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Background: Osteoporosis (OP) and its associated fractures have a significant impact on patients’ quality of life and are impacting their morbidity and mortality. For OP patients at high risk of fracture, guidelines recommend a pharmacological OP treatment. The aim of this study was to describe the real-world medication treatment of postmenopausal women with severe OP at high risk of fracture, their risk to experience a new fracture after having at least one previous fracture, and to assess the associated healthcare resource use (HCRU).Methods: This retrospective cohort study was based on anonymized German claims data (AOK PLUS). All included OP patients were female, ≥55 years old, and had a vertebral and/or femoral fracture. We conducted a cross-sectional analysis in 2018 and a longitudinal analysis, starting with an incident vertebral/femoral fracture (after or simultaneously with the first observed OP diagnosis). In both analyses, patient characteristics, rate of new incident fractures, OP treatment patterns, and HCRU associated with the treatment of patients were investigated.Results: In the cross-sectional setting, 12,180 patients with a mean age of 83.59 years were observed. Of these patients, 14.30% sustained at least one new incident fracture and 34.54% received a pharmaceutical OP treatment during 2018. In this year, 58.50% of the patients had at least one OP-related outpatient visit, and 26.35% had a fracture-related visit. In 160 patients (1.31%), at least one OP-related hospitalization was documented, and in 1,293 patients (10.62%) a fracture-related hospitalization in 2018.In the longitudinal setting, 10,323 patients with a mean age of 83.22 years were included. Of these, 18.96% experienced at least one new incident fracture within the first 12 months after the index fracture, and in total 30.85% in the entire follow-up period (mean 2.03 years). During the 12-month baseline period, 22.12% of the patients received an OP treatment. Three months after the index fracture, the proportion of treated patients remained at 22.30%. During the total follow-up time, 35.54% were prescribed with an OP treatment.Conclusion: We observed a considerable proportion of untreated patients and a high rate of subsequent fractures. The awareness for a proper risk assessment and the appropriate use of available treatments should be increased.

Objectives: The aim of this study was to investigate the antiepileptic drug (AED) treatment of adults suffering from focal epilepsies (FE) in Germany. Of special interest was the number and percentage of the patients 16 years and older receiving no treatment with an AED, treatment with one AED (monotherapy), treatment with more than one AED, and treatment with a novel AED. The definition for “novel” was newly approved at the time of market entry since 2006 (last 10 years): eslicarbazepine (ESL), lacosamide (LCM), perampanel (PER), and retigabine (RTG). Methods: The analysis was based on a claims data set covering the years 2007 to 2014, provided by AOK PLUS, a German statutory health insurance. Two patient samples were defined: (1) prevalent patients suffering from FE (at least one in- or outpatient diagnosis of FE and at least one prescription of an AED), and (2) incident FE patients (first in- or outpatient diagnosis of FE without any previous diagnoses/AED prescriptions in the preceding ). Patient observation started at date of first observed inpatient or outpatient focal epilepsy diagnosis within the analyzed period.Each patient was classified as a “no AED therapy”, “AED monotherapy” or “more than one AED therapy”. Patients were analyzed by number and type of concomitantly prescribed AEDs in yearly tranches (no, one, two, three, four, more than four AEDs; novel versus non-novel AEDs). Results: A total of 34,422 patients diagnosed with FE aged 16 year or older (mean age 59.6 years, 48.7% female) were identified. The mean follow-up period was 1,891 days (5.2 years) since first confirmed . The percentage of prevalent patients diagnosed with FE who received one AED (monotherapy) was stable overall and ranged between a minimum of 66.2% (2007) and a maximum of 68.9% (2010). The percentage of patients who received two AEDs ranged from 23.6% (2012) to 25.8% (2007). The remaining patients received therapies with three (6.0% in 2010 to 6.7% in 2007), four (1.0% in 2010 to 1.2% in 2009) or more than four AEDs (0.1% in 2014 to 0.3% in 2013). Between 8.1%–16.6% (2007; 2014) of the patients received no AED therapy in the observed period.In the first year after the diagnosis of FE (incident patients), 9.7% of patients didn’t receive any AED therapy. Of those treated with at least one AED, 80.0% received one AED (monotherapy) only, 17.0% received therapy with two AEDs, 2.6% with three AEDs, 0.3% with four AEDs, and 0.1% with >4 AEDs during the respective observation time window and remained stable throughout the four-year follow-up period.Of prevalent patients with a diagnosis of FE, 1,889 (5.5%) received at least one prescription of a novel AED during the observation period; 98.6% of these patients received the novel AED in combination with at least one other AED. Of those patients, 269 (14.2%) received AED. The analysis of the patients receiving novel AEDs by the time from the first confirmed diagnosis of FE until the prescription of a novel AED resulted in a mean duration of 4.0 years (SD 2.0) for ESL, 3.6 years (SD 2.2) for LCM, 5.7 years (SD 1.2) for PER, and (SD 0.8 years) for RTG. The mean number of AEDs prescribed before the novel AEDs were 3.2 for ESL, 2.4 for LCM, 5.0 for PER and 5.2 for RTG. Conclusions: Most patients aged 16 years or older, suffering from focal seizures, received AED monotherapy. Novel AEDs were prescribed in a small proportion of patients (

What controls species diversity and diversification is one of the major questions in evolutionary biology and paleontology. Previous studies have addressed this issue based on various plant and animal groups, geographic regions, and time intervals. However, as most previous research focused on terrestrial or marine ecosystems, our understanding of the controls on diversification of biota (and particularly invertebrates) in freshwater environments in deep time is still limited. Here, we infer diversification rates of North American freshwater gastropods from the Late Triassic to the Pleistocene and explore potential links between shifts in speciation and extinction and major changes in paleogeography, climate, and biotic interactions. We found that variation in the speciation rate is best explained by changes in continental fragmentation, with rate shifts coinciding with major paleogeographic reorganizations in the Mesozoic, in particular the retreat of the Sundance Sea and subsequent development of the Bighorn wetland and the advance of the Western Interior Seaway. Climatic events in the Cenozoic (Middle Eocene Climate Optimum, Miocene Climate Optimum) variably coincide with shifts in speciation and extinction as well, but no significant long-term association could be detected. Similarly, no influence of diversity dependence was found across the entire time frame of ~ 214 Myr. Our results indicate that short-term climatic events and paleogeographic changes are relevant to the diversification of continental freshwater biota, while long-term trends have limited effect.

The scarcity of high-resolution empirical data directly tracking diversity over time limits our understanding of speciation and extinction dynamics and the drivers of rate changes. Here, we analyze a continuous species-level fossil record of endemic diatoms from ancient Lake Ohrid, along with environmental and climate indicator time series since lake formation 1.36 million years (Ma) ago. We show that speciation and extinction rates nearly simultaneously decreased in the environmentally dynamic phase after ecosystem formation and stabilized after deep-water conditions established in Lake Ohrid. As the lake deepens, we also see a switch in the macroevolutionary trade-off, resulting in a transition from a volatile assemblage of short-lived endemic species to a stable community of long-lived species. Our results emphasize the importance of the interplay between environmental/climate change, ecosystem stability, and environmental limits to diversity for diversification processes. The study also provides a new understanding of evolutionary dynamics in long-lived ecosystems.