Falls prevention for the elderly

Background: An ageing population, a growing prevalence of chronic diseases and limited financial resources for health care underpin the importance of prevention of disabling health disorders and care dependency in the elderly. A wide variety of measures is generally available for the prevention of falls and fall-related injuries. The spectrum ranges from diagnostic procedures for identifying individuals at risk of falling to complex interventions for the removal or reduction of identified risk factors. However, the clinical and economic effectiveness of the majority of recommended strategies for fall prevention is unclear. Against this background, the literature analyses in this HTA report aim to support decision-making for effective and efficient fall prevention.Research questions: The pivotal research question addresses the effectiveness of single interventions and complex programmes for the prevention of falls and fall-related injuries. The target population are the elderly (> 60 years), living in their own housing or in long term care facilities. Further research questions refer to the cost-effectiveness of fall prevention measures, and their ethical, social and legal implications. Methods: Systematic literature searches were performed in 31 databases covering the publication period from January 2003 to January 2010. While the effectiveness of interventions is solely assessed on the basis of randomised controlled trials (RCT), the assessment of the effectiveness of diagnostic procedures also considers prospective accuracy studies. In order to clarify social, ethical and legal aspects all studies deemed relevant with regard to content were taken into consideration, irrespective of their study design. Study selection and critical appraisal were conducted by two independent assessors. Due to clinical heterogeneity of the studies no meta-analyses were performed.Results: Out of 12,000 references retrieved by literature searches, 184 meet the inclusion criteria. However, to a variable degree the validity of their results must be rated as compromised due to different biasing factors. In summary, it appears that the performance of tests or the application of parameters to identify individuals at risk of falling yields little or no clinically relevant information. Positive effects of exercise interventions may be expected in relatively young and healthy seniors, while studies indicate opposite effects in the fragile elderly. For this specific vulnerable population the modification of the housing environment shows protective effects. A low number of studies, low quality of studies or inconsistent results lead to the conclusion that the effectiveness of the following interventions has to be rated unclear yet: correction of vision disorders, modification of psychotropic medication, vitamin D supplementation, nutritional supplements, psychological interventions, education of nursing personnel, multiple and multifactorial programs as well as the application of hip protectors. For the context of the German health care system the economic evaluations of fall prevention retrieved by the literature searches yield very few useful results. Cost-effectiveness calculations of fall prevention are mostly based on weak effectiveness data as well as on epidemiological and cost data from foreign health care systems. Ethical analysis demonstrates ambivalent views of the target population concerning fall risk and the necessity of fall prevention. The willingness to take up preventive measures depends on a variety of personal factors, the quality of information, guidance and decision-making, the prevention program itself and social support. The analysis of papers regarding legal issues shows three main challenges: the uncertainty of which standard of care has to be expected with regard to fall prevention, the necessity to consider the specific conditions of every single case when measures for fall prevention are applied, and the difficulty to balance the rights to autonomous decision making and physical integrity. Discussion and conclusions: The assessment of clinical effectiveness of interventions for fall prevention is complicated by inherent methodological problems (esp. absence of blinding) and meaningful clinical heterogeneity of available studies. Therefore meta-analyses are not appropriate, and single study results are difficult to interpret. Both problems also impair the informative value of economic analyses. With this background it has to be stated that current recommendations regarding fall prevention in the elderly are not fully supported by scientific evidence. In particular, for the generation of new recommendations the dependency of probable effects on specific characteristics of the target populations or care settings should be taken into consideration. This also applies to the variable factors influencing the willingness of the target population to take up and pursue preventive measures. In the planning of future studies equal weight should be placed on methodological rigour (freedom from biases) and transferability of results into routine care. Economic analyses require input of German data, either in form of a “piggy back study“ or in form of a modelling study that reflects the structures of the German health care system and is based on German epidemiological and cost data

Paraneoplastic Necrotizing Myopathy with a Mild Inflammatory Component: A Case Report and Review of the Literature

Inflammatory myopathies such as dermatomyositis and polymyositis are well-recognized paraneoplastic syndromes. Little is known, however, about necrotizing myopathies in association with cancer. We here describe a case of paraneoplastic necrotizing myopathy with a mild inflammatory infiltrate in a patient with adenocarcinoma. After the rapid development of a severe, disabling muscle weakness, the patient experienced near complete recovery within 4 months under oral prednisone treatment. In the context of the presented case, we will review current knowledge about paraneoplastic necrotizing myopathies

Mapping Nanomedicine Terminology in the Regulatory Landscape

A common terminology is essential in any field of science and technology for a mutual understanding among different communities of experts and regulators, harmonisation of policy actions, standardisation of quality procedures and experimental testing, and the communication to the general public. It also allows effective revision of information for policy making and optimises research fund allocation. In particular, in emerging scientific fields with a high innovation potential, new terms, descriptions and definitions are quickly generated, which are then ambiguously used by stakeholders having diverse interests, coming from different scientific disciplines and/or from various regions. The application of nanotechnology in health -often called nanomedicine- is considered as such emerging and multidisciplinary field with a growing interest of various communities. In order to support a better understanding of terms used in the regulatory domain, the Nanomedicines Working Group of the International Pharmaceutical Regulators Forum (IPRF) has prioritised the need to map, compile and discuss the currently used terminology of regulatory scientists coming from different geographic areas. The JRC has taken the lead to identify and compile frequently used terms in the field by using web crawling and text mining tools as well as the manual extraction of terms. Websites of 13 regulatory authorities and clinical trial registries globally involved in regulating nanomedicines have been crawled. The compilation and analysis of extracted terms demonstrated sectorial and geographical differences in the frequency and type of nanomedicine related terms used in a regulatory context. Finally 31 relevant and most frequently used terms deriving from various agencies have been compiled, discussed and analysed for their similarities and differences. These descriptions will support the development of harmonised use of terminology in the future. The report provides necessary background information to advance the discussion among stakeholders. It will strengthen activities aiming to develop harmonised standards in the field of nanomedicine, which is an essential factor to stimulate innovation and industrial competitiveness.JRC.F.2-Consumer Products Safet

Epidemiologie und Resistenzlage der Gonorrhö in Deutschland im Jahr 2022

Das gramnegative Bakterium Neisseria gonorrhoeae (NG) ist der Erreger der Gonorrhö und wird durch direkten Schleimhautkontakt, z. B. beim Geschlechtsverkehr oder während der Geburt über-tragen. Infektionen mit NG können ein vielgestaltiges klinisches Bild zeigen und sind eine wesentliche Ursache von chronischen Entzündungen des kleinen Beckens, Unfruchtbarkeit, Fehlgeburten im ersten Trimenon und extrauterinen Schwangerschaften. Zusätzlich können Infektionen mit NG die Empfänglichkeit für HIV sowie das HIV-Übertragungsrisiko erhöhen. Innerhalb der letzten Jahrzehnte entwickelte NG zunehmend Resistenzen gegen alle wesentlichen Antibiotikaklassen, darunter Penicilline, Tetracycline, Makrolide sowie Fluorchinolone und seit einigen Jahren auch gegen Cephalosporine der dritten Generation. In der aktuell gültigen Leitlinie für Deutschland werden die Antibiotika Azithromycin, Cefixim und Ceftriaxon zur Behandlung der Gonorrhö empfohlen. Seit dem 1. März 2021 ist die nicht-namentliche Meldung von Infektionen mit NG mit verminderter Empfindlichkeit gegenüber mindestens einem dieser drei Antibiotika gemäß § 7 Abs. 3 des Infektionsschutzgesetztes verpflichtend. Der Beitrag gibt einen Überblick über die aktuelle Epidemiologie und Resistenzlage der Gonorrhö in Deutschland

The Biological and Ethical Basis of the Use of Human Embryonic Stem Cells for In Vitro Test Systems or Cell Therapy

Human embryonic stem cells (hESC) are now routinely cultured in many laboratories, and differentiation protocols are available to generate a large variety of cell types. In an ongoing ethical debate opinions of different groups are based on varying sets of religious, historical, cultural and scientific arguments as well as on widely differing levels of general information. We here give an overview of the biological background for non-specialists, and address all issues of the current stem cell debate that are of concern in different cultures and states. Thirty-five chapters address embryo definition, potential killing and the beginning of human life, in addition to matters of human dignity, patenting, commercialisation, and potential alternatives for the future, such as induced pluripotent (reprogrammed) stem cells. All arguments are compiled in a synopsis, and compromise solutions, e.g. for the definition of the beginning of personhood and for assigning dignity to embryos, are suggested. Until recently, the major application of hESC was thought to be transplantation of cells derived from hESC for therapeutic use. We discuss here that the most likely immediate uses will rather be in vitro test systems and disease models. Major and minor pharmaceutical companies have entered this field, and the European Union is sponsoring academic research into hESC-based innovative test systems. This development is supported by new testing strategies in Europe and the USA focussing on human cell-based in vitro systems for safety evaluations, and shifting the focus of toxicology away from classical animal experiments towards a more mechanistic understanding.JRC.I.3-In-vitro method

Development of a pluripotent stem cell derived neuronal model to identify chemically induced pathway perturbations in relation to neurotoxicity: Effects of CREB pathway inhibition

JRC.I.5-Systems Toxicolog

ECVAM Technical Report on the Status of Alternative Methods for Cosmetics Testing (2008-2009)

The ECVAM technical report presents the progress made in the development and validation of alternative methods for the human health effects relevant to the Cosmetics Directive. It provides an update on the activities described by ECVAM in 2005 , 2006 and 2007 . The report intends to present the latest scientific and technical developments in the field during 2008-2009. As required by Directive 2003/15/EC, the seventh amendment to Directive 76/768/EEC, developments in refinement and reduction methods are also described (EU, 2003). Most successes in the development of alternative methods are in acute local toxicity and short-term testing, such as e.g. skin and eye irritation/corrosion, phototoxicity and skin penetration The test methods consuming a high number of animals, however, are in long-term testing and systemic toxicity, such as e.g. reproductive toxicity and repeated dose toxicity. In these complex fields, several research initiatives are ongoing. However full replacement approaches are still lacking.JRC.DG.I.3-In-vitro method

Anticipation of regulatory needs for nanotechnology-enabled health products

Development of nanotechnology-based applications in health sector offer innovative therapeutic and diagnostic opportunities to address medical needs. At the moment, no specific regulatory framework exists for nano-enabled health products and the current regulatory practise might require additional guidance in order to fully cover the particularities of such products. This white paper summarizes the major challenges associated with the regulation of the nano-enabled health products. Depending on their mode of action nano-enabled health products are regulated either as medicinal products or medical devices. However, due to the increased complexity of such products and their size-related properties the selection of the regulatory path can become challenging since the primary mode of action might be difficult to determine. Due to the fast progress in the field and the lack of robust datasets, only initial guidance on regulatory information needs is currently available and the question remains whether these identified requirements are sufficient for a reliable characterisation of nano-enabled products. In relation to the need for additional information on the quality, safety and efficacy standardised methods have to be available. However, many conventional methods might not be suitable or reliable for nanomaterial testing due to the interference of nanomaterial with assays components. New state-of-art methods, instruments, approaches or tools have not yet sufficiently proven their reliability and relevance for the given purpose. As patents are expiring generic versions of the innovator products will require access to the market. Since the physicochemical characteristics can be very complex and depend on the manufacturing process, pharmacokinetic assessment might not be sufficient and more guidance is needed on how the bioequivalence can be demonstrated. For the nano-enabled health products classified as medical devices, the European Definition on nanomaterials will apply, determining its further classification and regulatory requirements. Yet, the implementation of the definition and the necessity to determine the exposure to nanomaterials may pose additional challenges. The regulatory challenges highlighted in this white paper should guide the research projects and the involved communities willing to advance the regulatory science in the area of nanomedicine.JRC.F.2-Consumer Products Safet

Predictors of treatment dropout in patients with posttraumatic stress disorder due to childhood abuse

Background: Knowledge about patient characteristics predicting treatment dropout for post-traumatic stress disorder (PTSD) is scarce, whereas more understanding about this topic may give direction to address this important issue. Method: Data were obtained from a randomized controlled trial in which a phase-based treatment condition (Eye Movement Desensitization and Reprocessing [EMDR] therapy preceded by Skills Training in Affect and Interpersonal Regulation [STAIR]; n = 57) was compared with a direct trauma-focused treatment (EMDR therapy only; n = 64) in people with a PTSD due to childhood abuse. All pre-treatment variables included in the trial were examined as possible predictors for dropout using machine learning techniques. Results: For the dropout prediction, a model was developed using Elastic Net Regularization. The ENR model correctly predicted dropout in 81.6% of all individuals. Males, with a low education level, suicidal thoughts, problems in emotion regulation, high levels of general psychopathology and not using benzodiazepine medication at screening proved to have higher scores on dropout. Conclusion: Our results provide directions for the development of future programs in addition to PTSD treatment or for the adaptation of current treatments, aiming to reduce treatment dropout among patients with PTSD due to childhood abuse