Substance use disorder of equimolar oxygen-nitrous oxide mixture in French sickle-cell patients: results of the PHEDRE study.

BACKGROUND: In many countries, nitrous oxide is used in a gas mixture (EMONO) for short-term analgesia. Cases of addiction, with significant misuse, have been reported in hospitalized patients. Patients suffering from sickle cell disease (SCD) could represent a high-risk population for substance use disorder (SUD) due to their significant pain crisis and repeated use of EMONO. The objective of the PHEDRE study was to assess the prevalence of SUD for EMONO in French SCD patients. RESULTS: A total of 993 patients were included. Among 339 EMONO consumers, only 38 (11%) had a SUD, with very few criteria, corresponding mainly to a mild SUD due to a use higher than expected (in quantity or duration) and relational tensions with the care teams. Almost all patients (99.7%) were looking for an analgesic effect, but 68% of patients were also looking for other effects. The independent risks factors associated with at least one SUD criterion were: the feeling of effects different from the expected therapeutic effects of EMONO, at least one hospitalization for vaso occlusive crisis in the past 12 months and the presence of a SUD for at least one other analgesic drug. CONCLUSIONS: The use of EMONO was not problematic for the majority of patients. Manifestations of SUD that led to tensions with healthcare teams should alert and lead to an evaluation, to distinguish a true addiction from a pseudoaddiction which may be linked to an insufficient analgesic treatment related to an underestimation of pain in SCD patients. TRIAL REGISTRATION: Clinical Trials, NCT02580565. Registered 16 October 2015, https://clinicaltrials.gov/.

Clinical evaluation of the BioFire Respiratory Pathogen Panel for the guidance of empirical antimicrobial therapy in critically ill patients with hospital-acquired pneumonia: A multicenter, quality improvement project.

BACKGROUND: We aimed to determine whether implementing antimicrobial stewardship based on multiplex bacterial PCR examination of respiratory fluid can enhance outcomes of critically ill patients with hospital-acquired pneumonia (HAP). METHODS: We conducted a quality improvement study in two hospitals in France. Adult patients requiring invasive mechanical ventilation with a diagnosis of HAP were included. In the pre-intervention period (August 2019 to April 2020), antimicrobial therapy followed European guidelines. In the «intervention¼ phase (June 2020 to October 2021), treatment followed a multiplex PCR-guided protocol. The primary endpoint was a composite endpoint made of mortality on day 28, clinical cure between days 7 and 10, and duration of invasive mechanical ventilation on day 28. The primary outcome was analyzed with a DOOR strategy. RESULTS: A total of 443 patients were included in 3 ICUs from 2 hospitals (220 pre-intervention; 223 intervention). No difference in the ranking of the primary composite outcome was found (DOOR: 50.3%; 95%CI, 49.9%-50.8%). The number of invasive mechanical ventilation-free days at day 28 was 10.0 [0.0; 19.0] in the baseline period and 9.0 [0.0; 20.0] days during the intervention period (p = 0.95). The time-to-efficient antimicrobial treatment was 0.43 ± 1.29 days before versus 0.55 ± 1.13 days after the intervention (p = 0.56). CONCLUSION: Implementation of Rapid Multiplex PCR to guide empirical antimicrobial therapy for critically ill patients with HAP was not associated with better outcomes. However, adherence to stewardship was low, and the study may have had limited power to detect a clinically important difference.

Giant cell arteritis associated with scalp, tongue or lip necrosis: A French multicenter case control study.

BACKGROUND: Scalp, tongue and/or lip necrosis are rare complications of GCA. OBJECTIVES: To describe characteristics and outcome of patients with giant cell arteritis (GCA) -related scalp, tongue and/or lip necrosis. METHODS: A retrospective nationwide multicenter study included 20 GCA patients with scalp, tongue, and/or lip necrosis diagnosed between 1998 and 2021 and 80 GCA control patients matched for age, sex and management period. Logistic regression analyses were conducted to identify baseline characteristics associated with scalp, tongue and/or lip necrosis. RESULTS: Compared to controls, patients with scalp, tongue and/or lip necrosis showed significantly more cranial manifestations (headache, p=0.045; scalp tenderness, p=0.006; jaw claudication, p=0.02). No differences were observed between both groups regarding the occurrence of visual symptoms or large vessel involvement. At diagnosis, GCA patients with necrosis more likely received IV methylprednisolone infusions and higher doses of oral prednisone. There were no differences regarding vascular complications during follow up. Compared to controls, survival was decreased in GCA patients with necrosis (p=0.003). In a multivariable logistic regression model, scalp tenderness [odds ratio (OR) 4.81(95 % CI: 1.57, 14.79), p = 0.006] and cognitive disorder [OR 6.42 (95 % CI: 1.01, 40.60), p=0.048] were identified as factors associated to scalp, tongue, and/or lip necrosis. CONCLUSION: Our results suggest that scalp, tongue, and/or lip necrosis is associated to higher mortality in GCA patients. Scalp tenderness and cognitive disorder were significant factors associated to this very rare complication of GCA.

Patients' preferences in therapeutic decision-making in digestive oncology: a single centre cross-sectional observational study.

Considering the preferences in Shared Decision Making (SDM) of patients with Digestive Cancer (DC) is crucial to ensure the quality of care. To date, there is limited information on preferences in SDM of patients with DC. The objectives of this study were to describe digestive cancer patients' preference for involvement in therapeutic decision-making and to identify variables associated with these preferences. An observational prospective study in a French university cancer center has been conducted. Patients completed two questionnaires to qualify and quantify their preference for involvement in therapeutic decision-making: the Control Preference Scale (CPS) and the Autonomy Preference Index (API), which is composed of the Decision Making (DM) score and the Information Seeking (IS) score. Associations between these scores and socio-demographic data, disease-related data, coping strategies (Brief-COPE), physical (QLQ-C30) and psychological (HADS) quality of life were tested. One-hundred fifteen patients returned the questionnaires. The majority of patients reported a passive (49.1%) or a collaborative (43.0%) CPS status. The mean DM score was 39.4 Variables associated with decision-making preferences were occupational status and time since diagnosis. The identification of variables associated with patients' preferences for involvement in decision-making can help make clinicians aware of patients' needs and wishes. However, it can only be determined by interviewing the patient individually.

High-flow oxygen therapy versus facemask preoxygenation in anticipated difficult airway management (PREOPTI-DAM): an open-label, single-centre, randomised controlled phase 3 trial.

Background: Difficult airway management remains a critical procedure with life-threatening adverse events. Current guidelines suggest high-flow therapy by nasal cannulae (HFNC) as a preoxygenation device in this setting. However, there is an evidence gap to support this recommendation. Methods: The PREOPTI-DAM study is an open-label, single-centre, randomised controlled phase 3 trial done at Nantes University Hospital, France. Patients were aged 18-90 years with one major or two minor criteria of anticipated difficult airway management, and requiring intubation for scheduled surgery, were eligible. Patients with body mass index >35 kg/m2 were excluded. Patients were randomly allocated (1:1) to receive 4-min preoxygenation by HFNC or facemask. Randomisation was stratified according to the intubation strategy (laryngoscopic versus fiberoptic intubation). The primary outcome was the incidence of oxygen desaturation ≤94% or of bag-mask ventilation during intubation. The primary and safety analyses included the intention to treat population. This trial is registered with ClinicalTrials.gov (NCT03604120) and EudraCT (2018-A00434-51). Findings: From September 4 2018 to March 31 2021, 186 patients were enrolled and randomly assigned. One participant withdrew consent and 185 (99.5%) were included in the primary analysis (HFNC, N = 95; Facemask, N = 90). The incidence of the primary outcome was not significantly different between the HFNC and the facemask groups, respectively 2 (2%) versus 7 (8%); adjusted difference, -5.6 [95% confidence interval (CI), -11.8 to 0.6], P = 0.10. In the HFNC group, 76 patients (80%) versus 53 (59%) in the facemask group, reported good or excellent intubation experiences; adjusted difference 20.5 [95% CI, 8.3-32.8], P = 0.016. Comparing HFNC with facemask, severe complication occurred in 22 (23%) versus 27 (30%) patients (P = 0.29), and moderate complication in 14 (15%) versus 18 (20%) patients (P = 0.35). No death or cardiac arrest occurred during the study. Interpretation: Compared with facemask, HFNC did not significantly reduce the incidence of desaturation ≤94% or bag-mask ventilation during anticipated difficult intubation but the trial was underpowered to rule out a clinically significant benefit. Patient satisfaction was improved with HFNC. Funding: Nantes University Hospital and Fisher & Paykel Healthcare.

Anxiety and depression symptoms in relatives of moderate-to-severe traumatic brain injury survivors - A multicentre cohort.

INTRODUCTION: The prevalence and risk factors of anxiety and depression symptoms in relatives of moderate to severe traumatic brain injury (TBI) survivors have not been thoroughly investigated. METHODS: Ancillary study of a multicentric prospective randomized-controlled trial in nine university hospitals in 370 moderate-to-severe TBI patients. TBI survivor-relative dyads were included in the 6th month of follow-up. Relatives responded to the Hospital Anxiety and Depression Scale (HADS). The primary endpoints were the prevalence of severe symptoms of anxiety (HADS-Anxiety ≥ 11) and depression (HADS-Depression ≥ 11) in relatives. We explored the risk factors of severe anxiety and depression symptoms. RESULTS: Relatives were predominantly women (80.7%), spouse-husband (47.7%), or parents (39%). Out of the 171 dyads included, 83 (50.6%) and 59 (34.9%) relatives displayed severe symptoms of anxiety and depression, respectively. Severe anxiety symptoms in relatives were independently associated with the patient's discharge at home (OR 2.57, 95%CI [1.04-6.37]) and the patient's higher SF-36 Mental Health domain scores (OR 1.03 95%CI [1.01-1.05]). Severe depression symptoms were independently associated with a lower SF-36 Mental Health domain score (OR = 0.98 95%CI [0.96-1.00]). No ICU organization characteristics were associated with psychological symptoms in relatives. DISCUSSION: There is a high prevalence of anxiety and depression symptoms among relatives of moderate-to-severe TBI survivors at 6 months. Anxiety and depression were inversely correlated with the patient's mental health status at 6 months. CONCLUSIONS: Long-term follow-up must provide psychological care to relatives after TBI.

Interferon gamma-1b for the prevention of hospital-acquired pneumonia in critically ill patients: a phase 2, placebo-controlled randomized clinical trial.

PURPOSE: We aimed to determine whether interferon gamma-1b prevents hospital-acquired pneumonia in mechanically ventilated patients. METHODS: In a multicenter, placebo-controlled, randomized trial conducted in 11 European hospitals, we randomly assigned critically ill adults, with one or more acute organ failures, under mechanical ventilation to receive interferon gamma-1b (100 µg every 48 h from day 1 to 9) or placebo (following the same regimen). The primary outcome was a composite of hospital-acquired pneumonia or all-cause mortality on day 28. The planned sample size was 200 with interim safety analyses after enrolling 50 and 100 patients. RESULTS: The study was discontinued after the second safety analysis for potential harm with interferon gamma-1b, and the follow-up was completed in June 2022. Among 109 randomized patients (median age, 57 (41-66) years; 37 (33.9%) women; all included in France), 108 (99%) completed the trial. Twenty-eight days after inclusion, 26 of 55 participants (47.3%) in the interferon-gamma group and 16 of 53 (30.2%) in the placebo group had hospital-acquired pneumonia or died (adjusted hazard ratio (HR) 1.76, 95% confidence interval (CI) 0.94-3.29; P = 0.08). Serious adverse events were reported in 24 of 55 participants (43.6%) in the interferon-gamma group and 17 of 54 (31.5%) in the placebo group (P = 0.19). In an exploratory analysis, we found that hospital-acquired pneumonia developed in a subgroup of patients with decreased CCL17 response to interferon-gamma treatment. CONCLUSIONS: Among mechanically ventilated patients with acute organ failure, treatment with interferon gamma-1b compared with placebo did not significantly reduce the incidence of hospital-acquired pneumonia or death on day 28. Furthermore, the trial was discontinued early due to safety concerns about interferon gamma-1b treatment.

Does Differential Item Functioning Jeopardize the Comparability of Health-Related Quality of Life Assessment Between Patients and Proxies in Patients with Moderate-to-Severe Traumatic Brain Injury?

BACKGROUND: Health-related quality of life (HRQoL) is clearly recognized as a patient-important outcome in patients with traumatic brain injury (TBI). Patient-reported outcomes are therefore often used and supposed to be directly reported by the patients without interpretation of their responses by a physician or anyone else. However, patients with TBI are often unable to self-report because of physical and/or cognitive impairments. Thus, proxy-reported measures, e.g., family members, are often used on the patient's behalf. Yet, many studies have reported that proxy and patient ratings differ and are noncomparable. However, most studies usually do not account for other potential confounding factors that may be associated with HRQoL. In addition, patients and proxies can interpret some items of the patient-reported outcomes differently. As a result, item responses may not only reflect patients' HRQoL but also the respondent's (patient or proxy) own perception of the items. This phenomenon, called differential item functioning (DIF), can lead to substantial differences between patient-reported and proxy-reported measures and compromise their comparability, leading to highly biased HRQoL estimates. Using data from the prospective multicenter continuous hyperosmolar therapy in traumatic brain-injured patients study (240 patients with HRQoL measured with the Short Form-36 (SF-36)), we assessed the comparability of patients' and proxies' reports by evaluating the extent to which items perception differs (i.e., DIF) between patients and proxies after controlling for potential confounders. METHODS: Items at risk of DIF adjusting for confounders were examined on the items of the role physical and role emotional domains of the SF-36. RESULTS: Differential item functioning was evidenced in three out of the four items of the role physical domain measuring role limitations due to physical health problems and in one out of the three items of the role emotional domain measuring role limitations due to personal or emotional problems. Overall, despite an expected similar level of role limitations between patients who were able to respond and those for whom proxies responded, proxies tend to give more pessimistic responses than patients in the case of major role limitations and more optimistic responses than patients in the case of minor limitations. CONCLUSIONS: Patients with moderate-to-severe TBI and proxies seem to have different perceptions of the items measuring role limitations due to physical or emotional problems, questioning the comparability of patient and proxy data. Therefore, aggregating proxy and patient responses may bias HRQoL estimates and alter medical decision-making based on these patient-important outcomes.

No Difference in Dislocation Rates Comparing DMC-THA for Displaced Femoral Neck Fracture and for Osteoarthritis-A Matched-Pair Analysis.

Background: We hypothesized the risk of prosthetic instability would be similar in patients treated for femoral neck fracture (FNF) comparatively to patients treated for osteoarthritis (OA) using a dual-mobility cup-total hip arthroplasty (DMC-THA). Methods: One hundred and nine patients (109 hips), with a mean age of 69.6 ± 3 years (65-75 years), underwent DMC-THA using a posterolateral approach for a FNF (study group). Patients were matched for age and sex with 109 OA patients treated by the same procedure (control). Results: Postoperatively, there were four dislocations of the large articulation in the study group, and none in the control (p = 0.12). Periprosthetic joint infection (PJI) was the most common surgical complication and was more frequent in the study group. Postoperatively, functional results were at least good in > 90% patients in both groups. At the last follow-up, patients in the study group had recovered autonomy and physical activity comparable to those of the preoperative period. Conclusion: We found no increased risk of dislocation after DMC-THA using a posterolateral approach for FNF as compared to the same procedure for OA. In this study, function and independence were restored postoperatively in the vast majority of patients. DMC-THA appears as a viable therapeutic option in autonomous patients with a displaced FNF.

Safety of High-Frequency Jet Ventilation During Image-Guided Thermal Ablation Procedures.

RATIONALE AND OBJECTIVE: Percutaneous thermal ablative technique is a common radiological procedure for malignant lesions treatment. Controlled assisted ventilation during general anesthesia is the usual mode of ventilation, but high-frequency jet ventilation (HFJV) can be a helpful alternative for the operator. The objective was to evaluate the safety of HFJV during thermal ablation procedures. MATERIALS AND METHODS: This monocentric prospective analysis included adult patients undergoing percutaneous thermal ablation procedures for abdominal tumor performed under HFJV. Procedures with a transpulmonary path were excluded. The primary outcome was the incidence of respiratory complications. Secondary outcomes included gas exchange modifications (hypercapnia, hypoxemia, pulmonary atelectasis) and the incidence of barotrauma. RESULTS: Sixty patients were included during the study period. The mean duration time was 88 min. All procedures went according to the protocol and there was no respiratory complication. There was no barotrauma event. Three patients had an exhaled capnia above 45 mmHg at the end of the procedure which normalized within 10 min of conventional ventilation. CONCLUSION: HFJV during thermal ablation procedures is safe regarding gas exchange and barotrauma. This technique could be an interesting alternative to conventional ventilation during image-guided thermal ablation procedures. Clinical Trials database This study was registered in Clinical Trials database (NCT04209608).

Effect of Remifentanil vs Neuromuscular Blockers During Rapid Sequence Intubation on Successful Intubation Without Major Complications Among Patients at Risk of Aspiration: A Randomized Clinical Trial.

Importance: It is uncertain whether a rapid-onset opioid is noninferior to a rapid-onset neuromuscular blocker during rapid sequence intubation when used in conjunction with a hypnotic agent. Objective: To determine whether remifentanil is noninferior to rapid-onset neuromuscular blockers for rapid sequence intubation. Design, Setting, and Participants: Multicenter, randomized, open-label, noninferiority trial among 1150 adults at risk of aspiration (fasting for <6 hours, bowel occlusion, recent trauma, or severe gastroesophageal reflux) who underwent tracheal intubation in the operating room at 15 hospitals in France from October 2019 to April 2021. Follow-up was completed on May 15, 2021. Interventions: Patients were randomized to receive neuromuscular blockers (1 mg/kg of succinylcholine or rocuronium; n = 575) or remifentanil (3 to 4 µg/kg; n = 575) immediately after injection of a hypnotic. Main Outcomes and Measures: The primary outcome was assessed in all randomized patients (as-randomized population) and in all eligible patients who received assigned treatment (per-protocol population). The primary outcome was successful tracheal intubation on the first attempt without major complications, defined as lung aspiration of digestive content, oxygen desaturation, major hemodynamic instability, sustained arrhythmia, cardiac arrest, and severe anaphylactic reaction. The prespecified noninferiority margin was 7.0%. Results: Among 1150 randomized patients (mean age, 50.7 [SD, 17.4] years; 573 [50%] women), 1130 (98.3%) completed the trial. In the as-randomized population, tracheal intubation on the first attempt without major complications occurred in 374 of 575 patients (66.1%) in the remifentanil group and 408 of 575 (71.6%) in the neuromuscular blocker group (between-group difference adjusted for randomization strata and center, -6.1%; 95% CI, -11.6% to -0.5%; P = .37 for noninferiority), demonstrating inferiority. In the per-protocol population, 374 of 565 patients (66.2%) in the remifentanil group and 403 of 565 (71.3%) in the neuromuscular blocker group had successful intubation without major complications (adjusted difference, -5.7%; 2-sided 95% CI, -11.3% to -0.1%; P = .32 for noninferiority). An adverse event of hemodynamic instability was recorded in 19 of 575 patients (3.3%) with remifentanil and 3 of 575 (0.5%) with neuromuscular blockers (adjusted difference, 2.8%; 95% CI, 1.2%-4.4%). Conclusions and Relevance: Among adults at risk of aspiration during rapid sequence intubation in the operating room, remifentanil, compared with neuromuscular blockers, did not meet the criterion for noninferiority with regard to successful intubation on first attempt without major complications. Although remifentanil was statistically inferior to neuromuscular blockers, the wide confidence interval around the effect estimate remains compatible with noninferiority and limits conclusions about the clinical relevance of the difference. Trial Registration: ClinicalTrials.gov Identifier: NCT03960801.

Transfusion-Related Renal Dysfunction After Cardiac Surgery: The Role of Myeloid-Related Protein_14 in Neutrophil-Mediated Tubular Damage.

Transfusion is a specific cause of acute kidney injury (AKI) after cardiac surgery. Whether there is an association between the composition of blood products and the onset of AKI is unknown. The present study suggests that the transfusion of packed red blood cells containing a high amount of myeloid-related protein 14 (MRP_14) could increase the incidence of AKI after cardiac surgery. In a mouse model, MRP_14 increased the influx of neutrophils in the kidney after ischemia-reperfusion and their ability to damage tubular cells. Higher concentrations of MRP_14 were found in packed red blood cells from female donors or prepared by whole blood filtration.

Parkinson's disease and iatrogenic impulsive-compulsive behaviors: A case/non-case study to build a complete model of individual vulnerability.

Background and aims: Parkinson's disease (PD) is one of the most prevalent neurodegenerative diseases. First-line medications consist of drugs that act by counteracting dopamine deficiency in the basal ganglia. Unfortunately, iatrogenic impulsive-compulsive behaviors (ICBs) can occur in up to 20% of PD patients over the course of their illness. ICBs must be considered multifactorial disorders that reflect the interactions of the medication with an individual's vulnerability and the underlying neurobiology of PD. We aimed to explore the predictive genetic, psychopathological and neurological factors involved in the development of ICBs in PD patients by building a complete model of individual vulnerability. Methods: The PARKADD study was a case/non-case study. A total of 225 patients were enrolled ("ICB" group, N = 75; "no ICB" group, N = 150), and 163 agreed to provide saliva samples for genetic analysis. Sociodemographic, neurological and psychiatric characteristics were assessed, and genotyping for the characterization of polymorphisms related to dopaminergic and opioid systems was performed. Results: Factors associated with "ICBs" were younger age of PD onset, personal history of ICB prior to PD onset and higher scores on the urgency and sensation seeking facets of impulsivity. No gene variant was significantly associated, but the association with the opioid receptor mu 1 (OPRM1) rs1799971 polymorphism was close to significance. Discussion and conclusions: The influence of gene-environment interactions probably exists, and additional studies are needed to decipher the possible role of the opioid system in the development of ICBs in PD patients.

Impact of targeted hypothermia in expanded-criteria organ donors on recipient kidney-graft function: study protocol for a multicentre randomised controlled trial (HYPOREME).

INTRODUCTION: Expanded-criteria donors (ECDs) are used to reduce the shortage of kidneys for transplantation. However, kidneys from ECDs are associated with an increased risk of delayed graft function (DGF), a risk factor for allograft loss and mortality. HYPOREME will be a multicentre randomised controlled trial (RCT) comparing targeted hypothermia to normothermia in ECDs, in a country where the use of machine perfusion for organ storage is the standard of care. We hypothesise that hypothermia will decrease the incidence of DGF. METHODS AND ANALYSIS: HYPOREME is a multicentre RCT comparing the effect on kidney function in recipients of targeted hypothermia (34°C-35°C) and normothermia (36.5°C-37.5°C) in the ECDs. The temperature intervention starts from randomisation and is maintained until aortic clamping in the operating room. We aim to enrol 289 ECDs in order to analyse the kidney function of 516 recipients in the 53 participating centres. The primary outcome is the occurrence of DGF in kidney recipients, defined as a requirement for renal replacement therapy within 7 days after transplantation (not counting a single session for hyperkalemia during the first 24 hours). Secondary outcomes include the proportion of patients with individual organs transplanted in each group; the number of organs transplanted from each ECD and the vital status and kidney function of the recipients 7 days, 28 days, 3 months and 1 year after transplantation. An interim analysis is planned after the enrolment of 258 kidney recipients. ETHICS AND DISSEMINATION: The trial was approved by the ethics committee of the French Intensive Care Society (CE-SRLF-16-07) on 26 April 2016 and by the competent French authorities on 20 April 2016 (Comité de Protection des Personnes-TOURS-Région Centre-Ouest 1, registration #2016-S3). Findings will be published in peer-reviewed journals and presented during national and international scientific meetings. TRIAL REGISTRATION NUMBER: NCT03098706.

Did the pattern of use of zolpidem change since the enforcement of a new prescription rule? A latent class analysis using the French health insurance database.

BACKGROUND: In recent years, zolpidem has been the subject of numerous reports of misuse, abuse and dependence. In view of these risks, the French drug agency decreed the implementation of secure prescription pads in April, 2017. The objective of this study was to characterize the impact of this regulatory change on the patterns of zolpidem use. RESEARCH DESIGN AND METHODS: We included patients with at least one reimbursement for zolpidem before and/or after the regulatory change using a sample of the French health insurance database. For each period, we identified profiles of users using a latent class analysis (LCA). RESULTS: In total, 15,550 zolpidem users were identified before the measure and 8,301 after the measure. We identified the same three profiles of zolpidem users before and after the measure: non-problematic users (the most prevalent), users whose drug prescriptions suggest psychiatric disorder and potential problematic users. The profile of potential problematic users was similar after the regulatory change but represented a lower absolute number of patients. CONCLUSION: In conclusion, the regulatory change had a positive impact on the patterns of zolpidem use, but the impact should be reevaluated, because withdrawal can take a long time, especially in long-term users. TRIAL REGISTRATION: The study was registered at www.clinicaltrials.gov under the reference number NCT03584542.

Methodological quality of multivariate prognostic models for intracranial haemorrhages in intensive care units: a systematic review.

OBJECTIVES: Patients with severe spontaneous intracranial haemorrhages, managed in intensive care units, face ethical issues regarding the difficulty of anticipating their recovery. Prognostic tools help clinicians in counselling patients and relatives and guide therapeutic decisions. We aimed to methodologically assess prognostic tools for functional outcomes in severe spontaneous intracranial haemorrhages. DATA SOURCES: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations, we conducted a systematic review querying Medline, Embase, Web of Science, and the Cochrane in January 2020. STUDY SELECTION: We included development or validation of multivariate prognostic models for severe intracerebral or subarachnoid haemorrhage. DATA EXTRACTION: We evaluated the articles following the CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies and Transparent Reporting of multivariable prediction model for Individual Prognosis Or Diagnosis statements to assess the tools' methodological reporting. RESULTS: Of the 6149 references retrieved, we identified 85 articles eligible. We discarded 43 articles due to the absence of prognostic performance or predictor selection. Among the 42 articles included, 22 did not validate models, 6 developed and validated models and 14 only externally validated models. When adding 11 articles comparing developed models to existing ones, 25 articles externally validated models. We identified methodological pitfalls, notably the lack of adequate validations or insufficient performance levels. We finally retained three scores predicting mortality and unfavourable outcomes: the IntraCerebral Haemorrhages (ICH) score and the max-ICH score for intracerebral haemorrhages, the SubArachnoid Haemorrhage International Trialists score for subarachnoid haemorrhages. CONCLUSIONS: Although prognostic studies on intracranial haemorrhages abound in the literature, they lack methodological robustness or show incomplete reporting. Rather than developing new scores, future authors should focus on externally validating and updating existing scores with large and recent cohorts.

Effect of dexamethasone on complications or all cause mortality after major non-cardiac surgery: multicentre, double blind, randomised controlled trial.

OBJECTIVE: To assess the effect of dexamethasone on complications or all cause mortality after major non-cardiac surgery. DESIGN: Phase III, randomised, double blind, placebo controlled trial. SETTING: 34 centres in France, December 2017 to March 2019. PARTICIPANTS: 1222 adults (>50 years) requiring major non-cardiac surgery with an expected duration of more than 90 minutes. The anticipated time frame for recruitment was 24 months. INTERVENTIONS: Participants were randomised to receive either dexamethasone (0.2 mg/kg immediately after the surgical procedure, and on day 1) or placebo. Randomisation was stratified on the two prespecified criteria of cancer and thoracic procedure. MAIN OUTCOMES MEASURES: The primary outcome was a composite of postoperative complications or all cause mortality within 14 days after surgery, assessed in the modified intention-to-treat population (at least one treatment administered). RESULTS: Of the 1222 participants who underwent randomisation, 1184 (96.9%) were included in the modified intention-to-treat population. 14 days after surgery, 101 of 595 participants (17.0%) in the dexamethasone group and 117 of 589 (19.9%) in the placebo group had complications or died (adjusted odds ratio 0.81, 95% confidence interval 0.60 to 1.08; P=0.15). In the stratum of participants who underwent non-thoracic surgery (n=1038), the primary outcome occurred in 69 of 520 participants (13.3%) in the dexamethasone group and 93 of 518 (18%) in the placebo group (adjusted odds ratio 0.70, 0.50 to 0.99). Adverse events were reported in 288 of 613 participants (47.0%) in the dexamethasone group and 296 of 609 (48.6%) in the placebo group (P=0.46). CONCLUSIONS: Dexamethasone was not found to significantly reduce the incidence of complications and death in patients 14 days after major non-cardiac surgery. The 95% confidence interval for the main result was, however, wide and suggests the possibility of important clinical effectiveness. TRIAL REGISTRATION: ClinicalTrials.gov NCT03218553.

Effect of Continuous Infusion of Hypertonic Saline vs Standard Care on 6-Month Neurological Outcomes in Patients With Traumatic Brain Injury: The COBI Randomized Clinical Trial.

Importance: Fluid therapy is an important component of care for patients with traumatic brain injury, but whether it modulates clinical outcomes remains unclear. Objective: To determine whether continuous infusion of hypertonic saline solution improves neurological outcome at 6 months in patients with traumatic brain injury. Design, Setting, and Participants: Multicenter randomized clinical trial conducted in 9 intensive care units in France, including 370 patients with moderate to severe traumatic brain injury who were recruited from October 2017 to August 2019. Follow-up was completed in February 2020. Interventions: Adult patients with moderate to severe traumatic brain injury were randomly assigned to receive continuous infusion of 20% hypertonic saline solution plus standard care (n = 185) or standard care alone (controls; n = 185). The 20% hypertonic saline solution was administered for 48 hours or longer if patients remained at risk of intracranial hypertension. Main Outcomes and Measures: The primary outcome was Extended Glasgow Outcome Scale (GOS-E) score (range, 1-8, with lower scores indicating worse functional outcome) at 6 months, obtained centrally by blinded assessors and analyzed with ordinal logistic regression adjusted for prespecified prognostic factors (with a common odds ratio [OR] >1.0 favoring intervention). There were 12 secondary outcomes measured at multiple time points, including development of intracranial hypertension and 6-month mortality. Results: Among 370 patients who were randomized (median age, 44 [interquartile range, 27-59] years; 77 [20.2%] women), 359 (97%) completed the trial. The adjusted common OR for the GOS-E score at 6 months was 1.02 (95% CI, 0.71-1.47; P = .92). Of the 12 secondary outcomes, 10 were not significantly different. Intracranial hypertension developed in 62 (33.7%) patients in the intervention group and 66 (36.3%) patients in the control group (absolute difference, -2.6% [95% CI, -12.3% to 7.2%]; OR, 0.80 [95% CI, 0.51-1.26]). There was no significant difference in 6-month mortality (29 [15.9%] in the intervention group vs 37 [20.8%] in the control group; absolute difference, -4.9% [95% CI, -12.8% to 3.1%]; hazard ratio, 0.79 [95% CI, 0.48-1.28]). Conclusions and Relevance: Among patients with moderate to severe traumatic brain injury, treatment with continuous infusion of 20% hypertonic saline compared with standard care did not result in a significantly better neurological status at 6 months. However, confidence intervals for the findings were wide, and the study may have had limited power to detect a clinically important difference. Trial Registration: ClinicalTrials.gov Identifier: NCT03143751.

Assessment of remifentanil for rapid sequence induction and intubation in patients at risk of pulmonary aspiration of gastric contents compared to rapid-onset paralytic agents: study protocol for a non-inferiority simple blind randomized controlled trial (the REMICRUSH study).

BACKGROUND: Rapid-onset paralytic agents are recommended to achieve muscle relaxation and facilitate tracheal intubation during rapid sequence induction in patients at risk of pulmonary aspiration of gastric contents. However, opioids are frequently used in this setting. The study's objective is to demonstrate the non-inferiority of remifentanil compared to rapid-onset paralytic agents, in association with an hypnotic drug, for tracheal intubation in patients undergoing  procedure under general anesthesia and at risk of pulmonary aspiration of gastric contents. METHODS: The REMICRUSH (Remifentanil for Rapid Sequence Induction of Anaesthesia) study is a multicenter, single-blinded, non-inferiority randomized controlled trial comparing remifentanil (3 to 4 µg/kg) with rapid-onset paralytic agents (succinylcholine or rocuronium 1 mg/kg) for rapid sequence induction in 1150 adult surgical patients requiring tracheal intubation during general anesthesia. Enrolment started in October 2019 in 15 French anesthesia units. The expected date of the final follow-up is October 2021. The primary outcome is the proportion of successful tracheal intubation without major complications. A non-inferiority margin of 7% was chosen. Analyses of the intent-to-treat and per-protocol populations are planned. DISCUSSION: The REMICRUSH trial protocol has been approved by the ethics committee of The Comité de Protection des Personnes Sud-Ouest et Outre-Mer II and will be carried out according to the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines. The results of this study will be disseminated through presentations at scientific conferences and publications in peer-reviewed journals. The REMICRUSH trial is the first randomized controlled trial powered to investigate whether remifentanil with hypnotics is non-inferior to rapid-onset paralytic agents with hypnotic in rapid sequence induction of anesthesia for full stomach patients considering successful tracheal intubation without major complication. TRIAL REGISTRATION: ClinicalTrials.gov NCT03960801. Registered on May 23, 2019.