Search

Purpose: Reporting of adverse drug reactions (ADRs) by patients is essential for a comprehensive risk–benefit evaluation of drugs after marketing, but only few data are available regarding patient-centred web-based ADR reporting systems. Hence, we aimed to analyze ADRs reported by patients with a particular emphasis on novel drugs and serious ADRs not yet labelled in the respective summary of product characteristics (SPC). Methods: All ADR reports received by a web-based, patient-centred platform (www.nebenwirkungen.de) between April 1, 2019, and September 1, 2020, were descriptively analyzed. ADRs and drugs were coded automatically according to MedDRA and ATC classification system. SPC labelling of reported ADRs for novel drugs marketed since 2015 was checked manually. Results: In total, 13,515 patient reports including 29,529 ADRs were received during the study period (serious ADRs [SADRs] n = 1,318; 4.5%). Women were affected in more than two-thirds of ADR reports. The most common patient-reported ADRs were nausea, dizziness and headache, whereas arrhythmia, intestinal obstruction and erectile dysfunction were the most frequent SADRs. Ciprofloxacin, levothyroxine and venlafaxine were the compounds most frequently suspected for causing both ADRs and SADRs. Regarding novel compounds, 289 reports including 739 ADRs were received (mainly fatigue, headache and myalgia). Three hundred thirty-one (44.8%) out of those ADRs were not yet labelled in the respective SPC, whereof twelve were SADRs. Conclusion: The majority of patient-reported ADRs were non-serious. However, a relevant number of non-labelled even serious ADRs was reported for novel compounds by patients. Despite well-known limitations of patient-reported ADRs, this web-based ADR reporting system contributes to the identification of new ADRs and thus can help to improve patients' safety complementing other pharmacovigilance instruments. [ABSTRACT FROM AUTHOR]

Purpose: Results from observational studies on inhaled long-acting beta-2-agonists (LABA) and acute myocardial infarction (AMI) risk are conflicting, presumably due to variation in methodology. We aimed to evaluate the impact of applying a common study protocol on consistency of results in three databases. Methods: In the primary analysis, we included patients from two GP databases (Dutch-Mondriaan, UK-CPRD GOLD) with a diagnosis of asthma and/or COPD and at least one inhaled LABA or a 'non-LABA inhaled bronchodilator medication' (short-acting beta-2-agonist or short-/long-acting muscarinic antagonist) prescription between 2002 and 2009. A claims database (USA-Clinformatics) was used for replication. LABA use was divided into current, recent (first 91 days following the end of a treatment episode), and past use (after more than 91 days following the end of a treatment episode). Adjusted hazard ratios (AMI-aHR) and 95 % confidence intervals (95 % CI) were estimated using time-dependent multivariable Cox regression models stratified by recorded diagnoses (asthma, COPD, or both asthma and COPD). Results: For asthma or COPD patients, no statistically significant AMI-aHRs (age- and sex-adjusted) were found in the primary analysis. For patients with both diagnoses, a decreased AMI-aHR was found for current vs. recent LABA use in the CPRD GOLD (0.78; 95 % CI 0.68-0.90) and in Mondriaan (0.55; 95 % CI 0.28-1.08), too. The replication study yielded similar results. Adjusting for concomitant medication use and comorbidities, in addition to age and sex, had little impact on the results. Conclusions: By using a common protocol, we observed similar results in the primary analysis performed in two GP databases and in the replication study in a claims database. Regarding differences between databases, a common protocol facilitates interpreting results due to minimized methodological variations. However, results of multinational comparative observational studies might be affected by bias not fully addressed by a common protocol. [ABSTRACT FROM AUTHOR]

This population-based registry was designed to provide robust and updated information on the characteristics and the epidemiology of chronic myeloid leukemia (CML). All cases of newly diagnosed Philadelphia positive, BCR-ABL1+ CML that occurred in a sample of 92.5 million adults living in 20 European countries, were registered over a median period of 39 months. 94.3% of the 2904 CML patients were diagnosed in chronic phase (CP). Median age was 56 years. 55.5% of patients had comorbidities, mainly cardiovascular (41.9%). High-risk patients were 24.7% by Sokal, 10.8% by EURO, and 11.8% by EUTOS risk scores. The raw incidence increased with age from 0.39/100 000/year in people 20-29 years old to 1.52 in those >70 years old, and showed a maximum of 1.39 in Italy and a minimum of 0.69 in Poland (all countries together: 0.99). The proportion of Sokal and Euro score high-risk patients seen in many countries indicates that trial patients were not a positive selection. Thus from a clinical point of view the results of most trials can be generalized to most countries. The incidences observed among European countries did not differ substantially. The estimated number of new CML cases per year in Europe is about 6370. [ABSTRACT FROM AUTHOR]

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]

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.)

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]

Marrow fibrosis (MF) has rarely been considered in therapy studies on chronic myeloid leukemia (CML), and there is a lack of long-term observations on the basis of sequential bone marrow biopsies (BMBs) taken prospectively during the course of disease. A total of 848 BMBs from 400 patients with Ph+ CML recruited in the German randomized CML study I were examined for MF before and during therapy. In total, 110 patients had been randomized to receive interferon (IFN)-a, and 290 to receive chemotherapy (hydroxyurea (HU): 154, busulfan: 136). During IFN-a and HU medication, MF was reduced or did not increase for about 2 years. Evolving or progressive MF was an independent and early predictor of therapy failure about 2 years earlier than indicated by changes in the peripheral blood, spleen size, marrow blast count and cytogenetics (P<0.00005), resulting in a significant shortening of the survival times of patients independent of the type of therapy applied including allografting (multivariate analyses; P<0.00005). The analyzed long-term observations strongly indicate that MF is an independent poor prognostic complication of CML, allowing an early prediction of therapy failure. Consideration of the fiber content in marrow may therefore significantly improve the prediction of therapy efficacy and outcome of disease.Leukemia (2003) 17, 2444-2453. doi:10.1038/sj.leu.2403172 Published online 16 October 2003 [ABSTRACT FROM AUTHOR]

Chronic myeloid leukemia (CML) in older patients has not been studied well. To assess the long-term outcome of older patients with Philadelphia- and/or BCR-ABL-positive CML, 199 patients aged ?60 years representing 23% of 856 patients enrolled in the German randomized CML-studies I (interferon a (IFN) vs hydroxyurea (HU) vs busulfan (BU) and II (IFN+HU vs HU alone) were analyzed after a median observation time of 7 years. In all, 45 patients were treated with Bu, 63 with HU, and 91 with IFN. The 5-year survival was 38% in patients ?60 years and 47% in patients <60 years (P<0.001). Whereas 5-year survival in chemotherapy-treated older patients was inferior to that in younger patients (33 vs 46%, P=0.006 for HU and 29 vs 38%, P=0.042 for Bu), no significant survival difference could be verified in IFN-treated patients (46 vs 53%, P=0.077). Calculation of age-adjusted, relative survival confirmed these results. Adverse effects of IFN were similar in both age groups, but IFN dosage to achieve treatment goals was lower in older patients. We conclude that the course of CML is not different in the elderly. They require lower IFN doses, achieve the same hematologic and cytogenetic response rates and the same survival advantage at comparable toxicity.Leukemia (2003) 17, 1820-1826. doi:10.1038/sj.leu.2403042 [ABSTRACT FROM AUTHOR]

The optimum treatment conditions of interferon (IFN) a therapy in chronic myeloid leukemia (CML) are still controversial. To evaluate the role of hydroxyurea (HU) for the outcome of IFN therapy, we conducted a randomized trial to compare the combination of IFN and HU vs HU monotherapy (CML-study II). From February 1991 to December 1994, 376 patients with newly diagnosed CML in chronic phase were randomized. In all, 340 patients were Ph/BCR-ABL positive and evaluable. Randomization was unbalanced 1:2 in favor of the combination therapy, since study conditions were identical to the previous CML-study I and it had been planned in advance to add the HU patients of study I (n=194) to the HU control group. Therefore, a total of 534 patients were evaluable (226 patients with IFN/HU and 308 patients with HU). Analyses were according to intention-to-treat. Median observation time of nontransplanted living patients was 7.6 years (7.9 years for IFN/HU and 7.3 years for HU). The risk profile (new CML score) was available for 532 patients: 200 patients (38%) were low, 239 patients (45%) intermediate, and 93 patients (17%) high risk. Complete hematologic response rates were higher in IFN/HU-treated patients (59 vs 32%). Of 169 evaluable IFN/HU-treated patients (75%), 104 patients (62%) achieved a cytogenetic response that was complete in 12% (n=21), major in 14% (n=24), and at least minimal in 35% (n=59). Of the 534 patients, 105 (20%) underwent allogeneic stem cell transplantation in first chronic phase. In the low-risk group, 65 of 200 patients were transplanted (33%), 30 (13%) in the intermediate-risk group, and nine (10%) in the high-risk group. Duration of chronic phase was 55 months for IFN/HU and 41 months for HU (P<0.0001). Median survival was 64 months for IFN/HU and 53 months for HU-treated patients (P=0.0063). We conclude that IFN in combination with HU achieves a significant long-term survival advantage over HU monotherapy. In view of the data of CML-study I, these results suggest that IFN/HU is also superior to IFN alone. HU should be combined with IFN in IFN-based therapies and for comparisons with new therapies.Leukemia (2003) 17, 1529-1537. doi:10.1038/sj.leu.2403006 [ABSTRACT FROM AUTHOR]

Due to eligibility criteria not all patients with the disease under investigation can be recruited for therapeutic studies. Thus, the external validity of study results cannot per se be taken for granted. The representativity of the admitted patients is the most relevant determinant for external validity and has to be assessed. As an example we examined the representativity of the patients recruited for the German multicenter study group for adult acute lymphoblastic leukemia (ALL) (GMALL). Lacking nationwide ALL incidence figures available in Germany, a methodology was developed to estimate incidence figures, too. All relevant study groups, hospitals, and diagnostic labs were asked to provide data about patients with ALL newly diagnosed between 1997 and 1998. A matching procedure was developed, as heterogeneous databases had to be pooled and checked for duplicates. Age- and sex-specific incidences of ALL were estimated and compared with the number of patients recruited for the GMALL in the same time period. The purpose was to develop a methodology for estimating incidence figures and evaluating the representativity of patients of the GMALL. The combination of various data sources allowed estimation of reliable incidence data for ALL in Germany. Comparisons with the incidence figures for ALL in other countries and crosschecks within Germany confirm our results. Sixty-two percent of all ALL patients in Germany were admitted to the GMALL study. The recruitment rate of more than 60% of the annual incidence of ALL to the GMALL suggests a high external validity as well as an impact of the study on the patterns of treatment and referral of ALL in adults in Germany. There is no selection bias of patients admitted to the GMALL compared to those patients not included in the study. [ABSTRACT FROM AUTHOR]

This study assessed the percentage of patients after 1 year who persisted on initially prescribed antihypertensive therapy. Medical records of 2416 patients with newly diagnosed hypertension who were prescribed initial antihypertensive monotherapy by general practitioners in Germany, France, and the United Kingdom were evaluated. Comparisons were made among the angiotensin II receptor antagonist (AIIRA) irbesartan, all other antihypertensive classes (including AIIRAs other than irbesartan), and the AIIRA losartan. Patients initiated on the AIIRA irbesartan scored highest with a persistence rate of 60.8%, followed by patients who received all other AIIRA agents with a persistence rate of 51.3%. Angiotensin-converting enzyme inhibitors, calcium channel blockers, beta-blockers, and Iosartan were associated with comparable persistence rates, between 42.0% and 49.7%. Patients who received diuretics scored lowest with a persistence rate of 34.4%. Persistence has emerged as an essential factor for blood pressure control. Prescribing an antihypertensive agent that provides a favourable efficacy and tolerability profile may provide greater persistence with therapy and hence a higher level of blood pressure control. [ABSTRACT FROM AUTHOR]

Copyright of Der Nervenarzt 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.)

Since, for obvious reasons, systematic testing of the teratogenic properties of drugs in humans is not possible in the premarketing phase, the epidemiological approaches to postmarketing risk evaluation are of major importance. Cohort studies, with their prospective exposure assessment, their ability to study even exposure to drugs not commonly used in pregnancy, and their ability to monitor both adverse and beneficial fetal outcomes, seem to be the most promising study type from a methodological viewpoint. Although there are numerous cohort studies on the harmful effects of drug use in pregnant women, only a few have been able to demonstrate a risk in terms of an increase in the prevalence of malformations. Most studies with significant findings were those investigating the risk potential of one group of drugs, the anticonvulsants. The lack of cohort studies showing a risk for drug use in pregnancy, however, is not necessarily indicative of some methodological deficiency. Rather, it may suggest that, for the majority of drugs, their use in pregnancy is not associated with an increased risk of congenital malformations. [ABSTRACT FROM AUTHOR]

Chronic renal insufficiency is often accompanied by hyperlipidaemia and subsequent coronary heart disease. Two groups of 15 patients with serum creatinine >2 mg/100 ml and serum cholesterol >250 mg/100 ml were given 3×50 mg magnesium pyridoxal 5-phosphate glutamate (MPPG) or placebo for 12 weeks in a double-blind, randomised study. Total cholesterol in the MPPG group (282.4 mg·100 ml) was lower than in the placebo group (354.3 mg·100 ml) after 12 weeks of treatment. Triglycerides in the MPPG group were 265.1 mg·100 ml compared to 361.9 mg·100 ml. After 12 weeks on MPPG the LDL/HDL ratio of 3.56 was lower than in the placebo group - 6.83. Side effects in the MPPG group were similar to those in the placebo group. Thus, MPPG was an effective antihyperlipidaemic agent in patients with renal insufficiency. [ABSTRACT FROM AUTHOR]

Background: Interferon alfa is a conservative and widely used alternative to bone marrow transplantation in treatment of patients with early chronic myeloid leukemia (CML). A meta-analysis was conducted to develop a reliable prognostic scoring system for estimation of survival of patients with CML treated with interferon alfa.Methods: Patients treated in prospective studies, including major randomized trials, were separated into learning and validation samples. Cox regression analysis and the minimum P-value approach were used to identify prognostic factors for patient survival and to discover groups in the learning sample with the greatest differences in survival. These findings were then validated by applying the new scoring system to patients in the validation sample.Results: We collected data on 1573 patients who were participants in 14 studies involving 12 institutions; 1303 patients (learning sample, n = 981; validation sample, n = 322) were eligible for inclusion in this analysis, and their median survival time was 69 months (range, 1-117 months). Because two previously described prognostic scoring systems failed to discriminate risk groups satisfactorily, we developed a new scoring system that utilizes the following covariates: age, spleen size, blast count, platelet count, eosinophil count, and basophil count. Among 908 patients with complete data in the learning sample, three distinct risk groups were identified (median survival times of 98 months [n = 369; 40.6%], 65 months [n = 406; 44.7%], or 42 months [n = 133;14.6%]; two-sided logrank test, P< or =.0001). The ability of the new scoring system to discriminate these risk groups was confirmed by analysis of 285 patients with complete data in the validation sample (two-sided logrank test, P = .0002).Conclusions: A new prognostic scoring system for estimating survival of patients with CML treated with interferon alfa has been developed and validated through use of a large dataset. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented about a study which determines the population-based age- and gender-specific incidences of chronic myeloid leukemia (CML) and other chronic myeloproliferative disorders, and myelomonocytic leukemia (CMML) in a representative region of Germany.

Focuses on the survival of chronic myeloid leukemia (CML) patients treated with imatinib mesylate. Significance of the approval of imatinib mesylate for the treatment of Philadelphia chromosome-positive CML; Examination on the cytogenetic response of patients treated with the novel agent; Assessment on the efficacy of the new treatment approach compared with interferon.

Objectives: Company observational post-marketing studies (COPS) claim to provide essential data about drug risks and effectiveness in special populations not admitted to pre-approval clinical trials. Since COPS are often mainly regarded as a marketing activity, this study-based analysis tries to evaluate the scientific contributions of COPS. Material and methods: Thirty-five COPS were identified by hand-searching through medical journals, writing to pharmaceutical manufacturers and using MEDLINE. Fourteen COPS evaluated cardiovascular drugs, 9 evaluated NSAIDs and 12 evaluated various other indications. Results: Thirty-five COPS listed effectiveness, 31 listed safety and 8 listed patient compliance as principal objectives. Not a single COPS included a control group. Seventeen of 21 evaluable COPS mentioned extensive exclusion criteria similar to those in clinical trials. Median observation time was 8 weeks, too short for chronic diseases and for adverse drug reactions with longer latency periods. One new adverse event was regarded. Global assessments of the outcomes by physicians dominated and were not based on objective clinical findings. None of the studies specified any details concerning the standardisation of observations or quality-control procedures. Discussion and conclusion: The current COPS scheme does not contribute significantly to our knowledge of drug safety and the effects in special populations. Despite serious criticism over the past 20 years, the poor quality of COPS – compared with dramatic improvements of pre-approval trials – implies a need for detailed guidelines for non-experimental phase IV research, similar to the Good Clinical Practice-Guideline of the European Community. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Declining Public Health Burden of Digoxin Toxicity From 1991 to 2004," by S. Schmiedl, M. Rottenkolber, J. Szymanski, J. Hasford, and P. A. Thuermann in the December 2008 issue.

Focuses on the comparison of immunomodulatory treatments which is a retrospective open label study in patients treated with beta interferons or glatiramer acetate (GA). Claim of the authors that the reduction of the relapse rate was significantly higher for GA-treated patients than with interferons; Highlights of the research; Significance of the absent of adjustment of the alpha levels of the statistical tests; Failure of the data bank-based cohort study to meet the accepted and essential quality criteria.

Introduction: In-hospital falls of elderly patients have considerable impact on health outcome1 and costs.2 During 2004–2009, the STRATIFY fall-risk screening was applied in a geriatric hospital to identify high-risk patients.3,4 As the results left room for improvement the LUCAS Fall-Risk Screening was developed and validated.5 High-risk patients are classified by ≥ 2/3 risk-factors (insecure mobility, fall-history, mental-status). The objective was to prospectively evaluate the LUCAS-Screening after implementation in 2010.Methods: The fall-prevention-interventions provided to high-risk patients as identified by STRATIFY and LUCAS have not been changed. Rates of fallers were compared using datasets a) STRATIFY (2004-2006) and b) LUCAS-Screening (2010–2011). Logistic regression analysis accounted for varying distribution of risk-factors. Expected and observed number of fallers was compared in the LUCAS dataset.Results: The LUCAS and STRATIFY datasets contained 2,337 and 4,735 patients; 66.8% vs. 69.9% females; mean age 82 years in both datasets. Due to changed risk profile the number of fallers increased: LUCAS 291 (12.5%) vs. STRATIFY 508 (10.7%). When adjusting for the risk-factor prevalence the rate of fallers as expected was 14.5%, but the 12.5% rate observed was significantly lower (p = 0.038).Conclusions: In-hospital fall prevention using the LUCAS-Screening was effective in reducing the number of fallers despite increasing prevalence of fall-risk factors.LREC: Hamburg General-Medical-Council-Ethics-Committee (No.PV-2980).Funding: Federal Ministry for Education and Research (BMBF), Berlin (No.01ET1002A). [ABSTRACT FROM AUTHOR]

Introduction: In-hospital falls of elderly patients have considerable impact on health outcome1 and costs.2 During 2004–2009, the STRATIFY fall-risk screening was applied in a geriatric hospital to identify high-risk patients.3,4 As the results left room for improvement the LUCAS Fall-Risk Screening was developed and validated.5 High-risk patients are classified by ≥ 2/3 risk-factors (insecure mobility, fall-history, mental-status). The objective was to prospectively evaluate the LUCAS-Screening after implementation in 2010.Methods: The fall-prevention-interventions provided to high-risk patients as identified by STRATIFY and LUCAS have not been changed. Rates of fallers were compared using datasets a) STRATIFY (2004-2006) and b) LUCAS-Screening (2010–2011). Logistic regression analysis accounted for varying distribution of risk-factors. Expected and observed number of fallers was compared in the LUCAS dataset.Results: The LUCAS and STRATIFY datasets contained 2,337 and 4,735 patients; 66.8% vs. 69.9% females; mean age 82 years in both datasets. Due to changed risk profile the number of fallers increased: LUCAS 291 (12.5%) vs. STRATIFY 508 (10.7%). When adjusting for the risk-factor prevalence the rate of fallers as expected was 14.5%, but the 12.5% rate observed was significantly lower (p = 0.038).Conclusions: In-hospital fall prevention using the LUCAS-Screening was effective in reducing the number of fallers despite increasing prevalence of fall-risk factors.LREC: Hamburg General-Medical-Council-Ethics-Committee (No.PV-2980).Funding: Federal Ministry for Education and Research (BMBF), Berlin (No.01ET1002A). [ABSTRACT FROM PUBLISHER]

Copyright of Infection 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.)