Clinimetric properties and suitability of selected quality indicators for assessing antibiotic use in hospitalized adults: a multicentre point prevalence study in 24 hospitals in Germany.

OBJECTIVES: The capability to measure and monitor the quality of antibiotic prescribing is an important component of antibiotic stewardship (ABS) programmes. Several catalogues of consensus-based structure and process-of-care quality indicators (QIs) have been proposed, but only a few studies have tested and validated ABS QIs in practice tests. This multicentre study determined the clinimetric properties and suitability of a set of 33 process QIs for ABS that had earlier been developed and in part recommended in a German-Austrian hospital ABS practice guideline. METHODS: Two point prevalence surveys were conducted in a convenience sample of 24 acute care hospitals throughout Germany, and data of all screened adult inpatients with prescription of a systemic antibiotic at a given day (n=4310) were included in the study. For each QI, the following clinimetric properties were assessed: applicability, feasibility, performance, case mix stability and interobserver reliability. RESULTS: Eighteen QIs were considered sufficiently feasible, applicable and reliable, and had adequate room for improvement. The finally selected QIs primarily cover antibiotic therapy of common infections (bloodstream infection, pneumonia and urinary tract infection), while two of the QIs each address surgical prophylaxis and general aspects of antibiotic administration. CONCLUSIONS: Practice tests may be important to test the suitability of consensus process-of-care QIs in the field of hospital ABS. The 18 selected QIs considered suitable enough for hospital ABS in this study should be regarded as priority QIs useful for internal quality control and assurance. More research and additional practice tests may be needed to confirm their suitability for external quality assessment schemes.

False-positive Candida and Aspergillus antigen testing in recipients of allogeneic haematopoietic cell transplantation due to administration of parenteral nutrition and fixed combinations of piperacillin-tazobactam.

False positivity of antigen immunoassays used as an early diagnostic tool to detect invasive fungal infections is known. Interpretation of the assay needs the identification of sources which could affect the specificity of the test. We focused on the influence of parenteral nutrition (PN) and piperacillin-tazobactam (TZP) on fungal immunoassays. Measurable amounts of Candida antigen mannan were detected in several compounds of PN and TZP in a previous in vitro study. In the current study, 84 patients undergoing allogeneic haematopoietic cell transplantation receiving either TZP, PN or both were monitored with Aspergillus and Candida antigen assay. Six patients were analysed closer in a kinetic analysis with more frequent blood sampling to detect mannan. PN in diverse compositions as well as TZP did not increase significantly the amount of mannan and the Aspergillus antigen in serum. We could not confirm the positive results of the in vitro study. Physicians should be aware that mannan antigenemia due to drug infusion could be a transient issue and should be considered in the interpretation of fungal immunoassays, although we could not find clinically relevant effects on mannan levels.

In vitro detection of Candida and Aspergillus antigen in parenteral nutrition and fixed combinations of piperacillin-tazobactam.

BACKGROUND: Screening for Aspergillus (Asp-AG) and Candida antigen (Ca-AG) with immunoassays is established for stem cell recipients at high risk for invasive fungal infections (IFI). While parenteral nutrition (PN) will be applied in case of complications leading to insufficient alimentation, piperacillin-tazobactam (TZP) is started at the onset of febrile neutropenia. OBJECTIVES: The aim of this study was to investigate drug-laboratory interactions between PN and TZP and both immunoassays which could affect the specificity of the assays and lead to the false assumption of an IFI. METHODS: Batches of TZP and PN were tested with both assays in vitro. In total, 380 samples of 83 batches were analysed. RESULTS: None of the examined preparations were tested positive with Asp-AG assay. Measurable amounts of Ca-AG were detected in a lipid emulsion, two different trace element supplements, a fat-soluble vitamin preparation and all tested brands of TZP. CONCLUSIONS: We conclude that false positivity of Asp-AG assay due to TZP and PN does not occur. Cross reactions with Ca-AG assay have been detected in some preparations. The in vivo relevance of Ca-AG positivity has to be reviewed in further studies considering an effect of dilution. Physicians should be aware of a possible cross reaction with Ca-AG assays which could lead to false-positive results.

[Medication safety in hospitals : Integration of clinical pharmacists to reduce drug-related problems in the inpatient setting]. / Arzneimitteltherapiesicherheit im Krankenhaus : Einbindung von Stationsapothekern zur Reduktion von arzneimittelbezogenen Problemen im stationären Medikationsprozess.

Drug-related problems (DRPs) are a significant and often preventable cause for morbidity and mortality. Hospitalization is associated with a high risk for DRPs, especially due to a lack of information transfer at transitions of care. At the same time, interventions during inpatient treatment usually require a change in drug therapy and additionally increase the risk of DRPs. Thereby, DRPs can occur at all levels of the medication process and can be caused by different groups of professionals. One way to improve medication safety in hospitals is to integrate clinical pharmacists into the medication process.According to available data, the integration of a clinical pharmacist in multi-professional teams during admission, hospitalization and discharge can significantly reduce DRPs, costs and increases efficacy of drug therapy. In addition, drug supply with unit-dose systems in combination with digitalization of the medication process can achieve an improvement in medication safety. Improvement in continuity of medical care through a structured medication review and seamless transmission of medically relevant information upon discharge contribute to a significant reduction of hospital readmissions and emergency admissions due to ABPs, as well as health costs. With a university education, the hospital pharmacist specialized in clinical pharmacy is the only professional group that can comprehensively support the physician in the field of drug therapy.

Long-Term Follow-Up and Impact of Comorbidity before Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Relapsed or Refractory Acute Myeloid Leukemia-Lessons Learned from the Prospective BRIDGE Trial.

In patients with relapsed or refractory (r/r) acute myeloid leukemia (AML), allogeneic hematopoietic stem cell transplantation (HSCT) is considered to be the only treatment providing long-term disease control. The BRIDGE trial studied the safety and efficacy of a clofarabine-based salvage therapy before HSCT in patients with r/r AML. Here, we report the long-term follow-up of this phase II multicenter trial and exploratory analyses on the impact of comorbidity on outcome. Eighty-four patients with a median age of 61 years (range, 40 to 75) were enrolled. Patients were scheduled for at least 1 cycle of salvage therapy with CLARA (clofarabine 30 mg/m2; cytarabine 1 g/m2, days 1 to 5). Chemo-responsive patients with a donor received HSCT after first CLARA. The conditioning regimen consisted of clofarabine 30 mg/m2, day -6 to -3, and melphalan 140 mg/m2 day -2. The Eastern Cooperative Oncology Group (ECOG) score, the hematopoietic cell transplantation-specific comorbidity index (HCT-CI), and the Cumulative Illness Rating Scale were obtained at study enrollment as well as before HSCT. Sixty-seven percent of the patients received HSCT within the trial. After a median follow up of 40 months, the estimated 3-year overall survival (OS) for all enrolled patients and those with HSCT within the trial was 40% and 55%, respectively. Relapse-free survival for patients who underwent transplantation with a complete remission afterwards (n = 50) was 48%, calculated from the day of transplantation. In multivariate analysis, both the HCT-CI and ECOG score had a statistically significant impact on OS with a hazard ratio of 1.22 (P = .025)and 1.72 (P = .001), respectively. Using a clofarabine-based salvage therapy combined with early allogeneic HSCT, we were able to achieve good long-term results for patients with r/r AML. In this cohort, both the HCT-CI and the ECOG scores gave prognostic information on OS, showing the feasibility and clinical relevance of comorbidity evaluation at the time of diagnosis of r/r AML patients.

Combined use of an ACE-inhibitor and spironolactone in patients with heart insufficiency. / Risikoreiche Kombination oder leitliniengerechte Verordnung? ACE-Hemmer und Spironolacton: Bei Herzinsuffizienz indiziert.

A patient with cardiac insufficiency takes the ACE-Inhibitor Enalapril as well as Spironolactone regularly. In the interaction monographs of the German ABDA-database there is a note that combined use of these substances should be avoided due to an increased risk of hyperkalemia ­ is there a medication related problem? There is evidence from clinical studies, that combined use of ACE-inhibitors and potassium-sparing agents indeed increases the risk of severe hyperkalemia. The risk seems to be related to the dose of the potassium-sparing agent. However, in patients with cardiac insufficiency NYHA-class II-IV and an ejection fraction of ≤ 35%, the addition of spironolactone to an ACE-inhibitor and betablocking agent reduces mortality and hospitalization for cardiovascular problems. Therefore the combination is indicated in these patients. To minimize the risk for severe adverse events close monitoring of serum potassium and renal function is mandatory. Moreover, additional risk factors for hyperkalemia such as intake of potassium supplements or NSAID should be avoided.

Cost-effectiveness comparison of prophylactic octreotide and pasireotide for prevention of fistula after pancreatic surgery.

PURPOSE: Postoperative pancreatic fistula (POPF) is a major determinant of pancreatic surgery outcome, and prevention of POPF is a relevant clinical challenge. The aim of the present study is to compare the cost-effectiveness of octreotide and pasireotide for POPF prophylaxis. METHODS: A systematic literature review and meta-analysis and a retrospective patient cohort provided the data. Cost-effectiveness was calculated by the incremental cost-effectiveness ratio (ICER) and by decision tree modelling of hospital stay duration. RESULTS: Six randomised trials on octreotide (1255 patients) and one trial on pasireotide (300 patients) were included. The median POPF incidence without prophylaxis was 19.6 %. The relative risks for POPF after octreotide or pasireotide prophylaxis were 0.54 or 0.45. Octreotide prophylaxis (21 × 0.1 mg) costs were 249.69 Euro, compared with 728.84 Euro for pasireotide (14 × 0.9 mg) resulting in an ICER of 266.19 Euro for an additional 1.8 % risk reduction with pasireotide. Decision tree modelling revealed no significant reduction of median hospital stay duration if pasireotide was used instead of octreotide. CONCLUSION: Prophylactic octreotide is almost as effective as pasireotide but incurs significantly fewer drug costs per case. However, the data quality is limited, because the effect of octreotide on clinically relevant POPF is unclear. Together with the lack of multicentric data on pasireotide and its effectiveness, a current off-label use of pasireotide does not appear to be justified.

[Release of antibiotics into urban wastewater: A secondary-data based analysis for the input assessment using the city of Dresden as an example]. / Antibiotikaeintrag in das urbane Abwasser : Eine sekundärdatenbasierte Analyse zur Eintragsabschätzung am Beispiel der Stadt Dresden.

Antibiotics are essential for the successful treatment of bacterial infections. Recently, the increasing number of resistant bacteria and the occurrence of residues of antibiotics in the environment has become the focus of scientific interest. The aim of the cooperative project ANTI-Resist was to investigate the release of antibiotics and the occurrence and distribution of antibiotic resistance in the urban waste water system of the city of Dresden.This article presents the main results of the secondary data analysis for the determination of outpatient and inpatient antibiotic consumption and provides an insight into the complexity of the topic antibiotics in waste water.Based on the data of outpatient prescriptions provided by the AOK PLUS for the period 2005 to 2013, thirteen focus substances were identified to estimate antibiotic consumption. Furthermore, delivery data from the pharmacies of three hospitals in Dresden were available.Depending on the substances investigated, seasonality and age dependency were determined. The results at a regional level were mostly in good accordance with general trends throughout Germany. It should be noted that the total amount of antibiotics used remained nearly constant over the whole period investigated, but the prescription of fluoroquinolones increased. This must be questioned when taking into account the increasingly critical situation in the treatment of Gram-negative bacteria in particular. Examinations of waste water conducted indicated that sewage treatment plants are not able to remove antibiotics or their metabolites completely from waste water. The residues are released into surface waters via the treatment plants. The impact cannot be assessed at the moment and further investigations are necessary.

Hospital use of systemic antifungal drugs: a multi-center surveillance update from Germany.

BACKGROUND: The consumption of antifungal agents increased over the last decade, resulting in the development of resistant organisms and causing a significant pharmaco economic burden. Antifungal drugs are widely used for the treatment of systemic fungal infections and high-risk patients, especially with severe hematological or oncological conditions. Up to date, there are no reliable and systematically reported data on the consumption of antifungal substances on a nationwide level available. The presented study gives an update to the previously published multicenter study investigating antifungal consumption in different settings from five university hospital centers in Germany from 2001 to 2003. METHODS: Consumption data for systemic antifungal drugs were obtained through the hospital pharmacies for 2001-2003 and 2008-2011 regarding the medical and surgical services of five university hospital centers in Germany (A-E). Drug use densities were calculated as yearly RDDs/100 patient days. These calculations were performed for the surgical and medical services, and independently for surgical and medical ICUs, as well as for the hematology-oncology services. RESULTS: We report an increased utilization of systemic antifungal drugs in both study periods. The mean drug use density (mean value of all 5 hospitals) in the medical services increased by 24% between 2001 and 2003. In 2011, this value was 37% above the level from 2001 (12.4 RDD/100 patient days in 2001, 15.4 RDD/100 patient days in 2003, 17.0 RDD/100 patient days in 2011). The 4-year average drug use density (2008-2011) of medical services ranged between 11.6 RDD/100 patient days (hospital E) and 23.8 RDD/100 patient days (hospital A). Drug use densities were in medical intensive care units 29.4 RDD/100 patient days and hematology-oncology services 49.9 RDD/100 patient days. CONCLUSIONS: Despite the variability of the prescribing patterns between the tertiary hospitals, the presented pharmaco-epidemiological data are a cornerstone for the initiation and implementation of effective antifungal stewardship programmes and might serve as important benchmarking information for other hospitals with similar structures and baseline settings.

[Medication reviews in community pharmacies: An approach to external quality assessment]. / Medikationsanalysen in öffentlichen Apotheken: Konzept zur externen Qualitätsüberprüfung.

BACKGROUND: A medication review aims at the optimization of medication use, the detection of drug-related problems (DRPs) and the recommendation of interventions. As part of the pilot project "Arzneimittelinitiative Sachsen-Thüringen" (ARMIN) and caused by the introduction of several training programs, numerous public pharmacies in Germany currently offer medication reviews for patients. However, a standardized method for external quality control has so far not been established. METHODS: A round robin test for medication reviews was designed in written form by five pharmacists with expertise in different areas (Drug information service ARMIN, Saxonian Chamber of pharmacists, public pharmacy, hospital pharmacy), based on the recommendations of the guideline for medication reviews of the German Federal Chamber of Pharmacists (Bundesapothekerkammer). On the basis of a fictitious case study the participants were asked to check a patient's medication data for the presence of DRPs, propose possible solutions and generate a medication plan. The solutions were assessed by two pharmacists of the drug information service ARMIN on the basis of a best practice solution that had been consented in the study group beforehand. RESULTS: 102 pharmacists and 13 pharmacy students in internship took part in the round robin test. On average, participants achieved a score of 7,62 out of 9 for recognizing DRPs and recommending solutions and a score of 0,79 out of 1 for generating a correct medication plan. 106 participants (92%) met the requirements for successful participation (recognizing the three most relevant DRPs and at least one further DRP as well as generating an adequate medication plan). The implementation of the approach described here proved to be practicable The State Directorate of Saxony accepted the round robin test as a measure for external quality assessment in accordance with legal requirements. CONCLUSIONS: Due to the nationwide introduction of medication reviews as a pharmaceutical service in June 2022, medication reviews performed by German community pharmacies will gain in importance in the coming years. This is why quality assurance is necessary. Since the participants' performance in medication analysis becomes comparable by completing the round robin test, this instrument appears to be potentially suitable for the external quality assessment of medications reviews nationwide.

[Scoring tool to identify patients at increased risk for drug-related problems: results of a point prevalence study at hospital admission]. / Scoring-Tool zu Identifizierung von Patienten mit erhöhtem Risiko für Arzneimittel-bezogene Probleme- Bericht einer Punkt-Prävalenzuntersuchung bei Aufnahme im Krankenhaus.

INTRODUCTION: Drug therapy is a high-risk process and requires special attention, especially at sectoral borders. Pharmaceutical services such as medication review are appropriate measures to identify drug-related problems and thus improve the safety of drug therapy. Risk-scoring tools have been described in the literature as helpful for prioritizing medication reviews for patients at high risk for drug-related problems. METHODS: In a multi-centre point prevalence study, we identified patients at increased risk for medication-related problems at hospital admission using the medication risk tool. In addition, the current level of implementation of pharmacy services was surveyed. RESULTS: A total of 11 (58%; 11/19) hospital pharmacies in Saxony participated in the point prevalence survey. The scoring tool identified 32% (279/875) of patients at increased risk for medication-related problems (Meris score >12 group) at admission. Thereby, the number of drugs in the Meris score >12 group was 10.6 (average; standard deviation 3.5; n=279), while in the Meris score ≤12 group it was only five drugs per patient (average 4.6; standard deviation 2.8; n=596). The age of patients in the Meris score >12 group averaged 75.9 ± 11 years, while the age of patients in the Meris score ≤12 group averaged 60.6 ± 17.9 years. DISCUSSION: Prioritization with the help of a risk-scoring tool is essential as pharmacy services in Saxon hospitals still need to be regularly established and in order to identify patients with an increased risk for drug-related problems at an early stage.

Half-dose glucarpidase as efficient rescue for toxic methotrexate levels in patients with acute kidney injury.

PURPOSE: High-dose methotrexate (HDMTX)-associated acute kidney injury with delayed MTX clearance has been linked to an excess in MTX-induced toxicities. Glucarpidase is a recombinant enzyme that rapidly hydrolyzes MTX into non-toxic metabolites. The recommended dose of glucarpidase is 50 U/kg, which has never been formally established in a dose finding study in humans. Few case reports, mostly in children, suggest that lower doses of glucarpidase might be equally effective in lowering MTX levels. METHODS: Seven patients with toxic MTX plasma concentrations following HDMTX therapy were treated with half-dose glucarpidase (mean 25 U/kg, range 17-32 U/kg). MTX levels were measured immunologically as well as by liquid chromatography-mass spectrometry (LC-MS). Toxicities were assessed according to National Cancer Institute-Common Terminology Criteria for Adverse Events (CTCAE) v5.0. RESULTS: All patients experienced HDMTX-associated kidney injury (median increase in creatinine levels within 48 h after HDMTX initiation compared to baseline of 251%, range 80-455%) and showed toxic MTX plasma concentrations (range 3.1-182.4 µmol/L) before glucarpidase injection. The drug was administered 42-70 h after HDMTX initiation. Within one day after glucarpidase injection, MTX plasma concentrations decreased by ≥ 97.7% translating into levels of 0.02-2.03 µmol/L. MTX rebound was detected in plasma 42-73 h after glucarpidase initiation, but concentrations remained consistent at < 10 µmol/L. CONCLUSION: Half-dose glucarpidase seems to be effective in lowering MTX levels to concentrations manageable with continued intensified folinic acid rescue.

Randomized trial on 14 versus 7 days of esomeprazole, moxifloxacin, and amoxicillin for second-line or rescue treatment of Helicobacter pylori infection.

BACKGROUND: Triple therapy with a proton pump inhibitor, moxifloxacin, and amoxicillin has been proven effective in first-line treatment of Helicobacter pylori infection. AIM: To explore 1, the value of triple therapy with esomeprazole, moxifloxacin, and amoxicillin in second-line or rescue treatment of Caucasian patients and 2, the impact of treatment duration on eradication success. METHODS: H. pylori-infected patients with at least one previous treatment failure were randomized to oral esomeprazole 20 mg b.i.d., moxifloxacin 400 mg o.d., and amoxicillin 1000 mg b.i.d. for either 7 (EMA-7) or 14 days (EMA-14). Eradication was confirmed by 13C urea breath test. Antimicrobial susceptibility testing was performed in all patients at baseline and in patients who failed treatment. RESULTS: Eighty patients were randomized, and 60% had ≥ 2 previous treatment failures. Pretreatment resistance against clarithromycin and metronidazole was found in 70.5 and 61.5% of cases, respectively. The intention-to-treat eradication rate was significantly higher after EMA-14 compared with EMA-7 (95.0 vs 78.9%, p = .036). No independent risk factor for treatment failure could be identified. There were no serious adverse events. Five of the EMA-14 patients (12.5%) compared with none of the EMA-7 patients discontinued prematurely because of adverse events (p = .031). Post-treatment resistance against moxifloxacin was found in one of seven patients with isolated organisms (14.3%). CONCLUSION: Second-line/rescue H. pylori eradication therapy with esomeprazole, moxifloxacin, and amoxicillin is very effective and well tolerated. Fourteen days of treatment significantly increase the eradication rate but also the rate of adverse events.

Clinical pharmacy services in Germany: a national survey.

OBJECTIVES: Clinical pharmacy services in German hospitals appear to be underdeveloped compared with other European countries. However, recent developments have increased the interest in expanding these services. Detailed data about the current state of clinical pharmacy services in Germany are lacking. This survey establishes the current level of pharmacy services in Germany and the barriers to implementation. METHODS: An online survey conducted in 2017 was distributed to directors of all 389 German hospital pharmacies. The survey contained 26 questions addressing hospital and pharmacy characteristics, clinical pharmacy services provided, the number of clinical pharmacists and the frequency as well as the quality assurance of these services. RESULTS: There were 133 responses (34%). Of these, 84 (63%) pharmacies provided some form of clinical pharmacy services. Based on the 389 contacted pharmacies, a clinical pharmacy service is available in at least 22% of hospital pharmacies in Germany. On average there are 2.4 full-time equivalent (FTE) clinical pharmacists per hospital employed, although there is a wide variation in numbers (0.3-22 FTE) and service provision between hospitals. Clinical pharmacy services are generally provided on a daily or weekly basis, with a principal focus on general surgery, critical care and general medicine wards. CONCLUSIONS: This is the first survey providing a detailed picture of clinical pharmacy services in Germany. There is wide variation in clinical service provision among hospitals, with some hospitals having developed a comprehensive range of clinical services. Compared with other countries, particularly the UK where the focus has shifted to provision of 7-day clinical services, the gap in clinical pharmacy services remains large. The focus should be turned to refining clinical pharmacy services in hospital admissions and discharge planning while also improving Health IT, the opportunities for specialisation and aligning education in accordance with the EAHP common training framework.

Analysis of secondary care data to evaluate the clinical relevance of the drug-drug interaction between amlodipine and simvastatin.

BACKGROUND: Pharmacokinetic analyses revealed an increase in the bioavailability of simvastatin when co-administered with amlodipine [Nishio S et al. Hypertensin research 2005; Son H et al. Drug metabolism and pharmacokinetics 2014]. This may induce an increased risk of muscle toxicity for patients who receive this combination. So far, no in vivo data on the clinical relevance of this interaction exist. The objective of the present analysis was to determine the number of patients with concomitant treatment of amlodipine and simvastatin. Subsequently, the data was analyzed for the indication of muscular discomfort. Patients with combined prescription of amlodipine and another hydroxymethylglutaryl-CoA-reductase inhibitor except simvastatin or patients receiving simvastatin without amlodipine served as control groups. METHODS: The present analysis used secondary data from the health insurance company AOK PLUS including information regarding diagnosis and drug prescriptions. RESULTS: In total, 67.081 patients corresponding to 4.93% of the analyzed collective received a combined prescription of amlodipine and simvastatin. The absolute frequency increased continuously over time. Muscular discomfort was detected in a) 6.20% of the patients receiving amlodipine and simvastatin, b) 6.60% of the patients receiving amlodipine and another hydroxymethylglutaryl-CoA- reductase inhibitor and c) 8.04% of the patients with simvastatin only. CONCLUSIONS: The present analysis shows an increasing trend of combined prescriptions of amlodipine and simvastatin. Evidence for simvastatin dose adaptation or therapy switch to another hydroxymethylglutaryl-CoA-reductase inhibitor, however, was not found. Muscular discomfort does not occur more often in patients with amlodipine and simvastatin compared to the two control groups. The results of the present analysis reveal no evidence for a clinically relevant interaction between amlodipine and simvastatin.

One-week once-daily triple therapy with esomeprazole, moxifloxacin, and rifabutin for eradication of persistent Helicobacter pylori resistant to both metronidazole and clarithromycin.

AIM: To investigate a 1-week once-daily triple therapy with esomeprazole, moxifloxacin, and rifabutin for rescue therapy of Helicobacter pylori infection. METHODS: Consecutive patients (n = 103) with at least one previous treatment failure and H. pylori infection resistant to both metronidazole and clarithromycin were treated with esomeprazole 40 mg, moxifloxacin 400 mg, and rifabutin 300 mg, given once daily for 7 days. Eradication was confirmed by histology and culture. CYP2C19 status was determined by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Intention-to-treat and per-protocol eradication rates were 77.7% (68.4-85.3) and 83.3% (74.4-90.2). Five patients discontinued prematurely (4.8%). Eradication was achieved in 93.1% of poor/intermediate metabolizers and in 78.8% of homozygous extensive metabolizers (p = .14). Eradication rates in patients with one, two, three, and four or more previous failures were 78.3%, 89.6%, 68.6%, and 88.9%, respectively (p = .21). The regimen was effective in seven of nine patients who previously failed quadruple therapy. Post-treatment resistance to moxifloxacin and rifabutin was detected in two (12.5%) and five (31%) patients after treatment failure. CONCLUSION: Once-daily triple therapy with esomeprazole, moxifloxacin, and rifabutin is a promising, safe, and convenient regimen for rescue therapy of H. pylori infection that may serve as a valuable alternative to quadruple therapy, particularly for patients with intolerance to amoxicillin.

[Medication Plans at Hospital Admission - a Multicentre Analysis Using Statutory Health Insurance Data]. / Medikationspläne bei Krankenhausaufnahme ­ eine multizentrische Analyse unter Nutzung von Routinedaten einer gesetzlichen Krankenversicherung.

INTRODUCTION: Changes in drug therapy at intersectoral interfaces can lead to clinically relevant drug-related problems. This study aimed, therefore, at comparing the drug prescription continuity of patients with and without a medication plan at hospital admission. METHODS: After ethical approval, patients of a health insurance company in 6 hospitals in Saxony were consecutively assigned to this study from November 2011 to January 2012 after written informed consent. We assessed the following drug-related data for patients with and without medication plan at hospital admission: (i) the medication prescribed by the hospital physician on the day of hospital admission and (ii) the medication of the hospital discharge letter. Patient-individual claims data were assigned to the inpatient data for a period of 6 months before and after inpatient treatment (data linkage). RESULTS: Of the 279 study participants, 173 (62 %) used a medication plan at hospital admission. Patients with a medication plan had a statistically significantly older age, higher numbers of drugs and diagnoses and fewer emergency admissions. At admission 53 % of the drugs were continued in patients with medication plan and 40 % in patients without a medication plan (p < 0.001). At hospital discharge 66 % and 64 % were continued after discharge (n. s.). Medication plans were mostly written by their GP (38 %) and in 12 % by the patients themselves. DISCUSSION: Even before implementation of the national medication plan, nearly two third of the patients had a medication plan at hospital admission. However, in many cases it had been prepared by the patients themselves. The existence of a medication plan can have an impact on the continuity of the drug prescription during hospitalisation but not after discharge.

[Utilising statutory health insurance data to evaluate pharmaceutical interventions in secondary care - a pilot study]. / Verwendung von Routinedaten der gesetzlichen Krankenkasse in einer Pilotstudie zur Evaluation pharmazeutischer Interventionen im Krankenhaus.

BACKGROUND: Intensive pharmaceutical and medical care can lead to fewer drug-related problems (DRPs) in hospitals. Currently available methods to track drug changes after transition from inpatient to outpatient care are susceptible to systemic bias. Therefore we analysed the feasibility of a data linkage between prescription data extracted from hospital medical records and claims data from a health insurance company. METHODS: At six Saxonian hospitals, patients with a written informed consent were consecutively assigned to a control (CG) or intervention group (IG) depending on the time of admission. Clinical pharmacists documented predetermined DRPs and prescribed medication on the day of hospital admission and in the discharge letter. In case of DRP (IG) or potentially life-threatening DRPs (CG), drug changes were recommended to the hospital physician. These data were patient-individually linked to claims data from a health insurance company comprising a period of six months before and six months after hospitalisation (data linkage). We analysed data consistency within the data linkage and the post-hospital prevalence of DRPs identified in the hospital setting. RESULTS: We enrolled 532 patients (CG/IG 280/252). The data linkage was feasible for 97.0% (CG) and 96.6% (IG) of the patients, respectively. A total of 318 DRPs (CG/IG 176/142) was detected. Because of restrictions in the reimbursement of drugs in the outpatient setting, 22 (12.5%, CG) and 13 (9.2%, IG) DRPs were not analysable. Insurance claims data during a 6-month follow-up showed no statistically significant difference between the CG (without intervention) and in the IG (with intervention) with respect to DRPs (43.4% vs 38.1%; p = 0.472). CONCLUSIONS: The linkage of inpatient and outpatient data was feasible for the majority of enrolled patients. Compared to similar studies, the risk for systemic bias decreased because fewer patients were lost to follow-up. Within this feasibility study the expected difference between IG and CG could not be demonstrated statistically.

Impact of pharmacokinetics on the toxicity and efficacy of clofarabine in patients with relapsed or refractory acute myeloid leukemia.

Common side effects of clofarabine (CFB) are liver toxicity, particularly a transient elevation of transaminases and skin toxicity. We studied the correlation of pharmacokinetic (PK) parameters with these toxicities and the efficacy of CFB in patients with relapsed or refractory acute myeloid leukemia. Clofarabine PK parameters showed large inter-individual variability. A higher CFB area under the curve was significantly associated with higher transaminase levels (p = .011 for aspartate aminotransferase (AST), adjusted for age, sex, cumulated CFB dosage, baseline AST, and glomerular filtration rate (GFR)). No significant association could be found between maximum concentration and the liver toxicity parameters. The occurrence of skin toxicity and the response to re-induction chemotherapy evaluated at day 15 were also not associated with PK. In conclusion, a higher individual CFB exposure is associated with increased liver toxicity reflected by elevated liver enzymes, without having an impact on anti-leukemic efficacy.

[Medication management: Simvastatin and Amlodipin - a clinically relevant drug-interaction?] / Medikationsmanagement: Simvastatin und Amlodipin: Eine klinisch relevante Wechselwirkung?

The clinical relevance of the drug-drug interaction simvastatin and amlodipine is appraised controversially by german simvastatin Summary of Product Characteristics (SPCs) and different drug interaction databases. Results of clinical trials have shown that simultaneous administration of simvastatin and amlodipine can increase simvastatin bioavailability. However, it is unclear whether this increase is associated with a higher risk for adverse drug events. So far there is no evidence that the combination might increase cases of myopathy or rhabdomyolysis. Therefore combined treatment with amlodipine and up to 40 mg simvastatin daily seems clinically justifiable if the patient does not report adverse events. If myopathy or muscle weakness occur, simvastatin dose should be reduced to 20 mg daily or the patient should be switched to pravastatin, fluvastatin or rosuvastatin. The highest approved dose of simvastatin (80 mg) is generally not recommended in new patients because of increased risk of muscle damage.