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Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs.
Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel.
Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1–25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0–88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE- syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%—subcutaneous; 29%—intravenous; 1%—unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy.
Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment.
Background: Treatment complexity rises in line with the number of drugs, single doses, and administration methods, thereby threatening patient adherence. Patients with multimorbidity often need flexible, individualised treatment regimens, but alterations during the course of treatment may further increase complexity. The objective of our study was to explore medication changes in older patients with multimorbidity and polypharmacy in general practice.
Methods: We retrospectively analysed data from the cluster-randomised PRIMUM trial (PRIoritisation of MUltimedication in Multimorbidity) conducted in 72 general practices. We developed an algorithm for active pharmaceutical ingredients (API), strength, dosage, and administration method to assess changes in physician-reported medication data during two intervals (baseline to six-months: ∆1; six- to nine-months: ∆2), analysed them descriptively at prescription and patient levels, and checked for intervention effects.
Results: Of 502 patients (median age 72 years, 52% female), 464 completed the study. Changes occurred in 98.6% of patients (changes were 19% more likely in the intervention group): API changes during ∆1 and ∆2 occurred in 414 (82.5%) and 338 (67.3%) of patients, dosage alterations in 372 (74.1%) and 296 (59.2%), and changes in API strength in 158 (31.5%) and 138 (27.5%) respectively. Administration method changed in 79 (16%) of patients in both ∆1 and ∆2. Simvastatin, metformin and aspirin were most frequently subject to alterations.
Conclusion: Medication regimens in older patients with multimorbidity and polypharmacy changed frequently. These are mostly due to discontinuations and dosage alterations, followed by additions and restarts. These findings cast doubt on the effectiveness of cross-sectional assessments of medication and support longitudinal assessments where possible.
Trial registration: 1. Prospective registration: Trial registration number: NCT01171339; Name of registry: ClinicalTrials.gov; Date of registration: July 27, 2010; Date of enrolment of the first participant to the trial: August 12, 2010.
2. Peer reviewed trial registration: Trial registration number: ISRCTN99526053; Name of registry: Controlled Trials; Date of registration: August 31, 2010; Date of enrolment of the first participant to the trial: August 12, 2010.
Large-scale genetic census of an elusive carnivore, the European wildcat (Felis s. silvestris)
(2016)
The European wildcat, Felis silvestris silvestris, serves as a prominent target species for the reconnection of central European forest habitats. Monitoring of this species, however, appears difficult due to its elusive behaviour and the ease of confusion with domestic cats. Recently, evidence for multiple wildcat occurrences outside its known distribution has accumulated in several areas across Central Europe, questioning the validity of available distribution data for this species. Our aim was to assess the fine-scale distribution and genetic status of the wildcat in its central European distribution range. We compiled and analysed genetic samples from roadkills and hundreds of recent hair-trapping surveys and applied phylogenetic and genetic clustering methods to discriminate wild and domestic cats and identify population subdivision. 2220 individuals were confirmed as either wildcat (n = 1792) or domestic cat (n = 342), and the remaining 86 (3.9 %) were identified as hybrids between the two. Remarkably, genetic distinction of domestic cats, wildcats and their hybrids was only possible when taking into account the presence of two highly distinct genetic lineages of wildcats, with a suture zone in central Germany. 44 % of the individual wildcats where sampled outside the previously published distribution. Our analyses confirm a relatively continuous spatial presence of wildcats across large parts of the study area in contrast to previous analyses indicating a highly fragmented distribution. Our results suggest that wildcat conservation and management should take advantage of the higher than previously assumed dispersal potential of wildcats, which may use wildlife corridors very efficiently.
Background Polypharmacy interventions are resource-intensive and should be targeted to those at risk of negative health outcomes. Our aim was to develop and internally validate prognostic models to predict health-related quality of life (HRQoL) and the combined outcome of falls, hospitalisation, institutionalisation and nursing care needs, in older patients with multimorbidity and polypharmacy in general practices.
Methods Design: two independent data sets, one comprising health insurance claims data (n=592 456), the other data from the PRIoritising MUltimedication in Multimorbidity (PRIMUM) cluster randomised controlled trial (n=502). Population: ≥60 years, ≥5 drugs, ≥3 chronic diseases, excluding dementia. Outcomes: combined outcome of falls, hospitalisation, institutionalisation and nursing care needs (after 6, 9 and 24 months) (claims data); and HRQoL (after 6 and 9 months) (trial data). Predictor variables in both data sets: age, sex, morbidity-related variables (disease count), medication-related variables (European Union-Potentially Inappropriate Medication list (EU-PIM list)) and health service utilisation. Predictor variables exclusively in trial data: additional socio-demographics, morbidity-related variables (Cumulative Illness Rating Scale, depression), Medication Appropriateness Index (MAI), lifestyle, functional status and HRQoL (EuroQol EQ-5D-3L). Analysis: mixed regression models, combined with stepwise variable selection, 10-fold cross validation and sensitivity analyses.
Results Most important predictors of EQ-5D-3L at 6 months in best model (Nagelkerke’s R² 0.507) were depressive symptoms (−2.73 (95% CI: −3.56 to −1.91)), MAI (−0.39 (95% CI: −0.7 to −0.08)), baseline EQ-5D-3L (0.55 (95% CI: 0.47 to 0.64)). Models based on claims data and those predicting long-term outcomes based on both data sets produced low R² values. In claims data-based model with highest explanatory power (R²=0.16), previous falls/fall-related injuries, previous hospitalisations, age, number of involved physicians and disease count were most important predictor variables.
Conclusions Best trial data-based model predicted HRQoL after 6 months well and included parameters of well-being not found in claims. Performance of claims data-based models and models predicting long-term outcomes was relatively weak. For generalisability, future studies should refit models by considering parameters representing well-being and functional status.
Background: Although polypharmacy can cause adverse health outcomes, patients often know little about their medication. A regularly conducted medication review (MR) can help provide an overview of a patient’s medication, and benefit patients by enhancing their knowledge of their drugs. As little is known about patient attitudes towards MRs in primary care, the objective of this study was to gain insight into patient-perceived barriers and facilitators to the implementation of an MR.
Methods: We conducted a qualitative study with a convenience sample of 31 patients (age ≥ 60 years, ≥3 chronic diseases, taking ≥5 drugs/d); in Hesse, Germany, in February 2016. We conducted two focus groups and, in order to ensure the participation of elderly patients with reduced mobility, 16 telephone interviews. Both relied on a semi-structured interview guide dealing with the following subjects: patients’ experience of polypharmacy, general design of MRs, potential barriers and facilitators to implementation etc. Interviews were audio-recorded, transcribed verbatim, and analysed by two researchers using thematic analysis.
Results: Patients’ average age was 74 years (range 62–88 years). We identified barriers and facilitators for four main topics regarding the implementation of MRs in primary care: patient participation, GP-led MRs, pharmacist-led MRs, and the involvement of healthcare assistants in MRs. Barriers to patient participation concerned patient autonomy, while facilitators involved patient awareness of medication-related problems. Barriers to GP-led MRs concerned GP’s lack of resources while facilitators related to the trusting relationship between patient and GP. Pharmacist-led MRs might be hindered by a lack of patients’ confidence in pharmacists’ expertise, but facilitated by pharmacies’ digital records of the patients’ medications. Regarding the involvement of healthcare assistants in MRs, a potential barrier was patients’ uncertainty regarding the extent of their training. Patients could, however, imagine GPs delegating some aspects of MRs to them.
Conclusions: Our study suggests that patients regard MRs as beneficial and expect indications for their medicines to be checked, and possible interactions to be identified. To foster the implementation of MRs in primary care, it is important to consider barriers and facilitators to the four identified topics.
We present simulations with the Chemical Lagrangian Model of the Stratosphere (CLaMS) for the Arctic winter 2002/2003. We integrated a Lagrangian denitrification scheme into the three-dimensional version of CLaMS that calculates the growth and sedimentation of nitric acid trihydrate (NAT) particles along individual particle trajectories. From those, we derive the HNO3 downward flux resulting from different particle nucleation assumptions. The simulation results show a clear vertical redistribution of total inorganic nitrogen (NOy), with a maximum vortex average permanent NOy removal of over 5 ppb in late December between 500 and 550 K and a corresponding increase of NOy of over 2 ppb below about 450 K. The simulated vertical redistribution of NOy is compared with balloon observations by MkIV and in-situ observations from the high altitude aircraft Geophysica. Assuming a globally uniform NAT particle nucleation rate of 3.4·10−6 cm−3 h−1 in the model, the observed denitrification is well reproduced. In the investigated winter 2002/2003, the denitrification has only moderate impact (<=10%) on the simulated vortex average ozone loss of about 1.1 ppm near the 460 K level. At higher altitudes, above 600 K potential temperature, the simulations show significant ozone depletion through NOx-catalytic cycles due to the unusual early exposure of vortex air to sunlight.
We present simulations with the Chemical Lagrangian Model of the Stratosphere (CLaMS) for the Arctic winter 2002/2003. We integrated a Lagrangian denitrification scheme into the three-dimensional version of CLaMS that calculates the growth and sedimentation of nitric acid trihydrate (NAT) particles along individual particle trajectories. From those, we derive the HNO3 downward flux resulting from different particle nucleation assumptions. The simulation results show a clear vertical redistribution of total inorganic nitrogen ( ), with a maximum vortex average permanent removal of over 5ppb in late December between 500 and 550K and a corresponding increase of of over 2ppb below about 450K. The simulated vertical redistribution of is compared with balloon observations by MkIV and in-situ observations from the high altitude aircraft Geophysica. Assuming a globally uniform NAT particle nucleation rate of 7.8x10-6cm-3h-1 in the model, the observed denitrification is well reproduced.
In the investigated winter 2002/2003, the denitrification has only moderate impact (≤14%) on the simulated vortex average ozone loss of about 1.1ppm near the 460K level. At higher altitudes, above 600K potential temperature, the simulations show significant ozone depletion through -catalytic cycles due to the unusual early exposure of vortex air to sunlight.
EUSOBI and 30 national breast radiology bodies support mammography for population-based screening, demonstrated to reduce breast cancer (BC) mortality and treatment impact. According to the International Agency for Research on Cancer, the reduction in mortality is 40 % for women aged 50–69 years taking up the invitation while the probability of false-positive needle biopsy is <1 % per round and overdiagnosis is only 1–10 % for a 20-year screening. Mortality reduction was also observed for the age groups 40–49 years and 70–74 years, although with “limited evidence”. Thus, we firstly recommend biennial screening mammography for average-risk women aged 50–69 years; extension up to 73 or 75 years, biennially, is a second priority, from 40–45 to 49 years, annually, a third priority. Screening with thermography or other optical tools as alternatives to mammography is discouraged. Preference should be given to population screening programmes on a territorial basis, with double reading. Adoption of digital mammography (not film-screen or phosphor-plate computer radiography) is a priority, which also improves sensitivity in dense breasts. Radiologists qualified as screening readers should be involved in programmes. Digital breast tomosynthesis is also set to become “routine mammography” in the screening setting in the next future. Dedicated pathways for high-risk women offering breast MRI according to national or international guidelines and recommendations are encouraged.