On variance estimation of the inverse probability-of-treatment weighting estimator: A tutorial for different types of propensity score weights.

Propensity score methods, such as inverse probability-of-treatment weighting (IPTW), have been increasingly used for covariate balancing in both observational studies and randomized trials, allowing the control of both systematic and chance imbalances. Approaches using IPTW are based on two steps: (i) estimation of the individual propensity scores (PS), and (ii) estimation of the treatment effect by applying PS weights. Thus, a variance estimator that accounts for both steps is crucial for correct inference. Using a variance estimator which ignores the first step leads to overestimated variance when the estimand is the average treatment effect (ATE), and to under or overestimated estimates when targeting the average treatment effect on the treated (ATT). In this article, we emphasize the importance of using an IPTW variance estimator that correctly considers the uncertainty in PS estimation. We present a comprehensive tutorial to obtain unbiased variance estimates, by proposing and applying a unifying formula for different types of PS weights (ATE, ATT, matching and overlap weights). This can be derived either via the linearization approach or M-estimation. Extensive R code is provided along with the corresponding large-sample theory. We perform simulation studies to illustrate the behavior of the estimators under different treatment and outcome prevalences and demonstrate appropriate behavior of the analytical variance estimator. We also use a reproducible analysis of observational lung cancer data as an illustrative example, estimating the effect of receiving a PET-CT scan on the receipt of surgery.

FX06 to rescue SARS-CoV-2-induced acute respiratory distress syndrome: a randomized clinical trial.

BACKGROUND: Vascular leakage is a major feature of acute respiratory distress syndrome (ARDS). We aimed to evaluate the efficacy of FX06, a drug under development that stabilizes interendothelial cell junctions, at reducing vascular leakage during SARS-CoV-2-induced ARDS. METHODS: This multicenter, double-blinded, randomized trial included adults with COVID-19-associated ARDS who had received invasive mechanical ventilation for < 5 days and were randomized to receive either intravenous FX06 (400 mg/d, for 5 days) or its vehicle as placebo. The primary endpoint was the lowering-from day 1 to day 7-of the transpulmonary thermodilution-derived extravascular lung-water index (EVLWi). RESULTS: Twenty-five patients were randomized to receive FX06 and 24 the placebo. Although EVLWi was elevated at baseline (median [IQR] 15.6 mL/kg [13.5; 18.5]), its declines from day 1 to day 7 were comparable for FX06 recipients and controls (respectively, - 1.9 [- 3.3; - 0.5] vs. - 0.8 [- 5.5; - 1.1] mL/kg; estimated effect - 0.8 [- 3.1; + 2.4], p = 0.51). Cardiac indexes, pulmonary vascular permeability indexes, and fluid balances were also comparable, as were PaO2/FiO2 ratios and durations of mechanical ventilation. Adverse event rates were similar for the 2 groups, although more FX06 recipients developed ventilator-associated pneumonia (16/25 (64%) vs. 6/24 (24%), p = 0.009). CONCLUSIONS: In this unique-dosing-regimen study, FX06 did not lower SARS-CoV-2-induced pulmonary vascular leakage. Future investigations will need to evaluate its efficacy at earlier times during the disease or using other regimens. Trial registration NCT04618042. Registered 5 November 2020.

Ability to predict rheumatoid arthritis relapse after tumour necrosis factor inhibitor tapering by the Multi-Biomarker Disease Activity Score: a post-hoc analysis of the STRASS trial.

OBJECTIVES: The aim was to evaluate the ability of baseline multi-biomarker disease activity (MBDA) score to discriminate between patients with rheumatoid arthritis (RA) in remission who are at high risk versus low risk of relapse after TNF-inhibitor (TNFi) tapering. METHODS: The study is a post-hoc analysis of patients who completed the Spacing of TNFi injections in Rheumatoid ArthritiS Study (STRASS), a multicentre 18-month equivalence randomised controlled study, of TNFi tapering in RA patients in remission, and had baseline serum samples available for MBDA testing. The primary endpoint of this study was the ability of the baseline MBDA score to predict relapse at any time during the 18 months following initiation of TNFi tapering. Secondary endpoints were the ability of baseline MBDA score to predict TNFi discontinuation at Month 18, and structural damage progression on x-rays assessed by the change in total van der Heijde-modified Sharp score from baseline to month 18. RESULTS: 64 and 73 patients were included in the spacing (S)-arm and maintenance (M)-arm, respectively. In the M-arm, the mean MBDA score at baseline was higher among patients who relapsed during the 18-month follow-up than those who did not relapse: 32.5 compared to 27.2 (p=0.053) whereas no difference in the MBDA score was observed in the S-arm between patients who relapsed or not 27 compared to 26.2 (p=0.57) 13 patients (21.3%) of the S-arm were able to discontinue TNFi, for which the predictive value of the MBDA score was low (AUC=0.560). Radiographic progression in both arms, although low (n=9) was not correlated with the MBDA score at baseline with a poor discriminative value in both arms (AUC=0.558). CONCLUSIONS: In our study MBDA score in baseline was not predictive of relapse, discontinuation of TNFi in patients with long-standing RA patients tapering TNFi.

Levosimendan in patients undergoing extracorporeal membrane oxygenation after cardiac surgery: an emulated target trial using observational data.

BACKGROUND: Retrospective cohorts have suggested that levosimendan may facilitate the weaning of veno-arterial extracorporeal membrane oxygenation (VA-ECMO). We therefore studied this clinical question by emulating a randomized trial with observational data. METHODS: All patients with refractory postcardiotomy cardiogenic shock and assisted with VA-ECMO, admitted to a surgical intensive care unit at La Pitié-Salpêtrière Hospital between 2016 and 2019, were eligible. To avoid immortal-time bias, we emulated a target trial sequentially comparing levosimendan administration versus no levosimendan administration in patients treated with VA-ECMO. The primary outcome was time to successful ECMO weaning. The secondary outcomes were 30-day and 1-year mortality. We performed a multivariable analysis to adjust for confounding at baseline. RESULTS: Two hundred and thirty-nine patients were included in the study allowing building a nested trials cohort of 1434 copies of patients. No association of levosimendan treatment and VA-ECMO weaning was found (HR = 0.91, [0.57; 1.45], p = 0.659 in multivariable analysis), or 30-day mortality (OR = 1.03, [0.52; 2.03], p = 0.940) and 1-year mortality (OR = 1.00, [0.53; 1.89], p = 0.999). CONCLUSIONS: Using the emulated target trial framework, this study did not find any association of levosimendan treatment and ECMO weaning success after postcardiotomy cardiogenic shock. However, the population of interest remains heterogeneous and subgroups might benefit from levosimendan.

Surgery for glioblastomas in the elderly: an Association des Neuro-oncologues d'Expression Française (ANOCEF) trial.

OBJECTIVE: The role of surgery in the treatment of malignant gliomas in the elderly is not settled. The authors conducted a randomized trial that compared tumor resection with biopsy only-both followed by standard therapy-in such patients. METHODS: Patients ≥ 70 years of age with a Karnofsky Performance Scale (KPS) score ≥ 50 and presenting with a radiological suspicion of operable glioblastoma (GBM) were randomly assigned between tumor resection and biopsy groups. Subsequently, they underwent standard radiotherapy during the first years of the trial (2008-2017), with the addition of adjunct therapy with temozolomide when this regimen became standard (2017-2019). The primary endpoint was survival, and secondary endpoints were progression-free survival (PFS), cognitive status (Mini-Mental State Examination), autonomy (KPS), quality of life (European Organisation for Research and Treatment of Cancer [EORTC] QLQ-C30 and QLQ-BN20), and perioperative morbidity and mortality. RESULTS: Between 2008 and 2019, 107 patients from 9 centers were enrolled in the study; 101 were evaluable for analysis because a GBM was histologically confirmed (50 in the surgery arm and 51 in the biopsy arm). There was no statistically significant difference in median survival between the surgery (9.37 months) and the biopsy (8.96 months, p = 0.36) arms (adjusted HR 0.79, 95% CI 0.52-1.21, p = 0.28). However, the surgery group had an increased PFS (5.06 vs 4.02 months; p = 0.034) (adjusted HR 0.50, 95% CI 0.32-0.78, p = 0.002). Less deterioration of quality of life and KPS score evolution than in the biopsy group was observed. Surgery was not associated with increased mortality or morbidity. CONCLUSIONS: This study suggests that debulking surgery is safe, and-compared to biopsy-is associated with a less severe deterioration of quality of life and autonomy, as well as a significant although modest improvement of PFS in elderly patients suffering from newly diagnosed malignant glioma. Although resection does not provide a significant survival benefit in the elderly, the authors believe that the risk/benefit analysis favors an attempt at optimal tumor resection in this population, provided there is careful preoperative geriatric evaluation. Clinical trial registration no.: NCT02892708 (ClinicalTrials.gov).

Cumulative incidence of SARS-CoV-2 infection and associated risk factors among frontline health care workers in Paris: the SEROCOV cohort study.

With the COVID-19 pandemic, documenting whether health care workers (HCWs) are at increased risk of SARS-CoV-2 contamination and identifying risk factors is of major concern. In this multicenter prospective cohort study, HCWs from frontline departments were included in March and April 2020 and followed for 3 months. SARS-CoV-2 serology was performed at month 0 (M0), M1, and M3 and RT-PCR in case of symptoms. The primary outcome was laboratory-confirmed SARS-CoV-2 infection at M3. Risk factors of laboratory-confirmed SARS-CoV-2 infection at M3 were identified by multivariate logistic regression. Among 1062 HCWs (median [interquartile range] age, 33 [28-42] years; 758 [71.4%] women; 321 [30.2%] physicians), the cumulative incidence of SARS-CoV-2 infection at M3 was 14.6% (95% confidence interval [CI] [12.5; 16.9]). Risk factors were the working department specialty, with increased risk for intensive care units (odds ratio 1.80, 95% CI [0.38; 8.58]), emergency departments (3.91 [0.83; 18.43]) and infectious diseases departments (4.22 [0.92; 18.28]); current smoking was associated with reduced risk (0.36 [0.21; 0.63]). Age, sex, professional category, number of years of experience in the job or department, and public transportation use were not significantly associated with laboratory-confirmed SARS-CoV-2 infection at M3. The rate of SARS-CoV-2 infection in frontline HCWs was 14.6% at the end of the first COVID-19 wave in Paris and occurred mainly early. The study argues for an origin of professional in addition to private life contamination and therefore including HCWs in the first-line vaccination target population. It also highlights that smokers were at lower risk.Trial registration The study has been registered on ClinicalTrials.gov: NCT04304690 first registered on 11/03/2020.

Impact of Anti-tumour Necrosis Factor Agents on the Risk of Colorectal Cancer in Patients with Ulcerative Colitis: Nationwide French Cohort Study.

BACKGROUND AND AIMS: Patients with ulcerative colitis [UC] are at increased risk of colorectal cancer. Anti-tumour necrosis factor agents [anti-TNF] aim to reduce chronic colonic inflammation and may lower the risk of colorectal cancer [CRC], but the impact of anti-TNF exposure has not yet been assessed in population-based cohort studies. The aim of this nationwide study was to assess the risk of CRC in patients with UC exposed to anti-TNF. METHODS: Based on the French health insurance database, patients aged 18 years or older with a diagnosis of UC, previously exposed to or initiating immunosuppressive treatment, were followed from January 1, 2009, until December 31, 2018. The risk of CRC associated with anti-TNF exposure was assessed using marginal structural Cox proportional hazard models adjusting for baseline and time-varying comorbidities including primary sclerosing cholangitis, UC disease activity, colonoscopic surveillance, and other medications. RESULTS: Among 32 403 patients with UC, 15 542 [48.0%] were exposed to anti-TNF. During a median follow-up of 6.1 years [198 249 person-years], 246 incident CRC occurred (incidence rate per 1000 person-years, 1.24; 95% confidence intrval [CI], 1.10-1.41). Whereas the risk of CRC associated with anti-TNF exposure was not decreased in the overall group of patients with UC (hazard ratio [HR], 0.85; 95% CI, 0.58-1.26), anti-TNF exposure was associated with a decreased risk of CRC in patients with long-standing colitis [disease duration ≥10 years] [HR, 0.41; 95% CI, 0.20-0.86]. CONCLUSIONS: In a nationwide cohort of patients with UC, anti-TNF exposure was associated with a decreased risk of CRC in patients with long-standing colitis.

Circulating Receptor Activator of Nuclear Factor kB Ligand and triglycerides are associated with progression of lower limb arterial calcification in type 2 diabetes: a prospective, observational cohort study.

BACKGROUND: Lower limb arterial calcification is a frequent, underestimated but serious complication of diabetes. The DIACART study is a prospective cohort study designed to evaluate the determinants of the progression of lower limb arterial calcification in 198 patients with type 2 diabetes. METHODS: Lower limb arterial calcification scores were determined by computed tomography at baseline and after a mean follow up of 31.20 ± 3.86 months. Serum RANKL (Receptor Activator of Nuclear factor kB Ligand) and bone remodeling, inflammatory and metabolic parameters were measured at baseline. The predictive effect of these markers on calcification progression was analyzed by a multivariate linear regression model. RESULTS: At baseline, mean ± SD and median lower limb arterial calcification scores were, 2364 ± 5613 and 527 respectively and at the end of the study, 3739 ± 6886 and 1355 respectively. Using multivariate analysis, the progression of lower limb arterial log calcification score was found to be associated with (ß coefficient [slope], 95% CI, p-value) baseline log(calcification score) (1.02, 1.00-1.04, p < 0.001), triglycerides (0.11, 0.03-0.20, p = 0.007), log(RANKL) (0.07, 0.02-0.11, p = 0.016), previous ischemic cardiomyopathy (0.36, 0.15-0.57, p = 0.001), statin use (0.39, 0.06-0.72, p = 0.023) and duration of follow up (0.04, 0.01-0.06, p = 0.004). CONCLUSION: In patients with type 2 diabetes, lower limb arterial calcification is frequent and can progress rapidly. Circulating RANKL and triglycerides are independently associated with this progression. These results open new therapeutic perspectives in peripheral diabetic calcifying arteriopathy. Trial registration NCT02431234.

Attributable Mortality of Hip Fracture in Older Patients: A Retrospective Observational Study.

Hip fracture (HF) in older patients is associated with a high six-month mortality rate. Several clinical conditions may affect outcome, including baseline characteristics, co-existing acute illnesses, perioperative factors, and postoperative complications. Our primary objective was to estimate the respective effect of these four domains on six-month mortality after HF. A retrospective observational study using a monocentric cohort of older patients was conducted. All patients ≥ 70 years old admitted to the emergency department for HF and hospitalized in our perioperative geriatric care unit from June 2009 to September 2018 were included. Among 1015 included patients, five (0.5%) were lost to follow-up, and 1010 were retained in the final analysis (mean age 86 ± 6 years). The six-month mortality rate was 14.8%. The six-month attributable mortality estimates were as follows: baseline characteristics (including age, gender, comorbidities, autonomy, type of fracture): 62.4%; co-existing acute illnesses (including acute events present before surgery that could result from the fracture or cause it): 0% (not significantly associated with six-month mortality); perioperative factors (including blood transfusion and delayed surgery): 12.3%; severe postoperative complications: 11.9%. Baseline characteristics explained less than two-thirds of the six-month mortality after HF. Optimizing patients care by improving management of perioperative factors and thus decreasing postoperative complications, could reduce by a maximum of one quarter of the six-month mortality rate after HF.

Risk Factors for Developing Severe Acute Kidney Injury in Adult Patients With Refractory Postcardiotomy Cardiogenic Shock Receiving Venoarterial Extracorporeal Membrane Oxygenation.

OBJECTIVES: Postcardiotomy cardiogenic shock occurs in 2-6% of patients undergoing cardiac surgery, and 1% of cardiac surgery patients will require mechanical circulatory support using venoarterial extracorporeal membrane oxygenation. Acute kidney injury is a frequent complication in this population and negatively impacts the survival. We aimed to determine whether the timing of extracorporeal membrane oxygenation implantation influences the renal prognosis of these patients. DESIGN: Retrospective observational cohort study between January 2013 and December 2016. SETTING: An 18-bed surgical ICU in a university hospital. PATIENTS: A total of 4,796 consecutive adult patients who underwent cardiac surgery were included in the study, and 347 (7.2%) were assisted with venoarterial extracorporeal membrane oxygenation for refractory postcardiotomy cardiogenic shock. The patients who died during the first 48 hours after venoarterial extracorporeal membrane oxygenation implantation were excluded. The complete-case analysis included 257 patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the occurrence, within 10 days following the venoarterial extracorporeal membrane oxygenation implantation, of a stage 3 acute kidney injury defined by the Kidney Disease: Improving Global Outcomes group. One hundred sixty-nine patients (65.7%) presented with a Kidney Disease: Improving Global Outcomes stage 3 acute kidney injury; 14 patients (5.4%) died before the end of the follow-up period, without developing the primary outcome. Ninety-two percent of patients with Kidney Disease: Improving Global Outcomes 3 acute kidney injury received renal replacement therapy, for a median duration of 7 days (3-16 d). Late implantation of venoarterial extracorporeal membrane oxygenation was independently associated with an increased risk of Kidney Disease: Improving Global Outcomes stage 3 acute kidney injury (odds ratio, 2.81 [95% CI, 1.31-6.07]; p = 0.008). The other factors associated with Kidney Disease: Improving Global Outcomes stage 3 acute kidney injury were preoperative left ventricular ejection fraction (odds ratio, 1.03 [95% CI, 1.01-1.05]; p = 0.007), intraoperative plasma transfusion (odds ratio, 1.13 [95% CI, 1.02-1.26]; p = 0.022), increased bilirubinemia level (odds ratio, 1.013 [95% CI, 1.001-1.026]; p = 0.032), and increased creatinine levels (odds ratio, 1.012 [95% CI, 1.006-1.018]; p < 0.001) on the day of implantation. CONCLUSIONS: Significant kidney dysfunction is particularly frequent in patients with refractory postcardiotomy cardiogenic shock assisted with venoarterial extracorporeal membrane oxygenation. Early implantation of extracorporeal membrane oxygenation may help prevent acute kidney injury.

Perioperative management of oral anticoagulated patients undergoing an oral, implant, or periodontal procedure: a survey of practices of members of two dental scientific societies, the PRADICO study.

OBJECTIVES: Studies on the perioperative management of patients on direct oral anticoagulants (DOACs) receiving oral invasive procedures are sparse. Moreover, the recommendations of the scientific societies on DOACs are discordant, and the practices are highly variable. We conducted a survey of general and specialized dentists in France to compare their practices concerning the management of patients receiving vitamin K antagonists (VKAs) and DOACs. MATERIALS AND METHODS: Members of two dental surgical societies were invited to participate in the survey. One hundred forty-one practitioners answered an online questionnaire focusing on the periprocedural management of oral anticoagulated patients (participation rate, 17.8%). RESULTS: Practitioners at hospitals or mixed practices and specialists treated significantly more anticoagulated patients and more frequently performed procedures with high hemorrhagic risk than practitioners with private practice and general dentists. Greater than 90% of practitioners did not modify the treatment for patients on VKAs and controlled the International Normalized Ratio (INR) preoperatively. Regarding DOACs, 62.9% of practitioners did not change the treatment, 70.8% did not prescribe any biological tests, and 13.9% prescribed an INR. Practitioners at hospitals and mixed practices and specialists had better training and knowledge about DOACs. CONCLUSIONS: This survey showed that anticoagulated patients were managed mostly by specialists in private or hospital care, notably when requiring oral procedures at high hemorrhagic risk. CLINICAL RELEVANCE: A growing proportion of anticoagulated patients are being treated by dentists in primary care. Consequently, they need training, especially concerning DOACs. Additionally, consensus recommendations are necessary for better coordination of stakeholders and patient safety. Trial registration on ClinicalTrials.gov : NCT03150303.

The effect of local anesthetic continuous wound infusion for the prevention of postoperative pneumonia after on-pump cardiac surgery with sternotomy: the STERNOCAT randomized clinical trial.

PURPOSE: Postoperative pain after cardiac surgery, exacerbated by cough and sternal mobilization, limits clearance of bronchopulmonary secretions and may predispose to postoperative pneumonia. In this study, we tested the ability of local anesthetic continuous wound infusion to prevent pneumonia after cardiac surgery with sternotomy and cardiopulmonary bypass (CPB) owing to better analgesia and bronchopulmonary drainage. METHODS: In this randomized, double-blind, placebo-controlled trial conducted in five academic centers, patients undergoing cardiac surgery with sternotomy and CPB were enrolled from February 2012 until November 2014, and were followed over 30 days. Patients were assigned to a 48-h infusion (10 ml h-1) of L-bupivacaine (12.5 mg h-1) or placebo (saline) via a pre-sternal multiperforated catheter. Anesthesia and analgesia protocols were standardized. The primary end point was the incidence of pneumonia during the study period, i.e., until hospital discharge or 30 days. We hypothesized a 30% reduction in the incidence of pneumonia. RESULTS: Among 1493 randomized patients, 1439 completed the trial. Pneumonia occurred in 36/746 patients (4.9%) in the L-bupivacaine group and in 42/739 patients (5.7%) in the placebo group (absolute risk difference taking into account center and baseline risk of postoperative pneumonia, - 1.3% [95% CI - 3.4; 0.8] P = 0.22). In the predefined subgroup of patients at high risk, L-bupivacaine decreased the incidence of pneumonia (absolute risk difference, - 5.6% [95% CI - 10.0; - 1.1], P = 0.01). CONCLUSIONS: After cardiac surgery with sternotomy, continuous wound infusion of L-bupivacaine failed to decrease the incidence of pneumonia. These findings do not support the use of local anesthetic continuous wound infusion in this indication. Further study should investigate its effect in high-risk patients. TRIAL REGISTRATION: EudraCT Number: 2011-003292-10; Clinicaltrials.gov Identifier: NCT01648777.

Effect of Cricoid Pressure Compared With a Sham Procedure in the Rapid Sequence Induction of Anesthesia: The IRIS Randomized Clinical Trial.

Importance: The use of cricoid pressure (Sellick maneuver) during rapid sequence induction (RSI) of anesthesia remains controversial in the absence of a large randomized trial. Objective: To test the hypothesis that the incidence of pulmonary aspiration is not increased when cricoid pressure is not performed. Design, Setting, and Participants: Randomized, double-blind, noninferiority trial conducted in 10 academic centers. Patients undergoing anesthesia with RSI were enrolled from February 2014 until February 2017 and followed up for 28 days or until hospital discharge (last follow-up, February 8, 2017). Interventions: Patients were assigned to a cricoid pressure (Sellick group) or a sham procedure group. Main Outcomes and Measures: Primary end point was the incidence of pulmonary aspiration (at the glottis level during laryngoscopy or by tracheal aspiration after intubation). It was hypothesized that the sham procedure would not be inferior to the cricoid pressure. The secondary end points were related to pulmonary aspiration, difficult tracheal intubation, and traumatic complications owing to the tracheal intubation or cricoid pressure. Results: Of 3472 patients randomized, mean (SD) age was 51 (19) years and 1777 (51%) were men. The primary end point, pulmonary aspiration, occurred in 10 patients (0.6%) in the Sellick group and in 9 patients (0.5%) in the sham group. The upper limit of the 1-sided 95% CI of relative risk was 2.00, exceeding 1.50, failing to demonstrate noninferiority (P = .14). The risk difference was -0.06% (2-sided 95% CI, -0.57 to 0.42) in the intent-to-treat population and -0.06% (2-sided 95% CI, -0.56 to 0.43) in the per protocol population. Secondary end points were not significantly different among the 2 groups (pneumonia, length of stay, and mortality), although the comparison of the Cormack and Lehane grade (Grades 3 and 4, 10% vs 5%; P <.001) and the longer intubation time (Intubation time >30 seconds, 47% vs 40%; P <.001) suggest an increased difficulty of tracheal intubation in the Sellick group. Conclusions and Relevance: This large randomized clinical trial performed in patients undergoing anesthesia with RSI failed to demonstrate the noninferiority of the sham procedure in preventing pulmonary aspiration. Further studies are required in pregnant women and outside the operating room. Trial Registration: ClinicalTrials.gov Identifier: NCT02080754.

A phase III double-blind placebo-controlled randomized study of dexamphetamine sulfate for fatigue in primary brain tumors patients: An ANOCEF trial (DXA).

BACKGROUND: Most patients suffering from a primary brain tumor (PBT) complain of chronic fatigue affecting their quality of life (QOL). We hypothesized that dexamphetamine sulfate, a psychostimulant drug, could improve fatigue in PBT patients. METHODS: A double-blind, phase III, multi-institutional, placebo-controlled randomized trial (1:1 allocation) assessed the efficacy and tolerability of dexamphetamine at a dosage of 30 mg/day in PBT patients with stable disease who complained of severe fatigue, defined as a Multidimensional Fatigue Inventory (MFI-20) score ≥60. The primary outcome was the variation of the MFI 20 score between inclusion and the evaluation at 3 months in nonprogressive patients. Mood, QOL and cognitive function were also evaluated. RESULTS: From April 2013 to November 2016, 46 patients were enrolled in the study, 41 of whom were evaluable for analysis (dexamphetamine group: 22; placebo group: 19). Tolerance was generally good, with no treatment-related deaths and no grade 4 toxicity. Patients in the dexamphetamine arm complained more frequently of psychiatric side effects (mostly hyperactivity, anxiety, sleep disorder, and irritability) than patients in the placebo arm (P = .018). There were no statistically significant differences at 3 months between the dexamphetamine and placebo arms in any of the outcomes (MFI-20, Norris Visual Analog Scale, Hospital Anxiety and Depression Scale (HADS), QOL (EORTC QLQ-C30/BN 20), Marin's Apathy Evaluation Scale, and cognitive evaluations). CONCLUSION: Dexamphetamine at a dosage of up to 30 mg/day for 3 months has acceptable tolerability in PBT patients but does not improve fatigue, cognitive function, or QOL.

Clinical impact of upper gastrointestinal endoscopy in critically ill patients with suspected bleeding.

BACKGROUND AND AIMS: Upper gastrointestinal endoscopies' (UGE) profitability is undisputable in patients admitted for an overt upper digestive tract bleeding. In critically ill subjects admitted for other causes, its performances have scarcely been investigated despite its broad use. We sought to question the performance of bedside UGE in intensive care unit (ICU) patients, admitted for another reason than overt bleeding. METHODS: This was a six-year (January 2007-December 2012) retrospective observational study of all UGE performed in a medico-surgical ICU. Exclusion of those performed: in patients admitted for a patent upper digestive bleeding; for a second-look gastroscopy of a known lesion; as a planned interventional procedure. Main demographic and clinical data were recorded; UGE indication and profitability were rated according to its findings and therapeutic impact. Operative values of the indications of UGE were calculated. This study received approval from the Ethics Committee of the French Society of Intensive Care (n° 12-363). RESULTS: Eighty-four patients (74% male, mean age 61 ± 14 years) underwent a diagnostic UGE, all for a suspected upper digestive tract bleeding. The main symptoms justifying the procedure were anemia (52%), digestive bleeding (27%), vomiting (15%), hemodynamic instability (3%) and hyperuremia (3%). The profitability of UGE was rated as major (n = 5; 5.8%); minor (n = 34; 40.5%); or null (n = 45; 53.6%). CONCLUSIONS: When ICU admission is not warranted by a digestive bleeding, UGE has limited diagnostic and therapeutic interest, despite being often performed.

Sustainability of TNF-blocker tapering in rheumatoid arthritis over 3 years: long-term follow-up of the STRASS (Spacing of TNF-blocker injections in Rheumatoid ArthritiS Study) randomised controlled trial.

INTRODUCTION: We have limited data on the sustainability of tumour necrosis factor (TNF)-blocker tapering in rheumatoid arthritis (RA) in remission over the long term in real-life settings. This study aimed to assess the probability of sustained dose reduction of TNF-blockers in an observational 3-year extended follow-up of the Spacing of TNF-blocker injections in Rheumatoid ArthritiS Study (STRASS), a randomised controlled trial comparing progressive TNF-blocker injections (spacing arm (S-arm) to maintenance arm (M-arm)) in patients with RA in stable remission. METHODS: In 2015, clinical data for the completer population were retrospectively collected at 1, 2 and 3 years after the end of the trial. The endpoints were the proportion of patients free of a biological disease-modifying antirheumatic drug (bDMARD) treatment, a sustainably spaced injection of TNF-blockers and a full-dose regimen as well as the mean dose of bDMARD intake and treatment switch rate. RESULTS: Overall, 96 patients (76.8% of the completers) had data available up to 3 years; 11.5% discontinued TNF-blockers (5.8% vs 18.2% in the M-arm and S-arm, p=0.06), 30.2% had a tapered regimen (28.8% vs 31.8%, p=0.76) and 37.5% retained a full dose (44.2% vs 29.5%, p=0.14). The mean TNF-blocker dose quotient was 66% of the full dose (74% vs 58% in the M-arm and S-arm, p=0.06); 20.8% switched to another bDMARD (21.2% vs 20.5%, p=0.94). CONCLUSION: Sustained TNF-blocker de-escalation or withdrawal is achievable in 41% of patients over 3 years with limited dose reduction. Optimal strategies remain to be determined to maintain remission after TNF-blocker tapering or discontinuation.

Diagnostic Performance of C-Reactive Protein in Detecting Post-Operative Infectious Complications After Laparoscopic Sleeve Gastrectomy.

BACKGROUND: Gastric leak is the most common and dreaded post-operative infectious complication (PIC) after laparoscopic sleeve gastrectomy (LSG). Accurate identification of patients at risk postoperatively is of cardinal importance. OBJECTIVE: The aim of this study is to assess the diagnostic performance of C-reactive protein (CRP) in predicting PICs and the most optimal time to measure it. METHODS: CRP results were collected in patients undergoing LSG between 2011 and 2015. CRP was systematically measured on post-operative days (POD) 1, 3, and 5. RESULTS: Of 1326 patients, 42 (3.2%) developed a PIC at a median of 5 days after surgery. The incidence of leakage was 1.9%. The best area under the curve was observed on POD5 (0.87; 95% CI 0.77-0.96). At this time point, a cut-off of 115 mg/L yielded a sensitivity of 66.7% (95% CI 46.5-86.8%), a specificity of 95.1% (95% CI 93.9-96.3%), a positive and negative predictive values of 19.4% (95% CI 10.3-28.6%) and 99.4% (95% CI 99.0-100%), respectively, and a positive and negative likelihood ratios (LRs) of 13.62 and 0.35, respectively. The combination of sequential assessments of CRP on POD3 and 5 provided a sensitivity of 84.4% (95% CI 71.8-97.0%), a specificity of 91.1% (95% CI 89.5-92.8%), a positive and negative predictive values of 20.9% (95% CI 14.0-27.9%) and 99.5% (95% CI 99.1-99.9%), respectively, and a positive and a negative LRs of 9.58 and 0.17, respectively. CONCLUSIONS: CRP may be useful to identify patients at risk of PICs after LSG and, therefore, to prompt early investigation. However, CRP does not help rule out PICs.

Prone positioning in acute respiratory distress syndrome after abdominal surgery: a multicenter retrospective study : SAPRONADONF (Study of Ards and PRONe position After abDOmiNal surgery in France).

BACKGROUND: The recent demonstration of prone position's strong benefit on patient survival has rendered proning a major therapeutic intervention in severe ARDS. Uncertainties remain as to whether or not ARDS patients in the postoperative period of abdominal surgery should be turned prone because of the risk of abdominal complications. Our aim was to investigate the prevalence of surgical complications between patients with and without prone position after abdominal surgery. METHODS: This study was a multicenter retrospective cohort of patients with ARDS in a context of recent abdominal surgery. Primary outcome was the number of patients who had at least one surgical complication that could be induced or worsened by prone position. Secondary outcomes included effects of prone position on oxygenation. Data from the prone group were compared with those from the supine group (not having undergone at least a prone position session). RESULTS: Among 98 patients included, 36 (37%) had at least one prone position session. The rate of surgical complications induced or worsened by prone position did not differ between prone and supine groups [respectively, 14 (39%) vs 27 (44%); p = 0.65]. After propensity score application, there was no significant difference between the two groups (OR 0.72 [0.26-2.02], p = 0.54). Revision surgery did not differ between the groups. The first prone session significantly increased PaO2/FiO2 ratio from 95 ± 47 to 189 ± 92 mmHg, p < 0.0001. CONCLUSION: Prone position of ARDS patients after abdominal surgery was not associated with an increased rate of surgical complication. Intensivists should not refrain from proning these patients.