Inference on Competing Risks in Breast Cancer Data

While nonparametric methods have been well established for inference on competing risks data, parametric methods for such data have not been developed as much. Because the cumulative incidence functions are improper by their nature, flexible distribution families accommodating improperness are needed for modeling competing data more accurately. Additionally, different types of events present in a competing risks setting may be correlated, yet current inference methods do not permit inferring such data taking into account the correlation between failure time distributions. This work first presents two new distributions which are well-suited for modeling competing risks data. In existing inference procedures for competing risks data, it appears that the correlation between failure time distributions of competing events are fixed as a constant. In the second part of this dissertation, a novel approach is proposed which allows researchers to model competing risks data by taking the correlation into account by estimating it. The methods are illustrated by analyzing survival data from a breast cancer trial of the National Surgical Adjuvant Breast and Bowel Project. Simulation studies are also presented for each of the proposed new distributions.Public Health Significance: Competing risks occur often in many clinical studies, and must be accounted for whenever researchers are interested in only one type of event. For example, researchers may be interested in investigating only local recurrences of breast cancer, but must also take into account all other possible types of events as competing. Parametric methods are not currently as well established as other methods for competing risks data. Development of flexible parametric inference procedures suitable for modeling competing risks data would provide more accurate information, which will serve to improve patient care in clinical settings

Influence of cantonal health policy frameworks & activities on the influenza vaccination rate in patients with non-communicable diseases in Switzerland

Background and objective Seasonal influenza may cause serious illness, especially in high-risk populations such as older adults and individuals suffering from non-communicable diseases (NCD) and may be prevented by a vaccination. However, an assessment of the impact of the Swiss legal frameworks and number of health activities on influenza vaccination coverage of the population at the cantonal level is lacking. Methods Two participating healthcare insurers sent out 25,000 semi-structured questionnaires to their subscribers aged 60–85 in five Swiss cantons selected according to the number of health activities and legal framework regarding influenza vaccination and linguistic region. Influenza vaccination coverage of the participants was evaluated and stratified by disease status, age, canton, and linguistic region. Results were compared by cantonal activities, legal framework, and linguistic region. Results 7,617 valid questionnaires were evaluated from the cantons Aargau, Jura, St. Gallen, Schwyz, and Vaud. 47.9 % stated to have an NCD, with the most frequent being muscle/ skeletal disease (36.7%). Before 2018, 48.6% were vaccinated against influenza, and 35.9% in 2019, with the highest in canton Vaud. In all cantons and in both survey periods, NCD patients and those aged 73–85 had a higher vaccination coverage than participants without NCD, and aged 60–72. There was no difference in the odds of getting an influenza shot based on legal framework. Although a comparison of the number of activities between the German-speaking cantons did not reveal any significant differences, the odds of the participants living in a French-speaking canton getting an influenza vaccination was more likely than those living in a German-speaking canton. Conclusion There was no association between the investigated cantonal frameworks and number of health activities and influenza vaccination coverage in NCD patients in the selected cantons. However, age, disease status and linguistic region appear to have an influence on vaccination uptake

The impact of seat height on 1-min sit-to-stand test performance in COPD: a randomised crossover trial

Study question Is there a difference in the number of repetitions in the 1-minute sit-to-stand (1MSTS) test using an individually adapted seat height to 90° knee flexion (1MSTSIND), compared with the commonly used standard chair seat height of 46 cm (1MSTSSTD), in people with COPD? Methods We conducted a single-centre, single-blinded, randomised crossover trial in people with COPD between August 2020 and March 2021 at a specialised rehabilitation clinic in Switzerland. After a learning 1MSTS test, all participants performed two 1MSTS tests in random order on consecutive days. Participants were blinded, as they did not receive detailed information on the testing protocols. Results 49 individuals with COPD (47% female) participated. In a regression model adjusted for sequence period and subject, 1MSTS test performance was lower on 1MSTSIND compared to 1MSTSSTD (−0.78 repetitions, 95% CI −1.47 to −0.11). In a second regression model additionally including the knee angle and an interaction term (1MSTSIND×knee angle), the interaction term was significant: 0.18 (95% CI 0.05 to 0.30). The limits of agreement were between −5.5 and 4 repetitions. Conclusion Although we observed a statistically significant difference between 1MSTSIND and 1MSTSSTD on a population level, the difference is negligible. Further studies may be needed to determine whether individual adaptation of seat height is needed for very tall or short people to ensure a valid assessment of 1MSTS test performance in COPD

Multiple Score Comparison: a network meta-analysis approach to comparison and external validation of prognostic scores

BACKGROUND Prediction models and prognostic scores have been increasingly popular in both clinical practice and clinical research settings, for example to aid in risk-based decision making or control for confounding. In many medical fields, a large number of prognostic scores are available, but practitioners may find it difficult to choose between them due to lack of external validation as well as lack of comparisons between them. METHODS Borrowing methodology from network meta-analysis, we describe an approach to Multiple Score Comparison meta-analysis (MSC) which permits concurrent external validation and comparisons of prognostic scores using individual patient data (IPD) arising from a large-scale international collaboration. We describe the challenges in adapting network meta-analysis to the MSC setting, for instance the need to explicitly include correlations between the scores on a cohort level, and how to deal with many multi-score studies. We propose first using IPD to make cohort-level aggregate discrimination or calibration scores, comparing all to a common comparator. Then, standard network meta-analysis techniques can be applied, taking care to consider correlation structures in cohorts with multiple scores. Transitivity, consistency and heterogeneity are also examined. RESULTS We provide a clinical application, comparing prognostic scores for 3-year mortality in patients with chronic obstructive pulmonary disease using data from a large-scale collaborative initiative. We focus on the discriminative properties of the prognostic scores. Our results show clear differences in performance, with ADO and eBODE showing higher discrimination with respect to mortality than other considered scores. The assumptions of transitivity and local and global consistency were not violated. Heterogeneity was small. CONCLUSIONS We applied a network meta-analytic methodology to externally validate and concurrently compare the prognostic properties of clinical scores. Our large-scale external validation indicates that the scores with the best discriminative properties to predict 3 year mortality in patients with COPD are ADO and eBODE

Perceptions towards mask use in school children during the SARS-CoV-2 pandemic: descriptive results from the longitudinal Ciao Corona cohort study

BACKGROUND: Mask wearing contributes to the reduction of transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In Switzerland, compulsory use of masks was introduced in indoor public spaces and later in schools. This study explored perceptions of the usefulness of masks in school and public in a cohort of children and adolescents in the canton of Zurich, Switzerland, in January to May 2021. METHODS: School children aged 10 to 17 years enrolled in Ciao Corona, a prospective school-based cohort study, responded to nested online surveys between 12 January and 24 March 2021 (Q1) and 10 March and 16 May 2021 (Q2). Secondary school children were surveyed at Q1 and Q2, and primary school children at Q2 only. Surveys for parents and their children included questions on the children’s perception of the usefulness of masks and mask wearing behaviour by applying a non-validated questionnaire. Associations between perceived usefulness of masks and child’s school level and gender, and parents’ educational attainment were analysed with Pearson’s and McNemar’s chi-square tests. Free-text comments provided by children were classified into categories of expressed attitude towards mask wearing. RESULTS: A total of 595 (54% girls) and 1118 (52% girls) school children with predominantly Swiss nationality and a high socioeconomic status responded to online questionnaires at Q1 and Q2, respectively. More than half of the school children perceived masks to be useful at school (Q1: 60% and Q2: 57%) and in public (Q1: 69% and Q2 :60%). Girls perceived masks as useful more often than boys (at Q2 at school: 61% versus 53%, in public: 64% versus 57%), and children of parents with high educational attainment more often than those of parents with lower educational attainment (at Q2 at school: 61% versus 49%, in public: 63% versus 54%). At Q1 and Q2 each, about 20% of children provided individual statements about masks, of which 36% at Q1 and 16% at Q2 reported side effects and discomfort such as skin irritations, headache or difficulties breathing during physical education. CONCLUSIONS: Approximately 60% of school children perceived masks at school and in public places as useful. A small but non-negligible proportion of children reported discomfort and side effects that should be considered to ensure high adherence to mask wearing among school children. A validation of the questionnaire is needed

SARS-CoV-2 seroprevalence in children, parents and school personnel from June 2020 to April 2021: cohort study of 55 schools in Switzerland

BACKGROUND: Few studies have directly examined the incidence or seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in children, parents and teachers from the same school communities. This study aimed to describe SARS-CoV-2 seroprevalence within cantonal districts and school communities in children, parents and school personnel in June-September 2020 and March-April 2021 in the canton of Zürich, Switzerland. METHODS: We invited children from 55 randomly selected primary and secondary schools and 275 classes within them to participate in the Ciao Corona study in June-July 2020. Parents of the participating children and all school personnel were invited in August-September 2020. Eligible classes, parents and school personnel were tested again in March-April 2021. Venous blood was tested for SARS-CoV-2 serology. We collected sociodemographic information of the participants in online questionnaires on enrolment in the study. We excluded vaccinated adults and those with unverified vaccination status from the main analysis. Seroprevalence estimates were adjusted for test accuracy. We assessed the variability of seroprevalence within and across cantonal districts and school communities and compared it with the per capita cumulative incidence of confirmed SARS-CoV-2 infections. RESULTS: In June-September 2020, 2,473 children, 1,608 school personnel and 2,045 parents participated in the study. In June-September 2020, seroprevalence was low (4.4% to 5.8%) in all cohorts. In March-April 2021, seroprevalence in children and parents (18.1% and 20.9%) was slightly higher than in school personnel (16.9%). We observed a large variation in seroprevalence estimates of the three cohorts within and between districts and school communities, with the median ratio of children’s seroprevalence to per capita confirmed cases in district inhabitants of 3.1 (interquartile range 2.6 to 3.9). Seroprevalence was lower in children in the upper school level and their parents, but not teachers. Children’s seroprevalence was slightly higher in classes with infected main teachers and families with one infected parent and substantially higher in families with two infected parents. CONCLUSIONS: We observed similar seroprevalence in children and parents, somewhat lower in school personnel in March-April 2021 and striking variation between districts and school communities. Children’s seroprevalence was higher in classes with infected main teachers and from families with infected parents

Individualised PPI prescription in patients on combination antiplatelet therapy and upper gastrointestinal events after percutaneous coronary intervention: a cohort study

Zusammenfassung: GRUNDLAGEN: In einer Patientenkohorte, welche nach perkutaner koronarer Intervention (PCI) kombinierte Thrombozytenaggregationshemmung (Aspirin und Clopidogrel) erhielt, wurde die Wirksamkeit einer individualisierten PPI-Gabe zur Reduktion unerwünschter gastrointestinaler Ereignisse untersucht. METHODIK: Das gastrointestinale Risikofaktorprofil und andere Parameter wurden aus einer speziell angelegten elektronischen Datenbank extrahiert. Die Patienten wurden via standardisierten Fragebogen kontaktiert und bei Patienten mit unerwünschten gastrointestinalen Ereignissen wurde zusätzlich ein strukturiertes Telefoninterview durchgeführt. ERGEBNISSE: In einer Kohorte von 718 Patienten erhielten 87 (12,1 %) eine prophylaktische PPI-Therapie. Bei insgesamt 12 % wurden unerwünschte gastrointestinale Ereignisse gefunden, wobei 18,4 % eine PPI-Prophylaxe und 11,1 % kein PPI hatten (OR 1,80, P = 0,054). Eine Komedikation mit Steroiden war der hauptsächliche Risikofaktor für unerwünschte gastrointestinale Ereignissen (adjusted OR 5,45, P = 0,014). SCHLUSSFOLGERUNGEN: Die individualisierte PPI-Therapie basierend auf einer Risikoabschätzung für gastrointestinale Blutungsereignisse scheint ein effizientes Instrument zu sein, um gastrointestinale Ereignisse nach PCI zu minimiere

Is radiographic progression of late-onset rheumatoid arthritis different from young-onset rheumatoid arthritis? Results from the Swiss prospective observational cohort

Objective. RA can be categorized into late-onset RA (LORA, >60-65 years) and young-onset RA (YORA, 30-55 years), depending on the patient's age at disease onset. Since the average age of the population is continuously increasing, LORA will most probably gain in importance in the future. Despite this growing importance, LORA has not been the focus of much interest in the past. The aim of this study was to analyse radiographic damage progression of early disease in LORA compared with YORA patients. Methods. We included all patients from the Swiss RA registry, Swiss Clinical Quality Management in RA, with recent-onset arthritis, either RA (disease duration ≤1 year) or undifferentiated arthritis, as diagnosed by the data-entering physician. Patients were followed for 5 years. The cut-off between YORA and LORA was operationally set at 60 years of age. The primary outcome of this study was disease progression and activity, which was assessed based on the 28-joint DAS (DAS28) and the progression of joint erosions using a validated scoring system (Ratingen score). Results. A total of 592 patients with early disease were analysed. The age at disease onset had a Gaussian distribution, with a single peak at 54 years of age; 366 patients were categorized as YORA and 226 as LORA at disease onset. DAS28 scores were significantly higher among LORA as compared with YORA patients (4.8 vs 4.5, P = 0.049). Corticosteroids were used in 68% of LORA patients as a first-line treatment, compared with 25.4% in YORA patients (χ2 test: 54.58; P < 0.0001). In contrast, DMARDs were used in 100% of the YORA patients as first-line treatment, compared with 91.2% of the LORA patients. During follow-up, new glucocorticoids, synthetic DMARDs or biologic DMARDs were initiated in 32.8%, 61.1% and 14.1% of all YORA patients and 17.5%, 54.6% and 6.6% of LORA patients, respectively (χ2 test: 7.08, 22.53, 54.4; all P < 0.01). The DAS28 scores decreased in both groups during the observed time period, and the initial differences in disease activity vanished after 6 months and during the subsequent follow-up. The Ratingen score was higher in LORA than in YORA patients at inclusion (12.7 vs 5.6, P < 0.0001). The rate of radiographic progression at 5 years was similar when comparing LORA and YORA (3.3 vs 2.6, respectively, P = 0.64). The Ratingen scores at onset and during follow-up over 5 years did not clearly separate LORA and YORA into two groups, but rather, increased linearly when comparing the patients in groups per decade from 20 to 92 years of age. Conclusion. Our results did not show LORA as a separate subgroup of RA with a different prognosis with regard to radiographic progressio