Publications by authors named "David Czock"

Quantitative systems pharmacology (QSP) models are rarely applied prospectively for decision-making in clinical practice. We therefore aimed to operationalize a QSP model for potas-sium homeostasis to predict potassium trajectories based on spironolactone administrations. For this purpose, we proposed a general workflow that was applied to electronic health records (EHR) from patients treated in a German tertiary care hospital.

View Article and Find Full Text PDF
Article Synopsis
  • The study examined the relationship between the CAIDE dementia risk score and modifiable factors in the LIBRA score among 807 German participants at high risk for Alzheimer's.
  • Results showed that higher cognitive activity and fruit/vegetable intake were linked to lower CAIDE scores, while diabetes increased risk.
  • The findings suggest that different dementia risk scores may classify individuals differently, highlighting the impact of lifestyle choices on dementia risk.
View Article and Find Full Text PDF

Background: General practitioners (GPs) play a crucial role in identifying cognitive impairment and dementia and providing post-diagnostic care. This study investigates (1) how promising GP consider lifestyle changes to maintain cognitive performance in general, (2) GP beliefs about the power of modifiable health and lifestyle factors to maintain cognitive performance, and (3) whether those beliefs vary by GP age.

Methods: As part of the AgeWell.

View Article and Find Full Text PDF

Introduction: Dementia risk scores constitute promising surrogate outcomes for lifestyle interventions targeting cognitive function. We investigated whether dementia risk, assessed using the LIfestyle for BRAin health (LIBRA) index, was reduced by the AgeWell.de intervention.

View Article and Find Full Text PDF

Purpose: Quality of Life (QoL) is associated with a bandwidth of lifestyle factors that can be subdivided into fixed and potentially modifiable ones. We know too little about the role of potentially modifiable factors in comparison to fixed ones. This study examines four aspects of QoL and its associations with 15 factors in a sample of elderly primary care patients with a high risk of dementia.

View Article and Find Full Text PDF

Individual sirolimus whole blood concentrations are highly variable, critically influenced by the concomitant use of cytochrome P450 (CYP) 3A inducers or inhibitors, and also modulated by food. Therapeutic drug monitoring is therefore recommended, especially at treatment start or in circumstances that can influence sirolimus exposure. In this case report, we highlight the challenge of achieving therapeutic sirolimus concentrations and present pragmatic solutions with regimen adaptions, pharmacokinetic enhancement (use of a drug–drug interaction), concentration monitoring, and subsequent modeling of population pharmacokinetics to support treatment decisions.

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF

Background: Adverse anticholinergic drug reactions are common, yet evidence on how to reduce exposure to anticholinergic activity and reliably measure successful deprescribing is still scant. This study proposes an algorithm-based approach to evaluate and reduce anticholinergic load, and reports the results of its pilot testing.

Methods: Based on published evidence and expert opinion, a list of 85 anticholinergic drugs and 21 algorithms for reducing anticholinergic load, e.

View Article and Find Full Text PDF

Tacrolimus is metabolized by cytochrome P450 3A (CYP3A) and is susceptible to interactions with the CYP3A and P-glycoprotein inducer St. John's Wort (SJW). CYP3A isozymes are predominantly expressed in the small intestine and liver.

View Article and Find Full Text PDF

Background And Objective: Although polypharmacy is a particular challenge in daily rheumatological practice, clinical research on the effects of hydroxychloroquine (HCQ), a commonly used drug for patients with rheumatic diseases, is sparse on cytochrome P450 (CYP)-mediated metabolism. We have shown that pre-treatment with pantoprazole does not alter HCQ absorption in healthy volunteers. In this paper, we report the effects of a single 400 mg dose of HCQ on specific CYP3A and CYP2D6 substrates in healthy volunteers.

View Article and Find Full Text PDF

Purpose: Early antiviral treatment with nirmatrelvir/ritonavir is recommended for SARS-CoV-2-infected patients at high risk for severe courses. Such patients are usually chronically ill and susceptible to adverse drug interactions caused by ritonavir. We investigated the interactions of short-term low-dose ritonavir therapy with atorvastatin and rosuvastatin, two statins commonly used in this population.

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF

To develop effective dementia prevention strategies, it is necessary to understand risk factors, associated factors and early signs of dementia. Subjective cognitive decline (SCD) is the earliest form of dementia. The aim of this study is to assess depression as a factor that is significantly associated with SCD.

View Article and Find Full Text PDF

Background: The administration of modified immune cells (MIC) before kidney transplantation led to specific immunosuppression against the allogeneic donor and a significant increase in regulatory B lymphocytes. We wondered how this approach affected the continued clinical course of these patients.

Methods: Ten patients from a phase I clinical trial who had received MIC infusions prior to kidney transplantation were retrospectively compared to 15 matched standard-risk recipients.

View Article and Find Full Text PDF

Bulevirtide is a first-in-class antiviral drug to treat chronic hepatitis B/D. We investigated the drug-drug interaction potential and pharmacokinetics of high-dose subcutaneous bulevirtide (5 mg twice daily) with organic anion transporting polypeptide 1B1 (OATP1B1) and cytochrome P450 (CYP) 3A4. This was a single-center, open-label, fixed-sequence drug-drug interaction trial in 19 healthy volunteers.

View Article and Find Full Text PDF

Aims: In patients of all ages, metamizole is a frequently used analgesic. Recently, metamizole has been identified as an inducer of, among others, cytochrome P450 (CYP) 3A activity, but the time course of this interaction has not been evaluated.

Methods: Using repeated oral microdoses (30 μg) of the CYP3A index substrate midazolam, we assessed changes in midazolam pharmacokinetics (area under the concentration-time curve from 2-4 h: AUC and estimated partial metabolic clearance: eCl ) before, at steady-state, and after discontinuation of 3 × 1000 mg metamizole/day orally for 8 days.

View Article and Find Full Text PDF

Background: Frailty makes older adults vulnerable to adverse health outcomes and can modify pharmacokinetics and drug exposure.

Objective: We aimed to explore the relationship between different frailty assessments and trough plasma concentrations of direct oral anticoagulants in older patients.

Methods: The frailty status of adults aged ≥ 70 years receiving regular direct oral anticoagulant medication was assessed by four different instruments: Fried physical phenotype, Rockwood frailty index, Short Physical Performance Battery, and FRAIL scale.

View Article and Find Full Text PDF
Article Synopsis
  • The TOL-2 Study is a phase-IIb clinical trial investigating the use of modified immune cells (MIC) from living donors to provide specific immunosuppression in kidney transplantation, comparing MIC treatment with standard care.
  • Sixty-three kidney transplant recipients will be randomly assigned to receive MIC treatment or serve as controls, with the trial aiming to assess the efficacy of MIC in reducing conventional immunosuppressive therapy while achieving operational tolerance-like results.
  • The study will monitor patient health, looking for infections and signs of transplant rejection, alongside ethical oversight to ensure safety and efficacy throughout the process.
View Article and Find Full Text PDF

A personalized vitamin D3 loading dose has not yet been tested in cancer patients. This interim analysis of the randomized, placebo-controlled VICTORIA trial analyzed the first recruited 74 German adults with nonmetastatic colorectal cancer, a tumor surgery within the past year, and 25-hydroxyvitamin D levels (25(OH)D) < 50 nmol/L. Study participants received a loading dose tailored for a baseline 25(OH)D level and BMI in the first 11 days, followed by a maintenance dose of 2000 IU of vitamin D3 daily until end of trial week 12.

View Article and Find Full Text PDF

Purpose: The use of two-dimensional (2D) printing technologies of drugs on orodispersible films (ODF) can promote dose individualization and facilitate drug delivery in vulnerable patients, including children. We investigated midazolam pharmacokinetics after the administration of 2D-printed ODF.

Methods: Midazolam doses of 0.

View Article and Find Full Text PDF

This study aims to describe social network and social participation and to assess associations with depressive symptoms in older persons with increased risk for dementia in Germany. We conducted a cross-sectional observational study in primary care patients (aged 60−77) as part of a multicenter cluster-randomized controlled trial (AgeWell.de).

View Article and Find Full Text PDF

Background: Although therapeutic drug monitoring of calcineurin inhibitor (CNI) concentrations is performed routinely in clinical practice, an identical concentration may lead to different effects in different patients. Although the quantification of nuclear factor of activated T-cell-regulated gene expression (NFAT-RGE) is a promising method for measuring individual CNI effects, CNI pharmacodynamics are as of yet incompletely understood.

Methods: CNI concentrations and NFAT-RGEs were quantified in 24 healthy volunteers receiving either ciclosporin or tacrolimus in 2 clinical trials.

View Article and Find Full Text PDF

Background: We recently demonstrated that donor-derived modified immune cells (MICs)-PBMCs that acquire immunosuppressive properties after a brief treatment-induced specific immunosuppression against the allogeneic donor when administered before kidney transplantation. We found up to a 68-fold increase in CD19 + CD24 hi CD38 hi transitional B lymphocytes compared with transplanted controls.

Methods: Ten patients from a phase 1 clinical trial who had received MIC infusions before kidney transplantation were followed to post-transplant day 1080.

View Article and Find Full Text PDF

Structured analyses of hospital administrative data may detect potentially preventable adverse drug events (ADE) and therefore are considered promising sources to prevent future harm and estimate cost savings. Whether results of these analyses indeed correspond to ADE that may be preventable in clinical routines needs to be verified. We exemplarily screened all adult inpatients admitted to a German University Hospital (n = 54,032) for International Classification of Diseases-10th revision (ICD-10) diagnoses coding for drug-induced kidney injury (AKI).

View Article and Find Full Text PDF