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Although liver transplantation is a widely accepted treatment for hepatocellular carcinoma (HCC), much controversy remains and there is no generally accepted set of guidelines. An international consensus conference was held on Dec 2–4, 2010, in Zurich, Switzerland, with the aim of reviewing current practice regarding liver transplantation in patients with HCC and to develop internationally accepted statements and guidelines. The format of the conference was based on the Danish model. 19 working groups of experts prepared evidence-based reviews according to the Oxford classification, and drafted recommendations answering 19 specific questions. An independent jury of nine members was appointed to review these submissions and make final recommendations, after debates with the experts and audience at the conference. This report presents the final 37 statements and recommendations, covering assessment of candidates for liver transplantation, criteria for listing in cirrhotic and non-cirrhotic patients, role of tumour downstaging, management of patients on the waiting list, role of living donation, and post-transplant management.

Diagnosis of pulmonary embolism requires clinical probability assessment. Implicit assessment is accurate but is not standardized, and current prediction rules have shortcomings. To construct a simple score based entirely on clinical variables and independent from physicians' implicit judgment. Derivation and external validation of the score in 2 independent management studies on pulmonary embolism diagnosis. Emergency departments of 3 university hospitals in Europe. Consecutive patients admitted for clinically suspected pulmonary embolism. Collected data included demographic characteristics, risk factors, and clinical signs and symptoms suggestive of venous thromboembolism. The variables statistically significantly associated with pulmonary embolism in univariate analysis were included in a multivariate logistic regression model. Points were assigned according to the regression coefficients. The score was then externally validated in an independent cohort. The score comprised 8 variables (points): age older than 65 years (1 point), previous deep venous thrombosis or pulmonary embolism (3 points), surgery or fracture within 1 month (2 points), active malignant condition (2 points), unilateral lower limb pain (3 points), hemoptysis (2 points), heart rate of 75 to 94 beats/min (3 points) or 95 beats/min or more (5 points), and pain on lower-limb deep venous palpation and unilateral edema (4 points). In the validation set, the prevalence of pulmonary embolism was 8% in the low-probability category (0 to 3 points), 28% in the intermediate-probability category (4 to 10 points), and 74% in the high-probability category (> or =11 points). Interobserver agreement for the score items was not studied. The proposed score is entirely standardized and is based on clinical variables. It has sustained internal and external validation and should now be tested for clinical usefulness in an outcome study.

Although practice guidelines recommend outpatient care for selected, haemodynamically stable patients with pulmonary embolism, most treatment is presently inpatient based. We aimed to assess non-inferiority of outpatient care compared with inpatient care. We undertook an open-label, randomised non-inferiority trial at 19 emergency departments in Switzerland, France, Belgium, and the USA. We randomly assigned patients with acute, symptomatic pulmonary embolism and a low risk of death (pulmonary embolism severity index risk classes I or II) with a computer-generated randomisation sequence (blocks of 2–4) in a 1:1 ratio to initial outpatient (ie, discharged from hospital ≤24 h after randomisation) or inpatient treatment with subcutaneous enoxaparin (≥5 days) followed by oral anticoagulation (≥90 days). The primary outcome was symptomatic, recurrent venous thromboembolism within 90 days; safety outcomes included major bleeding within 14 or 90 days and mortality within 90 days. We used a non-inferiority margin of 4% for a difference between inpatient and outpatient groups. We included all enrolled patients in the primary analysis, excluding those lost to follow-up. This trial is registered with ClinicalTrials.gov, number NCT00425542. Between February, 2007, and June, 2010, we enrolled 344 eligible patients. In the primary analysis, one (0·6%) of 171 outpatients developed recurrent venous thromboembolism within 90 days compared with none of 168 inpatients (95% upper confidence limit [UCL] 2·7%; p=0·011). Only one (0·6%) patient in each treatment group died within 90 days (95% UCL 2·1%; p=0·005), and two (1·2%) of 171 outpatients and no inpatients had major bleeding within 14 days (95% UCL 3·6%; p=0·031). By 90 days, three (1·8%) outpatients but no inpatients had developed major bleeding (95% UCL 4·5%; p=0·086). Mean length of stay was 0·5 days (SD 1·0) for outpatients and 3·9 days (SD 3·1) for inpatients. In selected low-risk patients with pulmonary embolism, outpatient care can safely and effectively be used in place of inpatient care. Swiss National Science Foundation, Programme Hospitalier de Recherche Clinique, and the US National Heart, Lung, and Blood Institute. Sanofi-Aventis provided free drug supply in the participating European centres.

Acute exacerbations are the leading causes of hospitalization and mortality in patients with COPD. Prognostic tools for patients with chronic COPD exist, but there are scarce data regarding acute exacerbations. We aimed to identify the prognostic factors of death and readmission after exacerbation of COPD. This was a retrospective study conducted in the Department of Internal Medicine of Geneva University Hospitals. All patients admitted to the hospital with a diagnosis of exacerbation of COPD between 2008 and 2011 were included. The studied variables included comorbidities, Global Initiative for Chronic Obstructive Lung Disease (GOLD) severity classification, and biological and clinical parameters. The main outcome was death or readmission during a 5-year follow-up. The secondary outcome was death. Survival analysis was performed (log-rank and Cox). We identified a total of 359 patients (195 men and 164 women, average age 72 years). During 5-year follow-up, 242 patients died or were hospitalized for the exacerbation of COPD. In multivariate analysis, age (hazard ratio [HR] 1.03, 95% CI 1.02-1.05; <0.0001), severity of airflow obstruction (forced expiratory volume in 1 s <30%; HR 4.65, 95% CI 1.42-15.1; =0.01), diabetes (HR 1.47, 95% CI 1.003-2.16; =0.048), cancer (HR 2.79, 95% CI 1.68-4.64; <0.0001), creatinine (HR 1.003, 95% CI 1.0004-1.006; =0.02), and respiratory rate (HR 1.03, 95% CI 1.003-1.05; =0.028) on admission were significantly associated with the primary outcome. Age, cancer, and procalcitonin were significantly associated with the secondary outcome. COPD remains of ominous prognosis, especially after exacerbation requiring hospitalization. Baseline pulmonary function remains the strongest predictor of mortality and new admission. Demographic factors, such as age and comorbidities and notably diabetes and cancer, are closely associated with the outcome of the patient. Respiratory rate at admission appears to be the most prognostic clinical parameter. A prospective validation is, however, still required to enable the identification of patients at higher risk of death or readmission.

Abstract Rationale An objective and simple prognostic model for patients with pulmonary embolism could be helpful in guiding initial intensity of treatment. Objectives To develop a clinical prediction rule that accurately classifies patients with pulmonary embolism into categories of increasing risk of mortality and other adverse medical outcomes. Methods We randomly allocated 15,531 inpatient discharges with pulmonary embolism from 186 Pennsylvania hospitals to derivation (67%) and internal validation (33%) samples. We derived our prediction rule using logistic regression with 30-day mortality as the primary outcome, and patient demographic and clinical data routinely available at presentation as potential predictor variables. We externally validated the rule in 221 inpatients with pulmonary embolism from Switzerland and France. Measurements We compared mortality and nonfatal adverse medical outcomes across the derivation and two validation samples. Main Results The prediction rule is based on 11 simple patient characteristics that were independently associated with mortality and stratifies patients with pulmonary embolism into five severity classes, with 30-day mortality rates of 0–1.6% in class I, 1.7–3.5% in class II, 3.2–7.1% in class III, 4.0–11.4% in class IV, and 10.0–24.5% in class V across the derivation and validation samples. Inpatient death and nonfatal complications were ⩽ 1.1% among patients in class I and ⩽ 1.9% among patients in class II. Conclusions Our rule accurately classifies patients with pulmonary embolism into classes of increasing risk of mortality and other adverse medical outcomes. Further validation of the rule is important before its implementation as a decision aid to guide the initial management of patients with pulmonary embolism.

Whether to continue oral anticoagulant therapy beyond 6 months after an “unprovoked” venous thromboembolism is controversial. We sought to determine clinical predictors to identify patients who are at low risk of recurrent venous thromboembolism who could safely discontinue oral anticoagulants. In a multicentre prospective cohort study, 646 participants with a first, unprovoked major venous thromboembolism were enrolled over a 4-year period. Of these, 600 participants completed a mean 18-month follow-up in September 2006. We collected data for 69 potential predictors of recurrent venous thromboembolism while patients were taking oral anticoagulation therapy (5–7 months after initiation). During follow-up after discontinuing oral anticoagulation therapy, all episodes of suspected recurrent venous thromboembolism were independently adjudicated. We performed a multivariable analysis of predictor variables (p<0.10) with high interobserver reliability to derive a clinical decision rule. We identified 91 confirmed episodes of recurrent venous thromboembolism during follow-up after discontinuing oral anticoagulation therapy (annual risk 9.3%, 95% CI 7.7%–11.3%). Men had a 13.7% (95% CI 10.8%– 17.0%) annual risk. There was no combination of clinical predictors that satisfied our criteria for identifying a low-risk subgroup of men. Fifty-two percent of women had 0 or 1 of the following characteristics: hyperpigmentation, edema or redness of either leg; d-dimer ≥ 250 μg/L while taking warfarin; body mass index ≥ 30 kg/m2; or age ≥ 65 years. These women had an annual risk of 1.6% (95% CI 0.3%–4.6%). Women who had 2 or more of these findings had an annual risk of 14.1% (95% CI 10.9%–17.3%). Women with 0 or 1 risk factor may safely discontinue oral anticoagulant therapy after 6 months of therapy following a first unprovoked venous thromboembolism. This criterion does not apply to men. (http://Clinicaltrials.govtrialregisternumberNCT00261014) Une version française de ce résumé est disponible à l'adresse www.cmaj.ca/cgi/content/full/179/5/417/DC1 CMAJ 2008;179(5):417-26

Identifying patients at high risk of hospital preventable readmission is an essential step towards selecting those who might benefit from specific transitional interventions. Derive and validate a predictive risk score for potentially avoidable readmission (PAR) based on analysis of readmissions, with a focus on medication. Retrospective analysis of all hospital admissions to internal medicine wards between 2011 and 2014. Comparison between patients readmitted within 30 days and non-readmitted patients, as identified using a specially designed algorithm. Univariate and multivariate regression analyses of demographic data, clinical diagnoses, laboratory results, and the medication data of patients admitted during the first period (2011-2013), to identify factors associated with PAR. Using these, derive a predictive score with a regression coefficient-based scoring method. Subsequently, validate this score with a second cohort of patients admitted in 2013-2014. Variables were identified at hospital discharge. The derivation cohort included 7,317 hospital stays. Multivariate logistic regressions found significant associations with PAR for: [adjusted OR (95% CI)] hospital length of stay > 4 days [1.3 (1.1-1.7)], admission in previous 6 months [2.3 (1.9-2.8)], heart failure [1.3 (1.0-1.7)], chronic ischemic heart disease [1.7 (1.2-2.3)], diabetes with organ damage [2.2 (1.3-3.8)], cancer [1.4 (1.0-1.9)], metastatic carcinoma [1.9 (1.3-3.0)], anemia [1.2 (1.0-1.5)], hypertension [1.3 (1.1-1.7)], arrhythmia [1.3 (1.0-1.6)], hyperkalemia [1.4 (1.0-1.7)], opioid drug prescription [1.3 (1.1-1.6)], and acute myocardial infarction [0.6 (0.4-0.9)]. The PAR-Risk Score, derived from these results, demonstrated fair discriminatory and calibration power (C-statistic = 0.699; Brier Score = 0.069). The results for the validation cohort's operating characteristics were similar (C-statistic = 0.687; Brier Score = 0.064). This study identified routinely-available factors that were significantly associated with PAR. A predictive score was derived and internally validated.

Percutaneous vertebroplasty (VP) and balloon kyphoplasty (BKP) for treating painful osteoporotic vertebral fractures are controversial. We assessed the regional variation in the use of VP/BKP in Switzerland. We conducted a population-based small area variation analysis using patient discharge data for VP/BKP from all Swiss hospitals and Swiss census data for calendar years 2012/13. We derived hospital service areas (HSAs) by analyzing patient flows, assigning regions from which most residents were discharged to the same VP/BKP specific HSA. We calculated age-/sex-standardized mean VP/BKP-rates and measures of regional variation (extremal quotient [EQ], systematic component of variation [SCV]). We estimated the reduction in variation of VP/BKP rates using negative binomial regression, with adjustment for patient demographic and regional socioeconomic factors (socioeconomic status, urbanization, and language region). We considered the residual, unexplained variation most likely to be unwarranted. Overall, 4955 VP/BKPs were performed in Switzerland in 2012/13. The age-/sex-standardized mean VP/BKP rate was 4.6/10,000 persons and ranged from 1.0 to 10.1 across 26 HSAs. The EQ was 10.2 and the SCV 57.6, indicating a large variation across VP/BKP specific HSAs. After adjustment for demographic and socioeconomic factors, the total reduction in variance was 32.2% only, with the larger part of the variation remaining unexplained. We found a 10-fold variation in VP/BKP rates across Swiss VP/BKP specific HSAs. As only one third of the variation was explained by differences in patient demographics and regional socioeconomic factors, VP/BKP in the highest-use areas may, at least partially, represent overtreatment.

Clinicians perform searches in PubMed daily, but retrieving relevant studies is challenging due to the rapid expansion of medical knowledge. Little is known about the performance of search strategies when they are applied to answer specific clinical questions. To compare the performance of 15 PubMed search strategies in retrieving relevant clinical trials on therapeutic interventions. We used Cochrane systematic reviews to identify relevant trials for 30 clinical questions. Search terms were extracted from the abstract using a predefined procedure based on the population, interventions, comparison, outcomes (PICO) framework and combined into queries. We tested 15 search strategies that varied in their query (PIC or PICO), use of PubMed's Clinical Queries therapeutic filters (broad or narrow), search limits, and PubMed links to related articles. We assessed sensitivity (recall) and positive predictive value (precision) of each strategy on the first 2 PubMed pages (40 articles) and on the complete search output. The performance of the search strategies varied widely according to the clinical question. Unfiltered searches and those using the broad filter of Clinical Queries produced large outputs and retrieved few relevant articles within the first 2 pages, resulting in a median sensitivity of only 10%-25%. In contrast, all searches using the narrow filter performed significantly better, with a median sensitivity of about 50% (all P < .001 compared with unfiltered queries) and positive predictive values of 20%-30% (P < .001 compared with unfiltered queries). This benefit was consistent for most clinical questions. Searches based on related articles retrieved about a third of the relevant studies. The Clinical Queries narrow filter, along with well-formulated queries based on the PICO framework, provided the greatest aid in retrieving relevant clinical trials within the 2 first PubMed pages. These results can help clinicians apply effective strategies to answer their questions at the point of care.

Community-acquired pneumonia (CAP) induces lung and systemic inflammation, leading to high morbidity and mortality. We systematically reviewed the risks and benefits of adjunctive corticotherapy in the management of patients with CAP. We systematically searched Pubmed, Embase and the Cochrane Library for randomized controlled trials comparing adjunctive corticotherapy and antimicrobial therapy with antimicrobial therapy alone in patients with CAP. The primary outcome was 30-day mortality. Secondary outcomes were length of hospital stay, time to clinical stability and severe complications. 14 trials (2077 patients) were included. The reported 30-day mortality was 7.9% (80/1018) among patients treated with adjunctive corticotherapy versus 8.3% (85/1028) among patients treated with antimicrobial therapy alone (RR 0.84; 95%CI 0.55 to1.29). Adjunctive corticotherapy was associated with a reduction of severe complications (RR 0.36; 95%CI 0.23 to 0.56), a shorter length of stay (9.0 days; 95%CI 7.6 to 10.7 vs 10.6 days; 95%CI 7.4 to 15.3) and a shorter time to clinical stability (3.3 days; 95% CI 2.8 to 4.1 vs 4.3 days; 95%CI 3.6 to 5.1). The risk of hyperglycemia was higher among patients treated with adjunctive corticotherapy (RR 1.59; 95%CI 1.06 to 2.38), whereas the risk of gastro-intestinal bleeding was similar (RR 0.83; 95%CI 0.35 to 1.93). In the subgroup analysis based on CAP severity, a survival benefit was found among patients with severe CAP (RR 0.47; 95%CI 0.23 to 0.96). Adjunctive corticotherapy is associated with a reduction of length of stay, time to clinical stability, and severe complications among patients with CAP, but the effect on mortality remains uncertain.