An Evaluation of the Effectiveness of Risk Minimization Measures for Tigecycline in the European Union

Background: Risk minimization measures (RMM) were implemented from February 2011 in the European Union to address risks of superinfection, off-label use and lack of efficacy associated with tigecycline. The objective of this study was to evaluate RMM effectiveness by describing prescription patterns among adults and children treated with any dose of tigecycline for any indication pre- and post-RMM implementation; incidence proportions of superinfection and lack of efficacy among adults treated with approved doses of tigecycline for complicated intra-abdominal infection and complicated skin and soft tissue infection were also evaluated. Methods: This was an observational, retrospective chart-abstraction study, including charts from 777 patients (399 pre-RMM, 378 post-RMM) at 13 sites across Austria, Germany, Italy, Greece and the United Kingdom (UK). Potential superinfection and lack of efficacy cases among those using tigecycline for on-label indication, age, dose, and duration were adjudicated. The distribution of indications for tigecycline was analyzed overall (i.e. across both study periods) and stratified by study period. Numbers and incidence proportions of superinfection and lack of efficacy cases (potential and adjudicated) were calculated overall and by study period. Results: Off-label use (indication or age) decreased from 54.2% [95% confidence interval (95% CI): 49.0, 59.3%] pre-RMM to 35.7% (95% CI 30.4, 41.2%) post-RMM. Overall, 45.7% (95% CI 41.9, 49.5%) of patients were prescribed tigecycline off-label; the most commonly reported off-label indications were characterized as \u201cother\u201d (25.5%), hospital acquired pneumonia (8.2%), other pneumonia (6.3%), bacteremia (5.2%) and diabetic foot infection (1.5%). Across study periods, incidence proportions of definite or probable superinfection and lack of efficacy in adults treated for approved indications, authorized treatment doses and duration were 4.5% (95% CI 2.1, 8.4%) and 5.5% (95% CI 2.8, 9.7%), respectively. Conclusions: Off-label use of tigecycline decreased following RMM implementation. Overall incidence proportions of definite or probable superinfection and lack of efficacy were low. EU PAS register number: EUPAS3674

The Function Biomedical Informatics Research Network Data Repository

The Function Biomedical Informatics Research Network (FBIRN) developed methods and tools for conducting multi-scanner functional magnetic resonance imaging (fMRI) studies. Method and tool development were based on two major goals: 1) to assess the major sources of variation in fMRI studies conducted across scanners, including instrumentation, acquisition protocols, challenge tasks, and analysis methods, and 2) to provide a distributed network infrastructure and an associated federated database to host and query large, multi-site, fMRI and clinical datasets. In the process of achieving these goals the FBIRN test bed generated several multi-scanner brain imaging data sets to be shared with the wider scientific community via the BIRN Data Repository (BDR). The FBIRN Phase 1 dataset consists of a traveling subject study of 5 healthy subjects, each scanned on 10 different 1.5 to 4 Tesla scanners. The FBIRN Phase 2 and Phase 3 datasets consist of subjects with schizophrenia or schizoaffective disorder along with healthy comparison subjects scanned at multiple sites. In this paper, we provide concise descriptions of FBIRN’s multi-scanner brain imaging data sets and details about the BIRN Data Repository instance of the Human Imaging Database (HID) used to publicly share the data

Additional file 1: of The effect of diabetes mellitus on outcomes of patients with nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus: data from a prospective double-blind clinical trial comparing treatment with linezolid versus vancomycin

Definitions of Clinical and Microbiologic Outcomes. Additional file 1: Table S1. defines the clinical outcomes [clinical cure, clinical improvement (only at EOT), clinical failure and indeterminate] and microbiologic outcomes [documented microbiologic eradication, presumed microbiologic eradication, presumed microbiologic persistence, superinfection, colonization and indeterminate]. (DOCX 14 kb

Clinical response and mortality in tigecycline complicated intra-abdominal infection and complicated skin and soft-tissue infection trials

An imbalance in all-cause mortality was noted in tigecycline phase 3 and 4 comparative clinical trials across all studied indications. We investigated clinical failure and mortality in phase 3 and 4 complicated skin and soft-tissue infection (cSSTI) and complicated intra-abdominal infection (cIAI) tigecycline trials using descriptive analyses of a blinded adjudication of mortality and multivariate regression analyses. Attributable mortality analyses of cSSTI revealed death due to infection in 0.1% of each treatment group (P = 1.000). In cIAI, there were no significant differences between tigecycline (1.2%) and comparator (0.7%) subjects who died due to infection (P = 0.243). For cIAI clinical failure, treatment interaction with organ dysfunction was observed with no difference observed between clinical cure for tigecycline (85.4%) and comparator (76.7%) treatment groups (odds ratio = 0.58, 95% confidence interval 0.28-1.19). Tigecycline-treated subjects had more adverse events of secondary pneumonias (2.1% vs. 1.2%) and more adverse events of secondary pneumonias with an outcome of death (0.5% vs. 0.1%). These analyses do not suggest that tigecycline is a factor either for failure (cSSTI and cIAI studies) or for death (cIAI studies)

Function Biomedical Informatics Research Network Recommendations for Prospective Multi-Center Functional Magnetic Resonance Imaging Studies

This report provides practical recommendations for the design and execution of Multi-Center functional Magnetic Resonance Imaging (MC-fMRI) studies based on the collective experience of the Function Biomedical Informatics Research Network (FBIRN). The paper was inspired by many requests from the fMRI community to FBIRN group members for advice on how to conduct MC-fMRI studies. The introduction briefly discusses the advantages and complexities of MC-fMRI studies. Prerequisites for MC-fMRI studies are addressed before delving into the practical aspects of carefully and efficiently setting up a MC-fMRI study. Practical multi-site aspects include: (1) establishing and verifying scan parameters including scanner types and magnetic fields, (2) establishing and monitoring of a scanner quality program, (3) developing task paradigms and scan session documentation, (4) establishing clinical and scanner training to ensure consistency over time, (5) developing means for uploading, storing, and monitoring of imaging and other data, (6) the use of a traveling fMRI expert and (7) collectively analyzing imaging data and disseminating results. We conclude that when MC-fMRI studies are organized well with careful attention to unification of hardware, software and procedural aspects, the process can be a highly effective means for accessing a desired participant demographics while accelerating scientific discovery