Real-world use of denosumab and bisphosphonates in patients with solid tumours and bone metastases in Germany.

PURPOSE: Bisphosphonates and denosumab prevent bone complications in patients with bone metastases from solid tumours. This retrospective, longitudinal, cohort study provides data on their real-world use in this setting in Germany. METHODS: Adults with bone metastases from breast, prostate or lung cancer who were newly initiated on a bisphosphonate or denosumab between 1 July 2011 and 31 December 2015 were identified from a German healthcare insurance claims database. Primary outcomes included persistence, compliance, discontinuation and switch rates at 12 months. RESULTS: This study included 1130 patients with bone metastases: 555 (49%) had breast cancer, 361 (32%) prostate cancer and 242 (21%) lung cancer. Mean age was 65 years for patients with breast or lung cancer and 74 years for those with prostate cancer. Across all tumour types, compared with any bisphosphonate, 12-month persistence was higher with denosumab (breast cancer 78% vs 54-58%, prostate cancer 58% vs 50%, lung cancer 68% vs 34-60%), median time to discontinuation was longer with denosumab and switch rates were lower for denosumab (breast cancer 5% vs 14-19%, prostate cancer 2% vs 11%, lung cancer 3% vs 7-12%). Compliance at 12 months was longer for denosumab than for any bisphosphonate in breast cancer (75% vs 42-48%) and in prostate cancer (47% vs 36%). CONCLUSIONS: Patients initiated on denosumab following a diagnosis of bone metastases from breast, prostate or lung cancer had greater medication persistence, longer time to discontinuation, improved compliance and lower switch rates than those initiated on a bisphosphonate.

Burden and epidemiology of status epilepticus in infants, children, and adolescents: A population-based study on German health insurance data.

OBJECTIVE: Status epilepticus (SE) is an important medical emergency condition with particularly unfavorable outcome in refractory and superrefractory SE (SRSE). The economic impact of SE and especially of SRSE in the pediatric population remains unclear. We aimed to determine the burden of illness of SE in a pediatric patient population. METHODS: Insurance records for patients aged 0-18 years admitted between 2008 and 2015 were selected from a nationwide insurance research database utilizing International Classification of Diseases and Related Health Problems, 10th Revision (ICD-10) codes for SE (G41), epilepsy (G40), or febrile convulsions (R56). Patients were further classified based on admission to the intensive care unit and use of mechanical ventilation. RESULTS: The algorithm identified 11 693 seizure-related admissions and classified 4% as SE. Of these cases, 282 (60.4%) were classified by the algorithm as nonrefractory SE (NRSE), 125 (26.8%) as refractory SE (RSE), and 60 (12.8%) as SRSE. The crude SE incidence was 17.6/100 000, with NRSE being 11.4/100 000, RSE 3.9/100 000, and SRSE 2.3/100 000. SRSE incidence peaked in the 0- to 1-year-old age subgroup accounting for 48.3% of all pediatric SRSE admissions. The median length of stay (LOS) for all SE cases was 7 days, with median 44.5 days in SRSE, 5 days in NRSE, and 12 days in RSE. Mean admission costs for total SE were €15 880, with a mean expense for SRSE of €75 358, for NRSE of €4119, and for RSE of €13 864. The mean LOS for non-SE epilepsy admissions was 3 days, with mean costs of €2697 for epilepsy and €1614 for febrile convulsion admissions. There were no deaths in non-SE and NRSE admissions, whereas the overall mortality for SE was 3%, with 5.6% in RSE and 11.7% in SRSE. SIGNIFICANCE: Although cases classified as SE represented 4% of the seizure-associated admissions, they accounted for 22% of the overall costs. These costs were disproportionately represented by SRSE cases, which accounted for 62% of all SE-associated costs.

Costs, length of stay, and mortality of super-refractory status epilepticus: A population-based study from Germany.

OBJECTIVE: Super-refractory status epilepticus (SRSE) is a severe condition in which a patient in status epilepticus (SE) for ≥24 h does not respond to first-, second-, or third-line therapy. The economic impact of SRSE treatment remains unclear. A health insurance research database was used for a population-based estimation of SRSE-associated inpatient costs, length of stay, and mortality in Germany. METHODS: An algorithm using International Classification of Diseases, 10th Edition coding and treatment parameters identified and classified patients in a German statutory health insurance database covering admissions from 2008 to 2013 as having refractory SE (RSE) or SRSE. Admissions data in our study refer to these classifications. Associated patient data included costs, procedures, and demographics. RESULTS: The algorithm identified 2,585 (all type) SE admissions, classified as 1,655 nonrefractory SE (64%), 592 (22.9%) RSE, and 338 (13.1%) SRSE, producing database incidence rates of 15.0 in 100,000, 5.2 in 100,000, and 3.0 in 100,000 per year, respectively. Median cost per admission was €4,063 for nonrefractory SE, €4,581 (p < 0.001) for RSE, and €32,706 (p < 0.001) for SRSE. Median length of stay varied significantly between 8 days (mean = 13.6) in nonrefractory SE, 14 days in RSE, and up to 37 days in SRSE. Discharge mortality increased from 9.6% in nonrefractory SE to 15.0% (p < 0.001) in RSE and 39.9% (p < 0.001) in SRSE. SIGNIFICANCE: This study evaluated the hospital treatment costs associated with admissions classified by the algorithm as SRSE in Germany. SRSE represented 13% of all SE admissions, but resulted in 56% of all SE-related costs. The lack of approved treatments and limited number of evidence-based treatment guidelines highlight the need for further evaluations of the SRSE burden of illness and the potential for further optimization of treatments for SRSE.

LocTree3 prediction of localization.

The prediction of protein sub-cellular localization is an important step toward elucidating protein function. For each query protein sequence, LocTree2 applies machine learning (profile kernel SVM) to predict the native sub-cellular localization in 18 classes for eukaryotes, in six for bacteria and in three for archaea. The method outputs a score that reflects the reliability of each prediction. LocTree2 has performed on par with or better than any other state-of-the-art method. Here, we report the availability of LocTree3 as a public web server. The server includes the machine learning-based LocTree2 and improves over it through the addition of homology-based inference. Assessed on sequence-unique data, LocTree3 reached an 18-state accuracy Q18=80±3% for eukaryotes and a six-state accuracy Q6=89±4% for bacteria. The server accepts submissions ranging from single protein sequences to entire proteomes. Response time of the unloaded server is about 90 s for a 300-residue eukaryotic protein and a few hours for an entire eukaryotic proteome not considering the generation of the alignments. For over 1000 entirely sequenced organisms, the predictions are directly available as downloads. The web server is available at http://www.rostlab.org/services/loctree3.