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Background During unplanned respiratory-related hospitalizations, gradual improvement in physiological variables and reduced dependence on treatment are crucial for discharge decisions, possibly supported by discharge care bundles designed to reduce post-hospitalization readmission and mortality. However, patients prioritize symptom relief. This study tested the hypothesis that a significant proportion of patients admitted to a pulmonology ward for an acute respiratory episode experience dyspnea on the day of discharge. It further aimed to describe this dyspnea in a multidimensional manner. Methods This 10-week prospective study was conducted at a single center and included patients admitted for acute respiratory conditions such as COPD or asthma exacerbation, pneumonia, pulmonary embolism, or pleural disease, who, on admission, reported a rating of 3 or higher on the “immediate breathing discomfort” item of the Multidimensional Dyspnea Profile (MDP-A1). Dyspnea was assessed both at admission and at discharge using a multidimensional recall-based tool (MDP) and an instant unidimensional tool, the 10-cm visual analog scale (D-VAS). Results Seventy consecutive patients were included in the study. Although dyspnea ratings showed a statistically significant decrease during the hospital stay, dyspnea remained both frequent and intense at discharge. At discharge, 84% of patients provided MDP-A1 recall ratings above 0, with 70% rating their MDP-A1 at 3 or more. In contrast, only 22% provided D-VAS instant ratings of 3 or higher. The median MDP-A1 score was 4.0 [2.0–6.0]. “Air hunger” was the most frequently selected sensory descriptor. Conclusions Persistent dyspnea remains frequent and intense among patients being discharged after an acute respiratory episode.

Background The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak is spreading worldwide. To date, no specific treatment has convincingly demonstrated its efficacy. Hydroxychloroquine and lopinavir/ritonavir have potential interest, but virological and clinical data are scarce, especially in critically ill patients. Methods The present report took the opportunity of compassionate use and successive drug shortages to compare the effects of two therapeutic options, lopinavir/ritonavir and hydroxychloroquine, as compared to standard of care only. The primary outcomes were treatment escalation (intubation, extra-corporeal membrane oxygenation support, or renal replacement therapy) after day 1 until day 28. Secondary outcomes included ventilator-free days at day 28, mortality at day 14 and day 28, treatment safety issues and changes in respiratory tracts, and plasma viral load (as estimated by cycle threshold value) between admission and day 7. Results Eighty patients were treated during a 4-week period and included in the analysis: 22 (28%) received standard of care only, 20 (25%) patients received lopinavir/ritonavir associated to standard of care, and 38 (47%) patients received hydroxychloroquine and standard of care. Baseline characteristics were well balanced between the 3 groups. Treatment escalation occurred in 9 (41%), 10 (50%), and 15 (39%) patients who received standard of care only, standard of care and lopinavir/ritonavir, and standard of care and hydroxychloroquine, respectively ( p  = 0.567). There was no significant difference between groups regarding the number of ventilator-free days at day 28 and mortality at day 14 and day 28. Finally, there was no significant change between groups in viral respiratory or plasma load between admission and day 7. Conclusion In critically ill patients admitted for SARS-CoV-2-related pneumonia, no difference was found between hydroxychloroquine or lopinavir/ritonavir as compared to standard of care only on the proportion of patients who needed treatment escalation at day 28. Further randomized controlled trials are required to demonstrate whether these drugs may be useful in this context.

PurposeAt the critical care level, the flu surveillance system is limited in France, with heterogeneous regional modalities of implementation.Materials, patients and methodsWe aimed at assessing the relevance of the Assistance Publique-Hôpitaux de Paris (AP-HP) clinical data warehouse for estimating the burden of the influenza epidemic on medical adult critical care units of the AP-HP, and outcome of patients during the flu season 2017–2018. This exploratory multi-site epidemiological study comprised all consecutive adult stays (n = 320) in 18 medical intensive care units (ICU) or intermediate care wards (ICW) for probable or confirmed Influenza virus infection during the 2017–2018 flu season.ResultsPatients admitted to ICU/ICW had low vaccination coverage (21%), required life support in 60% of cases, stayed in the ICU for a median of 8 days, and had high 28-day mortality rate (19.7%; 95% confidence interval 15.5–24.5). Early prognostic factors included age, core temperature, the acute organ failures score, and the early administration of antiviral therapy.ConclusionsData directly extracted from the electronic medical records stored in the data warehouse provide detailed clinical, care pathway and prognosis information. The real-time availability should enable to detect and assess the burden of the most severe cases. By a firmer and more acute monitoring and adjustment of care and patient management, hospitals could generate more ICU/ICW capacities, sensitize their emergency department and contribute to the recommendations from health authorities. This pilot study is of particular relevance in the context of emerging epidemics of severe acute respiratory diseases.

The objective of this study was to test the capacity of vibrotactile stimulation transmitted to the wrist bones by a vibrating wristband to awaken healthy individuals and patients requiring home mechanical ventilation during sleep. Healthy subjects (n = 20) and patients with central hypoventilation (CH) (Congenital Central Hypoventilation syndrome n = 7; non-genetic form of CH n = 1) or chronic obstructive pulmonary disease (COPD) (n = 9), underwent a full-night polysomnography while wearing the wristband. Vibrotactile alarms were triggered five times during the night at random intervals. Electroencephalographic (EEG), clinical (trunk lift) and cognitive (record the time on a sheet of paper) arousals were recorded. Cognitive arousals were observed for 94% of the alarms in the healthy group and for 66% and 63% of subjects in the CH and COPD groups, respectively (p < 0.01). The percentage of participants experiencing cognitive arousals for all alarms, was 72% for healthy subjects, 37.5% for CH patients and 33% for COPD patients (ns) (94%, 50% and 44% for clinical arousals (p < 0.01) and 100%, 63% and 44% for EEG arousals (p < 0.01)). Device acceptance was good in the majority of cases, with the exception of one CH patient and eight healthy participants. In summary this study shows that a vibrotactile stimulus is effective to induce awakenings in healthy subjects, but is less effective in patients, supporting the notion that a vibrotactile stimulus could be an effective backup to a home mechanical ventilator audio alarm for healthy family caregivers.

Due to the expanding use of non-invasive ventilation (NIV) in amyotrophic lateral sclerosis (ALS), the question of enteral nutrition is increasingly raised in NIV users ALS patients. Here, we aimed to determine the prognostic factors for survival after gastrostomy placement in routine NIV users, taking into consideration ventilator dependence. Ninety-two routine NIV users ALS patients, who underwent gastrostomy insertion for severe dysphagia and/or weight loss, were included. We used a Cox proportional hazards model to identify factors affecting survival and compared time from gastrostomy to death and 30-day mortality rate between dependent (daily use ≥ 16 h) and non-dependent NIV users. The hazard of death after gastrostomy was significantly affected by 3 factors: age at onset (HR 1.047, p  = 0.006), body mass index < 20 kg/m 2 at the time of gastrostomy placement (HR 2.012, p  = 0.016) and recurrent accumulation of airway secretions (HR 2.614, p  = 0.001). Mean time from gastrostomy to death was significantly shorter in the dependent than in the non-dependent NIV users group (133 vs. 250 days, p  = 0.04). The 30-day mortality rate was significantly higher in dependent NIV users (21.4% vs. 2.8%, p  = 0.03). Pre-operative ventilator dependence and airway secretion accumulation are associated with worse prognosis and should be key decision-making criteria when considering gastrostomy tube placement in NIV users ALS patients.

Background: Assessment of prognosis is of major importance when deciding on a therapeutic strategy in patients with pulmonary arterial hypertension (PAH). Objectives: The aim of this study was to investigate the prognostic value of pulmonary hemodynamics during exercise and changes during treatment in patients with PAH. Methods: Consecutive incident patients (n = 49) with PAH undergoing right heart catheterization at rest and during a constant workload cycle exercise in supine position were included. Predictors of survival were identified at baseline using Cox proportional hazard regression models in a univariate analysis unadjusted and adjusted for age and gender. Results: During a median follow-up period of 42 months, 13 (27%) of the 49 patients studied died. Two predictors of death were found: rest-to-exercise changes in heart rate and systolic pulmonary artery pressure. Adjusted hazard ratios were 0.92 (95% CI 0.86–0.99) and 0.93 (95% CI 0.88–0.99), respectively. These 2 variables were correlated with each other (r = 0.55, p < 0.001). Conclusions: Rest-to-exercise changes in heart rate and systolic pulmonary artery pressure measured at diagnosis are predictors of survival in patients with PAH. These measurements taken from an exercise test reflect right ventricular function.

Abstract Background The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak is spreading worldwide. To date, no specific treatment has convincingly demonstrated its efficacy. Hydroxychloroquine and lopinavir/ritonavir have potential interest, but virological and clinical data are scarce, especially in critically ill patients. Methods The present report took the opportunity of compassionate use and successive drug shortages to compare the effects of two therapeutic options, lopinavir/ritonavir and hydroxychloroquine, as compared to standard of care only. The primary outcomes were treatment escalation (intubation, extra-corporeal membrane oxygenation support, or renal replacement therapy) after day 1 until day 28. Secondary outcomes included ventilator-free days at day 28, mortality at day 14 and day 28, treatment safety issues and changes in respiratory tracts, and plasma viral load (as estimated by cycle threshold value) between admission and day 7. Results Eighty patients were treated during a 4-week period and included in the analysis: 22 (28%) received standard of care only, 20 (25%) patients received lopinavir/ritonavir associated to standard of care, and 38 (47%) patients received hydroxychloroquine and standard of care. Baseline characteristics were well balanced between the 3 groups. Treatment escalation occurred in 9 (41%), 10 (50%), and 15 (39%) patients who received standard of care only, standard of care and lopinavir/ritonavir, and standard of care and hydroxychloroquine, respectively ( p = 0.567). There was no significant difference between groups regarding the number of ventilator-free days at day 28 and mortality at day 14 and day 28. Finally, there was no significant change between groups in viral respiratory or plasma load between admission and day 7. Conclusion In critically ill patients admitted for SARS-CoV-2-related pneumonia, no difference was found between hydroxychloroquine or lopinavir/ritonavir as compared to standard of care only on the proportion of patients who needed treatment escalation at day 28. Further randomized controlled trials are required to demonstrate whether these drugs may be useful in this context.

Assessing species geographic distributions is critical to approximate their ecological niches, understand how global change may reshape their occurrence patterns, and predict their extinction risks. Yet, species records are over-aggregated across taxonomic, geographic, environmental, and anthropogenic dimensions. The under-sampling of remote locations biases the quantification of species geographic distributions and ecological niche for most species. Here, we used nearly one thousand environmental DNA (eDNA) samples across the world’s oceans, including polar regions and tropical remote islands, to determine the extent to which the geographic and ecological niche ranges of marine fishes are underestimated through the lens of global occurrence records based on conventional surveys. Our eDNA surveys revealed that the known geographic ranges for 93% of species and the ecological niche ranges for 7% of species were underestimated, and contributed to filling them. We show that the probability to detect a range filling for a given species is primarily shaped by the GBIF/OBIS sampling effort in a cell, but also by the number of occurrences available for the species. Most gap fillings were achieved by addressing a methodological sampling bias, notably when eDNA facilitated the detection of small fishes in previously sampled locations using conventional methods. Using a machine learning model, we found that a local effort of 10 eDNA samples would detect 24 additional fish species on average and a maximum of 98 species in previously unsampled tropical areas. Yet, a null model revealed that only half of ecological niche range fillings would be due to eDNA surveys, beyond a random allocation of classical sampling effort. Altogether, our results suggest that sampling in remote areas and performing eDNA surveys in over-sampled areas may both increase fish ecological niche ranges toward unexpected values with consequences in biodiversity modeling, management, and conservation.

ObjectivesSome patients with SLE or Gougerot-Sjögren’s disease (GSD) receive long-term treatment with hydroxychloroquine (HCQ), sometimes combined with immunosuppressive therapy (IS). This study sought to assess whether long-term HCQ therapy that had been initiated long before the COVID-19 pandemic had a protective or adverse effect on COVID-19 risk, severity of infection or immunity protection.MethodsThis prospective multicentre study included 547 patients with SLE, GSD, autoimmune hepatitis, primary biliary cholangitis or cured viral hepatitis C divided into four groups according to HCQ (+/−) and IS (+/−) intake prior to the pandemic: HCQ+IS+ (n=112), HCQ+IS− (n=121), HCQ−IS+ (n=115) and HCQ−IS− (n=199). When COVID-19 vaccination was possible, patients were vaccinated as recommended. Vaccination efficacy was prospectively assessed on the basis of the postvaccination antibody titre.ResultsCompared with HCQ+IS+ patients, HCQ−IS+ patients had a decreased risk of COVID-19 infection (p<0.001). Compared with HCQ+IS+ patients, HCQ−IS− patients had a decreased risk of contracting COVID-19 (p<0.001). Patients in the HCQ−IS+ or HCQ−IS− group had a lower risk of symptomatic or severe infection than HCQ+IS+ patients did (p=0.001 and p<0.001, respectively). Only patients who had two or more exposures (to vaccine and/or infection) had an increased likelihood of COVID-19 immunity after the last dose (p<0.001).ConclusionsHCQ treatment that was initiated before the pandemic did not protect against COVID-19 infection. Moreover, non-exposure to HCQ treatment (combined or not with IS) was associated with decreased risk of COVID-19 infection and of developing a symptomatic or severe infection. HCQ and IS do not influence the vaccine response. Only two or more doses of vaccine result in a good vaccine response.Trial registration numberNCT04481633.

Chronic nicotine exposure results in long-term homeostatic regulation of nicotinic acetylcholine receptors (nAChRs) that play a key role in the adaptative cellular processes leading to addiction. However, the relative contribution of the different nAChR subunits in this process is unclear. Using genetically modified mice and pharmacological manipulations, we provide behavioral, electrophysiological, and pharmacological evidence for a long-term mechanism by which chronic nicotine triggers opposing processes differentially mediated by β2*- vs. α7*nAChRs. These data offer previously undescribed insights into the understanding of nicotine addiction and the treatment of several human pathologies by nicotine-like agents chronically acting on β2*- or α7*nAChRs.