Assessment of Peak Inspiratory Flow in Young Infants with Acute Viral Bronchiolitis: Physiological Basis for Initial Flow Setting in Patients Supported with High-Flow Nasal Cannula.

OBJECTIVE: To assess the inspiratory demand in young infants with acute viral bronchiolitis to provide a physiological basis for initial flow setting for patients supported with high flow nasal cannula. STUDY DESIGN: Prospective study in 44 infants up to 6 months old with acute viral bronchiolitis, admitted to a pediatric intensive care unit from November 2017 to March 2019. Airflow measurements were performed using spirometry. The primary endpoint was the inspiratory demand as measured by peak tidal inspiratory flow (PTIF). The secondary endpoints were the relationships determined between PTIF, patient weight, and disease severity. RESULTS: Median (Q25-Q75) age and weight of the patients were 37 (20-67) days and 4.3 (3.5-5.0) kg, respectively. Mean PTIF was 7.45 (95% CI 6.51-8.39, min-max: 2.40-16.00) L/minute. PTIF indexed to weight was 1.68 (95% CI 1.51-1.85, min-max: 0.67-3.00) L/kg/minute. PTIF was <2.5 L/kg/minute in 89% (95% CI 75-96) of infants. PTIF was correlated with weight (ρ= 0 .55, P < .001) but not with markers of disease severity, including modified Woods clinical asthma score, Silverman-Andersen score, respiratory rate, fraction of inspired oxygen, and PCO2. CONCLUSIONS: High flow nasal cannula therapy is used commonly to support infants with acute viral bronchiolitis. The efficiency of the device is optimal if the flow setting matches the patient's inspiratory demand. According to our results, a flow rate of <2.5 L/kg/minute would be appropriate in most situations.

Patterns of adaptive servo-ventilation settings in a real-life multicenter study: pay attention to volume! : Adaptive servo-ventilation settings in real-life conditions.

BACKGROUNDS: To explain the excess cardiovascular mortality observed in the SERVE-HF study, it was hypothesized that the high-pressure ASV default settings used lead to inappropriate ventilation, cascading negative consequences (i.e. not only pro-arrythmogenic effects through metabolic/electrolyte abnormalities, but also lower cardiac output). The aims of this study are: i) to describe ASV-settings for long-term ASV-populations in real-life conditions; ii) to describe the associated minute-ventilations (MV) and therapeutic pressures for servo-controlled-flow versus servo-controlled-volume devices (ASV-F Philips®-devices versus ASV-V ResMed®-devices). METHODS: The OTRLASV-study is a cross-sectional, 5-centre study including patients who underwent ASV-treatment for at least 1 year. The eight participating clinicians were free to adjust ASV settings, which were compared among i) initial diagnosed sleep-disordered-breathing (SBD) groups (Obstructive-Sleep-Apnea (OSA), Central-Sleep-Apnea (CSA), Treatment-Emergent-Central-Sleep-Apnea (TECSA)), and ii) unsupervised groups (k-means clusters). To generate these clusters, baseline and follow-up variables were used (age, sex, body mass index (BMI), initial diagnosed Obstructive-Apnea-Index, initial diagnosed Central-Apnea-Index, Continuous-Positive-Airway-Pressure used before ASV treatment, presence of cardiopathy, and presence of a reduced left-ventricular-ejection-fraction (LVEF)). ASV-data were collected using the manufacturer's software for 6 months. RESULTS: One hundred seventy-seven patients (87.57% male) were analysed with a median (IQ25-75) initial Apnea-Hypopnea-Index of 50 (38-62)/h, an ASV-treatment duration of 2.88 (1.76-4.96) years, 61.58% treated with an ASV-V. SDB groups did not differ in ASV settings, MV or therapeutic pressures. In contrast, the five generated k-means clusters did (generally described as follows: (C1) male-TECSA-cardiopathy, (C2) male-mostly-CSA-cardiopathy, (C3) male-mostly-TECSA-no cardiopathy, (C4) female-mostly-elevated BMI-TECSA-cardiopathy, (C5) male-mostly-OSA-low-LVEF). Of note, the male-mostly-OSA-low-LVEF-cluster-5 had significantly lower fixed end-expiratory-airway-pressure (EPAP) settings versus C1 (p = 0.029) and C4 (p = 0.007). Auto-EPAP usage was higher in the male-mostly-TECSA-no cardiopathy-cluster-3 versus C1 (p = 0.006) and C2 (p < 0.001). MV differences between ASV-F (p = 0.002) and ASV-V (p < 0.001) were not homogenously distributed across clusters, suggesting specific cluster and ASV-algorithm interactions. Individual ASV-data suggest that the hyperventilation risk is not related to the cluster nor the ASV-monitoring type. CONCLUSIONS: Real-life ASV settings are associated with combinations of baseline and follow-up variables wherein cardiological variables remain clinically meaningful. At the patient level, a hyperventilation risk exists regardless of cluster or ASV-monitoring type, spotlighting a future role of MV-telemonitoring in the interest of patient-safety. TRIAL REGISTRATION: The OTRLASV study was registered on ClinicalTrials.gov (Identifier: NCT02429986 ). 1 April 2015.

Serum Phosphate Kinetics in Acute Kidney Injury After Cardiac Surgery: An Observational Study.

OBJECTIVE: Acute kidney injury (AKI) is a common complication after cardiac surgery and may affect prognosis. Serum phosphate (SPh) elevation is well-known to occur after AKI but not well-documented. The aim of the present study was to describe SPh changes during AKI after cardiac surgery and to assess the accuracy for the diagnosis of AKI severity and recovery. DESIGN: Prospective, single center, observational study. SETTING: Intensive care unit of a tertiary university hospital. PARTICIPANTS: All patients admitted consecutively to the intensive care unit between February 2015 and March 2016. MEASUREMENTS AND MAIN RESULTS: AKI was defined according to Kidney Disease Improving Global Outcomes criteria and classified as nonsevere (stage 1) and severe (stages 2 and 3). Receiver operating characteristic curve analysis was conducted to test reliability of SPh for AKI severity and recovery. AKI occurred in 86 of the 260 patients included (33%) in the study; 58 (67%) experienced nonsevere AKI, and 28 (33%) experienced severe AKI. A significant elevation of SPh values was observed in AKI patients, which peaked at 48 hours. At this time, an SPh of 1.33 mmol/L demonstrated a good accuracy for AKI severity, with an area under the curve of 0.91 (95% confidence interval 0.82-1.00). For kidney recovery, a 25% SPh decrease 24 hours after the peak had a positive predictive value of 100%, and a 2.5% decrease allowed for the reclassification of patients when the serum creatinine had not decreased enough. CONCLUSIONS: The results showed that SPh changes closely follow AKI severity and kidney recovery after cardiac surgery. In addition to serum creatinine, this simple biological marker may help predict early favorable outcome.

What is the remaining status of adaptive servo-ventilation? The results of a real-life multicenter study (OTRLASV-study) : Adaptive servo-ventilation in real-life conditions.

BACKGROUNDS: As a consequence of the increased mortality observed in the SERVE-HF study, many questions concerning the safety and rational use of ASV in other indications emerged. The aim of this study was to describe the clinical characteristics of ASV-treated patients in real-life conditions. METHODS: The OTRLASV-study is a prospective, 5-centre study including patients who underwent ASV-treatment for at least 1 year. Patients were consecutively included in the study during the annual visit imposed for ASV-reimbursement renewal. RESULTS: 177/214 patients were analysed (87.57% male) with a median (IQ25-75) age of 71 (65-77) years, an ASV-treatment duration of 2.88 (1.76-4.96) years, an ASV-usage of 6.52 (5.13-7.65) hours/day, and 54.8% were previously treated via continuous positive airway pressure (CPAP). The median Epworth Scale Score decreased from 10 (6-13.5) to 6 (3-9) (p < 0.001) with ASV-therapy, the apnea-hypopnea-index decreased from 50 (38-62)/h to a residual device index of 1.9 (0.7-3.8)/h (p < 0.001). The majority of patients were classified in a Central-Sleep-Apnea group (CSA; 59.3%), whereas the remaining are divided into an Obstructive-Sleep-Apnea group (OSA; 20.3%) and a Treatment-Emergent-Central-Sleep-Apnea group (TECSA; 20.3%). The Left Ventricular Ejection Fraction (LVEF) was > 45% in 92.7% of patients. Associated comorbidities/etiologies were cardiac in nature for 75.7% of patients (neurological for 12.4%, renal for 4.5%, opioid-treatment for 3.4%). 9.6% had idiopathic central-sleep-apnea. 6.2% of the patients were hospitalized the year preceding the study for cardiological reasons. In the 6 months preceding inclusion, night monitoring (i.e. polygraphy or oximetry during ASV usage) was performed in 34.4% of patients, 25.9% of whom required a subsequent setting change. According to multivariable, logistic regression, the variables that were independently associated with poor adherence (ASV-usage ≤4 h in duration) were TECSA group versus CSA group (p = 0.010), a higher Epworth score (p = 0.019) and lack of a night monitoring in the last 6 months (p < 0.05). CONCLUSIONS: In real-life conditions, ASV-treatment is often associated with high cardiac comorbidities and high compliance. Future research should assess how regular night monitoring may optimize devices settings and patient management. TRIAL REGISTRATION: The OTRLASV study is registered on ClinicalTrials.gov (Identifier: NCT02429986 ) on 1 April 2015.

Does programmed intermittent epidural bolus improve childbirth conditions of nulliparous women compared with patient-controlled epidural analgesia?: A multicentre, randomised, controlled, triple-blind study.

BACKGROUND: Epidural analgesia may change the mechanics of childbirth. These changes are related to the concentration of the local anaesthetic used epidurally but probably also to its mode of delivery into the epidural space. OBJECTIVE: To determine whether the administration of programmed intermittent epidural boluses (PIEB) improves the mechanics of second-stage labour compared with patient-controlled epidural analgesia (PCEA) with a background infusion. DESIGN: A randomised, controlled, triple-blind study. SETTING: Multicentre study including four level III maternity units, January 2014 until June 2016. PATIENTS: A total of 298 nulliparous patients in spontaneous labour were randomised to a PIEB or PCEA group. INTERVENTION: After epidural initiation with 15 ml of 0.1% levobupivacaine containing 10 µg of sufentanil, patients received either an hourly bolus of 8 ml (PIEB) or a continuous rate infusion of 8 ml h (PCEA): the drug mixture used was levobupivacaine 0.1% and sufentanil 0.36 µg ml. MAIN OUTCOME MEASURES: The primary outcome was a composite endpoint of objective labour events: a posterior occiput position in the second stage, an occiput position at birth, waiting time at full cervical dilatation before active maternal pushing more than 3 h, maternal active pushing duration more than 40 min, and foetal heart rate alterations. Vaginal instrumental delivery rates, analgesia and motor blockade scores were also recorded. RESULTS: From the 298 patients randomised, data from 249 (124 PIEB, 125 PCEA) were analysed. No difference was found in the primary outcome: 48.0% (PIEB) and 45.5% (PCEA) of patients, P = 0.70. In addition, no difference was observed between the groups for each of the individual events of the composite endpoint, nor in the instrumental vaginal delivery rate, nor in the degree of motor blockade. Despite an equivalent volume of medication in the groups, a significantly higher analgesia score at full dilatation was observed in the PIEB group, odds-ratio = 1.9 (95% confidence interval, 1.0 to 3.5), P = 0.04. CONCLUSION: The mechanics of the second stage did not differ whether PIEB or PCEA was used. Analgesic conditions appeared to be superior with PIEB, especially at full dilation. TRIAL REGISTRATION: NCT01856166.

A Regional Network Organization for Thrombectomy for Acute Ischemic Stroke in the Anterior Circulation; Timing, Safety, and Effectiveness.

BACKGROUND: Mechanical thrombectomy (MT) in association with intravenous thrombolysis is recommended for treatment of acute ischemic stroke (AIS), with large vessel occlusion (LVO) in the anterior circulation. Because MT is only available in comprehensive stroke centers (CSC), the challenge of stroke organization is to ensure equitable access to the fastest endovascular suite. Our aim was to evaluate the feasibility, efficacy, and safety of MT in patients initially managed in 1 CSC (mothership), compared with patients first managed in primary stroke center (PSC), and then transferred to the CSC for MT (drip-and-ship). METHODS: We retrospectively analyzed 179 consecutive patients (93 in the mothership group and 86 in the drip-and-ship group), with AIS secondary to LVO in the anterior cerebral circulation and a clinical-radiological mismatch (NIHSS ≥ 8 and DWI-ASPECT score ≥5), up to 6 hours after symptoms onset. We evaluated 3-month functional modified Rankin scale (mRS), periprocedural time management, mortality, and symptomatic intracranial haemorrhage (sICH). RESULTS: Despite significant longer process time in the drip-and-ship group, mRS ≤ 2 at 3 months (39.8% versus 44.1%, P = .562), Thrombolysis in cerebral infarction 2b-3 (85% versus 78%, P = .256), and sICH (7.0% versus 9.7%, P = .515) were similar in both group regardless of baseline clinical or radiological characteristics. After multivariate logistic regression, the predictive factors for favorable outcome were age (odds ratio [OR] -5years= 1.32, P < .001), initial NIHSS (OR -5points = 1.59, P = .010), absence of diabetes (OR = 3.35, P = .075), and the delay magnetic resonance imagining-puncture (OR -30min = 1.16, P = .048). CONCLUSIONS: Our study showed encouraging results from a regional protocol of MT comparing patients transferred from PSC or brought directly in CSC.

Benign paroxysmal torticollis, benign paroxysmal vertigo, and benign tonic upward gaze are not benign disorders.

AIM: Benign paroxysmal torticollis (BPT), benign paroxysmal vertigo (BPV), and benign tonic upward gaze (BTU) are characterized by transient and recurrent episodes of neurological manifestations. The purpose of this study was to analyse the clinical relationships between these syndromes, associated comorbidities, and genetic bases. METHOD: In this cross-sectional study, clinical data of patients with BPT, BPV, or BTU were collected with a focus on developmental achievements, learning abilities, and rehabilitation. Neuropsychological assessment and genetic testing were performed. RESULTS: Fifty patients (median age at inclusion 6y) were enrolled. Psychomotor delay, abnormal neurological examination, and low or borderline IQ were found in 19%, 32%, and 26% of the patients respectively. Cognitive dysfunction was present in 27% of the patients. CACNA1A gene mutation was identified in eight families, and KCNA1 and FGF14 mutation in one family respectively. The identification of a CACNA1A mutation was significantly associated with BTU (p=0.03) and with cognitive dysfunction (p=0.01). Patients with BPV were less likely to have cognitive dysfunction. INTERPRETATION: Children with BPT, BPV, or BTU are at high risk of impaired psychomotor and cognitive development. These syndromes should not be regarded as benign and should be considered as part of the spectrum of a neurodevelopmental disorder. WHAT THIS PAPER ADDS OK: Patients with benign paroxysmal torticollis (BPT), benign paroxysmal vertigo (BPV), and benign tonic upward gaze (BTU) have an increased risk of psychomotor delay. These patients also have an increased risk of abnormal neurological examination and cognitive dysfunction. Gene mutations, especially in CACNA1A, were identified in 21% of the families. BPT, BTU, and BPV should not be regarded as benign. BPT, BTU, and BPV should be considered as part of the spectrum of a neurodevelopmental disorder.

Clinical factors associated with decision to recommend methylphenidate treatment for children with ADHD in France.

European guidelines advise on best practices for the diagnosis and non-pharmacological and pharmacological treatment of attention-deficit hyperactivity disorder (ADHD). This study aimed to (1) assess whether clinician's decisions to initiate methylphenidate treatment in children diagnosed with ADHD are in accordance with European guidelines and (2) identify clinical factors associated with the decision to recommend methylphenidate prescription. 5 to 13-year-old patients with an ADHD diagnosis were consecutively evaluated in an outpatient child and adolescent psychiatry clinic in France. Patients underwent a multidisciplinary evaluation including a diagnostic interview, symptom severity assessments with parent questionnaires, and IQ testing. We compared children with (n = 105) and without (n = 55) recommended methylphenidate treatment using Student's t test or Wilcoxon Mann-Whitney test and Chi-square or Fisher's test. Multivariate logistic regression was implemented to determine the respective influence of each variable on treatment recommendation. Recommendation to initiate methylphenidate treatment was associated with (1) ADHD combined presentation, (2) co-occurring Oppositional Defiant Disorder/Conduct Disorder (ODD/CD), Developmental Coordination Disorder (DCD) and Learning Disorder (LD), (3) clinical severity and impairment indicated on parent questionnaires, and (4) reduced perceptual reasoning. Using a multivariate regression model, ADHD combined presentation [combined versus predominantly hyperactive/impulsive and unspecified OR 4.52 (1.23-16.55), p = 0.023], age [OR 1.46 (1.14-1.88), p = 0.003], ODD/CD [OR 5.53 (2.19-14.01), p < 0.001], DCD [OR 4.22 (1.70-10.48), p = 0.002], PRI [OR 0.97 (0.94-0.99), p = 0.01] were significantly associated with recommendation of methylphenidate treatment. Our results indicate that clinicians' treatment decision-making complies with European guidelines and is furthermore associated with the type and severity of ADHD symptoms but also with co-occurring disorders.

Prevalence of Antipsychotic-Treated Patients in a Cohort of Adult Addicted Patients.

PURPOSE: The objective of this cross-sectional study was to describe and estimate the prevalence of antipsychotics (AP) in a cohort of addicted patients, and to compare the profiles of addictive patients receiving AP or not. METHODS: We included all adult patients seen at the addiction care center of Montpellier University Hospital, between January 1, 2015, and March 31, 2015. Demographic, clinical, and therapeutic data were collected from the patients' medical records. RESULTS: During the study period, 415 patients were included, with a mean age of 38 ± 10 years. They were mostly men (73.3%), French (54.9%), and unemployed (61.8%). Among the study population, 93 patients (patients treated with AP [trAP], 22.4%) were treated by 111 different AP, mainly cyamemazine (29.0% of treated patients), aripiprazole (20.4%), olanzapine (17.2%), and quetiapine (16.1%), mostly in monotherapy (80.6%) and by oral route (93.2% of AP). Psychiatric history was more frequent in trAP than in those without AP (untrAP) (55.9% vs 35.4% respectively; P < 0.001). Professional activity tended to be less frequent in patients with AP (25.3% vs 38.9%, P = 0.08).When compared with untrAP, trAP consumed more amphetamine (10.8% vs 4.4%; P = 0.02) and tended to consume less opiates (7.5% vs 14.9%; P = 0.06); the consumptions of cannabis (43.0% vs 35.7%; P = 0.20) and cocaine (22.6% vs 16.8%; P = 0.20) were not statistically different.Opiate maintenance therapy was reported in 63.7% of trAP and 68.4% of untrAP (P = 0.41): it consisted of methadone (trAP, 60.3% vs untrAP, 56.5%) and buprenorphine (trAP, 39.7% vs untrAP, 43.5%). CONCLUSIONS: The concomitant management of psychiatric and substance use disorders in the same center may explain the high prevalence of trAP in this study. Cannabis and psychostimulants may have been used in these patients as self-medication for mental disease-related symptoms or adverse effects of APs.

Three Complementary Approaches to Characterize Buprenorphine Misuse.

BACKGROUND: In France, buprenorphine has been available for opioid maintenance therapy since 1996 and since then its misuse has been continuously evaluated by the French health authorities. OBJECTIVES: To characterize buprenorphine misuse in Languedoc-Roussillon (LR) region, using three different approaches. METHODS: Three different data sources were analyzed : (i) spontaneous reports (NotS) of buprenorphine misuse or dependence, (ii) a specific periodic survey from specialized care centers (OPPIDUM) over 11 years (2002-2012) and (iii) a drug reimbursement database (DRB). RESULTS: A total of 209 spontaneous reports were collected. The main type of buprenorphine misuse was use by an unintended route of administration. The main complications notified were directly related to the injection of buprenorphine. NotS enabled the collection of data about severe clinical complications or new diversion phenomenon. The OPPIDUM LR survey revealed a decrease in the buprenorphine misuse indicator through the study period. The DRB analysis identified one subgroup of patients with a buprenorphine deviant behavior, characterized by a significantly greater number of dispensing episodes, pharmacies, prescribers, daily dose and switch between buprenorphine forms (princeps and generic). The DRB analysis provides data on buprenorphine diversion in the context of outpatients care. CONCLUSION: The three complementary approaches allowed us to characterize buprenorphine misuse in LR area. The three approaches are complementary because each data source provides different types of information.

Impact of graft nephrectomy on outcomes of second kidney transplantation.

OBJECTIVES: To determine the impact of renal graft nephrectomy on second kidney transplantation survival. METHODS: We carried out a retrospective single-center study by analyzing cases performed from January 2000 to December 2011. Retransplanted patients who underwent previous allograft nephrectomy more than 3 months post-transplantation (group 1) were compared with those who did not (group 2) in terms of graft survival, incidences of acute rejection and delayed graft function. Multivariate Cox proportional hazard models were used to assess risk factors of graft loss after retransplantation. RESULTS: Overall, 146 patients were analyzed, including 52 (35.6%) in group 1 and 94 (64.4%) in group 2. Group 1 patients presented a significantly shorter first graft survival (0.8 vs 8.6 years, P < 0.001) and more anti-class I antibodies (90.5% vs 74.2%, P = 0.03). A total of 10 patients (19%) in group 1 and 16 patients (17%) in group 2 had at least one acute rejection episode (P = 0.74). Delayed graft function was observed in 13 patients (25%) in group 1 and 17 patients (18%) in group 2 (P = 0.32). Graft survival at 1, 5 and 10 years was, respectively, 94%, 81% and 58% in group 1, and 99%, 93% and 66% in group 2 (P = 0.10). Graft survival was decreased by increased donor age and serum creatinine, and tended to be associated with post-transplantation presence of anti-class I and II antibodies. Graft nephrectomy was not associated with graft survival in multivariate analysis. CONCLUSIONS: Graft nephrectomy, probably a marker of high immunological risk patients, is not a risk factor of increased retransplant failure.

ROX (Respiratory rate-OXygenation) index to predict early response to high-flow nasal cannula therapy in infants with viral bronchiolitis.

INTRODUCTION: High-flow nasal cannula (HFNC) is commonly used as first step respiratory support in infants with moderate-to-severe acute viral bronchiolitis (AVB). This device, however, fails to effectively manage respiratory distress in about a third of patients, and data are limited on determinants of patient response. The respiratory rate-oxygenation (ROX) index is a relevant tool to predict the risk for HFNC failure in adult patients with lower respiratory tract infections. The primary objective of this study was to assess the relationship between ROX indexes collected before and 1 h after HFNC initiation, and HFNC failure occurring in the following 48 h in infants with AVB. METHOD: This is an ancillary study to the multicenter randomized controlled trial TRAMONTANE 2, that included 286 infants of less than 6 months with moderate-to-severe AVB. Collection of physiological variables at baseline (H0), and 1 h after HFNC (H1), included heart rate (HR), respiratory rate (RR), fraction of inspired oxygen (FiO2), respiratory distress score (modified Wood's Clinical Asthma Score [mWCAS]), and pain and discomfort scale (EDIN). ROX and ROX-HR were calculated as SpO 2 FiO 2 RR $\frac{\left(\frac{{\mathrm{SpO}}_{2}}{{\mathrm{FiO}}_{2}}\right)}{\mathrm{RR}}$ and 100 × ROX HR $100\times \frac{\mathrm{ROX}}{\mathrm{HR}}$ , respectively. Predefined HFNC failure criteria included increase in respiratory distress score or RR, increase in discomfort, and severe apnea episodes. The accuracies of ROX, ROX-HR indexes and clinical variable to predict HFNC failure were assessed using receiver operating curve analysis. We analyzed predictive factors of HFNC failure using multivariate logistic regressions. RESULT: HFNC failure occurred in 111 of 286 (39%) infants, and for 56 (50% of the failure) of them within the first 6 h. The area under the curve of ROX indexes at H0 and H1 were, respectively, 0.56 (95% confidence interval [CI] 0.48-0.63, p = 0.14), 0.56 (95% CI 0.49-0.64, p = 0.09). ROX-HR performances were better but remained poorly discriminant. HFNC failure was associated with higher mWCAS score at H1 (p < 0.01) and lower decrease in EDIN scale during the first hour of HFNC delivery (p = 0.02). In the multivariate analyses, age and mWCAS score were were found to be independent factors associated with HFNC failure at H0. At H1, weight and mWCAS were associated factors. CONCLUSION: In this study, neither ROX index, nor physiological variables usually collected in infants with AVB had early discriminatory capacity to predict HFNC failure.

Predicting One-Year Mortality after Discharge Using Acute Heart Failure Score (AHFS).

Background: Acute heart failure (AHF) represents a leading cause of unscheduled hospital stays, frequent rehospitalisations, and mortality worldwide. The aim of our study was to develop a bedside prognostic tool, a multivariable predictive risk score, that is useful in daily practice, thus providing an early prognostic evaluation at admission and an accurate risk stratification after discharge in patients with AHF. Methods: This study is a subanalysis of the STADE HF study, which is a single-centre, prospective, randomised controlled trial enrolling 123 patients admitted to hospital for AHF. Here, 117 patients were included in the analysis, due to data exhaustivity. Regression analysis was performed to determine predictive variables for one-year mortality and/or rehospitalisation after discharge. Results: During the first year after discharge, 23 patients died. After modellisation, the variables considered to be of prognostic relevance in terms of mortality were (1) non-ischaemic aetiology of HF, (2) elevated creatinine levels at admission, (3) moderate/severe mitral regurgitation, and (4) prior HF hospitalisation. We designed a linear model based on these four independent predictive variables, and it showed a good ability to score and predict patient mortality with an AUC of 0.84 (95%CI: 0.76-0.92), thus denoting a high discriminative ability. A risk score equation was developed. During the first year after discharge, we observed as well that 41 patients died or were rehospitalised; hence, while searching for a model that could predict worsening health conditions (i.e., death and/or rehospitalisation), only two predictive variables were identified: non-ischaemic HF aetiology and previous HF hospitalisation (also included in the one-year mortality model). This second modellisation showed a more discrete discriminative ability with an AUC of 0.67 (95% C.I. 0.59-0.77). Conclusions: The proposed risk score and model, based on readily available predictive variables, are promising and useful tools to assess, respectively, the one-year mortality risk and the one-year mortality and/or rehospitalisations in patients hospitalised for AHF and to assist clinicians in the management of patients with HF aiming at improving their prognosis.

Sacubitril/valsartan has an underestimated impact on the right ventricle in patients with sleep-disordered breathing, especially central sleep apnoea syndrome.

BACKGROUND: Sacubitril/valsartan has been demonstrated to significantly improve left ventricular performance and remodelling in patients with heart failure. However, its effects on the right ventricle in patients with chronic heart failure and sleep-disordered breathing (SDB) have not been studied. AIM: To investigate the impact of sacubitril/valsartan treatment on right ventricular function in patients with SDB. METHODS: This was a subanalysis of an observational prospective multicentre study involving 101 patients. At inclusion, patients were evaluated by echocardiography and nocturnal ventilatory polygraphy, which allowed patients to be divided into three groups: "central-SDB"; "obstructive-SDB"; and "no-SDB". RESULTS: After 3 months of sacubitril/valsartan therapy, a positive impact on right ventricular function was observed. In the general population, tricuspid annular plane systolic excursion increased by +1.32±4.74mm (P=0.024) and systolic pulmonary artery pressure decreased by -3.1±10.91mmHg (P=0.048). The central-SDB group experienced the greatest echocardiographic improvement, with a significant increase in tricuspid annular plane systolic excursion of +2.1±4.9mm (P=0.045) and a significant reduction in systolic pulmonary artery pressure of -8.4±9.7mmHg (P=0.001). CONCLUSIONS: Sacubitril/valsartan improved right ventricular function in patients with heart failure and SDB after only 3 months of treatment. The greatest improvement in right ventricular function was observed in the central-SDB group.

Life expectancy of patients with hepatocellular carcinoma according to the upfront treatment: A nationwide analysis.

PURPOSE: The purpose of this study was to update the life expectancy of patients with hepatocellular carcinoma (HCC) in an exhaustive nationwide population according to the upfront treatment performed. MATERIALS AND METHODS: From the French Program for the Medicalization of Information System database, all patients older than 18 years diagnosed with a de novo HCC from January 2011 to December 2018 were retrospectively selected. Five-year survival rates (95% confidence intervals [CI]) were computed according to the first surgical or interventional radiology procedures performed. RESULTS: A total of 63,996 patients (80% men) with a median age of 68 years (Q1, Q3: 61, 77) were selected, including 24,007 patients who underwent at least one procedure (5-year survival of 45.5%; (95% CI: 44.8-46.2), and 39,989 with none (5-year survival, 9.6%; (95% CI: 9.3-10.0). Only 20.5% (13,101/63,996) of patients could undergo an upfront curative procedure. Liver transplantation achieved the best outcome, whether performed upfront (n = 791; 5-year survival, 79.0% [95% CI: 76.1-82.1]) or during subsequent steps (n = 2217; 5-year survival 80.9% [95% CI: 79.2-82.7]). Tumor ablation (n = 5306), open resection (n = 5171), and minimally-invasive resection (n = 1833) achieved 5-year survival rates of 53.8% (95% CI: 52.3-55.4), 54.1% (95% CI: 52.6-55.6), and 66.2% (95% CI: 63.7-68.7), respectively, with more patients with cirrhosis and subsequent procedures in the tumor ablation group. Patients with upfront transarterial (chemo)embolization (n = 10,247) and selective internal radiation therapy (n = 659) had 5-year survival rates of 31.3% (95% CI: 30.3-32.4) and 18.5% (95% CI: 15.2-22.5). CONCLUSION: While HCC remains mostly diagnosed at an advanced stage associated with a poor prognosis, all the curative options provide 5-year survival rates above 50%.

Multicytokine detection improves latent tuberculosis diagnosis in health care workers.

In a low-incidence setting, health care workers (HCW) are at a higher risk of tuberculosis than the general population. The suboptimal sensitivity of the QuantiFERON-TB Gold In-Tube (QFT) test remains a critical issue when identifying occupational latent tuberculosis infection (LTBI) in HCW. The aim of this study was to identify additional biomarkers in order to overcome the limits of gamma interferon (IFN-γ) release assays (IGRAs) and improve the performance of LTBI diagnosis within this population. Seventy Bacille Calmette-Guérin-vaccinated HCW regularly exposed to Mycobacterium tuberculosis were grouped according to QFT results into an LTBI-positive group (positive QFT, n = 8), an LTBI-negative group (normal QFT and negative tuberculin skin test [TST], n = 21), and an undetermined group (subpositive QFT and/or positive TST, n = 41). The secretion of 22 cytokines in response to QFT-specific stimulation was quantified using a multiparameter-based immunoassay. As a result, thresholds discriminating LTBI-positive from LTBI-negative HCW were established by comparing areas under the receiver operating characteristic curves for interleukin-2 (IL-2), IL-15, IFN-γ-induced protein 10 (IP-10), and the monokine induced by IFN-γ (MIG), which are biomarkers differentially secreted by the two groups. The combination of IL-15 and MIG provided a sensitivity of 100% and a specificity of 94.1% in distinguishing LTBI-positive from LTBI-negative HCW. When using IL-15 and MIG among the undetermined group, 6/45 HCW could be classified in the LTBI-positive group. The use of additional biomarkers after IGRA screening could improve the diagnosis of LTBI. The performance of these biomarkers and their use in combination with TST and/or QFT, as well as the cost-effectiveness of such a diagnostic strategy, should be evaluated in further larger clinical trials.

Survivorship of 4,748 Contemporary Total Ankle Replacements from the French Discharge Records Database.

BACKGROUND: Studies of survivorship of primary total ankle replacements (TARs) beyond 5 years have shown varying results among early and modern designs. National cohorts give valuable insights about TAR outcomes, revision risk factors, and specific designs. The purpose of this study was to investigate implant survivorship and risk factors for revision of contemporary TARs using our national database. METHODS: This observational study included patients identified in the national PMSI (Programme médicalisé des systèmes d'information) database as having undergone TAR from 2010 to 2019. Demographics, discharge data, concomitant procedures, and type of implant were extracted. Kaplan-Meier estimations were performed to determine time to revision using metal component revision for implant failure and revision for deep infection as end points. Weighted Cox models were used for risk factor analysis, including risks of early revision (within the first 2 years). The adjusted hazard ratios (HRadj) were reported with 95% confidence intervals. RESULTS: A cohort of 4,748 patients was extracted. The mean age at surgery was 63 years; 43% of the patients were female. The mean follow-up was 5 years (range, 1 to 10 years). Revisions were noted in 817 cases (17%), including 734 with metal component revision and 83 with revision due to deep infection. The 1-year, 2-year, 5-year, and 10-year survivorship free of metal component revision was 95%, 90%, 84%, and 78%, respectively. Younger age, implants derived from second-generation designs, and an institutional volume of ≤10 TARs per year were found to be independent predictors of revision for any cause. In addition to the above factors (except for implant generation), male sex and concomitant osteotomies and/or fusion were found to be significant predictors for any early revision. CONCLUSIONS: The 10-year survivorship free of metal component revision after TAR was 78%, which was consistent with other national registries. Revisions were associated with young age, associated arthritis or deformities requiring concomitant fusion or osteotomy, and implants derived from second-generation designs. Institutions where >10 procedures were performed per year were associated with better TAR survivorship. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Vascular complications and bleeding after balloon aortic valvuloplasty performed with or without heparin: HEPAVALVE randomized study.

Background: Vascular and bleeding events remain the main complications after balloon aortic valvuloplasty (BAV). While BAV is usually performed with per procedural heparin injection, BAV performed without heparin may reduce hemorrhagic events. We aimed to determine whether vascular and bleeding complications may be reduced with BAV performed without heparin. Methods: This randomized, double-blind, placebo-controlled study was conducted from January 2013 to September 2016. Patients were randomly assigned to placebo or intravenous unfractionated heparin (UH) 50 IU/kg bolus during the procedure. The primary endpoint included major vascular, bleeding and ischemic complications (stroke, transient ischemic attack, myocardial infarction) according to VARC-2 criteria. Results: Among 89 randomized patients, 82 completed the study (n = 39 in the UH group and n = 43 in the placebo group). At baseline, diabetes, sex male and renal failure were more frequent in the UH group and peripheral artery disease was more frequent in the placebo group. The primary endpoint was achieved in 7 patients (8.5%), 1 in the placebo group (2.3%) versus 6 in the UH group (15.4%). After adjustment on diabetes, sex, renal failure, peripheral artery disease, percutaneous closure device and chronic obstructive pulmonary disease, UH utilization was associated with a significant risk of major vascular, bleeding and ischemic complications (primary endpoint) (adjOR: 11.9; 95%CI: 1.2-117.2; p = 0.03). Hospitalization length was lower in the placebo group compared to the UH group (p = 0.03). Conclusions: BAV without per procedural UH was associated with a reduction of major VC and bleeding events without increasing the ischemic risk and with a shorter hospitalization length.

Cataract extraction and intraocular pressure-lowering agents delivery: A nationwide French study between 2005 and 2017.

PURPOSE: Cataract and glaucoma are among the leading causes of blindness worldwide in older people, and they are often concomitant. To assess topical intraocular (IOP)-lowering agents delivery changes after cataract extraction. MATERIAL AND METHODS: Longitudinal matched exposed-unexposed study from the French national healthcare database from January 1, 2005 to January 1, 2017. We compared individuals using topical IOP-lowering agents who underwent bilateral cataract extraction with individuals matched on IOP-lowering agents load, age, and sex who did not undergo cataract extraction. IOP-lowering agents number of drops was assessed 12 months before the first cataract extraction and compared with number of drops 12 months after the second cataract extraction. RESULTS: About 1194 individuals treated with IOP-lowering agents were included, 597 exposed to bilateral cataract extraction and 597 unexposed to any surgery (total mean age 74.8 ± 8.3 years; 69.0% women). Mean IOP-lowering agents delivery at baseline was 1.4 daily drops in both groups. The mean number of drops decreased greater in the exposed than unexposed group (-25.5% vs -3.5%; p < 0.0001). Overall, 159 (26.6%) and 48 (8.0%) individuals in the exposed and unexposed groups interrupted medication (p < 0.0001). CONCLUSIONS: A decrease of around one quarter of IOP-lowering agents delivery was observed after cataract extraction in the present real-life study with a longstanding interruption observed in one quarter of patients. Phacoemulsification as a standalone procedure reduces IOP-lowering agents delivery in ocular hypertension and glaucoma.