Glucocorticoid withdrawal and glucocorticoid-induced adrenal insufficiency: Study protocol of the randomized controlled «TOASST" (Taper Or Abrupt Steroid STop) multicenter trial.

BACKGROUND: Despite the widespread use of glucocorticoids in inflammatory and autoimmune disorders, there is uncertainty about the safe cessation of long-term systemic treatment, as data from prospective trials are largely missing. Due to potential disease relapse or glucocorticoid-induced hypocortisolism, the drug is often tapered to sub-physiological doses rather than stopped when the underlying disease is clinically stable, increasing the cumulative drug exposure. Conversely, the duration of exposure to glucocorticoids should be minimized to lower the risk of side effects. METHODS: We designed a multicenter, randomized, triple-blinded, placebo-controlled trial to test the clinical noninferiority of abrupt glucocorticoid stop compared to tapering after ≥28 treatment days with ≥420 mg cumulative and ≥7.5 mg mean daily prednisone-equivalent dose. 573 adult patients treated systemically for various disorders will be included after their underlying disease has been stabilized. Prednisone in tapering doses or matching placebo is administered over 4 weeks. A 250 mg ACTH-test, the result of which will be revealed a posteriori, is performed at study inclusion; all patients are instructed on glucocorticoid stress cover dosing. Follow-up is for 6 months. The composite primary outcome measure is time to hospitalization, death, initiation of unplanned systemic glucocorticoid therapy, or adrenal crisis. Secondary outcomes include the individual components of the primary outcome, cumulative glucocorticoid doses, signs and symptoms of hypocortisolism, and the performance of the ACTH test in predicting the clinical outcome. Cox proportional hazard, linear, and logistic regression models will be used for statistical analysis. CONCLUSION: This trial aims to demonstrate the clinical noninferiority and safety of abrupt treatment cessation after ≥28 days of systemic glucocorticoid therapy in patients with stabilized underlying disease. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03153527; EUDRA-CT: 2020-005601-48 https://clinicaltrials.gov/ct2/show/NCT03153527?term=NCT03153527&draw=2&rank=1.

Implementation fidelity of a multifactorial in-hospital fall prevention program and its association with unit systems factors: a single center, cross-sectional study.

BACKGROUND: Falls are a common, costly global public health burden. In hospitals, multifactorial fall prevention programs have proved effective in reducing falls' incidence; however, translating those programs accurately into daily clinical practice remains challenging. This study's aim was to identify ward-level system factors associated with implementation fidelity to a multifactorial fall prevention program (StuPA) targeting hospitalized adult patients in an acute care setting. METHODS: This retrospective cross-sectional study used administrative data on 11,827 patients admitted between July and December 2019 to 19 acute care wards at the University Hospital Basel, Switzerland, as well as data on the StuPA implementation evaluation survey conducted in April 2019. Data were analysed using descriptive statistics, Pearson's coefficients and linear regression modelling for variables of interest. RESULTS: The patient sample had an average age of 68 years and a median length of stay of 8.4 (IQR: 2.1) days. The mean care dependency score was 35.4 points (ePA-AC scale: from 10 points (totally dependent) to 40 points (totally independent)); the mean number of transfers per patient -(e.g., change of room, admission, discharge) was 2.6 (range: 2.4- 2.8). Overall, 336 patients (2.8%) experienced at least one fall, resulting in a rate of 5.1 falls per 1'000 patient days. The median inter-ward StuPA implementation fidelity was 80.6% (range: 63.9-91.7%). We found the mean number of inpatient transfers during hospitalisation and the mean ward-level patient care dependency to be statistically significant predictors of StuPA implementation fidelity. CONCLUSION: Wards with higher care dependency and patient transfer levels showed higher implementation fidelity to the fall prevention program. Therefore, we assume that patients with the highest fall prevention needs received greater exposure to the program. For the StuPA fall prevention program, our results suggest a need for implementation strategies contextually adapted to the specific characteristics of the target wards and patients.

Towards full clinical trial registration and results publication: longitudinal meta-research study in Northwestern and Central Switzerland.

OBJECTIVE: The registration of clinical trials is required by law in Switzerland. We investigated (1) the proportion of registered and prospectively registered clinical trials, (2) the availability of results for ethically approved trial protocols, (3) factors associated with increased registration, and (4) reasons for non-registration. DESIGN AND SETTING: We included all clinical trials with mandatory prospective registration, which were approved by the ethics committee of Northwestern and Central Switzerland between January 1, 2016, and December 31, 2020. METHODS: We extracted relevant trial characteristics from the Swiss Business Administration System for Ethics Committees and systematically searched the International Clinical Trials Registry Platform and primary trial registries for corresponding registry entries. We used multivariable logistic regression to examine the association between trial characteristics and registration. We qualitatively assessed reasons for non-registration of trials through an email questionnaire for trial investigators. RESULTS: Of 473 included clinical trials, 432 (91%) were registered at all and 326 (69%) were prospectively registered. While the percentages of registration and prospective registration of investigator-sponsored trials increased from 85 to 93% and from 59 to 70% over 5 years, respectively, industry-sponsored trials consistently remained at a high level of prospective registration (92 to 100%). Trials with multiple centres, higher risk category, or methodological support from the local clinical trials unit were independently associated with increased registration rates. Of 103 clinical trials completed before August 2020, results were available for 70% of industry-sponsored trials and 45% of investigator-sponsored trials as peer-reviewed journal publications or in trial registries. Most common reasons for non-registration provided by investigators were lack of time or resources (53%), lack of knowledge (22%), and lack of reminders by the ethics committee (36%). CONCLUSIONS: In Northwestern and Central Switzerland about 10% of clinical trials remained unregistered despite the obligation by law. More support for investigators and stricter enforcement by regulators are needed to improve the transparency of investigator-sponsored trials in particular.

Development of the Basel Version of the Awareness of Social Inference Test - Theory of Mind (BASIT-ToM) in healthy adults.

Impairments of Theory of Mind (ToM) abilities occur in a wide range of brain disorders. Therefore, reliable and ecologically valid examination of these abilities is a crucial part of any comprehensive neuropsychological assessment. An established and ecologically valid, English-language test identifying deficits in ToM abilities is "The Awareness of Social Inference Test - Social Inference Minimal (TASIT-SIM)". However, no comparable German-language ToM test currently exists. In this study, we aimed to develop the first German-language adaption of TASIT-SIM in healthy adults. We selected 13 scenes [four scenes per message type (i.e., honesty, simple sarcasm, paradoxical sarcasm) and one practice scene] out of the 30 TASIT-SIM scenes. In collaboration with a film institute, we filmed each scene at three different intensities. These intensity version scenes were then administered to 240 healthy adults, equally distributed in sex and age, ranging from 35 to 92 years. By applying Rasch analysis, we selected intensity versions that showed neither floor nor ceiling effects in the majority of ToM questions in participants whose ToM abilities were in the medium range. In conclusion, we have developed the first German-language adaption of TASIT-SIM, i.e., the "Basel Version of the Awareness of Social Inference Test - Theory of Mind (BASIT-ToM)". The BASIT-ToM incorporates the strengths of TASIT-SIM, while overcoming its limitations such as inconsistencies in cinematic realization and ceiling effects in healthy participants. Next, the BASIT-ToM needs to be validated in healthy people and clinical populations.

Vaccination completeness in children with rheumatic diseases: A longitudinal, observational multicenter cohort study in Switzerland.

Introduction: Children with pediatric inflammatory rheumatic diseases (PRD) have an increased infection risk. Vaccinations are effective to avoid vaccine-preventable diseases. This study aimed to assess the vaccination completeness in Swiss PRD patients stratified by immunosuppressive treatment (IST). Materials and methods: This multicenter observational cohort study of PRD patients was performed in Basel, Geneva, Lucerne, Lausanne, and Zurich in PRD patients aged < 18 years included in the Juvenile Inflammatory Rheumatism Cohort. Completeness was assessed for i) the overall vaccination status (Swiss national immunization program (NIP) and specific additional PRD-recommended vaccinations), ii) for all and each vaccination of the NIP at PRD diagnosis and reference date (RefD) and iii) all and each specific additional PRD-recommended vaccination at RefD. Completeness was assessed over the disease course and stratified by IST. Results: Of 616 eligible patients, 234 children were analyzed. Of these, 147 (63%) were girls. Median age at PRD diagnosis was 6.5 years (IQR 2.9-10.3) and 10.9 years at RefD (6.9-14.3). The median follow-up since PRD diagnosis was 3 years (1.1-5.5). 120/234 children received IST. At RefD, overall vaccination completeness was 3.8% (9/234 children), completeness for the NIP vaccinations was 70.1% (164/234 children; IST 65%, no IST: 75.4%) and for all specific additional PRD-recommended vaccinations was 3.8% (9/234 children; IST 2.5%; no IST 5.3%). Vaccination completeness against pneumococcal disease, hepatitis B virus, and human papilloma virus (HPV) was 50.4, 20, 37.9%, respectively. In 25/35 children with negative varicella zoster virus history vaccination status was complete (IST: 94.4%, no IST: 47%). Annual non-live influenza vaccination was complete in 24.2% of children during IST; adherence decreased over the disease course. Discussion: This study identified a low overall vaccination completeness in children with PRD. Particularly, the completeness of specific additional PRD-recommended vaccinations was low. If not performed early after PRD diagnosis, vaccination status remained frequently incomplete. Close collaboration between pediatrician and rheumatologist to improve vaccination completeness is essential. Exchange of vaccination records, standardized assessment of specific PRD-recommended vaccinations and those of the NIP, and annual reminder for influenza vaccination are crucial to improve vaccination completeness in this vulnerable pediatric population.

The Basel Version of the Awareness of Social Inference Test-Emotion Recognition (BASIT-ER): Preliminary validation analyses in healthy adults.

OBJECTIVE: Emotion recognition (ER) is commonly impaired in many brain disorders. Therefore, its reliable and ecologically valid examination is a crucial part of any comprehensive neuropsychological assessment. In this regard, an established English-language test identifying deficits in ER is "The Awareness of Social Inference Test-Emotion Evaluation Test" (TASIT-EET). However, no comparable German-language ER test currently exists. In this study, we aimed to develop and preliminarily validate the first German-language adaption of TASIT-EET in healthy adults. METHOD: We selected 22 scenes [three scenes per emotion (i.e., anger, disgust, fear, happiness, sadness, surprise, and neutral) and one practice scene] out of the 56 TASIT-EET scenes. In collaboration with a film institute and professional actors, we filmed each scene (except neutral) at three different emotional intensities. Then, we administered these intensity version scenes to 240 cognitively and mentally healthy participants, equally distributed in sex and age, ranging from 35 to 92 years. RESULTS: By applying Rasch analysis, the one intensity version per scene was selected that showed neither floor nor ceiling effects in participants whose ability in ER was in the medium range. CONCLUSIONS: We have conducted a preliminary validation of the first German-language adaption of TASIT-EET, i.e., the "Basel Version of the Awareness of Social Inference Test-Emotion Recognition" (BASIT-ER). The BASIT-ER comprises the strengths of the TASIT-EET, while it overcomes its limitations such as ceiling effects in healthy participants and the simple response format. Next, the BASIT-ER needs to be validated in clinical populations. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Prediction of RECRUITment In randomized clinical Trials (RECRUIT-IT)-rationale and design for an international collaborative study.

BACKGROUND: Poor recruitment of patients is the predominant reason for early termination of randomized clinical trials (RCTs). Systematic empirical investigations and validation studies of existing recruitment models, however, are lacking. We aim to provide evidence-based guidance on how to predict and monitor recruitment of patients into RCTs. Our specific objectives are the following: (1) to establish a large sample of RCTs (target n = 300) with individual patient recruitment data from a large variety of RCTs, (2) to investigate participant recruitment patterns and study site recruitment patterns and their association with the overall recruitment process, (3) to investigate the validity of a freely available recruitment model, and (4) to develop a user-friendly tool to assist trial investigators in the planning and monitoring of the recruitment process. METHODS: Eligible RCTs need to have completed the recruitment process, used a parallel group design, and investigated any healthcare intervention where participants had the free choice to participate. To establish the planned sample of RCTs, we will use our contacts to national and international RCT networks, clinical trial units, and individual trial investigators. From included RCTs, we will collect patient-level information (date of randomization), site-level information (date of trial site activation), and trial-level information (target sample size). We will examine recruitment patterns using recruitment trajectories and stratifications by RCT characteristics. We will investigate associations of early recruitment patterns with overall recruitment by correlation and multivariable regression. To examine the validity of a freely available Bayesian prediction model, we will compare model predictions to collected empirical data of included RCTs. Finally, we will user-test any promising tool using qualitative methods for further tool improvement. DISCUSSION: This research will contribute to a better understanding of participant recruitment to RCTs, which could enhance efficiency and reduce the waste of resources in clinical research with a comprehensive, concerted, international effort.