To evaluate the characteristics of therapeutic meta-analyses including both observational studies and randomized controlled trials (RCTs), how these studies were combined and whether there were ...differences in treatment effects.
Meta-epidemiological study of meta-analyses, including both observational studies and RCTs. We searched MEDLINE for the five leading journals of each medical category according to Journal Citation Reports) and Cochrane Database of Systematic Reviews, from 2014 to 2018 for eligible meta-analyses and extracted how observational studies and RCTs were combined and results for each study.
Of the 102 included meta-analyses, observational studies and RCTs were combined together without a subgroup analysis in 39 (38%) and with subgroup analysis in 15 (15%); they were pooled separately for the same outcome in 11 (11%) and not for the same outcome in 9 (9%). In 28 (27%) meta-analyses, only RCTs were combined, with a qualitative description of observational studies. Treatment effect estimates did not differ between observational studies and RCTs (ratio of estimates = 0.98 95% confidence interval 0.80–1.21), with substantial heterogeneity (I2 = 59%).
Many meta-analyses, including both observational studies and RCTs pool results from both study types. Although treatment effects did not differ between them on average, we identified situations for which estimates differed.
•Many meta-analyses combined observational studies with RCTs in meta-analysis. Overall, there was no difference in effects between RCTs and observational studies.•Heterogeneity across topics was substantial.•There were a few situations with significant differences between both study types.
Oral antithrombotic (AT) drugs, which include antiplatelet and anticoagulant therapies, are widely implicated in serious preventable bleeding events. Avoiding inappropriate oral AT combinations is a ...major concern. Numerous practical guidelines have been released; a document to enhance prescriptions of oral AT combinations for adults would be of great help.
To synthesize guidelines on the prescription of oral AT combinations in adults and to create a prescription support-tool for clinicians about chronic management (≥ one month) of oral AT combinations.
A systematic review of guidelines published between January 2012 and April 2017, in English or in French, from Trip database, Guideline International Network and PubMed, dealing with the prescription of oral ATs in adults was conducted. In-hospital management of ATs, bridging therapy and switches of ATs were not considered. Some specific topics requiring specialized follow-up (cancer, auto-immune disease, haemophilia, HIV, paediatrics and pregnancy) were excluded. Last update was made in November 2018.
A total of 885 guidelines were identified and 70 met the eligibility criteria. A prescription support-tool summarizing medical conditions requiring chronic management of oral AT combinations in adults with drug types, dosage and duration, on a double-sided page, was provided and tested by an external committee of physicians. The lack of specific guidelines for old people (age 75 years and older) is questioned considering the specific vulnerability of this age group to serious bleedings.
Recommendations on prescriptions about chronic management of oral AT combinations in adults were mainly consensual but dispersed in numerous guidelines according to the medical indication. We provide a prescription support-tool for clinicians. Further studies are needed to assess the impact of this tool on appropriate prescribing and the prevention of serious adverse drug events.
The Precision Neurology development process implements systems theory with system biology and neurophysiology in a parallel, bidirectional research path: a combined hypothesis-driven investigation of ...systems dysfunction within distinct molecular, cellular, and large-scale neural network systems in both animal models as well as through tests for the usefulness of these candidate dynamic systems biomarkers in different diseases and subgroups at different stages of pathophysiological progression. This translational research path is paralleled by an "omics"-based, hypothesis-free, exploratory research pathway, which will collect multimodal data from progressing asymptomatic, preclinical, and clinical neurodegenerative disease (ND) populations, within the wide continuous biological and clinical spectrum of ND, applying high-throughput and high-content technologies combined with powerful computational and statistical modeling tools, aimed at identifying novel dysfunctional systems and predictive marker signatures associated with ND. The goals are to identify common biological denominators or differentiating classifiers across the continuum of ND during detectable stages of pathophysiological progression, characterize systems-based intermediate endophenotypes, validate multi-modal novel diagnostic systems biomarkers, and advance clinical intervention trial designs by utilizing systems-based intermediate endophenotypes and candidate surrogate markers. Achieving these goals is key to the ultimate development of early and effective individualized treatment of ND, such as Alzheimer's disease. The Alzheimer Precision Medicine Initiative (APMI) and cohort program (APMI-CP), as well as the Paris based core of the Sorbonne University Clinical Research Group "Alzheimer Precision Medicine" (GRC-APM) were recently launched to facilitate the passageway from conventional clinical diagnostic and drug development toward breakthrough innovation based on the investigation of the comprehensive biological nature of aging individuals. The APMI movement is gaining momentum to systematically apply both systems neurophysiology and systems biology in exploratory translational neuroscience research on ND.
Several neurodegenerative brain proteinopathies, including Alzheimer's disease (AD), are associated with cerebral deposition of insoluble aggregates of α-synuclein. Previous studies reported a trend ...toward increased cerebrospinal fluid (CSF) α-synuclein (α-syn) concentrations in AD compared with other neurodegenerative diseases and healthy controls.
The pathophysiological role of CSF α-syn in asymptomatic subjects at risk of AD has not been explored. We performed a large-scale cross-sectional observational monocentric study of preclinical individuals at risk for AD (INSIGHT-preAD).
We found a positive association between CSF α-syn concentrations and brain β-amyloid deposition measures as mean cortical standard uptake value ratios. We demonstrate positive correlations between CSF α-syn and both CSF t-tau and p-tau
concentrations.
Animal models presented evidence, indicating that α-syn may synergistically and directly induce fibrillization of both tau and β-amyloid. Our data indicate an association of CSF α-syn with AD-related pathophysiological mechanisms, during the preclinical phase of the disease.
Family-based caregivers are increasingly important in the management of non-hospitalized lung cancer patients. However, lack of training can negatively impact care including diagnostic errors that ...can lead to delays in providing appropriate medical treatment. Acute respiratory failure (ARF) is common symptom of lung cancer and requires urgent intervention as well as adequate communication with healthcare professionals (HCPs) to enable appropriate decision-making and improve patient outcomes. Standardized tools such as the Situation, Background, Assessment, Recommendation (SBAR) tool and its French adaptation SAED, standing for Situation, Antécédent, Évaluation et Demande, are designed to facilitate communication among (HCPs).
Additionally, digital interventions, such as serious games, are increasingly used to train HCPs though its use for caregivers has not been studied. This pilot study aims to assess an innovative serious game training using the SAED tool combined with standard instructions on self-efficacy for family-based caregivers of lung cancer patients when facing a simulated situation of ARF. The study also aims to examine caregivers' emotional state, quality of life, satisfaction and knowledge about the SBAR tool.
A monocentric, randomized, controlled, open-label, superiority, parallel-arm trial will be conducted for 18 months with 3 mid-study assessments (NCT05839353). Family caregivers of lung cancer patients will be recruited at the University Hospital Center of Saint Pierre, Reunion Island, France. Participants will be randomized (1:1) into two groups: the experimental group receiving training using the SBAR/SAED tool and standard instructions for managing respiratory distress/dyspnea, and the control group, receiving standard instructions only. The primary outcome will be to determine perceived self-efficacy as measured by the Generalized Self-Efficacy Scale.
This study will present a preliminary assessment of training family caregivers in using the SBAR/SAED tool in simulated episodes of ARF in lung cancer patients. Our findings may provide valuable insights into effective training methods for caregivers in critical home care situations and could be widely used for lung cancer management.
•Family caregivers are increasingly involved in the care management of lung cancer patients.•Digital health solutions ( such as serious games) have emerged as innovative teaching interventions.•A pilot monocentric randomized, open-label, parallel-arm, superiority-controlled trial was designed to assess caregivers’ self-efficacy, knowledge and satisfaction.•Our methodology may generate a holistic and secure support system for lung cancer patients and their caregivers.•We will provide insights about knowledge transfer sessions and personalized recommendations to better manage lung cancer.
Accidental exposure to blood (AEB) poses a risk of bloodborne infections for healthcare workers (HCWs) during hospital activities. In this study, we identified individual behavioral and ...organizational predictors of AEB among HCWs.
The study was a prospective, 1-year follow-up cohort study conducted in university hospitals in Paris, France. Data were collected from the Stress at Work and Infectious Risk in Patients and Caregivers (STRIPPS) study. Eligible participants included nurses, nursing assistants, midwives, and physicians from 32 randomly selected wards in 4 hospitals. AEB occurrences were reported at baseline, 4 months, 8 months, and 12 months, and descriptive statistical and multilevel risk-factor analyses were performed.
The study included 730 HCWs from 32 wards, predominantly nurses (52.6%), nursing assistants (41.1%), physicians (4.8%), and midwives (1.5%). The incidence rate of AEB remained stable across the 4 visits. The multilevel longitudinal analysis identified several significant predictors of AEB occurrence. Individual-level predictors included younger age, occupation as nurses or midwives, irregular work schedule, rotating shifts, and lack of support from supervisors. The use of external nurses was the most significant ward-level predictor associated with AEB occurrence.
AEBs among HCWs are strongly associated with organizational predictors, highlighting the importance of complementing infection control policies with improved staff management and targeted training. This approach can help reduce AEB occurrences and enhance workplace safety for HCWs.
Restrictive allograft syndrome (RAS) after lung transplantation (LTx) is associated with the poorer graft survival in patients with chronic lung allograft dysfunction (CLAD). Nevertheless, its ...diagnostic criteria have not been clearly defined after single-LTx (SLTx). Hence, we studied an SLTx cohort with CLAD to investigate the utility of both computed tomography (CT)-score/volume measures and functional spirometric criteria for the early identification of RAS in this population.
We included 51 patients with SLTx (17 RAS, 17 bronchiolitis obliterans syndrome BOS, and 17 stable condition). The criteria for RAS diagnosis in SLTx included forced vital capacity (FVC) <80% baseline (BL) or forced expiratory volume in 1 second (FEV1) <80% BL with an FEV1/FVC ratio
and persistent CT-scan-lung opacities. We defined 4 time points (T): T-baseline, T-onset (first CT-scan-opacities), T-follow-up, and T-last.
In patients with RAS, the spirometric criteria for RAS at T-onset were reached in only 47% (FVC decline <80% BL (29% or FEV1 <80% BL/ratio
41%), whereas at the same T-onset date, the graft CT-score increased to 5 (4-6) vs 1 (0-2) at baseline (p < 0.001) (CT - score ≥2 at T-onset in 100% and ΔCT - score ≥2 in 74% of patients with RAS), and the median CT-scan graft volume decreased to 1,722 ml (vs 1,796 ml at T-baseline, p = 0.003) (decreased CT-graft - volume <90% BL in 50% of patients). In contrast, in patients with BOS, CT-score/volume were unchanged at T-onset vs T-baseline (p = 0.8, p = 0.68, respectively).
Our results suggest that the use of a simple CT-score and to a lesser extent, CT-volume measures, might allow for the early identification and/or prediction of RAS in SLTx rather than functional criteria.
A total of 2%–10% of patients with vascular liver disease (VLD) have paroxysmal nocturnal hemoglobinuria (PNH). Eculizumab reduces complement‐mediated haemolytic activity in PNH. This study was aimed ...at assessing the impact of eculizumab on VLD outcome. Retrospective cohort of PNH patients, in Valdig registry, who had VLD diagnosed between 1997 and 2019 is considered. Eculizumab was the exposure of interest. Studied outcomes were death, venous thrombosis, bleeding, arterial ischemic event, infection, and liver‐related complications. We compared survival and new thrombotic events from PNH/VLD cohort to Envie2 non‐PNH cohort. Sixty‐two patients (33 women), median age 35 years (28–48) and median follow‐up VLD diagnosis 4.7 years (1.2–9.5), were included. Clone size was 80% (70–90), median hemoglobin concentration was 10.0 g/dl (8–11), and lactate dehydrogenase (LDH) was 736 IU (482–1744). Forty‐two patients (68%) had eculizumab; median exposure time was 40.1 9.3–72.6 months. Mortality was significantly lower in exposed versus nonexposed period: 2.6 versus 8.7 per 100 (PY), incidence rate ratio (IRR) was 0.29, 95% CI (0.1–0.9), p = .035. Thrombosis recurrence occurred less frequently during the exposure to eculizumab: 0.5 versus 2.8 per 100 PY, IRR 0.22 (0.07–0.64). Other secondary end points (i.e., bleeding, arterial ischemic lesions, infection, and liver complications) were less common during the exposure to eculizumab, although not reaching statistical significance. Six‐year thrombosis‐free survival was 70%, 95% CI 0.60–0.83 for PNH cohort and 83%, 95% CI 0.70–1.00 for non‐PNH Envie 2 patients, (p < .001). In conclusion, patients with PNH and VLD are at higher risk of recurrent thrombosis than non‐PNH patients. Eculizumab is significantly associated with a lower mortality and less thrombotic recurrence in patients with PNH and VLD.
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