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Abstract Wildlife tagging provides critical insights into animal movement ecology, physiology, and behavior amid global ecosystem changes. However, the stress induced by capture, handling, and tagging can impact post-release locomotion and activity and, consequently, the interpretation of study results. Here, we analyze post-tagging effects on 1585 individuals of 42 terrestrial mammal species using collar-collected GPS and accelerometer data. Species-specific displacements and overall dynamic body acceleration, as a proxy for activity, were assessed over 20 days post-release to quantify disturbance intensity, recovery duration, and speed. Differences were evaluated, considering species-specific traits and the human footprint of the study region. Over 70% of the analyzed species exhibited significant behavioral changes following collaring events. Herbivores traveled farther with variable activity reactions, while omnivores and carnivores were initially less active and mobile. Recovery duration proved brief, with alterations diminishing within 4–7 tracking days for most species. Herbivores, particularly males, showed quicker displacement recovery (4 days) but slower activity recovery (7 days). Individuals in high human footprint areas displayed faster recovery, indicating adaptation to human disturbance. Our findings emphasize the necessity of extending tracking periods beyond 1 week and particular caution in remote study areas or herbivore-focused research, specifically in smaller mammals.

Introduction Germany and the European Union have experienced successive waves of refugees since 2014, resulting in over 1.6 million arrivals, including families with young children. These vulnerable populations often face xenophobia, discrimination, substandard living conditions and limited healthcare access, contributing to a high prevalence of mental health problems (MHP). Our primary goal is to proactively address MHP in refugee parents and prevent its potential impact on their children through effective early interventions. Using a low-threshold, primary care-based approach, we aim to enhance parenting skills and address parental psychopathology, creating a supportive environment for parents and children.Methods and analysis In this randomised controlled trial, 188 refugee parents of 6-year-old children or younger who meet the clinical cut-off on the MHP scale will participate. They are randomly assigned to either the experimental psychotherapeutic intervention, delivered by general practitioners (10-week Improve intervention), or treatment as usual, in a ratio of 1:1. The randomisation will be masked only for outcome assessors. Improve includes face-to-face sessions with general practitioners, an interactive online parenting programme (Triple P Online) and regular protocol-based telephone calls by psychologists. Primary outcomes will assess the intervention’s effects on parental and child MHP and parenting skills, with secondary outcomes including psychosocial and physical health indicators. Outcomes will be assessed at pre, post and at 3-month and 6-month follow-ups. The study is scheduled to run from February 2019 to July 2025.Ethics and dissemination The project Improve-MH (application number 602) was approved by the local ethics committee of Ruhr-University of Bochum and is being conducted in accordance with the Declaration of Helsinki. The study is also conducted in full accordance with the German Data Protection Act, and the Good Clinical Practice guideline (GCP) and is sensitive to specific ethical considerations. Results will be disseminated at scientific conferences, published in peer-reviewed journals and provided to consumers of healthcare.Trial registration number The trial was prospectively registered at the German Clinical Trials Register (Deutsches Register Klinischer Studien, DRKS-ID: DRKS00019072) on 16 March 2020.

Abstract Background Regular physical activity has multiple health benefits, especially in older people. Therefore, the World Health Organization recommends at least 2.5 h of moderate physical activity per week. The aim of the POWER Study was to investigate whether volunteer-assisted walking improves the physical performance and health of older people. Methods We approached people aged 65 years and older with restricted mobility due to physical limitations and asked them to participate in this multicentre randomised controlled trial. The recruitment took place in nursing homes and the community setting. Participants randomly assigned to the intervention group were accompanied by volunteer companions for a 30–50 min walk up to three times a week for 6 months. Participants in the control group received two lectures that included health-related topics. The primary endpoint was physical function as measured with the Short Physical Performance Battery (SPPB) at baseline and 6 and 12 months. The secondary and safety endpoints were quality of life (EQ-5D-5L), fear of falling (Falls Efficacy Scale), cognitive executive function (the Clock Drawing Test), falls, hospitalisations and death. Results The sample comprised 224 participants (79% female). We failed to show superiority of the intervention with regard to physical function (SPPB) or other health outcomes in the intention-to-treat analyses. However, additional exploratory analyses suggest benefits in those who undertook regular walks. The intervention appears to be safe regarding falls. Conclusions Regular physical activity is essential to preserve function and to improve health and quality of life. Against the background of a smaller-than-planned sample size, resulting in low power, and the interference of the COVID-19 pandemic, we suggest that community based low-threshold interventions deserve further exploration. Trial registration The trial was registered with the German Clinical Trials Register ( www.germanctr.de ), with number DRKS00015188 on 31/08/2018.

Abstract Background Chest pain is a common complaint and reason for consultation in primary care. Few data exist from a primary care setting whether male patients are treated differently than female patients. We examined whether there are gender differences in general physicians' (GPs) initial assessment and subsequent management of patients with chest pain, and how these differences can be explained Methods We conducted a prospective study with 1212 consecutive chest pain patients. The study was conducted in 74 primary care offices in Germany from October 2005 to July 2006. After a follow up period of 6 months, an independent interdisciplinary reference panel reviewed clinical data of every patient and decided about the etiology of chest pain at the time of patient recruitment (delayed type-reference standard). We adjusted gender differences of six process indicators for different models. Results GPs tended to assume that CHD is the cause of chest pain more often in male patients and referred more men for an exercise test (women 4.1%, men 7.3%, p = 0.02) and to the hospital (women 2.9%, men 6.6%, p < 0.01). These differences remained when adjusting for age and cardiac risk factors but ceased to exist after adjusting for the typicality of chest pain. Conclusions While observed gender differences can not be explained by differences in age, CHD prevalence, and underlying risk factors, the less typical symptom presentation in women might be an underlying factor. However this does not seem to result in suboptimal management in women but rather in overuse of services for men. We consider our conclusions rather hypothesis generating and larger studies will be necessary to prove our proposed model.

Abstract Background Disease management programmes (DMPs) are costly and impose additional work load on general practitioners (GPs). Data on their effectiveness are inconclusive. We therefore conducted a cluster-randomised controlled trial to evaluate the effectiveness of the Austrian DMP for diabetes mellitus type 2 on HbA1c and quality of care for adult patients in primary care. Methods All GPs of Salzburg-province were invited to participate. After cluster-randomisation by district, all patients with diabetes type 2 were recruited consecutively from 7-11/2007. The DMP, consisting mainly of physician and patient education, standardised documentation and agreement on therapeutic goals, was implemented in the intervention group while the control group received usual care. We aimed to show superiority of the intervention regarding metabolic control and process quality. The primary outcome measure was a change in HbA1c after one year. Secondary outcomes were days in the hospital, blood pressure, lipids, body mass index (BMI), enrolment in patient education and regular guideline-adherent examination. Blinding was not possible. Results 92 physicians recruited 1489 patients (649 intervention, 840 control). After 401 ± 47 days, 590 intervention-patients and 754 controls had complete data. In the intention to treat analysis (ITT) of all 1489 patients, HbA1c decreased 0.41% in the intervention group and 0.28% in controls. The difference of -0.13% (95% CI -0.24; -0.02) was significant at p = 0.026. Significance was lost in mixed models adjusted for baseline value and cluster-effects (adjusted mean difference -0.03 (95% CI -0.15; 0.09, p = 0.607). Of the secondary outcome measures, BMI and cholesterol were significantly reduced in the intervention group compared to controls in ITT after adjustments (-0.53 kg/m²; 95% CI -1.03;-0.02; p = 0.014 and -0.10 mmol/l; 95% CI -0.21; -0.003; p = 0.043). Additionally, more patients received patient education (49.5% vs. 20.1%, p < 0.0001), eye- (71.0% vs. 51.2%, p < 0.0001), foot examinations (73.8% vs. 45.1%, p < 0.0001), and regular HbA1c checks (44.1% vs. 36.0%, p < 0.01) in the intervention group. Conclusion The Austrian DMP implemented by statutory health insurance improves process quality and enhances weight reduction, but does not significantly improve metabolic control for patients with type 2 diabetes mellitus. Whether the small benefit seen in secondary outcome measures leads to better patient outcomes, remains unclear. Trial Registration Current Controlled trials Ltd., ISRCTN27414162.

Abstract Background Chest pain is a common complaint and reason for consultation in primary care. Research related to gender differences in regard to Coronary Heart Disease (CHD) has been mainly conducted in hospital but not in primary care settings. We aimed to analyse gender differences in aetiology and clinical characteristics of chest pain and to provide gender related symptoms and signs associated with CHD. Methods We included 1212 consecutive patients with chest pain aged 35 years and older attending 74 general practitioners (GPs). GPs recorded symptoms and findings of each patient and provided follow up information. An independent interdisciplinary reference panel reviewed clinical data of every patient and decided about the aetiology of chest pain at the time of patient recruitment. Multivariable regression analysis was performed to identify clinical predictors that help to rule in or out CHD in women and men. Results Women showed more psychogenic disorders (women 11,2%, men 7.3%, p = 0.02), men suffered more from CHD (women 13.0%, men 17.2%, p = 0.04), trauma (women 1.8%, men 5.1%, p < 0.001) and pneumonia/pleurisy (women 1.3%, men 3.0%, p = 0.04) Men showed significantly more often chest pain localised on the right side of the chest (women 9.1%, men 25.0%, p = 0.01). For both genders known clinical vascular disease, pain worse with exercise and age were associated positively with CHD. In women pain duration above one hour was associated positively with CHD, while shorter pain durations showed an association with CHD in men. In women negative associations were found for stinging pain and in men for pain depending on inspiration and localised muscle tension. Conclusions We found gender differences in regard to aetiology, selected clinical characteristics and association of symptoms and signs with CHD in patients presenting with chest pain in a primary care setting. Further research is necessary to elucidate whether these differences would support recommendations for different diagnostic approaches for CHD according to a patient's gender.

Abstract Background Due to its rising prevalence type 2 diabetes plays an important role concerning population health in Austria and other western countries. In various studies deficiencies in the care of diabetic patients have been revealed. These deficiencies may be overcome by disease-management-programmes (DMPs), but international experience shows that the effectiveness of DMPs is inconsistent. In particular large programmes designed by state-affiliated public health insurances have not been evaluated in randomized controlled trials (RCTs). We are therefore conducting a large scale RCT of the Austrian DMP for type 2 diabetic patients in the province of Salzburg to evaluate the programme regarding its effects on metabolic control, guideline adherent care and the quality of life of diabetic patients. Methods/Design The study is open for participation to all GPs and internists in the province of Salzburg. Physicians are randomized before recruitment of patients with the districts of Salzburg as clusters of randomisation. A total of over 1200 patients with type 2 diabetes will then be recruited. In the intervention group the DMP is applied for one year. Controls receive usual care. Endpoints are a decrease in HbA1c in the intervention group > 0,5% compared to controls, a higher percentage of patients with required diagnostic measures according to guidelines, improved cardiovascular risk profile and higher quality of life scores within one year. Current status of the study 98 Physicians agreed to participate in the study. 96 of them recruited 1494 patients, 654 in the intervention and 840 in the control group. Trail Registration This trial has been registered with Current Controlled Trials Ltd. (ISRCTN27414162).

Abstract Background Some capability dimensions may be more important than others in determining someone’s well-being, and these preferences might be dependent on ill-health experience. This study aimed to explore the relative preference weights of the 16 items of the German language version of the OxCAP-MH (Oxford Capability questionnaire-Mental Health) capability instrument and their differences across cohorts with alternative levels of mental ill-health experience. Methods A Best–Worst-Scaling (BWS) survey was conducted in Austria among 1) psychiatric patients (direct mental ill-health experience), 2) (mental) healthcare experts (indirect mental ill-health experience), and 3) primary care patients with no mental ill-health experience. Relative importance scores for each item of the German OxCAP-MH instrument were calculated using Hierarchical Bayes estimation. Rank analysis and multivariable linear regression analysis with robust standard errors were used to explore the relative importance of the OxCAP-MH items across the three cohorts. Results The study included 158 participants with complete cases and acceptable fit statistic. The relative importance scores for the full cohort ranged from 0.76 to 15.72. Findings of the BWS experiment indicated that the items Self-determination and Limitation in daily activities were regarded as the most important for all three cohorts. Freedom of expression was rated significantly less important by psychiatric patients than by the other two cohorts, while Having suitable accommodation appeared significantly less important by the expert cohort. There were no further significant differences in the relative preference weights of OxCAP-MH items between the cohorts or according to gender. Conclusions Our study indicates significant between-item but limited mental ill-health related heterogeneity in the relative preference weights of the different capability items within the OxCAP-MH. The findings support the future development of preference-based value sets elicited from the general population for comparative economic evaluation purposes.

BackgroundAs face masks became mandatory in most countries during the COVID-19 pandemic, adverse effects require substantiated investigation.MethodsA systematic review of 2,168 studies on adverse medical mask effects yielded 54 publications for synthesis and 37 studies for meta-analysis (on n = 8,641, m = 2,482, f = 6,159, age = 34.8 ± 12.5). The median trial duration was only 18 min (IQR = 50) for our comprehensive evaluation of mask induced physio-metabolic and clinical outcomes.ResultsWe found significant effects in both medical surgical and N95 masks, with a greater impact of the second. These effects included decreased SpO2 (overall Standard Mean Difference, SMD = −0.24, 95% CI = −0.38 to −0.11, p < 0.001) and minute ventilation (SMD = −0.72, 95% CI = −0.99 to −0.46, p < 0.001), simultaneous increased in blood-CO2 (SMD = +0.64, 95% CI = 0.31–0.96, p < 0.001), heart rate (N95: SMD = +0.22, 95% CI = 0.03–0.41, p = 0.02), systolic blood pressure (surgical: SMD = +0.21, 95% CI = 0.03–0.39, p = 0.02), skin temperature (overall SMD = +0.80 95% CI = 0.23–1.38, p = 0.006) and humidity (SMD +2.24, 95% CI = 1.32–3.17, p < 0.001). Effects on exertion (overall SMD = +0.9, surgical = +0.63, N95 = +1.19), discomfort (SMD = +1.16), dyspnoea (SMD = +1.46), heat (SMD = +0.70), and humidity (SMD = +0.9) were significant in n = 373 with a robust relationship to mask wearing (p < 0.006 to p < 0.001). Pooled symptom prevalence (n = 8,128) was significant for: headache (62%, p < 0.001), acne (38%, p < 0.001), skin irritation (36%, p < 0.001), dyspnoea (33%, p < 0.001), heat (26%, p < 0.001), itching (26%, p < 0.001), voice disorder (23%, p < 0.03), and dizziness (5%, p = 0.01).DiscussionMasks interfered with O2-uptake and CO2-release and compromised respiratory compensation. Though evaluated wearing durations are shorter than daily/prolonged use, outcomes independently validate mask-induced exhaustion-syndrome (MIES) and down-stream physio-metabolic disfunctions. MIES can have long-term clinical consequences, especially for vulnerable groups. So far, several mask related symptoms may have been misinterpreted as long COVID-19 symptoms. In any case, the possible MIES contrasts with the WHO definition of health.ConclusionFace mask side-effects must be assessed (risk-benefit) against the available evidence of their effectiveness against viral transmissions. In the absence of strong empirical evidence of effectiveness, mask wearing should not be mandated let alone enforced by law.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021256694, identifier: PROSPERO 2021 CRD42021256694.

Abstract Background Z-drugs are usually prescribed as first line pharmacological therapy for insomnia. However, the benefits and risks of Z-drugs may differ for older adults. This systematic review investigated the available evidence on the efficacy and safety of Z-drugs in the management of insomnia in older adults. Methods The Cochrane database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, PubMed/MEDLINE and EMBASE were searched for systematic reviews, meta-analyses, controlled interventional and observational studies using a pre-formulated search term. The target population was older adults (≥65 years old) with insomnia. Studies were included if they reported efficacy and/or safety outcomes of the use of Z-drugs for the management of insomnia compared to placebo, usual or no treatment, or other pharmacological agents. Results Eighteen studies were included (8 interventional and 10 observational studies). In short-term interventional studies, Z-drugs were similarly or better efficacious in improving both sleep and daytime parameters than placebo or other pharmacological treatments, while showing good results on measures of safety. However, in longer-term observational studies, Z-drugs significantly increased the risk for falls and fractures in comparison to no treatment or melatonin agonists. Conclusions Analyzing the evidence from short-term interventional studies, Z-drugs appear effective and safe for treatment of insomnia in older adults, but they may have unfavorable side effects when used for longer periods of time. We, therefore, recommend discontinuing Z-drugs, principally because of the high risk for falls and fractures. Nonetheless, quality and quantity of evidence are low. Due to the scarcity of data, especially concerning drug dependence after longer periods of treatment and due to the significantly increased risk for falls and fractures, further studies are needed to evaluate the benefit-risk profile of Z-drugs use in older patients, particularly for long-term use.

Abstract Background Evidence regarding clinically relevant effects of interventions aiming at reducing polypharmacy is weak, especially for the primary care setting. This study was initiated with the objective to achieve clinical benefits for older patients (aged 75+) by means of evidence-based reduction of polypharmacy (defined as ≥8 prescribed drugs) and inappropriate prescribing in general practice. Methods The cluster-randomised controlled trial involved general practitioners and patients in a northern-Italian region. The intervention consisted of a review of patient’s medication regimens by three experts who gave specific recommendations for drug discontinuation. Main outcome measures were non-elective hospital admissions or death within 24 months (composite primary endpoint). Secondary outcomes were drug numbers, hospital admissions, mortality, falls, fractures, quality of life, affective status, cognitive function. Results Twenty-two GPs/307 patients participated in the intervention group, 21 GPs/272 patients in the control group. One hundred twenty-five patients (40.7%) experienced the primary outcome in the intervention group, 87 patients (32.0%) in the control group. The adjusted rates of occurrence of the primary outcome did not differ significantly between the study groups (intention-to-treat analysis: adjusted odds ratio 1.46, 95%CI 0.99–2.18, p = 0.06; per-protocol analysis: adjusted OR 1.33, 95%CI 0.87–2.04, p = 0.2). Hospitalisations as single endpoint occurred more frequently in the intervention group according to the unadjusted analysis (OR 1.61, 95%CI 1.03–2.51, p = 0.04) but not in the adjusted analysis (OR 1.39, 95%CI 0.95–2.03, p = 0.09). Falls occurred less frequently in the intervention group (adjusted OR 0.55, 95%CI 0.31–0.98; p = 0.04). No significant differences were found regarding the other outcomes. Definitive discontinuation was obtained for 67 (16.0%) of 419 drugs rated as inappropriate. About 6% of the prescribed drugs were PIMs. Conclusions No conclusive effects were found regarding mortality and non-elective hospitalisations as composite respectively single endpoints. Falls were significantly reduced in the intervention group, although definitive discontinuation was achieved for only one out of six inappropriate drugs. These results indicate that (1) even a modest reduction of inappropriate medications may entail positive clinical effects, and that (2) focusing on evidence-based new drug prescriptions and prevention of polypharmacy may be more effective than deprescribing. Trial registration Current Controlled Trials (ID ISRCTN: 38449870), date: 11/09/2013.

Abstract Background Type 2 diabetes mellitus (T2DM) and coronary heart disease (CHD) are two chronic diseases that cause a tremendous burden. To reduce this burden, several programmes for optimising the care for these diseases have been developed. In Germany, so-called disease management programmes (DMPs), which combine components of Disease Management and the Chronic Care Model, are applied. These DMPs have proven effective. Nevertheless, there are opportunities for improvement. Current DMPs rarely address self-management of the disease, make no use of peer support, and provide no special assistance for persons with low health literacy and/or low patient activation. The study protocol presented here is for the evaluation of a programme that addresses these possible shortcomings and can be combined with current German DMPs for T2DM and CHD. This programme consists of four components: 1) Meetings of peer support groups 2) Personalised telephone-based health coaching for patients with low literacy and/or low patient activation 3) Personalised patient feedback 4) A browser-based web portal Methods Study participants will be adults enrolled in a DMP for T2DM and/or CHD and living in North Rhine-Westphalia, a state of the Federal Republic of Germany. Study participants will be recruited with the assistance of their general practitioners by the end of June 2021. Evaluation will be performed as a pragmatic randomised controlled trial with one intervention group and one waiting control group. The intervention group will receive the intervention for 18 months. During this time, the waiting control group will continue with usual care and the usual measures of their DMPs. After 18 months, the waiting control group will also receive a shortened intervention. The primary outcome is number of hospital days. In addition, the effects on self-reported health-state, physical activity, nutrition, and eight different psychological variables will be investigated. Differences between values at month 18 and at the beginning will be compared to judge the effectiveness of the intervention. Discussion If the intervention proves effective, it may be included into the DMPs for T2DM and CHD. Trial registration The study was registered in the German Clinical Trials Registry (Deutsches Register Klinischer Studien (DRKS)) in early 2019 under the number 00020592. This registry has been affiliated with the WHO Clinical Trials Network ( https://www.drks.de/drks_web/setLocale_EN.do ) since 2008. It is based on the WHO template, but contains some additional categories for which information has to be given ( https://www.drks.de/drks_web/navigate.do?navigationId=entryfields&messageDE=Beschreibung%20der%20Eingabefelder&messageEN=Description%20of%20entry%20fields ). A release and subsequent number assignment only take place when information for all categories has been given.

The recognition of the role of microglia cells in neurodegenerative diseases has steadily increased over the past few years. There is growing evidence that the uncontrolled and persisting activation of microglial cells is involved in the progression of diseases such as Alzheimer’s or Parkinson’s disease. The inflammatory activation of microglia cells is often accompanied by a switch in metabolism to higher glucose consumption and aerobic glycolysis. In this study, we investigate the changes induced by the natural antioxidant resveratrol in a human microglia cell line. Resveratrol is renowned for its neuroprotective properties, but little is known about its direct effect on human microglia cells. By analyzing a variety of inflammatory, neuroprotective, and metabolic aspects, resveratrol was observed to reduce inflammasome activity, increase the release of insulin-like growth factor 1, decrease glucose uptake, lower mitochondrial activity, and attenuate cellular metabolism in a 1H NMR-based analysis of whole-cell extracts. To this end, studies were mainly performed by analyzing the effect of exogenous stressors such as lipopolysaccharide or interferon gamma on the metabolic profile of microglial cells. Therefore, this study focuses on changes in metabolism without any exogenous stressors, demonstrating how resveratrol might provide protection from persisting neuroinflammation.

Abstract Background A precondition for developing strategies to reduce polypharmacy and its well-known harmful consequences is to study its epidemiology and associated factors. The objective of this study was to analyse the prevalence of polypharmacy (defined as ≥8 prescribed drugs), of potentially inappropriate medications (PIMs) and major drug-drug interactions (DDIs) among community-dwelling general practice patients aged ≥75 years and to identify characteristics being associated with polypharmacy. Methods This cross-sectional study is derived from baseline data (patients’ demographic/biometric characteristics, diagnoses, medication-related data, cognitive/affective status, quality of life) of a northern-Italian cluster-RCT. PIMs and DDIs were assessed using the 2012 Beers criteria and the Lexi-Interact® database. Data were analysed using descriptive methods, Wilcoxon rank-sum tests, Fisher’s exact tests and Spearman correlations. Results Of the eligible patients aged 75+, 13.4% were on therapy with ≥8 drugs. Forty-three general practitioners and 579 patients participated in the study. Forty five point nine percent of patients were treated with ≥1 Beers-listed drugs. The most frequent PIMs were benzodiazepines/hypnotics (19.7% of patients) and NSAIDs (6.6%). Sixty seven point five percent of patients were exposed to ≥1 major DDI, 35.2% to ≥2 major DDIs. Antithrombotic/anticoagulant medications (30.4%) and antidepressants/antipsychotics (23.1%) were the most frequently interacting drugs. Polypharmacy was significantly associated with a higher number of major DDIs (Spearman’s rho 0.33, p

Abstract Background Currently 21% of the German population is older than 65 years. Above this age, the risk of suffering from chronic disease and mental disorders increases rapidly. Therefore, physical inactivity is one of the most important public health concerns among older people. To address this issue, we have conceptualised and evaluated a simple and low-threshold intervention, which requires only minimal demand on the participants, targeting older people with inadequate activity levels. The aim of the POWER Study is to investigate whether volunteer-supported outdoor-walking improves physical function and quality of life in older people. Methods/design In a randomised, controlled interventional superiority-trial, individuals older than 65 years of age living in the community or nursing homes will be randomised into two groups. The study will be conducted in two study centres with assessments at baseline, 6 and 12 months. The intervention group will participate in a supported physical activity intervention for 6 months. An assigned volunteer will visit them three times a week for an outdoor walk between 30 and 50 min, or equivalent indoor activity. Persons in the control group will be invited to two lectures covering topics related to health. Primary endpoint is the physical function measured by the Short Physical Performance Battery (SPPB) at baseline, after 6 and 12 months. Secondary and safety endpoints will be quality of life (EQ. 5D), fear of falling (Falls Efficacy Scale), physical activity (activity diary), cognitive executive function (clock drawing test), falls requiring medical attention, hospitalisation and death. Primary analysis will be carried out by intention to treat. Discussion We expect the intervention to improve the overall health status of the participants in a wide range of health-related outcomes. If effectiveness can be shown, the intervention will close an important gap in current services for older people. We will disseminate our experiences and results in the form of informational documents (training manual) to allow municipalities and health care organisations to implement a similar intervention. Trial registration The trial was registered on 31 Aug 2018; German Clinical Trials Register (www.germanctr.de), Deutsches Register Klinischer Studien: DRKS00015188 .

Registration: PROSPERO: CRD42020210645 Introduction: We aimed to assess the safety of dipeptidyl peptidase-4 (DPP-4) inhibitors in older patients with type 2 diabetes with inadequate glycaemic control. Methods: We included randomized controlled trials (RCTs) in older (⩾65 years) patients with type 2 diabetes. The intervention group was randomized to treatment with any DPP-4 inhibitors. A systematic search in MEDLINE and Embase was performed in December 2020. For assessing the risk of bias, RoB 2 tool was applied. The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. We pooled outcomes using random effects meta-analyses. Results: We identified 16 RCTs that included 19,317 patients with a mean age of greater than 70 years. The mean HbA1c level ranged between 7.1 and 10.0 g/dl. Adding DPP-4 inhibitors to standard care alone may increase mortality slightly [risk ratio (RR) 1.04; 95% confidence interval (CI) 0.89–1.21]. Adding DPP-4 inhibitors to standard care increases the risk for hypoglycaemia (RR 1.08; 95% CI 1.01–1.16), but difference in overall adverse events is negligible. DPP-4 inhibitors added to standard care may reduce mortality compared with sulfonylureas (RR 0.88; 95% CI 0.75–1.04). DPP-4 inhibitors probably reduce the risk for hypoglycaemia compared with sulfonylureas (magnitude of effect not quantifiable because of heterogeneity) but difference in overall adverse events is negligible. There is insufficient evidence on hospitalizations, falls, fractures, renal impairment and pancreatitis. Conclusion: There is no evidence that DPP-4 inhibitors in addition to standard care decrease mortality but DPP-4 inhibitors increase hypoglycaemia risk. Second-line therapy in older patients should be considered cautiously even in drugs with a good safety profile such as DPP-4 inhibitors. In case second-line treatment is necessary, DPP-4 inhibitors appear to be preferable to sulfonylureas. Plain language summary Safety of dipeptidyl peptidase-4 inhibitors in older adults with type 2 diabetes Introduction: We performed the review to assess the safety of dipeptidyl peptidase-4 (DPP-4) inhibitors in older type 2 diabetes patients with blood sugar outside the normal level. Methods: To answer the question, we searched various electronic databases. We included studies in older (⩾65 years) patients with type 2 diabetes that assessed the safety of DPP-4 inhibitors. The data from the different studies were quantitatively summarized using statistical methods. We assessed the quality of the data to judge the certainty of the findings. Results: We identified 16 studies that included 19,317 patients with a mean age greater than 70 years. The average blood sugar level of patients in the included studies was slightly or moderately increased. Adding DPP-4 inhibitors to standard care alone may increase mortality slightly. Adding DPP-4 inhibitors to standard care increases the risk for hypoglycaemia, but difference in overall adverse events is negligible. DPP-4 inhibitors added to standard care may reduce mortality compared with sulfonylureas. DPP-4s probably reduce the risk of hypoglycaemia compared with sulfonylureas (magnitude of effect not quantifiable because of heterogeneity) but difference in overall adverse events is negligible. There is insufficient evidence on hospitalizations, falls, fractures, renal impairment and pancreatitis. Conclusion: There is no evidence that DPP-4 inhibitors in addition to standard care decrease mortality but DPP-4 inhibitors increase the risk that blood sugar falls below normal. Adding DPP-4 inhibitorss to standard care in older patients should be considered cautiously even in drugs with a good safety profile such as DPP-4 inhibitors. In case additional treatment is necessary, DPP-4 inhibitors appear to be preferable to sulfonylureas.

Vouacapoua americana (Fabaceae) is an economically important tree in the Amazon region and used for its highly resistant heartwood as well as for medicinal purposes. Despite its frequent use, phytochemical investigations have been limited and rather focused on ecological properties than on its pharmacological potential. In this study, we investigated the phytochemistry and bioactivity of V. americana stem bark extract and its constituents to identify eventual lead structures for further drug development. Applying hydrodistillation and subsequent GC-MS analysis, we investigated the composition of the essential oil and identified the 15 most abundant components. Moreover, the diterpenoids deacetylchagresnone (1), cassa-13(14),15-dien-oic acid (2), isoneocaesalpin H (3), (+)-vouacapenic acid (4), and (+)-methyl vouacapenate (5) were isolated from the stem bark, with compounds 2 and 4 showing pronounced effects on Methicillin-resistant Staphylococcus aureus and Enterococcus faecium, respectively. During the structure elucidation of deacetylchagresnone (1), which was isolated from a natural source for the first time, we detected inconsistencies regarding the configuration of the cyclopropane ring. Thus, the structure was revised for both deacetylchagresnone (1) and the previously isolated chagresnone. Following our works on Copaifera reticulata and Vatairea guianensis, the results of this study further contribute to the knowledge of Amazonian medicinal plants.