Suchergebnisse

Microaggregation by individual ranking (IR) is an important technique for masking confidential econometric data. While being a successful method for controlling the disclosure risk of observations, IR also affects the results of statistical analyses. We conduct a theoretical analysis on the estimation of arbitrary moments from a data set that has been anonymized by means of the IR method. We show that classical moment estimators remain both consistent and asymptotically normal under weak assumptions. This theory provides the justification for applying standard statistical estimation techniques to the anonymized data without having to correct for a possible bias caused by anonymization.

Microaggregation is a popular statistical disclosure control technique for continuous data. The basic principle of microaggregation is to group the observations in a data set and to replace them by their corresponding group means. However, while reducing the disclosure risk of data files, the technique also affects the results of statistical analyses. The paper deals with the impact of microaggregation on a multiple linear regression in continuous variables. We show that parameter estimates are biased if the dependent variable is used to form the groups. Using this result, we develop a consistent estimator that removes the aggregation bias, and derive its asymptotic covariance matrix.

Zusammenfassung
Hintergrund Multimorbidität ist in Praxis und Klinik eine
besondere Herausforderung. Epidemiologische Erkenntnisse basieren in Deutschland
auf Stichprobenuntersuchungen und methodische Probleme, wie das Fehlen einer
einheitlichen Definition, dominieren. Dies trotz der hohen geschätzten
Prävalenz unter Erwachsenen in Deutschland.
Methode Es wurden Daten der gesetzlichen Krankenversicherung, die als
'Informationssystem Versorgungsdaten' des ehemaligen Deutschen
Instituts für Medizinische Dokumentation und Information zur
Verfügung gestellt wurden, analysiert. Insgesamt konnten 67,3 Millionen
gesetzlich Versicherte des Jahres 2014 eingeschlossen werden.
Multimorbidität wurde durch das Vorhandensein von mindestens 3
Krankheiten aus einer Liste von 46 Krankheiten per ICD-10 definiert.
Ergebnisse Insgesamt sind 21.157.937 Personen und somit 31,4% des
Gesamtkollektivs als multimorbide definiert. Auffällig ist, dass
Männer einen späteren Verlaufsanstieg der
Multimorbidität im Alter von etwa 40 Jahren haben, während es
bei Frauen schon im Alter von etwa 35 Jahren zum Anstieg kommt. Unterschiedliche
Krankheitslast durch differierende Morbiditätskombinationen konnten in
den Alters- und Geschlechtsgruppen gezeigt werden.
Schlussfolgerung Das Verständnis der komplexen
Krankheitsinteraktionen in Abhängigkeit des Alters und Geschlechts muss
gestärkt werden. Interdisziplinäre Ansätze für
spezifische Versorgungskonzepte für Multimorbidität, adaptiert
an das Chronic Care Modell sollten erforscht werden, um eine optimale
Versorgungslage in Deutschland zu erwirken.

Abstract
Background
Cathodic protection by sacrificial anodes composed of aluminum-zinc-indium alloys is often applied to protect offshore support structures of wind turbines from corrosion. Given the considerable growth of renewable energies and thus offshore wind farms in Germany over the last decade, increasing levels of aluminum, indium and zinc are released to the marine environment. Although these metals are ecotoxicologically well-studied, data regarding their impact on marine organisms, especially sediment-dwelling species, as well as possible ecotoxicological effects of galvanic anodes are scarce. To investigate possible ecotoxicological effects to the marine environment, the diatom Phaedactylum tricornutum, the bacterium Aliivibrio fischeri and the amphipod Corophium volutator were exposed to dissolved galvanic anodes and solutions of aluminum and zinc, respectively, in standardized laboratory tests using natural seawater. In addition to acute toxicological effects, the uptake of these elements by C. volutator was investigated.

Results
The investigated anode material caused no acute toxicity to the tested bacteria and only weak but significant effects on algal growth. In case of the amphipods, the single elements Al and Zn showed significant effects only at the highest tested concentrations. Moreover, an accumulation of Al and In was observed in the crustacea species.

Conclusions
Overall, the findings of this study indicated no direct environmental impact on the tested marine organisms by the use of galvanic anodes for cathodic protection. However, the accumulation of metals in, e.g., crustaceans might enhance their trophic transfer within the marine food web.

Abstract Purpose: Currently, no outcome measures are clinically validated and accepted as clinical endpoints by regulatory agencies for drug development in intermediate age-related macular degeneration (iAMD). The MACUSTAR Consortium, a public-private research group funded by the European Innovative Medicines Initiative intends to close this gap. Procedures: Development of study protocol and statistical analysis plan including predictive modelling of multimodal endpoints based on a review of the literature and expert consensus. Results: This observational study consists of a cross-sectional and a longitudinal part. Functional outcome measures assessed under low contrast and low luminance have the potential to detect progression of visual deficit within iAMD and to late AMD. Structural outcome measures will be multimodal and investigate topographical relationships with function. Current patient-reported outcome measures (PROMs) are not acceptable to regulators and may not capture the functional deficit specific to iAMD with needed precision, justifying development of novel PROMs for iAMD. The total sample size will be n = 750, consisting mainly of subjects with iAMD (n = 600). Conclusions: As clinical endpoints currently accepted by regulators cannot detect functional loss or patient-relevant impact in iAMD, we will clinically validate novel candidate endpoints for iAMD. ; Name of action: Intermediate AMD: Development of novel clinical endpoints for clinical trials in patients with a regulatory and patient access intention - MACUSTAR This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 116076. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA.

Background Recruiting asymptomatic participants with early disease stages into studies is challenging and only little is known about facilitators and barriers to screening and recruitment of study participants. Thus we assessed factors associated with screening rates in the MACUSTAR study, a multi-centre, low-interventional cohort study of early stages of age-related macular degeneration (AMD). Methods Screening rates per clinical site and per week were compiled and applicable recruitment factors were assigned to respective time periods. A generalized linear mixed-effects model including the most relevant recruitment factors identified via in-depth interviews with study personnel was fitted to the screening data. Only participants with intermediate AMD were considered. Results A total of 766 individual screenings within 87 weeks were available for analysis. The mean screening rate was 0.6 ± 0.9 screenings per week among all sites. The participation at investigator teleconferences (relative risk increase 1.466, 95% CI [1.018–2.112]), public holidays (relative risk decrease 0.466, 95% CI [0.367–0.591]) and reaching 80% of the site's recruitment target (relative risk decrease 0.699, 95% CI [0.367–0.591]) were associated with the number of screenings at an individual site level. Conclusions Careful planning of screening activities is necessary when recruiting early disease stages in multi-centre observational or low-interventional studies. Conducting teleconferences with local investigators can increase screening rates. When planning recruitment, seasonal and saturation effects at clinical site level need to be taken into account. ; Name of action: Intermediate AMD: Development of novel clinical endpoints for clinical trials in patients with a regulatory and patient access intention - MACUSTAR This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 116076. This Joint Undertaking receives support from the European Union's Horizon 2020 research and ...

BACKGROUND: Immigration has taken the central stage in world politics, especially in the developed countries like Germany, where the continuous flow of immigrants has been well documented since 1960s. Strikingly, emerging data suggest that migrant patients have a poorer response to the treatment and lower survival rates in their new host country, raising concerns about health disparities. Herein, we present our investigation on the treatment response rate and cancer survival in German patients with and without an immigrant background that were treated at our comprehensive cancer center in Germany. METHODS: Initially, we considered 8162 cancer patients treated at the Center for Integrated Oncology (CIO), University Hospital Bonn, Germany (April 2002–December 2015) for matched-pair analysis. Subsequently, the German patients with a migration background and those from the native German population were manually identified and catalogued using a highly specific name-based algorithm. The clinical parameters such as demographic characteristics, tumor characteristics, defined staging criteria, and primary therapy were further adjusted. Using these stringent criteria, a total of 422 patients (n = 211, Germans with migration background; n = 211, native German population) were screened to compare for the treatment response and survival rates (i.e., 5-year overall survival, progression-free survival, and time to progression). RESULTS: Compared to the cohort with migration background, the cohort without migration background was slightly older (54.9 vs. 57.9 years) while having the same sex distribution (54.5% vs. 55.0% female) and longer follow-up time (36.9 vs. 42.6 months). We did not find significant differences in cancer survival (5-year overall survival, P = 0.771) and the response rates (Overall Remission Rate; McNemar's test, P = 0.346) between both collectives. CONCLUSION: Contrary to prior reports, we found no significant differences in cancer survival between German patients with immigrant background and native ...

25 páginas, 6 figuras, 2 tablas ; Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele. ; This work was funded by a grant (EADB) from the EU Joint Programme – Neurodegenerative Disease Research. INSERM UMR1167 is also funded by the INSERM, Institut Pasteur de Lille, Lille Métropole Communauté Urbaine and French government's LABEX DISTALZ program (development of innovative strategies for a transdisciplinary approach to AD). Full consortium acknowledgements and funding are in the Supplementary Not ; Peer reviewed