Thrombelastography and Conventional Coagulation Markers in Chronic Obstructive Pulmonary Disease: A Prospective Paired-Measurements Study Comparing Exacerbation and Stable Phases.

Chronic Obstructive Pulmonary Disease (COPD) exacerbation is known for its substantial impact on morbidity and mortality among affected patients, creating a significant healthcare burden worldwide. Coagulation abnormalities have emerged as potential contributors to exacerbation pathogenesis, raising concerns about increased thrombotic events during exacerbation. The aim of this study was to explore the differences in thrombelastography (TEG) parameters and coagulation markers in COPD patients during admission with exacerbation and at a follow-up after discharge. This was a multi-center cohort study. COPD patients were enrolled within 72 h of hospitalization. The baseline assessments were Kaolin-TEG and blood samples. Statistical analysis involved using descriptive statistics; the main analysis was a paired t-test comparing coagulation parameters between exacerbation and follow-up. One hundred patients participated, 66% of whom were female, with a median age of 78.5 years and comorbidities including atrial fibrillation (18%) and essential arterial hypertension (45%), and sixty-five individuals completed a follow-up after discharge. No significant variations were observed in Kaolin-TEG or conventional coagulation markers between exacerbation and follow-up. The Activated Partial Thromboplastin Clotting Time (APTT) results were near-significant, with p = 0.08. In conclusion, TEG parameters displayed no significant alterations between exacerbation and follow-up.

Incidence of community-acquired pneumonia hospitalisation in persons with bronchiectasis during the COVID-19 lockdown in Denmark: a retrospective cohort study.

BACKGROUND: Persons with bronchiectasis have a high risk of community-acquired pneumonia. Social distancing measures, implemented to prevent the spreading of SARS-CoV-2, could potentially reduce the incidence of other infectious diseases. RESEARCH QUESTION: Was the COVID-19 lockdown period, along with accompanying social distancing measures, associated with reduced hospital admissions for community-acquired pneumonia and decreased overall mortality rates among individuals with bronchiectasis? METHODS: Social distancing measures were introduced in Denmark by 12 March 2020 and were preserved until 20 May 2020 (social distancing period), after which the measures were gradually dismissed. The study included all adults (≥18 years) with bronchiectasis residing in Denmark. Confirmed cases of SARS-CoV-2 infection were excluded. We retrospectively investigated the incidence of community-acquired pneumonia hospital admission, death of all causes and respiratory antibiotic treatment in the 10-week social distancing period in 2020, compared with the same dates in 2019. 9344 persons were included in the study. RESULTS: In the social distancing period, the incidence rate of pneumonia-hospitalisation per 10 000 person-weeks was 9.2 compared with 13.8 in the reference period. This reduction corresponds to an incidence rate ratio (IRR) of 0.67 (95% CI 0.51 to 0.88, p<0.01). Mortality was unchanged (IRR 0.90, 95% CI 0.61 to 1.32, p=0.58). Fewer persons received respiratory antibiotics (IRR 0.85, 95% CI 0.78 to 0.94, p<0.001). CONCLUSION: The social distancing period was associated with a lower incidence of community-acquired pneumonia hospitalisations and respiratory antibiotic treatments in persons with bronchiectasis while all-cause mortality remained unchanged.

Sedating antihistamine treatment with promethazine in patients with severe COPD with and without asthma: death and severe exacerbations in a nationwide register study.

Background: Sedating antihistamines such as promethazine are used as anxiolytics and hypnotic agents for patients with chronic obstructive pulmonary disease (COPD) with and without asthma despite limited knowledge of its effects and side effects. We evaluated if treatment with promethazine had a lower risk of harmful outcome. Methods: Nationwide retrospective cohort study of Danish specialist diagnosed outpatients with COPD treated with promethazine or an active comparator (melatonin). Patients with collection of promethazine or melatonin were propensity score matched 1:1. The primary outcome was a composite of severe COPD exacerbations and death from all causes analyzed by Cox proportional hazards regression. We performed an interaction analysis for comorbid asthma. Results: In our registry of 56,523 patients with COPD, 5,661 collected promethazine (n = 3,723) or melatonin (n = 1,938). A cohort of 3,290 promethazine- or melatonin-treated patients matched 1:1 was available for the primary analysis.Within 1-year patients treated with promethazine were at higher risk of the primary outcome than matched controls with a Hazard Ratio (HR) of 1.42 (CI 1.27-1.58, p < 0.0001). Similarly, the risk of death was higher for promethazine-treated patients (HR 1.53, CI 1.32-1.77, p < 0.0001). An interaction analysis for comorbid asthma showed no interaction between comorbid asthma and the likelihood of a primary outcome when collecting promethazine (p = 0.19). Adjusted Cox analysis on the entire population indicated a further increased risk with more promethazine (HR for primary outcome among patients collecting ≥ 400 promethazine tablets/year=2.15, CI 1.94-2.38, p<0.0001). Conclusions: Promethazine-treated patients with COPD had a concerning excess risk of a composite outcome of severe exacerbations and death from all causes compared to melatonin.

SARS-CoV-2 and risk of psychiatric hospital admission and use of psychopharmaceuticals: A nationwide registry study of 4,585,083 adult Danish citizens.

BACKGROUND: Current evidence on the risk of admission- or medication-requiring psychiatric sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is limited to selected populations, short durations, and loss to follow-up. This study examined if SARS-CoV-2 infection was associated with increased long-term risk of psychiatric admissions and de novo prescription of psychoactive medication in the general population of Denmark. METHODS: Adults (≥18 years) were assigned to either the control or SARS-CoV-2 group based on polymerase chain reaction (PCR) tests between 1 January 2020 and 27 November 2021. Infected subjects were matched 1:5 to control subjects by propensity score. Incidence rate ratios (IRRs) were calculated. Adjusted Cox regression was applied to the unmatched population with SARS-CoV-2 infection as a time-dependent covariate. Follow-up time was 12 months or until the end of the study. RESULTS: A total of 4,585,083 adults were included in the study. Approximately 342,084 had a PCR-confirmed SARS-CoV-2 infection and were matched 1:5 with 1,697,680 controls. The IRR for psychiatric admission was 0.79 in the matched population (95% confidence interval [CI]: 0.73-0.85, p < 0.001). In the unmatched population, the adjusted hazard ratios (aHR) for psychiatric admission were either below 1.00 or with a 95% CI lower limit of 1.01. SARS-CoV-2 infection was associated with an increased risk of de novo prescription of psychoactive medication in both the matched (IRR 1.06, 95% CI: 1.02-1.11, p < 0.01) and unmatched population (HR 1.31, 95% CI: 1.28-1.34, p < 0.001). CONCLUSIONS: We found a signal of increased use of psychoactive medication, specifically benzodiazepines, among SARS-CoV-2-positive persons, but the risk of psychiatric admissions did not increase.

Time-Updated Phenotypic Guidance of Corticosteroids and Antibiotics in COPD: Rationale, Perspective and a Proposed Method.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease with distinct phenotypes, each having distinct treatment needs. Eosinophilic airway inflammation is present in a subset of COPD patients in whom it can act as a driver of exacerbations. Blood eosinophil counts are a reliable way to identify patients with an eosinophilic phenotype, and these measurements have proven to be successful in guiding the use of corticosteroids in moderate and severe COPD exacerbations. Antibiotic use in COPD patients induces a risk of Clostridium difficile infection, diarrhea, and antibiotic resistance. Procalcitonin could possibly guide antibiotic treatment in patients admitted with AECOPD. Current studies in COPD patients were successful in reducing exposure to antibiotics with no changes in mortality or length of stay. Daily monitoring of blood eosinophils is a safe and effective way to reduce oral corticosteroid exposure and side effects for acute exacerbations. No evidence on time-updated treatment guidance for stable COPD exists yet, but a current trial is testing an eosinophil-guided approach on inhaled corticosteroid use. Procalcitonin-guided antibiotic treatment in AECOPD shows promising results in safely and substantially reducing antibiotic exposure both in time-independent and time-updated algorithms.