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1دورية أكاديمية
المؤلفون: Claudia Langebrake, Karl Gottfried, Adrin Dadkhah, Jan Eggert, Tobias Gutowski, Moritz Rosch, Nils Schönbeck, Christopher Gundler, Sylvia Nürnberg, Frank Ückert, Michael Baehr
المصدر: Clinical eHealth, Vol 6, Iss , Pp 3-9 (2023)
مصطلحات موضوعية: 3D printing of drugs, Precision dosing, Medication management, Hospital pharmacy, Machine-learning, Smart wearables, Medicine
الوصف: 3D-printing of medicines is an innovative manufacturing method that is characterised by a high degree of digitalisation and automation and enables patient-specific care. Its integration into routine healthcare processes currently fails mainly due to the requirements of a digital environment. Our hospital was the first hospital in Europe to introduce a fully comprehensive patient record in 2011 and to digitalise and automate the drug supply process.The aim of our study is to evaluate the integration of a machine-learning assisted 3D printing of medicines into the already existing, fully digital medication process of the hospital (closed-loop medication management, CLMM). Here, the design of this feasibility study and first results of subprojects are presented.First, a suitable and clinically relevant active ingredient (levodopa/carbidopa) was identified in a multi-step approach by an interdisciplinary panel of experts using defined evaluation criteria, taking into account galenic, clinical and machine learning aspects. In the next step, a galenic formulation using a suitable printing technology for manufacturing a drug according to pharmaceutical quality criteria in different dosages is to be developed and to be evaluated for compliance with quality criteria according to the European Pharmacopoeia. Furthermore, an IT concept was developed and adapted to the hospital's current IT infrastructure. Likewise, a machine learning algorithm is to be developed to determine the optimal dose for each individual patient using data from smart wearable devices. For this purpose, a clinical trial was set up as a proof-of-principle study for the use of wearables to detect and grade clinical symptoms from Parkinson’s Disease. Finally, the process is to be connected to the digital medication process of the hospital taking into account regulatory requirements.Thus, this interdisciplinary feasibility study will provide important insights into the possibilities of integrating patient-specific 3D printing of medicines into everyday clinical practice in the hospital.
وصف الملف: electronic resource
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2دورية أكاديمية
المؤلفون: Franziska Marquard, Claudia Langebrake, Dietlinde Janson, Maida Mahmud, Adrin Dadkhah, Nicolaus Kröger, Francis Ayuk
المصدر: Frontiers in Oncology, Vol 13 (2023)
مصطلحات موضوعية: CAR-T-cell therapy, lymphodepletion, GFR < 30ml/min, fludarabine, cyclophosphamide, dialysis, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
الوصف: Acute kidney injury and chronic kidney disease is common in multiple myeloma. Fludarabine which is part of lymphodepletion before CAR-T cell therapy is renally eliminated and its use is not recommended for patients with severe renal impairment defined as a glomerular filtration rate below 30ml/min/1.73m2. We administered fludarabine to a 58-year-old female patient with myeloma-associated severe renal impairment as part of lymphodepletion before Idecabtagen vicleucel infusion. Fludarabine was administered in reduced dose (15mg/m2) and cyclophosphamide with a dose of 300mg/m2 followed by hemodialysis over six hours using a larger filter (FX-100). The therapy was well tolerated with excellent CAR-T cell expansion and complete remission which is ongoing now beyond 12 months.
وصف الملف: electronic resource
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3دورية أكاديمية
المؤلفون: Vivien Berger, Christian Sommer, Peggy Boje, Josef Hollmann, Julia Hummelt, Christina König, Susanne Lezius, Annika van der Linde, Corinna Marhenke, Simone Melzer, Nina Michalowski, Michael Baehr, Claudia Langebrake
المصدر: Frontiers in Pharmacology, Vol 13 (2022)
مصطلحات موضوعية: pharmacy service (hospital), medication therapy management, medication review, patient safety, closed loop medication management, drug related problems (DRP), Therapeutics. Pharmacology, RM1-950
الوصف: Background: Single elements of the Closed Loop Medication Management process (CLMM), including electronic prescribing, involvement of clinical pharmacists (CPs), patient individual logistics and digital administration/documentation, have shown to improve medication safety and patient health outcomes. The impact of the complete CLMM on patient safety, as reflected in pharmacists’ interventions (PIs), is largely unknown.Aim: To evaluate the extent and characterization of routine PIs performed by hospital-wide CPs at a university hospital with an implemented CLMM.Methods: This single-center study included all interventions documented by CPs on five self-chosen working days within 1 month using the validated online-database DokuPIK (Documentation of Pharmacists’ Interventions in the Hospital). Based on different workflows, two groups of CPs were compared. One group operated as a part of the CLMM, the “Closed Loop Clinical Pharmacists” (CL-CPs), while the other group worked less dependent of the CLMM, the “Process Detached Clinical Pharmacists” (PD-CPs). The professional experience and the number of medication reviews were entered in an online survey. Combined pseudonymized datasets were analyzed descriptively after anonymization.Results: A total of 1,329 PIs were documented by nine CPs. Overall CPs intervened in every fifth medication review. The acceptance rate of PIs was 91.9%. The most common reasons were the categories “drugs” (e.g., indication, choice of formulation/drug and documentation/transcription) with 42.7%, followed by “dose” with 29.6%. One-quarter of PIs referred to the therapeutic subgroup “J01 antibacterials for systemic use.” Of the 1,329 underlying PIs, 1,295 were classified as medication errors (MEs) and their vast majority (81.5%) was rated as “error, no harm” (NCC MERP categories B-D). Among PIs performed by CL-CPs (n = 1,125), the highest proportion of errors was categorized as B (56.5%), while in the group of PIs from PD-CPs (n = 170) errors categorized as C (68.2%) dominated (p < 0.001).Conclusion: Our study shows that a structured CLMM enables CPs to perform a high number of medication reviews while detecting and solving MEs at an early stage before they can cause harm to the patient. Based on key quality indicators for medication safety, the complete CLMM provides a suitable framework for the efficient medication management of inpatients.
وصف الملف: electronic resource
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4دورية أكاديمية
المؤلفون: Caroline Krüger, Ingmar Schäfer, Hendrik van den Bussche, Michael Baehr, Horst Bickel, Angela Fuchs, Jochen Gensichen, Wolfgang Maier, Steffi G. Riedel-Heller, Hans-Helmut König, Anne Dahlhaus, Gerhard Schön, Siegfried Weyerer, Birgitt Wiese, Wolfgang von Renteln-Kruse, Claudia Langebrake, Martin Scherer
المصدر: European Journal of General Practice, Vol 27, Iss 1, Pp 119-129 (2021)
مصطلحات موضوعية: pharmacotherapy, geriatrics, multimorbidity, polypharmacy, primary care, Medicine (General), R5-920
الوصف: Background The elderly population deals with multimorbidity (three chronic conditions) and increasinged drug use with age. A comprehensive characterisation of the medication – including prescription and over-the-counter (OTC) drugs – of elderly patients in primary care is still insufficient. Objectives This study aims to characterise the medication (prescription and OTC) of multimorbid elderly patients in primary care and living at home by identifying drug patterns to evaluate the relationship between drugs and drug groups and reveal associations with recently published multimorbidity clusters of the same cohort. Methods MultiCare was a multicentre, prospective, observational cohort study of 3189 multimorbid patients aged 65 to 85 years in primary care in Germany. Patients and general practitioners were interviewed between 2008 and 2009. Drug patterns were identified using exploratory factor analysis. The relations between the drug patterns with the three multimorbidity clusters were analysed with Spearman-Rank-Correlation. Results Patients (59.3% female) used in mean 7.7 drugs; in total 24,535 drugs (23.7% OTC) were detected. Five drug patterns for men (drugs for obstructive pulmonary diseases (D-OPD), drugs for coronary heart diseases and hypertension (D-CHD), drugs for osteoporosis (D-Osteo), drugs for heart failure and drugs for pain) and four drug patterns for women (D-Osteo, D-CHD, D-OPD and drugs for diuretics and gout) were detected. Significant associations between multimorbidity clusters and drug patterns were detectable (D-CHD and CMD: male: ρ = 0.376, CI 0.322–0.430; female: ρ = 0.301, CI 0.624–0.340). Conclusion The drug patterns demonstrate non-random relations in drug use in multimorbid elderly patients and systematic associations between drug patterns and multimorbidity clusters were found in primary care.
وصف الملف: electronic resource
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5دورية أكاديمية
المؤلفون: Gunhild von Amsberg, Mirjam Zilles, Wael Mansour, Philipp Gild, Winfried Alsdorf, Moritz Kaune, Lukas Böckelmann, Jessica Hauschild, Christoph Krisp, Tina Rohlfing, Ceren Saygi, Malik Alawi, Alexandra Zielinski, Claudia Langebrake, Su Jung Oh-Hohenhorst, Sven Perner, Derya Tilki, Hartmut Schlüter, Markus Graefen, Sergey A. Dyshlovoy, Carsten Bokemeyer
المصدر: International Journal of Molecular Sciences, Vol 23, Iss 23, p 14948 (2022)
مصطلحات موضوعية: cisplatin, ifosfamide, paclitaxel, TIP combinational therapy, aggressive variant of prostate cancer, metastatic castration-resistant prostate cancer, Biology (General), QH301-705.5, Chemistry, QD1-999
الوصف: Significant progress has been achieved in the treatment of metastatic castration-resistant prostate cancer (mCRPC). However, results in patients with aggressive variant prostate cancer (AVPC) have been disappointing. Here, we report retrospectively collected data from intensively pretreated AVPC patients (n = 17; 88.2% visceral metastases; 82% elevation of neuroendocrine markers) treated with salvage chemotherapy consisting of cisplatin, ifosfamide, and paclitaxel (TIP). At the interim analysis, 60% of patients showed radiographic response or stable disease (PFS = 2.5 months; OS = 6 months). In men who responded to chemotherapy, an OS > 15 months was observed. Preclinical analyses confirmed the high activity of the TIP regimen, especially in docetaxel-resistant prostate cancer cells. This effect was primarily mediated by increased cisplatin sensitivity in the emergence of taxane resistance. Proteomic and functional analyses identified a lower DNA repair capacity and cell cycle machinery deficiency to be causative. In contrast, paclitaxel showed inconsistent effects, partially antagonizing cisplatin and ifosfamide in some AVPC models. Consequently, paclitaxel has been excluded from the TIP combination for future patients. In summary, we report for the first time the promising efficacy of TIP as salvage therapy in AVPC. Our preclinical data indicate a pivotal role for cisplatin in overcoming docetaxel resistance.
وصف الملف: electronic resource
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6دورية أكاديمية
المؤلفون: Adrin Dadkhah, Sebastian Georg Wicha, Nicolaus Kröger, Alexander Müller, Christoph Pfaffendorf, Maria Riedner, Anita Badbaran, Boris Fehse, Claudia Langebrake
المصدر: Pharmaceutics, Vol 14, Iss 6, p 1145 (2022)
مصطلحات موضوعية: busulfan, sulfolane, myelofibrosis, population pharmacokinetics, Pharmacy and materia medica, RS1-441
الوصف: For patients with myelofibrosis, allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only curative treatment to date. Busulfan-based conditioning regimens are commonly used, although high inter-individual variability (IIV) in busulfan drug exposure makes individual dose selection challenging. Since data regarding the IIV in patients with myelofibrosis are sparse, this study aimed to develop a population pharmacokinetic (PopPK) model of busulfan and its metabolite sulfolane in patients with myelofibrosis. The influence of patient-specific covariates on the pharmacokinetics of drug and metabolite was assessed using non-linear mixed effects modeling in NONMEM®. We obtained 523 plasma concentrations of busulfan and its metabolite sulfolane from 37 patients with myelofibrosis. The final model showed a population clearance (CL) and volume of distribution (Vd) of 0.217 L/h/kg and 0.82 L/kg for busulfan and 0.021 L/h/kg and 0.65 L/kg for its metabolite. Total body weight (TBW) and a single-nucleotide polymorphism of glutathione-S-transferase A1 (GSTA1 SNP) displayed a significant impact on volume of distribution and metabolite clearance, respectively. This is the first PopPK-model developed to describe busulfan’s pharmacokinetics in patients with myelofibrosis. Incorporating its metabolite sulfolane into the model not only allowed the characterization of the covariate relationship between GSTA1 and the clearance of the metabolite but also improved the understanding of busulfan’s metabolic pathway.
وصف الملف: electronic resource
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7دورية أكاديمية
المؤلفون: Claudia Langebrake, Gerhard Schön, Ingmar Schäfer, Wolfgang von Renteln-Kruse, Birgitt Wiese, Jochen Gensichen, Caroline Krüger, Hendrik van den Bussche, Horst Bickel, Angela Fuchs, Wolfgang Maier, Karola Mergenthal, Siegfried Weyerer
المصدر: BMJ Open, Vol 11, Iss 3 (2021)
مصطلحات موضوعية: Medicine
الوصف: Objectives The aims of our study were to examine the anticholinergic drug use and to assess the association between anticholinergic burden and cognitive function in the multimorbid elderly patients of the MultiCare cohort.Setting MultiCare was conducted as a longitudinal cohort study in primary care, located in eight different study centres in Germany.Participants 3189 patients (59.3% female).Primary and secondary outcome measures Baseline data were used for the following analyses. Drugs were classified according to the well-established anticholinergic drug scale (ADS) and the recently published German anticholinergic burden (German ACB). Cognitive function was measured using a letter digit substitution test (LDST) and a mixed-effect multivariate linear regression was performed to calculate the influence of anticholinergic burden on the cognitive function.Results Patients used 1764 anticholinergic drugs according to ADS and 2750 anticholinergics according to the German ACB score (prevalence 38.4% and 53.7%, respectively). The mean ADS score was 0.8 (±1.3), and the mean German ACB score was 1.2 (±1.6) per patient. The most common ADS anticholinergic was furosemide (5.8%) and the most common ACB anticholinergic was metformin (13.7%). The majority of the identified anticholinergics were drugs with low anticholinergic potential: 80.2% (ADS) and 73.4% (ACB), respectively. An increasing ADS and German ACB score was associated with reduced cognitive function according to the LDST (−0.26; p=0.008 and −0.24; p=0.003, respectively).Conclusion Multimorbid elderly patients are in a high risk for using anticholinergic drugs according to ADS and German ACB score. We especially need to gain greater awareness for the contribution of drugs with low anticholinergic potential from the cardiovascular system. As anticholinergic drug use is associated with reduced cognitive function in multimorbid elderly patients, the importance of rational prescribing and also deprescribing needs to be further evaluated.Trial registration number ISRCTN89818205.
وصف الملف: electronic resource
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8دورية أكاديمية
المؤلفون: Dzenefa Alihodzic, Sebastian G. Wicha, Otto R. Frey, Christina König, Michael Baehr, Dominik Jarczak, Stefan Kluge, Claudia Langebrake
المصدر: Pharmaceutics, Vol 14, Iss 5, p 965 (2022)
مصطلحات موضوعية: ciprofloxacin, population pharmacokinetics, ECMO, ARDS, NONMEM, therapeutic drug monitoring, Pharmacy and materia medica, RS1-441
الوصف: Extracorporeal membrane oxygenation (ECMO) is utilized to temporarily sustain respiratory and/or cardiac function in critically ill patients. Ciprofloxacin is used to treat nosocomial infections, but data describing the effect of ECMO on its pharmacokinetics is lacking. Therefore, a prospective, observational trial including critically ill adults (n = 17), treated with ciprofloxacin (400 mg 8–12 hourly) during ECMO, was performed. Serial blood samples were collected to determine ciprofloxacin concentrations to assess their pharmacokinetics. The pharmacometric modeling was performed (NONMEM®) and utilized for simulations to evaluate the probability of target attainment (PTA) to achieve an AUC0–24/MIC of 125 mg·h/L for ciprofloxacin. A two-compartment model most adequately described the concentration-time data of ciprofloxacin. Significant covariates on ciprofloxacin clearance (CL) were plasma bicarbonate and the estimated glomerular filtration rate (eGFR). For pathogens with an MIC of ≤0.25 mg/L, a PTA of ≥90% was attained. However, for pathogens with an MIC of ≥0.5 mg/L, plasma bicarbonate ≥ 22 mmol/L or eGFR ≥ 10 mL/min PTA decreased below 90%, steadily declining to 7.3% (plasma bicarbonate 39 mmol/L) and 21.4% (eGFR 150 mL/min), respectively. To reach PTAs of ≥90% for pathogens with MICs ≥ 0.5 mg/L, optimized dosing regimens may be required.
وصف الملف: electronic resource
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9دورية أكاديمية
المؤلفون: Levente Kriston, Cynthia Olotu, Rainer Kiefmann, Claudia Langebrake, Corinna Bergelt, Julia Richter, Moritz Sebastian Schönfeld
المصدر: BMJ Open, Vol 10, Iss 11 (2020)
مصطلحات موضوعية: Medicine
الوصف: Introduction With increasing age, the risk of complications after surgery rises in elderly patients. Furthermore, the prevalence of multimorbidity and polypharmacy rises with age, making this elderly population especially vulnerable for drug-related problems and posing an additional risk for postoperative complications. Still, only few studies have concentrated on investigating how medication safety can be improved in these patients. The aim of this pilot study is to examine the impact of a comprehensive intervention (interprofessional systematic medication therapy management) on medication appropriateness in elderly polymedicated, multimorbid patients during hospital stay for elective surgery.Methods and analysis This pilot study will include a total number of 140 patients. Surgical high-risk patients ≥65 years taking more than five chronic systemic drugs will be recruited consecutively for 9 months in the control group capturing usual care regarding medication history and in-hospital medication therapy management without any study intervention. Recruitment of the intervention group will be conducted for another 9 months. The intervention consists of the following components: an additional medication history by a hospital pharmacist before admission, a subsequent medication review, optimisation of the long-term medication and recommendations to the patient’s general practitioner. A follow-up will be performed 3 months after surgery. As the primary study outcome, medication appropriateness will be measured using the Medication Appropriateness Index.Secondary outcomes are postoperative complications, incidence and frequency of adverse drug reactions and potentially inappropriate medication in the elderly, satisfaction with inpatient and outpatient care, medication reconciliation and health-related quality of life. Multivariable analyses will be used to analyse all quantitative research questions.Ethics and dissemination Ethics approval was obtained by the medical ethics committee of the Medical Chamber of Hamburg (study ID: PV5754). Data will be published in peer-reviewed journals and presented at conferences.Trial registration number The study is registered at www.drks.de: DRKS00014621.
وصف الملف: electronic resource
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10دورية أكاديمية
المؤلفون: Dzenefa Alihodzic, Astrid Broeker, Michael Baehr, Stefan Kluge, Claudia Langebrake, Sebastian Georg Wicha
المصدر: Frontiers in Pharmacology, Vol 11 (2020)
مصطلحات موضوعية: documentation, sampling time, infusion rate, uncertainty, precision dosing, therapeutic drug monitoring, Therapeutics. Pharmacology, RM1-950
الوصف: BackgroundRoutine clinical TDM data is often used to develop population pharmacokinetic (PK) models, which are applied in turn for model-informed precision dosing. The impact of uncertainty in documented sampling and infusion times in population PK modeling and model-informed precision dosing have not yet been systematically evaluated. The aim of this study was to investigate uncertain documentation of (i) sampling times and (ii) infusion rate exemplified with two anti-infectives.MethodsA stochastic simulation and estimation study was performed in NONMEM® using previously published population PK models of meropenem and caspofungin. Uncertainties, i.e. deviation between accurate and planned sampling and infusion times (standard deviation (SD) ± 5 min to ± 30 min) were added randomly in R before carrying out the simulation step. The estimation step was then performed with the accurate or planned times (replacing real time points by scheduled study values). Relative bias (rBias) and root mean squared error (rRMSE) were calculated to determine accuracy and precision of the primary and secondary PK parameters on the population and individual level. The accurate and the misspecified (using planned sampling times) model were used for Bayesian forecasting of meropenem to assess the impact on PK/PD target calculations relevant to dosing decisions.ResultsOn the population level, the estimates of the proportional residual error (prop.-err.) and the interindividual variability (IIV) on the central volume of distribution (V1) were most affected by erroneous records in the sampling and infusion time (e.g. rBias of prop.-err.: 75.5% vs. 183% (meropenem) and 10.1% vs. 109% (caspofungin) for ± 5 vs. ± 30 min, respectively). On the individual level, the rBias of the planned scenario for the typical values V1, Q and V2 increased with increasing uncertainty in time, while CL, AUC and elimination half-life were least affected. Meropenem as a short half-life drug (~1 h) was more affected than caspofungin (~ 9–11 h). The misspecified model provided biased PK/PD target information (e.g. falsely overestimated time above MIC (T > MIC) when true T > MIC was
وصف الملف: electronic resource
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