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BACKGROUND Mycoplasma pneumoniae is a major cause of community-acquired pneumonia (CAP) in school-aged children. Macrolides are the first-line treatment for this infection. However, it is unclear whether macrolides are effective in treating M. pneumoniae CAP, mainly due to limitations in microbiological diagnosis of previous studies. The extensive global use of macrolides has led to increasing antimicrobial resistance. The overall objective of this trial is to produce efficacy data for macrolide treatment in children with M. pneumoniae CAP. METHODS The MYTHIC Study is a randomized, double-blind, placebo-controlled, multicenter, non-inferiority trial in 13 Swiss pediatric centers. Previously healthy ambulatory and hospitalized children aged 3-17 years with clinically diagnosed CAP will be screened with a sensitive and commercially available M. pneumoniae-specific IgM lateral flow assay from capillary blood. Mycoplasma pneumoniae infection in screened patients will be verified retrospectively by respiratory PCR (reference test) and IgM antibody-secreting cell enzyme-linked immunospot (ELISpot) assay (confirmatory test for distinguishing between carriage and infection). Patients will be randomized 1:1 to receive a 5-day treatment of macrolides (azithromycin) or placebo. The co-primary endpoints are (1) time to normalization of all vital signs, including body temperature, respiratory rate, heart rate, and saturation of peripheral oxygen (efficacy), and (2) CAP-related change in patient care status (i.e., admission, re-admission, or intensive care unit transfer) within 28 days (safety). Secondary outcomes include adverse events (AEs), as well as antimicrobial and anti-inflammatory effects. For both co-primary endpoints, we aim to show non-inferiority of placebo compared to macrolide treatment. We expect no macrolide effect (hazard ratio of 1, absolute risk difference of 0) and set the corresponding non-inferiority margins to 0.7 and -7.5%. The "at least one" success crit

The FICUS trial is a cluster-randomized superiority trial to determine the effectiveness of a nurse-led, interprofessional family support intervention (FSI) on the quality of care, family management and individual mental health of family members of critically ill patients, compared to usual care. This paper describes the statistical analysis plan of the FICUS trial. The primary outcome is quality of family care, assessed by the Family Satisfaction in ICU Questionnaire (FS-ICU-24R) at patient discharge from the ICU. Several secondary outcomes are additionally assessed 3, 6, and 12 months thereafter. Sixteen clusters (ICUs) were randomly assigned 1:1 to FSI or usual care using minimization (8 per treatment). The target sample size is 56 patients per cluster (896 in total). Recruitment has been completed in January 2024. The follow-up of the last participant will be completed in early 2025. The primary and secondary outcomes will be analyzed by linear mixed-effects models (LMM). The main model for the primary outcome will include a random intercept per cluster with treatment (FSI vs. usual care) as the only explanatory variable due to the relatively small number of clusters. In addition, covariate-adjusted analyses will be conducted, including two cluster-level characteristics used in the minimization as well as participant-level characteristics. Moreover, a number of subgroup analyses by cluster- and participant-level characteristics are pre-specified.Trial registration ClinicalTrials.gov NCT05280691 . Registered on February 20, 2022.

AIMS To describe the point prevalence, risk factors and possible outcomes of delirium in inpatients. DESIGN A cross-sectional point prevalence study. BACKGROUND Delirium is an acute brain syndrome that negatively affects patients, healthcare professionals and institutions alike; it is common in inpatient settings and is preventable in about one third of cases. Although guidelines recommend systematic screening and assessment, delirium is often unrecognised, undiagnosed and uncoded. There is a lack of valid data on this patient safety indicator in German-speaking countries. METHODS The study was conducted in a tertiary care hospital in Switzerland on 5 July 2022. Specially trained registered nurses collected data from all patients meeting the inclusion criteria using CAM, ICDSC or mCAM-ED. Data were analysed descriptively with stratification by delirium status, setting and surgery. RESULTS The point prevalence across all settings was 6.9% (27/390), with large variation between settings: ICU 28.6% (4/14), IMC 28.0% (7/25), wards 4.6% (15/326) and ED 4% (1/25). Surgical patients were almost twice as likely to be affected as medical patients (8.9% vs. 4.8%). Patients with delirium differed most clearly from those without by having a larger number of ICD-10 F-diagnoses, a larger number of medications and higher age, which are known risk factors. Moreover, those with delirium had more missed diagnoses, increased mortality, more adverse events and higher costs. CONCLUSIONS A significant number of patients experienced delirium and adverse clinical outcomes. Missed delirium diagnoses may further jeopardise patient safety and result in lost revenue. It remains unclear to what extent the risk factors and effects of delirium are causal and what determinants underlie missed diagnoses. RELEVANCE TO CLINICAL PRACTICE Consistent identification of high-risk patients and treatment settings with elevated risk, accompanied by the implementation of effective preventive and management st

BACKGROUND: Burn patients are in a state of activated coagulation, putting them at risk for thromboembolic events. Additionally, certain patient-related factors are associated with an increased risk of thrombus formation. This study aimed to evaluate the incidence of thromboembolic events and identify potential risk factors, including patient characteristics, surgical treatment, anticoagulation strategies, and laboratory parameters. METHODS: A single-centre retrospective cohort study was conducted on all patients with burns treated between 2002 and 2020. Medical reports of patients with and without thromboembolic events were descriptively analysed. The association of time to thromboembolic events with total body surface area (TBSA) was assessed by cause-specific Cox models adjusted for different covariates. The association of time to thromboembolic events with type and dosage of anticoagulants was assessed using a cause-specific Cox proportional hazards model with time-dependent covariates, applied to a matched subset of patients. RESULTS: The incidence of thromboembolic events was 8.1% in a cohort of 642 patients. We found a statistically significant increase in the hazard for thromboembolic events by a factor of 1.02 (95% CI 1.00 to 1.03; P ≤ 0.05) per percent increase in TBSA. We identified former alcohol abuse (HR=2.54, CI 1.33 to 4.84, P = 0.005) and higher body mass index (HR=1.06, 95% CI 1.00 to 1.12, P = 0.046) as potential risk factors for the development of thromboembolic events. We further noted inadequate median anti-Factor-X activity levels and elevated C-reactive protein and procalcitonin levels at the time of the event. CONCLUSION: Our results showed a moderate risk of thromboembolic events among burn patients, underlining the importance of close monitoring with regard to thrombus formation. In particular, patients with higher TBSA, alcohol abuse and BMI may be evaluated more regularly for thromboembolic events. Anti-Factor-X activity levels should be

Background & aims With the increase in patients at risk of advanced liver disease due to the obesity epidemic, there will be a need for simple screening tools for advanced liver fibrosis. Soluble suppression of tumorigenicity 2 (sST2) is a serum biomarker for fibrotic processes. The aim of this study was to evaluate sST2 as marker for liver fibrosis in patients successfully treated for chronic hepatitis C. Methods 424 patients from the Swiss Hepatitis C Cohort Study were screened for inclusion in this post-hoc cohort study. Inclusion criteria were sustained virological response (SVR), available elastography (VCTE) and serum samples for biomarker analysis before and after treatment. For the validation of sST2, values were compared to VCTE, FIB-4 and APRI using Spearman’s correlation and AUROC analyses. Results Data of 164 subjects were finally analyzed. Median sST2 values slightly increased with VCTE-derived fibrosis stages and remained stable after reaching SVR within the respective fibrosis stage, suggesting that sST2 is not influenced by liver inflammation. However, correlation of sST2 pre- and post-treatment with VCTE was fair (Spearman’s rho = 0.39 and rho = 0.36). The area under the curve (AUROC) for sST2 in detecting VCTE-defined F4 fibrosis (vs. F0-F3) before therapy was 0.74 (95%CI 0.65–0.83), and 0.67(95%CI 0.56–0.78) for the discrimination of F3/F4 fibrosis vs. F0-F2. Adding sST2 to either APRI or FIB-4, respectively, increased diagnostic performance of both tests. Conclusions sST2 can potentially identify patients with advanced fibrosis as a single serum marker and in combination with APRI and FIB-4.

INTRODUCTION AND OBJECTIVES Our aim was to assess the impact of prosthetic pulmonary valve replacement (PVR) in patients with repaired tetralogy of Fallot (rTOF) on changes in biventricular volumes and function and on adverse cardiac events. METHODS Adults with rTOF were identified from the SACHER-registry. Data from serial cardiac magnetic resonance imaging, echocardiography, exercise capacity and n-terminal pro b-type natriuretic peptide (NT-proBNP) were collected. The primary endpoint was right ventricular ejection fraction (RVEF) as measured by cardiac magnetic resonance. Secondary endpoints were biventricular volumes, left ventricular ejection fraction, exercise capacity and NT-proBNP levels, and time to adverse cardiac outcomes (atrial and ventricular arrhythmia, endocarditis). Associations between previous PVR and longitudinal changes in functional outcomes and time to adverse cardiac outcomes were analyzed using linear mixed-effects models and Cox proportional hazards models, respectively. RESULTS A total of 308 patients (153 with and 155 without PVR) with 887 study visits were analyzed. Previous PVR was not significantly associated with changes in RVEF (CE, --1.33; 95%CI, -5.87 to 3.21; P = .566). Previous PVR was associated with lower right ventricular end-diastolic volume but had no significant effect on left ventricular ejection fraction, exercise capacity, or NT-proBNP-levels. Previous PVR was associated with an increased hazard of atrial arrhythmias (HR, 2.09; 95%CI, 1.17-3.72; P = .012) and infective endocarditis (HR, 12.72; 95%CI, 4.69-34.49; P < .0001) but not with an increased hazard of sustained ventricular arrhythmias (HR, 0.64; 95%CI, 0.18-2.27; P = .490). CONCLUSIONS Previous PVR was not significantly associated with changes in RVEF but was associated with an increased risk of atrial arrhythmias and infective endocarditis.

Simplified first-trimester abortion protocols are well established. However, data on the use of medical or surgical abortion protocols across Switzerland is lacking. We report protocol characteristics in abortion care for two different facility types, hospital vs private practices (office-based) in Switzerland. Furthermore, we investigate an association between protocol characteristics and the likelihood of following through with the abortion at the same facility. We also report abortion outcomes of an office-based cohort where doctors use simplified abortion protocols. This study consists of two parts. (i) Between April and July, 2019, we collected data regarding medical and surgical abortion protocols of institutions offering abortions, in a nationwide survey. We assessed whether the proportion of patients who followed through with the abortion (primary outcome) after first appointment was associated with predefined protocol characteristics, considered to complicate access to abortion services, using generalised estimating equations. (ii) We analysed abortion outcomes of six selected office-based facilities from January, 2008, to December, 2018, using simplified abortion protocols in accordance with the Worlds Health Organisation (WHO) guidelines. (i) We included a total of 39 institutions. Hospitals showed more protocol-based barriers to abortion access compared with office-based facilities. The odds of undergoing an abortion after the first appointment were increased using protocols with minimal barriers. Overall, office-based facilities applied higher gestational age limits, required fewer appointments, and administered mifepristone more often after the first visit than did hospitals. (ii) We included a total of 5274 patients with an incidence of complications requiring surgery of 2.5% in line with rates reported in published literature. Only a few hospitals provide abortion care with easy access to medical and surgical abortion, whereas most office-based facil

BACKGROUND & AIMS Machine perfusion is a novel method intended to optimize livers before transplantation. However, its effect on morbidity within a 1-year period after transplantation has remained unclear. METHODS In this multicenter controlled trial, we randomly assigned livers donated after brain death (DBD) for liver transplantation (LT). Livers were either conventionally cold stored (control group), or cold stored and subsequently treated by 1-2 h hypothermic oxygenated perfusion (HOPE) before implantation (HOPE group). The primary endpoint was the occurrence of at least one post-transplant complication per patient, graded by the Clavien score of ≥III, within 1-year after LT. The comprehensive complication index (CCI), laboratory parameters, as well as duration of hospital and intensive care unit stay, graft survival, patient survival, and biliary complications served as secondary endpoints. RESULTS Between April 2015 and August 2019, we randomized 177 livers, resulting in 170 liver transplantations (85 in the HOPE group and 85 in the control group). The number of patients with at least one Clavien ≥III complication was 46/85 (54.1%) in the control group and 44/85 (51.8%) in the HOPE group (odds ratio 0.91; 95% CI 0.50-1.66; p = 0.76). Secondary endpoints were also not significantly different between groups. A post hoc analysis revealed that liver-related Clavien ≥IIIb complications occurred less frequently in the HOPE group compared to the control group (risk ratio 0.26; 95% CI 0.07-0.77; p = 0.027). Likewise, graft failure due to liver-related complications did not occur in the HOPE group, but occurred in 7% (6 of 85) of the control group (log-rank test, p = 0.004, Gray test, p = 0.015). CONCLUSIONS HOPE after cold storage of DBD livers resulted in similar proportions of patients with at least one Clavien ≥III complication compared to controls. Exploratory findings suggest that HOPE decreases the risk of severe liver graft-related events. IMPACT AND IMPLICATIO

Background: Non-ventilator-associated hospital-acquired pneumonia (nvHAP) is a frequent, but under-researched infection. We aimed to simultaneously test an nvHAP prevention intervention and a multifaceted implementation strategy. Methods: In this single-centre, type 2 hybrid effectiveness-implementation study, all patients of nine surgical and medical departments at the University Hospital Zurich, Switzerland, were included and surveyed over three study periods: baseline (14-33 months, depending on department), implementation (2 months), and intervention (3-22 months, depending on department). The five-measure nvHAP prevention bundle consisted of oral care, dysphagia screening and management, mobilisation, discontinuation of non-indicated proton-pump inhibitors, and respiratory therapy. The implementation strategy comprised department-level implementation teams who conducted and locally adapted the core strategies of education, training, and changing infrastructure. Intervention effectiveness on the primary outcome measure of nvHAP incidence rate was quantified using a generalised estimating equation method in a Poisson regression model, with hospital departments as clusters. Implementation success scores and determinants were derived longitudinally through semistructured interviews with health-care workers. This trial is registered with ClinicalTrials.gov (NCT03361085). Findings: Between Jan 1, 2017, and Feb 29, 2020, 451 nvHAP cases occurred during 361 947 patient-days. nvHAP incidence rate was 1·42 (95% CI 1·27-1·58) per 1000 patient-days in the baseline period and 0·90 (95% CI 0·73-1·10) cases per 1000 patient-days in the intervention period. The intervention-to-baseline nvHAP incidence rate ratio, adjusted for department and seasonality, was 0·69 (95% CI 0·52-0·91; p=0·0084). Implementation success scores correlated with lower nvHAP rate ratios (Pearson correlation -0·71, p=0·034). Determinants of implementation success were positive core business alignment, hi

OBJECTIVES During the first 3 months of the coronavirus disease 2019 (COVID-19) pandemic, our hospital's quality management team determined a decline in the rate of cesarean deliveries (CD). Thus, in this study we examined both the factors associated with this decrease as well as neonatal outcomes. METHODS This was a retrospective observational cohort study comparing deliveries (n=597) between March and May 2020 (first nationwide "lockdown" in Switzerland) with those during the same period in 2018 and 2019 (n=1,063). A multivariable logistic regression analysis was used to examine the association between CD and the pandemic, adjusting for relevant risk factors for CD. RESULTS The overall rate of CD during the pandemic period was lower (30.0%), than during the pre-pandemic period (38.7%, unadjusted odds ratio 0.68, 95% confidence interval [95%CI]: 0.55 to 0.84, p=0.0004) a result that was supported by the adjusted odds ratio (0.73, 95%CI: 0.54 to 0.99, p=0.04). CONCLUSIONS The results of this study confirmed a significant reduction in the rate of CD in early 2020, during the first lockdown period due to COVID-19, but without major differences in maternal and infant health indicators or in obstetric risk factors than before the pandemic. These results may have been due to a difference in the composition of the obstetric team as well as the behavior of the obstetrics team and in the patients during the pandemic, given the burden it placed on healthcare systems. However, this hypothesis remains to be tested in further research.

Background & Aims: Machine perfusion is a novel method intended to optimize livers before transplantation. However, its effect on morbidity within a 1-year period after transplantation has remained unclear. Methods: In this multicenter controlled trial, we randomly assigned livers donated after brain death (DBD) for liver transplantation (LT). Livers were either conventionally cold stored (control group), or cold stored and subsequently treated by 1-2 h hypothermic oxygenated perfusion (HOPE) before implantation (HOPE group). The primary endpoint was the occurrence of at least one post-transplant complication per patient, graded by the Clavien score of ≥III, within 1-year after LT. The comprehensive complication index (CCI), laboratory parameters, as well as duration of hospital and intensive care unit stay, graft survival, patient survival, and biliary complications served as secondary endpoints. Results: Between April 2015 and August 2019, we randomized 177 livers, resulting in 170 liver transplantations (85 in the HOPE group and 85 in the control group). The number of patients with at least one Clavien ≥III complication was 46/85 (54.1%) in the control group and 44/85 (51.8%) in the HOPE group (odds ratio 0.91; 95% CI 0.50-1.66; p = 0.76). Secondary endpoints were also not significantly different between groups. A post hoc analysis revealed that liver-related Clavien ≥IIIb complications occurred less frequently in the HOPE group compared to the control group (risk ratio 0.26; 95% CI 0.07-0.77; p = 0.027). Likewise, graft failure due to liver-related complications did not occur in the HOPE group, but occurred in 7% (6 of 85) of the control group (log-rank test, p = 0.004, Gray test, p = 0.015). Conclusions: HOPE after cold storage of DBD livers resulted in similar proportions of patients with at least one Clavien ≥III complication compared to controls. Exploratory findings suggest that HOPE decreases the risk of severe liver graft-related events. Impact and

Background: Family members of critically ill patients face considerable uncertainty and distress during their close others' intensive care unit (ICU) stay. About 20-60% of family members experience adverse mental health outcomes post-ICU, such as symptoms of anxiety, depression, and posttraumatic stress. Guidelines recommend structured family inclusion, communication, and support, but the existing evidence base around protocolized family support interventions is modest and requires substantiation. Methods: To test the clinical effectiveness and explore the implementation of a multicomponent, nurse-led family support intervention in ICUs, we will undertake a parallel, cluster-randomized, controlled, multicenter superiority hybrid-type 1 trial. It will include eight clusters (ICUs) per study arm, with a projected total sample size of 896 family members of adult, critically ill patients treated in the German-speaking part of Switzerland. The trial targets family members of critically ill patients with an expected ICU stay of 48 h or longer. Families in the intervention arm will receive a family support intervention in addition to usual care. The intervention consists of specialist nurse support that is mapped to the patient pathway with follow-up care and includes psycho-educational and relationship-focused family interventions, and structured, interprofessional communication, and shared decision-making with families. Families in the control arm will receive usual care. The primary study endpoint is quality of family care, operationalized as family members' satisfaction with ICU care at discharge. Secondary endpoints include quality of communication and nurse support, family management of critical illness (functioning, resilience), and family members' mental health (well-being, psychological distress) measured at admission, discharge, and after 3, 6, and 12 months. Data of all participants, regardless of protocol adherence, will be analyzed using linear mixed-effects m

IMPORTANCE Intraventricular hemorrhage (IVH) is a major cause of neonatal morbidity and mortality in preterm infants without a specific medical treatment to date. OBJECTIVE To assess the safety and short-term outcomes of high-dose erythropoietin in preterm infants with IVH. DESIGN, SETTING, AND PARTICIPANTS Between April 1, 2014, and August 3, 2018, a randomized double-blind clinical trial enrolled 121 preterm infants (gestational age <32 weeks or birth weight <1500 g) aged 8 or less days with moderate to severe IVH identified by cerebral ultrasonography from 8 Swiss and Austrian tertiary neonatal units. Statistical analyses were performed between October 1, 2019, and September 12, 2022. INTERVENTIONS Infants received intravenous high-dose erythropoietin (2000 units/kg body weight) or placebo at 4 time points between weeks 1 and 4 of life. MAIN OUTCOMES AND MEASURES Secondary outcomes included (1) mortality and morbidity rates and (2) brain magnetic resonance imaging findings at term-equivalent age (TEA). The primary outcome was the composite intelligence quotient at 5 years of age (not available before 2023). RESULTS Sixty infants (48% male [n = 29]) were randomly assigned to receive erythropoietin, and 61 infants (61% male [n = 37]) were randomly assigned to receive placebo. The median birth weight was 832 g (IQR, 687-990 g) in the erythropoietin group and 870 g (IQR, 680-1110 g) in the placebo group. Median gestation was 26.1 weeks (IQR, 24.8-27.3 weeks) in the erythropoietin group and 27.0 weeks (24.9-28.1 weeks) in the placebo group. The 2 groups had similar baseline characteristics and morbidities. Up to TEA, 10 newborns died (16.7%) in the erythropoietin group, and 5 newborns (8.2%) died in the placebo group (adjusted odds ratio, 2.24 [95% CI, 0.74-7.66]; P = .15). Infants receiving erythropoietin had higher mean hematocrit levels. Conventional magnetic resonance imaging at TEA for 100 infants showed no significant differences in global or regional brain inju

Background: The number of children and adolescents living with life-limiting conditions and potentially in need for specialised paediatric palliative care (SPPC) is rising. Ideally, a specialised multiprofessional team responds to the complex healthcare needs of children and their families. The questions of, how SPPC is beneficial, for whom, and under what circumstances, remain largely unanswered in the current literature. This study's overall target is to evaluate the effectiveness of a SPPC programme in Switzerland with respect to its potential to improve patient-, family-, health professional-, and healthcare-related outcomes. Methods: This comparative effectiveness study applies a quasi-experimental design exploring the effectiveness of SPPC as a complex intervention at one treatment site in comparison with routine care provided in a generalised PPC environment at three comparison sites. As the key goal of palliative care, quality of life - assessed at the level of the patient-, the family- and the healthcare professional - will be the main outcome of this comparative effectiveness research. Other clinical, service, and economic outcomes will include patient symptom severity and distress, parental grief processes, healthcare resource utilisation and costs, direct and indirect health-related expenditure, place of death, and introduction of SPPC. Data will be mainly collected through questionnaire surveys and chart analysis. Discussion: The need for SPPC has been demonstrated through numerous epidemiological and observational studies. However, in a healthcare environment focused on curative treatment and struggling with limited resources, the lack of evidence contributes to a lack of acceptance and financing of SPPC which is a major barrier against its sustainability. This study will contribute to current knowledge by reporting individual and child level outcomes at the family level and by collecting detailed contextual information on healthcare provision. We hope

To assess the incidence and severity of changes in hearing threshold in patients undergoing high-dose pencil-beam-scanning proton therapy (PBS-PT). This retrospective cohort study included fifty-one patients (median 50 years (range, 13–68)) treated with PBS-PT for skull base tumors. No chemotherapy was delivered. Pure tone averages (PTAs)were determined before (baseline) and after PBS-PT as the average hearing thresholds at frequencies of 0.5, 1, 2, and 4 kHz. Hearing changes were calculated as PTA differences between pre-and post-PBS-PT. A linear mixed-effects model was used to assess the relationship between the PTA at the follow-up and the baseline, the cochlea radiation dose intensity, the increased age, and the years after PBS-PT. Included patients were treated for chordoma (n = 24), chondrosarcoma (n = 9), head and neck tumors (n = 9), or meningioma (n = 3), with a mean tumor dose of 71.1 Gy (RBE) (range, 52.0–77.8), and a mean dose of 37 Gy (RBE) (range, 0.0–72.7) was delivered to the cochleas. The median time to the first follow-up was 11 months (IQR, 5.5–33.7). The PTA increased from a median of 15 dB (IQR 10.0–25) at the baseline to 23.8 (IQR 11.3–46.3) at the first follow-up. In the linear mixed-effect model, the baseline PTA (estimate 0.80, 95%CI 0.64 to 0.96, p ≤ 0.001), patient’s age (0.30, 0.03 to 0.57, p = 0.029), follow-up time (2.07, 0.92 to 3.23, p ≤ 0.001), and mean cochlear dose in Gy (RBE) (0.34, 0.21 to 0.46, p ≤ 0.001) were all significantly associated with an increase in PTA at follow-up. The applied cochlear dose and baseline PTA, age, and time after treatment were significantly associated with hearing loss after proton therapy

BACKGROUND The reporting quality in medical research has recently been critically discussed. While reporting guidelines intend to maximize the value from funded research, and initiatives such as the EQUATOR network have been introduced to advance high quality reporting, the uptake of the guidelines by researchers could be improved. The aim of this study was to assess the contribution of a biostatistician to the reporting and methodological quality of health research, and to identify methodological knowledge gaps. METHODS In a retrospective, single center, observational cohort study, two groups of publications were compared. The group of exposed publications had an academic biostatistician on the author list, whereas the group of non-exposed publications did not include a biostatistician of the evaluated group. Rating of reporting quality was done in blinded fashion and in duplicate. The primary outcome was a sum score based on six dimensions, ranging between 0 (worst) and 11 (best). The study protocol was reviewed and approved as a registered report. RESULTS There were 131 publications in the exposed group published between 2017 and 2018. Of these, 95 were either RCTs, observational, or prediction / prognostic studies. Corresponding matches in the group of non-exposed publications were identified in a reproducible manner. Comparison of reporting quality overall revealed a 1.60 (95%CI from 0.92 to 2.28, p <0.0001) units higher reporting quality for exposed publications. A subgroup analysis within study types showed higher reporting quality across all three study types. CONCLUSION Our study is the first to report an association of a higher reporting quality and methodological strength in health research publications with a biostatistician on the author list. The higher reporting quality persisted through subgroups of study types and dimensions. Methodological knowledge gaps were identified for prediction / prognostic studies, and for reporting on statistical methods i

Background Direct-acting antivirals (DAA) have revolutionized the therapy of chronic hepatitis C (CHC) and have replaced previous PEG-interferon/ribavirin (PEG-IFN/RBV) treatment. Patients with CHC and advanced liver disease are at increased risk for hepatocellular carcinoma (HCC). However, the effects of DAA-based CHC treatment on subsequent HCC incidence remain poorly understood. Patients and Methods This retrospective single-institution cohort study included 243 consecutive patients after PEG-IFN/RBV and 263 patients after DAA treatment. Multivariable cause-specific Cox proportional hazards models were used to compare time to HCC between treatment types, censoring patients who died or had an orthotopic liver transplantation (OLT) at the time of the competing event. Age, gender, BMI, viral load, cirrhosis, fibrosis stage, diabetes, virus genotype and previous PEG-IFN/RBV (before DAA) were used as covariates. In addition, we performed a propensity score-matched analysis. Results Nineteen HCC cases were observed after DAA therapy compared to 18 cases after PEG-IFN/RBV treatment. Patients were followed for a median of 4.1 years (IQR: 3.5-4.7) for DAA and 9.3 years (IQR: 6.6-12.4) for the PEG-IFN/RBV group. In an unadjusted Cox model, a hazard ratio (HR) of 6.40 (CI: 2.20-18.61, p=0.006) for HCC following DAA vs PEG-IFN/RBV was estimated. In multivariable Cox proportional hazard models, age and liver cirrhosis were identified as further HCC risk factors but the HR estimates for DAA vs PEG-IFN/RBV still indicate a considerably increased hazard associated with DAA treatment (HR between 7.23 and 11.52, p≤0.001, depending on covariates). A HR of 6.62 (CI: 2.01-21.84, p=0.002) for DAA vs PEG-IFN/RBV was estimated in the propensity score-matched analysis. The secondary outcomes death and OLT did not differ between treatment groups. Conclusion In a cohort study from a tertiary care hospital rates of HCC after the start of DAA treatment were higher compared to PEG-IFN/RBV tre

Background: Adverse responses to critical illness, such as symptoms of depression, anxiety or posttraumatic stress, are relatively common among family members. The role of risk factors, however, remains insufficiently understood, but may be important to target those family members most in need for support. We therefore examined the association of patient-, family member- and care-related factors with post-ICU psychological distress in family members in a general population of critical ill patients. Methods: We conducted a prospective, single-centre observational study in a twelve-bed surgical ICU in a 900-bed University Hospital in Switzerland. Participants were family members of patients treated in ICU who completed the Family Satisfaction in ICU-24 Survey, the Hospital Anxiety Depression Scale, Impact of Event Scale-Revised-6, and a demographic form within the first 3 months after their close other’s ICU stay. Data were analysed using linear mixed-effects models, with depression, anxiety, and posttraumatic stress as outcome measures. Results: A total of 214 family members (53% return rate) returned a completed questionnaire. We found that higher levels of satisfaction were significantly associated with lower levels of depression, anxiety and posttraumatic stress. There was no statistically significant association between family member characteristics and any measure of psychological distress. Among the included patient characteristics, younger patient age was associated with higher levels of depression, and patient death was associated with higher levels of depression and posttraumatic stress. Conclusions: Our results suggest that satisfaction with ICU care is strongly associated with family well-being post-ICU. Family members of younger patients and of those who die seem to be most at risk for psychological distress, requiring specific support, whereas family member characteristics may have less relevance.

BACKGROUND With the goal of reducing the prevalence of early childhood caries, the city of Zurich, Switzerland, started a specific prevention programme in 2010. All 2-year-olds are invited to a free dental check-up at a local public dental health service before the first legally mandated yearly dental check-up for school children between 4 and 5 years of age (at kindergarten). However, for the success of this prevention programme, it is of particular importance that children at high risk of caries are reached. The objective of our study was to assess the effectiveness of the prevention programme in (1) reaching the children who needed it the most and (2) improving subsequent oral health. METHODS This retrospective cohort study included all children born between July 1, 2013 and July 15, 2014 who had lived in Zurich between the ages of 23 and 36 months. Socio-economic data were extracted from official school records, and dental health data from public dental clinic records. Binomial and quasi-binomial generalised linear models were used to identify the socio-economic factors associated with toddler check-up attendance and to assess the associations between attendance and caries experience (dmft [Formula: see text] 1) as well as degree of treatment (proportion m+f out of dmft) at the kindergarten check-up, adjusting for socio-economic factors. RESULTS From a total of 4376 children, 2360 (54%) attended the toddler check-up (mean age 2.4 years) and 3452 (79%) had a dental examination at kindergarten (mean age 5.3 years). Non-Swiss origin of the primary caretaker, presence of older siblings, low amount of savings and allocation to certain public dental clinics were associated with a lower odds of attendance. Factors associated with a higher odds of caries experience were similar to those associated with a lower odds of attendance at the toddler check-up, but additionally included low income. Attendance at the toddler check-up was non-significantly associated with a lower

BACKGROUND Klebsiella spp. are opportunistic pathogens which can cause severe infections, are often multi-drug resistant and are a common cause of hospital-acquired infections. Multiple new Klebsiella species have recently been described, yet their clinical impact and antibiotic resistance profiles are largely unknown. We aimed to explore Klebsiella group- and species-specific clinical impact, antimicrobial resistance (AMR) and virulence. METHODS We analysed whole-genome sequence data of a diverse selection of Klebsiella spp. isolates and identified resistance and virulence factors. Using the genomes of 3594 Klebsiella isolates, we predicted the masses of 56 ribosomal subunit proteins and identified species-specific marker masses. We then re-analysed over 22,000 Matrix-Assisted Laser Desorption Ionization - Time Of Flight (MALDI-TOF) mass spectra routinely acquired at eight healthcare institutions in four countries looking for these species-specific markers. Analyses of clinical and microbiological endpoints from a subset of 957 patients with infections from Klebsiella species were performed using generalized linear mixed-effects models. RESULTS Our comparative genomic analysis shows group- and species-specific trends in accessory genome composition. With the identified species-specific marker masses, eight Klebsiella species can be distinguished using MALDI-TOF MS. We identified K. pneumoniae (71.2%; n = 12,523), K. quasipneumoniae (3.3%; n = 575), K. variicola (9.8%; n = 1717), "K. quasivariicola" (0.3%; n = 52), K. oxytoca (8.2%; n = 1445), K. michiganensis (4.8%; n = 836), K. grimontii (2.4%; n = 425) and K. huaxensis (0.1%; n = 12). Isolates belonging to the K. oxytoca group, which includes the species K. oxytoca, K. michiganensis and K. grimontii, were less often resistant to 4th-generation cephalosporins than isolates of the K. pneumoniae group, which includes the species K. pneumoniae, K. quasipneumoniae, K. variicola and "K. quasivariicola" (odds ratio = 0.

BACKGROUND Neonatal mortality in Guinea accounts for about 30% of all fatalities in children younger than five years. Countrywide, specialized neonatal intensive care is provided in one single clinic with markedly limited resources. To implement targeted measures, prospective data on patient characteristics and factors of neonatal death are needed. OBJECTIVE To determine the rates of morbidity and mortality, to describe clinical characteristics of admitted newborns requiring intensive care, to assess the quality of disease management, and to identify factors contributing to neonatal mortality. METHODS Prospective observational cohort study of newborns admitted to the hospital between mid-February and mid-March 2019 after birth in other institutions. Data were collected on maternal/prenatal history, delivery, and in-hospital care via convenience sampling. Associations of patient characteristics with in-hospital death were assessed using cause-specific Cox proportional-hazards models. RESULTS Half of the 168 admitted newborns underwent postnatal cardiopulmonary resuscitation. Reasons for admission included respiratory distress (49.4%), poor postnatal adaptation (45.8%), prematurity (46.2%), and infections (37.1%). 101 newborns (61.2%) arrived in serious/critical general condition; 90 children (53.9%) showed clinical signs of neurological damage. Quality of care was poor: Only 59.4% of the 64 newborns admitted with hypothermia were externally heated; likewise, 57.1% of 45 jaundiced infants did not receive phototherapy. Death occurred in 56 children (33.3%) due to birth asphyxia (42.9%), prematurity (33.9%), and sepsis (12.5%). Newborns in serious/critical general condition at admission had about a fivefold higher hazard to die than those admitted in good condition (HR 5.21 95%-CI 2.42-11.25, p = <0.0001). Hypothermia at admission was also associated with a higher hazard of death (HR 2.00, 95%-CI 1.10-3.65, p = 0.023). CONCLUSION Neonatal mortality was strikingly high.

Background: Families of critically ill persons face uncertainty and experience distress during and after their close other's stay in an intensive care unit (ICU). Proactive nurse engagement and support is recommended to meet families' needs in the ICU, but little is known about its impact on quality of family care. We introduced a family support intervention that consisted of an interprofessional family support pathway and a new role of an advanced practice family nurse. Objectives: The aim of the study was to examine the effect of an advanced practice nurse-led family support intervention on family members' satisfaction, wellbeing, and psychological distress. Methods: We conducted a quasi-experimental before-and-after study with embedded qualitative interviews in a Swiss University Hospital from March 2018 to July 2019 using a questionnaire (Family Satisfaction in the ICU-24 Survey, Hospital Anxiety and Depression Scale, and Impact of Event Scale-Revised-6) and qualitative interviews (n = 19) after patient discharge. Results: Families in the intervention group (n = 75) showed a trend for increased overall satisfaction (difference of 5.544, 95% confidence interval [CI]: -0.11 to 11.20), a statistically significant increase in satisfaction with decision-making (7.258, 95% CI: 0.89 to 13.63), and a nonsignificant increase in satisfaction with care (4.178, 95% CI: -1.53 to 9.89). Psychological distress was higher in the intervention group, with depression reaching statistical significance (difference of 1.706, 95% CI: 0.16 to 3.25), which may be explained by longer ICU stays and higher proportion of deaths in the intervention group. Families receiving the intervention reported to be feeling cared for, well informed, and better able to cope. Data integration suggests that early onset, fit to need, and quality of intervention were the most important intervention characteristics impacting family wellbeing. Conclusions: Our study found that family members experience a nurs

Background: Measures of the sonorheometry based Quantra® viscoelastic hemostatic analyzer (HemoSonics, LCC, Charlottesville, VA, USA) were compared with corresponding results of the ROTEM® sigma device (Instrumentation Laboratory, Bedford, MA, USA). Methods: In thirty-eight patients scheduled for elective cardiac surgery between December 2018 and October 2019, blood samples were taken after induction of anesthesia (sample 1) and after heparin neutralization (sample 2) and measured on Quantra (QPlus® Cartridge) and ROTEM sigma (ROTEM® sigma complete + hep Cartridge). Clot times and clot stiffness values were recorded. Clot stiffness values of ROTEM amplitudes (A in mm) were converted to shear modulus (G) in hectoPascal (hPa): G (hPa) = (5 x A)/(100-A). Additionally, time-to-results was recorded. Spearman rank test correlation and Bland Altman analysis were performed. Results: Clot stiffness parameters of the Quantra correlated strongly with corresponding measurements of the ROTEM with r = 0.93 and 0.94 for EXTEM A10 vs CS and r = 0.94 and 0.96 for FIBTEM A10 vs FCS for sample 1 and 2, respectively. Quantra clot time correlated strongly with ROTEM INTEM CT with r = 0.71 for sample 1 and r = 0.75 for sample 2. However, Bland Altman analysis showed no agreement in all compared assays of both methods. The median time to delivery of first and complete results was significantly shorter for Quantra (412 and 658 s) compared to ROTEM sigma (839 and 1290 s). Conclusions: The Quantra showed a strong correlation with the ROTEM sigma for determining clot times and clot stiffness and the parameters assess similar aspects of clot development. However, these parameters are not directly interchangeable and implicate that separate cut-off values need to be established for users of the Quantra device. Word count: 278. Trial registration: The study was retrospectively registered with ClinicalTrials.gov (ID: NCT04210830 ) at December 20th 2019. Keywords: Quantra; ROTEM sigma, cardiac sur

Contains fulltext : 217065.pdf (publisher's version ) (Open Access), Locally, plant species richness supports many ecosystem functions. Yet, the mechanisms driving these often-positive biodiversity?ecosystem functioning relationships are not well understood. Spatial resource partitioning across vertical resource gradients is one of the main hypothesized causes for enhanced ecosystem functioning in more biodiverse grasslands. Spatial resource partitioning occurs if species differ in where they acquire resources and can happen both above- and belowground. However, studies investigating spatial resource partitioning in grasslands provide inconsistent evidence. We present the results of a meta-analysis of 21 data sets from experimental species-richness gradients in grasslands. We test the hypothesis that increasing spatial resource partitioning along vertical resource gradients enhances ecosystem functioning in diverse grassland plant communities above- and belowground. To test this hypothesis, we asked three questions. (1) Does species richness enhance biomass production or community resource uptake across sites? (2) Is there evidence of spatial resource partitioning as indicated by resource tracer uptake and biomass allocation above- and belowground? (3) Is evidence of spatial resource partitioning correlated with increased biomass production or community resource uptake? Although plant species richness enhanced community nitrogen and potassium uptake and biomass production above- and belowground, we found that plant communities did not meet our criteria for spatial resource partitioning, though they did invest in significantly more aboveground biomass in higher canopy layers in mixture relative to monoculture. Furthermore, the extent of spatial resource partitioning across studies was not positively correlated with either biomass production or community resource uptake. Our results suggest that spatial resource partitioning across vertical resource gradients alone does not offer a general explanation for enhanced ecosystem fu

Contains fulltext : 217065.pdf (publisher's version ) (Open Access), Locally, plant species richness supports many ecosystem functions. Yet, the mechanisms driving these often-positive biodiversity?ecosystem functioning relationships are not well understood. Spatial resource partitioning across vertical resource gradients is one of the main hypothesized causes for enhanced ecosystem functioning in more biodiverse grasslands. Spatial resource partitioning occurs if species differ in where they acquire resources and can happen both above- and belowground. However, studies investigating spatial resource partitioning in grasslands provide inconsistent evidence. We present the results of a meta-analysis of 21 data sets from experimental species-richness gradients in grasslands. We test the hypothesis that increasing spatial resource partitioning along vertical resource gradients enhances ecosystem functioning in diverse grassland plant communities above- and belowground. To test this hypothesis, we asked three questions. (1) Does species richness enhance biomass production or community resource uptake across sites? (2) Is there evidence of spatial resource partitioning as indicated by resource tracer uptake and biomass allocation above- and belowground? (3) Is evidence of spatial resource partitioning correlated with increased biomass production or community resource uptake? Although plant species richness enhanced community nitrogen and potassium uptake and biomass production above- and belowground, we found that plant communities did not meet our criteria for spatial resource partitioning, though they did invest in significantly more aboveground biomass in higher canopy layers in mixture relative to monoculture. Furthermore, the extent of spatial resource partitioning across studies was not positively correlated with either biomass production or community resource uptake. Our results suggest that spatial resource partitioning across vertical resource gradients alone does not offer a general explanation for enhanced ecosystem fu

Contains fulltext : 217065.pdf (publisher's version ) (Open Access), Locally, plant species richness supports many ecosystem functions. Yet, the mechanisms driving these often-positive biodiversity?ecosystem functioning relationships are not well understood. Spatial resource partitioning across vertical resource gradients is one of the main hypothesized causes for enhanced ecosystem functioning in more biodiverse grasslands. Spatial resource partitioning occurs if species differ in where they acquire resources and can happen both above- and belowground. However, studies investigating spatial resource partitioning in grasslands provide inconsistent evidence. We present the results of a meta-analysis of 21 data sets from experimental species-richness gradients in grasslands. We test the hypothesis that increasing spatial resource partitioning along vertical resource gradients enhances ecosystem functioning in diverse grassland plant communities above- and belowground. To test this hypothesis, we asked three questions. (1) Does species richness enhance biomass production or community resource uptake across sites? (2) Is there evidence of spatial resource partitioning as indicated by resource tracer uptake and biomass allocation above- and belowground? (3) Is evidence of spatial resource partitioning correlated with increased biomass production or community resource uptake? Although plant species richness enhanced community nitrogen and potassium uptake and biomass production above- and belowground, we found that plant communities did not meet our criteria for spatial resource partitioning, though they did invest in significantly more aboveground biomass in higher canopy layers in mixture relative to monoculture. Furthermore, the extent of spatial resource partitioning across studies was not positively correlated with either biomass production or community resource uptake. Our results suggest that spatial resource partitioning across vertical resource gradients alone does not offer a general explanation for enhanced ecosystem fu

Locally, plant species richness supports many ecosystem functions. Yet, the mechanisms driving these often-positive biodiversity–ecosystem functioning relationships are not well understood. Spatial resource partitioning across vertical resource gradients is one of the main hypothesized causes for enhanced ecosystem functioning in more biodiverse grasslands. Spatial resource partitioning occurs if species differ in where they acquire resources and can happen both above- and belowground. However, studies investigating spatial resource partitioning in grasslands provide inconsistent evidence. We present the results of a meta-analysis of 21 data sets from experimental species-richness gradients in grasslands. We test the hypothesis that increasing spatial resource partitioning along vertical resource gradients enhances ecosystem functioning in diverse grassland plant communities above- and belowground. To test this hypothesis, we asked three questions. (1) Does species richness enhance biomass production or community resource uptake across sites? (2) Is there evidence of spatial resource partitioning as indicated by resource tracer uptake and biomass allocation above- and belowground? (3) Is evidence of spatial resource partitioning correlated with increased biomass production or community resource uptake? Although plant species richness enhanced community nitrogen and potassium uptake and biomass production above- and belowground, we found that plant communities did not meet our criteria for spatial resource partitioning, though they did invest in significantly more aboveground biomass in higher canopy layers in mixture relative to monoculture. Furthermore, the extent of spatial resource partitioning across studies was not positively correlated with either biomass production or community resource uptake. Our results suggest that spatial resource partitioning across vertical resource gradients alone does not offer a general explanation for enhanced ecosystem functioning

Locally, plant species richness supports many ecosystem functions. Yet, the mechanisms driving these often‐positive biodiversity–ecosystem functioning relationships are not well understood. Spatial resource partitioning across vertical resource gradients is one of the main hypothesized causes for enhanced ecosystem functioning in more biodiverse grasslands. Spatial resource partitioning occurs if species differ in where they acquire resources and can happen both above‐ and belowground. However, studies investigating spatial resource partitioning in grasslands provide inconsistent evidence. We present the results of a meta‐analysis of 21 data sets from experimental species‐richness gradients in grasslands. We test the hypothesis that increasing spatial resource partitioning along vertical resource gradients enhances ecosystem functioning in diverse grassland plant communities above‐ and belowground. To test this hypothesis, we asked three questions. (1) Does species richness enhance biomass production or community resource uptake across sites? (2) Is there evidence of spatial resource partitioning as indicated by resource tracer uptake and biomass allocation above‐ and belowground? (3) Is evidence of spatial resource partitioning correlated with increased biomass production or community resource uptake? Although plant species richness enhanced community nitrogen and potassium uptake and biomass production above‐ and belowground, we found that plant communities did not meet our criteria for spatial resource partitioning, though they did invest in significantly more aboveground biomass in higher canopy layers in mixture relative to monoculture. Furthermore, the extent of spatial resource partitioning across studies was not positively correlated with either biomass production or community resource uptake. Our results suggest that spatial resource partitioning across vertical resource gradients alone does not offer a general explanation for enhanced ecosystem functioning

Locally, plant species richness supports many ecosystem functions. Yet, the mechanisms driving these often-positive biodiversity–ecosystem functioning relationships are not well understood. Spatial resource partitioning across vertical resource gradients is one of the main hypothesized causes for enhanced ecosystem functioning in more biodiverse grasslands. Spatial resource partitioning occurs if species differ in where they acquire resources and can happen both above- and belowground. However, studies investigating spatial resource partitioning in grasslands provide inconsistent evidence. We present the results of a meta-analysis of 21 data sets from experimental species-richness gradients in grasslands. We test the hypothesis that increasing spatial resource partitioning along vertical resource gradients enhances ecosystem functioning in diverse grassland plant communities above- and belowground. To test this hypothesis, we asked three questions. (1) Does species richness enhance biomass production or community resource uptake across sites? (2) Is there evidence of spatial resource partitioning as indicated by resource tracer uptake and biomass allocation above- and belowground? (3) Is evidence of spatial resource partitioning correlated with increased biomass production or community resource uptake? Although plant species richness enhanced community nitrogen and potassium uptake and biomass production above- and belowground, we found that plant communities did not meet our criteria for spatial resource partitioning, though they did invest in significantly more aboveground biomass in higher canopy layers in mixture relative to monoculture. Furthermore, the extent of spatial resource partitioning across studies was not positively correlated with either biomass production or community resource uptake. Our results suggest that spatial resource partitioning across vertical resource gradients alone does not offer a general explanation for enhanced ecosystem functioning

The success of habitat enhancements is typically assessed by subsequent monitoring of the focal taxonomic group. However, enhancement actions are likely to affect other, non-targeted species. On a south-facing slope in the Swiss Jura mountains, a mixed-forest stand was thinned out by irregular removal cuttings to improve the habitat conditions for reptiles. We used this enhancement action as a case study to monitor changes in the macrofungal community that came along with it. During 3 years before and after forest thinning, the site was visited between six and twelve times per year. Thereby, all apparent fungal species were recorded along a ringlike transect, split into 32 transect sections. We used site-occupancy models to estimate fungal species richness and abundance. These models allow to separately estimate occurrence probability and detection probability of species, and to account for differences in detection probability, depending on habitat and season. After the forest thinning, the occurrence probabilities of ectomycorrhizal and saprobic fungi were significantly higher than before. As a result, we estimated a mean increase in overall species richness by 4.4% (median 4.3%, CI 2.1–6.8%) and an increase in abundance by 20.0% (median 19.9%, CI 14.8–25.7%). The two major habitat changes associated with forest thinning, the decrease in living wood and the increase in dead wood on most transect sections, could not explain the whole extent of the estimated increase in species richness and abundance. We believe that forest thinning may have fostered fungal species richness by creating a larger density and diversity of suitable microhabitats. With some caution, we conclude that the small-scale habitat enhancement for reptiles at the Bolberg, creating islands of open forest, did not negatively affect species richness and abundance of macrofungi, a non-targeted species group.

INTRODUCTION Delirium is frequently observed in the intensive care unit (ICU) population, in particular. Until today, there is no evidence for any reliable pharmacological intervention to treat delirium. The Basel BOMP-AID (Better Outcome with Melatonin compared to Placebo Administered to normalize sleep-wake cycle and treat hypoactive ICU Delirium) randomised trial targets improvement of hypoactive delirium therapy in critically ill patients and will be conducted as a counterpart to the Basel ProDex Study (Study Protocol, BMJ Open, July 2017) on hyperactive and mixed delirium. The aim of the BOMP-AID trial is to assess the superiority of melatonin to placebo for the treatment of hypoactive delirium in the ICU. The study hypothesis is based on the assumption that melatonin administered at night restores a normal circadian rhythm, and that restoration of a normal circadian rhythm will cure delirium. METHODS AND ANALYSIS The Basel BOMP-AID study is an investigator-initiated, single-centre, randomised controlled clinical trial for the treatment of hypoactive delirium with the once daily oral administration of melatonin 4 mg versus placebo in 190 critically ill patients. The primary outcome measure is delirium duration in 8-hour shifts. Secondary outcome measures include delirium-free days and death at 28 days after study inclusion, number of ventilator days, length of ICU and hospital stay, and sleep quality. Patients will be followed after 3 and 12 months for activities of daily living and mortality assessment. Sample size was calculated to demonstrate superiority of melatonin compared with placebo regarding the duration of delirium. Results will be presented using an intention-to-treat approach. ETHICS AND DISSEMINATION This study has been approved by the Ethics Committee of Northwestern and Central Switzerland and will be conducted in compliance with the protocol, the current version of the Declaration of Helsinki, the International Conference on Harmonisation (ICH)

BACKGROUND Quality in medical research has recently been criticized for being low, especially in observational research. Methodology is increasingly difficult, but collaboration between clinical researchers and biostatisticians may improve research and reporting quality. The aim of this study is to quantify the value of a biostatistician in the team of authors. METHODS Single-center, retrospective observational study following the STROBE reporting guidelines. We will systematically review all medical publications with biostatisticians from our center as co-authors or authors and review corresponding papers without biostatisticians from our center during the same time range. We will compare aspects of reporting quality, overall and for the three study types observational, randomized trial, and prognostic separately. DISCUSSION We anticipate that the results of the study will raise awareness of the importance of high methodological quality, as well as appropriate reporting quality in clinical research. CONCLUSION Our study will have a direct impact on our center by making each of us more aware of the reporting guidelines for various research designs. This in turn will enhance reporting quality in future research with our involvement. Our study will also raise awareness of the important role that biostatisticians play in the design and analysis of health research projects.

BACKGROUND Over the past decades, stroke risk associated with carotid disease has decreased, reflecting improvements in medical therapy and a more rigorous control of vascular risk factors. It is less clear whether the procedural risk of carotid revascularization has declined over time. METHODS We analyzed temporal changes in procedural risks among 4597 patients with symptomatic carotid stenosis treated with carotid artery stenting (n=2326) or carotid endarterectomy (n=2271) in 4 randomized trials between 2000 and 2008, using generalized linear mixed-effects models with a random intercept for each source trial. Models were additionally adjusted for age and other baseline characteristics predicting treatment risk. The primary outcome event was any procedural stroke or death, occurring during or within 30 days after revascularization. RESULTS The procedural stroke or death risk decreased significantly over time in all patients (unadjusted odds ratio per year, 0.91; 95% CI, 0.85-0.97; P=0.006). This effect was driven by a decrease in the carotid endarterectomy group (unadjusted odds ratio per year, 0.82; 95% CI, 0.73-0.92; P=0.003), whereas no significant decrease was found after carotid artery stenting (unadjusted odds ratio, 0.96; 95% CI, 0.88-1.04; P=0.33). Carotid endarterectomy patients had a lower procedural stroke or death risk compared with carotid artery stenting patients, and the difference significantly increased over time (interaction P=0.031). After adjustment for baseline characteristics, the results remained essentially the same. CONCLUSIONS The risk of stroke or death associated with carotid endarterectomy for symptomatic carotid stenosis decreased over an 8-year period, independent of clinical predictors of procedural risk. No corresponding reduction in procedural risk was seen in patients treated with stenting. CLINICAL TRIAL REGISTRATION URL: https://www.clinicaltrials.gov; http://www.isrctn.com. Unique identifier: NCT00190398 (EVA-3S), NCT00004732 (

Importance: Therapeutic options for patients with secondary progressive multiple sclerosis (SPMS) are limited. Objective: To analyze disability progression in patients with SPMS treated with rituximab compared with matched control patients never treated with rituximab. Design, Setting, and Participants: This retrospective cohort study analyzed data obtained from patients with SPMS at 3 multiple sclerosis centers located in Basel and Lugano, Switzerland, and Amsterdam, the Netherlands, from 2004 to 2017. Patients were included for analysis if they had received a diagnosis of SPMS, were treated (57 eligible; 54 included) or never treated (504 eligible; 59 included) with rituximab, and had at least 1 follow-up visit. The variables used for propensity score matching were sex, age, Expanded Disability Status Scale (EDSS) score, and disease duration. Follow-up duration was up to 10 years, with a mean (SD) of 3.5 (2.6) years for rituximab-treated patients and 5.4 (2.4) years for controls in the total cohort and a mean (SD) of 3.5 (2.7) years for rituximab-treated patients and 4.8 (2.2) years for controls in the matched cohort. Exposures: Comparing EDSS score progression in patients with SPMS (treated with rituximab vs not treated with rituximab) using propensity score matching. Main Outcomes and Measures: The primary end point was progression of EDSS score after baseline, and the secondary end point was time to confirmed disability progression. Results: After 1:1 propensity score matching, 44 matched pairs (88 patients) were included in the analysis. At baseline, patients treated with rituximab had a mean (SD) age of 49.7 (10.0) years, mean (SD) disease duration of 18.2 (9.4) years, and mean (SD) EDSS score of 5.9 (1.4), and 26 (59%) were women, whereas controls had a mean (SD) age of 51.3 (7.4) years, mean (SD) disease duration of 19.4 (8.7) years, and mean (SD) EDSS score of 5.70 (1.29), and 27 (61%) were women. In the covariate-adjusted analysis of the matched set, pati

Persistent black holes (PBH) are associated with axonal loss and disability progression in multiple sclerosis (MS). The objective of this work was to determine if BHT-3009, a DNA plasmid-encoding myelin basic protein (MBP), reduces the risk of new lesions becoming PBH, compared to placebo, and to test if pre-treatment serum anti-MBP antibody levels impact on the effect of BHT-3009 treatment. In this retrospective, blinded MRI study, we reviewed MRI scans of 155 MS patients from a double-blind, randomized, phase II trial with three treatment arms (placebo, 0.5 and 1.5mg BHT-3009). New lesions at weeks 8 and 16 were tracked at week 48 and those appearing as T1-hypointense were classified as PBH. A subset of 46 patients with available pre-treatment serum anti-MBP IgM levels were analyzed separately. Overall, there was no impact of treatment on the risk for PBH. However, there was a significant interaction between anti-MBP antibodies and treatment effect: patients receiving 0.5mg BHT-3009 showed a reduced risk of PBH with higher antibody levels compared to placebo (p<0.01). Although we found no overall reduction of the risk for PBH in treated patients, there may be an effect of low-dose BHT-3009, depending on the patients' pre-treatment immune responses

With a new approach we assessed the relative contribution of stored and current carbon compounds to new shoot growth in alpine treeline conifers. Within a free air CO2 enrichment experiment at the alpine treeline in Switzerland, 13C-depleted fossil CO2 was used to trace new carbon in the two tree species Larix decidua L. and Pinus uncinata Ramond over two subsequent years. The deciduous L. decidua was found to supply new shoot growth (structural woody part) by 46% from storage. Surprisingly, the evergreen P. uncinata, assumed to use current-year photosynthates, also utilized a considerable fraction of storage (42%) for new wood growth. In contrast, the needles of P. uncinata were built up almost completely from current-year photosynthates. The isotopic composition of different wood carbon fractions revealed a similar relative allocation of current and stored assimilates to various carbon fractions. Elevated CO2 influenced the composition of woody tissue in a species-specific way, e.g. the water soluble fraction decreased in pine in 2001 but increased in larch in 2002 compared to ambient CO2. Heavy defoliation applied as an additional treatment factor in the second year of the experiment decreased the lipophilic fraction in current-year wood in both species compared to undefoliated trees. We conclude that storage may play an important role for new shoot growth in these treeline conifers and that altered carbon availability (elevated CO2, defoliation) results in significant changes in the relative amount of mobile carbon fractions in woody tissue. In particular, stored carbon seems to be of greater importance in the evergreen P. uncinata than has been previously thought

BACKGROUND: Randomized controlled trials have shown the efficacy of systemic treatments in moderate-to-severe psoriasis. Clinical outcomes in psoriasis patients under real-world conditions are less well understood. OBJECTIVE: This study compared Psoriasis Area and Severity Index (PASI) and Dermatological Life Quality Index (DLQI) improvement in all psoriasis patients registered in the Swiss Dermatology Network for Targeted Therapies. We asked whether outcomes differed between 4 treatment strategies, namely biologic monotherapy versus conventional systemic monotherapy, versus combined biologic and conventional systemic drugs, and versus therapy adaptation (switching from one type to another). METHODS: PASI and DLQI within 1 year after onset of systemic treatment, measured at 3, 6, and 12 months, were compared among the 4 groups using generalized linear mixed-effects models. RESULTS: Between March 2011 and December 2014, 334 patients were included; 151 received conventional systemic therapeutics, 145 biologics, 13 combined treatment, and 25 had a therapy adaptation. With regard to the absolute PASI, neither the biologic cohort nor the combined treatment cohort significantly differed from the conventional systemic therapeutics cohort. The odds of reaching PASI90 was significantly increased with combined therapy compared to conventional systemic therapeutics (p = 0.043) and decreased with a higher body mass index (p = 0.041). At visits 3 and 4, the PASI was generally lower than at visit 2 (visit 3 vs. visit 2, p = 0.0019; visit 4 vs. visit 2, p < 0.001). After 12 months, patients with biologic treatment had a significantly lower DLQI than those with conventional systemic therapeutics (p = 0.001). CONCLUSION: This study suggests that after 1 year of treatment, biologics are superior in improving the subjective disease burden compared to conventional systemic drugs.

Bayesian Data Analysis in Ecology Using Linear Models with R, BUGS, and STAN examines the Bayesian and frequentist methods of conducting data analyses. The book provides the theoretical background in an easy-to-understand approach, encouraging readers to examine the processes that generated their data. Including discussions of model selection, model checking, and multi-model inference, the book also uses effect plots that allow a natural interpretation of data. Bayesian Data Analysis in Ecology Using Linear Models with R, BUGS, and STAN introduces Bayesian software, using R for the simple modes, and flexible Bayesian software (BUGS and Stan) for the more complicated ones. Guiding the ready from easy toward more complex (real) data analyses ina step-by-step manner, the book presents problems and solutions?including all R codes?that are most often applicable to other data and questions, making it an invaluable resource for analyzing a variety of data types. Introduces Bayesian data analysis, allowing users to obtain uncertainty measurements easily for any derived parameter of interestWritten in a step-by-step approach that allows for eased understanding by non-statisticiansIncludes a companion website containing R-code to help users conduct Bayesian data analyses on their own dataAll example data as well as additional functions are provided in the R-package blmeco

Bayesian Data Analysis in Ecology Using Linear Models with R, BUGS, and STAN examines the Bayesian and frequentist methods of conducting data analyses. The book provides the theoretical background in an easy-to-understand approach, encouraging readers to examine the processes that generated their data. Including discussions of model selection, model checking, and multi-model inference, the book also uses effect plots that allow a natural interpretation of data. Bayesian Data Analysis in Ecology Using Linear Models with R, BUGS, and STAN introduces Bayesian software, using R for the simple modes, and flexible Bayesian software (BUGS and Stan) for the more complicated ones. Guiding the ready from easy toward more complex (real) data analyses ina step-by-step manner, the book presents problems and solutions?including all R codes?that are most often applicable to other data and questions, making it an invaluable resource for analyzing a variety of data types. Introduces Bayesian data analysis, allowing users to obtain uncertainty measurements easily for any derived parameter of interestWritten in a step-by-step approach that allows for eased understanding by non-statisticiansIncludes a companion website containing R-code to help users conduct Bayesian data analyses on their own dataAll example data as well as additional functions are provided in the R-package blmeco

Bayesian Data Analysis in Ecology Using Linear Models with R, BUGS, and STAN examines the Bayesian and frequentist methods of conducting data analyses. The book provides the theoretical background in an easy-to-understand approach, encouraging readers to examine the processes that generated their data. Including discussions of model selection, model checking, and multi-model inference, the book also uses effect plots that allow a natural interpretation of data. Bayesian Data Analysis in Ecology Using Linear Models with R, BUGS, and STAN introduces Bayesian software, using R for the simple modes, and flexible Bayesian software (BUGS and Stan) for the more complicated ones. Guiding the ready from easy toward more complex (real) data analyses ina step-by-step manner, the book presents problems and solutions?including all R codes?that are most often applicable to other data and questions, making it an invaluable resource for analyzing a variety of data types. Introduces Bayesian data analysis, allowing users to obtain uncertainty measurements easily for any derived parameter of interestWritten in a step-by-step approach that allows for eased understanding by non-statisticiansIncludes a companion website containing R-code to help users conduct Bayesian data analyses on their own dataAll example data as well as additional functions are provided in the R-package blmeco

Bayesian Data Analysis in Ecology Using Linear Models with R, BUGS, and STAN examines the Bayesian and frequentist methods of conducting data analyses. The book provides the theoretical background in an easy-to-understand approach, encouraging readers to examine the processes that generated their data. Including discussions of model selection, model checking, and multi-model inference, the book also uses effect plots that allow a natural interpretation of data. Bayesian Data Analysis in Ecology Using Linear Models with R, BUGS, and STAN introduces Bayesian software, using R for the simple modes, and flexible Bayesian software (BUGS and Stan) for the more complicated ones. Guiding the ready from easy toward more complex (real) data analyses ina step-by-step manner, the book presents problems and solutions?including all R codes?that are most often applicable to other data and questions, making it an invaluable resource for analyzing a variety of data types. Introduces Bayesian data analysis, allowing users to obtain uncertainty measurements easily for any derived parameter of interestWritten in a step-by-step approach that allows for eased understanding by non-statisticiansIncludes a companion website containing R-code to help users conduct Bayesian data analyses on their own dataAll example data as well as additional functions are provided in the R-package blmeco