Impact of sleep disturbances on outcomes in intensive care units.

BACKGROUND: Sleep deprivation is common in intensive care units (ICUs) and may alter respiratory performance. Few studies have assessed the role of sleep disturbances on outcomes in critically ill patients. OBJECTIVES: We hypothesized that sleep disturbances may be associated with poor outcomes in ICUs. METHODS: Post-hoc analysis pooling three observational studies assessing sleep by complete polysomnography in 131 conscious and non-sedated patients included at different times of their ICU stay. Sleep was assessed early in a group of patients admitted for acute respiratory failure while breathing spontaneously (n = 34), or under mechanical ventilation in patients with weaning difficulties (n = 45), or immediately after extubation (n = 52). Patients admitted for acute respiratory failure who required intubation, those under mechanical ventilation who had prolonged weaning, and those who required reintubation after extubation were considered as having poor clinical outcomes. Durations of deep sleep, rapid eye movement (REM) sleep, and atypical sleep were compared according to the timing of polysomnography and the clinical outcomes. RESULTS: Whereas deep sleep remained preserved in patients admitted for acute respiratory failure, it was markedly reduced under mechanical ventilation and after extubation (p < 0.01). Atypical sleep was significantly more frequent in patients under mechanical ventilation than in those breathing spontaneously (p < 0.01). REM sleep was uncommon at any time of their ICU stay. Patients with complete disappearance of REM sleep (50% of patients) were more likely to have poor clinical outcomes than those with persistent REM sleep (24% vs. 9%, p = 0.03). CONCLUSION: Complete disappearance of REM sleep was significantly associated with poor clinical outcomes in critically ill patients.

Similarities and differences of interstitial lung disease associated with pathogenic variants in SFTPC and ABCA3 in adults.

BACKGROUND AND OBJECTIVE: Variants in surfactant genes SFTPC or ABCA3 are responsible for interstitial lung disease (ILD) in children and adults, with few studies in adults. METHODS: We conducted a multicentre retrospective study of all consecutive adult patients diagnosed with ILD associated with variants in SFTPC or ABCA3 in the French rare pulmonary diseases network, OrphaLung. Variants and chest computed tomography (CT) features were centrally reviewed. RESULTS: We included 36 patients (median age: 34 years, 20 males), 22 in the SFTPC group and 14 in the ABCA3 group. Clinical characteristics were similar between groups. Baseline median FVC was 59% ([52-72]) and DLco was 44% ([35-50]). An unclassifiable pattern of fibrosing ILD was the most frequent on chest CT, found in 85% of patients, however with a distinct phenotype with ground-glass opacities and/or cysts. Nonspecific interstitial pneumonia and usual interstitial pneumonia were the most common histological patterns in the ABCA3 group and in the SFTPC group, respectively. Annually, FVC and DLCO declined by 1.87% and 2.43% in the SFTPC group, respectively, and by 0.72% and 0.95% in the ABCA3 group, respectively (FVC, p = 0.014 and DLCO , p = 0.004 for comparison between groups). Median time to death or lung transplantation was 10 years in the SFTPC group and was not reached at the end of follow-up in the ABCA3 group. CONCLUSION: SFTPC and ABCA3-associated ILD present with a distinct phenotype and prognosis. A radiologic pattern of fibrosing ILD with ground-glass opacities and/or cysts is frequently found in these rare conditions.

Auto-adjusted versus fixed positive airway pressure in patients with severe OSA: A large randomized controlled trial.

BACKGROUND AND OBJECTIVE: Continuous positive airway pressure (CPAP) in the treatment of severe obstructive sleep apnoea (OSA) can be used in fixed CPAP or auto-adjusted (APAP) mode. The aim of this prospective randomized controlled clinical study was to evaluate the 3 month-efficacy of CPAP used either in fixed CPAP or APAP mode. METHODS: Eight hundred one patients with severe OSA were included in twenty-two French centres. After 7 days during which all patients were treated with APAP to determine the effective pressure level and its variability, 353 and 351 patients were respectively randomized in the fixed CPAP group and APAP group. After 3 months of treatment, 308 patients in each group were analysed. RESULTS: There was no difference between the two groups in terms of efficacy whatever the level of efficient pressure and pressure variability (p = 0.41). Exactly, 219 of 308 patients (71.1%) in the fixed CPAP group and 212 of 308 (68.8%) in the APAP group (p = 0.49) demonstrated residual apnoea hypopnoea index (AHI) <10/h and Epworth Score <11. Tolerance and adherence were also identical with a similar effect on quality of life and blood pressure evaluation. CONCLUSION: The two CPAP modes, fixed CPAP and APAP, were equally effective and tolerated in severe OSA patients.

AVAPS-AE versus ST mode: A randomized controlled trial in patients with obesity hypoventilation syndrome.

BACKGROUND AND OBJECTIVE: Average volume-assured pressure support-automated expiratory positive airway pressure (AVAPS-AE) combines an automated positive expiratory pressure to maintain upper airway patency to an automated pressure support with a targeted tidal volume. The aim of this study was to compare the effects of 2-month AVAPS-AE ventilation versus pressure support (ST) ventilation on objective sleep quality in stable patients with OHS. Secondary outcomes included arterial blood gases, health-related quality of life, daytime sleepiness, subjective sleep quality and compliance to NIV. METHODS: This is a prospective multicentric randomized controlled trial. Consecutive OHS patients included had daytime Pa CO2 > 6 kPa, BMI ≥ 30 kg/m2 , clinical stability for more than 2 weeks and were naive from home NIV. PSG were analysed centrally by two independent experts. Primary endpoint was sleep quality improvement at 2 months. RESULTS: Among 69 trial patients, 60 patients had successful NIV setup. Baseline and follow-up PSG were available for 26 patients randomized in the ST group and 30 in the AVAPS-AE group. At baseline, Pa CO2 was 6.94 ± 0.71 kPa in the ST group and 6.61 ± 0.71 in the AVAPS-AE group (P = 0.032). No significant between-group difference was observed for objective sleep quality indices. Improvement in Pa CO2 was similar between groups with a mean reduction of -0.87 kPa (95% CI: -1.12 to -0.46) in the ST group versus -0.87 kPa (95% CI: -1.14 to -0.50) in the AVAPS-AE group (P = 0.984). Mean NIV use was 6.2 h per night in both groups (P = 0.93). NIV setup duration was shorter in the AVAPS-AE group (P = 0.012). CONCLUSION: AVAPS-AE and ST ventilation for 2 months had similar impact on sleep quality and gas exchange.

Effect of mandibular advancement therapy on inflammatory and metabolic biomarkers in patients with severe obstructive sleep apnoea: a randomised controlled trial.

Systemic inflammation and metabolic disorders are among the mechanisms linking obstructive sleep apnoea (OSA) and cardiovascular disease (CVD). In 109 patients with severe OSA and no overt CVD, biomarkers of inflammation (C reactive protein, interleukin-6, tumour necrosis factor-α and its receptors, adiponectin, leptin and P-selectin), glucose and lipid metabolism, and N-terminal pro-brain natriuretic peptide, were measured before and after 2 months of treatment with a mandibular advancement device (MAD) (n=55) or a sham device (n=54). MAD reduced the Apnoea-Hypopnoea Index (p<0.001) but had no effect on circulating biomarkers compared with the sham device, despite high treatment adherence (6.6 hour/night). TRIAL REGISTRATION NUMBER: NCT01426607.

Polyphenols Have No Impact on Endothelial Function in Patients with Obstructive Sleep Apnea: A Randomized Controlled Trial.

Background: Endothelial dysfunction, a pathophysiologic determinant of atherogenesis, has been found to occur in obstructive sleep apnea syndrome (OSA) and is improved by continuous positive airway pressure (CPAP). However, the efficacy of CPAP therapy is limited by variable adherence. Alternative treatment strategies are needed. The impact of polyphenols on endothelial function has never been evaluated in OSA. Objective: We evaluated the impact of 1-mo supplementation with grape juice polyphenols (GJPs) on the reactive hyperemia index (RHI), a validated measure of endothelial function in patients with severe OSA. Methods: Forty participants [75% men, median (IQR) age: 61 y (34, 64 y), BMI (in kg/m2): 30.6 (20.9, 33.7)] with severe OSA [median apnea-hypopnea index 43/h (33/h, 56/h)] were randomly assigned to receive GJPs (300 mg/d; n = 20) or placebo (n = 20) for 1 mo. The primary outcome was the change in RHI between baseline and after 1 mo of GJPs or placebo. Secondary outcome measures included changes in blood pressure (BP), heart rate (HR), and polysomnographic indexes. Results: No significant differences in RHI and BP outcomes were observed between the GJPs and placebo groups. A significant between-group difference was observed for HR changes [-1 bpm (-5, +5 bpm) in the GJPs group compared with +6 bpm (+3, +10 bpm) in the placebo group; P = 0.001]. A significant decrease in total sleep time was observed in the GJPs group compared with the placebo group [-10 min (-33, 6 min) compared with +15 min (-12, 40 min), respectively; P = 0.02], with no between-group differences in the distribution of sleep stages. Conclusions: In participants with severe OSA and no overt cardiovascular disease, 1-mo GJP supplementation had no effect on endothelial function. This trial was registered at clinicaltrials.gov as NCT01977924.

Impact of Mandibular Advancement Therapy on Endothelial Function in Severe Obstructive Sleep Apnea.

RATIONALE: Endothelial dysfunction, a major predictor of late cardiovascular events, is linked to the severity of obstructive sleep apnea (OSA). OBJECTIVES: To determine whether treatment with mandibular advancement device, the main alternative to continuous positive airway pressure, improves endothelial function in patients with severe OSA. METHODS: In this trial, we randomized patients with severe OSA and no overt cardiovascular disease to receive 2 months of treatment with either effective mandibular advancement device or a sham device. The primary outcome, change in reactive hyperemia index, a validated measurement of endothelial function, was assessed on an intention-to-treat basis. An embedded microsensor objectively measured treatment compliance. MEASUREMENTS AND MAIN RESULTS: A total of 150 patients (86% males; mean [SD] age, 54 [10] yr; median [interquartile range] apnea-hypopnea index, 41 [35-53]; mean [SD] Epworth sleepiness scale, 9.3 [4.2]) were randomized to effective mandibular advancement device (n = 75) or sham device (n = 75). On intention-to-treat analysis, effective mandibular advancement device therapy was not associated with improvement of endothelial function compared with the sham device. Office and ambulatory blood pressure outcomes did not differ between the two groups. Effective mandibular advancement device therapy was associated with significant improvements in apnea-hypopnea index (P < 0.001); microarousal index (P = 0.008); and symptoms of snoring, fatigue, and sleepiness (P < 0.001). Mean (SD) objective compliance was 6.6 (1.4) h/night with the effective mandibular advancement device versus 5.6 (2.3) h/night with the sham device (P = 0.006). CONCLUSIONS: In moderately sleepy patients with severe OSA, mandibular advancement therapy reduced OSA severity and related symptoms but had no effect on endothelial function and blood pressure despite high treatment compliance. Clinical trial registered with www.clinicaltrials.gov (NCT 01426607).

Association between obstructive sleep apnea severity and endothelial dysfunction in patients with type 2 diabetes.

BACKGROUND: Obstructive sleep apnea (OSA) and type 2 diabetes (T2D) are associated with endothelial dysfunction a main predictor of late cardiovascular (CV) events. Despite the high prevalence of OSA in patients with T2D, the impact of OSA severity on endothelial function has not been clearly elucidated. The aim of this cross-sectional study was to determine whether increasing OSA severity is associated with poorer endothelial function in patients with T2D. METHODS: 140 patients with T2D and no overt CV disease underwent polysomnography, peripheral arterial tonometry, clinic blood pressure (BP) measurement, biological assessment for CV risk factors, daytime sleepiness and health related quality of life (HRQL) questionnaires. The following commonly used cut-offs for apnea-hypopnea index (AHI) were used to define 3 categories of disease severity: AHI < 15 (no OSA or mild OSA), 15 ≤ AHI < 30 (moderate OSA), and AHI ≥ 30 (severe OSA). The primary outcome was the reactive hyperemia index (RHI), a validated assessment of endothelial function. RESULTS: 21.4% of patients had moderate OSA and 47.6% had severe OSA. Increasing OSA severity and nocturnal hypoxemia were not associated with a significant decrease in RHI. Endothelial dysfunction (RHI < 1.67) was found in 47.1, 44.4 and 39.2% of patients with no OSA or mild OSA, moderate OSA and severe OSA, respectively (p = 0.76). After adjustment for confounders including body mass index, increasing OSA severity was associated with higher systolic BP (p = 0.03), lower circulating levels of adiponectin (p = 0.0009), higher levels of sP-selectin (p = 0.03), lower scores in 3 domains of HRQL including energy/vitality (p = 0.02), role functioning (p = 0.01), and social functioning (p = 0.04). CONCLUSIONS: Moderate to severe OSA is very common but has no impact on digital micro-vascular endothelial function in patients with T2D.

Screening for primary immune deficiency among patients with bronchiectasis.

INTRODUCTION: To assess frequency and methods of PID (primary immune deficiency) screening among patients with bronchiectasis by pneumologists in clinical practice. METHODS: All the patients hospitalized in the department of pneumology of the Poitiers University Hospital between April 2013 and April 2020 with a diagnosis of bronchiectasis on chest computerized tomography were included. Patients aged 70 and over and those with already known PID were excluded. Primary endpoint was the proportion of patients having had serum immunoglobulin (Ig) assay and serum protein electrophoresis (SPE) analysis. Secondary endpoints were factors associated with prescription of SPE and/or Ig assay, proportion of patients with newly diagnosed PID and their characteristics and factors associated with repeated courses of antibiotics. RESULTS: Among the 133 patients included, 43% had SPE+Ig assay, 34% SPE only and 23% neither. The proportion of patients with asthma was higher in the "SPE+Ig assay" group (33.3%) compared to the "SPE only" (11.1%) and the "Neither SPE nor Ig assay" groups (6.4%) (P=0.002). Four patients were newly diagnosed for PID of whom 3 had subclass IgG deficiency. Factors associated with repeated courses of antibiotics were generalized bronchiectasis (P=0.02) and asthma (P=0.04). CONCLUSION: PID is underscreened by pneumologists among patients with bronchiectasis. Association of SPE+Ig assay+IgG subclass assay appears as the most accurate combination.

Sleep Assessment in Critically Ill Patients With Acute Hypoxemic Respiratory Failure.

BACKGROUND: Sleep deprivation alters respiratory muscle performance and may precipitate respiratory failure. This study aimed to assess sleep in subjects admitted to ICU for acute hypoxemic respiratory failure and its role in the risk of intubation. METHODS: This was a prospective observational single-center cohort study including subjects admitted to ICU for de novo acute hypoxemic respiratory failure defined as breathing frequency ≥ 25 breaths/min or clinical signs of respiratory distress and PaO2 /FIO2 < 300 mm Hg while receiving high-flow nasal oxygen. Subjects with altered consciousness, central nervous or psychiatric disorders, continuous sedation or neuroleptic medication, or were uncooperative were excluded. Sleep was assessed by complete polysomnography (PSG) the night following ICU admission. The main outcome was to assess sleep among subjects with acute hypoxemic respiratory failure and to compare sleep between subjects who eventually required intubation to those who did not. RESULTS: Over a 24-month inclusion period, 34 subjects had complete PSG, among whom 5 (15%) required intubation in the ICU. Total sleep time was 4.2 h in median (interquartile range 2.9-6.8); deep-sleep duration was 70 min (34-127), and rapid eye movement (REM) sleep duration was 9 min (0-28). Among them, 13 subjects (38%) had no REM sleep. Total sleep time and duration of deep and REM sleep stages did not differ between subjects who required intubation and those successfully treated with high-flow nasal oxygen. CONCLUSIONS: Whereas total sleep time remained relatively preserved in critically ill subjects with acute hypoxemic respiratory failure, REM sleep time was uncommon or completely absent in a large number of subjects. Sleep did not differ between subjects who required intubation and those who did not. However, given a trend toward an increased risk of intubation in subjects with a complete absence of REM sleep, further studies are needed to better explore the impact of REM sleep on the risk of intubation.

Influence of socio-economic status on functional recovery after ARDS caused by SARS-CoV-2: the multicentre, observational RECOVIDS study.

PURPOSE: Survivors after acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19) are at high risk of developing respiratory sequelae and functional impairment. The healthcare crisis caused by the pandemic hit socially disadvantaged populations. We aimed to evaluate the influence of socio-economic status on respiratory sequelae after COVID-19 ARDS. METHODS: We carried out a prospective multicenter study in 30 French intensive care units (ICUs), where ARDS survivors were pre-enrolled if they fulfilled the Berlin ARDS criteria. For patients receiving high flow oxygen therapy, a flow ≥ 50 l/min and an FiO2 ≥ 50% were required for enrollment. Socio-economic deprivation was defined by an EPICES (Evaluation de la Précarité et des Inégalités de santé dans les Centres d'Examens de Santé - Evaluation of Deprivation and Inequalities in Health Examination Centres) score ≥ 30.17 and patients were included if they performed the 6-month evaluation. The primary outcome was respiratory sequelae 6 months after ICU discharge, defined by at least one of the following criteria: forced vital capacity < 80% of theoretical value, diffusing capacity of the lung for carbon monoxide < 80% of theoretical value, oxygen desaturation during a 6-min walk test and fibrotic-like findings on chest computed tomography. RESULTS: Among 401 analyzable patients, 160 (40%) were socio-economically deprived and 241 (60%) non-deprived; 319 (80%) patients had respiratory sequelae 6 months after ICU discharge (81% vs 78%, deprived vs non-deprived, respectively). No significant effect of socio-economic status was identified on lung sequelae (odds ratio (OR), 1.19 [95% confidence interval (CI), 0.72-1.97]), even after adjustment for age, sex, most invasive respiratory support, obesity, most severe P/F ratio (adjusted OR, 1.02 [95% CI 0.57-1.83]). CONCLUSIONS: In COVID-19 ARDS survivors, socio-economic status had no significant influence on respiratory sequelae 6 months after ICU discharge.

Sirolimus-Induced Pulmonary Alveolar Proteinosis in the Context of Hematopoietic Stem Cells Transplant Rejection: A Case Report.

Pulmonary alveolar proteinosis (PAP) is a rare parenchymal pulmonary disease, characterized by the accumulation of surfactant material in alveoli. Rare cases of pulmonary alveolar proteinosis have been reported following the use of sirolimus. All published cases have been described following solid organ transplantation, and symptoms improved quickly after treatment's cessation. We describe a case of PAP secondary to sirolimus treating graft-versus-host reaction in a patient who received a stem cell transplant for chronic lymphocytic leukemia. Pulmonary alveolar proteinosis was cured after stopping sirolimus without any other therapeutic management. PAP can be a rare but serious side effect of sirolimus. It is important to rule out other causes of primary or secondary PAP before suggesting a toxic drug cause. The main challenge is to quickly diagnose this side effect to stop exposure to the toxic agent.

ß Agonist Delivery by High-Flow Nasal Cannula During COPD Exacerbation.

BACKGROUND: Whereas high-flow nasal cannula (HFNC) oxygen therapy is increasingly used in patients with exacerbation of COPD, the effectiveness of ß 2 agonist nebulization through HFNC has been poorly assessed. We hypothesized that salbutamol vibrating-mesh nebulization through HFNC improves pulmonary function tests in subjects with COPD. METHODS: We conducted a physiological crossover study including subjects admitted to the ICU for severe exacerbation of COPD. After subject improvement allowing a 3-h washout period without bronchodilator, pulmonary function tests were performed while breathing through HFNC alone and after salbutamol vibrating-mesh nebulization through HFNC. The primary end point consisted in the changes in FEV1 before and after salbutamol nebulization. Secondary end points included the changes in FVC, peak expiratory flow (PEF), airway resistance, and clinical parameters. RESULTS: Among the 15 subjects included, mean (SD) FEV1 significantly increased after salbutamol nebulization from 931 mL (383) to 1,019 (432), mean difference +87 mL (95% CI 30-145) (P = .006). Similarly, FVC and PEF significantly increased, +174 mL (95% CI 66-282) (P = .004) and +0.3 L/min (95% CI 0-0.6) (P = .037), respectively. Airway resistances and breathing frequency did not significantly differ, whereas heart rate significantly increased after nebulization. CONCLUSIONS: In subjects with severe exacerbation of COPD, salbutamol vibrating-mesh nebulization through HFNC induced a significant bronchodilator effect with volume and flow improvement.

Influence of socioeconomic status on functional recovery after ARDS caused by SARS-CoV-2: a multicentre, observational study.

INTRODUCTION: Prognosis of patients with COVID-19 depends on the severity of the pulmonary affection. The most severe cases may progress to acute respiratory distress syndrome (ARDS), which is associated with a risk of long-term repercussions on respiratory function and neuromuscular outcomes. The functional repercussions of severe forms of COVID-19 may have a major impact on quality of life, and impair the ability to return to work or exercise. Social inequalities in healthcare may influence prognosis, with socially vulnerable individuals more likely to develop severe forms of disease. We describe here the protocol for a prospective, multicentre study that aims to investigate the influence of social vulnerability on functional recovery in patients who were hospitalised in intensive care for ARDS caused by COVID-19. This study will also include an embedded qualitative study that aims to describe facilitators and barriers to compliance with rehabilitation, describe patients' health practices and identify social representations of health, disease and care. METHODS AND ANALYSIS: The "Functional Recovery From Acute Respiratory Distress Syndrome (ARDS) Due to COVID-19: Influence of Socio-Economic Status" (RECOVIDS) study is a mixed-methods, observational, multicentre cohort study performed during the routine follow-up of post-intensive care unit (ICU) functional recovery after ARDS. All patients admitted to a participating ICU for PCR-proven SARS-CoV-2 infection and who underwent chest CT scan at the initial phase AND who received respiratory support (mechanical or not) or high-flow nasal oxygen, AND had ARDS diagnosed by the Berlin criteria will be eligible. The primary outcome is the presence of lung sequelae at 6 months after ICU discharge, defined either by alterations on pulmonary function tests, oxygen desaturation during a standardised 6 min walk test or fibrosis-like pulmonary findings on chest CT. Patients will be considered to be socially disadvantaged if they have an "Evaluation de la Précarité et des Inégalités de santé dans les Centres d'Examen de Santé" (EPICES) score ≥30.17 at inclusion. ETHICS AND DISSEMINATION: The study protocol and the informed consent form were approved by an independent ethics committee (Comité de Protection des Personnes Sud Méditerranée II) on 10 July 2020 (2020-A02014-35). All patients will provide informed consent before participation. Findings will be published in peer-reviewed journals and presented at national and international congresses. TRIAL REGISTRATION NUMBER: NCT04556513.

Role of sleep on respiratory failure after extubation in the ICU.

BACKGROUND: Sleep had never been assessed immediately after extubation in patients still in the ICU. However, sleep deprivation may alter respiratory function and may promote respiratory failure. We hypothesized that sleep alterations after extubation could be associated with an increased risk of post-extubation respiratory failure and reintubation. We conducted a prospective observational cohort study performed at the medical ICU of the university hospital of Poitiers in France. Patients at high-risk of extubation failure (> 65 years, with any underlying cardiac or lung disease, or intubated > 7 days) were included. Patients intubated less than 24 h, with central nervous or psychiatric disorders, continuous sedation, neuroleptic medication, or uncooperative were excluded. Sleep was assessed by complete polysomnography just following extubation including the night. The main objective was to compare sleep between patients who developed post-extubation respiratory failure or required reintubation and the others. RESULTS: Over a 3-year period, 52 patients had complete polysomnography among whom 12 (23%) developed post-extubation respiratory failure and 8 (15%) required reintubation. Among them, 10 (19%) had atypical sleep, 15 (29%) had no deep sleep, and 33 (63%) had no rapid eye movement (REM) sleep. Total sleep time was 3.2 h in median [interquartile range, 2.0-4.4] in patients who developed post-extubation respiratory failure vs. 2.0 [1.1-3.8] in those who were successfully extubated (p = 0.34). Total sleep time, and durations of deep and REM sleep stages did not differ between patients who required reintubation and the others. Reintubation rates were 21% (7/33) in patients with no REM sleep and 5% (1/19) in patients with REM sleep (difference, - 16% [95% CI - 33% to 6%]; p = 0.23). CONCLUSIONS: Sleep assessment by polysomnography after extubation showed a dramatically low total, deep and REM sleep time. Sleep did not differ between patients who were successfully extubated and those who developed post-extubation respiratory failure or required reintubation.

Chlorhexidine plus alcohol versus povidone iodine plus alcohol, combined or not with innovative devices, for prevention of short-term peripheral venous catheter infection and failure (CLEAN 3 study): an investigator-initiated, open-label, single centre, randomised-controlled, two-by-two factorial trial.

BACKGROUND: Two billion peripheral venous catheters are sold globally each year, but the optimal skin disinfection and types of devices are not well established. We aimed to show the superiority of disinfection with 2% chlorhexidine plus alcohol over 5% povidone iodine plus alcohol in preventing infectious complications, and of closed integrated catheters, positive displacement needleless-connectors, disinfecting caps, and single-use prefilled flush syringes used in combination (innovation group) over open catheters and three-way stopcocks for treatment administration (standard group) in preventing catheter failure. METHODS: We did an open-label, randomised-controlled trial with a two-by-two factorial design, for which we enrolled adults (age ≥18 years) visiting the emergency department at the Poitiers University Hospital, France, and requiring one peripheral venous catheter before admission to the medical wards. Before catheter insertion, patients were randomly assigned (1:1:1:1) using a secure web-based random-number generator to one of four treatment groups based on skin preparation and type of devices (innovative devices or standard devices; 2% chlorhexidine plus alcohol or 5% povidone iodine plus alcohol). Primary outcomes were the incidence of infectious complications (local infection, catheter colonisation, or bloodstream infections) and time between catheter insertion and catheter failure (occlusion, dislodgment, infiltration, phlebitis, or infection). This study is registered with ClinicalTrials.gov, NCT03757143. FINDINGS: 1000 patients were recruited between Jan 7, and Sept 6, 2019, of whom 500 were assigned to the chlorhexidine plus alcohol group and 500 to the povidone iodine plus alcohol group (250 with innovative solutions and 250 with standard devices in each antiseptic group). No significant interaction was found between the two study interventions. Local infections occurred less frequently with chlorhexidine plus alcohol than with povidone iodine plus alcohol (0 [0%] of 496 patients vs six [1%] of 493 patients) and the same was observed for catheter colonisation (4/431 [1%] vs 70/415 [17%] catheters among the catheters cultured; adjusted subdistribution hazard ratio 0·08 [95% CI 0·02-0·18]). Median time between catheter insertion and catheter failure was longer in the innovation group compared with the standard group (50·4 [IQR 29·6-69·4] h vs 30·0 [16·6-52·6] h; p=0·0017). Minor skin reactions occurred in nine (2%) patients in the chlorhexidine plus alcohol group and seven (1%) patients in the povidone iodine plus alcohol group. INTERPRETATION: For skin antisepsis, chlorhexidine plus alcohol provides greater protection of peripheral venous catheter-related infectious complications than does povidone iodine plus alcohol. Use of innovative devices extends the catheter complication-free dwell time. FUNDING: Becton Dickinson.

Sleep apnoea and endothelial dysfunction: An individual patient data meta-analysis.

We performed an individual patient data meta-analysis to investigate the association between obstructive sleep apnoea (OSA) severity and the reactive hyperaemia index (RHI) measured by peripheral arterial tonometry (PAT), a validated measurement of endothelial function, and a strong predictor of late cardiovascular (CV) events. Patients from 12 studies underwent PAT and overnight polysomnography or respiratory polygraphy for suspected OSA. Endothelial dysfunction was defined by a log-transformed RHI<0.51. Subgroup analyses were performed to investigate this relationship in specific populations. Among 730 patients without overt CV disease, 387 (53.0%) had severe OSA (apnoea-hypopnea index ≥30) and 164 (22.5%) exhibited endothelial dysfunction. After adjustment for age, gender, diastolic blood pressure, obesity, diabetes and chronic obstructive pulmonary disease, endothelial dysfunction was associated with severe OSA (odds ratio, OR [95% confidence interval]: 2.27 [1.12-4.60]; p = 0.02), and nocturnal hypoxemia defined by >20 min with oxygen saturation <90% (OR: 1.83 [1.22-2.92]; p = 0.004) or mean oxygen saturation <92% (OR: 1.52 [1.17-1.96]; p = 0.002). On subgroup analyses, the association between severe OSA and endothelial dysfunction was not significant in patients with hypertension, obesity and/or diabetes. Among adults without overt CV disease, severe OSA is independently associated with an increased risk of endothelial dysfunction that may predispose to late CV events.