Anticoagulation strategy and safety in critically ill COVID-19 patients: a French retrospective multicentre study.

BACKGROUND: Patients with critical illness due to COVID-19 exhibit increased coagulability associated with a high risk of venous thrombo-embolism (VTE). Data on prophylactic anticoagulation for these patients are limited and conflicting. The purpose of this study was to evaluate whether intermediate-dose prophylactic anticoagulation in patients with COVID-19 requiring ICU admission was associated with better outcomes compared to standard-dose prophylactic anticoagulation. METHODS: We retrospectively included adults admitted with severe COVID-19 to any of 15 ICUs, in 2020 or 2021. We compared the groups given intermediate-dose vs. standard-dose prophylactic anticoagulation. The primary outcome was all-cause day-90 mortality. Secondary outcomes were VTE (pulmonary embolism or deep vein thrombosis), ICU stay length, and adverse effects of anticoagulation. RESULTS: Of 1174 included patients (mean age, 63 years), 399 received standard-dose and 775 intermediate-dose prophylactic anticoagulation. Of the 211 patients who died within 90 days, 86 (21%) received intermediate and 125 (16%) standard doses. After adjustment on early corticosteroid therapy and critical illness severity, there were no significant between-group differences in day-90 mortality (hazard ratio [HR], 0.73; 95%CI, 0.52-1.04; p = 0.09) or ICU stay length (HR, 0.93; 95%CI, 0.79-1.10; p = 0.38). Intermediate-dose anticoagulation was significantly associated with fewer VTE events (HR, 0.55; 95%CI, 0.38-0.80; p < 0.001). Bleeding events occurred in similar proportions of patients in the two groups (odds ratio, 0.86; 95%CI, 0.50-1.47; p = 0.57). CONCLUSIONS: Mortality on day 90 did not differ between the groups given standard-dose and intermediate-dose prophylactic anticoagulation, despite a higher incidence of VTE in the standard-dose group.

Early steroids and ventilator-associated pneumonia in COVID-19-related ARDS.

RATIONALE: Early corticosteroid treatment is used to treat COVID-19-related acute respiratory distress syndrome (ARDS). Infection is a well-documented adverse effect of corticosteroid therapy. OBJECTIVES: To determine whether early corticosteroid therapy to treat COVID-19 ARDS was associated with ventilator-associated pneumonia (VAP). METHODS: We retrospectively included adults with COVID-19-ARDS requiring invasive mechanical ventilation (MV) for ≥ 48 h at any of 15 intensive care units in 2020. We divided the patients into two groups based on whether they did or did not receive corticosteroids within 24 h. The primary outcome was VAP incidence, with death and extubation as competing events. Secondary outcomes were day 90-mortality, MV duration, other organ dysfunctions, and VAP characteristics. MEASUREMENTS AND MAIN RESULTS: Of 670 patients (mean age, 65 years), 369 did and 301 did not receive early corticosteroids. The cumulative VAP incidence was higher with early corticosteroids (adjusted hazard ratio [aHR] 1.29; 95% confidence interval [95% CI] 1.05-1.58; P = 0.016). Antibiotic resistance of VAP bacteria was not different between the two groups (odds ratio 0.94, 95% CI 0.58-1.53; P = 0.81). 90-day mortality was 30.9% with and 24.3% without early corticosteroids, a nonsignificant difference after adjustment on age, SOFA score, and VAP occurrence (aHR 1.15; 95% CI 0.83-1.60; P = 0.411). VAP was associated with higher 90-day mortality (aHR 1.86; 95% CI 1.33-2.61; P = 0.0003). CONCLUSIONS: Early corticosteroid treatment was associated with VAP in patients with COVID-19-ARDS. Although VAP was associated with higher 90-day mortality, early corticosteroid treatment was not. Longitudinal randomized controlled trials of early corticosteroids in COVID-19-ARDS requiring MV are warranted.

Comparison of the outcomes of the pediatric kidney transplantation between recipients below and above 15 kg: a single center retrospective study.

BACKGROUND: The renal transplantation is the best treatment for end-stage renal disease in children. We present the findings of an analysis of our institution's paediatric transplant outcomes comparing recipients under 15 kg, who represent this potentially higher risk group, to those above 15 kg. METHODS: We retrospectively identified consecutive paediatric kidney transplants from a prospectively collected database for analysis. We included all recipients under the age of 18 years at the time of transplant between 2006 and 2018 without any exclusion criteria. The primary outcome was death-censored graft survival at 1 year, 5 years and 10 years. RESULTS: 109 paediatric kidney transplants were performed in 100 children. Graft survival in the all population was 98%, 96% and 76% at 1 year, 5 years and 10 years, respectively. Recipient weight below 15 kg was not found to be a risk factor of graft loss. Overall, we found no individual factor to be statistically significantly associated with renal graft lost. The overall complication rate was 16% (18/109) with 12 early complications (11%) and 6 late ones (5%). CONCLUSION: Kidney transplantation in children weighing < 15 kg seems safe and offers the same patient and graft survival outcomes as in other (> 15 kg) pediatric recipients with equally low complication rates.

Benzodiazepine withdrawal in older people: what is the prevalence, what are the signs, and which patients?

PURPOSE: Benzodiazepines (BZDs) and related drugs (Z-drugs) are mainly taken chronically, and older people are much more likely to take them on a chronic basis despite recommendations. Withdrawal symptoms could be an obstacle to stopping BZD/Z-drug administration. The main objective of this study is to estimate the prevalence of withdrawal symptoms in patients aged 65 years and older who have experience a stop of BZD/Z-drug. The secondary objectives are to describe the withdrawal symptoms and identify factors associated. METHOD: This ancillary study was based on a national observational study in patients with chronic BZD/Z-drug consumption. Patients who made at least one BZD/Z-drug stop experience were selected. Withdrawal symptoms are described, and a logistic regression was carried out to identify the variables most associated with withdrawal symptoms. RESULTS: In total, 697 patients were selected: 78% experienced at least one withdrawal symptom after a stop administering BZDs or Z-drugs; most of the withdrawal symptoms were psychological disorders. CONCLUSION: Our study identifies a specific population experiencing withdrawal symptoms and who cannot stop administering BZD/Z-drug. We assume that withdrawal symptoms in patients with chronic use play an essential role in the nonstop use of BZD/Z-drugs.

Management of Congenital Melanocytic Naevi in Children: A French National Survey Using Clinical Vignettes.

Management of congenital melanocytic naevi in childhood may vary depending on the habits and experience of the treating clinician. The aim of this study was to assess current practice and determinants of surgical excision decision-making among French physicians. A national survey was conducted among dermatologists, paediatricians and surgeons, using clinical vignettes illustrating 29 scenarios. The primary outcome was the decision to perform surgical excision in each vignette. Of the 11,310 decisions made by the 390 participants (257 dermatologists, 35 surgeons, and 98 paediatricians) surgical excision was chosen in 33% of cases. The stated motivations for performing surgical excision were: melanoma risk, aesthetic/psychosocial risk, or both, in 39%, 34% and 27% of cases, respectively. Physicians with a higher level of experience in oncodermatology were more likely to opt for surgical excision. The age of the child, the size of the congenital melanocytic naevi, and the visibility of the lesion had no influence on the decision to perform surgical excision.

Calciphylaxis epidemiology, risk factors, treatment and survival among French chronic kidney disease patients: a case-control study.

BACKGROUND: Calcific Uremic Arteriolopathy (CUA) is a rare disease, causing painful skin ulcers in patients with end stage renal disease. Recommendations for CUA management and treatment are lacking. METHODS: We conducted a retrospective cohort study on CUA cases identified in western France, in order to describe its management and outcome in average clinical practices. Selection was based on the Hayashi diagnosis criteria (2013) extended to patients with eGFR < 30 mL/min/1.73m2. Dialyzed CUA cases were compared with 2 controls, matched for age, gender, region of treatment and time period. RESULTS: Eighty-nine CUA cases were identified between 2006 and 2016, including 19 non dialyzed and 70 dialyzed patients. Females with obesity (55.1%) were predominant. Bone mineral disease abnormalities, inflammation and malnutrition (weight loss, serum albumin decrease) preceded CUA onset for 6 months. The multimodal treatment strategy included wound care (98.9%), antibiotherapy (77.5%), discontinuation of Vitamin K antagonists (VKA) (70.8%) and intravenous sodium thiosulfate (65.2%). 40.4% of the patients died within the year after lesion onset, mainly under palliative care. Surgical debridement, distal CUA, localization to the lower limbs and non calcium-based phosphate binders were associated with better survival. Risks factors of developing CUA among dialysis patients were obesity, VKA, weight loss, serum albumin decrease or high serum phosphate in the 6 months before lesion onset. CONCLUSION: CUA involved mainly obese patients under VKA. Malnutrition and inflammation preceded the onset of skin lesions and could be warning signs among dialysis patients at risk. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02854046, registered August 3, 2016.

Tolerability of high-dose ceftriaxone in CNS infections: a prospective multicentre cohort study.

BACKGROUND: Ceftriaxone is widely used to treat community-acquired CNS bacterial infections. French guidelines for meningitis in adults promote 75-100 mg/kg/day ceftriaxone without an upper limit for dosage, yet little is known about the pharmacology and tolerability of such regimens. PATIENTS AND METHODS: A multicentre prospective cohort study was conducted in adult patients to assess the adverse drug reactions (ADRs) of high-dose ceftriaxone (i.e. daily dosage ≥4 g or ≥75 mg/kg) in CNS infections and to analyse their related factors. Drug causality was systematically assessed by an expert committee who reviewed the medical charts of all included patients. RESULTS: A total of 196 patients were enrolled over a 31 month period. Median dosage and duration of ceftriaxone were 96.4 mg/kg/day (7 g/day) and 8 days, respectively. Nineteen ceftriaxone-related ADRs (mainly neurological) occurred in 17 patients (8.7%), with only one case of treatment discontinuation (biliary pseudolithiasis). In univariate analysis, older age, male gender, renal impairment and high trough ceftriaxone plasma concentration were associated with ceftriaxone-related ADRs. CONCLUSIONS: High-dose ceftriaxone for CNS infection administered as recommended by French guidelines in adults was well tolerated overall, suggesting these recommendations could be applied and generalized. In patients with advanced age or renal insufficiency, prescription should be done with caution and therapeutic drug monitoring could be useful.

Postoperative morbidity of free flaps in head and neck cancer reconstruction: a report regarding 215 cases.

OBJECTIVES: The aim of this study was to identify the factors responsible for free flap failure, the surgical complications, and the non-oral feeding period in patients treated for an oral squamous cell carcinoma. MATERIALS AND METHODS: This multicentric study included 215 patients treated by tumour resection with immediate free flap reconstruction for an OSCC between 2010 and 2016. All of the patient medical files were reviewed and the data regarding the patient medical history, the tumour-related features, the surgical procedure, and the postoperative recovery were compiled. A statistical analysis with univariate and multivariate logistic regression was carried out. RESULTS: The free flap success rate was 94.4% in our series. A postoperative complication occurred in 101 patients (41%). Minor surgical complications were shown to increase the free flap failure rate (OR 3.32; p = 0.04). A major surgical complication was encountered in 48 patients (22.3%), and these were linked to minor surgical complications (OR 2.89; p = 0.004) and the use of a tracheostomy (OR 5.76, p = 0.002). Conversely, a medical history of high blood pressure had a protective effect (p = 0.04). The non-oral feeding rate at the end of the hospital stay was 28.4%, and it correlated with the tracheostomy (p = 0.002), as well as the major and the minor surgical complications (p = 0.04). CONCLUSION-CLINICAL RELEVANCE: Free flap reconstruction is a safe and reliable technique with head and neck cancer reconstruction. Postoperative care favouring early and safe oral-feeding, and avoiding a tracheostomy can reduce the incidence of surgical complications after OSCC reconstruction.

Fungal Prophylaxis with a Gastro-Resistant Posaconazole Tablet for Patients with Hematological Malignancies in the POSANANTES Study.

Posaconazole is an antifungal drug used in both prophylaxis and treatment of invasive fungal infections. Its oral formulation requires therapeutic drug monitoring. To overcome gastric acidity, a gastro-resistant posaconazole tablet has recently been developed. POSANANTES was a prospective noninterventional study that aimed to monitor plasma concentration trough level (Cmin) of posaconazole tablets used prophylactically in patients with hematological malignancies. Fifty patients were included. Group A (n = 31) included patients receiving induction chemotherapy for myeloid malignancies, and group B (n = 19) included patients treated for graft-versus-host disease after allogeneic hematopoietic stem cells transplantation. In multivariate analysis, female sex, group B assignment, and evaluation of Cmin at day 8 (versus any other day planned by the analysis) were associated with a higher Cmin, while diarrhea was associated with a lower Cmin (P < 0.05). Thirty-four percent (n = 17) of all included patients had to prematurely stop treatment, mainly in group A. In conclusion, this real-life prospective study showed good absorption of posaconazole tablets used for prophylaxis in patients with hematological malignancies, even though this strategy was somewhat limited due to the high number of patients in group A who had to stop their treatment in an untimely fashion.

Psychomotor retardation: What about the partial responders to magnetic transcranial stimulation in treatment resistant depression ?

OBJECTIVE: Psychomotor retardation is a core clinical component of Major Depressive Disorder responsible for disability and is known as a treatment response marker of biological treatments for depression. Our objective was to describe cognitive and motoric measures changes during a treatment by repetitive Transcranial Magnetic Stimulation (rTMS) within the THETAD-DEP trial for treatment-resistant depression (TRD), and compare those performances at the end of treatment and one month after between responders (>50% improvement on MADRS score), partial responders (25-50%) and non-reponders (no clinically relevant improvement). Our secondary aim was to investigate baseline psychomotor performances associated with non-response and response even partial. METHODS: Fifty-four patients with treatment-resistant unipolar depression and treated by either high frequency 10 Hz rTMS or iTBS for 4 weeks (20 sessions) underwent assessment including French Retardation Rating Scale for Depression (ERD), Verbal Fluency test, and Trail Making Test A. before, just after treatment and one month later. RESULTS: 20 patients were responders (R, 21 partial responders (PR) and 13 non-responders (NR). rTMS treatment improved psychomotor performances in the R and PR groups unlike NR patients whose psychomotor performance was not enhanced by treatment. At baseline, participants, later identified as partial responders, showed significantly higher performances than non-responders. CONCLUSION: Higher cognitivo-motor performances at baseline may be associated with clinical improvement after rTMS treatment. This work highlights the value of objective psychomotor testing for the identification of rTMS responders and partial responders, and thus may be useful for patient selection and protocol individualization such as treatment continuation for early partial responders.

Ketamine Compared With Morphine for Out-of-Hospital Analgesia for Patients With Traumatic Pain: A Randomized Clinical Trial.

Importance: Pain is a common out-of-hospital symptom among patients, and opioids are often prescribed. Research suggests that overprescribing for acute traumatic pain is still prevalent, even when limits restricting opioid prescriptions have been implemented. Ketamine hydrochloride is an alternative to opioids in adults with out-of-hospital traumatic pain. Objective: To assess the noninferiority of intravenous ketamine compared with intravenous morphine sulfate to provide pain relief in adults with out-of-hospital traumatic pain. Design, Setting, and Participants: The Intravenous Subdissociative-Dose Ketamine Versus Morphine for Prehospital Analgesia (KETAMORPH) study was a multicenter, single-blind, noninferiority randomized clinical trial comparing ketamine hydrochloride (20 mg, followed by 10 mg every 5 minutes) with morphine sulfate (2 or 3 mg every 5 minutes) in adult patients with out-of-hospital trauma and a verbal pain score equal to or greater than 5. Enrollment occurred from November 23, 2017, to November 26, 2022, in 11 French out-of-hospital emergency medical units. Interventions: Patients were randomly assigned to ketamine (n = 128) or morphine (n = 123). Main Outcomes and Measures: The primary outcome was the between-group difference in mean change in verbal rating scale pain scores measured from the time before administration of the study drug to 30 minutes later. A noninferiority margin of 1.3 was chosen. Results: A total of 251 patients were randomized (median age, 51 [IQR, 34-69] years; 111 women [44.9%] and 140 men [55.1%] among the 247 with data available) and were included in the intention-to-treat population. The mean pain score change was -3.7 (95% CI, -4.2 to -3.2) in the ketamine group compared with -3.8 (95% CI, -4.2 to -3.4) in the morphine group. The difference in mean pain score change was 0.1 (95% CI, -0.7 to 0.9) points. There were no clinically meaningful differences for vital signs between the 2 groups. The intravenous morphine group had 19 of 113 (16.8% [95% CI, 10.4%-25.0%]) adverse effects reported (most commonly nausea [12 of 113 (10.6%)]) compared with 49 of 120 (40.8% [95% CI, 32.0%-49.6%]) in the ketamine group (most commonly emergence phenomenon [24 of 120 (20.0%)]). No adverse events required intervention. Conclusions and Relevance: In the KETAMORPH study of patients with out-of-hospital traumatic pain, the use of intravenous ketamine compared with morphine showed noninferiority for pain reduction. In the ongoing opioid crisis, ketamine administered alone is an alternative to opioids in adults with out-of-hospital traumatic pain. Trial Registration: ClinicalTrials.gov Identifier: NCT03236805.

Features and outcomes of patients admitted to the ICU for chimeric antigen receptor T cell-related toxicity: a French multicentre cohort.

BACKGROUND: Chimeric antigen receptor T-cell (CAR-T) therapy is increasingly used in patients with refractory haematological malignancies but can induce severe adverse events. We aimed to describe the clinical features and outcomes of patients admitted to the intensive care unit (ICU) after CAR-T therapy. METHODS: This retrospective observational cohort study included consecutive adults admitted to either of two French ICUs in 2018-2022 within 3 months after CAR-T therapy. RESULTS: Among 238 patients given CAR-T therapy, 84 (35.3%) required ICU admission and were included in the study, a median of 5 [0-7] days after CAR-T infusion. Median SOFA and SAPSII scores were 3 [2-6] and 39 [30-48], respectively. Criteria for cytokine release syndrome were met in 80/84 (95.2%) patients, including 18/80 (22.5%) with grade 3-4 toxicity. Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 46/84 (54.8%) patients, including 29/46 (63%) with grade 3-4 toxicity. Haemophagocytic lymphohistiocytosis was diagnosed in 15/84 (17.9%) patients. Tocilizumab was used in 73/84 (86.9%) patients, with a median of 2 [1-4] doses. Steroids were given to 55/84 (65.5%) patients, including 21/55 (38.2%) given high-dose pulse therapy. Overall, 23/84 (27.4%) patients had bacterial infections, 3/84 (3.6%) had fungal infections (1 invasive pulmonary aspergillosis and 2 Mucorales), and 2 (2.4%) had cytomegalovirus infection. Vasopressors were required in 23/84 (27.4%), invasive mechanical ventilation in 12/84 (14.3%), and dialysis in 4/84 (4.8%) patients. Four patients died in the ICU (including 2 after ICU readmission, i.e., overall mortality was 4.8% of patients). One year after CAR-T therapy, 41/84 (48.9%) patients were alive and in complete remission, 14/84 (16.7%) were alive and in relapse, and 29/84 (34.5%) had died. These outcomes were similar to those of patients never admitted to the ICU. CONCLUSION: ICU admission is common after CAR-T therapy and is usually performed to manage specific toxicities. Our experience is encouraging, with low ICU mortality despite a high rate of grade 3-4 toxicities, and half of patients being alive and in complete remission at one year.

Does the VWF:CB Assay Help to Diagnose von Willebrand Factor Deficiency in Patients With a Bleeding Disorder of Unknown Cause?

INTRODUCTION: The entity entitled bleeding disorder of unknown cause (BDUC) qualifies individuals displaying a mild haemorrhagic profile but normal routine coagulation tests. This study was designed to evaluate whether collagen-binding assay for von Willebrand Factor (VWF) measurement (VWF:CB) could allow to diagnose VW disease in such patients. METHODS: A large screening was conducted prospectively in two University Hospitals, using the bleeding assessment tool (BAT) recommended by the International Society of Thrombosis and Hemostasis. Patients with an abnormal BAT were confirmed to have a normal complete hemostatic evaluation. A large range of VWF assays was then carried out on a new blood sample for the 68 individuals (91% women) thus identified. Of note, five VWF:CB using different types of collagen were performed, as well as a comprehensive sequencing of the VWF gene. RESULTS: Of this cohort, only 3 individuals (all blood group O), had a VWF:CB between 40 and 50 IU/dL. No unknown anomaly of the VWF gene was disclosed. Of note, 54% of these patients had unexplained abnormal occlusion times on PFA-200. CONCLUSION: This study identified 68 cases of BDUC, after screening of a large population, indicating a low incidence. Only 3 cases were potentially confirmed as displaying moderate von Willebrand disease. VWF:CB tests were globally normal in the 65 other patients of the cohort. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT0279220.

Optimization of cerebral oxygenation based on regional cerebral oxygen saturation monitoring during carotid endarterectomy: a Phase III multicenter, double-blind randomized controlled trial.

BACKGROUND: Whether the optimization of cerebral oxygenation based on regional cerebral oxygen saturation (rSO2) monitoring reduces the occurrence of cerebral ischemic lesions is unknown. METHODS: This multicenter, randomized, controlled trial recruited adults admitted for scheduled carotid endarterectomy. Patients were randomized between the standard of care or optimization of cerebral oxygenation based on rSO2 monitoring using near-infrared spectroscopy. In the intervention group, in case of a decrease in rSO2 in the intervention, the following treatments were sequentially recommended: (1) increasing oxygenotherapy, (2) reducing the tidal volume, (3) legs up-raising, (4) performing a fluid challenge and (5) initiating vasopressor support. The primary endpoint was the number of new cerebral ischemic lesions detected using magnetic resonance imaging pre- and postoperatively. Secondary endpoints included new neurological deficits and mortality on day 120 after surgery. RESULTS: Among the 879 patients who were randomized, 665 (75.7%) were men. There was no statistically significant difference between groups for the mean number of new cerebral ischemic lesions per patient up to 3 days after surgery: 0.35 (±1.05) in the standard group vs. 0.58 (±2.83), in the NIRS group; mean difference, 0.23 [95% CI, -0.06 to 0.52]; estimate, 0.22 [95% CI, -0.06 to 0.50]. New neurological deficits up to day 120 after hospital discharge were not different between the groups: 15 (3,39%) in the standard group vs. 42 (5,49%) in the NIRS group; absolute difference, 2,10 [95% CI, -0,62 to 4,82]. There was no significant difference between groups for the median [IQR] hospital length of stay: 4.0 [4.0-6.0] in the standard group vs. 5.0 [4.0-6.0] in the NIRS group; mean difference, -0.11 [95% CI, -0.65 to 0.44]. The mortality rate on day 120 was not different between the standard group (0.68%) vs. the NIRS group (0.92%); absolute difference = 0.24% [95% CI, -0.94 to 1.41]. CONCLUSIONS: Among patients undergoing carotid endarterectomy, optimization of cerebral oxygenation based on rSO2 did not reduce the occurrence of cerebral ischemic lesions postoperatively compared with controlled hypertensive therapy. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01415648.

Impact of response shift effects in the assessment of self-reported depression during treatment: Insights from a rTMS versus Venlafaxine randomized controlled trial.

PURPOSE: Patient-Reported Outcomes are essential to properly assess treatment effectiveness in randomized clinical trial (RCT) for Major Depressive Disorder (MDD). MDD self-assessment may vary over time depending on change in the meaning of patients' self-evaluation of depression, i.e. Response Shift (RS). Our aim was to investigate RS and its impact on different depression domains in a clinical trial comparing rTMS versus Venlafaxine. METHODS: The occurrence and type of RS was determined using Structural Equation Modeling applied to change over time in 3 domains (Sad Mood, Performance Impairment, Negative Self-Reference) of the short-form Beck Depression Inventory (BDI-13) in a secondary analysis of a RCT on 170 patients with MDD treated by rTMS, venlafaxine or both. RESULTS: RS was evidenced in the venlafaxine group in the Negative Self-Reference and Sad Mood domains. CONCLUSION: RS effects differed between treatment arms in self-reported depression domains in patients with MDD. Ignoring RS would have led to a slight underestimation of depression improvement, depending on treatment group. Further investigations of RS and advancing new methods are needed to better inform decision making based on Patient-Reported Outcomes.

Cost effectiveness and long-term outcomes of dexamethasone administration in major non-cardiac surgery.

STUDY OBJECTIVES: Postoperative administration of dexamethasone has been proposed to reduce morbidity and mortality in patients undergoing major non-cardiac surgery. In this ancillary study of the PACMAN trial, we aimed to evaluate the cost effectiveness of dexamethasone in patients undergoing major non-cardiac surgery. METHODS: Patients included in the multicentric randomized double-blind, placebo-controlled PACMAN trial were followed up for 12 months after their surgical procedure. Patients were randomized to receive either dexamethasone (0.2 mg/kg immediately after the surgical procedure, and on day 1) or placebo. Cost effectiveness between the dexamethasone and placebo groups was assessed for the 12-month postoperative period from a health payer perspective. RESULTS: Of 1222 randomized patients in PACMAN, 137 patients (11%) were followed up until 12 months after major surgery (71 in the DXM group and 66 in the placebo group). Postoperative dexamethasone administration reduced costs per patient at 1 year by €358.06 (95%CI -€1519.99 to €803.87). The probability of dexamethasone being cost effective was between 12% and 22% for a willingness to pay of €100,000 to €150,000 per life-year, which is the threshold that is usually used in France and was 52% for willingness to pay of €50,000 per life-year (threshold in USA). At 12 months, 9 patients (13.2%) in the DXM group and 10 patients (16.1%) in the placebo group had died. In conclusion, our study does not demonstrate the cost effectiveness of perioperative administration of DXM in major non-cardiac surgery.

Association Between Periodontitis and Preterm Birth in a Cohort of Pregnant Women in Ivory Coast.

PURPOSE: The aim of this study was to investigate the possible association between periodontitis and preterm birth in Ivory Coast. MATERIALS AND METHODS: A cohort study including 446 volunteers (pregnant women) aged 15-50 years was performed in the Gynecology-Obstetrics Department of the University Hospital Center of Cocody-Abidjan in Ivory Coast. Socioeconomic and periodontal status was obtained during pregnancy. After delivery, obstetric data was collected. Periodontitis was diagnosed according to the new 2018 EFP/AAP classification of Periodontal and Peri-Implant Diseases and Conditions, as follows: a subject presenting with interdental CAL at two non-adjacent teeth or buccal/oral CAL ≥ 3 mm with pocketing > 3 mm was diagnosed with periodontitis. Any birth before the 37th week was considered a preterm birth (PTB). RESULTS: The prevalence of periodontitis and preterm birth were 59.47% and 18.34%, respectively. Periodontitis was mainly stage 1. PTB was statistically significantly higher in pregnant women with periodontitis compared to women without periodontitis (p = 0.0002). Multivariate analysis showed that periodontitis was associated with PTB (p = 0.0002). Logistic regression showed that periodontitis is a risk factor for preterm birth (OR = 3.62; 95% CI: 1.80-7.31; p = 0.0003). CONCLUSION: The results of this study suggest that periodontitis is an additional risk factor for preterm birth in Ivory Coast.

Migration is associated with baseline severity and progress over time in autism spectrum disorder: Evidence from a French prospective longitudinal study.

BACKGROUND: The prevalence of autism-spectrum disorder (ASD) has been shown to be higher in migrant families, but it is also a challenge for health care professionals to offer adequate services to families that face multiple challenges. In the context of the EPIGRAM study (a French prospective, multisite, longitudinal observational study implementing integrative care practices (ICPs) for children with ASD), we aimed to assess the impact of migration on children with ASD. METHOD AND FINDINGS: 89 children with ASD aged 3 to 6 years old (92% males) were recruited and followed up for 12 months. The children were clinically assessed using several instruments. At baseline, children had severe autism on average on the Children Autism Rating Scale (CARS, mean = 44; SD = 6.51) and moderate autism on the PsychoEducational profile-3-R (PEP-3-R) maladaptive behavior category (mean = 30; SD = 29.89). Thirty percent of the families had a low socio-economic status, and 56% were first-generation immigrants. For all clinical variables, children of immigrant parents had more severe autism and developmental delays at baseline. A linear mixed model established an improvement in all clinical characteristics over the 12 months of the study. This trend may be attributed to ICPs or any naturally occurring event during that period. Families shared this positive view over time. However, the improvements were slower for two clinical dimensions of the PEP-3-R in children from migrant families. For the inappropriate behavior category, the time effect diminished by an average of 0.83 percentile/month for children whose parents were migrants vs. children whose parents were non-migrants. Similarly, for verbal behavior characteristics, the time effect diminished by an average of 1.32 percentile/month for children whose parents were migrants vs. children whose parents were non-migrants. CONCLUSION: Despite an overall positive improvement, we found that migration is associated baseline severity and progress over time in children with ASD. There is an urgent need to target the migrant population with specific research and understand the avenues that carry such higher severity. CLINICAL TRIAL REGISTRATION: Study registration on clinicaltrials.gov under the number NCT02154828.

Infected pancreatic necrosis complicating severe acute pancreatitis in critically ill patients: predicting catheter drainage failure and need for necrosectomy.

BACKGROUND: Recent guidelines advocate a step-up approach for managing suspected infected pancreatic necrosis (IPN) during acute pancreatitis. Nearly half the patients require secondary necrosectomy after catheter drainage. Our primary objective was to assess the external validity of a previously reported nomogram for catheter drainage, based on four predictors of failure. Our secondary objectives were to identify other potential predictors of catheter-drainage failure. We retrospectively studied consecutive patients admitted to the intensive care units (ICUs) of three university hospitals in France between 2012 and 2016, for severe acute pancreatitis with suspected IPN requiring catheter drainage. We assessed drainage success and failure rates in 72 patients, with success defined as survival without subsequent necrosectomy and failure as death and/or subsequent necrosectomy required by inadequate improvement. We plotted the receiver operating characteristics (ROC) curve for the nomogram and computed the area under the curve (AUROC). RESULTS: Catheter drainage alone was successful in 32 (44.4%) patients. The nomogram predicted catheter-drainage failure with an AUROC of 0.71. By multivariate analysis, catheter-drainage failure was independently associated with a higher body mass index [odds ratio (OR), 1.12; 95% confidence interval (95% CI), 1.00-1.24; P = 0.048], heterogeneous collection (OR, 16.7; 95% CI, 1.83-152.46; P = 0.01), and respiratory failure onset within 24 h before catheter drainage (OR, 18.34; 95% CI, 2.18-154.3; P = 0.007). CONCLUSION: Over half the patients required necrosectomy after failed catheter drainage. Newly identified predictors of catheter-drainage failure were heterogeneous collection and respiratory failure. Adding these predictors to the nomogram might help to identify patients at high risk of catheter-drainage failure. CLINICALTRIALS: gov number: NCT03234166.