Is There an Association Between Inflammation and Serum-Vitamin D? - Results of a Retrospective Analysis of Hospitalized Geriatric Patients.

Purpose: Vitamin D deficiency is a common finding in geriatric patients. The ESPEN micronutrient guideline states that vitamin D serum levels significantly decrease in the presence of inflammation and should be interpreted with caution. This is of great interest for hospital care and would imply a significant change to the current approach to hospitalized patients with suspected vitamin D deficiency. Patients and methods: To evaluate the association of vitamin D and inflammation, we reanalyzed the data set of serum 25(OH)D-Levels of 687 consecutive geriatric hospitalized patients of a previously published study. Results: We found that vitamin D deficiency (<20 ng/dl) was prevalent in 78.0% and vitamin D insufficiency (20-30 ng/dl) in 9.9% of patients. Sperman's correlation showed a significant but very weak correlation (R = -0.100, P < 0.01) of serum vitamin D and C-reactive protein. However, linear regression with the inclusion of age and gender revealed no significant association (beta-coefficient -0.070; p=0.067). Conclusion: In this study, we could not confirm a significant and clinically relevant association between serum vitamin D levels and inflammation, contrasting with a previous study. However, longitudinal studies need to be performed to draw a final conclusion.

A volunteer-supported walking programme to improve physical function in older people with restricted mobility (the POWER Study): a randomised controlled trial.

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.

Does residential exposure to air pollutants influence mortality and cardiovascular morbidity of older people from primary care?

BACKGROUND: Diseases affecting the cardiovascular system are the most common cause of death worldwide. In addition to classical risk factors of atherosclerosis, long-term exposure to particulate matter with particles of size up to 10 µm (PM10) in the atmosphere has become an increasing focus of scientific attention in recent decades. This study analyses the associations of residential-associated air pollutants exposure with all-cause mortality and cardiovascular morbidity of older patients in a primary care setting. METHODS: The "German Epidemiological Trial on Ankle Brachial Index" (getABI) is a prospective cohort study that started in 2001 and included 6,880 primary care patients with a follow-up of 7 years. The PM10 and nitrogen dioxide (NO2) concentrations in the atmosphere are interpolated values from the study "Mapping of background air pollution at a fine spatial scale across the European Union". The primary outcome in this analysis is death of any cause, a secondary outcome is onset of PAD. Cox proportional hazards regression was used in a two-step modelling, the first step with basic adjustment only for age, sex, and one or more air pollutants, the second with additional risk factors. RESULTS: A total of 6,819 getABI patients were included in this analysis. 1,243 of them died during the study period. The hazard ratio (HR) (1.218, 95%-confidence-interval (CI) 0.949-1.562) for the risk of death from any cause was elevated by 22% per 10 µg/m3 increase of PM10 in the fully adjusted model, although not statistically significant. Increased PM10 exposure in combination with the presence of PAD had a significantly increased risk (HR = 1.560, 95%-CI: 1.059-2.298) for this endpoint in the basic adjustment, but not in the fully adjusted model. 736 patients developed peripheral artery disease (PAD) during the course of the study. There was no association of air pollutants and the onset of PAD. CONCLUSIONS: Our analysis renders some hints for the impact of air pollutants (PM10, NO2, and proximity to major road) on mortality. Interaction of PAD with PM10 was found. There was no association of air pollutants and the onset of PAD. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00029733 (19/09/2022).

Experiences of participants of a volunteer-supported walking intervention to improve physical function of nursing home residents - a mixed methods sub-study of the POWER-project.

BACKGROUND: Regular physical activity improves physical health and mental well-being and reduces the risk of falling in older adults. The randomized controlled "Prevention by lay-assisted Outdoor-Walking in the Elderly at Risk" POWER-study investigates whether volunteer-supported outdoor-walking improves physical function and quality of life in older people living independently or in nursing homes. This sub-study explores the experiences of older participants and volunteers in relation to their physical and psychosocial well-being as well as the challenges faced by both groups. A further aim was to explore volunteers' experience with people living in nursing homes during the first pandemic lockdown (spring 2020). METHODS: The sub-study was designed as mixed-methods approach consisting of 11 individual semi-structured guide-based interviews (nursing home residents), two focus group interviews (volunteers), and a cross-sectional questionnaire survey (volunteers). The interviews were audiotaped, transcribed verbatim, and analyzed by content analysis as described by Kuckartz. Topics addressed in the interviews were triangulated by means of a questionnaire. The quantitative data were analyzed using descriptive statistics. RESULTS: Participants' evaluation of the intervention was generally positive. Nursing home residents appreciated the social interaction associated with the assisted walking, which motivated them to take part regularly, provided a sense of safety, and caused pleasure on both sides. The impact on physical health status of the nursing home residents of this sub-study varied to a large degree as reported in interviews: in some cases, an improvement in physical performance, a decrease in physical complaints, and an improvement in gait or independence was reported. If not, reference was made to previous or sudden illnesses and the advanced age of the participants. Despite the COVID-19-lockdown and the associated restrictions, about 60% of contacts were still possible and participants planned to continue the assisted walks after the lockdown. CONCLUSION: Volunteers have a positive effect on the quality of life, mobility, and general health of nursing home residents. Even more than the improvement of physical performance, social interaction was seen as helpful. Despite their advanced age, the nursing home residents were curious and open to new contacts. When removing the identified barriers, it might be possible to integrate this program into the long-term everyday life of nursing homes. TRIAL REGISTRATION: DRKS-ID: DRKS00015188, date of registration: 31.08.2018.

Fall prevention by reactive balance training on a perturbation treadmill: is it feasible for prefrail and frail geriatric patients? A pilot study.

PURPOSE: Prefrail and frail geriatric patients are at high risk of falling. Perturbation-based balance training on a treadmill appears to be highly effective, but there are no studies in prefrail and frail geriatric hospital patients. The aim of the work is to characterize the study population in whom reactive balance training on a perturbation treadmill was feasible. METHODS: The study is recruiting patients with at least one fall event in the past year (age ≥ 70). The patients complete a minimum of 60-min treadmill training with/without perturbations on at least 4 occasions. RESULTS: Until now, 80 patients (mean age 80 ± 5) took part in the study. More than half of the participants had some cognitive impairment with < 24 pts. (median MoCA 21 pts.), 35% were prefrail and 61% were frail. The drop-out rate was initially 31% and was reduced to 12% after adding a short pre-test on the treadmill. CONCLUSION: Reactive balance training on a perturbation treadmill is feasible for prefrail and frail geriatric patients. Its effectiveness in fall prevention in this population needs to be proven. TRIAL REGISTRATION: German Clinical trial register (DRKS-ID: DRKS00024637 on 24.02.2021).

Sarcopenic Dysphagia Revisited: A Cross-Sectional Study in Hospitalized Geriatric Patients.

Oropharyngeal dysphagia (OD) is a frequent finding in older patients with potentially lethal complications such as aspiration pneumonia, malnutrition, and dehydration. Recent studies describe sarcopenia as a causative factor for OD, which is occasionally referred to as "sarcopenic dysphagia" in the absence of a neurogenic etiology. In most of the previous studies on sarcopenic dysphagia, the diagnosis was based only on clinical assessment. In this study, flexible endoscopic evaluation of swallowing (FEES) was used as an objective method to evaluate the presence of OD, its association with sarcopenia, and the presence of pure sarcopenic dysphagia. In this retrospective cross-sectional study, 109 acute care geriatric hospital patients with suspected OD received FEES examination and bioimpedance analysis (BIA) in clinical routine. 95% of patients had at least one neurological disease, 70% fulfilled the criteria for sarcopenia, and 45% displayed moderate or severe OD. Although the prevalence of sarcopenia and OD was high, there was no significant association between OD and sarcopenia. Considering these results, both the association between sarcopenia and OD and pure sarcopenic dysphagia appear questionable. Further prospective studies are needed to elucidate if sarcopenia is merely an epiphenomenon of severe disease or whether it plays a causative role in the development of OD.

Acute disease induced cognitive dysfunction in older patients - an unrecognized syndrome.

BACKGROUND: It is unknown, how many older hospitalized patients experience cognitive changes independently from delirium. METHODS: In this retrospective study, cognitive function was assessed with the Montreal Cognitive Assessment on admission and discharge in 103 acute care geriatric hospital patients. RESULTS: Mean age was 80.8 ± 7.3 years. The total MoCA score on admission was 17.8 (±4.5) and at discharge 17.7 (±4.4). The mean difference of the total MoCA score was - 0.1 (±3.5). 12 (11.7%) patients suffered from delirium. 46 (44.7%) patients experienced significant changes of cognitive function <- 2 or > 2 MoCA points without delirium. There was no significant association between delirium during hospital stay and the prevalence and magnitude of changes in total MoCA score. CONCLUSION: Cognitive changes frequently occur during acute disease of geriatric patients independently from delirium. We propose the term "acute disease induced cognitive dysfunction" (ADICD) for this entity. TRIAL REGISTRATION: German Clinical trial register (DRKS-ID: DRKS00025157 on 28.04.2021).

The Efficacy of Short-Term Bridging Strategies With High- and Low-Dose Prednisolone on Radiographic and Clinical Outcomes in Active Early Rheumatoid Arthritis: A Double-Blind, Randomized, Placebo-Controlled Trial.

OBJECTIVE: In active early rheumatoid arthritis (RA), glucocorticoids are often used for bridging, due to the delayed action of methotrexate. This study was undertaken to compare the effect of 3 bridging strategies, including high-dose and low-dose prednisolone, on radiographic and clinical outcomes. METHODS: Adult RA patients from 1 rheumatology hospital and 23 rheumatology practices who presented with moderate/high disease activity were randomized (1:1:1) to receive 60 mg prednisolone (high-dose prednisolone [HDP]) or 10 mg prednisolone (low-dose prednisolone [LDP]) daily (tapered to 0 mg within 12 weeks) or placebo. The 12-week intervention period was followed by 40 weeks of therapy at the physicians' discretion. The primary outcome measure was radiographic change at 1 year measured using the total modified Sharp/van der Heijde score (SHS). Disease activity was assessed with the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR). RESULTS: Of 395 randomized patients (HDP, n = 132; LDP, n = 131; placebo, n = 132), 375 (95%) remained in the modified intention-to-treat analysis. Mean ± SD changes in SHS scores in the 3 groups after 1 year were comparable: mean ± SD 1.0 ± 2.0 units in the HDP group, 1.1 ± 2.2 units in the LDP group, and 1.1 ± 1.5 units in the placebo group. The primary analysis showed no superiority of HDP compared to placebo (estimated difference of the mean change -0.04 [95% confidence interval (95% CI) -0.5, 0.4]). At week 12, the mean DAS28-ESR differed: -0.6 (95% CI -1.0, -0.2) for HDP versus placebo; -0.8 (95% CI -1.2, -0.5) for LDP versus placebo. At week 52, there was no significant difference in DAS28-ESR between the 3 groups (range 2.6-2.8). Serious adverse events occurred similarly often. CONCLUSION: Short-term glucocorticoid bridging therapy at a high dose showed no benefit with regard to progression of radiographic damage at 1 year.

The Structured Delegation of Medical Care Services for Patients With Inflammatory Rheumatic Diseases.

BACKGROUND: In some areas of Germany, there is a shortage of specialist physicians for patients with inflammatory rheumatic diseases. Delegating certain medical care services to qualified, specialized rheumatological assistants (SRAs) might be an effective way to supplement the available capacity for specialized medical care. METHODS: Patients under stable treatment for rheumatoid arthritis (RA) or psoriatic arthritis (PsA) were included in this trial, which was designed to demonstrate, in a first step, the non-inferiority of a form of care involving delegation of physicians' tasks to SRAs (team-based care), in comparison to standard care, with respect to changes in disease activity at one year. "Non-inferiority," in this context, means either superiority or else an irrelevant extent of inferiority. In a second step, in case non-inferiority could be shown, the superiority of team-based care with respect to changes in patients' health-related quality of life would be tested as well. Disease activity was measured with the Disease Activity Score 28, and health-related quality of life with the EQ-5D-5L. This was a randomized, multicenter, rater-blinded trial with two treatment arms (team-based care and standard care). The statistical analysis was performed with mixed linear models (DRKS00015526). RESULTS: From September 2018 to June 2019, 601 patients from 14 rheumatological practices and 3 outpatient rheumatological clinics in the German states of North Rhine-Westphalia and Lower Saxony were randomized to either team-based or standard care. Team-based care was found to be non-inferior to standard care with respect to changes in disease activity (adjusted difference = -0.19; 95% confidence interval [-0.36; -0.02]; p <0.001 for non-inferiority). Superiority with respect to health-related quality of life was not demonstrated (adjusted difference = 0.02 [-0.02; 0.05], p = 0.285). CONCLUSION: Team-based care, with greater integration of SRAs, is just as good as standard care in important respects. Trained SRAs can effectively support rheumatologists in the care of stable patients with RA or PsA.

Interrater reliability of routine screening for risk of malnutrition with the Mini Nutritional Assessment Short-Form in hospital.

BACKGROUND/OBJECTIVES: The Mini Nutritional Assessment Short-Form (MNA-SF) is the recommended screening tool for older persons. Data on interrater reliability in clinical routine are rare. Thus, we wanted to quantify the interrater reliability of the MNA-SF in hospital. SUBJECTS/METHODS: This observational cross-sectional study was undertaken retrospectively. The study population comprised 105 participants. Risk of malnutrition was measured twice with the routine MNA-SF performed by nurses (within 24 h after admission) and a dedicated dietician (one to three days after the first MNA-SF). The MNA-SF score was analyzed for interrater reliability between nurse and dietician. RESULTS: Participants' mean age was 82.4 (±7.1) years and 71 (68%) were women. The mean total MNA-SF score was 7.4 (±2.4) assessed by dietician and 7.8 (±2.3) assessed by nurse. The intra-class correlation coefficient between the total MNA-SF scores was 0.74 (0.61; 0.82), indicating moderate reliability. For the MNA-SF nutritional status, Cohens Kappa was 0.37 (p < 0.05) showing a fair agreement. CONCLUSION: Multiple misclassifications were observed between malnutrition and risk of malnutrition. Because mean scores were near the border between malnutrition and risk of malnutrition, we recommend to consider the total MNA-SF score in addition to the three risk groups to assess nutritional risk in geriatric hospital patients.

Inflammation as a diagnostic criterion in the GLIM definition of malnutrition-what CRP-threshold relates to reduced food intake in older patients with acute disease?

BACKGROUND/OBJECTIVES: In the recently introduced GLIM diagnosis of malnutrition (Global Leadership Initiative on Malnutrition), details of how to classify inflammation as an etiologic criterion are lacking. This study aimed to determine at what level of serum C-reactive protein (CRP) the risk of low food intake increases in acutely ill older hospitalized patients. SUBJECTS/METHODS: A total of 377 patients, who were consecutively admitted to a geriatric acute care ward, were analyzed. Nutritional intake was determined using the food intake item of Nutritional Risk Screening and the plate diagram method and patients were grouped into three categories as >75%, 50-75% and ≤50% of requirements. CRP was analyzed according to standard procedures and patients were classified into different CRP groups as follows: 0.0-0.99 mg/dl, 1.0-1.99 mg/dl, 2.0-2.99 mg/dl, 3.0-4.99 mg/dl, 5.0-9.99 mg/dl and ≥10.0 mg/dl. RESULTS: Of the total population (mean age of 82.2 ± 6.6 years; 241 females), 82 (22%) had intake <50% of requirements and 126 (33%) demonstrated moderate to severe inflammation. Patients with food intake <50% of requirements had a significantly higher median CRP level compared to patients with food intake >75% of requirements (P < 0.001). The group with serum-CRP levels above 3.0 mg/dl had a markedly higher proportion of patients with low food intake; i.e., <50% and <75% of the requirements. CONCLUSION: A serum-CRP of 3.0 mg/dl appears to be a reasonable threshold of acute inflammation leading to reduced food intake to serve as an orientation with regard to the inflammation criterion of the GLIM diagnosis in acutely ill older patients.

Osteosarcopenia, an Asymmetrical Overlap of Two Connected Syndromes: Data from the OsteoSys Study.

Osteoporosis and sarcopenia are two chronic conditions, which widely affect older people and share common risk factors. We investigated the prevalence of low bone mineral density (BMD) and sarcopenia, including the overlap of both conditions (osteosarcopenia) in 572 older hospitalized patients (mean age 75.1 ± 10.8 years, 78% women) with known or suspected osteoporosis in this prospective observational multicenter study. Sarcopenia was assessed according to the revised definition of the European Working Group on Sarcopenia in Older People (EWGSOP2). Low BMD was defined according to the World Health Organization (WHO) recommendations as a T-score < -1.0. Osteosarcopenia was diagnosed when both low BMD and sarcopenia were present. Low BMD was prevalent in 76% and the prevalence of sarcopenia was 9%, with 90% of the sarcopenic patients showing the overlap of osteosarcopenia (8% of the entire population). Conversely, only few patients with low BMD demonstrated sarcopenia (11%). Osteosarcopenic patients were older and frailer and had lower BMI, fat, and muscle mass, handgrip strength, and T-score compared to nonosteosarcopenic patients. We conclude that osteosarcopenia is extremely common in sarcopenic subjects. Considering the increased risk of falls in patients with sarcopenia, they should always be evaluated for osteoporosis.

Use of an electronic decision support tool to reduce polypharmacy in elderly people with chronic diseases: cluster randomised controlled trial.

OBJECTIVE: To evaluate the effects of a computerised decision support tool for comprehensive drug review in elderly people with polypharmacy. DESIGN: Pragmatic, multicentre, cluster randomised controlled trial. SETTING: 359 general practices in Austria, Germany, Italy, and the United Kingdom. PARTICIPANTS: 3904 adults aged 75 years and older using eight or more drugs on a regular basis, recruited by their general practitioner. INTERVENTION: A newly developed electronic decision support tool comprising a comprehensive drug review to support general practitioners in deprescribing potentially inappropriate and non-evidence based drugs. Doctors were randomly allocated to either the electronic decision support tool or to provide treatment as usual. MAIN OUTCOME MEASURES: The primary outcome was the composite of unplanned hospital admission or death by 24 months. The key secondary outcome was reduction in the number of drugs. RESULTS: 3904 adults were enrolled between January and October 2015. 181 practices and 1953 participants were assigned to electronic decision support (intervention group) and 178 practices and 1951 participants to treatment as usual (control group). The primary outcome (composite of unplanned hospital admission or death by 24 months) occurred in 871 (44.6%) participants in the intervention group and 944 (48.4%) in the control group. In an intention-to-treat analysis the odds ratio of the composite outcome was 0.88 (95% confidence interval 0.73 to 1.07; P=0.19, 997 of 1953 v 1055 of 1951). In an analysis restricted to participants attending practice according to protocol, a difference was found favouring the intervention (odds ratio 0.82, 95% confidence interval 0.68 to 0.98; 774 of 1682 v 873 of 1712, P=0.03). By 24 months the number of prescribed drugs had decreased in the intervention group compared with control group (uncontrolled mean change -0.42 v 0.06: adjusted mean difference -0.45, 95% confidence interval -0.63 to -0.26; P<0.001). CONCLUSIONS: In intention-to-treat analysis, a computerised decision support tool for comprehensive drug review of elderly people with polypharmacy showed no conclusive effects on the composite of unplanned hospital admission or death by 24 months. Nonetheless, a reduction in drugs was achieved without detriment to patient outcomes. TRIAL REGISTRATION: Current Controlled Trials ISRCTN10137559.

Nurse-led care versus physician-led care in the management of rheumatoid arthritis and psoriatic arthritis (StaerkeR): study protocol for a multi-center randomized controlled trial.

BACKGROUND: In Germany, the care of patients with inflammatory arthritis could be improved. Although specialized rheumatology nurses could take over substantial aspects of patient care, this hardly occurs in Germany. Thus, the aim of the study is to examine structured nursing consultation in rheumatology practices. METHODS/DESIGN: In total, 800 patients with a stable course of rheumatoid arthritis or psoriatic arthritis in 20 centers in North Rhine-Westphalia and Lower Saxony will be randomized to either nurse-led care or standard care. Participating nurses will study for a special qualification in rheumatology and trial-specific issues. It is hypothesized that nurse-led care is non-inferior to standard care provided by rheumatologists with regard to a reduction of disease activity (DAS28) while it is hypothesized to be superior regarding changes in health-related quality of life (EQ-5D-5L) after 1 year. Secondary outcomes include functional capacity, patient satisfaction with treatment, and resource consumption. DISCUSSION: Since there is insufficient care of rheumatology patients in Germany, the study may be able to suggest improvements. Nurse-led care has the potential to provide more efficient and effective patient care. This includes a more stringent implementation of the treat-to-target concept, which may lead to a higher percentage of patients reaching their treatment targets, thereby improving patient-related outcomes, such as quality of life, functional capacity, and participation. Additionally, nurse-led care may be highly cost-effective. Finally, this project may form the basis for a sustainable implementation of nurse-led care in standard rheumatology care in Germany. TRIAL REGISTRATION: German Clinical Trials Register, DRKS00015526. Registered on 11 January 2019.

Polypharmacy in older patients with chronic diseases: a cross-sectional analysis of factors associated with excessive polypharmacy.

BACKGROUND: Polypharmacy is common in older people and associated with potential harms. The aim of this study was to analyse the characteristics of an older multimorbid population with polypharmacy and to identify factors contributing to excessive polypharmacy in these patients. METHODS: This cross-sectional analysis is based on the PRIMA-eDS trial, a large randomised controlled multicentre study of polypharmacy in primary care. Patients' baseline data were used for analysis. A number of socioeconomic and medical data as well as SF-12-scores were entered into a generalized linear mixed model to identify variables associated with excessive polypharmacy (taking ≥10 substances daily). RESULTS: Three thousand nine hundred four participants were recruited. Risk factors significantly associated with excessive polypharmacy were frailty (OR 1.45; 95% CI 1.22-1.71), > 8 diagnoses (OR 2.64; 95% CI 2.24-3.11), BMI ≥30 (OR 1.18; 95% CI 1.02-1.38), a lower SF-12 physical health composite score (OR 1.47; 95% CI 1.26-1.72), and a lower SF-12 mental health composite score (OR 1.33; 95% CI 1.17-1.59) than the median of the study population (≤36.6 and ≤ 48.7, respectively). Age ≥ 85 years (OR 0.83; 95% CI 0.70-0.99) led to a significantly lower risk for excessive polypharmacy. No association with excessive polypharmacy could be found for female sex, low educational level, and smoking. Regarding the study centres, being recruited in the UK led to a significantly higher risk for excessive polypharmacy compared to being recruited in Germany 1/Rostock (OR 1.71; 95% CI 1.27-2.30). Being recruited in Germany 2/Witten led to a slightly significant lower risk for excessive polypharmacy compared to Germany 1/Rostock (OR 0.74; 95% CI 0.56-0.97). CONCLUSIONS: Frailty, multimorbidity, obesity, and decreased physical as well as mental health status are risk factors for excessive polypharmacy. Sex, educational level, and smoking apparently do not seem to be related to excessive polypharmacy. Physicians should especially pay attention to their frail, obese patients who have multiple diagnoses and a decreased health-related quality of life, to check carefully whether all the drugs prescribed are evidence-based, safe, and do not interact in an unfavourable way. TRIAL REGISTRATION: This trial has been registered with Current Controlled Trials Ltd. on 31 July 2014 (ISRCTN10137559).

The risk of peripheral artery disease in older adults - seven-year results of the getABI study.

BACKGROUND: To assess the risk of peripheral artery disease (PAD) in older adults and the contribution of traditional and novel risk factors to the incidence of PAD. PATIENTS AND METHODS: 344 general practitioners (GPs), trained by vascular specialists all over Germany, enrolled 6,880 unselected participants aged 65 years or older (getABI study). The onset of PAD was determined by a regression method in the course of repeated measurements of the ankle brachial index (ABI) over seven years. PAD onset was defined by the declining linear regression ABI line reaching 0.9 or by PAD symptoms. RESULTS: The cumulative PAD incidence over seven years was 12.9%, corresponding to an incidence rate of 20.3 per 1000 person years (95% confidence interval [95%CI] 18.8 to 21.7). Logistic regression analysis showed that traditional risk factors contributed significantly to the risk of PAD: current smoker status (odds ratio 2.65, 95%CI 2.08 to 3.37), diabetes (1.35, 95%CI 1.13 to 1.62), and low-density lipoprotein >130 mg/dl (1.26, 95%CI 1.07 to 1.48). Three novel risk factor candidates showed significant impact on PAD incidence: elevated sensitive C-reactive protein level (1.23, 95%CI 1.05 to 1.45), impaired estimated glomerular filtration rate (1.27, 95%CI 1.03 to 1.56), and elevated homocysteine level (1.19, 95%CI 1.01 to 1.41). CONCLUSIONS: Older adults in Germany have a PAD risk of 12.9% per seven years. Potentially modifiable traditional PAD risk factors yield high impact on PAD incidence. Novel risk factor candidates may contribute to the risk of PAD.

Polypharmacy in chronic diseases-Reduction of Inappropriate Medication and Adverse drug events in older populations by electronic Decision Support (PRIMA-eDS): study protocol for a randomized controlled trial.

BACKGROUND: Multimorbidity is increasing in aging populations with a corresponding increase in polypharmacy as well as inappropriate prescribing. Depending on definitions, 25-50 % of patients aged 75 years or older are exposed to at least five drugs. Evidence is increasing that polypharmacy, even when guidelines advise the prescribing of each drug individually, can potentially cause more harm than benefit to older patients, due to factors such as drug-drug and drug-disease interactions. Several approaches reducing polypharmacy and inappropriate prescribing have been proposed, but evidence showing a benefit of these measures regarding clinically relevant endpoints is scarce. There is an urgent need to implement more effective strategies. We therefore set out to develop an evidence-based electronic decision support (eDS) tool to aid physicians in reducing inappropriate prescribing and test its effectiveness in a large-scale cluster-randomized controlled trial. METHODS: The "Polypharmacy in chronic diseases-Reduction of Inappropriate Medication and Adverse drug events in older populations" (PRIMA)-eDS tool is a tool comprising an indication check and recommendations for the reduction of polypharmacy and inappropriate prescribing based on systematic reviews and guidelines, the European list of inappropriate medications for older people, the SFINX-database of interactions, the PHARAO-database on adverse effects, and the RENBASE-database on renal dosing. The tool will be evaluated in a cluster-randomized controlled trial involving 325 general practitioners (GPs) and around 3500 patients across five study centres in the United Kingdom, Germany, Austria and Italy. GP practices will be asked to recruit 11 patients aged 75 years or older who are taking at least eight medications and will be cluster-randomized after completion of patient recruitment. Intervention GPs will have access to the PRIMA-eDS tool, while control GPs will treat their patients according to current guidelines (usual care) without access to the PRIMA-eDS tool. After an observation time of 2 years, intervention and control groups will be compared regarding the primary composite endpoint of first non-elective hospitalization or death. DISCUSSION: The principal hypothesis is that reduction of polypharmacy and inappropriate prescribing can improve the clinical composite outcome of hospitalization or death. A positive result of the trial will contribute substantially to the improvement of care in multimorbidity. The trial is necessary to investigate not only whether the reduction of polypharmacy improves outcome, but also whether GPs and patients are willing to follow the recommendations of the PRIMA-eDS tool. TRIAL REGISTRATION: This trial has been registered with Current Controlled Trials Ltd. on 31 July 2014 (ISRCTN10137559).

Comparison of the efficacy and safety of two starting dosages of prednisolone in early active rheumatoid arthritis (CORRA): study protocol for a randomized controlled trial.

BACKGROUND: Although glucocorticoids are widely used in the treatment of patients with early rheumatoid arthritis, the best dosage of glucocorticoids with regards to efficacy and safety is not known.The aim of the study 'Comparison of the efficacy and safety of two starting dosages of prednisolone in early active rheumatoid arthritis' (CORRA) is to compare two standard glucocorticoid starting dosages and the non-use of glucocorticoids in the treatment of patients with early active rheumatoid arthritis on the background of the established 'anchor' therapy with methotrexate. METHODS/DESIGN: CORRA is an investigator-initiated, randomized, multicenter, double-blind, placebo-controlled trial with two treatment arms, starting with 60 mg or 10 mg prednisolone per day, tapered down to 5 mg prednisolone within eight weeks, and one placebo arm, each arm comprising 150 patients. The duration of the intervention is 12 weeks. In parallel, all patients will be treated with methotrexate (usual dosage 15 mg/week). The primary efficacy endpoint is the progression of radiographic joint damage after one year compared to baseline. Important secondary endpoints are the percentage of patients in remission, patient global assessment of disease activity, and changes of functional capacity. Safety monitoring is performed.The statistical analysis is performed in three hierarchical steps. The first step is an analysis of covariance (α = 0.05) to compare the group with the initial prednisolone dosage of 60 mg and the placebo group. In case of a statistically significant result, the comparison of the group starting with 10 mg prednisolone with the placebo group will be performed as a second step (α = 0.05). In case of superiority of the 10 mg prednisolone group versus the placebo group, the third step will be a non-inferiority test for the 10 mg prednisolone group versus the 60 mg prednisolone group (α = 0.025). DISCUSSION: The CORRA trial will yield information concerning the optimal glucocorticoid dosage schedule in the treatment of patients with early rheumatoid arthritis. TRIAL REGISTRATION: This trial was registered on 19 November 2013 at ClinicalTrials.gov. REGISTRATION NUMBER: NCT02000336.

Falls and EQ-5D rated quality of life in community-dwelling seniors with concurrent chronic diseases: a cross-sectional study.

BACKGROUND: Although recommended for use in studies investigating falls in the elderly, the European Quality of Life Group instrument, EQ-5D, has not been widely used to assess the impact of falls on quality of life. The aim of this study was to investigate the association of single and frequent falls with EQ-5D rated quality of life in a sample of German community-dwelling seniors in primary care suffering a variety of concurrent chronic diseases and conditions. METHODS: In a cross-sectional study, a sample of community-dwelling seniors aged ≥ 72 years was interviewed by means of a standardised telephone interview. According to the number of self-reported falls within twelve months prior to interview, participants were categorised into one of three fall categories: no fall vs. one fall vs. two or more falls within twelve months. EQ-5D values as well as other characteristics were compared across the fall categories. Adjustments for a variety of concurrent chronic diseases and conditions and further variables were made by using multiple linear regression analysis, with EQ-5D being the target variable. RESULTS: In total, 1,792 participants (median age 77 years; 53% female) were analysed. The EQ-5D differed between fall categories. Participants reporting no fall had a mean EQ-5D score of 81.1 (standard deviation [s.d.]: 15.4, median: 78.3), while participants reporting one fall (n = 265; 14.8%) and participants with two or more falls (n = 117; 6.5%) had mean total scores of 77.0 (s.d.: 15.8, median: 78.3; mean difference to participants without a fall: -4.1, p < 0.05) and 72.1 (s.d.: 17.6, median: 72.5; mean difference: -9.0, p < 0.05), respectively. The mean difference between participants with one fall and participants with two or more falls was -4.9 (p < 0.05). Under adjustment for a variety of chronic diseases and conditions, the mean decrease in the total EQ-5D score was about -1.0 score point for one fall and about -2.5 points for two or more falls within twelve months. In quantity, this decrease is comparable to other chronic diseases adjusted for. Among the variables with the greatest negative association with EQ-5D ratings in multivariate analysis were depression and fear of falling. CONCLUSIONS: The findings suggest that falls are negatively associated with EQ-5D rated quality of life independent of a variety of chronic diseases and conditions.