Usability of German hospital administrative claims data for healthcare research: General assessment and use case of multiple myeloma in Munich university hospital in 2015-2017.

OBJECTIVES: To assess the usability of German hospital administrative claims data (GHACD) to determine inpatient management patterns, healthcare resource utilization, and quality-of-care in patients with multiple myeloma (PwMM). METHODS: Based on German tertiary hospital's claims data (2015-2017), PwMM aged >18 years were included if they had an International Classification of Diseases, Tenth Revision, code of C90.0 or received anti-MM therapy. Subgroup analysis was performed on stem cell transplantation (SCT) patients. RESULTS: Of 230 PwMM, 59.1% were men; 56.1% were aged ≥65 years. Hypertension and infections were present in 50% and 67.0%, respectively. Seventy percent of PwMM received combination therapy. Innovative drugs such as bortezomib and lenalidomide were given to 36.1% and 10.9% of the patients, respectively. Mean number of admissions and mean hospitalization length/patient were 3.69 (standard deviation (SD) 2.71 (1-16)) and 12.52 (SD 9.55 (1-68.5)) days, respectively. In-hospital mortality was recorded in 12.2%. Seventy-two percent of SCT patients (n = 88) were aged ≤65 years, 22.7% required second transplantation, and 89.8% received platelet transfusion at a mean of 1.42(SD 0.63 (1-3)). CONCLUSION: GHACD provided relevant information essential for healthcare studies about PwMM from routine care settings. Data fundamental for quality-of-care assessment were also captured.

Budget Impact Analysis of CAR T-cell Therapy for Adult Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma in Germany.

The aim was to assess the incremental costs of chimeric antigen receptor (CAR) T-cell therapy (axicabtagene ciloleucel, tisagenlecleucel) compared with standard of care in adult patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL) from the German third-party payer perspective. A budget impact model was established over a 6-year period. Estimation of the third-line population: partitioned survival model based on outcome data from peer-reviewed literature, a top-down approach based on population forecasts, and age-standardized incidences. Cost data were derived from the controlling department of a tertiary hospital and a German cost-of-illness study. In the scenario analysis, the budget impact of treating second-line DLBCL patients was calculated. One-way deterministic sensitivity analyses were conducted to test the robustness of the model. For the period 2021-2026, 788-867 (minimum population, min) and 1,068-1,177 (maximum population, max) adult third-line r/r DLBCL patients were estimated. The budget impact ranged from €39,419,562; €53,426,514 (min; max) in year 0 to €122,104,097; €165,763,001 (min; max) in year 5. The scenario analysis resulted in a budget impact of €65,987,823; €89,558,611 (min; max) and €204,485,031; €277,567,601 (min; max) for years 0 and 5, respectively. This budget impact analysis showed a significant but reasonable financial burden associated with CAR T-cell therapy for a limited number of patients requiring individualized care. Further, this study presents challenges and future needs in data acquisition associated with cost analysis in personalized medicine. For comprehensive economic discussions, complementary cost-effectiveness analyses are required to determine the value of innovative therapies for r/r DLBCL.

Transparency on Platelet Transfusion in Routine Cancer Care: The Key for Optimal Blood Usage?

INTRODUCTION: In Germany, up to 75% of platelet concentrates (PCs) are administered to haematological and oncological patients. Only limited transparency exists on the characteristics of haematological/oncological patients receiving PC transfusions, treatment patterns, and guideline adherence in daily clinical routine care. This information would be key for managing platelet supply and optimal platelet usage strategies. This study aimed to analyse data from clinical routine transfusions to fill the aforementioned information gaps and to create an inventory as a blueprint for electronic data capturing systems that allow simplified, recurring analyses. METHODS: Prospective open-label, single-centre, observational study in a German tertiary teaching haematological/oncological setting. All inpatients who received any transfusion of PCs (pathogen-inactivated or conventional) in routine use over a period of 3 months (March 2015-May 2015) were consecutively included. Except for age (≥18 years), no exclusion criteria were applied. For guideline adherence, the Cross-Sectional Guidelines for Therapy with Blood Components and Plasma Derivatives - amended edition 2020 were used. An inventory blueprint was created through a narrative literature review and the data collected in this study. RESULTS: Ninety-four patients received 942 PCs. The mean (±SD) age was 54.6 (±13.9) years, 68% were male and 86% were diagnosed with a haematological disease. Thirteen patients received 42% of all transfused PCs. The mean ± SD number of transfused PC per patient was 10.81 ± 9.24. Five (0.5% per transfusion) minor adverse events were documented. Approximately 19% of PCs were not administered according to existing guidelines. The mean transfusion interval was 1.71 ± 1.1 days, and the mean increment was 12.62 ± 14.7 G/L. The inventory showed which platelet transfusion-specific data should be documented for answering questions in terms of quality, effectiveness, and management of PC transfusions. CONCLUSIONS: Platelet transfusions in a haematological/oncological setting are highly individual in terms of the total number of transfusions and transfusion intervals. The majority of all PC transfusions were given to only a small group of patients. Continuous, structured real-world data collection/evaluation and benchmarking with data from more centres seems essential in determining specific needs in this vulnerable patient group, assessing the quality of transfusion practices, determining effectiveness, and anticipating future demand for platelets and a sustainable blood supply. So far, not all relevant data are collected routinely. The advancing digitalization of health systems offers opportunities to collect and link data and thus make them more accessible and evaluable.

Inpatient treatment of relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL): A health economic perspective.

INTRODUCTION: Patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL) require highly individualized therapies. Limited information exists regarding inpatient treatment patterns, outcomes, resource-use, and costs from the perspective of third-party payers in Germany. The aim of this study was to collect and evaluate routine inpatient care data to fill aforementioned gaps. METHODS: Retrospective single center observational study in a German tertiary teaching hospital. Data were collected from patient records, the hospital-pharmacy database, and claims data. RESULTS: Eighty-four patients (47 male; mean age at initial diagnosis, 59 years) were identified and grouped by treatment line (L): 2L (n = 78), 3L (n = 32), and >3L (n = 12). Prescribed treatments in 2L were chemotherapy 56%, auto-SCT 31%, allo-SCT 1%, other 12%; 3L: 50%, 16%, 6%, 28%, respectively, and >3L: 42%, 0%, 33%, 25%, respectively. Mean number of hospital admissions and length of inpatient stay (days) were: 2L (4, 44), 3L (2, 26), and >3L (5, 63). Average cost/patient: 2L = 44,750€, 3L = 32,589€ and >3L = 88,668€. Mean treatment costs per patient for stem-cell-transplanted patients were 55,468€ for autologous SCT (n = 28) and 131,264€ for allogeneic SCT (n = 7). Documented death was 21%, 28%, and 41% for 2L, 3L, and >3L, respectively. CONCLUSION: Individualized DLBCL treatment in patients ≥ 2L is costly and results in a huge variability in resource consumption. The number of documented deaths and length of hospitalization signal a high economic burden on patients and families. A multicenter comprehensive evaluation of health and economic burdens of r/r DLBCL and linkage with other data sources (eg, registries, payers' claims data) is essential.

Patient-reported measures of well-being in older multiple myeloma patients: use of secondary data source.

BACKGROUND: Changes in well-being of patients with multiple myeloma (MM) before and after diagnosis have not been quantified. AIMS: Explore the use of secondary data to examine the changes in the well-being of older patients with MM. METHODS: We used the Health and Retirement Study (HRS), linked to Medicare claims to identify older MM patients. We compared patient-reported measures (PRM), including physical impairment, sensory impairment, and patient experience (significant pain, self-rated health, depression) in the interviews before and after MM diagnosis using McNemar's test. We propensity-matched each MM patient to five HRS participants without MM diagnosis based on baseline characteristics. We compared the change in PRM between the MM patients and their matches. RESULTS: We identified 92 HRS patients with MM diagnosis (mean age = 74.6, SD = 8.4). Among the surviving patients, there was a decline in well-being across most measures, including ADL difficulty (23% to 40%, p value = 0.016), poor or fair self-rated health (38% to 61%, p value = 0.004), and depression (15% to 30%, p value = 0.021). Surviving patients reported worse health than participants without MM across most measures, including ADL difficulty (40% vs. 27%, p value = 0.04), significant pain (38% vs. 22%, p value = 0.01), and depression (29% vs. 11%, p value = 0.003). DISCUSSION: Secondary data were used to identify patients with MM diagnosis, and examine changes across multiple measures of well-being. MM diagnosis negatively affects several aspects of patients' well-being, and these declines are larger than those experienced by similar participants without MM. CONCLUSION: The results of this study are valuable addition to understanding the experience of patients with MM, despite several data limitations.

Improving quality of antifungal use through antifungal stewardship interventions.

PURPOSE: In recent years antifungal stewardship (AFS) programmes have been increasingly recommended to provide optimal antifungal treatment. In a previous study (study I) in the department of haematology and oncology of a German tertiary care hospital we found areas for improvement concerning antifungal prescription. Subsequently, AFS measures were implemented and their impact on quality of antifungal use was assessed in this study. METHODS: AFS measures included medical training (two sessions), a pocket card summarising main recommendations for antifungal use, and daily pharmaceutical counselling on the ward. In a 6-month observational study, antifungal prescriptions were analysed and compared to the previously collected data (study I) concerning indication, choice of drug, dosing, duration and drug-drug interactions. The study was approved by the university hospital ethical review board. RESULTS: Antifungal agents were prescribed for 103/1169 inpatients. Compared to study I, a significant increase in dosage accuracy (+ 19.3%; p < 0.05) and correct choice of drug (+ 15.9%; p < 0.05) was noted, as well as a decrease in potential clinically relevant drug-drug interactions with concomitant medication (- 13.9%; p < 0.05). However, no significant improvement in indication and duration of antifungal treatment was identified. 56 recommendations were given to the prescribing physicians (acceptance rate: 66.1%). CONCLUSIONS: The implementation of AFS interventions based on pharmaceutical presence on the ward was associated with an improvement in antifungal use; however, indication and duration of therapy need to be communicated by infectious disease specialists. Considering the proportionally short observation period, the long-term effects of our AFS interventions need to be further investigated.

Burden of Oral Mucositis: A Systematic Review and Implications for Future Research.

BACKGROUND: Surprisingly little is known about the burden of oral mucositis (OM). We provide a systematic review of studies on the burden of OM (incidence, economic impact, health-related quality of life (HRQoL)). METHODS: Systematic literature searches were made in BIOSIS, EMBASE, and MEDLINE. Inclusion criteria were studies on OM in hematology/oncology patients of ≥ 18 years, journal articles, English language, and published between 2000 and 2016; OM treatment studies were excluded. Quality assessment was performed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: We screened 4,996 hits, and identified 68 studies of which 13 were without transparency on OM grading. The evidence level of 65 studies was rated 'low' or 'very low' in 58.5%, 'moderate' in 20% and 'high' in 21.5%. Mean value of incidence (7 studies) was 83.5% for all grades of OM with hematopoietic stem cell transplantation. OM incidence for all grades in head and neck cancer patients was 59.4-100%. Considering the economic impact, 16 studies showed highly variable numbers. HRQoL was measured in 16 studies using 13 different instruments. Statistically significant changes in HRQoL scores were demonstrated. CONCLUSION: OM is common, burdensome, costly and imposes major reductions in HRQoL. However, from a quality standpoint, the level of current evidence in OM is disappointing. The field needs continued attention to address methodological challenges.

Antifungal treatment in haematological and oncological patients: Need for quality assessment in routine care.

Invasive fungal infections in haematological and oncological patients have a major impact on morbidity, mortality and treatment costs. Therefore, rational use of antifungal agents is important for optimal patient care and resource use. The study's objective was to analyse antifungal usage in a German tertiary teaching hospital, department of haematology and oncology, to evaluate quality of antifungal treatment and to assess the need for an antifungal stewardship programme. This retrospective observational study included patients ≥18 years receiving systemic antifungals for prophylaxis or therapy of invasive fungal infection between January and June 2016. Appropriateness of antifungal prescriptions was evaluated in accordance with guidelines of the German Society of Haematology and Oncology (DGHO) and drug labelling. In total, 104/1278 (8.1%) patients received antifungals. One hundred seventy-one antifungals were prescribed: 48 for prophylaxis, 104 for empirical and 19 for targeted therapy. In 127 (74.3%) prescriptions, indication was appropriate, and in 132 (77.2%), choice of drug. Antifungals were correctly dosed in 131 prescriptions (76.6%). Thirty-four antifungals (20.0%) were co-administrated with interacting drugs (5 mild to moderate, 29 severe interactions). Results of this analysis demonstrate that use of systemic antifungals in routine care differs in a substantial number of patients from guideline and labelling recommendations. To optimise antifungal use, the implementation of antifungal stewardship programmes seems to be justified.

Burden of oral mucositis in stem cell transplant patients-the patients' perspective.

PURPOSE: Purpose of this study was to determine the impact of Oral Mucositis (OM) on health-related quality of life (HRQoL) and quality of life associated symptoms and functions in patients undergoing hematopoietic stem cell transplantation (HSCT). METHODS: Prospective, non-interventional single-center observational study at a German tertiary teaching hospital. Inpatient allogenic and autologous stem cell transplant patients ≥18-year-old with high-dose chemotherapy. OM was assessed with the WHO Oral Toxicity Scale, pain according to the Numeric Rating Scale (NRS) and the performance status using the ECOG Score. QOL was captured with the EORTC QLQ-C30 and the QLQ-OH15 questionnaires. RESULTS: Forty-five stem cell transplant patients (20 autologous, 25 allogenic) were enrolled between August 2016 and February 2017. Twenty-six (58%, 95% CI: 42% - 72%) patients developed OM (10 grade I, 4 grade II, 8 grade III, 4 grade IV). OM affected patients suffered more from pain, sore mouth and sensitive mouth. A lower physical functioning (34.5 vs 7.5, p = 0.003) and a lower oral health-related quality of life (24.3 vs 7.7, p = 0.006) was found in patients with OM development. There was found a positive correlation between the grade of OM and the NRS-value (r = 0.93, 95% CI: 0.89-0.96, p < 0.001). CONCLUSION: OM is associated with health-related quality of life and quality of life associated functions and symptoms. More research should be performed to find ways to prevent OM and to stabilize patients' quality of life during HSCT.

White to beige conversion in PDE3B KO adipose tissue through activation of AMPK signaling and mitochondrial function.

Understanding mechanisms by which a population of beige adipocytes is increased in white adipose tissue (WAT) reflects a potential strategy in the fight against obesity and diabetes. Cyclic adenosine monophosphate (cAMP) is very important in the development of the beige phenotype and activation of its thermogenic program. To study effects of cyclic nucleotides on energy homeostatic mechanisms, mice were generated by targeted inactivation of cyclic nucleotide phosphodiesterase 3b (Pde3b) gene, which encodes PDE3B, an enzyme that catalyzes hydrolysis of cAMP and cGMP and is highly expressed in tissues that regulate energy homeostasis, including adipose tissue, liver, and pancreas. In epididymal white adipose tissue (eWAT) of PDE3B KO mice on a SvJ129 background, cAMP/protein kinase A (PKA) and AMP-activated protein kinase (AMPK) signaling pathways are activated, resulting in "browning" phenotype, with a smaller increases in body weight under high-fat diet, smaller fat deposits, increased ß-oxidation of fatty acids (FAO) and oxygen consumption. Results reported here suggest that PDE3B and/or its downstream signaling partners might be important regulators of energy metabolism in adipose tissue, and potential therapeutic targets for treating obesity, diabetes and their associated metabolic disorders.

Patient database analysis of fulvestrant 500 mg in the treatment of metastatic breast cancer: A European perspective.

INTRODUCTION: Clinical guidelines recommend that patients with hormone receptor (HR)-positive metastatic breast cancer (MBC) should be preferentially treated with endocrine therapy. Fulvestrant (a selective estrogen receptor degrader) is approved for use in these patients following relapse after, or relapse or progression during, antiestrogen therapy. This descriptive study analyzed European treatment patterns for HR-positive MBC in real-world clinical practice. METHODS: The IMS Oncology Analyzer (OA), a retrospective cancer treatment database reporting physician-entered patient case histories, was used to identify records for postmenopausal women with HR-positive MBC from April 1, 2004 to June 30, 2013 in France, Germany, Italy, and Spain. Treatments were allocated to mutually exclusive categories (fulvestrant-containing, aromatase inhibitor [AI]-containing, tamoxifen-containing, or chemotherapy-containing regimens) and assessed by line of therapy for MBC. Fulvestrant use was also assessed pre- and post-2010 (when fulvestrant 500 mg dosing was approved). RESULTS: In total, 27,214 eligible patients were included (France: 6801; Germany: 6852; Italy: 7061; Spain: 6500). Chemotherapy-based regimens were the most common first-line treatments for MBC across all countries. Across countries, the proportion of patients initiating on each treatment category ranged from: chemotherapy, 57.5-70.4%; AI, 23.5-30.1%; tamoxifen, 2.7-9.8%; fulvestrant 0.8-2.6%. When administered, fulvestrant was usually given as first- or second-line treatment. Post-2010, more patients received fulvestrant 500 mg than fulvestrant 250 mg in France, Germany, and Spain; in Italy, more patients continued to receive fulvestrant 250 mg. CONCLUSION: Most patients with HR-positive MBC receive chemotherapy over endocrine therapy; fulvestrant constitutes a small proportion of treatments for such patients.

Economic and clinical aspects of intravenous versus oral busulfan in adult patients for conditioning prior to HSCT.

PURPOSE: Busulfan (BU) used as cytoreductive conditioning prior to hematopoietic stem cell transplantation (HSCT) is available as intravenous (IV) and oral (O) preparation. IV-BU has clinical advantages associated with relevant incremental costs. The aim was to determine the economic impact of IV-BU versus O-BU in adult HSCT recipients from a German health care providers' perspective. METHODS: A budget-impact model (BIM) including costs and risks for oral mucositis (OM), infection with OM, and hepatic sinusoidal obstruction syndrome (SOS) was developed. Model inputs are literature data comparing clinical effects of IV-BU versus O-BU and German cost data (conditioning therapy, treatment of OM, infections, SOS without/with multiorgan failure) from literature and tariff lists. RESULTS: Base case calculations resulted the following: total costs of adverse events were €86,434 with O-BU and €44,376 with IV-BU for ten patients each. Considering costs of adverse events and drugs, about €5840 for ten patients receiving IV-BU are saved. Sensitivity analyses were conducted in several ways. Cost savings range between €4910 and €12,640 per ten patients for all adverse events and €2070 or €1140 per ten patients considering SOS only. Drug treatment of SOS and treatment of multiorgan failure during severe SOS are major cost drivers. Worst case scenario calculations (assuming -25% risk of all adverse events for O-BU and +25% for IV-BU) yield up to €27,570 per ten patients with IV-BU. CONCLUSIONS: Considering costs of adverse events and drugs, IV-BU is the dominant alternative from a German providers' perspective. For more comprehensive economic evaluations, additional epidemiological data, evidence on clinical outcomes, patient-reported outcomes, and treatment patterns are needed.

Model calculations to quantify clinical and economic effects of pathogen inactivation in platelet concentrates.

BACKGROUND: Future shortages in platelet supply are expected in Germany due to demographic changes. A rising cancer incidence will lead to an increasing demand for platelet concentrates (PCs) while the number of potential donors will decrease. Pathogen inactivation (PI) aims to inactivate various infectious agents including emerging pathogens to extend the shelf-life of PCs and reduce the frequency of acute transfusion reactions (ATRs). In this context, the clinical and economic impact of PI on platelet transfusion was evaluated. MATERIAL AND METHODS: Model calculations were conducted for 2 scenarios considering different production settings. Frequencies of ATRs were based on literature analyses, platelet and ATR costs on cost analyses. RESULTS: The estimated average costs for ATRs of grade 1 and 2, irrespective of origin, and grade 3 (allergic) were € 104, € 238, and € 1,200, respectively. Approximately 400 PC-related ATRs per 10(5) transfusions can be avoided, with estimated savings amounting to € 77,000. The total cost increase was calculated to approximately € 30-50 per PI-treated PC. CONCLUSION: PI potentially saves plasma, prolongs shelf-life, decreases donor deferral, and reduces ATRs. Model calculations considering clinical and safety benefits of PI show a rational cost increase. The impact of PI should be further evaluated from a societal perspective regarding future blood supply and infectious disease globalization.

Green tea powder and Lactobacillus plantarum affect gut microbiota, lipid metabolism and inflammation in high-fat fed C57BL/6J mice.

BACKGROUND: Type 2 diabetes is associated with obesity, ectopic lipid accumulation and low-grade inflammation. A dysfunctional gut microbiota has been suggested to participate in the pathogenesis of the disease. Green tea is rich in polyphenols and has previously been shown to exert beneficial metabolic effects. Lactobacillus plantarum has the ability to metabolize phenolic acids. The health promoting effect of whole green tea powder as a prebiotic compound has not been thoroughly investigated previously. METHODS: C57BL/6J mice were fed a high-fat diet with or without a supplement of 4% green tea powder (GT), and offered drinking water supplemented with Lactobacillus plantarum DSM 15313 (Lp) or the combination of both (Lp + GT) for 22 weeks. Parameters related to obesity, glucose tolerance, lipid metabolism, hepatic steatosis and inflammation were examined. Small intestinal tissue and caecal content were collected for bacterial analysis. RESULTS: Mice in the Lp + GT group had significantly more Lactobacillus and higher diversity of bacteria in the intestine compared to both mice in the control and the GT group. Green tea strongly reduced the body fat content and hepatic triacylglycerol and cholesterol accumulation. The reduction was negatively correlated to the amount of Akkermansia and/or the total amount of bacteria in the small intestine. Markers of inflammation were reduced in the Lp + GT group compared to control. PLS analysis of correlations between the microbiota and the metabolic variables of the individual mice showed that relatively few components of the microbiota had high impact on the correlation model. CONCLUSIONS: Green tea powder in combination with a single strain of Lactobacillus plantarum was able to promote growth of Lactobacillus in the intestine and to attenuate high fat diet-induced inflammation. In addition, a component of the microbiota, Akkermansia, correlated negatively with several metabolic parameters known to be risk factors for the development of type 2 diabetes.

A retrospective observational single-centre study on the burden of immune thrombocytopenia (ITP).

BACKGROUND: German data on economic consequences of immune thrombocytopenia (ITP) are limited. PATIENTS AND METHODS: A retrospective, observational study based on chart review of adult patients with a confirmed diagnosis of ITP was conducted at a German university hospital. Costs are presented from the hospital perspective. RESULTS: Of 50 eligible patients, 45 could be classified by disease duration: 19 patients < 3 months (38%, newly diagnosed ITP), 12 patients ≥ 3 to < 12 months (24%, persistent ITP), 19 patients ≥ 12 months (38%, chronic ITP). Complications included 85 bleeding events in 43 patients, including 3 intracranial haemorrhages. Documented were 955 outpatient visits in 43 patients (86%) and 92 inpatient hospital admissions in 45 patients (90%). Of the 46 patients (92%) treated, all received corticosteroids, 25 (50%) intravenous immunoglobulin, and 7 (14%) further therapies. 12 patients (24%) underwent splenectomy. Average total direct medical costs (mean (standard deviation)) were 17,091 (18,859) per patient, 12,749 (11,663) in 17 newly diagnosed ITP patients with a 0.88-month (0.65 months) average disease duration, and 29,868 (29,397) in 13 chronic ITP patients with a 33.5-month (16.8 months) average disease duration. Inpatient stays were the main cost drivers. CONCLUSION: These data concerning current healthcare provision for ITP patients in Germany indicate considerable resource consumption and the need for more effective treatment options in individual patients.

Blood component use and associated costs after standard dose chemotherapy--a prospective analysis of routine hospital care in lymphoproliferative disorders and NSCLC in Germany.

PURPOSE: The purpose of this study was to describe blood component (BC) use and respective cost after standard dose chemotherapy (CT) in routine hospital care. METHODS: Analysis of data from a prospective, multicenter, longitudinal, observational study on lymphoproliferative disorder (LPD) and non-small cell lung cancer (NSCLC) patients undergoing first or second line standard dose (immuno-)CT. Data were collected from patient interviews and pre-planned chart reviews. Costs of BC are presented from provider perspective. RESULTS: One hundred eighty patients (n = 85 NSCLC, n = 95 LPD) receiving 189 CT lines/633 CT cycles) were evaluable (mean ± SD age, 59 ± 13.2 years, 68% stage III/IV, 14% Eastern Cooperative Oncology Group ≥ 2). During 11% of cycles, BC were transfused to 27% of patients (n = 49; n = 22 NSCLC, n = 27 LPD). Of 310 transfused units (TU), 68% were red blood cells (RBC). Mean number of TU per cycle with transfusion was 3.3 ± 2.9 (median = 2, range = 2-17) for RBC, 4.8 ± 6.8 (median = 2, range = 1-23) for platelets (PLT) and 12.8 ± 14.6 (median = 8, range = 2-33) for fresh frozen plasma (FFP). Fifteen per cent of RBC units, 60% of PLT units and 92% of FFP in this study were transfused in cycles with sepsis. Mean BC cost per CT line were euro 602 ± 1,458 (median = 135, range = 135-9,385; NSCLC: euro 292 ± 376, median = 135, range = 135-2,124; LPD: euro 1,010 ± 2,137, median = 212, range = 135-9,385, p = 0.2137). For 55% of transfused RBC units, haemoglobin levels on the day of transfusion were 8.0-8.9 g/dl, for 38% <8 g/dl and for 7% ≥ 9 g/dl. Seventy-five per cent of PLT units were transfused at a PLT count <11,000/µl and 21% at 20,000-11,000/µl. CONCLUSIONS: The results reflect the diversity of BC use after standard dose CT. High transfusion need is associated with infectious complications, i.e. sepsis emphasising the need for adequate prophylaxis and further knowledge of baseline risk factors.

Management of febrile neutropenia--a German prospective hospital cost analysis in lymphoproliferative disorders, non-small cell lung cancer, and primary breast cancer.

BACKGROUND: Febrile neutropenia/leukopenia (FN/FL) is the most frequent dose-limiting toxicity of myelosuppressive chemotherapy, but German data on economic consequences are limited. PATIENTS AND METHODS: A prospective, multicentre, longitudinal, observational study was carried out to evaluate the occurrence of FN/FL and its impact on health resource utilization and costs in non-small cell lung cancer (NSCLC), lymphoproliferative disorder (LPD), and primary breast cancer (PBC) patients. Costs are presented from a hospital perspective. RESULTS: A total of 325 consecutive patients (47% LPD, 37% NSCLC, 16% PBC; 46% women; 38% age = 65 years) with 68 FN/FL episodes were evaluated. FN/FL occurred in 22% of the LPD patients, 8% of the NSCLC patients, and 27% of the PBC patients. 55 FN/FL episodes were associated with at least 1 hospital stay (LPD n = 34, NSCLC n = 10, PBC n = 11). Mean (median) cost per FN/FL episode requiring hospital care amounted to € 3,950 (€ 2,355) and varied between € 4,808 (€ 3,056) for LPD, € 3,627 (€ 2,255) for NSCLC, and € 1,827 (€ 1,969) for PBC patients. 12 FN/FL episodes (LPD n = 9, NSCLC n = 3) accounted for 60% of the total expenses. Main cost drivers were hospitalization and drugs (60 and 19% of the total costs). CONCLUSIONS: FN/FL treatment has economic relevance for hospitals. Costs vary between tumour types, being significantly higher for LPD compared to PBC patients. The impact of clinical characteristics on asymmetrically distributed costs needs further evaluation.

Treatment outcomes and resource use of patients with neurogenic detrusor overactivity receiving botulinum toxin A (BOTOX) therapy in Germany.

PURPOSE: To evaluate treatment outcomes and resource consumption of patients with neurogenic detrusor overactivity (NDO) before and after botulinum toxin A (Botox) therapy in Germany. METHODS: In a multi-center, cross-sectional, retrospective cohort study, data of patients with NDO 12 months before and after the first Botox therapy were analyzed. RESULTS: 214 patients (mean age 38 +/- 14.8 years, 145 male, 69 female) with NDO due to spinal cord injury (81%); myelomeningocele (14%), or Multiple Sclerosis (5%) from seven hospitals were included. Mean interval between treatments was 8 months. Following treatment, mean maximum detrusor pressure, maximum cystometric capacity and detrusor compliance improved significantly. Prior to Botox therapy, 68% reported urinary tract infections (UTI), 63% had incontinence episodes, and 58% used incontinence aids. These numbers decreased significantly (p < 0.05) after treatment to 28, 33, and 28%, respectively. In patients using incontinence aids, mean costs per patient decreased from 2euro to 1euro per day, whereas the mean cost of drugs to treat UTIs per patient decreased from 163euro to 80euro per year, respectively. CONCLUSION: This is the first study demonstrating the clinical usefulness of Botox therapy in clinical practice. Successful treatment resulted in lower costs for NDO associated morbidity due to less need for incontinence aids and UTI medication.

In vitro interactions with repeated grapefruit juice administration--to peel or not to peel?

Interactions of acutely administered grapefruit juice (GFJ) with cytochrome P450 isoform 3A4 (CYP3A4) and P-glycoprotein (Pgp) function are well established. In this study, we investigated in vitro the effect of repeated administration of GFJ and its major constituents (the flavonoid naringin, its aglycone naringenin and the furanocoumarin bergamottin) on mRNA expression of MDR1 and CYP3A4 in LS180 cells. Since the bergamottin content is higher in the peel than in the fruit, we compared GFJ containing peel (GFJP+) with juice without any peel extract (GFJP-). GFJP- (1%) showed no significant effect on MDR1 and CYP3A4 mRNA expression, whereas 1% GFJP+ increased expression of MDR1 3.7-fold (P<0.01) and CYP3A4 2.3-fold (P<0.05). Of the tested constituents, only 10 microM bergamottin and 200 microM naringenin induced MDR1 mRNA levels 2.9- and 4.0-fold, respectively (P<0.01 for both), and CYP3A4 mRNA levels 3.2- and 15.6-fold (P<0.01 for both), respectively. Western blot analysis and rhodamine 123 uptake experiments partly confirmed these findings on the protein and the functional level. In summary, GFJ containing no peel extract may have a lower potential for interactions with CYP3A4 or P-glycoprotein.