Test-retest reliability of lung diffusing capacity for nitric oxide during light to moderate intensity cycling exercise

This study examined test-retest reliability of single-breath lung diffusing capacity for nitric oxide (DLNO) and carbon monoxide (DLCO) during exercise. Sixteen healthy subjects (age 20-67 years) performed DLNO-DLCO tests during light and moderate intensity cycling exercise at 50% and 80% of individual anaerobic threshold (IAT). Primary endpoint was DLNO at 80% IAT. Precision of DLNO, DLCO, and alveolar volume was quantified by within-subject standard deviation (SDws, measurement error) and intraclass correlation coefficients (ICC). Reproducibility was determined by SDws* 2.77. Overall, reliability was excellent for all outcomes. SDws and reproducibility for DLNO at 80% IAT were 4.6 and 12.7 mL.min-1.mmHg-1, and the ICC was 0.99 (95% confidence interval 0.98-0.99). Median breathlessness at 80% IAT was 4 (interquartile range 3-6) on a 0-10 scale. Our data suggest excellent reliability of single-breath DLNO during moderate intensity exercise, but perceived levels of breathlessness may limit its usefulness, especially at exercise intensities beyond IAT. Keywords: Diffusing capacity for nitric oxide; Exercise; Reliability; Reproducibility; Single breat

Hospitalisations Related to Adverse Drug Reactions in Switzerland in 2012-2019: Characteristics, In-Hospital Mortality, and Spontaneous Reporting Rate

INTRODUCTION Adverse drug reactions (ADRs) contribute to morbidity, and serious ADRs may cause hospitalisation and death. This study characterises and quantifies ADR-related hospitalisations and subsequent in-hospital deaths, and estimates the spontaneous reporting rate to regulatory authorities in Switzerland, where healthcare professionals are legally obliged to report ADRs. METHODS This retrospective cohort study from 2012 to 2019 analysed nationwide data from the Federal Statistical Office. ICD-10 coding rules identified ADR-related hospitalisations. To estimate the reporting rate, individual case safety reports (ICSRs) collected in the Swiss spontaneous reporting system during the same period were considered. RESULTS Among 11,240,562 inpatients, 256,550 (2.3%) were admitted for ADRs, 132,320 (51.6%) were female, 120,405 (46.9%) were aged ≥ 65 (median of three comorbidities, interquartile range [IQR] 2-4), and 16,754 (6.5%) were children/teenagers (0 comorbidities, IQR 0-1). Frequent comorbidities were hypertension (89,938 [35.1%]), fluid/electrolyte disorders (54,447 [21.2%]), renal failure (45,866 [17.9%]), cardiac arrhythmias (37,906 [14.8%]), and depression (35,759 [13.9%]). Physicians initiated 113,028 (44.1%) of hospital referrals, and patients/relatives 73,494 (28.6%). Frequently ADR-affected were the digestive system (48,219 [18.8%], e.g. noninfective gastroenteritis and colitis), the genitourinary system (39,727 [15.5%], e.g. acute renal failure), and the mental/behavioural state (39,578 [15.4%], e.g. opioid dependence). In-hospital mortality was 2.2% (5669). Since ICSRs indicated 14,109 hospitalisations and 700 in-hospital deaths, estimated reporting rates were 5% and 12%, respectively. CONCLUSIONS This 8-year observation in Switzerland revealed that 2.3%, or roughly 32,000 admissions per year, were caused by ADRs. The majority of ADR-related admissions were not reported to the regulatory authorities, despite legal obligations

Frequency-based rare diagnoses as a novel and accessible approach for studying rare diseases in large datasets: a cross-sectional study

BACKGROUND Up to 8% of the general population have a rare disease, however, for lack of ICD-10 codes for many rare diseases, this population cannot be generically identified in large medical datasets. We aimed to explore frequency-based rare diagnoses (FB-RDx) as a novel method exploring rare diseases by comparing characteristics and outcomes of inpatient populations with FB-RDx to those with rare diseases based on a previously published reference list. METHODS Retrospective, cross-sectional, nationwide, multicenter study including 830,114 adult inpatients. We used the national inpatient cohort dataset of the year 2018 provided by the Swiss Federal Statistical Office, which routinely collects data from all inpatients treated in any Swiss hospital. Exposure: FB-RDx, according to 10% of inpatients with the least frequent diagnoses (i.e.1.decile) vs. those with more frequent diagnoses (deciles 2-10). Results were compared to patients having 1 of 628 ICD-10 coded rare diseases. PRIMARY OUTCOME In-hospital death. SECONDARY OUTCOMES 30-day readmission, admission to intensive care unit (ICU), length of stay, and ICU length of stay. Multivariable regression analyzed associations of FB-RDx and rare diseases with these outcomes. RESULTS 464,968 (56%) of patients were female, median age was 59 years (IQR: 40-74). Compared with patients in deciles 2-10, patients in the 1. were at increased risk of in-hospital death (OR 1.44; 95% CI: 1.38, 1.50), 30-day readmission (OR 1.29; 95% CI 1.25, 1.34), ICU admission (OR 1.50; 95% CI 1.46, 1.54), increased length of stay (Exp(B) 1.03; 95% CI 1.03, 1.04) and ICU length of stay (1.15; 95% CI 1.12, 1.18). ICD-10 based rare diseases groups showed similar results: in-hospital death (OR 1.82; 95% CI 1.75, 1.89), 30-day readmission (OR 1.37; 95% CI 1.32, 1.42), ICU admission (OR 1.40; 95% CI 1.36, 1.44) and increased length of stay (OR 1.07; 95% CI 1.07, 1.08) and ICU length of stay (OR 1.19; 95% CI 1.16, 1.22). CONCLUSION(S) This study suggests that FB-RDx may not only act as a surrogate for rare diseases but may also help to identify patients with rare disease more comprehensively. FB-RDx associate with in-hospital death, 30-day readmission, intensive care unit admission, and increased length of stay and intensive care unit length of stay, as has been reported for rare diseases

Geografische Unterschiede in der Inanspruchnahme von Gesundheitsleistungen

Geografische Variabilität der Inanspruchnahme von Gesundheitsleistungen hat vielfältige Ursachen. Sie kann auf Qualitätsprobleme im Gesundheitswesen hinweisen. Über die Situation in der Schweiz war bisher wenig bekannt. Die Studie «Geographic variation in the utilisation of health care inter­ventions: what is the role of recommendations and other influences?» widmete sich diesem Fragen­komplex

Independent Information of Nonspecific Biomarkers in Exhaled Breath Condensate

Background: Exhaled breath condensate (EBC) has been used for diagnosing and monitoring respiratory disorders. For clinical purposes the assessment of easy-to-obtain nonspecific markers seems particularly interesting. Objectives: As these measures are related to each other, our objective was to extract the independent information in global EBC markers across a range of respiratory disorders. Methods: EBC was collected from patients with asthma (n = 18), chronic obstructive pulmonary disease (n = 17), and cystic fibrosis (n = 46), as well as from lung transplant (LTX) recipients (n = 14) and healthy controls (n = 26). Samples were assessed for electrical conductivity, ammonia, pH, and nitrite/nitrate. pH was measured after both deaeration with argon and CO(2) standardization. Additionally, the fraction of exhaled nitric oxide (FE(NO)) was assessed. Factor analysis was applied to identify major factors concerning these measures. Results: Three independent factors were detected; the first comprised conductivity, ammonia, and pH, especially when standardized using CO(2), the second nitrite/nitrate, and the third FE(NO). Conductivity and ammonia were highly correlated (r = 0.968; p < 0.001). FE(NO) provided independent information mainly in asthma. The nonspecific EBC markers showed considerable overlap between patient groups and healthy subjects. However, conductivity, ammonia, pH standardized for CO(2) and nitrite/nitrate were increased in LTX recipients compared to healthy controls (p < 0.05 each). Conclusions: A panel of nonspecific easy-to-obtain exhaled breath markers could be reduced to 3 independent factors. The information content of conductivity, ammonia, and pH after CO(2) equilibration appeared to be similar, while FE(NO) was independent. The increased levels of these biomarkers in LTX might indicate a potential for their use in these patients. Copyright (C) 2010 S. Karger AG, Base

Occupations and geographical distribution of mesothelioma in Switzerland 1989-2018 - record linkage of an asbestos-exposed population with the Swiss National Cohort

OBJECTIVE We investigated the possibility of linking the data of the Swiss Laboratory for Particle Analysis (Silag), a valuable but incomplete data source in the field of asbestos-related diseases, to the Swiss National Cohort (SNC). With the resulting comprehensive dataset, we intended to provide a source for further research in the field. We also conducted preliminary analyses of data focusing on occupations and regional distribution of malignant pleural mesothelioma cases. METHODS Data of asbestos-exposed individuals available from the Silag were anonymously linked with the SNC by means of deterministic record linkage. From this linkage, data on occupation classified according to the international standard classification of occupations (ISCO) as well as the canton of residence in Switzerland could be retrieved. RESULTS Of 838 eligible individuals from the Silag data, 788 (94.0%) could be linked to the SNC database, including 476 mesothelioma cases. In 340 cases of the latter, data on occupation and industries were available. Although the majority of them were blue-collar workers, a significant proportion (n = 44, 12.9%) had executive professions. The Canton of residence in 1990 was established in 430 of subjects with mesothelioma. A cluster could be identified in eastern Switzerland, especially in the canton of Glarus. CONCLUSIONS It was possible to link the datasets to a large extent thereby creating a data source for further research. Of note, the linkage provided data on occupation of a selection of mesothelioma cases in Switzerland

Datenquellen zur Häufigkeit des malignen Pleuramesothelioms in der Schweiz seit 2001

Objective: Malignant pleural mesothelioma is a cancer of the membranes of the pulmonary pleurae and is caused predominantly by asbestos. While no exact incidence data are available for Switzerland, the case numbers have been increasing for many years and pleural mesothelioma is a topic of concern. Case numbers can be estimated, however, thanks to a variety of data sources. The purpose of this article is to present and compare these sources and to present corresponding analyses. Methods: We determined the numbers of patients with malignant pleura mesothelioma from 2001 to 2019 by using various datasets, including data from accident insurers, the National Institute for Cancer Epidemiology and Registration (NICER), the causes of death statistics and hospital inpatient data. The analysis of the latter dataset was specifically conducted for this publication. Results: All analyses showed increasing numbers of patients with malignant pleural mesothelioma during the study period. The numbers from the accident insurers and the causes of death statistics converged during the observation period. The numbers from NICER and from inpatient data were considerably higher than those from the other two datasets. Conclusions: This is the first study that describes the incidence of pleural mesothelioma in various data sources in Switzerland. A comparative study of different data sources is shown to provide valuable additional information. The comparison of accident statistics and the causes of death statistics suggest that the recording of malignant pleural mesothelioma as an occupational disease is becoming increasingly thorough. Keywords: malignant pleural mesothelioma – asbestos – routine data – Switzerlan

Exhaled and nasal nitric oxide in laryngectomized patients

<p>Abstract</p> <p>Background</p> <p>Nitric oxide (NO) shows differing concentrations in lower and upper airways. Patients after total laryngectomy are the only individuals, in whom a complete separation of upper and lower airways is guaranteed. Thus the objective of our study was to assess exhaled and nasal NO in these patients.</p> <p>Methods</p> <p>Exhaled bronchial NO (FE_NO) and nasal nitric oxide (nNO) were measured in patients after total laryngectomy (n = 14) and healthy controls (n = 24). To assess lung function we additionally performed spirometry. Co-factors possibly influencing NO, such as smoking, infections, and atopy were excluded.</p> <p>Results</p> <p>There was a markedly (p < 0.001) lower FE_NOin patients after total laryngectomy (median (range): 4 (1-22) ppb) compared to healthy controls 21 (9-41) ppb). In contrast, nNO was comparable between groups (1368 <it>versus </it>1380 in controls) but showed higher variability in subjects after laryngectomy.</p> <p>Conclusions</p> <p>Our data suggest that either bronchial NO production in patients who underwent laryngectomy is very low, possibly due to alterations of the mucosa or oxidant production/inflammation, or that substantial contributions to FE_NOarise from the larynx, pharynx and mouth, raising FE_NOdespite velum closure. The data fit to those indicating a substantial contribution to FE_NOby the mouth in healthy subjects. The broader range of nNO values found in subjects after laryngectomy may indicate chronic alteration or oligo-symptomatic inflammation of nasal mucosa, as frequently found after total laryngectomy.</p

Exhaled nitric oxide: Independent effects of atopy, smoking, respiratory tract infection, gender and height

SummaryMeasurement of exhaled nitric oxide is widely used in respiratory research and clinical practice, especially in patients with asthma. However, interpretation is often difficult, due to common interfering factors, and little is known about interactions between factors. We assessed the influences and interactions of factors such as smoking, respiratory tract infections and respiratory allergy concerning exhaled nitric oxide values, with the aim to derive a scheme for adjustment. We studied 897 subjects (514 females, 383 males; mean age±standard deviation 34.5±13.0 years) with and without respiratory allergy (allergic rhinitis and/or asthma), smoking and respiratory tract infection. Logarithmic nitric oxide levels were described by an additive model comprising respiratory allergy, smoking, respiratory tract infection, gender and height (p⩽0.001 each), without significant interaction terms. Geometric mean was 17.5ppb in a healthy female non smoker of height 170cm, whereby respiratory allergy corresponded to a change by factor 1.50, smoking 0.63, infection 1.24, male gender 1.17, and each 10cm increase (decrease) in height to 1.11 (0.90). Factors were virtually identical when excluding asthma and using the category allergic rhinitis instead of respiratory allergy (n=863). Within each category formed by combinations of these different predictors, the range of residual variation was approximately constant. We conclude that the factors influencing exhaled nitric oxide, which we analyzed, act independently of each other. Thus, circumstances such as smoking and respiratory tract infection do not appear to affect the usefulness of exhaled nitric oxide, provided that appropriate factors for adjustment are applied

Electronic Health Diary Campaigns to Complement Longitudinal Assessments in Persons With Multiple Sclerosis: Nested Observational Study

BACKGROUND Electronic health diaries hold promise in complementing standardized surveys in prospective health studies but are fraught with numerous methodological challenges. OBJECTIVE The study aimed to investigate participant characteristics and other factors associated with response to an electronic health diary campaign in persons with multiple sclerosis, identify recurrent topics in free-text diary entries, and assess the added value of structured diary entries with regard to current symptoms and medication intake when compared with survey-collected information. METHODS Data were collected by the Swiss Multiple Sclerosis Registry during a nested electronic health diary campaign and during a regular semiannual Swiss Multiple Sclerosis Registry follow-up survey serving as comparator. The characteristics of campaign participants were descriptively compared with those of nonparticipants. Diary content was analyzed using the Linguistic Inquiry and Word Count 2015 software (Pennebaker Conglomerates, Inc) and descriptive keyword analyses. The similarities between structured diary data and follow-up survey data on health-related quality of life, symptoms, and medication intake were examined using the Jaccard index. RESULTS Campaign participants (n=134; diary entries: n=815) were more often women, were not working full time, did not have a higher education degree, had a more advanced gait impairment, and were on average 5 years older (median age 52.5, IQR 43.25-59.75 years) than eligible nonparticipants (median age 47, IQR 38-55 years; n=524). Diary free-text entries (n=632; participants: n=100) most often contained references to the following standard Linguistic Inquiry and Word Count word categories: negative emotion (193/632, 30.5%), body parts or body functioning (191/632, 30.2%), health (94/632, 14.9%), or work (67/632, 10.6%). Analogously, the most frequently mentioned keywords (diary entries: n=526; participants: n=93) were "good," "day," and "work." Similarities between diary data and follow-up survey data, collected 14 months apart (median), were high for health-related quality of life and stable for slow-changing symptoms such as fatigue or gait disorder. Similarities were also comparatively high for drugs requiring a regular application, including interferon beta-1a (Avonex) and glatiramer acetate (Copaxone), and for modern oral therapies such as fingolimod (Gilenya) and teriflunomide (Aubagio). CONCLUSIONS Diary campaign participation seemed dependent on time availability and symptom burden and was enhanced by reminder emails. Electronic health diaries are a meaningful complement to regular structured surveys and can provide more detailed information regarding medication use and symptoms. However, they should ideally be embedded into promotional activities or tied to concrete research study tasks to enhance regular and long-term participation