Defining publication bias: protocol for a systematic review of highly cited articles and proposal for a new framework.

BACKGROUND: Selective publication of studies, which is commonly called publication bias, is widely recognized. Over the years a new nomenclature for other types of bias related to non-publication or distortion related to the dissemination of research findings has been developed. However, several of these different biases are often still summarized by the term 'publication bias'. METHODS/DESIGN: As part of the OPEN Project (To Overcome failure to Publish nEgative fiNdings) we will conduct a systematic review with the following objectives:- To systematically review highly cited articles that focus on non-publication of studies and to present the various definitions of biases related to the dissemination of research findings contained in the articles identified.- To develop and discuss a new framework on nomenclature of various aspects of distortion in the dissemination process that leads to public availability of research findings in an international group of experts in the context of the OPEN Project.We will systematically search Web of Knowledge for highly cited articles that provide a definition of biases related to the dissemination of research findings. A specifically designed data extraction form will be developed and pilot-tested. Working in teams of two, we will independently extract relevant information from each eligible article.For the development of a new framework we will construct an initial table listing different levels and different hazards en route to making research findings public. An international group of experts will iteratively review the table and reflect on its content until no new insights emerge and consensus has been reached. DISCUSSION: Results are expected to be publicly available in mid-2013. This systematic review together with the results of other systematic reviews of the OPEN project will serve as a basis for the development of future policies and guidelines regarding the assessment and prevention of publication bias.

A pilot feasibility, safety and biological efficacy multicentre trial of therapeutic hypercapnia after cardiac arrest: study protocol for a randomized controlled trial.

BACKGROUND: Cardiac arrest causes ischaemic brain injury. Arterial carbon dioxide tension (PaCO2) is a major determinant of cerebral blood flow. Thus, mild hypercapnia in the 24 h following cardiac arrest may increase cerebral blood flow and attenuate such injury. We describe the Carbon Control and Cardiac Arrest (CCC) trial. METHODS/DESIGN: The CCC trial is a pilot multicentre feasibility, safety and biological efficacy randomized controlled trial recruiting adult cardiac arrest patients admitted to the intensive care unit after return of spontaneous circulation. At admission, using concealed allocation, participants are randomized to 24 h of either normocapnia (PaCO2 35 to 45 mmHg) or mild hypercapnia (PaCO2 50 to 55 mmHg). Key feasibility outcomes are recruitment rate and protocol compliance rate. The primary biological efficacy and biological safety measures are the between-groups difference in serum neuron-specific enolase and S100b protein levels at 24 h, 48 h and 72 h. Secondary outcome measure include adverse events, in-hospital mortality, and neurological assessment at 6 months. DISCUSSION: The trial commenced in December 2012 and, when completed, will provide clinical evidence as to whether targeting mild hypercapnia for 24 h following intensive care unit admission for cardiac arrest patients is feasible and safe and whether it results in decreased concentrations of neurological injury biomarkers compared with normocapnia. Trial results will also be used to determine whether a phase IIb study powered for survival at 90 days is feasible and justified. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12612000690853 .

Reliability of P-drive in occupational therapy following a short training session: A promising instrument measuring seniors' on-road driving competencies

Introduction Occupational therapists could play an important role in facilitating driving cessation for ageing drivers. This, however, requires an easy-to-learn, standardised on-road evaluation method. This study therefore investigates whether use of P-drive' could be reliably taught to occupational therapists via a short half-day training session. Method Using the English 26-item version of P-drive, two occupational therapists evaluated the driving ability of 24 home-dwelling drivers aged 70 years or over on a standardised on-road route. Experienced driving instructors' on-road, subjective evaluations were then compared with P-drive scores. Results Following a short half-day training session, P-drive was shown to have almost perfect between-rater reliability (ICC2,1=0.950, 95% CI 0.889 to 0.978). Reliability was stable across sessions including the training phase even if occupational therapists seemed to become slightly less severe in their ratings with experience. P-drive's score was related to the driving instructors' subjective evaluations of driving skills in a non-linear manner (R-2=0.445, p=0.021). Conclusion P-drive is a reliable instrument that can easily be taught to occupational therapists and implemented as a way of standardising the on-road driving test.

Medication incidents in primary care medicine: protocol of a study by the Swiss Federal Sentinel Reporting System.

BACKGROUND/RATIONALE: Patient safety is a major concern in healthcare systems worldwide. Although most safety research has been conducted in the inpatient setting, evidence indicates that medical errors and adverse events are a threat to patients in the primary care setting as well. Since information about the frequency and outcomes of safety incidents in primary care is required, the goals of this study are to describe the type, frequency, seasonal and regional distribution of medication incidents in primary care in Switzerland and to elucidate possible risk factors for medication incidents. Label="METHODS AND ANALYSIS" ="METHODS"/> <AbstractText STUDY DESIGN AND SETTING: We will conduct a prospective surveillance study to identify cases of medication incidents among primary care patients in Switzerland over the course of the year 2015. PARTICIPANTS: Patients undergoing drug treatment by 167 general practitioners or paediatricians reporting to the Swiss Federal Sentinel Reporting System. INCLUSION CRITERIA: Any erroneous event, as defined by the physician, related to the medication process and interfering with normal treatment course. EXCLUSION CRITERIA: Lack of treatment effect, adverse drug reactions or drug-drug or drug-disease interactions without detectable treatment error. PRIMARY OUTCOME: Medication incidents. RISK FACTORS: Age, gender, polymedication, morbidity, care dependency, hospitalisation. STATISTICAL ANALYSIS: Descriptive statistics to assess type, frequency, seasonal and regional distribution of medication incidents and logistic regression to assess their association with potential risk factors. Estimated sample size: 500 medication incidents. LIMITATIONS: We will take into account under-reporting and selective reporting among others as potential sources of bias or imprecision when interpreting the results. ETHICS AND DISSEMINATION: No formal request was necessary because of fully anonymised data. The results will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT0229537.

Detection of Clinically Significant Prostate Cancer Using Magnetic Resonance Imaging-Ultrasound Fusion Targeted Biopsy: A Systematic Review.

CONTEXT: The current standard for diagnosing prostate cancer in men at risk relies on a transrectal ultrasound-guided biopsy test that is blind to the location of the cancer. To increase the accuracy of this diagnostic pathway, a software-based magnetic resonance imaging-ultrasound (MRI-US) fusion targeted biopsy approach has been proposed. OBJECTIVE: Our main objective was to compare the detection rate of clinically significant prostate cancer with software-based MRI-US fusion targeted biopsy against standard biopsy. The two strategies were also compared in terms of detection of all cancers, sampling utility and efficiency, and rate of serious adverse events. The outcomes of different targeted approaches were also compared. EVIDENCE ACQUISITION: We performed a systematic review of PubMed/Medline, Embase (via Ovid), and Cochrane Review databases in December 2013 following the Preferred Reported Items for Systematic reviews and Meta-analysis statement. The risk of bias was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. EVIDENCE SYNTHESIS: Fourteen papers reporting the outcomes of 15 studies (n=2293; range: 13-582) were included. We found that MRI-US fusion targeted biopsies detect more clinically significant cancers (median: 33.3% vs 23.6%; range: 13.2-50% vs 4.8-52%) using fewer cores (median: 9.2 vs 37.1) compared with standard biopsy techniques, respectively. Some studies showed a lower detection rate of all cancer (median: 50.5% vs 43.4%; range: 23.7-82.1% vs 14.3-59%). MRI-US fusion targeted biopsy was able to detect some clinically significant cancers that would have been missed by using only standard biopsy (median: 9.1%; range: 5-16.2%). It was not possible to determine which of the two biopsy approaches led most to serious adverse events because standard and targeted biopsies were performed in the same session. Software-based MRI-US fusion targeted biopsy detected more clinically significant disease than visual targeted biopsy in the only study reporting on this outcome (20.3% vs 15.1%). CONCLUSIONS: Software-based MRI-US fusion targeted biopsy seems to detect more clinically significant cancers deploying fewer cores than standard biopsy. Because there was significant study heterogeneity in patient inclusion, definition of significant cancer, and the protocol used to conduct the standard biopsy, these findings need to be confirmed by further large multicentre validating studies. PATIENT SUMMARY: We compared the ability of standard biopsy to diagnose prostate cancer against a novel approach using software to overlay the images from magnetic resonance imaging and ultrasound to guide biopsies towards the suspicious areas of the prostate. We found consistent findings showing the superiority of this novel targeted approach, although further high-quality evidence is needed to change current practice.

CoDiab-VD: protocol of a prospective population-based cohort study on diabetes care in Switzerland.

BACKGROUND: Diabetes represents an increasing health burden worldwide. In 2010, the Public Health Department of the canton of Vaud (Switzerland) launched a regional diabetes programme entitled "Programme cantonal Diabète" (PcD), with the objectives to both decrease the incidence of diabetes and improve care for patients with diabetes. The cohort entitled CoDiab-VD emerged from that programme. It specifically aimed at following quality of diabetes care over time, at evaluating the coverage of the PcD within this canton and at assessing the impact of the PcD on care of patients with diabetes. METHODS/DESIGN: The cohort CoDiab-VD is a prospective population-based cohort study. Patients with diabetes were recruited in two waves (autumn 2011--summer 2012) through community pharmacies. Eligible participants were non-institutionalised adult patients (≥ 18 years) with diabetes diagnosed for at least one year, residing in the canton of Vaud and coming to a participating pharmacy with a diabetes-related prescription. Women with gestational diabetes, people with obvious cognitive impairment or insufficient command of French were not eligible. Self-reported data collected, included the following primary outcomes: processes-of-care indicators (annual checks) and outcomes of care such as HbA1C, (health-related) quality of life measures (Short Form-12 Health Survey--SF-12, Audit of Diabetes-Dependent Quality of Life 19--ADDQoL) and Patient Assessment of Chronic Illness Care (PACIC). Data on diabetes, health status, healthcare utilisation, health behaviour, self-management activities and support, knowledge of, or participation to, campaigns/activities proposed by the PcD, and socio-demographics were also obtained. For consenting participants, physicians provided few additional pieces of information about processes and laboratory results. Participants will be followed once a year, via a mailed self-report questionnaire. The core of the follow-up questionnaires will be similar to the baseline one, with the addition of thematic modules adapting to the development of the PcD. Physicians will be contacted every 2 years. DISCUSSION: CoDiab-VD will allow obtaining a broad picture of the care of patients with diabetes, as well as their needs regarding their chronic condition. The data will be used to evaluate the PcD and help prioritise targeted actions. TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov, identifier NCT01902043, July 9, 2013.

Comparison of accelerated T1-weighted whole-brain structural-imaging protocols.

Imaging in neuroscience, clinical research and pharmaceutical trials often employs the 3D magnetisation-prepared rapid gradient-echo (MPRAGE) sequence to obtain structural T1-weighted images with high spatial resolution of the human brain. Typical research and clinical routine MPRAGE protocols with ~1mm isotropic resolution require data acquisition time in the range of 5-10min and often use only moderate two-fold acceleration factor for parallel imaging. Recent advances in MRI hardware and acquisition methodology promise improved leverage of the MR signal and more benign artefact properties in particular when employing increased acceleration factors in clinical routine and research. In this study, we examined four variants of a four-fold-accelerated MPRAGE protocol (2D-GRAPPA, CAIPIRINHA, CAIPIRINHA elliptical, and segmented MPRAGE) and compared clinical readings, basic image quality metrics (SNR, CNR), and automated brain tissue segmentation for morphological assessments of brain structures. The results were benchmarked against a widely-used two-fold-accelerated 3T ADNI MPRAGE protocol that served as reference in this study. 22 healthy subjects (age=20-44yrs.) were imaged with all MPRAGE variants in a single session. An experienced reader rated all images of clinically useful image quality. CAIPIRINHA MPRAGE scans were perceived on average to be of identical value for reading as the reference ADNI-2 protocol. SNR and CNR measurements exhibited the theoretically expected performance at the four-fold acceleration. The results of this study demonstrate that the four-fold accelerated protocols introduce systematic biases in the segmentation results of some brain structures compared to the reference ADNI-2 protocol. Furthermore, results suggest that the increased noise levels in the accelerated protocols play an important role in introducing these biases, at least under the present study conditions.

Do therapist behaviors differ with Hispanic youth? A brief look at within-session therapist behaviors and youth treatment response.

Brief addiction treatments, including motivational interviewing (MI), have shown promise with youth. One underexamined factor in this equation is the role of therapist behaviors. We therefore sought to assess whether and how therapist behaviors differ for Hispanic versus non-Hispanic youth and how that may be related to treatment outcome. With 80 substance-using adolescents (M age = 16 years; 65% male; 59% Hispanic; 41% non-Hispanic), we examined the relationship between youth ethnicity and therapist behaviors across two brief treatments (MI and alcohol/marijuana education [AME]). We then explored relationships to youth 3-month treatment response across four target outcomes: binge drinking days, alcohol-related problems, marijuana use days, and marijuana-related problems. In this study, therapists showed significantly more MI skills within the MI condition and more didactic skills in the AME condition. With respect to youth ethnicity, across both conditions (MI and AME), therapists used less MI skills with Hispanic youth. Contrary to expectations, therapists' use of MI skills was not connected to poorer outcomes for Hispanic youth across the board (e.g., for binge drinking days, marijuana use days, or marijuana-related problems). Rather, for Hispanic youth, therapists' use of lower MI skills was related only to poorer treatment outcomes in the context of alcohol-related problems. The observed relationships highlight the importance of investigating salient treatment interactions between therapist factors and youth ethnicity to guide improvements in youth treatment response. (PsycINFO Database Record

Cost evaluation and comparison of three decision strategies for cardiac revascularization : results of the suspected CAD protocol of the European CMR registry

Background: The public health burden of coronary artery disease (CAD) is important. Perfusion cardiac magnetic resonance (CMR) is generally accepted to detect and monitor CAD. Few studies have so far addressed its costs and costeffectiveness. Objectives: To compare in a large CMR registry the costs of a CMR-guided strategy vs two hypothetical invasive strategies for the diagnosis and the treatment of patients with suspected CAD. Methods: In 3'647 patients with suspected CAD included prospectively in the EuroCMR Registry (59 centers; 18 countries) costs were calculated for diagnostic examinations, revascularizations as well as for complication management over a 1-year follow-up. Patients with ischemia-positive CMR underwent an invasive X-ray coronary angiography (CXA) and revascularization at the discretion of the treating physician (=CMR+CXA strategy). Ischemia was found in 20.9% of patients and 17.4% of them were revascularized. In ischemia-negative patients by CMR, cardiac death and non-fatal myocardial infarctions occurred in 0.38%/y. In a hypothetical invasive arm the costs were calculated for an initial CXA followed by FFR testing in vessels with ≥50% diameter stenoses (=CXA+FFR strategy). To model this hypothetical arm, the same proportion of ischemic patients and outcome was assumed as for the CMR+CXA strategy. The coronary stenosis - FFR relationship reported in the literature was used to derive the proportion of patients with ≥50% diameter stenoses (Psten) in the study cohort. The costs of a CXA-only strategy were also calculated. Calculations were performed from a third payer perspective for the German, UK, Swiss, and US healthcare systems.