Patient perceptions of the re-usable Respimat® Soft MistTM inhaler in current users and those switching to the device : a real-world, non-interventional COPD study

Acknowledgements: Medical writing assistance, in the form of the preparation and revision of the manuscript, was supported financially by Boehringer Ingelheim and provided by Paul Todd, PhD, at MediTech Media, UK under the authors’ conceptual direction and based on feedback from the authors. Funding: Support for this project, medical writing support and in the study and collection, analysis, and interpretation of data was provided by Boehringer Ingelheim International GmBH.Peer reviewedPublisher PD

A novel haemocytometric COVID-19 prognostic score developed and validated in an observational multicentre European hospital-based study

COVID-19 induces haemocytometric changes. Complete blood count changes, including new cell activation parameters, from 982 confirmed COVID-19 adult patients from 11 European hospitals were retrospectively analysed for distinctive patterns based on age, gender, clinical severity, symptom duration, and hospital days. The observed haemocytometric patterns formed the basis to develop a multi-haemocytometric-parameter prognostic score to predict, during the first three days after presentation, which patients will recover without ventilation or deteriorate within a two-week timeframe, needing intensive care or with fatal outcome. The prognostic score, with ROC curve AUC at baseline of 0.753 (95% CI 0.723-0.781) increasing to 0.875 (95% CI 0.806-0.926) on day 3, was superior to any individual parameter at distinguishing between clinical severity. Findings were confirmed in a validation cohort. Aim is that the score and haemocytometry results are simultaneously provided by analyser software, enabling wide applicability of the score as haemocytometry is commonly requested in COVID-19 patients

A novel haemocytometric covid-19 prognostic score developed and validated in an observational multicentre european hospital-based study

COVID-19 induces haemocytometric changes. Complete blood count changes, including new cell activation parameters, from 982 confirmed COVID-19 adult patients from 11 European hospitals were retrospectively analysed for distinctive patterns based on age, gender, clinical severity, symptom duration and hospital days. The observed haemocytometric patterns formed the basis to develop a multi-haemocytometric-parameter prognostic score to predict, during the first three days after presentation, which patients will recover without ventilation or deteriorate within a two-week timeframe, needing intensive care or with fatal outcome. The prognostic score, with ROC curve AUC at baseline of 0.753 (95% CI 0.723-0.781) increasing to 0.875 (95% CI 0.806-0.926) on day 3, was superior to any individual parameter at distinguishing between clinical severity. Findings were confirmed in a validation cohort. Aim is that the score and haemocytometry results are simultaneously provided by analyser software, enabling wide applicability of the score as haemocytometry is commonly requested in COVID-19 patients

Fact or Factitious? A Psychobiological Study of Authentic and Simulated Dissociative Identity States

BACKGROUND: Dissociative identity disorder (DID) is a disputed psychiatric disorder. Research findings and clinical observations suggest that DID involves an authentic mental disorder related to factors such as traumatization and disrupted attachment. A competing view indicates that DID is due to fantasy proneness, suggestibility, suggestion, and role-playing. Here we examine whether dissociative identity state-dependent psychobiological features in DID can be induced in high or low fantasy prone individuals by instructed and motivated role-playing, and suggestion. METHODOLOGY/PRINCIPAL FINDINGS: DID patients, high fantasy prone and low fantasy prone controls were studied in two different types of identity states (neutral and trauma-related) in an autobiographical memory script-driven (neutral or trauma-related) imagery paradigm. The controls were instructed to enact the two DID identity states. Twenty-nine subjects participated in the study: 11 patients with DID, 10 high fantasy prone DID simulating controls, and 8 low fantasy prone DID simulating controls. Autonomic and subjective reactions were obtained. Differences in psychophysiological and neural activation patterns were found between the DID patients and both high and low fantasy prone controls. That is, the identity states in DID were not convincingly enacted by DID simulating controls. Thus, important differences regarding regional cerebral bloodflow and psychophysiological responses for different types of identity states in patients with DID were upheld after controlling for DID simulation. CONCLUSIONS/SIGNIFICANCE: The findings are at odds with the idea that differences among different types of dissociative identity states in DID can be explained by high fantasy proneness, motivated role-enactment, and suggestion. They indicate that DID does not have a sociocultural (e.g., iatrogenic) origin

A novel haemocytometric COVID-19 prognostic score developed and validated in an observational multicentre European hospital-based study

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Do-not-intubate status and COVID-19 mortality in patients admitted to Dutch non-ICU wards

Mortality from COVID-19 has been particularly high in elderly patients on mechanical ventilation. Treatment outcomes for patients with do-not-intubate (DNI) status are unknown. One hundred patients admitted to the non-ICU ward during the “first wave” were retrospectively analyzed.

Poor outcome of SARS-CoV-2 infection in patients with severe asthma on biologic therapy

Background: It is unclear whether asthma and asthma medications increase or decrease the risk of severe COVID-19, and this is particularly true for patients with severe asthma receiving biologics. Objectives: The aim of this study was to assess incidence and disease course of COVID-19 in patients with severe asthma on biologic therapy (omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab), as compared with COVID-19 data from the general Dutch population. Methods: COVID-19 cases were identified through a prospective ongoing survey between March 17 and April 30, 2020 among all severe asthma specialists from 15 hospitals of the Dutch Severe Asthma Registry RAPSODI. From these cases, data was collected on patient characteristics, including co-morbidities, COVID-19 disease progression and asthma exacerbations. Findings were then compared with COVID-19 data from the general Dutch population. Results: Of 634 severe asthma patients who received biologic therapy in RAPSODI, 9 (1.4%) were diagnosed with COVID-19. Seven patients (1.1%) required hospitalization for oxygen therapy, of which 5 were admitted to the intensive care for intubation and mechanical ventilation. One patient died (0.16%). All intubated patients had ≥1 co-morbidities. Odds (95%CI) for COVID-19 related hospitalization and intubations were 14 (6.6–29.5) and 41 (16.9–98.5) times higher, respectively, compared to the Dutch population. One patient presented with an asthma exacerbation. Conclusion: Patients with severe asthma using biologic therapy showed to have a more severe course of COVID-19 compared to the general population. This may be due to co-morbidities, the severity of asthmatic airway inflammation, the use of biologics, or a combination of these

Antibodies Against Angiotensin II Receptor Type 1 and Endothelin A Receptor Are Associated With an Unfavorable COVID19 Disease Course

Background: Lung histopathology demonstrates vasculopathy in a subset of deceased COVID19 patients, which resembles histopathology observed in antibody-mediated lung transplant rejection. Autoantibodies against angiotensin II type 1 receptor (AT1R) and Endothelin receptor Type A (ETAR) have been demonstrated in antibody-mediated rejection and may also be associated with severe COVID19 infection. Objective To assess AT1R and ETAR auto-antibodies in COVID19 patients and controls, and explore their association with disease course. Methods: 65 hospitalized patients with COVID19 infection were included. Clinical and laboratory findings were retrospectively assessed. Patients with unfavorable disease course, admitted at the intensive care unit and/or deceased during hospital admission (n=33) were compared to admitted COVID19 patients with favorable disease course (n=32). The presence of antinuclear antibodies (ANA) and auto-antibodies against AT1R or ETAR in peripheral blood were compared between COVID19 with unfavorable and favorable disease course and age matched controls (n=20). Results: The presence of ANA was not significantly different between COVID19 patients with unfavorable (n=7/33; 21%) and favorable disease course (n=6/32; 19%) (p= 0.804) and controls (n=3/20; 15%). Auto-antibodies against AT1R were significantly increased in unfavorable disease course (median 14.59 U/mL, IQR 11.28 – 19.89) compared to favorable disease course (median 10.67 U/mL, IQR 8.55 – 13.0, p< 0.01). ETAR antibody titers were also significantly increased in unfavorable disease course (median 7.21, IQR 5.0 – 10.45) as compared to favorable disease course (median 4.0, IQR 3.0 – 6.0, p <0.05). Conclusion: Auto-antibodies against AT1R and ETAR are significantly increased in COVID19 patients with an unfavorable disease course

IL-1R1-Dependent Signals Improve Control of Cytosolic Virulent Mycobacteria In Vivo

International audienceMycobacterium tuberculosis infections claim more than a million lives each year, and better treatments or vaccines are required. A crucial pathogenicity factor is translocation from phagolysosomes to the cytosol upon phagocytosis by macrophages. Translocation from the phagolysosome to the cytosol is an ESX-1-dependent process, as previously shown in vitro Here, we show that in vivo, mycobacteria also translocate to the cytosol but mainly when host immunity is compromised. We observed only low numbers of cytosolic bacilli in mice, armadillos, zebrafish, and patient material infected with M. tuberculosis, M. marinum, or M. leprae In contrast, when innate or adaptive immunity was compromised, as in severe combined immunodeficiency (SCID) or interleukin-1 receptor 1 (IL-1R1)-deficient mice, significant numbers of cytosolic M. tuberculosis bacilli were detected in the lungs of infected mice. Taken together, in vivo, translocation to the cytosol of M. tuberculosis is controlled by adaptive immune responses as well as IL-1R1-mediated signals.IMPORTANCE For decades, Mycobacterium tuberculosis has been one of the deadliest pathogens known. Despite infecting approximately one-third of the human population, no effective treatment or vaccine is available. A crucial pathogenicity factor is subcellular localization, as M. tuberculosis can translocate from phagolysosome to the cytosol in macrophages. The situation in vivo is more complicated. In this study, we establish that high-level cytosolic escape of mycobacteria can indeed occur in vivo but mainly when host resistance is compromised. The IL-1 pathway is crucial for the control of the number of cytosolic mycobacteria. The establishment that immune signals result in the clearance of cells containing cytosolic mycobacteria connects two important fields, cell biology and immunology, which is vital for the understanding of the pathology of M. tuberculosis