Beurteilung der Posttransplantationsosteopathie unter oraler Ibandronattherapie nach Lebertransplantation: ein 5-Jahres-Follow-Up

Fragestellung: Die Posttransplantationsosteopathie rückt in den letzten Jahren in den Vordergrund der Langzeitbetreuung nach solider Organtransplantation. Eine Therapie mit Bisphosphonaten in Kombination mit Kalzium und Vitamin D3 hat sich bereits etabliert. In dieser Studie berichten wir von einer oralen Ibandronattherapie nach Lebertransplantation in Form eines Langzeit-Follow-up’s, mit Hauptaugenmerk auf Frakturauftreten und Knochenmineraldichtemessungen nach Beendigung der medikamentösen Therapie. Methodik: Wir schlossen 57 der 142 von Mai 2006 bis Dezember 2008 lebertransplantierten Patienten in die Studie ein. 40 Patienten wurden über einen Zeitraum von 5 Jahren nachbeobachtet. Diese Patienten erhielten eine orale Ibandronattherapie über min-destens 24 Monate. 33 Patienten wurden retrospektiv in die Kontrollgruppe aufge-nommen. Es erfolgten Laboruntersuchungen und DXA- Messungen der LWS und des Femur zum Zeitpunkt vor LTX, 3, 6, 12, 24, 36, 48, 60 Monate nach LTX. Ergebnis: Unter oraler Ibandronattherapie zeigte sich ab 6 Monate nach LTX eine signifikante höhere absolute lumbale Knochenmineraldichte im Vergleich zur Kon-trollgruppe. Die prozentualen Veränderungen erreichten statistische Signifikanz zum Zeitpunkt 12, 48 und 60 Monate nach LTX. Die Ibandronatgruppe wies eine signifi-kant niedrigere Frakturhäufigkeit als die Kontrollgruppe auf. Eine präoperative Pred-nisolontherapie hat einen signifikanten Einfluss auf die lumbale Knochenmineral-dichte 3 und 12 Monate nach Lebertransplantation. Schlussfolgerung: Eine orale Ibandronattherapie nach Lebertransplantation redu-ziert das Auftreten pathologischer Knochenfrakturen und steigert die Knochenmi-neraldichte im Posttransplantationszeitraum von 5 Jahren

Socioeconomic disparities between oral cavity cancer patients in Germany

Objective: In many countries the access to high quality medical service depends on socioeconomic factors. Therefore, these factors are associated with the treatment and prognosis of many diseases. In Germany health care is claimed to be independent from such factors due to obligatory health insurance and a well-developed medical infrastructure. Thus, socioeconomically caused health disparities should be absent. The aim of this study was to analyze the association between socioeconomic factors and the survival of oral cavity cancer in Germany. Patients and methods: In this descriptive cohort study socioeconomic status related factors as well as demographic, tumor-specific, and comorbidity factors of 500 patients treated for oral cavity cancer were obtained in the university hospital of Dresden. Pearson correlation was used to describe associations between continuous variables. Associations between categorical variables were assessed using the chi-square test. Overall and recurrence-free survival were studied using the Kaplan-Meier method. Log-rank test was carried out to test between-group differences. Cox proportional hazard models were used to estimate the risk of death and the risk of recurrence. Results: Significant differences in overall survival were found between the different educational levels and sex. Seventy-nine percent of the patients did not have a university degree or master craftsman/craftswoman. Less discrepancy was observed according to the marital status (49.4% married/engaged vs. 47.8% single, divorced, or widowed). In the multivariable analysis only sex, age at diagnosis, the Charlson score, the number of positive lymph nodes, and the nodal status were identified as independent predictors for overall survival whereas sex and the age at diagnosis were identified as independent predictors for recurrence-free survival. Conclusion: Despite the equitable health system in Germany, significant associations between overall survival of oral cavity cancer and different socioeconomic factors could be found. For elimination of these disparities, health education programs should be established in socially deprived areas. Furthermore, clinicians should keep these factors in mind when determining recall periods for dental check-ups

A Novel Mutation Involving the Initiation Codon of FGF3 in a Family Described with Complete Inner Ear Agenesis, Microtia and Major Microdontia (LAMM Syndrome)

LAMM syndrome (OMIM #610706) is a rare autosomal recessive syndrome characterized by the association of Michel aplasia, microdontia and malformation of the external ear. Different mutations in FGF3 gene were reported in several families presenting with this syndrome. Clinical features and genetic results observed in a family with LAMM syndrome are reported. The diagnosis of isolated Michel aplasia was initially made in this family composed of two affected children. Microtia and microdontia was recently evidenced in both patients suggesting the diagnosis of LAMM syndrome. New auditory and orodental iconography was performed permitting to describe the patients’ phenotype in depth and to report rare findings of LAMM syndrome. The sequencing of FGF3 gene identified a novel missense mutation (c.2T>G), substituting the first initiator methionine in arginine, in the fibroblast growth factor 3 (FGF3) at the homozygous state in both patients. LAMM syndrome was confirmed and appropriate genetic counseling performed

Evaluation of individual and ensemble probabilistic forecasts of COVID-19 mortality in the United States

Short-term probabilistic forecasts of the trajectory of the COVID-19 pandemic in the United States have served as a visible and important communication channel between the scientific modeling community and both the general public and decision-makers. Forecasting models provide specific, quantitative, and evaluable predictions that inform short-term decisions such as healthcare staffing needs, school closures, and allocation of medical supplies. Starting in April 2020, the US COVID-19 Forecast Hub (https://covid19forecasthub.org/) collected, disseminated, and synthesized tens of millions of specific predictions from more than 90 different academic, industry, and independent research groups. A multimodel ensemble forecast that combined predictions from dozens of groups every week provided the most consistently accurate probabilistic forecasts of incident deaths due to COVID-19 at the state and national level from April 2020 through October 2021. The performance of 27 individual models that submitted complete forecasts of COVID-19 deaths consistently throughout this year showed high variability in forecast skill across time, geospatial units, and forecast horizons. Two-thirds of the models evaluated showed better accuracy than a naïve baseline model. Forecast accuracy degraded as models made predictions further into the future, with probabilistic error at a 20-wk horizon three to five times larger than when predicting at a 1-wk horizon. This project underscores the role that collaboration and active coordination between governmental public-health agencies, academic modeling teams, and industry partners can play in developing modern modeling capabilities to support local, state, and federal response to outbreaks

The United States COVID-19 Forecast Hub dataset

Academic researchers, government agencies, industry groups, and individuals have produced forecasts at an unprecedented scale during the COVID-19 pandemic. To leverage these forecasts, the United States Centers for Disease Control and Prevention (CDC) partnered with an academic research lab at the University of Massachusetts Amherst to create the US COVID-19 Forecast Hub. Launched in April 2020, the Forecast Hub is a dataset with point and probabilistic forecasts of incident cases, incident hospitalizations, incident deaths, and cumulative deaths due to COVID-19 at county, state, and national, levels in the United States. Included forecasts represent a variety of modeling approaches, data sources, and assumptions regarding the spread of COVID-19. The goal of this dataset is to establish a standardized and comparable set of short-term forecasts from modeling teams. These data can be used to develop ensemble models, communicate forecasts to the public, create visualizations, compare models, and inform policies regarding COVID-19 mitigation. These open-source data are available via download from GitHub, through an online API, and through R packages

Dysfunctional Parental Styles Perceived during Childhood in Outpatients with Substance Use Disorders

International audiencePeople who suffer from substance use disorders (SUDs) frequently report to have undergone childhood adversity that is often associated with father or mother dysfunction, or both. Yet that issue has been barely addressed in opiate dependent patients. Therefore we sought to evaluate parent-specific dysfunctional styles perceived during childhood in a clinical sample from an outpatient addiction treatment program using the Measure Of Parental Styles (MOPS) questionnaire. DSM-IV diagnoses of substance use disorders and history of suicide attempts, family structure and changes of caregiver during childhood were obtained from 159 consecutive outpatients, along with their perception of parental bonding with the MOPS, in which mother and father scores are separate. Mother neglect dimension was significantly correlated with an earlier age at onset of several substances' use, the number of prior hospitalizations and of lifetime suicide attempts. Most of these associations remained significant in multivariate models. This was the first assessment of a representative sample of outpatients with SUDs by the MOPS questionnaire. Given its excellent acceptance and its association with several key correlates of SUDs, it should be used to design specific interventions targeted at attachment and familial management as well as in research models on gene \texttimes environment interactions

Microgrid Systems: Towards a Technical Performance Assessment Frame

A microgrid is an independent power system that can be connected to the grid or operated in an islanded mode. This single grid entity is widely used for furthering access to energy and ensuring reliable energy supply. However, if islanded, microgrids do not benefit from the high inertia of the main grid and can be subject to high variations in terms of voltage and frequency, which challenge their stability. In addition, operability and interoperability requirements, standards as well as directives have addressed main concerns regarding a microgrid’s reliability, use of distributed local resources and cybersecurity. Nevertheless, microgrid systems are quickly evolving through digitalization and have a large range of applications. Thus, a consensus over their testing must be further developed with the current technological development. Here, we describe existing technical requirements and assessment criteria for a microgrid’s main functionalities to foster harmonization of functionality-level testing and an international conception of system-level one. This framework is proposed as a reference document for assessment frame development serving both microgrid research and implementation for a comprehensive understanding of technical microgrid performance and its current assessment challenges, such as lack of standardization and evolving technology

How and why educational interventions work to increase knowledge of delirium among healthcare professionals in nursing homes: a protocol for a realist review

Background Delirium is a neuropathological condition that impairs cognitive performance, attention and consciousness and can be potentially life-threatening. Nursing home residents are particularly vulnerable to developing delirium, but research thus far tends to focus on the acute hospital setting. Healthcare professionals (HCPs) working in nursing homes seem to be little aware of delirium. To improve healthcare for affected or at-risk individuals, increasing knowledge among HCPs is highly relevant. Using the realist review method helps to understand how and why an educational intervention for HCPs on delirium in nursing homes works.Methods and analysis In accordance with the Realist And Meta-narrative Evidence Syntheses: Evolving Standards publication standards for realist syntheses, the review process will include the following five steps: (1) search strategy and literature review; (2) study selection and assessment; (3) data extraction; (4) data synthesis and (5) development of an initial programme theory. The literature search will be conducted in the databases Medline (PubMed), CINAHL (Ebsco), Scopus, Web of Science, GeroLit and Carelit. Additional focuses are on snowballing techniques, hand research and grey literature. Studies of any design will be included to develop the initial programme theory. The literature will be selected by two researchers independently. In addition, the experiences of HCPs from nursing homes will be reflected in group discussions. To this end, Context–Mechanism–Outcome configurations (CMOcs) will be established to develop an initial programme theory.Ethics and dissemination The results will be disseminated within the scientific community. For this purpose, presentations at scientific conferences as well as publications in peer-reviewed journals are scheduled. In the next step, the CMOcs could serve for the development of a complex educational intervention to increase the knowledge of HCPs on delirium in nursing homes.Registration details This protocol has been registered at Open Science Framework (https://doi.org/10.17605/OSF.IO/HTFU4)

Educational interventions aimed at improving knowledge of delirium among nursing home staff—a realist review

Abstract Background Delirium is a neuropathological syndrome that is characterised by fluctuating impairments in attention, cognitive performance, and consciousness. Since delirium represents a medical emergency, it can be associated with adverse clinical and economic outcomes. Although nursing home residents face a high risk of developing delirium, health care professionals in this field appear to have limited knowledge of delirium despite the critical role they play in the prevention, diagnosis, and treatment of delirium in nursing homes. Objective The purpose of this realist review is to develop an initial programme theory with the goal of understanding how, why, and under what circumstances educational interventions can improve the delirium-specific knowledge of health care professionals in nursing homes. Methods This realist review was conducted in accordance with the RAMESES (Realist And Meta-narrative Evidence Synthesis: and Evolving Standards) guidelines and includes the following steps: (1) search strategy and literature review; (2) study selection and assessment; (3) data extraction; (4) data synthesis; and (5) development of an initial programme theory. It also included stakeholder discussions with health care professionals recruited from nursing home care, which focused on their experiences with delirium. Results From a set of 1703 initially identified publications, ten publications were included in this realist review. Based on these publications, context-mechanism-outcome configurations were developed; these configurations pertained to (1) management support, (2) cognitive impairments among residents, (3) familiarity with residents, (4) participatory intervention development, (5) practical application, (6) case scenarios, (7) support from experts and (8) relevance of communication. Conclusions Educational interventions aimed at improving the delirium-specific knowledge of health care professionals should feature methodological diversity if they are to enhance health care professionals’ interest in delirium and highlight the fundamental contributions they make to the prevention, diagnosis, and treatment of delirium. Educational interventions should also take into account the multidimensional contextual factors that can have massive impacts on the relevant mode of action as well as the responses of health care professionals in nursing homes. The identification of delirium in residents is a fundamental responsibility for nursing home staff. Trial registration This review has been registered at Open Science Framework https://doi.org/10.17605/OSF.IO/6ZKM

Simultaneous analysis of pMHC binding and reactivity unveils virus-specific CD8 T cell immunity to a concise epitope set

CD8 T cells provide immunity to virus infection through recognition of epitopes presented by peptide major histocompatibility complexes (pMHCs). To establish a concise panel of widely recognized T cell epitopes from common viruses, we combined analysis of TCR down-regulation upon stimulation with epitope-specific enumeration based on barcode-labeled pMHC multimers. We assess CD8 T cell binding and reactivity for 929 previously reported epitopes in the context of 1 of 25 HLA alleles representing 29 viruses. The prevalence and magnitude of CD8 T cell responses were evaluated in 48 donors and reported along with 137 frequently recognized virus epitopes, many of which were underrepresented in the public domain. Eighty-four percent of epitope-specific CD8 T cell populations demonstrated reactivity to peptide stimulation, which was associated with effector and long-term memory phenotypes. Conversely, nonreactive T cell populations were associated primarily with naive phenotypes. Our analysis provides a reference map of epitopes for characterizing CD8 T cell responses toward common human virus infections.</p