Recombinant human erythropoiesis-stimulating agents and mortality in patients with cancer: a meta-analysis of randomised trials

BACKGROUND: Erythropoiesis-stimulating agents reduce anaemia in patients with cancer and could improve their quality of life, but these drugs might increase mortality. We therefore did a meta-analysis of randomised controlled trials in which these drugs plus red blood cell transfusions were compared with transfusion alone for prophylaxis or treatment of anaemia in patients with cancer. METHODS: Data for patients treated with epoetin alfa, epoetin beta, or darbepoetin alfa were obtained and analysed by independent statisticians using fixed-effects and random-effects meta-analysis. Analyses were by intention to treat. Primary endpoints were mortality during the active study period and overall survival during the longest available follow-up, irrespective of anticancer treatment, and in patients given chemotherapy. Tests for interactions were used to identify differences in effects of erythropoiesis-stimulating agents on mortality across prespecified subgroups. FINDINGS: Data from a total of 13 933 patients with cancer in 53 trials were analysed. 1530 patients died during the active study period and 4993 overall. Erythropoiesis-stimulating agents increased mortality during the active study period (combined hazard ratio [cHR] 1.17, 95% CI 1.06-1.30) and worsened overall survival (1.06, 1.00-1.12), with little heterogeneity between trials (I(2) 0%, p=0.87 for mortality during the active study period, and I(2) 7.1%, p=0.33 for overall survival). 10 441 patients on chemotherapy were enrolled in 38 trials. The cHR for mortality during the active study period was 1.10 (0.98-1.24), and 1.04 (0.97-1.11) for overall survival. There was little evidence for a difference between trials of patients given different anticancer treatments (p for interaction=0.42). INTERPRETATION: Treatment with erythropoiesis-stimulating agents in patients with cancer increased mortality during active study periods and worsened overall survival. The increased risk of death associated with treatment with these drugs should be balanced against their benefits. FUNDING: German Federal Ministry of Education and Research, Medical Faculty of University of Cologne, and Oncosuisse (Switzerland).

Three-year cost analysis of function-centred versus pain-centred inpatient rehabilitation in patients with chronic non-specific low back pain

OBJECTIVE: To compare costs of function- and pain-centred inpatient treatment in patients with chronic low back pain over 3 years of follow-up. DESIGN: Cost analysis of a randomized controlled trial. PATIENTS: A total of 174 patients with chronic low back pain were randomized to function- or pain-centred inpatient treatment. METHODS: Data on direct and indirect costs were gathered by questionnaires sent to patients, health insurance providers, employers, and the Swiss Disability Insurance Company. RESULTS: There was a non-significant difference in total medical costs after 3 years' follow-up. Total costs were 77,305 Euros in the function-centred inpatient treatment group and 83,085 Euros in the pain-centred inpatient treatment group. Likewise, indirect costs after 3 years from lost work days were non-significantly lower in the function-centred in-patient treatment group (6354 Euros; 95% confidence interval -20,892, 8392) and direct medical costs were non-significantly higher in the function-centred inpatient treatment group (574 Euros; 95% confidence interval -862, 2011). CONCLUSION: The total costs of function-centred and pain-centred inpatient treatment were similar over the whole 3-year follow-up.

Noisy kriging-based optimization methods: A unified implementation within the DiceOptim package

Kriging-based optimization relying on noisy evaluations of complex systems has recently motivated contributions from various research communities. Five strategies have been implemented in the DiceOptim package. The corresponding functions constitute a user-friendly tool for solving expensive noisy optimization problems in a sequential framework, while offering some flexibility for advanced users. Besides, the implementation is done in a unified environment, making this package a useful device for studying the relative performances of existing approaches depending on the experimental setup. An overview of the package structure and interface is provided, as well as a description of the strategies and some insight about the implementation challenges and the proposed solutions. The strategies are compared to some existing optimization packages on analytical test functions and show promising performances.

Streaming Support for Data Intensive Cloud-Based Sequence Analysis

Cloud computing provides a promising solution to the genomics data deluge problem resulting from the advent of next-generation sequencing (NGS) technology. Based on the concepts of “resources-on-demand” and “pay-as-you-go”, scientists with no or limited infrastructure can have access to scalable and cost-effective computational resources. However, the large size of NGS data causes a significant data transfer latency from the client’s site to the cloud, which presents a bottleneck for using cloud computing services. In this paper, we provide a streaming-based scheme to overcome this problem, where the NGS data is processed while being transferred to the cloud. Our scheme targets the wide class of NGS data analysis tasks, where the NGS sequences can be processed independently from one another. We also provide the elastream package that supports the use of this scheme with individual analysis programs or with workflow systems. Experiments presented in this paper show that our solution mitigates the effect of data transfer latency and saves both time and cost of computation.

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.

The timing of significant arch dimensional changes with fixed orthodontic appliances: data from a multicenter randomised controlled trial.

OBJECTIVES To identify the timing of significant arch dimensional increases during orthodontic alignment involving round and rectangular nickel-titanium (NiTi) wires and rectangular stainless steel (SS). A secondary aim was to compare the timing of changes occurring with conventional and self-ligating fixed appliance systems. METHODS In this non-primary publication, additional data from a multicenter randomised trial initially involving 96 patients, aged 16 years and above, were analysed. The main pre-specified outcome measures were the magnitude and timing of maxillary intercanine, interpremolar, and intermolar dimensions. Each participant underwent alignment with a standard Damon (Ormco, Orange, CA) wire sequence for a minimum of 34 weeks. Blinding of clinicians and patients was not possible; however, outcome assessors and data analysts were kept blind to the appliance type during data analysis. RESULTS Complete data were obtained from 71 subjects. Significant arch dimensional changes were observed relatively early in treatment. In particular, changes in maxillary inter-first and second premolar dimensions occurred after alignment with an 0.014in. NiTi wire (P<0.05). No statistical differences in transverse dimensions were found between rectangular NiTi and working SS wires for each transverse dimension (P>0.05). Bracket type had no significant effect on the timing of the transverse dimensional changes. CONCLUSIONS Arch dimensional changes were found to occur relatively early in treatment, irrespective of the appliance type. Nickel-titanium wires may have a more profound effect on transverse dimensions than previously believed. CLINICAL SIGNIFICANCE On the basis of this research orthodontic expansion may occur relatively early in treatment. Nickel-titanium wires may have a more profound effect on transverse dimensions than previously believed.

Analysis of TNF-antagonist switch over time and associated risk factors in the Swiss Inflammatory Bowel Disease Cohort

BACKGROUND AND AIMS Limited data from large cohorts are available on tumor necrosis factor (TNF) antagonists (infliximab, adalimumab, certolizumab pegol) switch over time. We aimed to evaluate the prevalence of switching from one TNF antagonist to another and to identify associated risk factors. METHODS Data from the Swiss Inflammatory Bowel Diseases Cohort Study (SIBDCS) were analyzed. RESULTS Of 1731 patients included into the SIBDCS (956 with Crohn's disease [CD] and 775 with ulcerative colitis [UC]), 347 CD patients (36.3%) and 129 UC patients (16.6%) were treated with at least one TNF antagonist. A total of 53/347 (15.3%) CD patients (median disease duration 9 years) and 20/129 (15.5%) of UC patients (median disease duration 7 years) needed to switch to a second and/or a third TNF antagonist, respectively. Median treatment duration was longest for the first TNF antagonist used (CD 25 months; UC 14 months), followed by the second (CD 13 months; UC 4 months) and third TNF antagonist (CD 11 months; UC 15 months). Primary nonresponse, loss of response and side effects were the major reasons to stop and/or switch TNF antagonist therapy. A low body mass index, a short diagnostic delay and extraintestinal manifestations at inclusion were identified as risk factors for a switch of the first used TNF antagonist within 24 months of its use in CD patients. CONCLUSION Switching of the TNF antagonist over time is a common issue. The median treatment duration with a specific TNF antagonist is diminishing with an increasing number of TNF antagonists being used.

Injury severity and mortality of adult zebra crosswalk and non-zebra crosswalk road crossing accidents: a cross-sectional analysis

PRINCIPALS Over a million people worldwide die each year from road traffic injuries and more than 10 million sustain permanent disabilities. Many of these victims are pedestrians. The present retrospective study analyzes the severity and mortality of injuries suffered by adult pedestrians, depending on whether they used a zebra crosswalk. METHODS Our retrospective data analysis covered adult patients admitted to our emergency department (ED) between 1 January 2000 and 31 December 2012 after being hit by a vehicle while crossing the road as a pedestrian. Patients were identified by using a string term. Medical, police and ambulance records were reviewed for data extraction. RESULTS A total of 347 patients were eligible for study inclusion. Two hundred and three (203; 58.5%) patients were on a zebra crosswalk and 144 (41.5%) were not. The mean ISS (injury Severity Score) was 12.1 (SD 14.7, range 1-75). The vehicles were faster in non-zebra crosswalk accidents (47.7 km/n, versus 41.4 km/h, p<0.027). The mean ISS score was higher in patients with non-zebra crosswalk accidents; 14.4 (SD 16.5, range 1-75) versus 10.5 (SD13.14, range 1-75) (p<0.019). Zebra crosswalk accidents were associated with less risk of severe injury (OR 0.61, 95% CI 0.38-0.98, p<0.042). Accidents involving a truck were associated with increased risk of severe injury (OR 3.53, 95%CI 1.21-10.26, p<0.02). CONCLUSION Accidents on zebra crosswalks are more common than those not on zebra crosswalks. The injury severity of non-zebra crosswalk accidents is significantly higher than in patients with zebra crosswalk accidents. Accidents involving large vehicles are associated with increased risk of severe injury. Further prospective studies are needed, with detailed assessment of motor vehicle types and speed.

Impact of anti-inflammatory treatment on the onset of uveitis in juvenile idiopathic arthritis: Longitudinal analysis from a nation-wide paediatric rheumatological database

PURPOSE Based on a nation-wide database, this study analysed the influence of methotrexate (MTX), TNF inhibitors and a combination of the two on uveitis occurrence in JIA patients. METHODS Data from the National Paediatric Rheumatological Database in Germany were used in this study. Between 2002 and 2013, data from JIA patients were annually documented at the participating paediatric rheumatological sites. Patients with JIA disease duration of less than 12 months at initial documentation and ≥2 years of follow-up were included in this study. The impact of anti-inflammatory treatment on the occurrence of uveitis was evaluated by discrete-time survival analysis. RESULTS A total of 3,512 JIA patients (mean age 8.3±4.8 years, female 65.7%, ANA-positive 53.2%, mean age at arthritis onset 7.8±4.8 years) fulfilled the inclusion criteria. Mean total follow-up time was 3.6±2.4 years. Uveitis developed in a total of 180 patients (5.1%) within one year after arthritis onset. Uveitis onset after the first year was observed in another 251 patients (7.1%). DMARD treatment in the year before uveitis onset significantly reduced the risk for uveitis: MTX (HR 0.63, p=0.022), TNF inhibitors (HR 0.56, p<0.001) and a combination of the two (HR 0.10, p<0.001). Patients treated with MTX within the first year of JIA had an even a lower uveitis risk (HR 0.29, p<0.001). CONCLUSION The use of DMARDs in JIA patients significantly reduced the risk for uveitis onset. Early MTX use within the first year of disease and the combination of MTX with a TNF inhibitor had the highest protective effect. This article is protected by copyright. All rights reserved.

Combining qualitative and quantitative methods to analyze serious games outcomes: A pilot study for a new cognitive screening tool

Computer games for a serious purpose - so called serious games can provide additional information for the screening and diagnosis of cognitive impairment. Moreover, they have the advantage of being an ecological tool by involving daily living tasks. However, there is a need for better comprehensive designs regarding the acceptance of this technology, as the target population is older adults that are not used to interact with novel technologies. Moreover given the complexity of the diagnosis and the need for precise assessment, an evaluation of the best approach to analyze the performance data is required. The present study examines the usability of a new screening tool and proposes several new outlines for data analysis.

Systematic analysis of factors associated with progression and regression of ulcerative colitis in 918 patients.

BACKGROUND Studies that systematically assess change in ulcerative colitis (UC) extent over time in adult patients are scarce. AIM To assess changes in disease extent over time and to evaluate clinical parameters associated with this change. METHODS Data from the Swiss IBD cohort study were analysed. We used logistic regression modelling to identify factors associated with a change in disease extent. RESULTS A total of 918 UC patients (45.3% females) were included. At diagnosis, UC patients presented with the following disease extent: proctitis [199 patients (21.7%)], left-sided colitis [338 patients (36.8%)] and extensive colitis/pancolitis [381 (41.5%)]. During a median disease duration of 9 [4-16] years, progression and regression was documented in 145 patients (15.8%) and 149 patients (16.2%) respectively. In addition, 624 patients (68.0%) had a stable disease extent. The following factors were identified to be associated with disease progression: treatment with systemic glucocorticoids [odds ratio (OR) 1.704, P = 0.025] and calcineurin inhibitors (OR: 2.716, P = 0.005). No specific factors were found to be associated with disease regression. CONCLUSIONS Over a median disease duration of 9 [4-16] years, about two-thirds of UC patients maintained the initial disease extent; the remaining one-third had experienced either progression or regression of the disease extent.