High burden of RSV and influenza in patients presenting with suspected pneumonia in the emergency room of a German tertiary hospital in fall of 2022.

PURPOSE: Bacterial pneumonia, a major cause of respiratory tract infections (RTI), can be challenging to diagnose and to treat adequately, especially when seasonal viral pathogens co-circulate. The aim of this study was to give a real-world snapshot of the burden of respiratory disease and treatment choices in the emergency department (ED) of a tertiary care hospital in Germany in the fall of 2022. METHODS: Anonymized analysis of a quality control initiative that prospectively documented all patients presenting to our ED with symptoms suggestive of RTI from Nov 7th to Dec 18th, 2022. RESULTS: 243 patients were followed at the time of their ED attendance. Clinical, laboratory and radiographic examination was performed in 92% of patients (224/243). Microbiological work-up to identify causative pathogens including blood cultures, sputum or urine-antigen tests were performed in 55% of patients (n = 134). Detection of viral pathogens increased during the study period from 7 to 31 cases per week, while bacterial pneumonias, respiratory tract infections without detection of a viral pathogen and non-infectious etiologies remained stable. A high burden of bacterial and viral co-infections became apparent (16%, 38/243), and co-administration of antibiotic and antiviral treatments was observed (14%, n = 35/243). 17% of patients (41/243) received antibiotic coverage without a diagnosis of a bacterial etiology. CONCLUSION: During the fall of 2022, the burden of RTI caused by detectable viral pathogens increased unusually early. Rapid and unexpected changes in pathogen distribution highlight the need for targeted diagnostics to improve the quality of RTI management in the ED.

Pharmacokinetics of meropenem in septic patients on sustained low-efficiency dialysis: a population pharmacokinetic study.

BACKGROUND: The aim of the study was to describe the population pharmacokinetics (PK) of meropenem in critically ill patients receiving sustained low-efficiency dialysis (SLED). METHODS: Prospective population PK study on 19 septic patients treated with meropenem and receiving SLED for acute kidney injury. Serial blood samples for determination of meropenem concentrations were taken before, during and after SLED in up to three sessions per patient. Nonparametric population PK analysis with Monte Carlo simulations were used. Pharmacodynamic (PD) targets of 40% and 100% time above the minimal inhibitory concentration (f T > MIC) were used for probability of target attainment (PTA) and fractional target attainment (FTA) against Pseudomonas aeruginosa. RESULTS: A two-compartment linear population PK model was most appropriate with residual diuresis supported as significant covariate affecting meropenem clearance. In patients without residual diuresis the PTA for both targets (40% and 100% f T > MIC) and susceptible P. aeruginosa (MIC ≤ 2 mg/L) was > 95% for a dose of 0.5 g 8-hourly. In patients with a residual diuresis of 300 mL/d 1 g 12-hourly and 2 g 8-hourly would be required to achieve a PTA of > 95% and 93% for targets of 40% f T > MIC and 100% f T > MIC, respectively. A dose of 2 g 8-hourly would be able to achieve a FTA of 97% for 100% f T > MIC in patients with residual diuresis. CONCLUSIONS: We found a relevant PK variability for meropenem in patients on SLED, which was significantly influenced by the degree of residual diuresis. As a result dosing recommendations for meropenem in patients on SLED to achieve adequate PD targets greatly vary. Therapeutic drug monitoring may help to further optimise individual dosing. TRIAL REGISTRATION: Clincialtrials.gov, NCT02287493 .

Population pharmacokinetics and dosing simulations of ceftazidime in critically ill patients receiving sustained low-efficiency dialysis.

Objectives: To describe the population PKs of ceftazidime in critically ill patients receiving sustained low-efficiency dialysis (SLED). Patients and methods: This study was performed in ICUs of a university hospital. We collected blood samples during three consecutive days of SLED sessions in patients receiving ceftazidime. Concentration versus time curves were analysed using a population PKs approach with Pmetrics ® . Monte Carlo simulation for the first 24 h including a 6 h SLED session was performed with the final model. The fractional target attainment against the MIC of Pseudomonas aeruginosa was executed using targets of 50 and 100% fT > MIC . Results: In total, 211 blood samples of 16 critically ill patients under SLED were collected. SLED treatments were 299.3 (68.4) min in duration. A two-compartment linear population PK model was most appropriate. The mean (SD) CL of ceftazidime on SLED, and off SLED were 5.32 (3.2), 1.06 (1.0) L/h respectively. The PTA for 50% fT > MIC for a dose of 1 g intravenously every 8 h was 98%. Assuming a target of 100% fT > MIC a dose of 2 g every 12 h covers isolates with MIC ≤8 mg/L with a PTA of 96%. Conclusion: In critically ill patients receiving SLED, ceftazidime 1 g every 8 h and ceftazidime 2 g every 12 h appear to be sufficient for achieving traditional (50% fT > MIC ) and aggressive PD targets (100% fT > MIC ) for susceptible isolates (MIC ≤8 mg/L), respectively.

Risk factors for excessively prolonged meropenem use in the intensive care setting: a case-contol study.

BACKGROUND: Inappropriate use of broad-spectrum antimicrobials affects adversely both the individual patient and the general public. The aim of the study was to identify patients at risk for excessively prolonged carbapenem treatment in the ICU as a target for antimicrobial stewardship interventions. METHODS: Case-control study in a network of 11 ICUs of a university hospital. Patients with uninterrupted meropenem therapy (MT) > 4 weeks were compared to controls. Controls were defined as patients who stayed on the ICU > 4 weeks and received meropenem for ≤ 2 weeks. Associations between case-control status and potential risk factors were determined in a multivariate logistic regression model. RESULTS: Between 1st of January 2013 and 31st of December 2015, we identified 36 patients with uninterrupted MT > 4 weeks. Patients with prolonged MT were more likely to be surgical patients (72.2% of cases vs. 31.5% of controls; p ≤ 0.001) with peritonitis being the most common infection (n = 16, 44.4%). In the multivariate logistic regression model colonization with multidrug-resistant (MDR) Gram-negative bacteria (OR 7.52; 95% CI 1.88-30.14, p = 0.004) and the type of infection (peritonitis vs. pneumonia: OR 16.96, 95% CI 2.95-97.49) were associated with prolonged MT. CONCLUSION: Surgical patients with peritonitis and patients with known colonization with MDR Gram-negative bacteria are at risk for excessively prolonged carbapenem therapy and represent an important target population for antimicrobial stewardship interventions.

[Formal criteria for good prescribing in the hospital]. / Formale Kriterien für eine gute Verordnung im stationären Bereich.

The provision of drugs to hospitalised patients is a complex process with the involvement of different healthcare professionals. As pharmacotherapy is (1) one of the most common medical interventions, (2) a high-risk procedure, and (3) affects the majority of hospitalised patients, medication errors have sustainable impact on patient safety. Although medication errors can occur at different stages of drug use (prescribing, dispensing, administration), they are most likely within the prescribing process. According to the Reason's model of accident causation, these errors can be divided into active failures, error-provoking conditions, and latent conditions. Commonly, the complex interaction between lacking knowledge and/or experience, rule-based mistakes, skill-based slips and memory lapses, inadequate working environment (exessive work load, fatigue) as well as poor communication and safety culture is causative for prescribing errors. Therefore, good prescribing should include the following items: Adherence to formal criteria (e. g. avoidance of abbreviations), performance of medication reconciliation, implementation of an electronic prescribing system (computerised physician order entry, CPOE) - preferably combined with a clinical decision support system (CDSS), education and training as well as the establishment of a positive error management culture. The implementation of recommendations to reduce prescribing errors is described on the basis of established processes in hospitals.

Medication complexity, prescription behaviour and patient adherence at the interface between ambulatory and stationary medical care.

PURPOSE: A hospital stay is often accompanied by changes in medication therapy. The purpose of this study was to investigate the impact of a transfer across the interfaces on the complexity of therapeutic regimens and patient adherence as well as the attitudes of patients and general practitioners (GPs) towards pharmacotherapies. METHODS: This was a prospective observational study that analysed the complexity of medication therapies and the adherence and attitudes of internal medicine and urology patients towards their medication(s) at three time points (hospital admission, discharge and 6 weeks after discharge). GPs of the patients recruited to the study were questioned about the follow-up medication therapy and their opinion on the medication prescribed in hospital. RESULTS: At the time of hospital admission, 60.2 % of the study population were nonadherent. During hospitalization, the number decreased to 37.6 %, but increased to 61.2 % 6 weeks after discharge. Changes in the overall complexity of the therapy regimens were marginal and not statistically significant. Of the long-term medication regimens, 48.6 % were modified during hospital stay. The patients preferred regimens with a minimum of drug administrations. GPs stated to be willing to continue hospital prescriptions but were restricted by financial budgets. CONCLUSION: The results of this study confirm that an increase in adherence during a hospital stay is only transient, underlining the need for interventions to ameliorate medication adherence. They also suggest that patients prefer simple regimens. Although GPs are willing to consider their patient's preferences on pharmacotherapy, they state limitations due to financial budgets. Further studies are needed that investigate the extent to which medication therapies can be simplified and the effect of simplification on adherence.

Clinical pharmacy services in critical care: results of an observational study comparing ward-based with remote pharmacy services.

BACKGROUND: Pharmacists are essential team members in critical care and contribute to the safety of pharmacotherapy for this vulnerable group of patients, but little is known about remote pharmacy services in intensive care units (ICU). AIM: We compared the acceptance of pharmacist interventions (PI) in ICU patients working remotely with ward-based service. We evaluated both pharmacy services, including further information on PI, including reasons, actions and impact. METHOD: Over 5 months, a prospective single-centre observational study divided into two sequential phases (remote and ward-based) was performed on two ICU wards at a university hospital. After a structured medication review, PI identified were addressed to healthcare professionals. For documentation, the national database (ADKA-DokuPIK) was used. Acceptance was used as the primary endpoint. All data were analysed using descriptive methods. RESULTS: In total, 605 PI resulted from 1023 medication reviews. Acceptance was 75% (228/304) for remote and 88% (265/301; p < 0.001) for ward-based services. Non-inferiority was not demonstrated. Most commonly, drug- (44% and 36%) and dose-related (36% and 35%) reasons were documented. Frequently, drugs were stopped/paused (31% and 29%) and dosage changed (31% and 30%). PI were classified as "error, no harm" (National Coordinating Council for Medication Error Reporting and Prevention [NCC MERP] categories B to D; 83% and 81%). The severity and clinical relevance were at least ranked as "significant" (68% and 66%) and at least as "important" for patients (77% and 83%). CONCLUSION: The way pharmacy services are provided influences the acceptance of PI. Remote pharmacy services may be seen as an addition, but acceptance rates in remote services failed to show non-inferiority.

Development of an immediate release excipient composition for 3D printing via direct powder extrusion in a hospital.

3D printing offers the possibility to prepare personalized tablets on demand, making it an intriguing technology for hospital pharmacies. For the implementation of 3D-printed tablets into the digital Closed Loop Medication Management system, the required tablet formulation and development of the manufacturing process as well as the pharmaceutical validation were conducted. The goal of the formulation development was to enable an optimal printing process and rapid dissolution of the printed tablets for the selected model drugs Levodopa/Carbidopa. The 3D printed tablets were prepared by direct powder extrusion. Printability, thermal properties, disintegration, dissolution, physical properties and storage stability were investigated by employing analytical methods such as HPLC-UV, DSC and TGA. The developed formulation shows a high dose accuracy and an immediate drug release for Levodopa. In addition, the tablets exhibit high crushing strength and very low friability. Unfortunately, Carbidopa did not tolerate the printing process. This is the first study to develop an immediate release excipient composition via direct powder extrusion in a hospital pharmacy setting. The developed process is suitable for the implementation in Closed-Loop Medication Management systems in hospital pharmacies and could therefore contribute to medication safety.

A Unified Data Architecture for Assessing Motor Symptoms in Parkinson's Disease.

INTRODUCTION: The diagnosis and treatment of Parkinson's disease depend on the assessment of motor symptoms. Wearables and machine learning algorithms have emerged to collect large amounts of data and potentially support clinicians in clinical and ambulant settings. STATE OF THE ART: However, a systematical and reusable data architecture for storage, processing, and analysis of inertial sensor data is not available. Consequently, datasets vary significantly between studies and prevent comparability. CONCEPT: To simplify research on the neurodegenerative disorder, we propose an efficient and real-time-optimized architecture compatible with HL7 FHIR backed by a relational database schema. LESSONS LEARNED: We can verify the adequate performance of the system on an experimental benchmark and in a clinical experiment. However, existing standards need to be further optimized to be fully sufficient for data with high temporal resolution.

Ciprofloxacin in Patients Undergoing Extracorporeal Membrane Oxygenation (ECMO): A Population Pharmacokinetic Study.

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.

The impact of pharmacists' interventions within the Closed Loop Medication Management process on medication safety: An analysis in a German university hospital.

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.

Development of the "Hamburg Best Practice Guidelines for ICV-Enzyme Replacement therapy (ERT) in CLN2 Disease" Based on 6 Years Treatment Experience in 48 Patients.

Intracerebroventricular enzyme replacement therapy (ICV-ERT) for CLN2 disease represents the first approved treatment for neuronal ceroid lipofuscinosis (NCL) diseases. It is the first treatment where a recombinant lysosomal enzyme, cerliponase alfa, is administered into the lateral cerebral ventricles to reach the central nervous system, the organ affected in CLN2 disease. If untreated, CLN2 children show first symptoms such as epilepsy and language developmental delay at 2-4 years followed by rapid loss of motor and language function, vision loss, and early death. Treatment with cerliponase alfa has shown to slow the rapid neurologic decline. However, the mode of administration by 4 hour-long intracerebroventricular infusions every 14 days represents a potentially greater risk of infection compared to intravenous enzyme replacement therapies. The Hamburg NCL Specialty Clinic was the first site worldwide to perform intracerebroventricular enzyme replacement therapy in children with CLN2 disease. In order to ensure maximum patient safety, we analysed data from our center from more than 3000 intracerebroventricular enzyme replacement therapies in 48 patients over 6 years with regard to the occurrence of device-related adverse events and device infections. Since starting intracerebroventricular enzyme replacement therapy, we have also developed and continuously improved the "Hamburg Best Practice Guidelines for ICV-Enzyme Replacement Therapy (ERT) in CLN2 Disease." Results from this study showed low rates for device-related adverse events and infections with 0.27% and 0.33%, respectively. Therefore, following our internal procedural guidelines has shown to improve standardization and patient safety of intracerebroventricular enzyme replacement therapy for CLN2 disease.

Non-random relations in drug use expressed as patterns comprising prescription and over-the-counter drugs in multimorbid elderly patients in primary care: Data of the exploratory analysis of the multicentre, observational cohort study MultiCare.

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.

Impact of Inaccurate Documentation of Sampling and Infusion Time in Model-Informed Precision Dosing.

BACKGROUND: Routine 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. METHODS: A 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. RESULTS: On 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 <0.4 and thus patients at risk of undertreatment), while the accurate model gave precise estimates of the indices across all simulated patients. CONCLUSIONS: Even 5-minute-uncertainties caused bias and significant imprecision of primary population and individual PK parameters. Thus, our results underline the importance of accurate documentation of time.

Potentially Inappropriate Medication Use in Multimorbid Elderly Inpatients: Differences Between the FORTA, PRISCUS and STOPP Ratings.

BACKGROUND: Several classifications to identify and avoid use of potentially inappropriate medications (PIMs) in the elderly have been published. To what extent these classifications match each other and whether there are differences in the prevalence of PIM use at admission, during the inpatient stay and at discharge are largely unreported. OBJECTIVES: To determine the PIM prevalence in elderly patients at a university hospital, with a special focus on different classification systems and the chronological sequence, and to examine a possible association between PIM use and the reason for admission, as well as severe side effects and consequences of PIM use during hospitalization. METHODS: On the basis of the criteria provided by FORTA (Fit for the Aged), PRISCUS (Latin for 'time-honoured') and STOPP (Screening Tool of Older Persons' Potentially Inappropriate Prescriptions), medication in patients over the age of 65 years was screened retrospectively within four point prevalence analyses at admission, during the inpatient stay and at discharge. Evaluation of a possible association between PIM use and the primary diagnosis or severe side effects during hospitalization was performed according to an analysis using the World Health Organization Uppsala Monitoring Centre system for standardized case causality assessment. RESULTS: Of 200 patients, 176 (88 %) received at least one PIM at admission, during the inpatient stay and/or at discharge (116 patients according to FORTA, 113 according to PRISCUS and 138 according to STOPP). When the PIM prevalence was compared between the three different sets of criteria, STOPP identified significantly more patients receiving PIMs than FORTA (P = 0.022) and PRISCUS (P = 0.010). At the patient level and at the drug level, the use of PIMs increased during the inpatient stay; however, the PIM prevalence was similar at admission and at discharge, both at the patient level and at the drug level. CONCLUSION: Medication is rated significantly differently by FORTA, PRISCUS and STOPP. In addition, a significant rise in prescribing of PIMs during the inpatient stay illustrates that a reduction in PIM use during the inpatient stay is essential, as it is known that avoiding PIM use in older adults is one strategy to decrease the risk of adverse events.

Comparing and combining naltrexone and acamprosate in relapse prevention of alcoholism: a double-blind, placebo-controlled study.

BACKGROUND: Naltrexone and acamprosate have been shown to be effective in relapse prevention of alcoholism via different pharmacologic mechanisms. Since it remains uncertain whether both substances are equally efficient and whether a combination of both drugs potentiates the efficacy, we conducted the first published controlled study comparing and combining both compounds. METHODS: After detoxification, 160 patients with alcoholism participated in a randomized, double-blind, placebo-controlled protocol. Patients received naltrexone, acamprosate, naltrexone plus acamprosate, or placebo for 12 weeks. Patients were assessed weekly by interview, self-report, questionnaires, and laboratory screening. Time to first drink, time to relapse, and the cumulative abstinence time were the primary outcome measures. RESULTS: Naltrexone, acamprosate, and the combined medication were significantly more effective than placebo. Comparing the course of nonrelapse rates between naltrexone and acamprosate, the naltrexone group showed a tendency for a better outcome regarding time to first drink and time to relapse. The combined medication was most effective with significantly lower relapse rates than placebo and acamprosate but not naltrexone. CONCLUSIONS: The results of this study support the efficacy of pharmacotherapeutic strategies in the relapse prevention of alcoholism. Naltrexone and acamprosate, especially in combination, considerably enhance the potential of relapse prevention.

Reducing cardiovascular medication complexity in a German university hospital: effects of a structured pharmaceutical management intervention on adherence.

BACKGROUND: Patient adherence is necessary for successful medication therapy. However, highly complex medication regimens may lead to poor adherence, which decreases the effectiveness of treatment and often results in treatment failure, excessive morbidity and mortality, and higher costs.  OBJECTIVE: To examine whether patient adherence can be increased indirectly through reducing medication complexity by (a) pharmaceutical counseling of hospital medical staff and (b) additional information in the discharge letter for the primary care provider (PCP) about the simplified discharge medication.  METHODS: At the Medical Center Hamburg-Eppendorf, a tertiary care university hospital in Germany, 240 chronically ill inpatients with hypertension, diabetes, and/or dyslipidemia were enrolled in this prospective, semirandomized study. For the intervention group, hospital doctors were counseled by a clinical pharmacist on feasible simplifications of cardiovascular and antidiabetic medications. In 1 randomized subgroup, the PCP received additional explanatory information in the discharge letter. Adherence (self-reporting using the Medication Adherence Rating Scale [MARS-D]) and medication complexity (using the Medication Regimen Complexity Index [MRCI-D]) were recorded at admission to the hospital, discharge from the hospital, and 6 weeks after discharge. Patient quality of life (QoL) and satisfaction with information about medications were assessed at admission and after discharge.   RESULTS: At discharge, the medication regimen in the intervention group was significantly less complex than in the comparison group. Yet, 6 weeks  after discharge, the complexity of the outpatient medication had increased to values similar to the comparison group, unless the PCP received additional information in the discharge letter. Propensity adjusted complete adherence rates at discharge were slightly, but not significantly, higher in the intervention group than in the comparison group. Within the intervention group, complete adherence was more frequent in the subgroup with additional information for the PCP. Patient QoL and satisfaction with information were comparable in both groups.   CONCLUSION: The complexity of cardiovascular and antidiabetic hospital medications can be reduced by counseling the hospital doctors. However, for a sustainable simplification of outpatient medication, the PCPs must receive explicit information about the modifications. Patient adherence was not significantly influenced by this intervention. To verify these results, further research with objective measures of adherence and in patients with other diseases is needed. 

Incomplete medication adherence of chronically ill patients in German primary care.

BACKGROUND: Incomplete medication adherence is a major problem in health care worldwide. Patients who adhere to medical treatment have a better prognosis and create fewer costs. OBJECTIVE: To assess the degree of incomplete adherence of chronically ill routine primary care patients in a German setting and analyze the association between incomplete medication adherence, as well as clinical and sociodemographic patient characteristics. METHODS: In a cross-sectional survey, chronically ill patients were asked to assess their adherence in primary care retrospectively using the Medication Adherence Report Scale (MARS-D) questionnaire. To investigate the association of incomplete adherence with sociodemographic and clinical data, univariate and multivariate analyses were conducted. RESULTS: In total, 62.1% of 190 patients were categorized as incompletely adherent. The mean MARS-D score was 23.5 (standard deviation = 2.7). Analyses revealed no statistically significant associations at P < 0.05 between degree of adherence and patient characteristics. The total explained variance amounted to 11.8% (Nagelkerke's R(2) = 0.118) in the multivariate analysis. CONCLUSION: Previously reported results regarding associations of sociodemographic and clinical data with incomplete medication adherence could not be confirmed for this sample of chronically ill patients. In order to be able to provide guidelines for the reduction of incomplete medication adherence in German primary care, further research is needed.

Development and psychometric evaluation of the German version of the Medication Regimen Complexity Index (MRCI-D).

BACKGROUND: Several factors contribute to the complexity of pharmacotherapeutic regimens, like the total number of medications to be taken, the number of dosage units to take at a time, dosage frequency, as well as specific directions concerning the administration. The Medication Regimen Complexity Index (MRCI) is a validated instrument developed in English for the measurement of the complexity of a given pharmacotherapeutic regimen. OBJECTIVES: Translation of the MRCI into German and evaluation of the translated instrument (MRCI-D) in order to make it more easily accessible for use in German practice and research. METHODS: The process of validation included the translation of the English version to German, back-translation into English, comparison of the back-translated and the original versions, pre-tests, and pilot-testing of the German version by three raters using 20 medication regimens for inpatients. The subsequent psychometric evaluation included the calculation of inter-rater and test-retest reliability, as well as the assessment of convergent validity. RESULTS: The number of medications correlated highly and statistically significantly with the MRCI-D score (0.91, P < 0.001), indicating sufficient convergent validity of the instrument. Both inter-rater and test-retest reliability were very high (intraclass correlation coefficients above 0.80 in all cases). CONCLUSION: Our results demonstrate that the German version of the MRCI reflects the complexity of therapeutic regimens with similar validity and reliability as the established English version. Thus, it may be a valuable tool to analyse therapeutic regimens in both clinical practice and science.

Drug dosing and monitoring in obese patients undergoing allogenic stem cell transplantation.

BACKGROUND: The effects of physiological changes in patients with obesity on pharmacokinetic parameters and the time course of drug response, especially in the field of haematology/oncology, are poorly understood. For some antimicrobial drugs, dosing considerations exist, while for cytostatic drugs, dose modifications for obese patients are not consistently recommended. Glomerular filtration rate and renal perfusion appear to be similar in obese and normal weight individuals, thus elimination of hydrophilic and extensively renally cleared drugs mainly depends upon creatinine clearance. AIM OF THE REVIEW: To provide information about drug dosing in morbidly obese patients undergoing allogenic haematopoietic stem cell transplantation and to develop dosing recommendations for those patients, based on literature data, pharmacokinetic properties and own experiences. METHOD: A review on the literature on drug dosing in obese patients as well as on the pharmacokinetic properties of drugs which are supposed to be used in the field of stem cell transplantation was combined with own data on drug dosing and pharmacokinetic drug monitoring in a morbidly obese patient undergoing matched-unrelated allogenic peripheral blood stem cell transplantation. RESULTS: For hydrophilic and extensively renally cleared drugs (e.g. piperacillin/sulbactam, cotrimoxazole, fludarabine) standard dosages for adult patients or dosing based on ideal body weight (IBW) (e.g. aciclovir, methotrexate) can be used. For ciclosporin and digitoxin we could show that high initial doses are needed to achieve sufficient plasma concentrations. After steady state distribution was completed, maintenance doses comparable to normal weight patients are sufficient. Likewise, distribution of enoxaparin and phenytoin seems to take longer in obese patients. Dosing recommendations of 25 drugs that can be used in morbidly obese patients undergoing allogenic stem cell transplantation are given. CONCLUSIONS: Pharmacotherapy in morbidly obese patients undergoing allogenic stem cell transplantation is possible, if pharmacokinetic properties of the drugs are considered and close monitoring of plasma concentrations is performed.