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Abstract Background Morphine relieves dyspnea in various clinical circumstances. Whether or not this applies to patients admitted to intensive care units (ICUs) for acute respiratory failure (ARF) is unknown. We evaluated the efficacy and safety of low-dose morphine on dyspnea in patients admitted to the ICU for ARF. Methods In this single-center, double-blind, phase 2, randomized, controlled trial, we assigned non-intubated adults admitted to the ICU for ARF with severe dyspnea, defined by a visual analog scale for dyspnea (dyspnea-VAS) from zero (no dyspnea) to 100 mm (worst imaginable dyspnea) ≥40 mm, to receive a low dose of Morphine Hydrochloride (intravenous titration followed by subcutaneous relay) or Placebo. All patients received standard therapy, including etiological treatment and non-invasive respiratory support. Results Twenty-two patients were randomized, 11 in each group. The average dyspnea (median [interquartile range]) over 24 hours did not significantly differ between the two groups (40 [25 – 43] mm in the Morphine group vs. 40 [36 – 49] mm in the Placebo group, p=0.411). Dyspnea-VAS was lower in the Morphine group than in the Placebo group at the end of intravenous titration (30 [11 – 30] vs. 35 [30 – 44], p=0.044) and four hours later (18 [10 – 29] vs. 50 [30 – 60], p=0.043). The cumulative probability of intubation was higher in the Morphine group than in the Placebo group (p=0.046) Conclusion In this phase 2 pilot trial, morphine did not improve 24-hour average dyspnea in adult patients with ARF, even though it had a statistically significant immediate effect. Of concern, Morphine use was associated with a higher intubation rate. Trial registration The protocol was declared on the ClinicalTrial.gov database (no. NCT04358133) and was published in September 2022.

The teaching of medical humanities is increasingly being integrated into medical school curricula. We developed a podcast called Le Serment d’Augusta (Augusta’s Oath), consisting of six episodes tackling hot topics in the modern world of healthcare related to the patient-doctor relationship, professionalism, and ethics. This podcast aimed to provide scientific content in an entertaining way, while promoting debate among medical students. The Le Serment d’Augusta podcast was proposed as one of the various optional modules included in the second- to fifth-year curriculum at the School of Medicine of Sorbonne University (Paris). We asked students to report their lived experience of listening to the podcast. We then used a text-mining approach focusing on two main aspects: i) students’ perspective of the use of this educational podcast to learn about medical humanities; ii) self-reported change in their perception of and knowledge about core elements of healthcare after listening to the podcast. 478 students were included. Students were grateful for the opportunity to participate in this teaching module. They greatly enjoyed this kind of learning tool and reported that it gave them autonomy in learning. They appreciated the content as well as the format, highlighting that the topics were related to the very essence of medical practice and that the numerous testimonies were of great added value. Listening to the podcast resulted in knowledge acquisition and significant change of perspective. These findings further support the use of podcasts in medical education, especially to teach medical humanities, and their implementation in the curriculum.

Abstract Background Cardiac surgery-associated acute kidney injury (CSA-AKI) is frequent. While two network meta-analyses assessed the impact of pharmacological interventions to prevent CSA-AKI, none focused on non-pharmacological interventions. We aim to assess the effectiveness of non-pharmacological interventions to reduce the incidence of CSA-AKI. Methods We searched PubMed, Embase, Central and clinical trial registries from January 1, 2004 (first consensus definition of AKI) to July 1, 2023. Additionally, we conducted manual screening of abstracts of major anesthesia and intensive care conferences over the last 5 years and reference lists of relevant studies. We selected all randomized controlled trials (RCTs) assessing a non-pharmacological intervention to reduce the incidence of CSA-AKI, without language restriction. We excluded RCTs of heart transplantation or involving a pediatric population. The primary outcome variable was CSA-AKI. Two reviewers independently identified trials, extracted data and assessed risk of bias. Random-effects meta-analyses were conducted to calculate risk ratios (RRs) with 95% confidence intervals (CIs). We used the Grading of Recommendations Assessment, Development, and Evaluation to assess the quality of evidence. Results We included 86 trials (25,855 patients) evaluating 10 non-pharmacological interventions to reduce the incidence of CSA-AKI. No intervention had high-quality evidence to reduce CSA-AKI. Two interventions were associated with a significant reduction in CSA-AKI incidence, with moderate quality of evidence: goal-directed perfusion (RR, 0.55 [95% CI 0.40–0.76], I 2 = 0%; P het = 0.44) and remote ischemic preconditioning (RR, 0.86 [0.78–0.95]; I 2 = 23%; P het = 0.07). Pulsatile flow during cardiopulmonary bypass was associated with a significant reduction in CSA-AKI incidence but with very low quality of evidence (RR = 0.69 [0.48; 0.99]; I 2 = 53%; P het

Context: Midurethral slings (MUSs) are the most used therapy for the treatment of stress urinary incontinence (SUI). While warning signals about potential complications have been raised worldwide, there is a lack of safety data especially in the long term. Objective: Our objective was to evaluate synthetic MUS safety outcomes at long term in adult women. Evidence acquisition: We included all studies evaluating MUSs in adult women with SUI. All synthetic MUSs have been considered: tension-free vaginal tape (TVT), transobturator tape (TOT), and mini-slings. The primary outcome was the reoperation rate at 5 yr. Evidence synthesis: Of 5586 references screened after duplicate removal, 44 studies (8218 patients) were included. Among these, nine were randomized controlled trials and 35 were cohort studies. The overall reoperation rates at 5 yr varied between 0% and 19% for TOT (11 studies), 0% and 13% for TVT (17 studies), and 0% and 19% for mini-slings (two studies). The overall reoperation rates at 10 yr varied between 5% and 15% for TOT (four studies) and between 2% and 17% for TVT (four studies). There were few safety data beyond 5 yr: 22.7% of the articles reported a follow-up at ≥10 yr and 2.3% at ≥15 yr. Conclusions: The incidence rates of reoperations and complications are heterogeneous, and data beyond 5 yr are rare. Patient summary: There is an urgent need to improve safety monitoring of mesh as our review highlights that available safety data are heterogeneous and of insufficient quality to guide the decision.

Abstract Purpose To evaluate the heterogeneity in the definition of delirium in randomized controlled trials (RCTs) included in meta-analyses of delirium in intensive care units (ICUs) and to explore whether intervention effect depends on the definition used. Methods We searched PubMed for meta-analyses including RCTs evaluating prevention or treatment strategies of delirium in ICU. The definition of delirium was collected from RCTs and classified as validated (DSM criteria, CAM-ICU, ICDSC, NEECHAM, DRS-R98) or non-validated (non-validated scales, set of symptoms, physician appreciation or not reported). We conducted a meta-epidemiological analysis to compare intervention effects between trials using or not a validated definition by a two-step method as primary analysis and a multilevel model as secondary analysis. A ratio of odds ratios (ROR)

Abstract Background Many clinical practice guidelines are based on randomised controlled trials conducted in secondary or tertiary care setting and general practitioners frequently question their relevance for primary care patients. Our aim was to compare the intervention effect estimates between primary care setting randomised controlled trials (PC-RCTs) and secondary or tertiary care setting randomised controlled trials (ST-RCTs). Methods Meta-epidemiological study of meta-analyses (MAs) of a binary outcome including at least one PC-RCT and one ST-RCT. PC-RCTs were defined as trials recruiting patients in general practices, primary care practices, family practices, community centers or community pharmacies. ST-RCTs were defined as trials recruiting in hospitals, including hospitalized patients, hospital outpatients and patients from emergency departments. For each MA, we estimated a ratio of odds ratio (ROR) by using random-effects meta-regression, with an ROR less than 1 indicating lower estimates of the intervention effect in PC-RCTs than ST-RCTs. Finally, we estimated a combined ROR across MAs by using a random-effects meta-analysis. We performed subgroup analyses considering the type of outcomes (objective vs subjective), type of experimental intervention (pharmacological vs non-pharmacological), and control group (active vs inactive) as well as analyses adjusted on items of the Cochrane Risk of Bias tool. Results Among 1765 screened reviews, 76 MAs with 230 PC-RCTs and 384 ST-RCTs were selected. The main medical fields were pneumology (13.2%) and psychiatry or addictology (38.2%). Intervention effect estimates did not significantly differ between PC-RCTs and ST-RCTs (ROR = 0.97, 95% confidence interval 0.88 to 1.08), with moderate heterogeneity across MAs (I2 = 45%). Subgroup and adjusted analyses led to consistent results. Conclusion We did not observe any significant difference in intervention effect estimates between PC-RCTs and ST-RCTs. Nevertheless, most of the medical fields in this meta-epidemiological study were not representative of the pathologies encountered in primary care. Further studies with pathologies more frequently encountered in primary care are needed.

Abstract Systematic reviews and meta-analyses have been proposed as an approach to synthesize the literature and counteract the lack of power of small preclinical studies. We aimed to evaluate (1) the methodology of these reviews, (2) the methodological quality of the studies they included and (3) whether study methodological characteristics affect effect size. We searched MEDLINE to retrieve 212 systematic reviews with meta-analyses of preclinical studies published from January, 2018 to March, 2020. Less than 15% explored the grey literature. Selection, data extraction and risk of bias assessment were performed in duplicate in less than two thirds of reviews. Most of them assessed the methodological quality of included studies and reported the meta-analysis model. The risk of bias of included studies was mostly rated unclear. In meta-epidemiological analysis, none of the study methodological characteristics was associated with effect size. The methodological characteristics of systematic reviews with meta-analyses of recently published preclinical studies seem to have improved as compared with previous assessments, but the methodological quality of included studies remains poor, thus limiting the validity of their results. Our meta-epidemiological analysis did not show any evidence of a potential association between methodological characteristics of included studies and effect size.

Abstract Background Dyspnea is common and severe in intensive care unit (ICU) patients managed for acute respiratory failure. Dyspnea appears to be associated with impaired prognosis and neuropsychological sequels. Pain and dyspnea share many similarities and previous studies have shown the benefit of morphine on dyspnea in patients with end-stage onco-hematological disease and severe heart or respiratory disease. In these populations, morphine administration was safe. Here, we hypothesize that low-dose opioids may help to reduce dyspnea in patients admitted to the ICU for acute respiratory failure. The primary objective of the trial is to determine whether the administration of low-dose titrated opioids, compared to placebo, in patients admitted to the ICU for acute respiratory failure with severe dyspnea decreases the mean 24-h intensity of dyspnea score. Methods In this single-center double-blind randomized controlled trial with 2 parallel arms, we plan to include 22 patients (aged 18–75 years) on spontaneous ventilation with either non-invasive ventilation, high flow oxygen therapy or standard oxygen therapy admitted to the ICU for acute respiratory failure with severe dyspnea. They will be assigned after randomization with a 1:1 allocation ratio to receive in experimental arm administration of low-dose titrated morphine hydrochloride for 24 h consisting in an intravenous titration relayed subcutaneously according to a predefined protocol, or a placebo (0.9% NaCl) administered according to the same protocol in the control arm. The primary endpoint is the mean 24-h dyspnea score assessed by a visual analog scale of dyspnea. Discussion To our knowledge, this study is the first to evaluate the benefit of opioids on dyspnea in ICU patients admitted for acute respiratory failure. Trial registration ClinicalTrials.gov NCT04358133 . Registered on 24 April 2020.

BackgroundAmong available digital apps, those providing personalized video exercises may be helpful for individuals undergoing functional rehabilitation. ObjectiveWe aimed to assess the effectiveness of apps providing personalized video exercises to support rehabilitation for people with short- and long-term disabling conditions, on functional capacity, confidence in exercise performance, health care consumption, health-related quality of life, adherence, and adverse events. MethodsIn this systematic review, we searched MEDLINE, CENTRAL, and Embase databases up to March 2022. All randomized controlled trials evaluating the effect of apps providing personalized video exercises to support rehabilitation for any condition requiring physical rehabilitation were included. Selection, extraction, and risk of bias assessment were performed by 2 independent reviewers. The primary outcome was functional capacity at the end of the intervention. The secondary outcomes included confidence in exercise performance, care consumption, health-related quality of life, adherence, and adverse events. A meta-analysis was performed where possible; the magnitude of the effect was assessed with the standardized mean difference (SMD). ResultsFrom 1641 identified references, 10 papers (n=1050 participants, 93% adults) were included: 7 papers (n=906 participants) concerned musculoskeletal disorders and 3 (n=144 participants) concerned neurological disorders. Two (n=332 participants) were employee based. The apps were mostly commercial (7/10); the videos were mostly elaborated on by a physiotherapist (8/10). The duration of app use was 3-48 weeks. All included studies had a high overall risk of bias. Low-quality evidence suggested that the use of apps providing personalized video exercises led to a significant small to moderate improvement in physical function (SMD 0.35, 95% CI 0.19-0.51; Phet=.86; I2=0%) and confidence in exercise performance (SMD 0.67; 95% CI 0.37-0.96; Phet=.22; I2=33%). Because of the very low quality of the evidence, the effects on quality of life and exercise adherence were uncertain. Apps did not influence the rate of adverse events. ConclusionsApps providing personalized video exercises to support exercise performance significantly improved physical function and confidence in exercise performance. However, the level of evidence was low; more robust studies are needed to confirm these results. Trial RegistrationPROSPERO CRD42022323670; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=323670

BackgroundCovidom was a telemonitoring solution for home monitoring of patients with mild to moderate COVID-19, deployed in March 2020 in the Greater Paris area in France to alleviate the burden on the health care system. The Covidom solution included a free mobile application with daily monitoring questionnaires and a regional control center to quickly handle patient alerts, including dispatching emergency medical services when necessary. ObjectiveThis study aimed to provide an overall evaluation of the Covidom solution 18 months after its inception in terms of effectiveness, safety, and cost. MethodsOur primary outcome was to measure effectiveness using the number of handled alerts, response escalation, and patient-reported medical contacts outside of Covidom. Then, we analyzed the safety of Covidom by assessing its ability to detect clinical worsening, defined as hospitalization or death, and the number of patients with clinical worsening without any preceding alert. We evaluated the cost of Covidom and compared the cost of hospitalization for Covidom and non-Covidom patients with mild COVID-19 cases seen in the emergency departments of the largest network of hospitals in the Greater Paris area (Assistance Publique-Hôpitaux de Paris). Finally, we reported on user satisfaction. ResultsOf the 60,073 patients monitored by Covidom, the regional control center handled 285,496 alerts and dispatched emergency medical services 518 times. Of the 13,204 respondents who responded to either of the follow-up questionnaires, 65.8% (n=8690) reported having sought medical care outside the Covidom solution during their monitoring period. Of the 947 patients who experienced clinical worsening while adhering to daily monitoring, only 35 (3.7%) did not previously trigger alerts (35 were hospitalized, including 1 who died). The average cost of Covidom was €54 (US $1=€0.8614) per patient, and the cost of hospitalization for COVID-19 worsening was significantly lower in Covidom than in non-Covidom patients with mild COVID-19 cases seen in the emergency departments of Assistance Publique-Hôpitaux de Paris. The patients who responded to the satisfaction questionnaire had a median rating of 9 (out of 10) for the likelihood of recommending Covidom. ConclusionsCovidom may have contributed to alleviating the pressure on the health care system in the initial months of the pandemic, although its impact was lower than anticipated, with a substantial number of patients having consulted outside of Covidom. Covidom seems to be safe for home monitoring of patients with mild to moderate COVID-19.

Background Literature focusing on migration and maternal health inequalities is inconclusive, possibly because of the heterogeneous definitions and settings studied. We aimed to synthesize the literature comparing the risks of severe maternal outcomes in high-income countries between migrant and native-born women, overall and by host country and region of birth. Methods and findings Systematic literature review and meta-analysis using the Medline/PubMed, Embase, and Cochrane Library databases for the period from January 1, 1990 to April 18, 2023. We included observational studies comparing the risk of maternal mortality or all-cause or cause-specific severe maternal morbidity in high-income countries between migrant women, defined by birth outside the host country, and native-born women; used the Newcastle-Ottawa scale tool to assess risk of bias; and performed random-effects meta-analyses. Subgroup analyses were planned by host country and region of birth. The initial 2,290 unique references produced 35 studies published as 39 reports covering Europe, Australia, the United States of America, and Canada. In Europe, migrant women had a higher risk of maternal mortality than native-born women (pooled risk ratio [RR], 1.34; 95% confidence interval [CI], 1.14, 1.58; p < 0.001), but not in the USA or Australia. Some subgroups of migrant women, including those born in sub-Saharan Africa (pooled RR, 2.91; 95% CI, 2.03, 4.15; p < 0.001), Latin America and the Caribbean (pooled RR, 2.77; 95% CI, 1.43, 5.35; p = 0.002), and Asia (pooled RR, 1.57, 95% CI, 1.09, 2.26; p = 0.01) were at higher risk of maternal mortality than native-born women, but not those born in Europe or in the Middle East and North Africa. Although they were studied less often and with heterogeneous definitions of outcomes, patterns for all-cause severe maternal morbidity and maternal intensive care unit admission were similar. We were unable to take into account other social factors that might interact with migrant status to determine maternal health because many of these data were unavailable. Conclusions In this systematic review of the existing literature applying a single definition of 'migrant' women, we found that the differential risk of severe maternal outcomes in migrant versus native-born women in high-income countries varied by host country and region of origin. These data highlight the need to further explore the mechanisms underlying these inequities. Trial Registration PROSPERO CRD42021224193., Author(s): Maxime Eslier 1,*, Elie Azria 1,2, Konstantinos Chatzistergiou 2, Zelda Stewart 1, Agnès Dechartres 3, Catherine Deneux-Tharaux 1 Introduction Economic crises, wars, natural disasters, and increased inequalities between countries [...]

Background The prognosis of asthmatic outpatients with COVID-19 needs to be clarified. The objectives of this study were: 1) to investigate the characteristics and outcomes of asthmatic patients receiving initial ambulatory care and home monitoring for COVID-19 with Covidom, a telesurveillance solution; and 2) to compare the characteristics and outcomes between asthmatic and non-asthmatic patients. Methods Inclusion criteria were age ≥18 years, suspected or confirmed COVID-19 diagnosis allowing initial ambulatory care, registration in Covidom between March 2020 and April 2021 and completion of the initial medical questionnaire. We compared clinical characteristics and outcomes between asthmatic and non-asthmatic patients, and we evaluated whether asthma was independently associated with clinical worsening (hospitalisation or death) within 30 days follow-up using a multivariate logistic regression model. Results 33 815 patients met the inclusion criteria. Asthma was reported in 4276 (12.6%). The main comorbidities among asthmatic patients were obesity (23.1%), hypertension (12.7%) and diabetes (4.5%). As compared with non-asthmatic patients, asthmatic patients were more often female (70.0 versus 62.1%, p

Introduction Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are life-threatening conditions that can progress to death without treatment. Although strong medication adherence (MA) is known to enhance outcomes in chronic illnesses, its association with PAH and CTEPH was sporadically explored. This study aims to examine the MA of patients with PAH or CTEPH, identify factors associated with low adherence and explore the resulting outcomes. Methods A systematic review was conducted by searching multiple databases (Medline, Embase, Cochrane Central, ClinicalTrials.gov, Scopus, Web of Science and Google Scholar) from 6 March 1998 to 6 July 2023. We included studies reporting MA as primary or secondary end-points. Study selection, data extraction and methodological quality assessment were performed in duplicate. Results 20 studies involving 22 675 patients met the inclusion criteria. Heterogeneity was observed, particularly in the methods employed. MA means ranged from 0.62 to 0.96, with the proportion of patients exhibiting high MA varying from 40% (95% CI 35–45%) to 94% (95% CI 88–97%). Factors associated with low adherence included increased treatment frequency, time since diagnosis and co-payment. High MA seems to be associated with reduced hospitalisation rates, inpatient stays, outpatient visits and healthcare costs. Conclusions This systematic review underscores the heterogeneity of MA across studies. Nevertheless, the findings suggest that high MA could improve patients’ clinical outcomes and alleviate the economic burden. Identifying factors consistently associated with poor MA could strengthen educational efforts for these patients, ultimately contributing to improved outcomes. [ABSTRACT FROM AUTHOR]

Introduction: The COVID-19 pandemic created challenges to healthcare systems worldwide. To allow overwhelmed hospitals to focus on the most fragile and severely ill patients, new types of management had to be set up. During the pandemic, patients with COVID-19 from greater Paris area were monitored at home using a web-based remote system called COVIDOM™, using self-administered questionnaires, which triggered alerts to a regional control center. To ease hospital discharge and to prevent hospital from being overwhelmed, patients still requiring low-flow oxygen therapy discharged home were also included in this telemedicine solution. We aim to evaluate the safety of this original management.Methods: We conducted a retrospective multicenter cohort of patients discharged home from hospital after COVID-19 and still requiring nasal oxygen therapy, who were monitored by questionnaire and trained physicians using COVIDOM. During late follow-up, the status of the patients using a Euro-Qol (EQ-5D-5L) questionnaire, and the Medical Research Council (MRC) Dyspnea scale was collected.Results: From March 21st to June 21st 2020, 73 COVID-19 patients still receiving nasal oxygen at hospital discharge were included. Median [Inter-Quartile Range (IQR)] age was 62.0 [52.5–69.0] years, 64.4% were male. Altogether, risk factors were observed in 49/73 (67%) patients, mainly hypertension (35.6%), diabetes mellitus (15.1%) and active neoplasia (11.0%). Among the cohort, 26% of patients were previously managed in ICU. Oxygen therapy was required for a median [IQR] of 20 [16–31] days. No death or urgent unplanned hospitalization were observed during the COVIDOM telemonitoring. During the late follow-up evaluation (6 months after inclusion), the mean EQ-5D-5L questionnaire score was 7.0 ± 1.6, and the mean MRC dyspnea scale was 0.8 ± 1.0, indicating absence of dyspnea. Five patients have died from non-COVID causes.Conclusions: In this preliminary study, early discharge home of patients with severe COVID-19 disease who still required low-oxygen therapy seems to be safe.

Introduction: Bevacizumab-containing therapy is considered a standard-of-care front-line option for stage IIIB–IV ovarian cancer based on results of randomized phase 3 trials. The multicenter non-interventional ENCOURAGE prospective cohort study assessed treatment administration and outcomes in the French real-world setting.Patients and Methods: Eligible patients were aged ≥ 18 years with planned bevacizumab-containing therapy for newly diagnosed ovarian cancer. The primary objective was to assess the safety profile of front-line bevacizumab in routine clinical practice; secondary objectives were to describe patient characteristics, indications/contraindications for bevacizumab, treatment regimens and co-medications, follow-up and monitoring, progression-free survival, and treatment at recurrence. In this non-interventional study, treatment was administered as chosen by the investigator and participation in the trial had no influence on the management of the disease.Results: Of 1,290 patients screened between April 2013 and February 2015, 468 were eligible. Most patients (86%) received bevacizumab 15 mg/kg every 3 weeks or equivalent, typically with carboplatin (99%) and paclitaxel (98%). The median duration of bevacizumab was 12.2 (range 0–28, interquartile range 6.9–14.9) months; 8% of patients discontinued bevacizumab because of toxicity. The most common adverse events were hypertension (38% of patients), fatigue (35%), and bleeding (32%). There were no treatment-related deaths. Most physicians (90%) reported blood pressure measurement immediately before each bevacizumab infusion and almost all (97%) reported monitoring for proteinuria before each bevacizumab infusion. Median progression-free survival was 17.4 (95% CI, 16.4–19.1) months. The 3-year overall survival rate was 62% (95% CI, 58–67%). The most commonly administered chemotherapies at recurrence were carboplatin and pegylated liposomal doxorubicin.Discussion: Clinical outcomes and tolerability with bevacizumab in this real-life setting are consistent with randomized trial results, notwithstanding differences in the treated patient population and treatment schedule.Clinical Trial Registration:ClinicalTrials.gov, Identifier NCT01832415.

Purpose: Describe the clinical and virological characteristics of viral necrotizing retinitis (VNR) and assess its prognostic factors. Methods: Retrospective study (Pitié Salpêtrière Hospital, Paris) of consecutive VNR patients diagnosed and monitored by qPCR on aqueous humor between 2015 and 2019. All patients received induction therapy with intravenous +/− intravitreal injections (IVI) of antivirals. Results: Forty-one eyes of 37 patients with a mean age of 56 years were included. Involved viruses were VZV (44%), CMV (37%) and HSV2 (19%). Acute retinal necrosis represented 51%, progressive outer retinal necrosis 12% and CMV retinitis 37% of eyes. Forty-six percent of patients were immunocompromised. Median BCVA was 0.7 LogMAR at baseline and 0.8 LogMAR after an average of 14.1 months. VNR bilateralized in 27% of cases after 32 months. Retinal detachment (RD) occurred in 27% of cases after a mean duration of 98 days. Factors associated with a “poor BCVA” at 1 month were: advanced age, low baseline BCVA, high vitritis grade and viral load (VL) at baseline and the “slow responder” status (i.e., VL decrease

Objective To evaluate the consistency of causal statements in observational studies published in The BMJ.Design Review of observational studies published in a general medical journal.Data source Cohort and other longitudinal studies describing an exposure-outcome relationship published in The BMJ in 2018. We also had access to the submitted papers and reviewer reports.Main outcome measures Proportion of published research papers with ‘inconsistent’ use of causal language. Papers where language was consistently causal or non-causal were classified as ‘consistently causal’ or ‘consistently not causal’, respectively. For the ‘inconsistent’ papers, we then compared the published and submitted version.Results Of 151 published research papers, 60 described eligible studies. Of these 60, we classified the causal language used as ‘consistently causal’ (48%), ‘inconsistent’ (20%) and ‘consistently not causal’(32%). Eleven out of 12 (92%) of the ‘inconsistent’ papers were already inconsistent on submission. The inconsistencies found in both submitted and published versions were mainly due to mismatches between objectives and conclusions. One section might be carefully phrased in terms of association while the other presented causal language. When identifying only an association, some authors jumped to recommending acting on the findings as if motivated by the evidence presented.Conclusion Further guidance is necessary for authors on what constitutes a causal statement and how to justify or discuss assumptions involved. Based on screening these papers, we provide a list of expressions beyond the obvious ‘cause’ word which may inspire a useful more comprehensive compendium on causal language.

Introduction: In spite of increasing diffusion, Enhanced Recovery Pathways (ERP) have been scarcely assessed in large scale programs of lung cancer surgery. The aim of this study was auditing our practice. Methods: A two-step audit program was established: the first dealing with our initial ERP experience in patients undergoing non-extended anatomical segmentectomies and lobectomies, the second including all consecutive patients undergoing all kind of lung resections for NSCLC. The first step aimed at auditing results of ERP on occurrence of postoperative complications and at assessing which ERP components are associated with improved short-term outcomes. We also audited late results by assessing long-term survival of patients in the first step of our study. The second step aimed at auditing on large-scale short-term results of the ERP in a real-life setting. Results: Over a one-year period, 166 patients were included. The median number of ERP procedures per patient was three (IQR 3–4). No postoperative death occurred. The overall adverse events rate was 30%. In multivariate analyzes, the only element associated with reduced adverse postoperative events was chest tube withdrawal within POD2 (OR = 0.21, 95% CI (0.10–0.46)). The 1-, 3-, and 5-year survival rates were 97%, 86.1%, and 76.3%, respectively. In the second period, 1077 patients were included in our ERP; 11 patients died during the postoperative period or within 30 days of operation (1.02%). The overall postoperative adverse event rate was 30.3%, major complication occurring in 134 (12.4%), and minor ones in 192 (17.8%). Respiratory complications occurred in 64 (5.9%). Thoracoscore independently predicted postoperative death, the occurrence of complications (all-kind, minor, major, or respiratory ones). Conclusions: Compliance to ERP procedures and early chest tube removal are associated with reduced postoperative events in patients with lung resection surgery. In a large setting scale, ERP can be applied with satisfactory results in terms of mortality and morbidity. Thoracoscore is a useful tool in predicting mortality and postoperative adverse events.

In a matter of months, COVID-19 has escalated from a cluster of cases in Wuhan, China, to a global pandemic. As the number of patients with COVID-19 grew, solutions for the home monitoring of infected patients became critical. This viewpoint presents a telesurveillance solution—Covidom—deployed in the greater Paris area to monitor patients with COVID-19 in their homes. The system was rapidly developed and is being used on a large scale with more than 65,000 registered patients to date. The Covidom solution combines an easy-to-use and free web application for patients (through which patients fill out short questionnaires on their health status) with a regional control center that monitors and manages alerts (triggered by questionnaire responses) from patients whose health may be deteriorating. This innovative solution could alleviate the burden of health care professionals and systems while allowing for rapid response when patients trigger an alert.

Abstract Background Inadequate planning, selective reporting, and incomplete reporting of outcomes in randomized controlled trials (RCTs) contribute to the problem of waste of research. We aimed to describe such a waste and to examine to what extent this waste could be avoided. Methods This research-on-research study was based on RCTs included in Cochrane reviews with a summary of findings (SoF) table. We considered the outcomes reported in the SoF tables as surrogates for important outcomes for patients and other decision makers. We used a three-step approach. (1) First, in each review, we identified, for each important outcome, RCTs that were excluded from the corresponding meta-analysis. (2) Then, for these RCTs, we systematically searched for registrations and protocols to distinguish between inadequate planning (an important outcome was not reported in registries or protocols), selective reporting (an important outcome was reported in registries or protocols but not in publications), and incomplete reporting (an important outcome was incompletely reported in publications). (3) Finally, we assessed, with the consensus of five experts, the feasibility and cost of measuring the important outcomes that were not planned. We considered inadequately planned or selectively or incompletely reported important outcomes as avoidable waste if the outcome could have been easily measured at no additional cost based on expert evaluation. Results Of the 2711 RCTs included in the main comparison of 290 reviews, 2115 (78%) were excluded from at least one meta-analysis of important outcomes. Every trial contributed to 55%, on average, of the meta-analyses of important outcomes. Of the 310 RCTs published in 2010 or later, 156 were registered. Inadequate planning affected 79% of these RCTs, whereas incomplete and selective reporting affected 41% and 15%, respectively. For 63% of RCTs, we found at least one missing important outcome for which the waste was avoidable and for 30%, the waste was avoidable for all important outcomes. Conclusions Most of the RCTs included in our sample did not contribute to all the important outcomes in meta-analyses, mostly because of inadequate planning or incomplete reporting. A large part of this waste of research seemed to be avoidable.

Fibroblast growth factor 23 (FGF23) could contribute to cardiovascular morbidity in chronic kidney disease. In studies of kidney transplant recipients, a high circulating level of FGF23 has been associated with death and graft loss independently of estimated glomerular filtration rate (GFR). Whether FGF23 is associated with adverse outcomes in the early posttransplantation period is unknown. Methods: We analyzed a cohort of 845 kidney transplant recipients in stable condition who had GFR measured in the first years after transplantation with a median follow-up of 71 months. Results: A high FGF23 concentration was associated with death or graft loss in univariate analysis, but this association was lost after adjustment for measured GFR. In contrast, FGF23 remained significantly associated with the composite outcome when estimated GFR was substituted for measured GFR. We also observed that follow-up duration modified the association between FGF23 and outcome. Although FGF23 was not associated with any endpoint in the full duration of the study, we found an independent association between FGF23 and the incidence of graft loss within the 4 years after FGF23 measurement. We did not find an association between FGF23 levels and left ventricular mass in a subgroup of 227 patients who had echocardiography performed within 3 months of FGF23 measurement. Discussion: This study demonstrates that FGF23 measured during the first year after transplantation is not an independent predictor of death and graft loss and is not associated with left ventricular hypertrophy in the posttransplantation period. It further unveils important factors modifying the association between FGF23 and outcome in this population.

Purpose: This study aimed to describe cerebral Near InfraRed Spectroscopy (NIRS) profiles during neonatal intubation using two different premedication regimens.Methods: Neonates requiring non-emergency intubation were enrolled in an ancillary study, conducted in two French Neonatal Intensive Care Units participating in a larger on-going multicenter, double blind, randomized, controlled trial. Patients were randomly assigned to the “atropine-propofol” (Prop) group or the “atropine-atracurium-sufentanil” (SufTrac) group. Regional cerebral oxygen saturation (rScO2), pulse oxymetry (SpO2), mean arterial blood pressure (MABP), and transcutaneous partial pressure of carbon dioxide (TcPCO2) were collected at 9 predefined time points from 1 min before to 60 min after the first drug injection. The two primary outcomes were a decrease in rScO2 value >20% from baseline and a decrease in fractional cerebral tissue oxygen extraction (FTOE) value >10% from baseline, at any time point. Secondary outcomes included physiological parameters changes over time and correlations between mean arterial blood pressure, and FTOE at different time points. Descriptive results were obtained and exploratory statistical analyses were performed for 24 included patients.Results: rScO2 decreased in 5/11 (46%) infants from the Prop group and 10/13 (77%) from the SufTrac group (p = 0.11); FTOE decreased in 10/11 (91%) infants from the Prop group, and 12/13 (92%) from the SufTrac group (p = 0.90). rScO2 values decreased over time in both groups, whereas FTOE's pattern appeared more stable. SpO2 and transcutaneous TcPCO2 seemed more preserved in the Prop group while MABP seemed more preserved in the SufTrac group. No important correlation was observed between MABP and FTOE (r = 0.08 to 0.12 across the time points).Conclusion: Our results suggest a frequent decrease in cerebral oxygenation without obvious impairment in cerebral autoregulation during neonatal intubation with premedication. This study confirms the feasibility and the informative value of cerebral NIRS monitoring in this setting.Clinical Trial Registration:www.ClinicalTrials.gov, identifier NCT02700893.

Objectives: Few is known on pregnant women with mild COVID-19 managed in a community setting with a telemedicine solution, including their outcomes. The objective of this study is to evaluate the adverse fetal outcomes and hospitalization rates of pregnant COVID-19 outpatients who were monitored with the Covidom© telemedicine solution. Methods: A nested study was conducted on pregnant outpatients with confirmed COVID-19, who were managed with Covidom© between March and November 2020. The patients were required to complete a standard medical questionnaire on co-morbidities and symptoms at inclusion, and were then monitored daily for 30 days after symptom onset. Adverse fetal outcome was defined as a composite of preterm birth, low birthweight, or stillbirth, and was collected retrospectively through phone contact with a standardized questionnaire. Results: The study included 714 pregnant women, with a median age of 32.0 [29.0–35.0] and a median BMI of 23.8 [21.3–27.0]. The main comorbidities observed were smoking (53%), hypertension (19%). The most common symptoms were asthenia (45.6%), cough (40.3%) and headache (25.7%), as well as anosmia (28.4%) and agueusia (32.3%). Adverse fetal outcomes occurred in 64 (9%) cases, including 38 (5%) preterm births, 33 (5%) low birthweights, and 6 (1%) stillbirths. Hospitalization occurred in 102 (14%) cases and was associated with adverse fetal outcomes (OR 2.4, 95% CI 1.3–4.4). Conclusions: Our study suggests that adverse fetal outcomes are rare in pregnant women with mild COVID-19 who are monitored at home with telemedicine. However, hospitalization for COVID-19 and pregnancy-induced hypertension are associated with a higher risk of adverse fetal outcome. [ABSTRACT FROM AUTHOR]

Abstract Background There is an increasing number of meta-analyses including data from non-randomized studies for therapeutic evaluation. We aimed to systematically assess the methods used in meta-analyses including non-randomized studies evaluating therapeutic interventions. Methods For this methodological review, we searched MEDLINE via PubMed, from January 1, 2013 to December 31, 2013 for meta-analyses including at least one non-randomized study evaluating therapeutic interventions. Etiological assessments and meta-analyses with no comparison group were excluded. Two reviewers independently assessed the general characteristics and key methodological components of the systematic review process and meta-analysis methods. Results One hundred eighty eight meta-analyses were selected: 119 included both randomized controlled trials (RCTs) and non-randomized studies of interventions (NRSI) and 69 only NRSI. Half of the meta-analyses (n = 92, 49 %) evaluated non-pharmacological interventions. “Grey literature” was searched for 72 meta-analyses (38 %). An assessment of methodological quality or risk of bias was reported in 135 meta-analyses (72 %) but this assessment considered the risk of confounding bias in only 33 meta-analyses (18 %). In 130 meta-analyses (69 %), the design of each NRSI was not clearly specified. In 131 (70 %), whether crude or adjusted estimates of treatment effect for NRSI were combined was unclear or not reported. Heterogeneity across studies was assessed in 182 meta-analyses (97 %) and further explored in 157 (84 %). Reporting bias was assessed in 127 (68 %). Conclusions Some key methodological components of the systematic review process—search for grey literature, description of the type of NRSI included, assessment of risk of confounding bias and reporting of whether crude or adjusted estimates were combined—are not adequately carried out or reported in meta-analyses including NRSI.

Ensuring the appropriateness of prescriptions of oral antithrombotics (ATs, including antiplatelet and anticoagulant agents) is a crucial safety issue, particularly for patients with multiple chronic conditions. Our main objective was to assess the impact of a prescription support tool, synthesized from international guidelines on oral ATs in adult outpatients, on improving physician adherence to the guidelines for prescription of oral ATs. A web-based, open randomized controlled trial using clinical vignettes was conducted in France from November 2018 to February 2019. General practitioners and cardiologists with outpatient practice were contacted to participate in a web-based survey involving three clinical vignettes illustrating cases of adult outpatients with common neuro-cardiovascular diseases. They were asked to answer four multiple-choice questions related to the number of oral AT(s), drug class, dosage and duration of the prescription. Physicians assigned to the experimental arm had access to the prescription support tool. Physicians assigned to the control arm had no access to the tool. The primary outcome measure was the appropriate prescription of oral ATs (i.e., complied with guidelines in terms of the number, drug class, dosage and duration of prescription). An intent-to-treat analysis was performed using a logistic mixed model with a clinical vignette effect and a physician effect nested in the arm of the trial. Four hundred and forty-one general practitioners and 37 cardiologists were randomized to the experimental (n = 238) and to the control arm (n = 240), respectively. In the experimental arm, 55.0% of the prescriptions were appropriate versus 29.4% in the control arm (Odds Ratio (OR): 3.61 (2.60 to 5.02)). Access to the first prescription support tool synthesizing the use of oral ATs for outpatients significantly improved the rate of appropriate oral AT prescriptions according to the guidelines.

Cochrane reviewers are strongly encouraged to evaluate the quality of evidence for the most important outcomes by using the GRADE approach and to report these results in a Summary of Findings (SoF) table. We aimed to assess whether outcomes reported in the SoF table of Cochrane reviews could be considered patient-important outcomes (PIOs) and the quality of the available evidence for these outcomes.We performed a methodological review of Cochrane reviews published between March 2011 and September 2014. For a random sample of Cochrane reviews reporting a SoF table, we extracted all outcomes reported in this table and evaluated whether they could be considered PIOs (i.e., mortality, other clinical events, adverse events, function, pain, quality of life and therapeutic decisions). Then, we collected the quality of evidence for every outcome in these SoF tables.We included 290 reviews issued by 47 of the 53 Cochrane Review Groups. Every SoF table included a median of 5 outcomes, for a total of 1414 outcomes; 1089 (77%) could be considered PIOs. Almost all reviews (n = 278, 96%) included at least one PIO in their SoF table. The quality of evidence for the outcomes was high for 12% (n = 168), moderate for 28% (n = 402) and low or very low for 45% (n = 640). Less than one quarter of reviews (n = 63) included at least one PIO with high-quality evidence that favoured a benefit of the experimental intervention evaluated in half of them (n = 34 reviews).Many outcomes reported in the SoF table of recent Cochrane reviews can be considered PIOs. However, the quality of available evidence remains limited for these outcomes.