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Data comparing long-term outcomes in lenalidomide-treated and untreated patients with myelodysplastic syndromes (MDS) with del(5q) are limited. We evaluated clinical outcomes of 295 lenalidomide-treated patients from two clinical trials (MDS-003 and MDS-004) and 125 untreated red blood cell (RBC) transfusion-dependent patients with del(5q) Low- or Intermediate-1 (Int-1)-risk MDS from a large multicenter registry. Risk factors for acute myeloid leukemia (AML) progression and mortality were assessed using Cox proportional hazards models with left truncation to adjust for study entry differences between cohorts. Baseline characteristics were well balanced across cohorts, except for a higher RBC transfusion burden in lenalidomide-treated patients (median, 6 vs 2 units/8 weeks). Median follow-up was 4.3 years from first dose for lenalidomide-treated patients and 4.6 years from diagnosis for untreated patients. Two-year cumulative AML progression incidences were 6.9% (95% confidence interval (CI): 3.3-13.9) and 12.1% (95% CI: 7.0-20.3) and 2-year overall survival (OS) probabilities were 89.9% (95% CI: 84.1-96.0) and 74.4% (95% CI: 66.1-83.7), respectively. AML progression risk was similar in both cohorts (hazard ratio (HR) 0.969, P=0.930); however, lenalidomide treatment was associated with significant improvement in survival (HR 0.597, P=0.012), after adjusting for all other covariates. In conclusion, lenalidomide treatment does not increase AML progression risk, but instead confers a possible survival benefit in RBC transfusion-dependent patients with del(5q) Low- or Int-1-risk MDS. [ABSTRACT FROM AUTHOR]

Objectives: In-hospital falls in older patients are frequent, but the identification of patients at risk of falling is challenging. Aim of this study was to improve the identification of high-risk patients. Therefore, a simplified screening-tool was developed, validated, and compared to the STRATIFY predictive accuracy. Design: Retrospective analysis of 4,735 patients; evaluation of predictive accuracy of STRATIFY and its single risk factors, as well as age, gender and psychotropic medication; splitting the dataset into a learning and a validation sample for modelling fall-risk screening and independent, temporal validation. Setting: Geriatric clinic at an academic teaching hospital in Hamburg, Germany. Participants: 4,735 hospitalised patients ≥65 years. Measurements: Sensitivity, specificity, positive and negative predictive value, Odds Ratios, Youden-Index and the rates of falls and fallers were calculated. Results: There were 10.7% fallers, and the fall rate was 7.9/1,000 hospital days. In the learning sample, mental alteration (OR 2.9), fall history (OR 2.1), and insecure mobility (Barthel-Index items 'transfer' + 'walking' score = 5, 10 or 15) (OR 2.3) had the most strongest association to falls. The LUCAS Fall-Risk Screening uses these risk factors, and patients with ≥2 risk factors contributed to the high-risk group (30.9%). In the validation sample, STRATIFY SENS was 56.8, SPEC 59.6, PPV 13.5 and NPV 92.6 vs. LUCAS Fall-Risk Screening was SENS 46.0, SPEC 71.1, PPV 14.9 and NPV 92.3. Conclusions: Both the STRATIFY and the LUCAS Fall-Risk Screening showed comparable results in defining a high-risk group. Impaired mobility and cognitive status were closely associated to falls. The results do underscore the importance of functional status as essential fall-risk factor in older hospitalised patients. [ABSTRACT FROM AUTHOR]

Copyright of Zeitschrift für Gerontologie und Geriatrie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The aim of this work was to provide guidelines for appropriate statistical analyses regarding most common endpoints in clinical trials on chronic myeloid leukemia: hematologic, cytogenetic and molecular results, failure-free and event-free survival, and progression-free and overall survival. The reasons for the specified recommendations are explained and important issues are outlined by comprehensive examples. Particular attention is paid to the warning of the application of suboptimal methods that may lead to seriously biased results and conclusions. In the presence of a competing risk like death, Kaplan-Meier analysis should not be applied for time-to-remission endpoints. The appropriate method to estimate the probabilities of a time-to-remission endpoint is the calculation of its cumulative incidence function. However, the exact date of remission is hardly known. Detection of remission depends strongly on evaluation frequencies. Complex composite endpoints comprising many events with considerably heterogeneous severity imply difficulties with interpretation. Time-to-remission and complex composite endpoints are not recommended for primary judgment on efficacy. It is rather advisable to investigate remission status at a fixed time point as a primary endpoint, followed by progression-free and overall survival. For patients with the intended remission success at the time point of interest, relapse-free survival provides an additional primary outcome. [ABSTRACT FROM AUTHOR]

Copyright of Zeitschrift für Gerontologie und Geriatrie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract: Objectives: The methodology for the critical assessment of medical interventions is well established. Regulatory agencies and institutions adhere, in principle, to the same standards. This consistency, however, is not always the case in practice. Study Design and Setting: Using the evaluation of the CAPRIE (Clopidogrel versus Aspirin in Patients at risk of Ischemic Events) trial by the British National Institute for Health and Clinical Excellence (NICE) and the German Institute for Quality and Efficiency in Health Care (IQWiG), we illustrate that there was no consensus for the interpretation of possible heterogeneity in treatment comparisons across subgroups. Results: The NICE concluded that CAPRIE demonstrated clinical benefit for the overall intention-to-treat (ITT) population with sufficient robustness to possible sources of heterogeneity. The IQWiG interpreted the alleged heterogeneity as implying that the clinical benefit only applied to the subgroup of patients with a statistically significant result irrespective of the results of the ITT analysis. Conclusion: International standards for the performance and interpretation of subgroup analyses as well as for the assessment of heterogeneity between strata are needed. [Copyright &y& Elsevier]

To cite this article: Hasford J, Uricher J, Tauscher M, Bramlage P, Virchow JC. Persistence with asthma treatment is low in Germany especially for controller medication – a population based study of 483 051 patients. Allergy 2010; 65: 347–354. Background: The objective of the present analysis was to evaluate treatment patterns and persistence with treatment of an unselected patient population with a diagnosis of asthma. Methods: The database of the Bavarian statutory health insurance physician’s association (Kassenärztliche Vereinigung) covering 83% of the population was analyzed for an index period from April 2005 to March 2006. Defined daily doses (DDDs) were used to quantify treatment persistence. Results were compared with recent guidelines. Results: The prevalence of physician diagnosed asthma in Bavaria was 4.8% in females and 4.5% in males; only 61.4% of these patients (of a total of n = 483 051) received any anti-asthmatic pharmacotherapy; 68.3% received medical care from their general practitioner, and 8.3% from a pulmonologist alone. Most patients (65.1%) received no more than 90 DDDs of controller medication in the index period of 365 days, only about 1% received medication for the complete index period. Long- (40.1%) and short-acting β2-agonists (65.6%) were used more frequently than inhaled corticosteroids (ICS). 52.8% of asthma patients were treated in accordance with guidelines. Conclusions: Persistence of asthma patients with medical treatment is low, especially for controller medication. The discrepancy between current knowledge, guidelines and clinical practice is substantial and may question the value of current guidelines for the treatment of patients with asthma in ambulatory care. In addition, the results of this study cast doubt on the impact of contemporary treatment on the decline of asthma mortality seen in recent years in Germany. [ABSTRACT FROM AUTHOR]

We investigated the impact of a cytogenetic response (CyR) to IFN prior to and at the time of allogeneic hematopoietic stem cell transplantation (HSCT) on transplant-related mortality (TRM), relapse rate and survival probability after HSCT in 162 transplanted patients with chronic myeloid leukemia. One-hundred-one patients (62.3%) achieved a CyR prior to HSCT. Survival probabilities were higher in patients, who achieved any CyR prior to HSCT than in patients without CyR (63.6 vs 49.2%: P=0.019). Survival probabilities in patients, who achieved a major CyR were better than in patients with minimal and minor CyR or in patients with no CyR (69.4 vs 58.8% vs 49.2%: P=0.040). TRM and survival of chronic phase patients without CyR at the time of HSCT were similar to that of patients transplanted in advanced phase. Both groups combined had an outcome inferior to patients with at least minimal CyR (TRM, Gray test: P=0.016, survival, log-rank test: P=0.002). Univariate and multivariate analyses identified CyR prior to or at HSCT as a strong and independently favorable prognostic factor. We therefore conclude that allogeneic HSCT in CyR should be investigated prospectively as an alternative treatment option in defined patient groups.Leukemia (2006) 20, 477–484. doi:10.1038/sj.leu.2404100; published online 2 February 2006 [ABSTRACT FROM AUTHOR]

Objectives: In chronic myeloid leukemia, after promising results in major cytogenetic remission (MCR), long-term survival data on imatinib treatment is of particular interest, especially in relation to former standard treatment based on interferon-alpha. However, data is still unavailable and due to high remission rates, most patients randomized to interferon-alpha in a clinical trial crossed over to imatinib. Therefore, to assess the expected long-term survival advantage with imatinib, a simulation study based on prognostic factors validated for interferon-alpha treatment was performed.Methods: In interferon-alpha-treated patients with intermediate-risk and low-risk according to the established New CML score, survival probabilities of patients with MCR were significantly higher than those of patients without MCR. Three samples with simulated survival data for imatinib-treated intermediate-risk patients were constituted by randomly drawing varying percentages of their survival times from interferon-alpha-treated intermediate-risk patients with MCR and the remaining data from intermediate-risk patients without MCR. The same procedure was applied to low-risk patients.Results: The 10-year survival probabilities of inter-feron-alpha-treated intermediate-risk and low-risk patients were 0.22 and 0.37. In the simulated samples, when 80%, 65%, and 50% of survival times were as favorable as for interferon-alpha-treated patients with MCR, respectively, the corresponding survival probabilities were 0.43 and 0.57, 0.36 and 0.49, and 0.30 and 0.42.Conclusions: In all simulation samples, increments of survival probabilities by imatinib were predicted, although survival probabilities of patients with MCR were assumed to be lower than with interferon-alpha. Prognosticated survival advantage with imatinib is backed by increasing observation time of imatinib-treated patients in real studies. [ABSTRACT FROM AUTHOR]

Gender-related aspects in chronic myeloid leukemia (CML) have not been studied well. We therefore analyzed 856 patients with Ph/BCR-ABL-positive CML from the German randomized CML-studies I (interferona(IFN) vs hydroxyurea (HU) vs busulfan) and II (IFN+HU vs HU alone). The median observation time was 8.6 years. A total of 503 patients (59%) were male. Female patients were older (51 vs 46 years; P<0.0001), presented with lower hemoglobin (11.7 vs 12.5?g/dl; P<0.0001), higher platelet counts (459 vs 355×109/l; P<0.0001), smaller spleen size (3 vs 4?cm below costal margin; P=0.0097), a lower rate of additional cytogenetic aberrations (9 vs 15%; P=0.018) and a less favorable risk profile (P=0.036). The transplantation rate was 14%for female (n=48) and 22%for male patients (n=113). Median survival was longer in female patients (58 vs 49 months; P=0.035) mainly attributable to better survival in the low- and intermediate-risk groups and, independent from risk groups, in the HU group. These results were confirmed by matched-pair analyses based on German population data (n=496, 59 vs 45 months; P=0.0006). This is the first analysis of gender aspects in CML using randomized trials. It demonstrates the relevance of analyses of gender differences in CML and in malignant disease at large.Leukemia (2005) 19, 984-989. doi:10.1038/sj.leu.2403756 Published online 14 April 2005 [ABSTRACT FROM AUTHOR]

Bone marrow fibrosis (MF) has been shown to indicate therapy failure in Ph+ chronic myeloid leukemia (CML). However, the results on the development of MF during interferon-a therapy of CML are controversial. The significance of the interferon dose has not been considered as yet. In total, 627 bone marrow biopsies taken prospectively from 200 patients with CML recruited in two studies using different doses of interferon-a ± low-dose cytosine arabinoside were examined for MF before and during therapy. The results showed that the risk of MF depended significantly on the interferon-a dose applied (P<0.000005). MF progressed during low-dose therapy (3 × 5 × 106?IU/week), but was prevented from progression when applying high dose (5 × 106?IU/m2/per day). MF disappeared when high-dose interferon-a was combined with low-dose cytosine arabinoside (P<0.000005). The risk of death markedly increased when MF occurred or progressed (P<0.0009), independent of all other prognostic factors evaluated including the cytogenetic response. In conclusion, the effectiveness of interferon-a on MF depends on the treatment intensity. MF reverses when combining high-dose interferon-a with low-dose cytosine arabinoside, but progresses when applying low-dose interferon-a. MF appears to be a significant early indicator of ineffective therapy in CML.Leukemia (2004) 18, 1460-1467. doi:10.1038/sj.leu.2403451 Published online 29 July 2004 [ABSTRACT FROM AUTHOR]