Institutionelle Grenzen erweitern - der Life-Space von Bewohnern in der stationären Altenpflege und dessen Modifikation mittels eines Trainingsprogramms zur Steigerung der körperlichen Aktivität

Diese publikationsbasierte Dissertation widmet sich der Beschreibung des Life-Space von Bewohnern der stationären Altenpflege sowie der Entwicklung und Evaluation eines individualisierten, mehrdimensionalen Interventionsansatzes zur Life-Space Modifikation mit Schwerpunkt auf körperlichem Training. Manuskript I ist eine systematische Übersichtsarbeit (systematisches Review) zu randomisierten, kontrollierten Interventionsstudien (RCTs) im Pflegeheim und deren Effekte auf körperliche Aktivität von Pflegeheimbewohnern. Lediglich in acht RCTs wurde körperliche Aktivität erfasst, nur eine Studie betrachtete diese als primären Endpunkt. Interventionen, welche zusätzlich zu körperlichem Training auch psycho¬soziale und Verhaltensaspekte berücksichtigten und Pflegeheimpersonal miteinbe¬zogen, zeigten die vielversprechendsten Effekte. Die starke Heterogeni¬tät der Interventionsprogramme und meist unzureichende psychometrische Qualität der Erhe¬bungsmethoden schränkte die Interpretierbarkeit der Ergebnisse jedoch ein. Basierend auf den Erkenntnissen aus dem systematischen Review wurden die Interventionsbausteine und Erhebungsmethoden zur Erfassung des Bewegungs-verhaltens in Form von Life-Space Nutzung und körperlicher Aktivität konzipiert. Das entsprechende Studienprotokoll stellt Manuskript II dar. In Manuskript III wird der Life-Space von Pflegeheimbewohnern erstmals unter Einsatz eines kabellosen Sensornetzwerks technisch sowie räumlich und zeitlich aufgelöst beschrieben. Der Life-Space der Bewohner (n = 65) war nahezu gänzlich auf das eigene Zimmer (36,6% des Tages wurden dort verbracht) und den das Zimmer umgebenden Wohnbereich (53,8%) beschränkt. Mittels linearer Regression wurde gezeigt, dass sozidodemografische Faktoren, motorische Leistung, kognitiver Status und psychosoziale Faktoren signifikant mit Life-Space-Parametern assoziiert sind. Die Hauptdeterminante der Life-Space-Nutzung stellte allerdings die institutio-nelle Essensroutine dar, die sowohl den Aufenthalt im öffent¬lichen Speiseraum als auch die Raumwechselhäufigkeit der Bewohner weitestgehend bestimmte. In Manuskript IV werden positive Effekte der Intervention auf erfasste Life-Space-Parameter mittels generalized linear mixed models (GLMMs) analysiert und belegt (n = 143). Diese Analysestrategie toleriert dem Studienkollektiv entsprechend erwart-baren Datenausfall und die Nicht-Normalverteilung der Ergebnisvariablen. Die Para¬meter waren ein im Rahmen der Arbeit entwickelter Life-Space Summenscore, welcher die „durchschnittliche“ Zone (Zone 1 = Privatzimmer; Zone 2 = Wohn-bereich; Zone 3 = außerhalb des Wohnbereichs; Zone 4 = außerhalb des Gebäudes) beschreibt, in welcher sich ein Bewohner über den Tag aufhält (LSSc); die am weitesten vom jeweiligen Privatzimmer entfernte, vom Bewohner aufgesuchte Zone (MaxZ) als Maß für die absolute Aus¬dehnung des individuellen Life-Space; die Zeit, die ein Bewohner außerhalb des eigenen Zimmers verbringt (TAFR) als Maß für das Potenzial, an sozialen Inter¬aktionen teilzuhaben. Es zeigten sich signifikante Gruppenunterschiede in LSSc (β = .13, p = .003), TAFR (β = .28, p = .015) und MaxZ (β = .29, p = .003) zwischen Prä- und Posttest in der Interven-tions¬gruppe (n = 78) verglichen mit der Kontrollgruppe (n = 65). Ein signifi¬kan¬ter Effekt blieb zum Follow-Up nach drei Monaten für den Parameter MaxZ bestehen (β = .39, p = .012). Manuskript V ist ein praxisorientiertes Handbuch, dass der Forderung einer breiten Dissemination und freien Verfügbarkeit des Programms nachkommen sowie eine praktische Implementierung des Interventionsprogramms seitens interessierter End-nutzer ermöglichen soll. Es beinhaltet Leitlinien für die Durchführung wissenschaft-licher Studien im Pflegeheimsetting, theoretischen und methodisch-didaktischen Hintergrund zu den Interventionsinhalten aus LTCMo, ein Assessmenttool zur Zuweisung von Teilnehmern zu geeigneten Trainingskomponenten und bebilderte Beschreibungen zahlreicher im Projekt eingesetzter Übungen. Insgesamt belegen die Studienergebnisse einen sehr eingeschränkten Life-Space von Pflegeheimbewohnern, der jedoch trotz des engen institutionel¬len Rahmens durch den mehrdimensionalen Interventionsansatz mit Schwer¬punkt auf individual-isiertem körperlichen Training positiv verändert werden konnte. Dies gilt nahezu für das ganze Bewohnerspektrum der untersuchten Pflegeheime, ungeachtet schwe¬rer kogni¬tiver und motorisch-funktioneller Einschränkungen. Der Nachweis des Poten-zials des Programms für eine nachhaltige Implementierung in Institutionen wurde durch die Studienergebnisse sowie die Tatsache, dass das Programm in beiden Studien¬heimen unabhängig fortgeführt wurde, erbracht. Die bisherige, auf frage-bogenbasierten Erhebungsmethoden aufbauende Evidenz auf diesem Gebiet wurde mit der vorliegenden Arbeit durch neuartige, sensor-basierte Daten ergänzt. Während der Zusam¬men¬hang von Life-Space mit soziodemografischen, motorisch-funktio¬nellen, kognitiven und psycho¬sozialen Faktoren nachgewiesen wurde, stellt der Zu¬sammenhang mit weiteren bedeutsamen Faktoren wie sozialer Teilhabe und Lebens¬qualität eine hochrelevante Fragestellung für zukünftige Forschungsvorhaben dar

Life-space and movement behavior in nursing home residents: results of a new sensor-based assessment and associated factors

Background: Studies on life-space (LS) and its determinants have previously been limited to community-dwelling subjects but are lacking in institutionalized older persons. The purpose of this study was to provide an advanced descriptive analysis of LS in nursing home residents and to identify associated factors based on an established theoretical framework, using an objective, sensor-based assessment with a high spatiotemporal resolution. Methods: Cross-sectional study in two nursing homes in Heidelberg, Germany (n = 65; mean age: 82.9 years; 2/3 female). Changes of location in the nursing home (Transits) as well as time spent away from the private room (TAFR) were assessed using a wireless sensor network. Measures of physical, psychosocial, cognitive, socio-demographic, and environmental factors were assessed via established motor performance tests, interviews, and proxy-reports. Results: LS of residents was largely restricted to the private room and the surrounding living unit (90%); 10% of daytime was spent outside the living unit and/or the facility. On average, TAFR was 5.1 h per day (±2.3; Range: 0–8); seven Transits (6.9 ± 3.2; Range: 0–18) were performed per day. Linear regression analyses revealed being male, lower gait speed, higher cognitive status, and lower apathy to be associated with more Transits; higher gait speed, lower cognitive status, and less depressive symptoms were associated with more TAFR. LS was significantly increased during institutional routines (mealtimes) as compared to the rest of the day. Conclusions: The sensor-based LS assessment provided new, objective insights into LS of institutionalized persons living in nursing homes. It revealed that residents’ LS was severely limited to private rooms and adjacent living units, and that in institutional settings, daily routines such as meal times seem to be the major determinant of LS utilization. Gait speed, apathy, and depressive symptoms as well as institutional meal routines were the only modifiable predictors of Transits and/or TAFR, and thus have greatest potential to lead to an enhancement of LS when targeted with interventions. Trial registration: Current Controlled Trials ISRCTN96090441 (retrospectively registered)

Acute and medium term effects of a 10-week running intervention on mood state in apprentices

Exercise and physical activity have proven benefits for physical and psychological well-being. However, it is not clear if healthy young adults can enhance mood in everyday life through regular exercise. Earlier studies mainly showed positive effects of acute exercise and exercise programs on psychological well-being in children, older people and in clinical populations. Few studies controlled participants' physical activity in daily life, performed besides the exercise program, which can impact results. In addition the transition from mood enhancement induced by acute exercise to medium or long-term effects due to regular exercise is not yet determined. The purpose of this pilot study was to examine the acute effects of an aerobic running training on mood and trends in medium term changes of mood in everyday life of young adults. We conducted a 10-week aerobic endurance training with frequent mood assessments and continuous activity monitoring. 23 apprentices, separated into experimental and control group, were monitored over 12 weeks. To control the effectiveness of the aerobic exercise program, participants completed a progressive treadmill test pre and post the intervention period. The three basic mood dimensions energetic arousal, valence and calmness were assessed via electronic diaries. Participants had to rate their mood state frequently on 3 days a week at five times of measurement within 12 weeks. Participants' physical activity was assessed with accelerometers. All mood dimensions increased immediately after acute endurance exercise but results were not significant. The highest acute mood change could be observed in valence (p = 0.07; η(2) = 0.27). However, no medium term effects in mood states could be observed after a few weeks of endurance training. Future studies should focus on the interaction between acute and medium term effects of exercise training on mood. The decreasing compliance over the course of the study requires the development of strategies to maintain compliance over longer periods

Comparison of a group-delivered and individually delivered lifestyle-integrated functional exercise (LiFE) program in older persons: a randomized noninferiority trial

Background: The Lifestyle-Integrated Functional Exercise (LiFE) program is effective in improving strength, balance, and physical activity (PA) while simultaneously reducing falls in older people by incorporating exercise activities in recurring daily tasks. However, implementing the original LiFE program includes substantial resource requirements. Therefore, as part of the LiFE-is-LiFE project, a group format (gLiFE) of the LiFE program has been developed, which will be tested regarding its noninferiority to the individually delivered LiFE in terms of PA-adjusted fall incidence and overall cost-effectiveness. Methods: In a multi-centre, single-blinded noninferiority trial, an envisaged sample of N = 300 participants (> 70 years; faller and/or confirmed falls risk; community-dwelling) will be randomized in either LiFE or gLiFE. Both groups will undergo the same strength and balance activities as well as PA promotion activities and habitualization strategies as described in the LiFE programme, however, based on different approaches of delivery: During the 6-month intervention phase, LiFE participants will receive seven home visits and two telephone calls; in gLiFE, the program will be delivered in seven group sessions and also two telephone calls. Main outcomes are a) fall incidence per PA and b) incremental cost-effectiveness ratio comparing costs and quality-adjusted life years between the two interventions. Secondary outcomes include PA behaviour, motor performance, health status, psychosocial status, program evaluation, and adherence. Measurements will be conducted at baseline, 6-month and 12-month follow-up; evaluation of intervention sessions and assessment of psychosocial variables related to execution and habitualization of LiFE activities will be made during the intervention period as well. Discussion: Compared to LiFE, we expect gLiFE to (a) reduce falls per PA by a similar rate; (b) be more cost-effective; (c) comparably enhance physical performance in terms of strength and balance as well as PA. By investigating the economic and societal benefit, this study will be of high practical relevance as noninferiority of gLiFE would facilitate large-scale implementation due to lower resource usage. This would result in better reach and increased accessibility, which is important for subjects with a history of falls and/or being at risk of falls. Trial registration ClinicalTrials.gov NCT03462654. Registered on March 12, 2018

A single cell atlas of frozen shoulder capsule identifies features associated with inflammatory fibrosis resolution

Frozen shoulder is a spontaneously self-resolving chronic inflammatory fibrotic human disease, which distinguishes the condition from most fibrotic diseases that are progressive and irreversible. Using single-cell analysis, we identify pro-inflammatory MERTKlowCD48+ macrophages and MERTK + LYVE1 + MRC1+ macrophages enriched for negative regulators of inflammation which co-exist in frozen shoulder capsule tissues. Micro-cultures of patient-derived cells identify integrin-mediated cell-matrix interactions between MERTK+ macrophages and pro-resolving DKK3+ and POSTN+ fibroblasts, suggesting that matrix remodelling plays a role in frozen shoulder resolution. Cross-tissue analysis reveals a shared gene expression cassette between shoulder capsule MERTK+ macrophages and a respective population enriched in synovial tissues of rheumatoid arthritis patients in disease remission, supporting the concept that MERTK+ macrophages mediate resolution of inflammation and fibrosis. Single-cell transcriptomic profiling and spatial analysis of human foetal shoulder tissues identify MERTK + LYVE1 + MRC1+ macrophages and DKK3+ and POSTN+ fibroblast populations analogous to those in frozen shoulder, suggesting that the template to resolve fibrosis is established during shoulder development. Crosstalk between MerTK+ macrophages and pro-resolving DKK3+ and POSTN+ fibroblasts could facilitate resolution of frozen shoulder, providing a basis for potential therapeutic resolution of persistent fibrotic diseases

Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium

Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, using MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets in the ENIGMA consortium, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macro-structural asymmetry may reflect differences at the molecular, cytoarchitectonic or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Connecting real-world digital mobility assessment to clinical outcomes for regulatory and clinical endorsement–the Mobilise-D study protocol

Background: The development of optimal strategies to treat impaired mobility related to ageing and chronic disease requires better ways to detect and measure it. Digital health technology, including body worn sensors, has the potential to directly and accurately capture real-world mobility. Mobilise-D consists of 34 partners from 13 countries who are working together to jointly develop and implement a digital mobility assessment solution to demonstrate that real-world digital mobility outcomes have the potential to provide a better, safer, and quicker way to assess, monitor, and predict the efficacy of new interventions on impaired mobility. The overarching objective of the study is to establish the clinical validity of digital outcomes in patient populations impacted by mobility challenges, and to support engagement with regulatory and health technology agencies towards acceptance of digital mobility assessment in regulatory and health technology assessment decisions. Methods/design: The Mobilise-D clinical validation study is a longitudinal observational cohort study that will recruit 2400 participants from four clinical cohorts. The populations of the Innovative Medicine Initiative-Joint Undertaking represent neurodegenerative conditions (Parkinson’s Disease), respiratory disease (Chronic Obstructive Pulmonary Disease), neuro-inflammatory disorder (Multiple Sclerosis), fall-related injuries, osteoporosis, sarcopenia, and frailty (Proximal Femoral Fracture). In total, 17 clinical sites in ten countries will recruit participants who will be evaluated every six months over a period of two years. A wide range of core and cohort specific outcome measures will be collected, spanning patient-reported, observer-reported, and clinician-reported outcomes as well as performance-based outcomes (physical measures and cognitive/mental measures). Daily-living mobility and physical capacity will be assessed directly using a wearable device. These four clinical cohorts were chosen to obtain generalizable clinical findings, including diverse clinical, cultural, geographical, and age representation. The disease cohorts include a broad and heterogeneous range of subject characteristics with varying chronic care needs, and represent different trajectories of mobility disability. Discussion: The results of Mobilise-D will provide longitudinal data on the use of digital mobility outcomes to identify, stratify, and monitor disability. This will support the development of widespread, cost-effective access to optimal clinical mobility management through personalised healthcare. Further, Mobilise-D will provide evidence-based, direct measures which can be endorsed by regulatory agencies and health technology assessment bodies to quantify the impact of disease-modifying interventions on mobility. Trial registration: ISRCTN12051706