A test for reporting bias in trial networks: simulation and case studies

Networks of trials assessing several treatment options available for the same condition are increasingly considered. Randomized trial evidence may be missing because of reporting bias. We propose a test for reporting bias in trial networks. We test whether there is an excess of trials with statistically significant results across a network of trials. The observed number of trials with nominally statistically significant p-values across the network is compared with the expected number. The performance of the test (type I error rate and power) was assessed using simulation studies under different scenarios of selective reporting bias. Examples are provided for networks of antidepressant and antipsychotic trials, where reporting biases have been previously demonstrated by comparing published to Food and Drug Administration (FDA) data. In simulations, the test maintained the type I error rate and was moderately powerful after adjustment for type I error rate, except when the between-trial variance was substantial. In all, a positive test result increased moderately or markedly the probability of reporting bias being present, while a negative test result was not very informative. In the two examples, the test gave a signal for an excess of statistically significant results in the network of published data but not in the network of FDA data. The test could be useful to document an excess of significant findings in trial networks, providing a signal for potential publication bias or other selective analysis and outcome reporting biases

Tumor burden and liver function in HCC patient selection for selective internal radiation therapy: SARAH post-hoc study

Aim: To determine whether a liver tumor burden ≤25% and well-preserved liver function (albumin-bilirubin grade 1) are appropriate criteria for identifying patients with unresectable hepatocellular carcinoma who may benefit from selective internal radiation therapy (SIRT) using 90yttrium resin microspheres versus sorafenib. Patients & methods: Post-hoc analysis of patients in the intention-to-treat population of the SARAH trial (SIRT vs sorafenib) with ≤25% tumor burden and albumin-bilirubin grade 1. Primary end point: overall survival. Results: Median overall survival was 21.9 months (95% CI: 15.2–32.5, n = 37) with SIRT and 17.0 months (11.6–20.8, n = 48) with sorafenib (hazard ratios: 0.73; 95% CI: 0.44–1.21; p = 0.22). Conclusion: A combination of good liver function and low tumor burden may be relevant for selection of hepatocellular carcinoma patients for SIRT

Improving stress echocardiography accuracy for detecting left circumflex artery stenosis: A new echocardiographic sign?

SummaryBackgroundThe accuracy and reproducibility of stress echocardiography (SE) for the detection of coronary artery lesions requires improvement, particularly in the left circumflex artery (LCx).AimsTo evaluate the feasibility and diagnostic value of a new sign: Rise of the Apical lateral wall and/or Horizontal displacement of the Apex toward the septum (“RA-HA”) in apical echocardiographic views.MethodsConsecutive patients with normal left ventricular function at rest, positive SE and an indication for coronary angiography were included. SEs were analysed blindly by three independent cardiologists: two seniors (S1 and S2) and one junior (J).ResultsOf 81 patients, 58 had an exercise SE and 23 had a dobutamine SE. Significant coronary stenosis was found in 59 of 77 patients who underwent coronary angiography (76.6%). Interobserver reproducibility for the presence of RA-HA was very good between S1 and S2 (κ=0.86), and good between S1 and J (0.67) and S2 and J (0.70). The sensitivity, specificity and positive and negative predictive values of RA-HA for the detection of significant coronary artery stenosis were, respectively, 39–41%, 83–89%, 88–92% and 29–31% for S1/S2; and 29%, 83%, 85% and 26% for J. To predict LCx stenosis (single or multivessel): 67–70%, 89%, 80–81% and 80–82% for S1/S2, respectively, and 50%, 89%, 75% and 74% for J.ConclusionWith a short learning curve, RA-HA is easily diagnosed with a very good interobserver reproducibility. It has high specificity and PPV for the detection of a coronary artery stenosis, particularly in the LCx artery, during exercise or dobutamine SE

French academic physicians had a poor knowledge of terms used in clinical epidemiology

Objectives: To assess academic physicians' understanding and usage of basic epidemiological terms commonly used in medical journals. Study Design and Setting: Observational study. A total of 274 physicians, working in a teaching hospital in Paris, France were asked to answer a questionnaire including four vignettes presenting the results of a therapeutic, a diagnostic, a prognostic study and a meta-analysis of clinical trials. Results: A total of 130 (47%) questionnaires were returned. We observed the highest proportion of good answers for questions about absolute risk reduction (87.7%), sensitivity (84.6%), and specificity (80%); and the lowest for the calculation and use of the likelihood ratio (16.9% and 9.2%, respectively). The global mean score was 5.0/10 (95% confidence interval54.6e5.4, range 0e9.4). Physicians got higher scores for questions related to treatment than for questions related to diagnosis: mean scores 7.1 (6.6e7.6) vs. 4.2 (3.8e4.6). Regression analysis did not reveal any significant relationship between global performance and physicians' age (r250.002, not significant [NS]). Conclusion: Physicians demonstrated only moderate knowledge and usage of clinical epidemiology terms used in major medical journals. Their capacity to interpret quantitative data from medical scientific literature may be limited. [Authors]]]> Epidemiology ; Health Knowledge, Attitudes, Practice ; Medical Staff, Hospital ; Physicians oai:serval.unil.ch:BIB_470C9DE8C422 2022-05-07T01:17:02Z openaire documents urnserval <oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd"> https://serval.unil.ch/notice/serval:BIB_470C9DE8C422 A neuron-specific deletion of the microRNA-processing enzyme DICER induces severe but transient obesity in mice. info:doi:10.1371/journal.pone.0116760 info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0116760 info:eu-repo/semantics/altIdentifier/pmid/25629159 Mang, G.M. Pradervand, S. Du, N.H. Arpat, A.B. Preitner, F. Wigger, L. Gatfield, D. Franken, P. info:eu-repo/semantics/article article 2015 PLoS One, vol. 10, no. 1, pp. e0116760 info:eu-repo/semantics/altIdentifier/eissn/1932-6203 urn:issn:1932-6203 <![CDATA[MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate gene expression post-transcriptionally. MiRNAs are implicated in various biological processes associated with obesity, including adipocyte differentiation and lipid metabolism. We used a neuronal-specific inhibition of miRNA maturation in adult mice to study the consequences of miRNA loss on obesity development. Camk2a-CreERT2 (Cre+) and floxed Dicer (Dicerlox/lox) mice were crossed to generate tamoxifen-inducible conditional Dicer knockouts (cKO). Vehicle- and/or tamoxifen-injected Cre+;Dicerlox/lox and Cre+;Dicer+/+ served as controls. Four cohorts were used to a) measure body composition, b) follow food intake and body weight dynamics, c) evaluate basal metabolism and effects of food deprivation, and d) assess the brain transcriptome consequences of miRNA loss. cKO mice developed severe obesity and gained 18 g extra weight over the 5 weeks following tamoxifen injection, mainly due to increased fat mass. This phenotype was highly reproducible and observed in all 38 cKO mice recorded and in none of the controls, excluding possible effects of tamoxifen or the non-induced transgene. Development of obesity was concomitant with hyperphagia, increased food efficiency, and decreased activity. Surprisingly, after reaching maximum body weight, obese cKO mice spontaneously started losing weight as rapidly as it was gained. Weight loss was accompanied by lowered O2-consumption and respiratory-exchange ratio. Brain transcriptome analyses in obese mice identified several obesity-related pathways (e.g. leptin, somatostatin, and nemo-like kinase signaling), as well as genes involved in feeding and appetite (e.g. Pmch, Neurotensin) and in metabolism (e.g. Bmp4, Bmp7, Ptger1, Cox7a1). A gene cluster with anti-correlated expression in the cerebral cortex of post-obese compared to obese mice was enriched for synaptic plasticity pathways. While other studies have identified a role for miRNAs in obesity, we here present a unique model that allows for the study of processes involved in reversing obesity. Moreover, our study identified the cortex as a brain area important for body weight homeostasis

Readability of the Written Study Information in Pediatric Research in France

BACKGROUND: The aim was to evaluate the readability of research information leaflets (RIL) for minors asked to participate in biomedical research studies and to assess the factors influencing this readability. METHODS AND FINDINGS: All the pediatric protocols from three French pediatric clinical research units were included (N = 104). Three criteria were used to evaluate readability: length of the text, Flesch's readability score and presence of illustrations. We compared the readability of RIL to texts specifically written for children (school textbooks, school exams or extracts from literary works). We assessed the effect of protocol characteristics on readability. The RIL had a median length of 608 words [350 words, 25(th) percentile; 1005 words, 75(th) percentile], corresponding to two pages. The readability of the RIL, with a median Flesch score of 40 [30; 47], was much poorer than that of pediatric reference texts, with a Flesch score of 67 [60; 73]. A small proportion of RIL (13/91; 14%) were illustrated. The RIL were longer (p<0.001), more readable (p<0.001) and more likely to be illustrated (p<0.009) for industrial than for institutional sponsors. CONCLUSION: Researchers should routinely compute the reading ease of study information sheets and make greater efforts to improve the readability of written documents for potential participants

0130: Mortality related to cardiogenic shock in critically ill patients in France, 1997-2012

IntroductionMost of data reporting epidemiology of cardiogenic shock (CS) concern patients with acute myocardial infarction admitted in intensive care unit of cardiology. However, CS patients managed in critical care unit (CCU) have often multiorgan failure and seem to have different characteristics and outcome. To our best knowledge no study reported characteristics and clinical outcomes of CS patients admitted in CCU.AimTo report key features, Mortality and Trends in mortality in a large cohort of patients with CS admitting in 33 French CCUs from 1997 to 2012.Methods and resultsWe queried the 1997–2012 database of Parisian area ICUs-the CubRea (Intensive Care Database User Group) database to identify all hospital stays with a principal or an associated diagnosis of CS (National classification of disease R 570). Among 303 314 hospital stays, 17 494 (5.8%) were CS. The patients were managed in 60% of cases in universitary centers. Mean age was 64.3±17.0. Men accounted for 11047 (63.1%). Mean SAPS II was 62.0±24.3. Among CS, only 535 (3.06%) were AMI whereas 2685 (15.3%) were cardiac arrest and 858 (4.9%) were drug intoxications. Mechanical ventilation was required in 12967 (74.1%) of cases, inotropes in 14640 (83.7%) of cases and renal support in 3886 (22.2%) of cases. Mean duration of hospital was 19.1 days±24.7. Intrahospital Mortality was high (46.2%). Predictors of intrahospital death are reported in Table. Over the 15-year period, mortality decreased (49.8% in 1997-2000 and 42.7% in 2009-2012, p<0.001) whereas the patients were more critically ill (SAPS II 58.8±25.4 in 1997-2000 vs 64.2 8±23.6 in 2009-2012, p<0.001).Conclusionit is the first study reporting the prevalence, determinants and prognostic factors of CS patients managed in reanimation. The mortality of these very critically ill patients remains high. However over the 15-year period, even if these patients are more and more critically ill, early mortality decreased.Abstratct 0130 – TableVariablesOR95% CIDrug intoxication.307.236.401Age (<60 yo).436.383.496Mechanical circulatory support.681.3781.228Sepsis.715.637.8022009-2012.998.8851.125SAPS II1.0361.0331.038Acidosis1.4531.2641.670Mechanical ventilation1.7181.4831.990Acute respiratory distress syndrome1.7941.5582.0661997-20001.8141.4522.267Hemodialysis1.8201.6092.060Inotropic use1.9821.1133.530Disseminated intravascular coagulation2.1191.5912.822Cardiac arrest4.3333.8404.88

NEMESIS: Noninferiority, Individual-Patient Metaanalysis of Selective Internal Radiation Therapy with ⁹⁰Y Resin Microspheres Versus Sorafenib in Advanced Hepatocellular Carcinoma

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Meropenem/colistin synergy testing for multidrug-resistant Acinetobacter baumannii strains by a two-dimensional gradient technique applicable in routine microbiology

Objectives Precise assessment of potential therapeutic synergy, antagonism or indifference between antimicrobial agents currently depends on time-consuming and hard-to-standardize in vitro chequerboard titration methods. We here present a method based on a novel two-dimensional antibiotic gradient technique named Xact™. Methods We used a test comprising a combination of perpendicular gradients of meropenem and colistin in a single quadrant. We compared test outcomes with those obtained with classical chequerboard microbroth dilution testing in a study involving 27 unique strains of multidrug-resistant Acinetobacter baumannii from diverse origins. Results We were able to demonstrate 92% concordance between the new technology and classical chequerboard titration using the A. baumannii collection. Two strains could not be analysed by Xact™ due to their out-of-range MIC of meropenem (>128 mg/L). Conclusions The new test was shown to be diagnostically useful, easy to implement and less labour intensive than the classical metho

Carotid stenting: is there an operator effect? A pooled analysis from the carotid stenting trialists' collaboration.

BACKGROUND AND PURPOSE: Randomized clinical trials show higher 30-day risk of stroke or death after carotid artery stenting compared with surgery. We examined whether operator experience is associated with 30-day risk of stroke or death in the Carotid Stenting Trialists' Collaboration database. METHODS: The Carotid Stenting Trialists' Collaboration is a pooled individual patient database including all patients recruited in 3 randomized trials of stenting versus endarterectomy for symptomatic carotid stenosis (Endarterectomy Versus Angioplasty in patients with Symptomatic Severe Carotid Stenosis trial, Stent-Protected Angioplasty versus Carotid Endarterectomy trial, and International Carotid Stenting Study). Lifetime carotid artery stenting experience, lifetime experience in stenting procedures excluding the carotid, and annual number of procedures performed within the trial (in-trial volume), divided into tertiles, were used to measure operator experience. The outcome event was the occurrence of any stroke or death within 30 days of the procedure. The analysis was done per protocol. RESULTS: Among 1546 patients who underwent carotid artery stenting, 120 (7.8%) had a stroke or death within 30 days of the procedure. The 30-day risk of stroke or death did not differ according to operator lifetime carotid artery stenting experience (P=0.8) or operator lifetime stenting experience excluding the carotid (P=0.7). In contrast, the 30-day risk of stroke or death was significantly higher in patients treated by operators with low (mean ≤3.2 procedures/y; risk 10.1%; adjusted risk ratio=2.30 [1.36-3.87]) and intermediate annual in-trial volumes (3.2-5.6 procedures/y; 8.4%; adjusted risk ratio=1.93 [1.14-3.27]) compared with patients treated by high annual in-trial volume operators (>5.6 procedures/y; 5.1%). CONCLUSIONS: Carotid stenting should only be performed by operators with annual procedure volume ≥6 cases per year