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.

Assessing the quality of evidence on safety: specifications for application and suggestions for adaptions of the GRADE-criteria in the context of preparing a list of potentially inappropriate medications for older adults.

BACKGROUND: Systematic reviews that synthesize safety outcomes pose challenges (e.g. rare events), which raise questions for grading the strength of the body of evidence. This is maybe one reason why in many potentially inappropriate medication (PIM) lists the recommendations are not based on formalized systems for assessing the quality of the body of evidence such as GRADE. In this contribution, we describe specifications and suggest adaptions of the GRADE system for grading the quality of evidence on safety outcomes, which were developed in the context of preparing a PIM-list, namely PRISCUS. METHODS: We systematically assessed each of the five GRADE domains for rating-down (study limitations, imprecision, inconsistency, indirectness, publication bias) and the criteria for rating-up, considering if special considerations or revisions of the original approach were indicated. The result was gathered in a written document and discussed in a group-meeting of five members with various background until consensus. Subsequently, we performed a proof-of-concept application using a convenience sample of systematic reviews and applied the approach to systematic reviews on 19 different clinical questions. RESULTS: We describe specifications and suggest adaptions for the criteria "study limitations", imprecision, "publication bias" and "rating-up for large effect". In addition, we suggest a new criterion to account for data from subgroup-analyses. The proof-of-concept application did not reveal a need for further revision and thus we used the approach for the systematic reviews that were prepared for the PRISCUS-list. We assessed 51 outcomes. Each of the proposed adaptions was applied. There were neither an excessive number of low and very low ratings, nor an excessive number of high ratings, but the different methodological quality of the safety outcomes appeared to be well reflected. CONCLUSION: The suggestions appear to have the potential to overcome some of the challenges when grading the methodological quality of harms and thus may be helpful for producers of evidence syntheses considering safety.

Does the relative importance of the OxCAP-MH's capability items differ according to mental ill-health experience?

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.

Efficacy and safety of Z-substances in the management of insomnia in older adults: a systematic review for the development of recommendations to reduce potentially inappropriate prescribing.

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.

Efficacy and safety of adrenergic alpha-1 receptor antagonists in older adults: a systematic review and meta-analysis supporting the development of recommendations to reduce potentially inappropriate prescribing.

BACKGROUND: Adrenergic alpha-1 receptor antagonists (alpha-1 antagonists) are frequently used medications in the management of lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) and in the management of therapy-resistant arterial hypertension, two conditions frequently found in older adults. This systematic review aims at presenting a complete overview of evidence over the benefits and risks of alpha-1 antagonist treatment in people ≥ 65 years, and at deriving recommendations for a safe application of alpha-1 antagonists in older adults from the evidence found. METHODS: A comprehensive literature search was performed (last update March 25th 2022) including multiple databases (Medline/Pubmed, Embase, the Cochrane Library) and using the PICOS framework to define search terms. The selection of the studies was done by two independent reviewers in a two-step approach, followed by a systematic data extraction. Quality appraisal was performed for each study included using standardised appraisal tools. The studies retrieved and additional literature were used for the development of recommendations, which were rated for strength and quality according to the GRADE methodology. RESULTS: Eighteen studies were included: 3 meta-analyses, 6 randomised controlled trials and 9 observational trials. Doxazosin in the management of arterial hypertension was associated with a higher risk of cardiovascular disease, particularly heart failure, than chlorthalidone. Regarding treatment of LUTS suggestive of BPH, alpha-1 antagonists appeared to be effective in the relief of urinary symptoms and improvement of quality of life. They seemed to be less effective in preventing disease progression. Analyses of the risk profile indicated an increase in vasodilation related adverse events and sexual adverse events for some agents. The risk of falls and fractures as well as the effects of long-term treatment remained unclear. All meta-analyses and 5 out of 6 interventional studies were downgraded in the quality appraisal. 7 out of 9 observational studies were of good quality. CONCLUSIONS: It cannot be recommended to use doxazosin as first-line antihypertensive agent neither in older adults nor in younger patients. In the management of BPH alpha-1 antagonists promise to effectively relieve urinary symptoms with uncertainty regarding their efficacy in preventing long-term progression events.

Factors influencing the implementation of person-centred care in nursing homes by practice development champions: a qualitative process evaluation of a cluster-randomised controlled trial (EPCentCare) using Normalization Process Theory.

BACKGROUND: Person-centred care (PCC) has been suggested as the preferred model of dementia care in all settings. The EPCentCare study showed that an adapted PCC approach was difficult to implement and had no effect on prescription of antipsychotics in nursing home residents in Germany. This paper reports the qualitative process evaluation to identify facilitators and barriers of the implementation of PCC in German nursing homes from the perspective of participating practice development champions. METHODS: Five individual and 14 group interviews were conducted with 66 participants (staff and managers) from 18 nursing homes. The analysis was based on inductive coding to identify factors influencing the PCC implementation process. Identified factors were systematised and structured by mapping them to the four constructs (coherence, cognitive participation, collective action, reflexive monitoring) of the Normalization Process Theory (NPT) as a framework that explains implementation processes. RESULTS: Facilitating implementation factors included among others broadening of the care perspective (coherence), tolerance development within the care team regarding challenging behaviour (cognitive participation), testing new approaches to solutions as a multi-professional team (collective action), and perception of effects of PCC measures (reflexive monitoring). Among the facilitating factors reported in all the NPT constructs, thus affecting the entire implementation process, were the involvement of relatives, multi-professional teamwork and effective collaboration with physicians. Barriers implied uncertainties about the implementation and expectation of a higher workload (coherence), concerns about the feasibility of PCC implementation in terms of human resources (cognitive participation), lack of a person-centred attitude by colleagues or the institution (collective action), and doubts about the effects of PCC (reflexive monitoring). Barriers influencing the entire implementation process comprised insufficient time resources, lack of support, lack of involvement of the multi-professional team, and difficulties regarding communication with the attending physicians. CONCLUSIONS: The findings provide a comprehensive and detailed overview of facilitators and barriers structured along the implementation process. Thus, our findings may assist both researchers and clinicians to develop and reflect more efficiently on PCC implementation processes in nursing homes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02295462 ; November 20, 2014.

Second-generation antidepressants for treatment of seasonal affective disorder.

BACKGROUND: Seasonal affective disorder (SAD) is a seasonal pattern of recurrent depressive episodes that is often treated with second-generation antidepressants (SGAs), light therapy, or psychotherapy. OBJECTIVES: To assess the efficacy and safety of second-generation antidepressants (SGAs) for the treatment of seasonal affective disorder (SAD) in adults in comparison with placebo, light therapy, other SGAs, or psychotherapy. SEARCH METHODS: This is an update of an earlier review first published in 2011. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 1) in the Cochrane Library (all years), Ovid MEDLINE, Embase, and PsycINFO (2011 to January 2020), together with the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR) (all available years), for reports of randomised controlled trials (RCTs). We hand searched the reference lists of all included studies and other systematic reviews. We searched ClinicalTrials.gov for unpublished/ongoing trials. We ran a separate update search for reports of adverse events in the Ovid databases.  SELECTION CRITERIA: For efficacy we included RCTs of SGAs compared with other SGAs, placebo, light therapy, or psychotherapy in adult participants with SAD. For adverse events we also included non-randomised studies. DATA COLLECTION AND ANALYSIS: Two review authors independently screened abstracts and full-text publications against the inclusion criteria. Data extraction and 'Risk of bias' assessment were conducted individually. We pooled data for meta-analysis where the participant groups were similar, and the studies assessed the same treatments with the same comparator and had similar definitions of outcome measures over a similar duration of treatment. MAIN RESULTS: In this update we identified no new RCT on the effectiveness of SGAs in SAD patients. We included 2 additional single-arm observational studies that reported on adverse events of SGAs.  For efficacy we included three RCTs of between five and eight weeks' duration with a total of 204 participants. For adverse events we included two RCTs and five observational (non-randomised) studies of five to eight weeks' duration with a total of 249 participants. All participants met the DSM (Diagnostic and Statistical Manual of Mental Disorders) criteria for SAD. The average age ranged from 34 to 42 years, and the majority of participants were female (66% to 100%). Results from one trial with 68 participants showed that fluoxetine (20/36) was numerically superior to placebo (11/32) in achieving clinical response; however, the confidence interval (CI) included both a potential benefit as well as no benefit of fluoxetine (risk ratio (RR) 1.62, 95% CI 0.92 to 2.83, very low-certainty evidence). The number of adverse events was similar in both groups (very low-certainty evidence). Two trials involving a total of 136 participants compared fluoxetine versus light therapy. Meta-analysis showed fluoxetine and light therapy to be approximately equal in treating seasonal depression: RR of response 0.98 (95% CI 0.77 to 1.24, low-certainty evidence), RR of remission 0.81 (95% CI 0.39 to 1.71, very low-certainty evidence). The number of adverse events was similar in both groups (low-certainty evidence). We did not identify any eligible study comparing SGA with another SGA or with psychotherapy. Two RCTs and five non-randomised studies reported adverse event data on a total of 249 participants who received bupropion, fluoxetine, escitalopram, duloxetine, nefazodone, reboxetine, light therapy, or placebo. We were only able to obtain crude rates of adverse events, therefore caution is advised regarding interpretation of this information. Between 0% and 100% of participants who received an SGA suffered an adverse event, and between 0% and 25% of participants withdrew from the study due to adverse events. AUTHORS' CONCLUSIONS: Evidence for the effectiveness of SGAs is limited to one small trial of fluoxetine compared with placebo showing a non-significant effect in favour of fluoxetine, and two small trials comparing fluoxetine against light therapy suggesting equivalence between the two interventions. The lack of available evidence precluded us from drawing any overall conclusions on the use of SGAs for SAD. Further, larger RCTs are required to expand and strengthen the evidence base on this topic, and should also include comparisons with psychotherapy and other SGAs. Data on adverse events were sparse, and a comparative analysis was not possible. The data we obtained on adverse events is therefore not robust, and our confidence in the data is limited. Overall, up to 25% of participants treated with SGAs for SAD withdrew from the study early due to adverse events.

Quality improvement in chronic care by self-audit, benchmarking and networking in general practices in South Tyrol, Italy: results from an interventional study.

BACKGROUND: Systematic strategies promoting quality of care in general practice are yet under-represented in several European countries. OBJECTIVE: This interventional study assessed whether a combined intervention (self-audit, benchmarking, quality circles) improved quality of care in Salzburg, Austria and South Tyrol, Italy. The present publication reports the Italian results. METHODS: We developed quality indicators for general practice in a consensus process based on pre-existing quality programmes. The indicators addressed diagnosis and treatment regarding eight common chronic conditions. A quality score comprising 91 indicators was calculated (0-5 points per indicator depending on fulfilment, maximum 455 points). We collected anonymous data from the electronic health records of the participating physicians in 2012, 2013 and 2014. Wilcoxon signed-rank tests were used for pre-post analysis. RESULTS: Thirty-six GPs participated in the study. The median quality score increased significantly from 177.0 points at baseline to 272.0 points at the second follow-up (P = 0.000). Improvements concerned process and intermediate outcome indicators particularly between baseline and the first follow-up. CONCLUSION: Performance was relatively low at baseline and improved considerably, mainly in the first study period. The intervention investigated in this study can serve as a model for future quality programmes. A customized electronic health record for the implementation of this intervention as well as standardized and consistent documentation by GPs is a prerequisite. Use of a limited set of quality indicators (QIs) and regular QI modification is probably advisable to increase the benefits. Long-term prospective studies should investigate the impact of QI-based interventions on end-result outcomes.

Epidemiology and associated factors of polypharmacy in older patients in primary care: a northern Italian cross-sectional study.

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 < 0.001) and chronic conditions (Spearman's rho 0.20, p < 0.001), higher 5-GDS scores (thus, lower affective status) (Spearman's rho 0.12, p = 0.003) and lower EQ-5D-5L scores (thus, lower quality of life) (Spearman's rho - 0.14, p = 0.001). Patients' age/sex, 6-CIT scores (cognitive status), BMI or PIM use were not correlated with the number of drugs. CONCLUSIONS: The prevalence of polypharmacy, PIMs and major DDIs was considerable. Results indicate that physicians should particularly observe their patients with multiple conditions, reduced health and affective status, independently from other patients' characteristics. Careful attention about indication, benefit and potential risk should be paid especially to patients on therapy with specific drug classes identified as potentially inappropriate or prone to major DDIs in older persons (e.g., benzodiazepines, NSAIDs, protonic pump inhibitors, antithrombotics/anticoagulants, antidepressants/antipsychotics). TRIAL REGISTRATION: The cluster-RCT on which this cross-sectional analysis is based was registered with Current Controlled Trials Ltd. (ID ISRCTN: 38449870 ) on 2013-09-11.

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

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 .

Expert-based medication reviews to reduce polypharmacy in older patients in primary care: a northern-Italian cluster-randomised controlled trial.

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.

[Motivation for Specialisation in General Practice - A Quantitative Study of NRW's Medical Students in Support of Targeted Recruitment]. / Motivationale Faktoren für die Präferenz der Fachrichtung Allgemeinmedizin ­ eine quantitative Untersuchung unter Medizinstudierenden NRWs für eine zielgerichtete Nachwuchsgewinnung.

AIM OF STUDY: Due to forecasted shortage of general practitioners, we conducted an online survey of all medical students in North-Rhine-Westphalia to identify and quantify determinants in medical students' decision to specialize in general practice (GP). METHODOLOGY: To identify the motives driving the choice of GP as a career, responses of 3976 participants (22.6% of medical students invited) were subjected to factor analysis. Relationships between extracted factors and career choice were ascertained via regression analysis adjusted for population characteristics. All participants who had positioned themselves distinctly for/against GP were included in regression analysis (n=2862). RESULTS: Four of five identified factors were significantly associated with the intended choice of GP. "Comprehensive patient contact" (OR 4.02; 95% CI [3.5-4.6]), and "flexible working hours" (OR 1.35; 95% CI [1.2-1.5]) represent factors associated with choosing GP despite the perception of "superior career opportunities, income and status in other specializations" (OR 1.14; 95% CI [1.0-1.3]). Meanwhile, preference for "specialization, research and teamwork in other disciplines" (OR 0.55; 95% CI [0.5-0.6]) obstructs the intended choice of GP. CONCLUSION: GP recruitment can profit from focused sponsorship of students' interest in patient contact within GP clerkships, appropriate GP teaching structure at the universities, enhanced research and teamwork opportunities, and increased flexibility of working hours.

Effect of person-centred care on antipsychotic drug use in nursing homes (EPCentCare): a cluster-randomised controlled trial.

BACKGROUND: antipsychotic drugs are regularly prescribed as first-line treatment for neuropsychiatric symptoms in persons with dementia although guidelines clearly prioritise non-pharmacological interventions. OBJECTIVE: we investigated a person-centred care approach, which has been successfully evaluated in nursing homes in the UK, and adapted it to German conditions. DESIGN: a 2-armed 12-month cluster-randomised controlled trial. SETTING: nursing homes in East, North and West Germany. METHODS: all prescribing physicians from both study arms received medication reviews for individual patients and were offered access to 2 h of continuing medical education. Nursing homes in the intervention group received educational interventions on person-centred care and a continuous supervision programme. Primary outcome: proportion of residents receiving at least one antipsychotic prescription after 12 months of follow-up. Secondary outcomes: quality of life, agitated behaviour, falls and fall-related medical attention, a health economics evaluation and a process evaluation. RESULTS: the study was conducted in 37 nursing homes with n = 1,153 residents (intervention group: n = 493; control group: n = 660). The proportion of residents with at least one antipsychotic medication changed after 12 months from 44.6% to 44.8% in the intervention group and from 39.8 to 33.3% in the control group. After 12 months, the difference in the prevalence was 11.4% between the intervention and control groups (95% confidence interval: 0.9-21.9; P = 0.033); odds ratio: 1.621 (95% confidence interval: 1.038-2.532). CONCLUSIONS: the implementation of a proven person-centred care approach adapted to national conditions did not reduce antipsychotic prescriptions in German nursing homes. TRIAL REGISTRATION: ClinicalTrials.gov NCT02295462.

Correction to: Effectiveness and safety of vitamin K antagonists and new anticoagulants in the prevention of thromboembolism in atrial fibrillation in older adults - a systematic review of reviews and the development of recommendations to reduce inappropriate prescribing.

CORRECTION: After publication of the original article [1] it was found that author Marc Krause's name had been spelt incorrectly. In the original article it is presented as Mark Krause, rather than Marc Krause. The revised spelling has been included in the author list for this Correction.

Reduction of inappropriate medication in older populations by electronic decision support (the PRIMA-eDS study): a qualitative study of practical implementation in primary care.

BACKGROUND: Within the EU-funded project PRIMA-eDS (Polypharmacy in chronic diseases: Reduction of Inappropriate Medication and Adverse drug events in older populations by electronic Decision Support) an electronic decision support tool (the "PRIMA-eDS-tool") was developed for general practitioners (GPs) to reduce inappropriate medication in their older polypharmacy patients. After entering patient data relevant to prescribing in an electronic case report form the physician received a comprehensive medication review (CMR) on his/her screen displaying recommendations regarding missing indications, necessary laboratory tests, evidence-base of current medication, dose adjustments for renal malfunction, potentially harmful drug-drug interactions, contra-indications, and possible adverse drug events. We set out to explore the usage of the PRIMA-eDS tool and the adoption of the recommendations provided by the CMR to optimise the tool and prepare it for its future implementation. METHODS: In a qualitative study carried out in North Rhine-Westphalia, Germany, 21 GPs using the PRIMA-eDS tool within the PRIMA-eDS study were interviewed. Interviews encompassed the GPs' attitudes regarding use of the electronic case report form and the CMR, their response to the recommendations, and the implementation of the tool into daily practice routine. The collected data were analysed applying thematic qualitative text analysis. RESULTS: GPs found the patient data entry into the electronic case report form to be inconvenient and time-consuming. The CMR was conducted often outside practice hours and without the patient present. GPs found that the PRIMA-eDS CMR provided relevant information for and had several positive effects on the caring process. However, they encountered several barriers when wanting to change medication. CONCLUSIONS: It is unlikely that the PRIMA-eDS CMR will be used in the future as it is now as patient data entry is too time-consuming. Several barriers towards deprescribing medications were found which are common in deprescribing studies. Given the positive attitude towards the CMR, a new way of entering patient data into the PRIMA-eDS tool to create the CMR needs to be developed.

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).

A set of systematic reviews to help reduce inappropriate prescribing to older people: study protocol.

BACKGROUND: Multimorbidity and polypharmacy are common in older people. Assessment tools or lists of criteria aimed at supporting prescription decisions for older people exist, but have often been based on expert opinion with insufficient consideration of the evidence available. The present paper describes the methods we are using to systematically review the existing evidence on the efficacy and safety of the most commonly prescribed drugs for older people in the management of their chronic medical conditions and to develop recommendations to reduce inappropriate prescriptions for incorporation into the Comprehensive Medication Review (CMR) tool developed by the PRIMA-eDS European project. METHODS: We selected the 20 most relevant drugs/drug classes in terms of prescription volumes and risk of hospitalisation for older people and the most relevant indications for the most common chronic conditions among older people and a total of 35 distinct drug-indication pairs were chosen. Based on clinical considerations we collapsed some indications together, reducing the 35 pairs to a final total of 22 separate systematic reviews (SR). A common methodology will be used for each individual SR, based on the methodological manuals of the Cochrane collaboration and the PRISMA statement for reporting systematic reviews. Our search strategy will have a staged approach where we initially search for systematic reviews and meta-analyses, but if relevant reviews are not found, then search for individual studies (controlled intervention and observational studies). Our pilot work and initial scoping of the literature suggested that very few, relevant individual trials or existing systematic reviews have researched or reported exclusively on older people. Therefore, sufficient data might not be available to perform meta-analysis but we will provide a narrative synthesis describing characteristics and findings of included studies. The collected evidence will be used to construct recommendations on when not to use or to discontinue a drug, or when to reduce its dose. Recommendations will be developed in team meetings using the GRADE methodology to reflect the strength of the recommendation and the quality of the evidence. Recommendations will be built into the CMR tool. DISCUSSION: This protocol has been prepared for a series of systematic reviews which will provide research-based evidence to develop recommendations to reduce inappropriate polypharmacy in older people as part of the CMR tool of the PRIMA-eDS project.

Effectiveness and patient safety of platelet aggregation inhibitors in the prevention of cardiovascular disease and ischemic stroke in older adults - a systematic review.

BACKGROUND: Platelet aggregation inhibitors (PAI) are among the most frequently prescribed drugs in older people, though evidence about risks and benefits of their use in older adults is scarce. The objectives of this systematic review are firstly to identify the risks and benefits of their use in the prevention and treatment of vascular events in older adults, and secondly to develop recommendations on discontinuing PAI in this population if risks outweigh benefits. METHODS: Staged systematic review consisting of three searches. Searches 1 and 2 identified systematic reviews and meta-analyses. Search 3 included controlled intervention and observational studies from review-articles not included in searches 1 and 2. All articles were assessed by two independent reviewers regarding the type of study, age of participants, type of intervention, and clinically relevant outcomes. After data extraction and quality appraisal we developed recommendations to stop the prescribing of specific drugs in older adults following the Grading of Recommendations Assessment Development and Evaluation (GRADE) methodology. RESULTS: Overall, 2385 records were screened leading to an inclusion of 35 articles reporting on 22 systematic reviews and meta-analyses, 11 randomised controlled trials, and two observational studies. Mean ages ranged from 57.0 to 84.6 years. Ten studies included a subgroup analysis by age. Overall, based on the evaluated evidence, three recommendations were formulated. First, the use of acetylsalicylic acid (ASA) for primary prevention of cardiovascular disease (CVD) in older people cannot be recommended due to an uncertainty in the risk-benefit ratio (weak recommendation; low quality of evidence). Secondly, the combination of ASA and clopidogrel in patients without specific indications should be avoided (strong recommendation; moderate quality of evidence). Lastly, to improve the effectiveness and reduce the risks of stroke prevention therapy in older people with atrial fibrillation (AF) and a CHA2DS2-VASc score of ≥ 2, the use of ASA for the primary prevention of stroke should be discontinued in preference for the use of oral anticoagulants (weak recommendation; low quality of evidence). CONCLUSIONS: The use of ASA for the primary prevention of CVD and the combination therapy of ASA and clopidogrel for the secondary prevention of vascular events in older people may not be justified. The use of oral anticoagulants instead of ASA in older people with atrial fibrillation may be recommended. Further high quality studies with older adults are needed.

Efficacy and safety of metformin in the management of type 2 diabetes mellitus in older adults: a systematic review for the development of recommendations to reduce potentially inappropriate prescribing.

BACKGROUND: Metformin is usually prescribed as first line therapy for type 2 diabetes mellitus (DM2). However, the benefits and risks of metformin may be different for older people. This systematic review examined the available evidence on the safety and efficacy of metformin in the management of DM2 in older adults. The findings were used to develop recommendations for the electronic decision support tool of the European project PRIMA-eDS. METHODS: The systematic review followed a staged approach, initially searching for systematic reviews and meta-analyses first, and then individual studies when prior searches were inconclusive. The target population was older people (≥65 years old) with DM2. Studies were included if they reported safety or efficacy outcomes with metformin (alone or in combination) for the management of DM2 compared to placebo, usual or no treatment, or other antidiabetics. Using the evidence identified, recommendations were developed using GRADE methodology. RESULTS: Fifteen studies were included (4 intervention and 11 observational studies). In ten studies at least 80% of participants were 65 years or older and 5 studies reported subgroup analyses by age. Comorbidities were reported by 9 studies, cognitive status was reported by 4 studies and functional status by 1 study. In general, metformin showed similar or better safety and efficacy than other specific or non-specific active treatments. However, these findings were mainly based on retrospective observational studies. Four recommendations were developed suggesting to discontinue the use of metformin for the management of DM2 in older adults with risk factors such as age > 80, gastrointestinal complaints during the last year and/or GFR ≤60 ml/min. CONCLUSIONS: On the evidence available, the safety and efficacy profiles of metformin appear to be better, and certainly no worse, than other treatments for the management of DM2 in older adults. However, the quality and quantity of the evidence is low, with scarce data on adverse events such as gastrointestinal complaints or renal failure. Further studies are needed to more reliably assess the benefits and risks of metformin in very old (>80), cognitively and functionally impaired older people.

Thiazides in the management of hypertension in older adults - a systematic review.

BACKGROUND: Thiazides are commonly prescribed to older people for the management of hypertension. The objective of this study was to identify the evidence on the risks and benefits of their use among adults aged ≥65 years and to develop recommendations to reduce potentially inappropriate use. METHODS: Systematic review (SR) of the literature covering six databases. We applied a staged search approach, where each search was undertaken only if the previous one did not yield high quality results. Searches 1 and 2 identified relevant SRs and meta-analyses published up to December 2015 from all databases. Search 3 identified additional individual interventional studies (IS) and observational studies (OS) not identified by the preceding searches. We included all studies evaluating the effect of thiazides on patient-relevant outcomes in the management of hypertension with a sufficient number of participants aged ≥65 years or a subgroup analysis based on age. Two independent reviewers extracted data and carried out quality appraisal. Recommendations were developed using the GRADE methodology. RESULTS: Searches 1 to 3 were performed. We included 34 articles reporting on 12 IS and 4 OS. Mean ages ranged from 59 to 83.8 years. Four studies had performed a subgroup analysis by age. Information on comorbidity, polypharmacy and frailty of the participants was scarce or not available. The IS compared thiazides to placebo or other antihypertensive drugs and evaluated cardiovascular endpoints or all-cause-mortality as primary outcomes. The OS investigated the association between thiazide use and the risk of gout, fractures and adverse effects. Our results suggest that thiazides are efficacious in preventing cardiovascular events for this population group. Low-dose regimens of thiazides may be safer than high-dose (low quality of evidence), and a history of gout may increase the risk of adverse events (low quality of evidence). Three recommendations were developed. CONCLUSIONS: The use of low dose treatment with thiazides for the management of hypertension in adults aged 65 and older seems justified, unless a history of gout is present. The quality of the evidence is low and studies rarely describe characteristics of the participants such as polypharmacy and frailty. Further good quality studies are needed.