairs. CONCLUSION: Les coûts associés à un programme de surveillance de la troponine T pour détecter les lésions myocardiques après CNC étaient modérés. Le coût marginal estimé par gain de santé indique que la mise en œuvre de ce type de programme pourrait être une option intéressante, surtout pour les patients à risque élevé de lésion myocardique après CNC.

Efficacy and safety of tiotropium and olodaterol in COPD: a systematic review and meta-analysis.

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. CLINICAL TRIAL REGISTRATION: PROSPERO register of systematic reviews ( CRD42016040162 ).

Evidence mapping based on systematic reviews of therapeutic interventions for gastrointestinal stromal tumors (GIST).

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.

Elevation of the head during intensive care management in people with severe traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) is a major public health problem and a fundamental cause of morbidity and mortality worldwide. The burden of TBI disproportionately affects low- and middle-income countries. Intracranial hypertension is the most frequent cause of death and disability in brain-injured people. Special interventions in the intensive care unit are required to minimise factors contributing to secondary brain injury after trauma. Therapeutic positioning of the head (different degrees of head-of-bed elevation (HBE)) has been proposed as a low cost and simple way of preventing secondary brain injury in these people. The aim of this review is to evaluate the evidence related to the clinical effects of different backrest positions of the head on important clinical outcomes or, if unavailable, relevant surrogate outcomes. OBJECTIVES: To assess the clinical and physiological effects of HBE during intensive care management in people with severe TBI. SEARCH METHODS: We searched the following electronic databases from their inception up to March 2017: Cochrane Injuries' Specialised Register, CENTRAL, MEDLINE, Embase, three other databases and two clinical trials registers. The Cochrane Injuries' Information Specialist ran the searches. SELECTION CRITERIA: We selected all randomised controlled trials (RCTs) involving people with TBI who underwent different HBE or backrest positions. Studies may have had a parallel or cross-over design. We included adults and children over two years of age with severe TBI (Glasgow Coma Scale (GCS) less than 9). We excluded studies performed in children of less than two years of age because of their unfused skulls. We included any therapeutic HBE including supine (flat) or different degrees of head elevation with or without knee gatch or reverse Trendelenburg applied during the acute management of the TBI. DATA COLLECTION AND ANALYSIS: Two review authors independently checked all titles and abstracts, excluding references that clearly didn't meet all selection criteria, and extracted data from selected studies on to a data extraction form specifically designed for this review. There were no cases of multiple reporting. Each review author independently evaluated risk of bias through assessing sequence generation, allocation concealment, blinding, incomplete outcome data, selective outcome reporting, and other sources of bias. MAIN RESULTS: We included three small studies with a cross-over design, involving a total of 20 participants (11 adults and 9 children), in this review. Our primary outcome was mortality, and there was one death by the time of follow-up 28 days after hospital admission. The trials did not measure the clinical secondary outcomes of quality of life, GCS, and disability. The included studies provided information only for the secondary outcomes intracranial pressure (ICP), cerebral perfusion pressure (CPP), and adverse effects.We were unable to pool the results as the data were either presented in different formats or no numerical data were provided. We included narrative interpretations of the available data.The overall risk of bias of the studies was unclear due to poor reporting of the methods. There was marked inconsistency across studies for the outcome of ICP and small sample sizes or wide confidence intervals for all outcomes. We therefore rated the quality of the evidence as very low for all outcomes and have not included the results of individual studies here. We do not have enough evidence to draw conclusions about the effect of HBE during intensive care management of people with TBI. AUTHORS' CONCLUSIONS: The lack of consistency among studies, scarcity of data and the absence of evidence to show a correlation between physiological measurements such as ICP, CCP and clinical outcomes, mean that we are uncertain about the effects of HBE during intensive care management in people with severe TBI.Well-designed and larger trials that measure long-term clinical outcomes are needed to understand how and when different backrest positions can affect the management of severe TBI.

Long-term follow-up of a randomized controlled trial on additional core stability exercises training for improving dynamic sitting balance and trunk control in stroke patients.

OBJECTIVE: Analyse the effect of core stability exercises in addition to conventional physiotherapy training three months after the intervention ended. DESIGN: A randomized controlled trial. SETTING: Outpatient services. SUBJECTS: Seventy-nine stroke survivors. INTERVENTIONS: In the intervention period, both groups underwent conventional physiotherapy performed five days/week for five weeks, and in addition the experimental group performed core stability exercises for 15 minutes/day. Afterwards, during a three-month follow-up period, both groups underwent usual care that could eventually include conventional physiotherapy or physical exercise but not in a controlled condition. MAIN MEASURES: Primary outcome was trunk control and dynamic sitting balance assessed by the Spanish-Version of Trunk Impairment Scale 2.0 and Function in Sitting Test. Secondary outcomes were standing balance and gait evaluated by the Berg Balance Scale, Tinetti Test, Brunel Balance Assessment, Spanish-Version of Postural Assessment Scale for Stroke and activities of daily living using the Barthel Index. RESULTS: A total of 68 subjects out of 79 completed the three-month follow-up period. The mean difference (SD) between groups was 0.78 (1.51) points ( p = 0.003) for total score on the Spanish-Version of Trunk Impairment Scale 2.0, 2.52 (6.46) points ( p = 0.009) for Function in Sitting Test, dynamic standing balance was 3.30 (9.21) points ( p= 0.009) on the Berg Balance Scale, gait was 0.82 (1.88) points ( p = 0.002) by Brunel Balance Assessment (stepping), and 1.11 (2.94) points ( p = 0.044) by Tinetti Test (gait), all in favour of core stability exercises. CONCLUSIONS: Core stability exercises plus conventional physiotherapy have a positive long-term effect on improving dynamic sitting and standing balance and gait in post-stroke patients.

Active body surface warming systems for preventing complications caused by inadvertent perioperative hypothermia in adults.

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; I² = 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; I² = 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; I² = 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 explained by the fact that many studies applied concomitant procedures that are routinely in place as co-interventions to prevent hypothermia, whether passive or active warming systems based in other physiological mechanisms (e.g. irrigation fluid or gas warming), as well as a stricter control of temperature in the context of the study compared with usual practice. These may have had a beneficial effect on the participants in the control group, leading to an underestimation of the net benefit of ABSW.

Selective serotonin reuptake inhibitors for fibromyalgia syndrome.

BACKGROUND: Fibromyalgia is a clinically well-defined chronic condition with a biopsychosocial aetiology. Fibromyalgia is characterized by chronic widespread musculoskeletal pain, sleep problems, cognitive dysfunction, and fatigue. Patients often report high disability levels and poor quality of life. Since there is no specific treatment that alters the pathogenesis of fibromyalgia, drug therapy focuses on pain reduction and improvement of other aversive symptoms. OBJECTIVES: The objective was to assess the benefits and harms of selective serotonin reuptake inhibitors (SSRIs) in the treatment of fibromyalgia. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 5), MEDLINE (1966 to June 2014), EMBASE (1946 to June 2014), and the reference lists of reviewed articles. SELECTION CRITERIA: We selected all randomized, double-blind trials of SSRIs used for the treatment of fibromyalgia symptoms in adult participants. We considered the following SSRIs in this review: citalopram, fluoxetine, escitalopram, fluvoxamine, paroxetine, and sertraline. DATA COLLECTION AND ANALYSIS: Three authors extracted the data of all included studies and assessed the risks of bias of the studies. We resolved discrepancies by discussion. MAIN RESULTS: The quality of evidence was very low for each outcome. We downgraded the quality of evidence to very low due to concerns about risk of bias and studies with few participants. We included seven placebo-controlled studies, two with citalopram, three with fluoxetine and two with paroxetine, with a median study duration of eight weeks (4 to 16 weeks) and 383 participants, who were pooled together.All studies had one or more sources of potential major bias. There was a small (10%) difference in patients who reported a 30% pain reduction between SSRIs (56/172 (32.6%)) and placebo (39/171 (22.8%)) risk difference (RD) 0.10, 95% confidence interval (CI) 0.01 to 0.20; number needed to treat for an additional beneficial outcome (NNTB) 10, 95% CI 5 to 100; and in global improvement (proportion of patients who reported to be much or very much improved: 50/168 (29.8%) of patients with SSRIs and 26/162 (16.0%) of patients with placebo) RD 0.14, 95% CI 0.06 to 0.23; NNTB 7, 95% CI 4 to 17.SSRIs did not statistically, or clinically, significantly reduce fatigue: standard mean difference (SMD) -0.26, 95% CI -0.55 to 0.03; 7.0% absolute improvement on a 0 to 10 scale, 95% CI 14.6% relative improvement to 0.8% relative deterioration; nor sleep problems: SMD 0.03, 95 % CI -0.26 to 0.31; 0.8 % absolute deterioration on a 0 to 100 scale, 95% CI 8.3% relative deterioration to 6.9% relative improvement.SSRIs were superior to placebo in the reduction of depression: SMD -0.39, 95% CI -0.65 to -0.14; 7.6% absolute improvement on a 0 to 10 scale, 95% CI 2.7% to 13.8% relative improvement; NNTB 13, 95% CI 7 to 37. The dropout rate due to adverse events was not higher with SSRI use than with placebo use (23/146 (15.8%) of patients with SSRIs and 14/138 (10.1%) of patients with placebo) RD 0.04, 95% CI -0.06 to 0.14. There was no statistically or clinically significant difference in serious adverse events with SSRI use and placebo use (3/84 (3.6%) in patients with SSRIs and 4/84 (4.8%) and patients with placebo) RD -0.01, 95% CI -0.07 to 0.05. AUTHORS' CONCLUSIONS: There is no unbiased evidence that SSRIs are superior to placebo in treating the key symptoms of fibromyalgia, namely pain, fatigue and sleep problems. SSRIs might be considered for treating depression in people with fibromyalgia. The black box warning for increased suicidal tendency in young adults aged 18 to 24, with major depressive disorder, who have taken SSRIs, should be considered when appropriate.

Early versus delayed erythropoietin for the anaemia of end-stage kidney disease.

BACKGROUND: Anaemia is a common complication in people with chronic kidney disease (CKD) and mainly develops as a consequence of relative erythropoietin (EPO) deficiency. Anaemia develops early in the course of disease and peaks among people with end-stage kidney disease (ESKD). Many types of EPO - also called erythropoiesis-stimulating agents (ESAs) - are used to treat anaemia in people with ESKD.ESAs have changed treatment of severe anaemia among people with CKD by relieving symptoms and avoiding complications associated with blood transfusion. However, no benefits have been found in relation to mortality rates and non-cardiac fatal events, except quality of life. Moreover, a relationship between ESA use and increased cardiovascular morbidity and mortality in patients with CKD has been reported in studies with fully correcting anaemia comparing with partial anaemia correction. Until 2012, guidelines recommended commencing ESA treatment when haemoglobin was less than 11 g/dL; the current recommendation is EPO commencement when haemoglobin is between 9 and 10 g/dL. However, advantages in commencing therapy when haemoglobin levels are greater than 10 g/dL but less than 11 g/dL remain unknown, especially among older people whose life expectancy is limited, but in whom EPO therapy may improve quality of life. OBJECTIVES: To assess the clinical benefits and harms of early versus delayed EPO for anaemia in patients with ESKD undergoing haemodialysis or peritoneal dialysis SEARCH METHODS: We searched the Cochrane Kidney and Transplant Specialised Register to 8 July 2015 through contact with the Trials' Search Co-ordinator using search terms relevant to this review. SELECTION CRITERIA: We planned to include randomised controlled trials (RCTs) and quasi-RCTs evaluating at the clinical benefits and harms of early versus delayed EPO for anaemia in patients with ESKD undergoing haemodialysis or peritoneal dialysis. Studies comparing EPO with another EPO, placebo or no treatment were eligible for inclusion. DATA COLLECTION AND ANALYSIS: It was planned that two authors would independently extract data from included studies and assess risk of bias using the Cochrane risk of bias tool. For dichotomous outcomes (all-cause mortality, cardiovascular mortality, overall myocardial infarction, overall stroke, vascular access thrombosis, adverse effects of treatment, transfusion), we planned to use the risk ratio (RR) with 95% confidence intervals (CI). We planned to calculate the mean difference (MD) and CI 95% for continuous data (haemoglobin level) and the standardised mean difference (SMD) with CI 95% for quality of life if different scales had been used. MAIN RESULTS: Literature searches yielded 1910 records, of these 1534 were screened after duplicates removed, of which 1376 were excluded following title and abstract assessment. We assessed 158 full text records and identified 18 studies (66 records) that were potentially eligible for inclusion. However, none matched our inclusion criteria and were excluded. AUTHORS' CONCLUSIONS: We found no evidence to assess the benefits and harms of early versus delayed EPO for the anaemia of ESKD.

A randomized controlled trial of fentanyl in the pre-emptive treatment of pain associated with turning in patients under mechanical ventilation: research protocol.

AIM: To compare the effectiveness and safety of fentanyl with placebo as pre-emptive treatment for pain associated with turning in patients in intensive care units. BACKGROUND: Turning is frequently a painful procedure in this setting. Pre-emptive administration of supplementary analgesia may help decrease this pain. However, medical literature on pre-emptive analgesia in these patients is scarce. DESIGN: A randomized, double-blind, controlled clinical trial. METHODS: This study will assess the benefits and risks of pre-emptive analgesia with fentanyl compared with placebo on turning-associated pain. Eighty patients will be recruited from among those older than 18 years and needing mechanical ventilation for at least 24 hours. Pain intensity will be assessed using the Behavioral Pain Scale. Primary outcome will be pain intensity between the baseline and 30 minutes after turning, measured by the area under the curve of the pain scale scores. Secondary outcomes will be the usefulness of physiological parameters and the Bispectral Index to measure pain and the safety of pre-emptive fentanyl in turning. The study protocol was approved in February 2011. DISCUSSION: If pre-emptive fentanyl is more effective than placebo and reasonably safe, the results of the current study may change nursing attitude in managing turning in critically ill patients. As a consequence, pain may be decreased during this nursing procedure.

Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial.

BACKGROUND: For women with oestrogen receptor (ER)-positive early breast cancer, treatment with tamoxifen for 5 years substantially reduces the breast cancer mortality rate throughout the first 15 years after diagnosis. We aimed to assess the further effects of continuing tamoxifen to 10 years instead of stopping at 5 years. METHODS: In the worldwide Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) trial, 12,894 women with early breast cancer who had completed 5 years of treatment with tamoxifen were randomly allocated to continue tamoxifen to 10 years or stop at 5 years (open control). Allocation (1:1) was by central computer, using minimisation. After entry (between 1996 and 2005), yearly follow-up forms recorded any recurrence, second cancer, hospital admission, or death. We report effects on breast cancer outcomes among the 6846 women with ER-positive disease, and side-effects among all women (with positive, negative, or unknown ER status). Long-term follow-up still continues. This study is registered, number ISRCTN19652633. FINDINGS: Among women with ER-positive disease, allocation to continue tamoxifen reduced the risk of breast cancer recurrence (617 recurrences in 3428 women allocated to continue vs 711 in 3418 controls, p=0·002), reduced breast cancer mortality (331 deaths vs 397 deaths, p=0·01), and reduced overall mortality (639 deaths vs 722 deaths, p=0·01). The reductions in adverse breast cancer outcomes appeared to be less extreme before than after year 10 (recurrence rate ratio [RR] 0·90 [95% CI 0·79­1·02] during years 5­9 and 0·75 [0·62­0·90] in later years; breast cancer mortality RR 0·97 [0·79­1·18] during years 5­9 and 0·71 [0·58­0·88] in later years). The cumulative risk of recurrence during years 5­14 was 21·4% for women allocated to continue versus 25·1% for controls; breast cancer mortality during years 5­14 was 12·2% for women allocated to continue versus 15·0% for controls (absolute mortality reduction 2·8%). Treatment allocation seemed to have no effect on breast cancer outcome among 1248 women with ER-negative disease, and an intermediate effect among 4800 women with unknown ER status. Among all 12,894 women, mortality without recurrence from causes other than breast cancer was little affected (691 deaths without recurrence in 6454 women allocated to continue versus 679 deaths in 6440 controls; RR 0·99 [0·89­1·10]; p=0·84). For the incidence (hospitalisation or death) rates of specific diseases, RRs were as follows: pulmonary embolus 1·87 (95% CI 1·13­3·07, p=0·01 [including 0·2% mortality in both treatment groups]), stroke 1·06 (0·83­1·36), ischaemic heart disease 0·76 (0·60­0·95, p=0·02), and endometrial cancer 1·74 (1·30­2·34, p=0·0002). The cumulative risk of endometrial cancer during years 5­14 was 3·1% (mortality 0·4%) for women allocated to continue versus 1·6% (mortality 0·2%) for controls (absolute mortality increase 0·2%). INTERPRETATION: For women with ER-positive disease, continuing tamoxifen to 10 years rather than stopping at 5 years produces a further reduction in recurrence and mortality, particularly after year 10. These results, taken together with results from previous trials of 5 years of tamoxifen treatment versus none, suggest that 10 years of tamoxifen treatment can approximately halve breast cancer mortality during the second decade after diagnosis. FUNDING: Cancer Research UK, UK Medical Research Council, AstraZeneca UK, US Army, EU-Biomed.

Rationale and design of the steroids in cardiac surgery trial.

BACKGROUND: Steroids may improve outcomes in high-risk patients undergoing cardiac surgery with the use of cardiopulmonary bypass (CBP). There is a need\ for a large randomized controlled trial to clarify the effect of steroids in such patients. METHODS: We plan to randomize 7,500 patients with elevated European System for Cardiac Operative Risk Evaluation who are undergoing cardiac surgery with the use of CBP to methylprednisolone or placebo. The first coprimary outcome is 30-day all-cause mortality, and the most second coprimary outcome is a composite of death, MI, stroke, renal failure, or respiratory failure within 30 days. Other outcomes include a composite of MI or mortality at 30 days, new onset atrial fibrillation, bleeding and transfusion requirements, length of intensive care unit stay and hospital stay, infection, stroke, wound complications, gastrointestinal complications, delirium, postoperative insulin use and peak blood glucose, and all-cause mortality at 6 months. RESULTS: As of October 22, 2013, 7,034 patients have been recruited into SIRS in 82 centers from 18 countries. Patient's mean age is 67.3 years, and 60.4% are male. The average European System for Cardiac Operative Risk Evaluation is 7.0 with 22.1% having an isolated coronary artery bypass graft procedure, and 66.1% having a valve procedure. CONCLUSIONS: SIRS will lead to a better understanding of the safety and efficacy of prophylactic steroids for cardiac surgery requiring CBP.

Vasodilators for women undergoing fertility treatment.

BACKGROUND: Since 1978, when Patrick Steptoe and Robert Edwards achieved the birth of the first test tube baby, assisted reproductive techniques have been refined and improved. However, the rate of successful pregnancies brought to term has barely increased. Therefore closer evaluation of the interventions is needed along with working towards improving uterus receptivity. Vasodilators have been proposed to increase endometrial receptivity, thicken the endometrium and favour uterine relaxation, all of which could improve uterine receptivity and enhance the chances for successful assisted pregnancies. OBJECTIVES: To evaluate the effectiveness and safety of vasodilators in women undergoing fertility treatment. SEARCH METHODS: We searched the following electronic databases, trial registers and websites: the Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, MEDLINE, the Menstrual Disorders and Subfertility Group (MDSG) Specialised Register of controlled trials, PsycINFO, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), The Cochrane Library, Web of Knowledge, the Open System for Information on Grey Literature in Europe (OpenSIGLE), the Latin American and Caribbean Health Science Information Database (LILACS) and ClinicalTrials.gov. The search was conducted in February 2014. No language restrictions were applied. SELECTION CRITERIA: Randomised controlled trials (RCTs) of vasodilators alone or in combination with other treatments compared with placebo or with other agents in women undergoing fertility treatment. DATA COLLECTION AND ANALYSIS: Two review authors independently selected the studies, assessed the risk of bias and extracted data. Risk ratios (RRs) were calculated using the numbers of events in the control and intervention groups of each study. Study data were combined using a random-effects model, and evidence quality was assessed using Grades of Recommendation, Assessment, Development and Evaluation Working Group (GRADE) methods. MAIN RESULTS: Ten studies with a total of 797 women were included in this review. Most of the studies were judged as having an unclear risk of bias. Three studies reported live births, two reported vasodilator-related side effects, 10 reported clinical pregnancies (diagnosed by differing criteria) and four reported other side effects (multiple gestation, miscarriage, ectopic pregnancy).Overall, no evidence suggested that treatment with vasodilators increased live birth rates compared with placebo or no treatment (RR 1.18, 95% confidence interval (CI) 0.82 to 1.69, P value 0.37, three RCTs, 350 women, I(2) = 0%, moderate-quality evidence). This indicates that among women undergoing fertility treatment who have a 24% chance of live birth without the use of vasodilators, between 19% and 40% will achieve live birth with the use of vasodilators.No evidence was found of a difference between vasodilators and placebo or no treatment in the incidence of treatment side effects (RR 1.63, 95% CI 0.33 to 7.93, P value 0.55, two RCTs, 258 women, I(2) = 32%, low-quality evidence). Nor did any evidence show a difference between them in terms of multiple gestation, spontaneous abortion/miscarriage or ectopic pregnancy rates. However few relevant data were available.Overall, treatment with vasodilators was associated with an increased clinical pregnancy rate compared with placebo or no treatment (RR 1.38, 95% CI 1.00 to 1.92, P value 0.05, eight RCTs, 717 women, I(2) = 0%, low-quality evidence). However, confidence intervals do not rule out no effect of the intervention, and when studies of vasodilators combined with another medication (vitamin E or oestrogen) were excluded, the effects of treatment with vasodilators alone on clinical pregnancy rates were more uncertain.The evidence was of low or moderate quality, and the main limitations were imprecision and lack of clarity about study methods. Risk of publication bias could not be assessed because of the low number of identified studies. AUTHORS' CONCLUSIONS: Evidence was insufficient to show that vasodilators increased the live birth rate in women undergoing fertility treatment. However, low-quality evidence suggests that vasodilators may increase clinical pregnancy rates in comparison with placebo or no treatment. Evidence was insufficient to show whether any particular vasodilator, administered alone or in combination with other active medications, was superior, and evidence was insufficient to allow the review authors to reach any conclusions regarding adverse effects. Adequately powered studies are needed so that each treatment can be evaluated more accurately.

Frequency of anticancer drug use at the end of life: a scoping review.

PURPOSE: Anticancer drug use at the end of life places potential extra burdens on patients and the healthcare system. Previous articles show variability in methods and outcomes; thus, their results are not directly comparable. This scoping review describes the methods and extent of anticancer drug use at end of life. METHODS: Systematic searches in Medline and Embase were conducted to identify articles reporting anticancer drug use at the end of life. RESULTS: We selected 341 eligible publications, identifying key study features including timing of research, disease status, treatment schedule, treatment type, and treatment characteristics. Among the subset of 69 articles of all cancer types published within the last 5 years, we examined the frequency of anticancer drug use across various end of life periods. CONCLUSION: This comprehensive description of publications on anticancer drug use at end of life underscores the importance of methodological factors when designing studies and comparing outcomes.

Mortality and major postoperative complications within 1 year after vascular surgery: a prospective cohort study.

INTRODUCTION: Patients undergoing vascular procedures are prone to developing postoperative complications affecting their short­term mortality. Prospective reports describing the incidence of long­term complications after vascular surgery are lacking. OBJECTIVES: We aimed to describe the incidence of complications 1 year after vascular surgery and to evaluate an association between myocardial injury after noncardiac surgery (MINS) and 1­year mortality. PATIENTS AND METHODS: This is a substudy of a large prospective cohort study Vascular Events in Noncardiac Surgery Patients Cohort Evaluation (VISION). Recruitment took place in 28 centers across 14 countries from August 2007 to November 2013. We enrolled patients aged 45 years or older undergoing vascular surgery, receiving general or regional anesthesia, and hospitalized for at least 1 night postoperatively. Plasma cardiac troponin T concentration was measured before the surgery and on the first, second, and third postoperative day. The patients or their relatives were contacted 1 year after the procedure to assess the incidence of major postoperative complications. RESULTS: We enrolled 2641 patients who underwent vascular surgery, 2534 (95.9%) of whom completed 1­year follow­up. Their mean (SD) age was 68.2 (9.8) years, and the cohort was predominantly male (77.5%). The most frequent 1­year complications were myocardial infarction (224/2534, 8.8%), amputation (187/2534, 7.4%), and congestive heart failure (67/2534, 2.6%). The 1­year mortality rate was 8.8% (223/2534). MINS occurred in 633 patients (24%) and was associated with an increased 1­year mortality (hazard ratio, 2.82; 95% CI, 2.14-3.72; P <0.001). CONCLUSIONS: The incidence of major postoperative complications after vascular surgery is high. The occurrence of MINS is associated with a nearly 3­fold increase in 1­year mortality.