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The COVID-19 pandemic has led to many studies of seroprevalence. A number of methods exist in the statistical literature to correctly estimate disease prevalence or seroprevalence in the presence of diagnostic test misclassification, but these methods seem to be not routinely used in the public health literature. We aimed to examine how widespread the problem is in recent publications, and to quantify the magnitude of bias introduced when correct methods are not used. A systematic review was performed to estimate how often public health researchers accounted for diagnostic test performance in estimates of seroprevalence. Of the seroprevalence studies sampled, 77% (95% CI 72%-82%) failed to account for sensitivity and specificity. In high impact journals, 72% did not correct for test characteristics, and 34% did not report sensitivity or specificity. The most common type of correction was the Rogen-Gladen formula (57%, 45%-69%), followed by Bayesian approaches (32%, 21%-44%). Rates of correction increased slightly over time, but type of correction did not change. Researchers conducting studies of prevalence should report sensitivity and specificity of the diagnostic test and correctly account for these characteristics.

We have recently reported reduced physical activity (PA) in people with cystic fibrosis (pwCF) with and without lung transplantation (LTX) during a 6-week stringent lockdown in Switzerland. This follow-up study explores the impact of coronavirus-2019 disease (COVID-19) related pandemic restrictions on individuals' therapy regimens and health-related aspects in pwCF. We conducted a cross-sectional web-based national survey in Spring 2021. The survey included questions on daily PA, airway clearance and inhalation therapy, questions on COVID-19-compatible symptoms, diagnostic tests and vaccination status, and enquired health-related aspects covering the pandemic period between March 2020 to April 2021. 193 individuals with CF (53% female; 25% LTX recipients) participated. Among pwCF, 10 reported COVID-19 (n = 2 LTX recipients), two subjects were hospitalized, no invasive ventilation required, no deaths. The clinical course was generally mild. Overall, 46% reported less PA during the pandemic, mostly due to closed fitness facilities (85%), lack of motivation (34%), and changes in daily structures (21%). In contrast, 32/193 (17%) pwCF were able to increase their PA levels: 12 (38%) and 11 (34%) reported undertaking home-based training and outdoor activities more frequently; 6 (19%) reported an increase in routine PA, and another 3 (9%) started new activities. Among pwCF without LTX, 5% and 4% reported to undertake less airway clearance and inhalation therapy, respectively. Our study reveals unfavorable consequences of COVID-19 pandemic restrictions on PA of pwCF with unknown long-term consequences for their overall physical fitness and lung health. Strategies to overcome this undesirable situation are needed; increased uptake of telehealth PA programs and virtual exercise classes to promote PA participation might be one promising approach along with vaccination of pwCF and their close contacts.

In metastatic hormone-sensitive prostate cancer (mHSPC) treatment, survival benefits have been shown by adding docetaxel or recent androgen receptor axis-targeted therapies (ARATs) abiraterone, apalutamide, or enzalutamide to androgen deprivation therapy (ADT). However, the optimal treatment strategy in terms of costs and effects is unclear, not least due to high ARAT costs. To assess treatment cost-effectiveness, we developed a Markov cohort model with health states of progression-free disease, progressive disease and death for men with newly diagnosed mHSPC, with a 30-year time horizon. Survival data, adverse events and utilities were informed by randomized controlled trial results, our meta-analysis of re-created individual patient survival data, and publicly available sources of unit costs. We applied a Swiss healthcare payer perspective and discounted costs and effects by 3%. We found a significant overall survival benefit for ADT+abiraterone versus ADT+docetaxel. The corresponding incremental cost-effectiveness ratio (ICER) was predicted to be EUR 39,814 per quality-adjusted life-year (QALY) gained. ADT+apalutamide and ADT+enzalutamide incurred higher costs and lower QALYs compared to ADT+abiraterone. For all ARATs, drug costs constituted the most substantial cost component. Results were stable except for a large univariable reduction in the pre-progression utility under ADT+abiraterone and very large variations in drug prices. Our model projected ADT+abiraterone to be cost-effective compared to ADT+docetaxel at a willingness-to-pay threshold of EUR 70,400/QALY (CHF 100,000 applying purchasing power parities). Given lower estimated QALYs for ADT+apalutamide and ADT+enzalutamide compared to ADT+abiraterone, the former only became cost-effective (the preferred) treatment option(s) at substantial 75-80% (80-90%) price reductions.

The allostatic load (AL) index is a multi-systemic measure of physiologic dysregulation known to be associated with chronic exposure to stress and adverse health outcomes. We examined the relationship between AL and serum 25-hydroxyvitamin D (25(OH)D) concentration in non-institutionalized US adults. Data from the Third National Health and Nutrition Examination Survey (NHANES III, 1988-94) were used to calculate two versions of AL including 9 biomarkers and another two with 14 biomarkers (systolic and diastolic blood pressure, pulse rate, serum cholesterol, serum HDL-cholesterol, glycated hemoglobin, sex-specific waist-to-hip ratio, serum albumin, and serum C-reactive protein for AL1, and, additionally body mass index, serum triglyceride, serum creatinine, and serum herpes I & II antibodies for AL2), each set defined by predefined cut-offs or by quartiles. Serum vitamin D concentration was ranked into quartiles. Logistic regression, Poisson regression and linear regression were used to examine the association of serum 25(OH)D concentrations on AL, after adjusting for biological, physiological, socioeconomic, lifestyle, and health variables. Odds Ratios (OR) for high AL of the lowest 25(OH)D serum quartile were between 1.45 (95% CI: 1.28, 1.67) and 1.79 (95% CI: 1.39, 2.32) for the fully adjusted model, depending on AL version. Inverse relationships between vitamin D serum concentrations were observed for all AL versions and every adjustment. This relationship was consistent after stratification by sex, age or ethnic background. Sensitivity to low 25(OH)D concentrations was highest among the youngest group (20-39 years) with an OR of 2.11 (95% CI: 1.63, 2.73) for the lowest vitamin D quartile Q1. Vitamin D had a consistent and statistically significant inverse association with all tested models of high AL, which remained consistent after adjusting for biological, socioeconomic, lifestyle and health variables. Our study adds evidence linking low 25(OH)D concentrations with poorer health, further-reaching than bone health.

ObjectivesIt is essential to have simple, reliable and valid tests to measure children’s functional capacity in schools or medical practice. The 1-minute sit-to-stand (STS) test is a quick fitness test requiring little equipment or space that is increasingly used in both healthy populations and those with chronic disease. We aimed to provide age-specific and sex-specific reference values of STS test in healthy children and adolescents and to evaluate its short-term reliability and construct validity.Design setting and participantsCross-sectional convenience sample from six public schools and one science fair in central Europe. Overall, 587 healthy participants aged 5–16 years were recruited and divided into age groups of 3 years each.Outcomes1-minute STS. To evaluate short-term reliability, some children performed the STS test twice. To evaluate construct validity, some children also performed a standing long jump (SLJ) and a maximal incremental exercise test.ResultsData from 547 youth aged 5–16 years were finally included in the analyses. The median number of repetitions in 1 min in males (females) ranged from 55 [95% CI: 38 to 72] (53 [95% CI: 35 to 76]) in 14–16-year olds to 59 [95% CI: 41 to 77] (60 [95% CI: 38 to 77]) in 8–10-year olds. Children who repeated STS showed a learning effect of on average 4.8 repetitions more than the first test (95% limits of agreement: −6.7 to 16.4). Moderate correlations were observed between the STS and the SLJ (r=0.48) tests and the maximal exercise test (r=0.43).ConclusionsThe reported STS reference values can be used to interpret STS test performance in children and adolescents. The STS appears to have good test–retest reliability, but a learning effect of about 10%. The association of STS with other measures of physical fitness should be further explored in a larger study and technical standards for its conduct are needed.

Understanding the development of humoral immune responses of children and adolescents to SARS-CoV-2 is essential for designing effective public health measures. Here we examine the changes of humoral immune response in school-aged children and adolescents during the COVID-19 pandemic (June 2020 to July 2022), with a specific interest in the Omicron variant (beginning of 2022). In our study “Ciao Corona”, we assess in each of the five testing rounds between 1874 and 2500 children and adolescents from 55 schools in the canton of Zurich with a particular focus on a longitudinal cohort (n=751). By July 2022, 96.9% (95% credible interval 95.3–98.1%) of children and adolescents have SARS-CoV-2 anti-spike IgG (S-IgG) antibodies. Those with hybrid immunity or vaccination have higher S-IgG titres and stronger neutralising responses against Wildtype, Delta and Omicron BA.1 variants compared to those infected but unvaccinated. S-IgG persist over 18 months in 93% of children and adolescents. During the study period one adolescent was hospitalised for less than 24 hours possibly related to an acute SARS-CoV-2 infection. These findings show that the Omicron wave and the rollout of vaccines boosted S-IgG titres and neutralising capacity. Trial registration number: NCT04448717. https://clinicaltrials.gov/ct2/show/NCT04448717 . Understanding the immune responses of school-aged children to SARS-CoV-2 is important for designing public health measures. Here, the authors report findings from cross-sectional and longitudinal anti-SARS-CoV-2 antibody measurements in a school-based study in Zurich, Switzerland, from 2020-2022.

BackgroundDepression and anxiety have increased in prevalence since the start of the COVID-19 pandemic.ObjectiveTo evaluate the consumption of antidepressants and anxiolytics from 2012 to 2022 and the pandemic’s potential impact in France.MethodsWe conducted an interrupted time series analysis of routine drug sales data (Medic'AM) from all French outpatient pharmacies from 2012 to 2022. We investigated trends in defined daily doses of antidepressants and anxiolytics sold per 1000 inhabitants (DDD/TID) and related expenditures before and after pandemic onset and in relation with stringency of pandemic mitigation measures. Analyses were performed descriptively and using segmented linear regression, autoregressive and autoregressive integrated moving average models.FindingsFrom 2012 to 2019, overall monthly antidepressant sales increased (+0.02 DDD/TID) while monthly anxiolytic sales decreased (−0.07 DDD/TID). With pandemic onset, there was a relevant and persisting trend increase (+0.20 DDD/TID per month) for antidepressant sales overall, with an estimated excess of 112.6 DDD/TID sold from May 2020 until December 2022. Anxiolytic sales were elevated from February 2020 throughout the pandemic but returned to expected levels by December 2022, with an estimated excess of 33.8 DDD/TID. There was no evident association between stringency and antidepressant or anxiolytic sales.ConclusionsThis study showed a protracted trend increase in the consumption of antidepressants since pandemic onset, while increases in anxiolytic consumption were temporary.Clinical implicationsWe provide evidence that the COVID-19 pandemic may have had long-lasting consequences on the prevalence and treatment of depression and anxiety disorders, requiring further actions by researchers and policy-makers to address this potential public mental health crisis.

Objective Long-term results of sentinel node biopsy (SNB) in early (T1/T2) oral and oropharyngeal squamous cell carcinoma (OSCC) in a single-institution experience. Methods Prospective consecutive cohort analysis of 79 patients (67% male, median age 60 years, age range 34–87 years) included between 2000 and 2006. Lymphatic mapping consisted of preoperative lymphoscintigraphy, single photon emission computed tomography (SPECT/CT), and intraoperative use of a handheld gamma probe. Endpoints of the study were neck control rate, overall (OS), disease-specific (DSS), and disease-free survival (DFS). Results Twenty-nine of 79 patients (37%) had positive sentinel nodes (SN). Six of 29 (21%) patients showed isolated tumor cells, 14/29 (48%) micrometastases, and 9/29 (31%) macrometastases. OS, DFS, and DSS at 5 years for the entire cohort were 80, 85, and 87%, for SN-negative patients were 88, 96, and 96%, and for SN-positive patients were 74, 73, and 77%, respectively. Only the difference in DSS achieved statistical significance. The neck control rate after 5 years was 96% in SN-negative and 74% in SN-positive patients. This difference was statistically significant. Conclusions SNB is a safe and accurate staging modality to select patients with clinically stage I/II OSCC with occult lymph node disease for elective neck dissection (END). The promising reported short-term results have been sustained by long-term follow-up. Patients with negative SN and no END achieve an excellent neck control rate which compares favorably with reports on primary END. The neck control rate in SN-negative patients is superior to that in SN-positive patients, which is reflected in superior DSS.

Recent studies have shown a link between iron status and immune response following infection or vaccination. We aimed to investigate whether plasma ferritin and plasma iron concentrations at time of vaccination were associated with the development and temporal decay of immune response to SARS-CoV-2 vaccination over 6 months. We used data from the Zurich SARS-CoV-2 Vaccine Cohort (n=572). Participants were recruited from a random sample stratified by age groups (18-64 years, >65 years) and vaccine types (Pfizer-BioNTech BNT162b2, Moderna mRNA-1273, Johnson & Johnson JNJ-78436735). Iron parameters were measured at baseline (prior to vaccination), whereas different immunity markers were measured at baseline, 4 weeks, 6 weeks, 3 months, and 6 months. We investigated the association between plasma ferritin and plasma iron levels and immunity markers using linear mixed-effect models, and estimated half-life based on linear decay models. Plasma ferritin and plasma iron concentrations were within the normal physiological range, and the prevalence of iron deficiency (4.5%) and inflammation (2.3%) was low. For every 50 μg/L increase in plasma ferritin concentration, we observed a 5.2% increase in Anti-S IgG antibodies, and a 13.6-19.9% increase in neutralizing antibodies against the Ancestral, Delta, and Omicron BA1 viral variants. Similarly, the highest plasma ferritin quartile showed a 14.9% increase in Anti-S IgG antibodies, and a 47.1-82.2% increase in Anti-Ancestral, Anti-Delta, and Anti-Omicron neutralizing antibodies compared to the lowest quartile. Despite high concentrations at 6 months, shorter mean half-lives of Anti-S IgG antibodies were observed in the highest quartiles of plasma ferritin concentrations (Q3: 121.4 days; Q4: 109.8 days . Q1: 152.1 days). Plasma iron results were less consistent and generally no evidence for associations was found. In this predominantly iron-replete cohort, higher plasma ferritin at the time of vaccination was associated with stronger vaccination-induced humoral immune responses to SARS-CoV-2 over 6 months.

Background Although the majority of solitary fibrous tumors of the pleura (SFTP) follow a benign course, 10–25% of patients suffer from recurrence or metastatic disease. Several scoring models have been proposed to predict the outcome. However, none of these included immunohistochemical (IHC) markers as possible prognosticators. Methods In this multicenter study, we collected clinical data and formalin-fixed and paraffin-embedded (FFPE) tissue blocks of patients with histologically proven SFTP which had been surgically resected between 2000 und 2015. After systematic and extensive IHC staining on tissue microarrays, the results were analyzed and compared to histomorphological and clinical data for their possible prognostic value. Results In total, 78 patients (mean age 61 ± 11 years) were included. Of these, 9 patients (11%) had an adverse outcome including SFTP recurrence ( n  = 6) or SFTP-related death ( n  = 3). Mean overall survival was 172 ± 13 months. 1 and 10-year event-free survival rates were 99% and 93%. In the multivariable analysis only MIB-1 proliferation index (Ki-67) ≥10% (HR 12.3, CI 1.1–139.5, p  = 0.043), ≥4 mitoses per 10 high power fields (HR 36.5, CI 1.2–1103.7, p  = 0.039) and tumor size larger than 10 cm (HR 81.8, CI 1.7–4016.8, p  = 0.027) were independently associated with adverse outcome. Conclusion A high proliferation rate by MIB-1 IHC was associated with impaired outcome. Upon this, we established a new score using mitosis, necrosis, size of the tumor and MIB-1, which performed better than the traditional scores in our data set. This prognostic score could help to better evaluate outcome of SFTP, but requires external validation.