A novel approach for identifying and addressing case‐mix heterogeneity in individual participant data meta‐analysis

Case-mix heterogeneity across studies complicates meta-analyses. As a result of this, treatments that are equally effective on patient subgroups may appear to have different effectiveness on patient populations with different case mix. It is therefore important that meta-analyses be explicit for what patient population they describe the treatment effect. To achieve this, we develop a new approach for meta-analysis of randomized clinical trials, which use individual patient data (IPD) from all trials to infer the treatment effect for the patient population in a given trial, based on direct standardization using either outcome regression (OCR) or inverse probability weighting (IPW). Accompanying random-effect meta-analysis models are developed. The new approach enables disentangling heterogeneity due to case mix from that due to beyond case-mix reasons

Key stakeholders' perspectives and experiences with defining, identifying and displaying gaps in health research: a qualitative study

IntroductionMapping the current body of evidence including what is missing helps provide a better understanding of what research is available, ongoing and needed and should be prioritised. Identifying research gaps can inform the design and conduct of health research by providing additional context information about the body of evidence in a given topic area. Despite the commonly used term 'research gap' in scientific literature, little is written on how to find a 'research gap' in the first place. Moreover, there is no clear methodological guidance to identify and display gaps.ObjectiveThis study aimed to explore how key stakeholders define research gaps and characterise methods/practices used to identify and display gaps in health research to further advance efforts in this area.DesignThis was an exploratory qualitative study using semistructured in-depth interviews. The study sample included the following stakeholder groups: researchers, funders, healthcare providers, patients/public and policy-makers. Interview transcripts were subjected to thematic analysis.ResultsAmong the 20 interviews conducted (20 participants), a variety of research gap definitions were expressed (ie, five main themes, including gaps in information, knowledge/evidence gaps, uncertainties, quality and patient perspective). We identified three main themes for methods used to identify gaps (primary, secondary and both primary and secondary) and finally six main themes for the methods to display gaps (forest plots, diagrams/illustrations, evidence maps, mega maps, 3IE gap maps and info graphics).ConclusionThis study provides insights into issues related to defining research gaps and methods used to identify and display gaps in health research from the perspectives of key stakeholders involved in the process. Findings will be used to inform methodological guidance on identifying research gaps

Central and peripheral quadriceps fatigue in congestive heart failure

AbstractAimsThe clinical syndrome of heart failure includes exercise limitation that is not directly linked to measures of cardiac function. Quadriceps fatigability may be an important component of this and this may arise from peripheral or central factors.Methods and resultsWe studied 10 men with CHF and 10 healthy age-matched controls. Compared with a rest condition, 10min after incremental maximal cycle exercise, twitch quadriceps force in response to supramaximal magnetic femoral nerve stimulation fell in both groups (CHF 14.1%±18.1%, p=0.037; Control: 20.8±11.0%, p<0.001; no significant difference between groups). There was no significant change in quadriceps maximum voluntary contraction voluntary force. The difference in the motor evoked potential (MEP) response to transcranial magnetic stimulation of the motor cortex between rest and exercise conditions at 10min, normalised to the peripheral action potential, also fell significantly in both groups (CHF: 27.3±38.7%, p=0.037; Control: 41.1±47.7%, p=0.024). However, the fall in MEP was sustained for a longer period in controls than in patients (p=0.048).ConclusionsThe quadriceps is more susceptible to fatigue, with a similar fall in TwQ occurring in CHF patients at lower levels of exercise. This is associated with no change in voluntary activation but a lesser degree of depression of quadriceps motor evoked potential

Relationship between Fungal Colonisation of the Respiratory Tract in Lung Transplant Recipients and Fungal Contamination of the Hospital Environment

International audienceBackgroundAspergillus colonisation is frequently reported after lung transplantation. The question of whether aspergillus colonisation is related to the hospital environment is crucial to prevention.MethodTo elucidate this question, a prospective study of aspergillus colonisation after lung transplantation, along with a mycological survey of the patient environment, was performed.ResultsForty-four consecutive patients were included from the day of lung transplantation and then examined weekly for aspergillus colonisation until hospital discharge. Environmental fungal contamination of each patient was followed weekly via air and surface sampling. Twelve patients (27%) had transient aspergillus colonisation, occurring 1–13 weeks after lung transplantation, without associated manifestation of aspergillosis. Responsible Aspergillus species were A. fumigatus (6), A. niger (3), A. sydowii (1), A. calidoustus (1) and Aspergillus sp. (1). In the environment, contamination by Penicillium and Aspergillus was predominant. Multivariate analysis showed a significant association between occurrence of aspergillus colonisation and fungal contamination of the patient’s room, either by Aspergillus spp. in the air or by A.fumigatus on the floor. Related clinical and environmental isolates were genotyped in 9 cases of aspergillus colonisation. For A. fumigatus (4 cases), two identical microsatellite profiles were found between clinical and environmental isolates collected on distant dates or locations. For other Aspergillus species, isolates were different in 2 cases; in 3 cases of aspergillus colonisation by A. sydowii, A. niger and A. calidoustus, similarity between clinical and environmental internal transcribed spacer and tubulin sequences was >99%.ConclusionTaken together, these results support the hypothesis of environmental risk of hospital acquisition of aspergillus colonisation in lung transplant recipients

230: Heightened risk of coronary atheroma conferred by a decrease in the plasma concentrations of lithocholic acid

ContextThe bile acids receptors Farsenoid X and TGR5 protect against the formation of atheroma in mice, though no evidence have linked coronary atheroma and bile acid in human. Bile acids links these receptors with more or less efficient activation, depending on the species.ObjectiveTo test the hypothesis that changes in concentrations of circulating bile acid species influence the risk of developing coronary atheromas in humans.MethodsPilot, prospective, observational study conducted between June and September 2010. The serum concentrations of cholic, chenodeoxycholic, deoxycholic, and lithocholic acids were measured in a fasting blood sample. Consecutive hospitalized or ambulatory patients undergoing emergency or elective coronary angiograms were eligible for inclusion. Post-cardiac arrest and non-fasting states, hepatic disease, and treatment with antimicrobials, corticosteroids, statins or fibrates were exclusion criteria. Of 393 screened patients, 44 met the study entry criteria, and were divided between 27 patients with (Group A) and 17 without (Group B) angiographically visible coronary atheromas. The pool of circulating bile acids was analyzed to measure the plasmatic concentrations of 28 different bile acid species. The variables associated with the presence of angiographically visible coronary atheromas were examined by single and multiple variable logistic regression analysis.ResultsThe serum lithocholic acid concentration was significantly lower in group A than in group B. By multiple variable analysis, lithocholic acid was the only predictor of coronary atheroma independently of patient gender (odds ratio 2.41 per 0.05 decrease; 95% confidence interval 1.11 to 5.25, P=0.027ConclusionA low serum concentration of lithocholic acid was an independent predictor of coronary atheroma in human

Hyperglycaemia and apoptosis of microglial cells in human septic shock

International audienceIntroductionThe effect of hyperglycaemia on the brain cells of septic shock patients is unknown. The objective of this study was to evaluate the relationship between hyperglycaemia and apoptosis in the brains of septic shock patients.MethodsIn a prospective study of 17 patients who died from septic shock, hippocampal tissue was assessed for neuronal ischaemia, neuronal and microglial apoptosis, neuronal Glucose Transporter (GLUT) 4, endothelial inducible Nitric Oxide Synthase (iNOS), microglial GLUT5 expression, microglial and astrocyte activation. Blood glucose (BG) was recorded five times a day from ICU admission to death. Hyperglycaemia was defined as a BG 200 mg/dL g/l and the area under the BG curve (AUBGC) > 2 g/l was assessed.ResultsMedian BG over ICU stay was 2.2 g/l. Neuronal apoptosis was correlated with endothelial iNOS expression (rho = 0.68, P = 0.04), while microglial apoptosis was associated with AUBGC > 2 g/l (rho = 0.70; P = 0.002). Neuronal and microglial apoptosis correlated with each other (rho = 0.69, P = 0.006), but neither correlated with the duration of septic shock, nor with GLUT4 and 5 expression. Neuronal apoptosis and ischaemia tended to correlate with duration of hypotension.ConclusionsIn patients with septic shock, neuronal apoptosis is rather associated with iNOS expression and microglial apoptosis with hyperglycaemia, possibly because GLUT5 is not downregulated. These data provide a mechanistic basis for understanding the neuroprotective effects of glycemic control

Management of Kaposi sarcoma after solid organ transplantation:A European retrospective study

Background: Systemic therapeutic management of post-transplant Kaposi sarcoma (KS) is mainly based on 3 axes: reduction of immunosuppression, conversion to mammalian target of rapamycin (mTOR) inhibitors, chemotherapy, or a combination of these.Objective: To obtain an overview of clinical strategies about the current treatment of KS.Methods: We conducted a multicenter retrospective cohort study including 145 solid organ transplant recipients diagnosed with KS between 1985 and 2011 to collect data regarding first-line treatment and response at 6 months.Results: Overall, 95%, 28%, and 16% of patients had reduction of immunosuppression, conversion to mTOR inhibitor, and chemotherapy, respectively. Patients treated with chemotherapy or mTOR inhibitor conversion were more likely to have visceral KS. At 6 months, 83% of patients had response, including 40% complete responses.Limitations: The retrospective design of the study.Conclusion: Currently available therapeutic options seem to be effective to control KS in most patients. Tapering down the immunosuppressive regimen remains the cornerstone of KS management.Dermatology-oncolog