Feasibility, safety and effectiveness of prednisolone and vitamin B1, B6, and B12 in patients with post-COVID-19-syndrome (PreVitaCOV) - protocol of a randomised, double-blind, placebo-controlled multicentre trial in primary care (phase IIIb).

BACKGROUND: After infection with SARS-CoV-2 a relevant proportion of patients complains about persisting symptoms, a condition termed Post-COVID-19-syndrome (PC19S). So far, possible treatments are under investigation. Among others, neurotropic vitamins and anti-inflammatory substances are potential options. Thus, the PreVitaCOV trial aims to assess feasibility, safety, and effectiveness of treating patients in primary care with prednisolone and/or vitamin B1, B6 and B12. METHODS: The phase IIIb, multi-centre randomised, double-blind, and placebo-controlled PreVitaCOV trial has a factorial design and is planned as a two-phase approach. The pilot phase assessed feasibility and safety and was transformed into a confirmatory phase to evaluate effectiveness since feasibility was proven. Adult patients with PC19S after a documented SARS-CoV-2 infection at least 12 weeks ago are randomly assigned to 4 parallel treatments: prednisolone 20 mg for five days followed by 5 mg for 23 days (trial drug 1), B vitamins (B1 (100 mg OD), B6 (50 mg OD), and B12 (500 µg OD)) for 28 days (trial drug 2), trial drugs 1 and 2, or placebo. The primary outcome of the pilot phase was defined as the retention rate of the first 100 patients. Values of ≥ 85% were considered as confirmation of feasibility, this criterion was even surpassed by a retention rate of 98%. After transformation, the confirmatory phase proceeds by enrolling 240 additional patients. The primary outcome for the study is the change of symptom severity from baseline to day 28 as assessed by a tailored Patient Reported Outcomes Measurement Information System (PROMIS) total score referring to five symptom domains known to be typical for PC19S (fatigue, dyspnoea, cognition, anxiety, depression). The confirmatory trial is considered positive if superiority of any treatment is demonstrated over placebo operationalised by an improvement of at least 3 points on the PROMIS total score (t-score). DISCUSSION: The PreVitaCOV trial may contribute to the understanding of therapeutic approaches in PC19S in a primary care context. TRIAL REGISTRATION: EudraCT: 2022-001041-20. DRKS: DRKS00029617. CLINICALTRIALS: gov: F001AM02222_1 (registered: 05 Dec 2022).

A multidomain intervention against cognitive decline in an at-risk-population in Germany: Results from the cluster-randomized AgeWell.de trial.

INTRODUCTION: We investigated the effectiveness of a multidomain intervention to preserve cognitive function in older adults at risk for dementia in Germany in a cluster-randomized trial. METHODS: Individuals with a Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) risk score ≥ 9 aged 60 to 77 years were recruited. After randomization of their general practitioner (GP), patients received a multidomain intervention (including optimization of nutrition and medication, and physical, social, and cognitive activity) or general health advice and GP treatment as usual over 24 months. Primary outcome was global cognitive performance (composite z score, based on domain-specific neuropsychological tests). RESULTS: Of 1030 participants at baseline, n = 819 completed the 24-month follow-up assessment. No differences regarding global cognitive performance (average marginal effect = 0.010, 95% confidence interval: -0.113, 0.133) were found between groups at follow-up. Perceived restrictions in intervention conduct by the COVID-19 pandemic did not impact intervention effectiveness. DISCUSSION: The intervention did not improve global cognitive performance. HIGHLIGHTS: Overall, no intervention effects on global cognitive performance were detected. The multidomain intervention improved health-related quality of life in the total sample. In women, the multidomain intervention reduced depressive symptoms. The intervention was completed during the COVID-19 pandemic.

MRI in patients with implanted active devices: how to combine safety and image quality using a limited transmission field?

OBJECTIVES: Radio frequency (RF) pulses in magnetic resonance imaging (MRI) can interact with implanted devices and cause tissue damage. However, there are new devices that can safely perform measurements with liberal MRI conditions such as an RF transmission field B1+rms ≤ 2.0 µT. We investigated whether MRI in this case is limited for these technical reasons. METHODS: We selected typical MRI protocols of six body regions (brain, cervical spine, lumbar spine, knee, liver, heart) using two typical 1.5T MRI scanners. Overall, we adapted 62 sequences to B1+rms conditions and evaluated their diagnostic quality. For this, we measured signal-to-noise-ratio (SNR), contrast-to-noise-ratio (CNR), and geometric deviation (GD) as quality parameters, using phantom studies. For questionnaire studies, we selected pairs of original and adapted sequences in healthy volunteers. Blinded radiologists rated the images as single sequence rating and in direct comparison. RESULTS: Roughly one-third of the checked sequences were below the B1+rms limit. Here, 56 of the 62 adapted sequences showed at least the same image quality in single ratings. A reduction in SNR and/or CNR was found with 31 sequences and only one sequence with considerably increased GD. Especially, sequences with original high B1+rms values, PD sequences, and sequences of the Siemens knee and heart protocol were difficult to adapt, whereas most TSE and IR sequences had no clinical limitations. CONCLUSION: By limiting the transmission field to B1+rms ≤ 2.0 µT, clinically relevant MR sequences can be adapted with nearly no reduction in image quality. Despite limiting the transmission field, high-quality MR imaging is possible. We could derive strategies for adaptation. KEY POINTS: • Despite limiting the transmission field, high-quality MRI is possible. • We could derive strategies for adapting the sequences to B1+rms≤ 2.0 µT. • This enables high-quality MRI of different body regions for patients with AD.

Factors Associated with Lower Social Activity in German Older Adults at Increased Risk of Dementia: A Cross-Sectional Analysis.

Background: Studies demonstrate associations between low social activity in older adults and cognitive decline. Little has been investigated regarding which factors are associated with low social activity in older adults at increased risk of dementia. Objective: We investigate which sociodemographic, psychological, health-related, and environmental factors are associated with low social activity in older adults at increased risk of dementia. Additionally, we describe the stages of health behavior change, the types of social activities, and the duration of the current level of social activity. Methods: We used baseline data of 1,015 participants from the AgeWell.de trial. We conducted logistic and Poisson regression analyses to investigate factors associated with low social activity. We report descriptive statistics on the stages of change in the sample, the types of social activities most frequently pursued, and the duration of the current level of social activity. Results: Lower income, non-usage of public transport, depressive symptoms, cognitive, mobility, and hearing impairment were negatively associated with social activity. The majority of the sample was in the maintenance stage, followed by the precontemplation stage. The most common social activities were traveling and hobbies with others. Participants have maintained their current level of social activity for several years. Conclusions: We identified a lack of resources (income, transport), depressive symptoms and poorer health (cognitive, mobility and hearing impairment) as barriers to social activity. Interventions promoting social activity in older adults at risk of dementia may specifically target individuals with these risk factors. Low-threshold opportunities for social activity may be particularly beneficial.

Adherence to a lifestyle intervention - just a question of self-efficacy? Analysis of the AgeWell.de-intervention against cognitive decline.

BACKGROUND: Aim of this study was to detect predictors of better adherence to the AgeWell.de-intervention, a two-year randomized multi-domain lifestyle intervention against cognitive decline. METHODS: Data of 317 intervention group-participants comprising a risk group for dementia (Cardiovascular Risk Factors, Ageing and Dementia (CAIDE) score of ≥ 9; mean age 68.9 years, 49.5% women) from the AgeWell.de intervention study were analysed. Regression models with four blocks of predictors (sociodemographic, cognitive and psychosocial, lifestyle factors and chronic conditions) were run on adherence to the components of nutrition, enhancement of social and physical activity and cognitive training. Adherence to each component was operationalised by assessing the degree of goal achievement per component at up to seven time points during the intervention period, measured using a 5-point Likert scale (mean score of goal achievement). RESULTS: Increasing age was negatively associated with adherence, while higher education positively predicted adherence. Participants with better mental state (Montreal Cognitive Assessment (MoCA)-score > 25) at baseline and higher self-efficacy adhered better. Diabetes and cardiovascular conditions were not associated with adherence, whereas smoking negatively affected adherence. Highest education and quitting smoking in the past were the only predictors associated with all four intervention components. CONCLUSION: Results identified predictors for better and worse adherence. Particularly self-efficacy seems to be of considerable influence on adherence. This should be considered when designing future intervention trials. TRIAL REGISTRATION: German Clinical Trials Register (ref. number: DRKS00013555).

Ethik First - extracurricular support for medical students and young physicians facing moral dilemmas in hospital routine.

Introduction: Moral value conflicts play an increasingly central role in everyday hospital life. Clinical ethics, however, is only marginally represented in the compulsory curriculum for human medicine and the additional education regulations. The aim of the Ethik First project at the University Medical Center Schleswig-Holstein, Campus Kiel is to close this gap with an extracurricular offer and to support medical students from the fifth clinical semester onward and during their practical year as well as assistant doctors in dealing with moral dilemmas in everyday hospital life. The project has taken the concomitant learning objectives from the national competency-based learning objective catalog for medicine. According to the target group, the address in particular, showed higher taxonomy levels. Project description: The multimodal concept is based on three pillars: In monthly principle-based case conferences, participants practice ethical reflection and moral judgment primarily on the basis of concrete cases introduced by them using the methods of problem-based learning and consideration-based deliberation. If participants do not bring forth a case, they discuss ethical aspects of current political relevance. Moreover, there is an annual public speaker event. Results: Since the project began in 2017, ~20 students and interns have taken part in Ethik First one or more times. In a web-based interim evaluation (N=13), all respondents fully agreed that they considered the format helpful for dealing with ethical questions at the clinic. They rated the relevance for their later profession as high. There is evidence for support in moral dilemma situations. Discussion: The first evaluation results of the voluntary extracurricular offer show the acceptance of the selected format, which goes beyond pure teaching in its conception in that it addresses moral stress as well and strengthens the participants' individual resilience. Conclusion: Ethik First reinforces the role of ethical aspects in the training of (prospective) doctors and focuses on reflecting on cases they have experienced firsthand. We formulate a desideratum for appropriate advanced training concepts both in medical studies and in advanced medical training such that the training and development of comparable projects at medical faculties and at medical associations with student participation can be discussed.