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Background: Effective interventions to reduce drowning incidents require accurate and reliable data for scientific analysis. However, the lack of high-quality evidence and the variability in drowning terminology, definitions, and outcomes present significant challenges in assessing studies to inform drowning guidelines. Many drowning reports use inappropriate classifications for drowning incidents, which significantly contributes to the underreporting of drowning. In particular, non-fatal drowning incidents are underreported because many countries do not routinely collect this data. The Danish Drowning Cohort: The Danish Drowning Cohort was established in 2016 to facilitate research to improve preventative, rescue, and treatment interventions to reduce the incidence, mortality, and morbidity of drowning. The Danish Drowning Cohort contains nationwide data on all fatal and non-fatal drowning incidents treated by the Danish Emergency Medical Services. Data are extracted from the Danish prehospital electronic medical record using a text-search algorithm (Danish Drowning Formula) and a manual validation process. The WHO definition of drowning, supported by the clarification statement for non-fatal drowning, is used as the case definition to identify drowning. All drowning patients are included, including unwitnessed incidents, non-conveyed patients, patients declared dead prehospital, or patients with obvious clinical signs of irreversible death. This method allows syndromic surveillance and monitors a nationwide cohort of fatal and non-fatal drowning incidents in near-real time to inform future prevention strategies. The Danish Drowning Cohort complies with the Utstein style for drowning reporting guidelines. The 30-day mortality is obtained through the Civil Personal Register to differentiate between fatal and non-fatal drowning incidents. In addition to prehospital data, new data linkages with other Danish registries via the patient's civil registration number will enable the examination of various additional factors associated with drowning risk. Conclusion: The Danish Drowning Cohort contains nationwide prehospital data on all fatal and non-fatal drowning incidents treated by the Danish Emergency Medical Service. It is a basis for all research on drowning in Denmark and may improve preventative, rescue, and treatment interventions to reduce the incidence, mortality, and morbidity of drowning. Plain Language Summary: The Danish Drowning Cohort includes data on fatal and non-fatal drowning incidents treated by the Emergency Medical Services from 2016 and onwards and serves as the foundation for drowning research in Denmark. Data are extracted from the Danish Prehospital Electronic Medical Record using the Danish Drowning Formula and manual validation. The research data can advance prevention, rescue, and treatment interventions, aiming to decrease drowning incidence, mortality, and morbidity. The research data follows the Utstein style for drowning reporting guidelines linked with 30-day survival. [ABSTRACT FROM AUTHOR]

Author(s): Mathias G. Holgersen [sup.1] , June K. Marthin [sup.1] , Kim G. Nielsen [sup.1] Author Affiliations: (Aff1) grid.475435.4, Danish PCD & chILD Centre, CF Centre Copenhagen, Paediatric Pulmonary Service, [...], Introduction Nasal nitric oxide (nNO) is extremely low in individuals with primary ciliary dyskinesia (PCD) and is recommended as part of early workup. We investigated whether tidal breathing sampling for a few seconds was as discriminative between PCD and healthy controls (HC) as conventional tidal breathing sampling (cTB-nNO) for 20-30 s. Methods We performed very rapid sampling of tidal breathing (vrTB-nNO) for 2, 4 and 6 s, respectively. Vacuum sampling with applied negative pressure (vrTB-nNO.sub.vac; negative pressure was applied by pinching the sampling tube) for < 2 s resulted in enhanced suction of nasal air during measurement. Feasibility, success rate, discriminatory capacity, repeatability and agreement were assessed for all four sampling modalities. Results We included 13 patients with PCD, median (IQR) age of 21.8 (12.2-27.7) years and 17 HC, 25.3 (14.5-33.4) years. Measurements were highly feasible (96.7% success rate). Measured NO values with vrTB-nNO modalities differed significantly from TB-nNO measurements (HC: p < 0.001, PCD: p < 0.05). All modalities showed excellent discrimination. The vacuum method gave remarkably high values of nNO in both groups (1865 vs. 86 ppb), but retained excellent discrimination. vrTB-nNO.sub.4sec, vrTB-nNO.sub.6sec and vrTB-nNO.sub.vac showed identical specificity to cTB-nNO (all: 1.0, 95% CI 0.77-1.0). Conclusion vrTB-nNO sampling requires only a few seconds of probe-in-nose time, is feasible, and provides excellent discrimination between PCD and HC. Rapid TB-nNO sampling needs standardisation and further investigations in infants, young children and patients referred for PCD workup.

Accurate, reliable, and sufficient data is required to reduce the burden of drowning by targeting preventive measures and improving treatment. Today's drowning statistics are informed by various methods sometimes based on data sources with questionable reliability. These methods are likely responsible for a systematic and significant underreporting of drowning. This study's aim was to assess the 30-day survival of patients with out-of-hospital cardiac arrest (OHCA) identified in the Danish Cardiac Arrest Registry (DCAR) after applying the Danish Drowning Formula. This nationwide, cohort, registry-based study with 30-day follow-up used the Danish Drowning Formula to identify drowning-related OHCA with a resuscitation attempt from the DCAR from January 1st, 2016, through December 31st, 2021. The Danish Drowning Formula is a text-search algorithm constructed for this study based on trigger-words identified from the prehospital medical records of validated drowning cases. The primary outcome was 30-day survival from OHCA. Data were analyzed using multiple logistic regression. Drowning-related OHCA occurred in 374 (1%) patients registered in the DCAR compared to 29,882 patients with OHCA from other causes. Drowning-related OHCA more frequently occurred at a public location (87% vs 25%, p < 0.001) and were more frequently witnessed by bystanders (80% vs 55%, p < 0.001). Both 30-day and 1-year survival for patients with drowning-related OHCA were significantly higher compared to OHCA from other causes (33% vs 14% and 32% vs 13%, respectively, p < 0.001). The adjusted odds ratio for 30-day survival for drowning-related OHCA and other causes of OHCA was 2.3 [1.7–3.2], p < 0.001. Increased 30-day survival was observed for drowning-related OHCA occurring at swimming pools compared to public location OHCA from other causes with an OR of 11.6 [6.0–22.6], p < 0.001. This study found higher 30-day survival among drowning-related OHCA compared to OHCA from other causes. This study proposed that a text-search algorithm (Danish Drowning Formula) could explore unstructured text fields to identify drowning persons. This method may present a low-resource solution to inform the drowning statistics in the future. Registration: This study was registered at ClinicalTrials.gov before analyses (NCT05323097). [ABSTRACT FROM AUTHOR]

Objectives: Primary ciliary dyskinesia (PCD) is a rare congenital disease with defective mucociliary clearance causing frequent and often persistent pulmonary infections. Achromobacter species are opportunistic pathogens renowned for the difficulty of effective treatments and deteriorating effects on lung function. We aimed to describe the occurrence, treatment, and rate of successful eradication of Achromobacter species in patients with PCD. Methods: We retrospectively reviewed 18 years of historical microbiological samples and 10 years of electronic health records for PCD patients in Denmark. Results: We included 136 patients. Twenty-six patients had isolates of Achromobacter species. On average, 5% of the cohort had at least one annual isolate. Infections became persistent in 38% with a median length of 6.6 years leading to a significant number of antibiotic treatments. Resistance toward tobramycin and ciprofloxacin was prevalent. Overall, successful eradication was achieved in 62% of patients. We found the course of lung function significantly worse during persistent Achromobacter species infection than during the two preceding years, but not different to the course in unaffected age-matched controls. Conclusion The prevalence of Achromobacter species in patients with PCD is in line with what has been reported in cystic fibrosis and can occur transiently, intermittently, or develop into a serious persistent lung infection associated with long-term antibiotic treatment. [ABSTRACT FROM AUTHOR]

Rationale: Primary ciliary dyskinesia is a rare genetic disorder characterized by progressive lung disease. Pseudomonas aeruginosa is a major pathogen in this disease, known to impact lung function. Previous genotype-phenotype studies have been limited by cross-sectional designs, isolated adult or pediatric populations, small numbers, or short follow-up durations. Objectives: We aimed to explore long-term lung function in primary ciliary dyskinesia grouped by genotypes and ultrastructural defects, considering the influence of P. aeruginosa . Methods: In this retrospective, observational study, we analyzed 43 years of spirometry and 20 years of microbiology data. Using linear mixed-effects models, we estimated FEV 1 z-score trends and compared them at ages 10, 25, and 50 years, while Generalized Estimating Equations were used to assess P. aeruginosa prevalence between groups. In a secondary analysis, we matched spirometry and microbiology samples to evaluate the influence of P. aeruginosa on lung function. Measurements and Main Results: We included 127 genotyped subjects, 6,691 spirometries and 10,082 microbiology samples. CCDC39 and CCDC40 variants showed early onset and sustained decline in lung function, while DNAH11 and HYDIN variants demonstrated relative stability. Lung function in the proximity of positive P. aeruginosa cultures were on average 0.06 z-score lower. Despite this, differences between groups remained largely unaffected by P. aeruginosa . Conclusion: Long-term lung function in primary ciliary dyskinesia follows discrete genotype specific profiles and appear independent of P. aeruginosa infection. We confirm and extend previous findings of CCDC39 and CCDC4 0 as variants associated with early onset severe lung function impairment persisting in the long term.

Background: Primary ciliary dyskinesia is a genetic disorder caused by aberrant motile cilia function that results in defective ciliary airway clearance and subsequently leads to recurrent airway infections and bronchiectasis. We aimed to determine: how many functional multiciliated airway cells are sufficient to maintain ciliary airway clearance?, Methods: To answer this question we exploited the molecular defects of the X-linked recessive primary ciliary dyskinesia variant caused by pathogenic variants in DNAAF6 ( PIH1D3 ), characterised by immotile cilia in affected males. We carefully analysed the clinical phenotype and molecular defect (using immunofluorescence and transmission electron microscopy) and performed in vitro studies (particle tracking in air-liquid interface cultures) and in vivo studies (radiolabelled tracer studies) to assess ciliary clearance of respiratory cells from female individuals with heterozygous and male individuals with hemizygous pathogenic DNAAF6 variants., Results: Primary ciliary dyskinesia male individuals with hemizygous pathogenic DNAAF6 variants displayed exclusively immotile cilia, absence of ciliary clearance and severe primary ciliary dyskinesia symptoms. Owing to random or skewed X-chromosome inactivation in six female carriers with heterozygous pathogenic DNAAF6 variants, 54.3±10% (range 38-70%) of multiciliated cells were defective. Nevertheless, in vitro and in vivo assessment of the ciliary airway clearance was normal or slightly abnormal. Consistently, heterozygous female individuals showed no or only mild respiratory symptoms., Conclusions: Our findings indicate that having 30-62% of multiciliated respiratory cells functioning can generate either normal or slightly reduced ciliary clearance. Because heterozygous female carriers displayed either no or subtle respiratory symptoms, complete correction of 30% of cells by precision medicine could improve ciliary airway clearance in individuals with primary ciliary dyskinesia, as well as clinical symptoms., Competing Interests: Conflict of interest: The authors have no potential conflicts of interest to declare., (Copyright ©The authors 2024.)

Background: Primary ciliary dyskinesia (PCD) represents a group of rare hereditary disorders characterised by deficient ciliary airway clearance that can be associated with laterality defects. We aimed to describe the underlying gene defects, geographical differences in genotypes and their relationship to diagnostic findings and clinical phenotypes., Methods: Genetic variants and clinical findings (age, sex, body mass index, laterality defects, forced expiratory volume in 1 s (FEV 1 )) were collected from 19 countries using the European Reference Network's ERN-LUNG international PCD Registry. Genetic data were evaluated according to American College of Medical Genetics and Genomics guidelines. We assessed regional distribution of implicated genes and genetic variants as well as genotype correlations with laterality defects and FEV 1 ., Results: The study included 1236 individuals carrying 908 distinct pathogenic DNA variants in 46 PCD genes. We found considerable variation in the distribution of PCD genotypes across countries due to the presence of distinct founder variants. The prevalence of PCD genotypes associated with pathognomonic ultrastructural defects (mean 72%, range 47-100%) and laterality defects (mean 42%, range 28-69%) varied widely among countries. The prevalence of laterality defects was significantly lower in PCD individuals without pathognomonic ciliary ultrastructure defects (18%). The PCD cohort had a reduced median FEV 1 z-score (-1.66). Median FEV 1 z-scores were significantly lower in CCNO (-3.26), CCDC39 (-2.49) and CCDC40 (-2.96) variant groups, while the FEV 1 z-score reductions were significantly milder in DNAH11 (-0.83) and ODAD1 (-0.85) variant groups compared to the whole PCD cohort., Conclusion: This unprecedented multinational dataset of DNA variants and information on their distribution across countries facilitates interpretation of the genetic epidemiology of PCD and indicates that the genetic variant can predict diagnostic and phenotypic features such as the course of lung function., Competing Interests: Conflict of interest: The authors have no potential conflicts of interest to disclose., (Copyright ©The authors 2024.)