Treatment and outcome of 2904 CML patients from the EUTOS population-based registry.

The European Treatment and Outcome Study (EUTOS) population-based registry includes data of all adult patients newly diagnosed with Philadelphia chromosome-positive and/or BCR-ABL1+ chronic myeloid leukemia (CML) in 20 predefined countries and regions of Europe. Registration time ranged from 12 to 60 months between January 2008 and December 2013. Median age was 55 years and median observation time was 29 months. Eighty percent of patients were treated first line with imatinib, and 17% with a second-generation tyrosine kinase inhibitor, mostly according to European LeukemiaNet recommendations. After 12 months, complete cytogenetic remission (CCyR) and major molecular response (MMR) were achieved in 57% and 41% of patients, respectively. Patients with high EUTOS risk scores achieved CCyR and MMR significantly later than patients with low EUTOS risk. Probabilities of overall survival (OS) and progression-free survival for all patients at 12, 24 and 30 months was 97%, 94% and 92%, and 95%, 92% and 90%, respectively. The new EUTOS long-term survival score was validated: the OS of patients differed significantly between the three risk groups. The probability of dying in remission was 1% after 24 months. The current management of patients with tyrosine kinase inhibitors resulted in responses and outcomes in the range reported from clinical trials. These data from a large population-based, patient sample provide a solid benchmark for the evaluation of new treatment policies.

Prognosis of long-term survival considering disease-specific death in patients with chronic myeloid leukemia.

In patients with chronic myeloid leukemia (CML), first-line imatinib treatment leads to 8-year overall survival (OS) probabilities above 80%. Many patients die of reasons unrelated to CML. This work tackled the reassessment of prognosis under particular consideration of the probabilities of dying of CML. Analyses were based on 2290 patients with chronic phase CML treated with imatinib in six clinical trials. 'Death due to CML' was defined by death after disease progression. At 8 years, OS was 89%. Of 208 deceased patients, 44% died of CML. Higher age, more peripheral blasts, bigger spleen and low platelet counts were significantly associated with increased probabilities of dying of CML and determined a new long-term survival score with three prognostic groups. Compared with the low-risk group, the patients of the intermediate- and the high-risk group had significantly higher probabilities of dying of CML. The score was successfully validated in an independent sample of 1120 patients. In both samples, the new score differentiated probabilities of dying of CML better than the Sokal, Euro and the European Treatment and Outcome Study (EUTOS) score. The new score identified 61% low-risk patients with excellent long-term outcome and 12% high-risk patients. The new score supports the prospective assessment of long-term antileukemic efficacy and risk-adapted treatment.

Pro-Active Fall-Risk Management is Mandatory to Sustain in Hospital-Fall Prevention in Older Patients--Validation of the LUCAS Fall-Risk Screening in 2,337 Patients.

OBJECTIVES: Prevention of in-hospital falls contributes to improvement of patient safety. However, the identification of high-risk patients remains a challenge despite knowledge of fall-risk factors. Hence, objective was to prospectively validate the performance of the LUCAS (Longitudinal Urban Cohort Ageing Study) fall-risk screening, based on routine data (fall history, mobility, mental status) and applied by nurses. DESIGN: Observational study comparing two groups of patients who underwent different fall-risk screenings; the LUCAS screening (2010 - 2011) and the STRATIFY (St. Thomas's Risk Assessment Tool In Falling Elderly Inpatients) (2004 - 2006). SETTING: Urban teaching hospital. PARTICIPANTS: Consecutively hospitalized patients (≥ 65 years old) were screened on admission; LUCAS n = 2,337, STRATIFY n = 4,735. MEASUREMENTS: The proportions of fallers were compared between the STRATIFY and the LUCAS time periods. The number of fallers expected was compared to that observed in the LUCAS time period. Standardized fall-incidence recording included case-note checks for unreported falls. Plausibility checks of fall-risk factors and logistic regression analysis for variable fall-risk factors were performed. RESULTS: The proportions of fallers during the two time periods were LUCAS n = 291/2,337 (12.5%) vs. STRATIFY n = 508/4,735 (10.7%). After adjustment for risk-factor prevalence, the proportion of fallers expected was 14.5% (334/2,337), the proportion observed was 12.5% (291/2,337) (p = 0.038). CONCLUSIONS: In-hospital fall prevention including systematic use of the LUCAS fall-risk screening reduced the proportion of fallers compared to that expected from the patients' fall-risk profile. Raw proportions of fallers are not suitable to evaluate fall prevention in hospital because of variable prevalence of patients' fall-risk factors over time. Continuous communication, education and training is needed to sustain in-hospital falls prevention.

The EUTOS population-based registry: incidence and clinical characteristics of 2904 CML patients in 20 European Countries.

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.

Reflectance confocal microscopy for monitoring the density of Demodex mites in patients with rosacea before and after treatment.

BACKGROUND: Demodex mites seem to serve as a pathogenic trigger in many Demodex-associated diseases such as rosacea. In facial skin of patients with rosacea significantly higher numbers of Demodex mites have been shown compared with healthy controls. Reflectance confocal microscopy (RCM) allows the detection and quantification of Demodex mites in vivo noninvasively. It is hypothesized that a reduction of Demodex mites under rosacea therapy can be monitored by RCM. OBJECTIVES: To use RCM to monitor the density of Demodex mites in patients with rosacea before and after treatment. METHODS: In 25 patients with facial rosacea RCM was performed before and after therapy. Mosaics of 5 × 5 mm(2) and 8 × 8 mm(2) were scanned, and the total numbers of mites per follicle and per area were counted, along with the number of follicles per area. RESULTS: In all patients Demodex folliculorum could be detected and quantified using RCM. RCM showed significant differences pre- and post-treatment (P = 0.0053 for 5 × 5 mm(2) and P < 0.001 for 8 × 8 mm(2)). The mean numbers of mites per follicle were 0.63 (range 0.16-2.28) per 8 × 8 mm(2) area and 0.70 (range 0.11-2.20) per 5 × 5 mm(2) area before treatment, and 0.41 (range 0.074-1.75) and 0.51 (range 0.094-1.70), respectively, after treatment. The corresponding mean numbers of mites were 155 (range 45-446) and 86.2 (range 12-286), respectively, before treatment and 96.2 (range 18-363) and 58.5 (range 12-230), respectively, after treatment. CONCLUSIONS: By RCM, a reduction in the density of Demodex mites in facial skin of patients with rosacea under therapy, correlating to clinical improvement, can be quantified and monitored noninvasively. Possible reasons for this therapeutic effect are discussed.

The EUTOS prognostic score: review and validation in 1288 patients with CML treated frontline with imatinib.

The introduction of tyrosine kinase inhibitors (TKI) in the treatment of Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) has revolutionized the outcome, but the prognosis of the disease is still based on prognostic systems that were developed in the era of conventional chemotherapy and interferon (IFN)-alfa. A new prognostic score including only two variables, spleen size and basophils, was developed for the prediction of complete cytogenetic response (CCyR) and progression-free survival (PFS). The score was based on a large series of patients who were enrolled in prospective multicenter studies of first-line imatinib treatment. The prognostic value of the EUTOS (European Treatment and Outcome Study for CML) score has now been tested in an independent, multicenter, multinational series of 1288 patients who were treated first-line with imatinib outside prospective studies. It was found that also in these patients, the EUTOS prognostic score was predictive for CCyR, PFS and overall survival (OS). In addition, the prognostic value of the score was reported to be significant in seven of the eight other independent studies of almost 2000 patients that were performed in Europe, the Americas and Asia. The EUTOS risk score is a valid tool for the prediction of the therapeutic effects of TKI, particularly imatinib.

In-hospital fall-risk screening in 4,735 geriatric patients from the LUCAS project.

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.

Noninvasive in vivo detection and quantification of Demodex mites by confocal laser scanning microscopy.

BACKGROUND: In many Demodex-associated skin diseases Demodex mites are present in abundance and seem to be at least partially pathogenic. So far all diagnostic approaches such as scraping or standardized superficial skin biopsy are (semi-)invasive and may cause discomfort to the patient. OBJECTIVES: To see whether confocal laser scanning microscopy (CLSM) - a noninvasive method for the visualization of superficial skin layers - is able to detect and quantify D. folliculorum in facial skin of patients with rosacea. METHODS: Twenty-five patients (34-72 years of age) with facial rosacea and 25 age- and sex-matched normal controls were examined by CLSM. Mosaics of 8 × 8 mm and 5 × 5 mm were created by scanning horizontal layers of lesional skin and quantification of mites per follicle and per area as well as follicles per area was performed. RESULTS: In all patients D. folliculorum could be detected by CLSM and presented as roundish or lengthy cone-shaped structures. CLSM allowed the quantification of Demodex mites and revealed significant differences (P < 0·0001): the mean number of mites was 165·4 per 8 × 8 mm area and 94·2 per 5 × 5 mm area in the patients compared with 34·7 and 22·4, respectively, in the controls. The corresponding mean number of mites per follicle was 0·7 and 0·8, respectively, in the patients and 0·1 and 0·2, respectively, in the controls. CONCLUSIONS: With the help of CLSM it is possible to detect, image and quantify Demodex mites noninvasively in facial skin of patients with rosacea.