Rationale and design of BERLIN VT study: a multicenter randomised trial comparing preventive versus deferred ablation of ventricular tachycardia

Introduction Catheter ablation ( CA) has shown to effectively reduce the burden of ventricular tachycardia in patients with implanted cardioverter-defibrillator (ICD). However, in patients with ICD implantation for secondary prevention of ventricular tachycardia (VT), the appropriate time point of CA and its effect on mortality and heart failure progression remains a matter of debate. Methods and analysis We present the design of the ongoing preventive aBlation of vEntriculartachycaRdia in patients with myocardiaLINfarction (BERLIN VT) study that aims to prospectively enrol 208 patients with a stable ischaemic cardiomyopathy, a left ventricular ejection fraction of 30% to 50% and documented ventricular tachycardia. Patients will be 1: 1 randomised to undergo CA at the time of ICD implantation or CA after the third appropriate ICD shock for ventricular tachycardia. ICD implantation will be performed in all patients. The primary endpoint is defined as the time to first event comprising all-cause mortality and unplanned hospital admission for congestive heart failure or for symptomatic VT/ventricular fibrillation. The patients will be followed until study termination according to the event driven design. Completion of enrolment is expected for mid of 2019. Ethics and dissemination The study had been approved by the "Ethik-kommission der Landesarztekammer Hamburg" as well as the local institutional review boards for each of the participation sites. The results of the trial will be published in peer-reviewed journal

Patterns of Multimorbidity in the Aged Population. Results from the KORA-Age Study

Multimorbidity is a common problem in aged populations with a wide range of individual and societal consequences. The objective of the study was to explore patterns of comorbidity and multimorbidity in an elderly population using different analytical approaches. Data were gathered from the population-based KORA-Age project, which included 4,127 persons aged 65–94 years living in the city of Augsburg and its two surrounding counties in Southern Germany. Information on the presence of 13 chronic conditions was collected in a standardized telephone interview and a self-administered questionnaire. Patterns of comorbidity and multimorbidity were analyzed using prevalence figures, logistic regression models and exploratory tetrachoric factor analysis. The prevalence of multimorbidity (≥2 diseases) was 58.6% in the total sample. Hypertension and diabetes (Odds Ratio [OR] 2.95, 99.58% confidence interval [CI] [2.19–3.96]), as well as hypertension and stroke (OR 2.00, 99.58% CI [1.26–3.16]) most often occurred in combination. This association was independent of age, sex and the presence of other conditions. Using factor analysis, we identified four patterns of multimorbidity: the first pattern includes cardiovascular and metabolic diseases, the second includes joint, liver, lung and eye diseases, the third covers mental and neurologic diseases and the fourth pattern includes gastrointestinal diseases and cancer. 44% of the persons were assigned to at least one of the four multimorbidity patterns; 14% could be assigned to both the cardiovascular/metabolic and the joint/liver/lung/eye pattern. Further common pairs were the mental/neurologic pattern combined with the cardiovascular/metabolic pattern (7.2%) or the joint/liver/lung/eye pattern (5.3%), respectively. Our results confirmed the existence of co-occurrence of certain diseases in elderly persons, which is not caused by chance. Some of the identified patterns of multimorbidity and their overlap may indicate common underlying pathological mechanisms

Development and investigation of an absorbable scaffold for the treatment of articular cartilage defects

Aufgrund der unzureichenden regenerativen Fähigkeiten des Gelenkknorpels führen bereits kleine Läsionen zu progressiven Gelenkbeschwerden, die in einer Arthrose und nachfolgender Invalidität enden können. Bedingt ist diese Problematik durch die spezielle Anatomie des Knorpelgewebes, insbesondere durch seine Avaskularität. Da die bisher eingesetzten konventionellen Behandlungsmethoden bei der Regeneration von zonal aufgebautem, hyalinem Knorpel scheitern, werden seit etwa 20 Jahren neue, regenerative Therapien erforscht. Den Startpunkt dieser Methoden bildete 1994 die von Brittberg beschriebene autologe Chondrozyten-Transplantation (ACT), bei der körpereigene Knorpelzellen für die Reparatur des Defekts genutzt werden. Aufgrund von operationstechnischen und zellbiologischen Problemen wurde diese Methode zu trägerassoziierten Verfahren weiterentwickelt, bei denen resorbierbare Zellträger für eine dreidimensionalen Anordnung der Chondrozyten und des sich bildenden Gewebes sorgen. Das Trägermaterial muss dabei verschiedene Anforderungen bezüglich der Biokompatibilität, der Struktur, der chemischen und mechanischen Stabilität sowie der Oberflächeneigenschaften erfüllen. Im Rahmen dieser Arbeit sollte ein Zellträgermaterial, basierend auf Gelatine und dem synthetischen Polymer PLGA, hergestellt werden, das die Anforderungen an ein Trägermaterial möglichst weitgehend erfüllt. Durch die anfängliche Rezepturoptimierung gelang es dabei, das PLGA lösemittelfrei und homogen in der Gelatinebasis zu integrieren. Anschließend erfolgte die Herstellung der schwammförmigen Zellträger mittels gerichtetem Einfrieren und Gefriertrocknung, wobei durch Anpassung der Herstellungsparameter eine gleichmäßige und parallel angeordnete, durchgängige Porenstruktur erzeugt werden konnte. Die nachfolgende Vernetzung und Sterilisation des Materials gelang in einem einzigen Prozessschritt durch eine dehydrothermale Behandlung. Anhand der folgenden physikochemischen Charakterisierung der entstandenen Gelatine-PLGA-Scaffolds konnte eine optimale Porosität und Porengröße für die Besiedelung der Zellträger festgestellt werden. Weiterhin zeigte die Untersuchung zur in vitro Degradation des Materials bei konstantem physiologischen pH-Wert und der Abwesenheit von spezifischen Enzymen eine gute chemische Stabilität der Scaffolds. Mit Hilfe von in vitro Zytotoxizitäts-Versuchen sowie einer in vivo Studie zur Gewebeverträglichkeit gemäß DIN EN ISO 10993 wurde außerdem eine gute Biokompatibilität des Materials festgestellt. Zusätzlich waren an den histologischen Präparaten der in vivo Studie eine bessere Gewebeintegration und eine geringere Fremdkörperreaktion, verglichen mit dem bereits zugelassenen Kontrollmaterial Ethisorb®, feststellbar. Bei weiterführenden in vitro Versuchen zur Besiedelbarkeit der Zellträger mit primären Chondrozyten konnte durch eine dynamische Besiedelungsmethode und Optimierung der Zelldichte eine gleichmäßige Zellverteilung auf und in dem Scaffold-Material erreicht werden. Immunhistologische Untersuchungen bezüglich des Gehalts an Kollagen II in der synthetisierten Matrix zeigten dabei, dass der differenzierte Status der Chondrozyten erhalten blieb. Eine erste Funktionalitätsstudie am Gelenkknorpeldefekt von Ziegen deutete zudem im Vergleich zur bisherigen operativen Standardmethode Mikrofrakturierung auf eine bessere Geweberegeneration des Defekts nach Mikrofrakturierung mit anschließender Applikation des Trägermaterials (AMIC-Verfahren) hin. Der entwickelte Gelatine-PLGA-Scaffold stellt demnach aufgrund der untersuchten Eigenschaften und insbesondere seiner optimalen Struktur einen geeigneten Zellträger zur Unterstützung der Knorpelregeneration dar.Since articular cartilage has only insufficient regenerative properties, even small lesions lead to pro-gressive joint complains, which can end up in osteoarthritis and subsequent disability. This problem is caused by the special anatomy of cartilage tissue, in particular its avascularity. Because previously used conventional treatments fail in the regeneration of zonal hyaline cartilage, new regenerative therapies are being researched for approximately 20 years. The starting point of these methods was described in 1994 by Brittberg as the autologous chondrocyte transplantation (ACT), which uses endogenous cells for the repair of cartilage defects. Because of its technical and cell biological prob-lems, this method was further developed to carrier-associated techniques, which utilize absorbable scaffolds for a 3D arrangement of chondrocytes and the newly formed tissue. Hence, the scaffold material has to meet different requirements regarding the biocompatibility, the structure, the chemical and mechanical stability as well as appropriate surface properties. The purpose of this thesis was to develop and characterize a scaffold, based on gelatine and the synthetic polymer PLGA, which should largely fulfill the requirements for cell-carriers. The initial optimization of the formulation led to a solvent-free and homogenous integration of the PLGA into the gelatine base. The porous gelatine-PLGA scaffolds were subsequently fabricated using a unidirectional freeze drying method. Thereby, it was possible to generate a consistent pore structure with continuous and parallel oriented pore channels by modulating the production parameters. The following crosslinking also successfully sterilized the material in a single process using a dehydrothermal treatment. The morphological characterization of the generated constructs revealed optimal porosity as well as pore size, indicating a good applicability for culturing the scaffolds with chondrocytes. Furthermore, the analysis of the in vitro degradation showed that the scaffolds are chemically very stable at physiological pH values and the absence of specific enzymes. With the help of in vitro cytotoxicity assays and an in vivo study regarding tissue compatibility, which were performed according to DIN EN ISO 10993, a good biocompatibility of the material was determined. Additionally, the histological preparations of the in vivo study revealed improved tissue integration and a lower foreign body reaction compared to the already licensed control material Ethisorb®. Further in vitro experiments regarding the seeding of the gelatine-PLGA scaffolds with primary chondrocytes showed that a dynamic seeding-method combined with an optimal cell density led to a homogenous cell distribution on the scaffold surface as well as within the constructs. Immunhistochemical analysis of collagen type II revealed the secretion of cartilaginous extracellular matrix, indicating the maintenance of the differentiated chondrocyte status. Besides that, a first study of functionality in cartilage defects of goats pointed to a better tissue regeneration after application of microdrilling and scaffold (AMIC method) compared to microdrilling alone, which is the actual conventional standard method. In summary, due to its properties and especially its optimal structure the gelatine-PLGA scaffold represents an appropriate cell-carrier for supporting the cartilage regeneration

The Ariadne principles : how to handle multimorbidity in primary care consultations

Multimorbidity is a health issue mostly dealt with in primary care practice. As a result of their generalist and patient-centered approach, long-lasting relationships with patients, and responsibility for continuity and coordination of care, family physicians are particularly well placed to manage patients with multimorbidity. However, conflicts arising from the application of multiple disease oriented guidelines and the burden of diseases and treatments often make consultations challenging. To provide orientation in decision making in multimorbidity during primary care consultations, we developed guiding principles and named them after the Greek mythological figure Ariadne. For this purpose, we convened a two-day expert workshop accompanied by an international symposium in October 2012 in Frankfurt, Germany. Against the background of the current state of knowledge presented and discussed at the symposium, 19 experts from North America, Europe, and Australia identified the key issues of concern in the management of multimorbidity in primary care in panel and small group sessions and agreed upon making use of formal and informal consensus methods. The proposed preliminary principles were refined during a multistage feedback process and discussed using a case example. The sharing of realistic treatment goals by physicians and patients is at the core of the Ariadne principles. These result from i) a thorough interaction assessment of the patient’s conditions, treatments, constitution, and context; ii) the prioritization of health problems that take into account the patient's preferences – his or her most and least desired outcomes; and iii) individualized management realizes the best options of care in diagnostics, treatment, and prevention to achieve the goals. Goal attainment is followed-up in accordance with a re-assessment in planned visits. The occurrence of new or changed conditions, such as an increase in severity, or a changed context may trigger the (re-)start of the process. Further work is needed on the implementation of the formulated principles, but they were recognized and appreciated as important by family physicians and primary care researchers

A multidimensional approach to older patients during COVID-19 pandemic: a position paper of the Special Interest Group on Comprehensive Geriatric Assessment of the European Geriatric Medicine Society (EuGMS)

Purpose: The COVID-19 pandemic has been a dramatic trigger that has challenged the intrinsic capacity of older adults and of society. Due to the consequences for the older population worldwide, the Special Interest Group on Comprehensive Geriatric Assessment (CGA) of the European Geriatric Medicine Society (EuGMS) took the initiative of collecting evidence on the usefulness of the CGA-based multidimensional approach to older people during the COVID-19 pandemic. Methods: A narrative review of the most relevant articles published between January 2020 and November 2022 that focused on the multidimensional assessment of older adults during the COVID-19 pandemic. Results: Current evidence supports the critical role of the multidimensional approach to identify older adults hospitalized with COVID-19 at higher risk of longer hospitalization, functional decline, and short-term mortality. This approach appears to also be pivotal for the adequate stratification and management of the post-COVID condition as well as for the adoption of preventive measures (e.g., vaccinations, healthy lifestyle) among non-infected individuals. Conclusion: Collecting information on multiple health domains (e.g., functional, cognitive, nutritional, social status, mobility, comorbidities, and polypharmacy) provides a better understanding of the intrinsic capacities and resilience of older adults affected by SARS-CoV-2 infection. The EuGMS SIG on CGA endorses the adoption of the multidimensional approach to guide the clinical management of older adults during the COVID-19 pandemic

Comprehensive geriatric assessment in older people : an umbrella review of health outcomes

Background: Comprehensive geriatric assessment (CGA) has been in use for the last three decades. However, some doubts remain regarding its clinical use. Therefore, we aimed to capture the breadth of outcomes reported and assess the strength of evidence of the use of comprehensive geriatric assessment (CGA) for health outcomes in older Methods: Umbrella review of systematic reviews of the use of CGA in older adults searching in Pubmed, Embase, Scopus, Cochrane library and CINHAL until 05 November 2021. All possible health outcomes were eligible. Two independent reviewers extracted key data. The grading of evidence was carried out using the GRADE for intervention studies, whilst data regarding systematic reviews were reported as narrative findings. Results: Among 1,683 papers, 31 systematic reviews (19 with meta-analysis) were considered, including 279,744 subjects. Overall, 13/53 outcomes were statistically significant (P < 0.05). There was high certainty of evidence that CGA reduces nursing home admission (risk ratio [RR] = 0.86; 95% confidence interval [CI]: 0.75–0.89), risk of falls (RR = 0.51; 95%CI: 0.29–0.89), and pressure sores (RR = 0.46; 95%CI: 0.24–0.89) in hospital medical setting; decreases the risk of delirium (OR = 0.71; 95%CI: 0.54–0.92) in hip fracture; decreases the risk of physical frailty in community-dwelling older adults (RR = 0.77; 95%CI: 0.64–0.93). Systematic reviews without meta-analysis indicate that CGA improves clinical outcomes in oncology, haematology, and in emergency department. Conclusions: CGA seems to be beneficial in the hospital medical setting for multiple health outcomes, with a high certainty of evidence. The evidence of benefits is less strong for the use of CGA in other settings