Risk factors for long-term invasive mechanical ventilation: a longitudinal study using German health claims data.

BACKGROUND: Long-term invasive mechanical ventilation (IMV) is a major burden for those affected and causes high costs for the health care system. Early risk assessment is a prerequisite for the best possible support of high-risk patients during the weaning process. We aimed to identify risk factors for long-term IMV within 96 h (h) after the onset of IMV. METHODS: The analysis was based on data from one of Germany's largest statutory health insurance funds; patients who received IMV ≥ 96 h and were admitted in January 2015 at the earliest and discharged in December 2017 at the latest were analysed. OPS and ICD codes of IMV patients were considered, including the 365 days before intubation and 30 days after discharge. Long-term IMV was defined as evidence of invasive home mechanical ventilation (HMV), IMV ≥ 500 h, or readmission with (re)prolonged ventilation. RESULTS: In the analysis of 7758 hospitalisations, criteria for long-term IMV were met in 38.3% of cases, of which 13.9% had evidence of HMV, 73.1% received IMV ≥ 500 h and/or 40.3% were re-hospitalised with IMV. Several independent risk factors were identified (p < 0.005 each), including pre-diagnoses such as pneumothorax (OR 2.10), acute pancreatitis (OR 2.64), eating disorders (OR 1.99) or rheumatic mitral valve disease (OR 1.89). Among ICU admissions, previous dependence on an aspirator or respirator (OR 5.13), and previous tracheostomy (OR 2.17) were particularly important, while neurosurgery (OR 2.61), early tracheostomy (OR 3.97) and treatment for severe respiratory failure such as positioning treatment (OR 2.31) and extracorporeal lung support (OR 1.80) were relevant procedures in the first 96 h after intubation. CONCLUSION: This comprehensive analysis of health claims has identified several risk factors for the risk of long-term ventilation. In addition to the known clinical risks, the information obtained may help to identify patients at risk at an early stage. Trial registration The PRiVENT study was retrospectively registered at ClinicalTrials.gov (NCT05260853). Registered at March 2, 2022.

A multidimensional approach to the management of patients in prolonged weaning from mechanical ventilation - the concept of treatable traits - a narrative review.

Background Established structured weaning approaches, which are effective for patients in simple and difficult weaning, are often not appropriate for patients undergoing prolonged weaning. Addressing the complexity of weaning failure requires personalized precision medicine. The therapeutic concept of Treatable Traits (TTs) has been proposed as a new paradigm for the management of chronic respiratory diseases. It is based on a multidimensional assessment of specific characteristics, which can be addressed by specific interventions that go beyond traditional diagnostic criteria. The concept is increasingly adopted for other complex diseases. Summary This is a narrative review and an expert opinion on the development of a concept of TTs for patients undergoing prolonged weaning. The proposed TTs are based on a systematic review of risk factors for prolonged weaning, an analysis of claims data to assess risk factors within 96 hours of IMV onset and data from the WEAN-SAFE study. A multidisciplinary team identified clinically important TTs and determined appropriate interventions. The following TTs have been identified: Airway disorders and complications associated with tracheostomy or intubation, such as airway obstruction, strictures or tracheomalacia, infectious aspects, anxiety, depression, delirium, post-traumatic stress disorder, anemia, pulmonary and cardio-renal disease. The multidimensional holistic approach also includes tailored sedation and pain management, nutritional therapy, early mobilization and physiotherapy. Key message We propose a framework of relevant considerations for a multidimensional approach to the management of patients undergoing prolonged weaning that supports the regain of respiratory capacity, reduces the respiratory load and thus could resolve the respiratory workload imbalance.

E-learning-an interventional element of the PRiVENT project to improve weaning expertise.

BACKGROUND: PRiVENT (PRevention of invasive VENTilation) is an evaluation of a bundle of interventions aimed at the prevention of long-term invasive mechanical ventilation. One of these elements is an e-learning course for healthcare professionals to improve weaning expertise. The aim of our analysis is to examine the implementation of the course in cooperating intensive care units. METHODS: The course has been developed through a peer review process by pulmonary and critical care physicians in collaboration with respiratory therapists, supported by health services researchers and a professional e-learning agency. The e-learning platform "weLearn" was made available online to participating healthcare professionals. Feedback on the e-learning programme was obtained and discussed in quality circles (QCs). We measured the acceptance and use of the programme through access statistics. RESULTS: The e-learning course "Joint Prevention of Long-Term Ventilation" consists of 7 separate modules with practice-oriented training units as well as a cross-module area and corresponding interactive case studies. Users can receive 23 CME (continuing medical education) credits. The platform was released on July 1, 2021. By June 28, 2023, 214 users from 33 clinics had registered. Most users (77-98%) completed the modules, thus performing well in the test, where 90-100% passed. In the QCs, the users commended the structure and practical relevance of the programme, as well as the opportunity to earn CME credits. CONCLUSION: Especially for medical staff in intensive care units, where continuous training is often a challenge during shift work, e-learning is a useful supplement to existing medical training. TRIAL REGISTRATION: The PRiVENT study is registered at ClinicalTrials.gov (NCT05260853) on 02/03/2022.

Causes and Risk Factors for Absenteeism among Medical Staff in German Specialized Lung Clinics during the COVID Pandemic.

BACKGROUND: Staff shortages pose a major challenge to the health system. OBJECTIVES: The objective of this study was to clarify the role of different causative factors we investigated on staff absenteeism during the COVID pandemic. METHODS: The prospective multicentre cohort study assessed the private and professional impact of the pandemic on health care workers (HCWs) using a specially developed questionnaire. HCWs from 7 specialist lung clinics throughout Germany were surveyed from December 1 to December 23, 2021. The current analysis addresses pandemic-related absenteeism. RESULTS: 1,134 HCW (55% female; 18.4% male, 26.3% not willing to provide information on age or gender) participated. 72.8% had received at least one vaccination dose at the time of the survey, and 9.4% reported a COVID infection. Of those with positive tests, 98% reported home quarantine for median (IQR) 14 (12-17) days; 10.3% of those who ultimately tested negative also reported quarantine periods of 14 (7-14) days. 32.2% of vaccinated respondents reported absenteeism due to vaccine reactions of 2 (1-3) days. Overall, 37% (n = 420) of HCW reported pandemic-related absenteeism, with 3,524 total days of absenteeism, of which 2,828 were due to illness/quarantine and 696 to vaccination effects. Independent risk factors for COVID-related absenteeism ≥5 days included already having COVID, but also concern about long-term effects of COVID (OR 1,782, p = 0.014); risk factors for vaccine-related absenteeism ≥2 days included concerns of late effects of vaccination (OR 2.2, 95% CI: 1.4-3.1, p < 0.000). CONCLUSION: Staff shortages due to quarantine or infections and vaccine reactogenicity have put a strain on German respiratory specialists. The fact that staff concerns also contributed to absenteeism may be helpful in managing future pandemic events to minimize staff absenteeism.

Prevention of invasive ventilation (PRiVENT)-a prospective, mixed-methods interventional, multicentre study with a parallel comparison group: study protocol.

BACKGROUND: Invasive mechanical ventilation (IMV) is a standard therapy for intensive care patients with respiratory failure. With increasing population age and multimorbidity, the number of patients who cannot be weaned from IMV increases, resulting in impaired quality of life and high costs. In addition, human resources are tied up in the care of these patients. METHODS: The PRiVENT intervention is a prospective, mixed-methods interventional, multicentre study with a parallel comparison group selected from insurance claims data of the health insurer Allgemeine Ortskrankenkasse Baden-Württemberg (AOK-BW) conducted in Baden-Württemberg, Germany, over 24 months. Four weaning centres supervise 40 intensive care units (ICUs), that are responsible for patient recruitment. The primary outcome, successful weaning from IMV, will be evaluated using a mixed logistic regression model. Secondary outcomes will be evaluated using mixed regression models. DISCUSSION: The overall objective of the PRiVENT project is the evaluation of strategies to prevent long-term IMV. Additional objectives aim to improve weaning expertise in and cooperation with the adjacent Intensive Care Units. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov (NCT05260853).

Endobronchial ultrasound in real life: primary diagnosis and mediastinal staging of lung cancer in patients submitted to thoracic surgery.

BACKGROUND: Since the first articles published for over 10 years ago, endobronchial ultrasound (EBUS) has gained a strong scientific backing and has been incorporated into routine medical practice in pulmonology and thoracic surgery centers. How is EBUS performing outside the scientific environment, as a diagnostic and mediastinal staging tool in a subset of patients that undergo thoracic surgery, is an interesting question. METHODS: This study evaluated consecutive patients who, during the period from January 2010 to August 2012, were submitted to EBUS and later to thoracic surgery. The samples obtained by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) were compared to surgical samples. The primary endpoint was the proportion of patients with a final diagnosis of non-small cell lung cancer (NSCLC) by EBUS-TBNA correctly subtyped. The secondary endpoint was the negative predictive value (NPV) of EBUS-TBNA for mediastinal staging of lung cancer. RESULTS: Two hundred eighty seven patients were studied. Considering 84 patients with a final diagnosis of NSCLC by EBUS-TBNA, 79 % (CI 95 % 70.1-87.3) were correctly subclassified. The NPV of EBUS-TBNA for mediastinal staging was 89 % (IC 95 % 84.9-92.7). From a total of 21 false negative cases of mediastinal staging, 16 (76 %) did not undergo positron emission tomography-computed tomography (PET-CT) before the EBUS and in 15 (71 %) the affected lymph node chain was not punctured by EBUS-TBNA. Ten (47 %) patients had only lymph node metastases not directly accessible by the EBUS. CONCLUSIONS: Performed in hospital routine and in patients submitted to thoracic surgery, EBUS-TBNA proved to be a good tool for proper pathological diagnosis of lung cancer. The negative predictive value of 89 % for mediastinal staging of lung cancer is comparable to that reported in previous studies, but the relatively high number of 21 false negative cases points to the need for standardization of routine strategies before, during and after EBUS.

The Baveno Classification as a Predictor of CPAP Titration Pressure in Obstructive Sleep Apnea Syndrome.

INTRODUCTION: Obstructive sleep apnea syndrome (OSAS) is a clinical condition characterised by repeated periods of partial or full obstruction of airflow throughout sleep, with impairment of the quality of life and increased mortality with socioeconomic impacts. CPAP therapy is a simple and effective treatment option for OSAS patients. To overcome the clinical and prognostic limitations of AHI-as a sole index of OSAS-the Baveno classification was recently set out and introduced into clinical practice. This study aims to analyse the effect of the Baveno classification on the optimum CPAP titration pressure. METHODS: A retrospective analysis of the records of sleep studies in two centres between 2018 and 2021 was carried out. Patients diagnosed with OSAS and recruited for CPAP titration were included. Based on the Baveno classification, the patients were categorised into four groups (A, B, C, and D). RESULTS: Consequently, 700 patients were analysed and 427 patients were included. A significant positive correlation was detected between the CPAP optimum titration pressure and OSAS severity, neck circumference, the oxygen desaturation index (ODI), mean oxygen saturation, the AHI, the BMI, and cumulative sleep time when the SpO2 was <90% (T90) on the other side (p: <0.0001). A non-significant correlation was seen between the Epworth Sleepiness Scale (ESS), symptom severity, end organ impact, and Baveno classification of the CPAP optimum titration pressure (p: 0.8, 0.4, 0.5, and 0.7, respectively). CONCLUSIONS: The Baveno classification is not useful in the prediction of CPAP optimum titration pressure. However, the ODI and neck circumference were significant independent predictors of a higher CPAP titration pressure.

Transbronchial lung cryobiopsy performed in acute COVID-19 pneumonia: first report.

A COVID-19 diagnosis is usually based on PCR detection of viral RNA in airway specimens in a patient with typical clinical fea-tures. Histological features of the COVID-19 lung disease are reported from autopsies. Transbronchial cryobiopsy (TBCB) is an evolving technique usually performed in the diagnosis of interstitial lung disease. We report a TBCB in a 76-year-old female patient who had repeatedly tested negative for SARS-CoV-2 infection. The pathological examination revealed the presence of interstitial pneumonia with lymphocytic infiltration. The qRT-PCR against SARS-CoV-2 from a pharyngeal swab was positive after performing the TBCB.

Peripheral ischemic limb necrosis (Acro-ischemia) associated with severe COVID-19 patients (COVID-19 limbs): A report of three cases.

The association between severe coronavirus disease 2019 and hypercoagulable state was observed in many reports. This may be explained by the presence of hypoxia, severe systemic inflammatory response, immobilization due to intensive care unit (ICU) admission, and diffuse intravascular coagulation. We report three patients who were admitted to our respiratory ICU with acute severe respiratory distress syndrome (ARDS) requiring mechanical ventilation due severe acute respiratory syndrome coronavirus 2 infection, who developed severe limb ischemia during the course of the disease.

GLPG2737 in lumacaftor/ivacaftor-treated CF subjects homozygous for the F508del mutation: A randomized phase 2A trial (PELICAN).

BACKGROUND: Triple combinations of cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulators demonstrate enhanced clinical efficacy in CF patients with F508del mutation, compared with modest effects of dual combinations. GLPG2737 was developed as a novel corrector for triple combination therapy. METHODS: This multicenter, randomized, double-blind, placebo-controlled, phase 2a study evaluated GLPG2737 in F508del homozygous subjects who had been receiving lumacaftor 400mg/ivacaftor 250mg for ≥12weeks. The primary outcome was change from baseline in sweat chloride concentration. Other outcomes included assessment of pulmonary function, respiratory symptoms, safety, tolerability, and pharmacokinetics. RESULTS: Between November 2017 and April 2018, 22 subjects were enrolled and randomized to oral GLPG2737 (75mg; n=14) or placebo (n=8) capsules twice daily for 28days. A significant decrease from baseline in mean sweat chloride concentration occurred at day 28 for GLPG2737 versus placebo (least-squares-mean difference-19.6mmol/L [95% confidence interval (CI) -36.0, -3.2], p=.0210). The absolute improvement, as assessed by least-squares-mean difference in change from baseline, in forced expiratory volume in 1s (percent predicted) at day 28 for GLPG2737 versus placebo was 3.4% (95% CI -0.5, 7.3). Respiratory symptoms in both groups remained stable. Mild/moderate adverse events occurred in 10 (71.4%) and 8 (100%) subjects receiving GLPG2737 and placebo, respectively. Lower exposures of GLPG2737 (and active metabolite M4) were observed than would be expected if administered alone (as lumacaftor induces CYP3A4). Lumacaftor and ivacaftor exposures were as expected. CONCLUSIONS: GLPG2737 was well tolerated and yielded significant decreases in sweat chloride concentration versus placebo in subjects homozygous for F508del receiving lumacaftor/ivacaftor, demonstrating evidence of increased CFTR activity when added to a potentiator-corrector combination. FUNDING: Galapagos NV. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03474042.

Efficacy and safety of trimodulin, a novel polyclonal antibody preparation, in patients with severe community-acquired pneumonia: a randomized, placebo-controlled, double-blind, multicenter, phase II trial (CIGMA study).

PURPOSE: The CIGMA study investigated a novel human polyclonal antibody preparation (trimodulin) containing ~ 23% immunoglobulin (Ig) M, ~ 21% IgA, and ~ 56% IgG as add-on therapy for patients with severe community-acquired pneumonia (sCAP). METHODS: In this double-blind, phase II study (NCT01420744), 160 patients with sCAP requiring invasive mechanical ventilation were randomized (1:1) to trimodulin (42 mg IgM/kg/day) or placebo for five consecutive days. Primary endpoint was ventilator-free days (VFDs). Secondary endpoints included 28-day all-cause and pneumonia-related mortality. Safety and tolerability were monitored. Exploratory post hoc analyses were performed in subsets stratified by baseline C-reactive protein (CRP; ≥ 70 mg/L) and/or IgM (≤ 0.8 g/L). RESULTS: Overall, there was no statistically significant difference in VFDs between trimodulin (mean 11.0, median 11 [n = 81]) and placebo (mean 9.6; median 8 [n = 79]; p = 0.173). Twenty-eight-day all-cause mortality was 22.2% vs. 27.8%, respectively (p = 0.465). Time to discharge from intensive care unit and mean duration of hospitalization were comparable between groups. Adverse-event incidences were comparable. Post hoc subset analyses, which included the majority of patients (58-78%), showed significant reductions in all-cause mortality (trimodulin vs. placebo) in patients with high CRP, low IgM, and high CRP/low IgM at baseline. CONCLUSIONS: No significant differences were found in VFDs and mortality between trimodulin and placebo groups. Post hoc analyses supported improved outcome regarding mortality with trimodulin in subsets of patients with elevated CRP, reduced IgM, or both. These findings warrant further investigation. TRIAL REGISTRATION: NCT01420744.

Physiological modeling of responses to upper versus lower lobe lung volume reduction in homogeneous emphysema.

RATIONALE: In clinical trials, homogeneous emphysema patients have responded well to upper lobe volume reduction but not lower lobe volume reduction. MATERIALS/METHODS: To understand the physiological basis for this observation, a computer model was developed to simulate the effects of upper and lower lobe lung volume reduction on RV/TLC and lung recoil in homogeneous emphysema. RESULTS: Patients with homogeneous emphysema received either upper or lower lobe volume reduction therapy based on findings of radionucleotide scintigraphy scanning. CT analysis of lobar volumes showed that patients undergoing upper (n = 18; -265 mL/site) and lower lobe treatment (LLT; n = 11; -217 mL/site) experienced similar reductions in lung volume. However, only upper lobe treatment (ULT) improved FEV(1) (+11.1 ± 14.7 versus -4.4 ± 15.8%) and RV/TLC (-5.4 ± 8.1 versus -2.4 ± 8.6%). Model simulations provided an unexpected explanation for this response. Increases in transpulmonary pressure subsequent to volume reduction increased RV/TLC in upper lobe alveoli, while caudal shifts in airway closure decreased RV/TLC in lower lobe alveoli. ULT, which eliminates apical alveoli with high RV/TLC values, lowers the average RV/TLC of the lung. Conversely, LLT, which eliminates caudal alveoli with low RV/TLC values, has less effect. CONCLUSION: LLT in homogeneous emphysema is uniformly less effective than ULT.