Organ donation in Switzerland - an analysis of factors associated with consent rate

BACKGROUND AND AIM Switzerland has a low post mortem organ donation rate. Here we examine variables that are associated with the consent of the deceased's next of kin (NOK) for organ donation, which is a prerequisite for donation in Switzerland. METHODS AND ANALYSIS During one year, we registered information from NOK of all deceased patients in Swiss intensive care units, who were approached for consent to organ donation. We collected data on patient demographics, characteristics of NOK, factors related to the request process and to the clinical setting. We analyzed the association of collected predictors with consent rate using univariable logistic regression models; predictors with p-values <0.2 were selected for a multivariable logistic regression. RESULTS Of 266 NOK approached for consent, consent was given in 137 (51.5%) cases. In multivariable analysis, we found associations of consent rates with Swiss nationality (OR 3.09, 95% CI: 1.46-6.54) and German language area (OR 0.31, 95% CI: 0.14-0.73). Consent rates tended to be higher if a parent was present during the request (OR 1.76, 95% CI: 0.93-3.33) and if the request was done before brain death was formally declared (OR 1.87, 95% CI: 0.90-3.87). CONCLUSION Establishing an atmosphere of trust between the medical staff putting forward a request and the NOK, allowing sufficient time for the NOK to consider donation, and respecting personal values and cultural differences, could be of importance for increasing donation rates. Additional measures are needed to address the pronounced differences in consent rates between language regions.

Oral or transdermal opioids for osteoarthritis of the knee or hip.

BACKGROUND Osteoarthritis is the most common form of joint disease and the leading cause of pain and physical disability in older people. Opioids may be a viable treatment option if people have severe pain or if other analgesics are contraindicated. However, the evidence about their effectiveness and safety is contradictory. This is an update of a Cochrane review first published in 2009. OBJECTIVES To determine the effects on pain, function, safety, and addiction of oral or transdermal opioids compared with placebo or no intervention in people with knee or hip osteoarthritis. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and CINAHL (up to 28 July 2008, with an update performed on 15 August 2012), checked conference proceedings, reference lists, and contacted authors. SELECTION CRITERIA We included randomised or quasi-randomised controlled trials that compared oral or transdermal opioids with placebo or no treatment in people with knee or hip osteoarthritis. We excluded studies of tramadol. We applied no language restrictions. DATA COLLECTION AND ANALYSIS We extracted data in duplicate. We calculated standardised mean differences (SMDs) and 95% confidence intervals (CI) for pain and function, and risk ratios for safety outcomes. We combined trials using an inverse-variance random-effects meta-analysis. MAIN RESULTS We identified 12 additional trials and included 22 trials with 8275 participants in this update. Oral oxycodone was studied in 10 trials, transdermal buprenorphine and oral tapentadol in four, oral codeine in three, oral morphine and oral oxymorphone in two, and transdermal fentanyl and oral hydromorphone in one trial each. All trials were described as double-blind, but the risk of bias for other domains was unclear in several trials due to incomplete reporting. Opioids were more beneficial in pain reduction than control interventions (SMD -0.28, 95% CI -0.35 to -0.20), which corresponds to a difference in pain scores of 0.7 cm on a 10-cm visual analogue scale (VAS) between opioids and placebo. This corresponds to a difference in improvement of 12% (95% CI 9% to 15%) between opioids (41% mean improvement from baseline) and placebo (29% mean improvement from baseline), which translates into a number needed to treat (NNTB) to cause one additional treatment response on pain of 10 (95% CI 8 to 14). Improvement of function was larger in opioid-treated participants compared with control groups (SMD -0.26, 95% CI -0.35 to -0.17), which corresponds to a difference in function scores of 0.6 units between opioids and placebo on a standardised Western Ontario and McMaster Universities Arthritis Index (WOMAC) disability scale ranging from 0 to 10. This corresponds to a difference in improvement of 11% (95% CI 7% to 14%) between opioids (32% mean improvement from baseline) and placebo (21% mean improvement from baseline), which translates into an NNTB to cause one additional treatment response on function of 11 (95% CI 7 to 14). We did not find substantial differences in effects according to type of opioid, analgesic potency, route of administration, daily dose, methodological quality of trials, and type of funding. Trials with treatment durations of four weeks or less showed larger pain relief than trials with longer treatment duration (P value for interaction = 0.001) and there was evidence for funnel plot asymmetry (P value = 0.054 for pain and P value = 0.011 for function). Adverse events were more frequent in participants receiving opioids compared with control. The pooled risk ratio was 1.49 (95% CI 1.35 to 1.63) for any adverse event (9 trials; 22% of participants in opioid and 15% of participants in control treatment experienced side effects), 3.76 (95% CI 2.93 to 4.82) for drop-outs due to adverse events (19 trials; 6.4% of participants in opioid and 1.7% of participants in control treatment dropped out due to adverse events), and 3.35 (95% CI 0.83 to 13.56) for serious adverse events (2 trials; 1.3% of participants in opioid and 0.4% of participants in control treatment experienced serious adverse events). Withdrawal symptoms occurred more often in opioid compared with control treatment (odds ratio (OR) 2.76, 95% CI 2.02 to 3.77; 3 trials; 2.4% of participants in opioid and 0.9% of participants control treatment experienced withdrawal symptoms). AUTHORS' CONCLUSIONS The small mean benefit of non-tramadol opioids are contrasted by significant increases in the risk of adverse events. For the pain outcome in particular, observed effects were of questionable clinical relevance since the 95% CI did not include the minimal clinically important difference of 0.37 SMDs, which corresponds to 0.9 cm on a 10-cm VAS.

Tools & Techniques - Statistics: Propensity score techniques.

Propensity score (PS) techniques are useful if the number of potential confounding pretreatment variables is large and the number of analysed outcome events is rather small so that conventional multivariable adjustment is hardly feasible. Only pretreatment characteristics should be chosen to derive PS, and only when they are probably associated with outcome. A careful visual inspection of PS will help to identify areas of no or minimal overlap, which suggests residual confounding, and trimming of the data according to the distribution of PS will help to minimise residual confounding. Standardised differences in pretreatment characteristics provide a useful check of the success of the PS technique employed. As with conventional multivariable adjustment, PS techniques cannot account for confounding variables that are not or are only imperfectly measured, and no PS technique is a substitute for an adequately designed randomised trial.

Validation and reclassification of MGAP and GAP in hospital settings using data from the Trauma Audit and Research Network.

BACKGROUND Recently, two simple clinical scores were published to predict survival in trauma patients. Both scores may successfully guide major trauma triage, but neither has been independently validated in a hospital setting. METHODS This is a cohort study with 30-day mortality as the primary outcome to validate two new trauma scores-Mechanism, Glasgow Coma Scale (GCS), Age, and Pressure (MGAP) score and GCS, Age and Pressure (GAP) score-using data from the UK Trauma Audit and Research Network. First, an assessment of discrimination, using the area under the receiver operating characteristic (ROC) curve, and calibration, comparing mortality rates with those originally published, were performed. Second, we calculated sensitivity, specificity, predictive values, and likelihood ratios for prognostic score performance. Third, we propose new cutoffs for the risk categories. RESULTS A total of 79,807 adult (≥16 years) major trauma patients (2000-2010) were included; 5,474 (6.9%) died. Mean (SD) age was 51.5 (22.4) years, median GCS score was 15 (interquartile range, 15-15), and median Injury Severity Score (ISS) was 9 (interquartile range, 9-16). More than 50% of the patients had a low-risk GAP or MGAP score (1% mortality). With regard to discrimination, areas under the ROC curve were 87.2% for GAP score (95% confidence interval, 86.7-87.7) and 86.8% for MGAP score (95% confidence interval, 86.2-87.3). With regard to calibration, 2,390 (3.3%), 1,900 (28.5%), and 1,184 (72.2%) patients died in the low, medium, and high GAP risk categories, respectively. In the low- and medium-risk groups, these were almost double the previously published rates. For MGAP, 1,861 (2.8%), 1,455 (15.2%), and 2,158 (58.6%) patients died in the low-, medium-, and high-risk categories, consonant with results originally published. Reclassifying score point cutoffs improved likelihood ratios, sensitivity and specificity, as well as areas under the ROC curve. CONCLUSION We found both scores to be valid triage tools to stratify emergency department patients, according to their risk of death. MGAP calibrated better, but GAP slightly improved discrimination. The newly proposed cutoffs better differentiate risk classification and may therefore facilitate hospital resource allocation. LEVEL OF EVIDENCE Prognostic study, level II.

Effect of standardized training on the reliability of the Cochrane risk of bias assessment tool: a study protocol

BACKGROUND The Cochrane risk of bias (RoB) tool has been widely embraced by the systematic review community, but several studies have reported that its reliability is low. We aim to investigate whether training of raters, including objective and standardized instructions on how to assess risk of bias, can improve the reliability of this tool. We describe the methods that will be used in this investigation and present an intensive standardized training package for risk of bias assessment that could be used by contributors to the Cochrane Collaboration and other reviewers. METHODS/DESIGN This is a pilot study. We will first perform a systematic literature review to identify randomized clinical trials (RCTs) that will be used for risk of bias assessment. Using the identified RCTs, we will then do a randomized experiment, where raters will be allocated to two different training schemes: minimal training and intensive standardized training. We will calculate the chance-corrected weighted Kappa with 95% confidence intervals to quantify within- and between-group Kappa agreement for each of the domains of the risk of bias tool. To calculate between-group Kappa agreement, we will use risk of bias assessments from pairs of raters after resolution of disagreements. Between-group Kappa agreement will quantify the agreement between the risk of bias assessment of raters in the training groups and the risk of bias assessment of experienced raters. To compare agreement of raters under different training conditions, we will calculate differences between Kappa values with 95% confidence intervals. DISCUSSION This study will investigate whether the reliability of the risk of bias tool can be improved by training raters using standardized instructions for risk of bias assessment. One group of inexperienced raters will receive intensive training on risk of bias assessment and the other will receive minimal training. By including a control group with minimal training, we will attempt to mimic what many review authors commonly have to do, that is-conduct risk of bias assessment in RCTs without much formal training or standardized instructions. If our results indicate that an intense standardized training does improve the reliability of the RoB tool, our study is likely to help improve the quality of risk of bias assessments, which is a central component of evidence synthesis.

Biolimus-eluting stent with biodegradable polymer improves clinical outcomes in patients with acute myocardial infarction

OBJECTIVE To investigate clinical outcomes of coronary intervention using a biolimus-eluting stent (BES) compared with a sirolimus-eluting stent (SES) in patients with acute myocardial infarction (AMI) in the Limus Eluted from A Durable versus ERodable Stent (LEADERS) coating trial at the final 5-year follow-up. METHODS The LEADERS trial is a multicentre all-comer study, where patients (n=1707) were randomised to percutaneous intervention with either BES containing biodegradable polymer or SES containing durable polymer. Out of 1707 patients enrolled in this trial, 573 patients had percutaneous coronary intervention for AMI (BES=280, SES=293) and were included in the current analysis. Patient-oriented composite endpoint (POCE, including all death, all myocardial infarction (MI) and all revascularisations), major adverse cardiac events (MACE, including cardiac death, MI and clinically indicated target vessel revascularisation) and stent thrombosis were assessed at 5-year follow-up. RESULTS The baseline clinical, angiographic and procedural characteristics were well matched between BES and SES groups. In all patients with AMI, coronary intervention with a BES, compared with SES, significantly reduced POCE (28.9% vs 42.3%; relative risk (RR) 0.61, 95% CI 0.47 to 0.82, p=0.001) at 5-year follow-up. There was also a reduction in MACE rate in the BES group (18.2% vs 25.9%; RR 0.67, 95% CI 0.47 to 0.95, p=0.025); however, there was no difference in cardiac death and stent thrombosis. In patients with ST-elevation MI (STEMI), coronary intervention with BES significantly reduced POCE (24.4% vs 39.3%; RR 0.55, 95% CI 0.36 to 0.85, p=0.006), MACE (12.6% vs 25.0%; RR 0.47, 95% CI 0.26 to 0.83, p=0.008) and cardiac death (3.0% vs 11.4%; RR 0.25, 95% CI 0.08 to 0.75, p=0.007), along with a trend towards reduction in definite stent thrombosis (3.7% vs 8.6%; RR 0.41, 95% CI 0.15 to 1.18, p=0.088), compared with SES. CONCLUSIONS BES, compared with SES, significantly improved safety and efficacy outcomes in patients with AMI, especially those with STEMI, at 5-year follow-up. TRIAL REGISTRATION NUMBER NCT 00389220.

Additive effect of anemia and renal impairment on long-term outcome after percutaneous coronary intervention

INTRODUCTION Anemia and renal impairment are important co-morbidities among patients with coronary artery disease undergoing Percutaneous Coronary Intervention (PCI). Disease progression to eventual death can be understood as the combined effect of baseline characteristics and intermediate outcomes. METHODS Using data from a prospective cohort study, we investigated clinical pathways reflecting the transitions from PCI through intermediate ischemic or hemorrhagic events to all-cause mortality in a multi-state analysis as a function of anemia (hemoglobin concentration <120 g/l and <130 g/l, for women and men, respectively) and renal impairment (creatinine clearance <60 ml/min) at baseline. RESULTS Among 6029 patients undergoing PCI, anemia and renal impairment were observed isolated or in combination in 990 (16.4%), 384 (6.4%), and 309 (5.1%) patients, respectively. The most frequent transition was from PCI to death (6.7%, 95% CI 6.1-7.3), followed by ischemic events (4.8%, 95 CI 4.3-5.4) and bleeding (3.4%, 95% CI 3.0-3.9). Among patients with both anemia and renal impairment, the risk of death was increased 4-fold as compared to the reference group (HR 3.9, 95% CI 2.9-5.4) and roughly doubled as compared to patients with either anemia (HR 1.7, 95% CI 1.3-2.2) or renal impairment (HR 2.1, 95% CI 1.5-2.9) alone. Hazard ratios indicated an increased risk of bleeding in all three groups compared to patients with neither anemia nor renal impairment. CONCLUSIONS Applying a multi-state model we found evidence for a gradient of risk for the composite of bleeding, ischemic events, or death as a function of hemoglobin value and estimated glomerular filtration rate at baseline.

Active surveillance for rheumatic heart disease in endemic regions: a systematic review and meta-analysis of prevalence among children and adolescents

BACKGROUND Rheumatic heart disease accounts for up to 250 000 premature deaths every year worldwide and can be regarded as a physical manifestation of poverty and social inequality. We aimed to estimate the prevalence of rheumatic heart disease in endemic countries as assessed by different screening modalities and as a function of age. METHODS We searched Medline, Embase, the Latin American and Caribbean System on Health Sciences Information, African Journals Online, and the Cochrane Database of Systematic Reviews for population-based studies published between Jan 1, 1993, and June 30, 2014, that reported on prevalence of rheumatic heart disease among children and adolescents (≥5 years to <18 years). We assessed prevalence of clinically silent and clinically manifest rheumatic heart disease in random effects meta-analyses according to screening modality and geographical region. We assessed the association between social inequality and rheumatic heart disease with the Gini coefficient. We used Poisson regression to analyse the effect of age on prevalence of rheumatic heart disease and estimated the incidence of rheumatic heart disease from prevalence data. FINDINGS We included 37 populations in the systematic review and meta-analysis. The pooled prevalence of rheumatic heart disease detected by cardiac auscultation was 2·9 per 1000 people (95% CI 1·7-5·0) and by echocardiography it was 12·9 per 1000 people (8·9-18·6), with substantial heterogeneity between individual reports for both screening modalities (I(2)=99·0% and 94·9%, respectively). We noted an association between social inequality expressed by the Gini coefficient and prevalence of rheumatic heart disease (p=0·0002). The prevalence of clinically silent rheumatic heart disease (21·1 per 1000 people, 95% CI 14·1-31·4) was about seven to eight times higher than that of clinically manifest disease (2·7 per 1000 people, 1·6-4·4). Prevalence progressively increased with advancing age, from 4·7 per 1000 people (95% CI 0·0-11·2) at age 5 years to 21·0 per 1000 people (6·8-35·1) at 16 years. The estimated incidence was 1·6 per 1000 people (0·8-2·3) and remained constant across age categories (range 2·5, 95% CI 1·3-3·7 in 5-year-old children to 1·7, 0·0-5·1 in 15-year-old adolescents). We noted no sex-related differences in prevalence (p=0·829). INTERPRETATION We found a high prevalence of rheumatic heart disease in endemic countries. Although a reduction in social inequalities represents the cornerstone of community-based prevention, the importance of early detection of silent rheumatic heart disease remains to be further assessed. FUNDING UBS Optimus Foundation.

Association of radiographic osteoarthritis, pain on passive movement and knee range of motion: A cross-sectional study

BACKGROUND Knee pain is associated with radiographic knee osteoarthritis, but the relationships between physical examination, pain and radiographic features are unclear. OBJECTIVE To examine whether deficits in knee extension or flexion were associated with radiographic severity and pain during clinical examination in persons with knee pain or radiographic features of osteoarthritis. DESIGN Cross-sectional data of the Somerset and Avon Survey of Health (SASH) cohort study. METHODS Participants with knee pain or radiographic features of osteoarthritis were included. We assessed the range of passive knee flexion and extension, pain on movement and Kellgren and Lawrence (K/L) grades. Odds ratios were calculated for the association between range of motion and pain as well as radiographic severity. RESULTS/FINDINGS Of 1117 participants with a clinical assessment, 805 participants and 1530 knees had complete data and were used for this analysis. Pain and radiographic changes were associated with limited range of motion. In knees with pain on passive movement, extension and flexion were reduced per one grade of K/L by -1.4° (95% CI -2.2 to -0.5) and -1.6° (95% CI -2.8 to -0.4), while in knees without pain the reduction was -0.3° (95% CI -0.6 to -0.1) (extension) and -1.1° (-1.8 to -0.3) (flexion). The interaction of pain with K/L was significant (p = 0.021) for extension but not for flexion (p = 0.333). CONCLUSIONS Pain during passive movement, which may be an indicator of reversible soft-tissue changes, e.g., reversible through physical therapy, is independently associated with reduced flexion and extension of the knee.

Systematic reviews and meta-analyses of randomized trials: principles and pitfalls

Systematic reviews and meta-analyses allow for a more transparent and objective appraisal of the evidence. They may decrease the number of false-negative results and prevent delays in the introduction of effective interventions into clinical practice. However, as for any other tool, their misuse can result in severely misleading results. In this article, we discuss the main steps that should be taken when conducting systematic reviews and meta-analyses, namely the preparation of a review protocol, identification of eligible trials, and data extraction, pooling of treatment effects across trials, investigation of potential reasons for differences in treatment effects across trials, and complete reporting of the review methods and findings. We also discuss common pitfalls that should be avoided, including the use of quality assessment tools to derive summary quality scores, pooling of data across trials as if they belonged to a single large trial, and inappropriate uses of meta-regression that could result in misleading estimates of treatment effects because of regression to the mean or the ecological fallacy. If conducted and reported properly, systematic reviews and meta-analyses will increase our understanding of the strengths and weaknesses of the available evidence, which may eventually facilitate clinical decision making.

Sono-Electro-Magnetic Therapy for Treating Chronic Pelvic Pain Syndrome in Men: A Randomized, Placebo-Controlled, Double-Blind Trial.

OBJECTIVE To assess the efficacy and safety of sono-electro-magnetic therapy compared to placebo in men with refractory CPPS. PATIENTS AND METHODS In a randomized, placebo-controlled, double-blind single center trial, we assessed the effect of sono-electro-magnetic therapy in men with treatment refractory CPPS. Sixty male patients were randomly assigned to treatment with either sono-electro-magnetic (n = 30) or placebo therapy (n = 30) for 12 weeks. The primary outcome was a change in the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) from baseline to 12 weeks. RESULTS The 12-week difference between sono-electro-magnetic and placebo therapy in changes of the NIH-CPSI total score was -3.1 points (95% CI -6.8 to 0.6, p = 0.11). In secondary comparisons of NIH-CPSI sub-scores, we found differences between groups most pronounced for the quality-of-life sub-score (difference at 12 weeks -1.6, 95% CI -2.8 to -0.4, p = 0.015). In stratified analyses, the benefit of sono-electro-magnetic therapy appeared more pronounced among patients who had a symptom duration of 12 months or less (difference in NIH-CPSI total score -8.3, 95% CI -14.5 to 2.6) than in patients with a longer symptom duration (-0.8, 95% CI -4.6 to 3.1; p for interaction = 0.023). CONCLUSIONS Sono-electro-magnetic therapy did not result in a significant improvement of symptoms in the overall cohort of treatment refractory CPPS patients compared to placebo treatment. Subgroup analysis indicates, however, that patients with a symptom-duration of 12 months or less may benefit from sono-electro-magnetic therapy, warranting larger randomized controlled trials in this subpopulation. TRIAL REGISTRATION ClinicalTrials.gov NCT00688506.