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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.

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.

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.

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.

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 p 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.

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. Supplementary Information The online version contains supplementary material available at 10.1186/s12877-020-01988-9.

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 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 .

The aim of this work is to present an exemplary methodological review of the quality of included studies on drug therapy in older patients, using a published series of six systematic reviews (SRs). These six SRs included 48 systematic reviews, 65 intervention studies and 33 observational studies. The series of SRs has been carried out in the PRIMA-eDS-project (www.prima-eds.eu) to develop recommendations for the treatment of elderly patients with polypharmacy.The research question was to which extent recommendations on drug therapy in older patients are based on sound evidence. To this purpose, we performed a quality assessment of all studies included using AMSTAR for systematic reviews, CASP for observational studies, and the Cochrane "Risk of Bias" tool for intervention studies.The evidence base for commonly prescribed drugs in the elderly is weak. The studies identified by the systematic reviews revealed a significant lack of studies addressing the target population as well as a lack of high-quality evidence. Among the 33 observational studies, it was unclear in nearly half of the publications whether the follow-up was sufficiently long and complete. For one-third, the conclusions did not match the observed evidence. The greatest risk of bias in the intervention trials was due to selection and incorrect blinding. Quality deficits of the systematic reviews consisted in the provision of a complete study list and the lack of consideration of potential publication bias.Overall, many methodological deficits were revealed, making it difficult or almost impossible to derive reliable recommendations.Our work illustrates the immense need for research in the treatment of older patients as well as the importance of ensuring the highest quality standards when conducting intervention and observational studies or carrying out systematic reviews.

Objective We sought to investigate the experiences of general practitioners (GPs) with an electronic decision support tool to reduce inappropriate polypharmacy in older patients (the PRIMA-eDS [Polypharmacy in chronic diseases: Reduction of Inappropriate Medication and Adverse drug events in older populations by electronic Decision Support] tool) in a multinational sample of GPs and to quantify the findings from a prior qualitative study on the PRIMA-eDS-tool. Materials and Methods Alongside the cluster randomized controlled PRIMA-eDS trial, a survey was conducted in all 5 participating study centers (Bolzano, Italy; Manchester, United Kingdom; Salzburg, Austria; Rostock, Germany; and Witten, Germany) between October 2016 and July 2017. Data were analyzed using descriptive statistics and chi-square tests. Results Ninety-one (n = 160) percent of the 176 questionnaires were returned. Thirty-two percent of the respondents reported that they did not cease drugs because of the medication check. The 68% who had discontinued drugs comprise 57% who had stopped on average 1 drug and 11% who had stopped 2 drugs or more per patient. The PRIMA-eDS tool was found to be useful (69%) and the recommendations were found to help to increase awareness (86%). The greatest barrier to implementing deprescribing recommendations was the perceived necessity of the medication (69%). The majority of respondents (65%) would use the electronic medication check in routine practice if it was part of the electronic health record. Conclusions GPs generally viewed the PRIMA-eDS medication check as useful and as informative. Recommendations were not always followed due to various reasons. Many GPs would use the medication check if integrated into the electronic health record.

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 The PRIMA-eDS study was supported by a grant from the European Commission within the 7th Framework Programme (Grant No. 305388–2). The work of YVM was also supported by a grant from the NIHR Greater Manchester Primary Care Patient Safety Translational Research Centre. The publication charge was funded by the University of Witten/Herdecke

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. The PRIMA-eDS study was supported by a grant from the European Commission within the 7th Framework Programme (Grant No. 305388–2). The work of YVM was also supported by a grant from the NIHR Greater Manchester Primary Care Patient Safety Translational Research Centre. Publication of this article was funded by the UK National Institute for Health Research School for Primary Care Research, University of Manchester.

BACKGROUND: Preventable drug-related hospital admissions can be associated with drugs used in diabetes and the benefits of strict diabetes control may not outweigh the risks, especially in older populations. The aim of this study was to look for evidence on risks and benefits of DPP-4 inhibitors in older adults and to use this evidence to develop recommendations for the electronic decision support tool of the PRIMA-eDS project. METHODS: Systematic review using a staged approach which searches for systematic reviews and meta-analyses first, then individual studies only if prior searches were inconclusive. The target population were older people (≥65 years old) with type 2 diabetes. We included studies reporting on the efficacy and/or safety of DPP-4 inhibitors for the management of type 2 diabetes. Studies were included irrespective of DPP-4 inhibitors prescribed as monotherapy or in combination with any other drug for the treatment of type 2 diabetes. The target intervention was DPP-4 inhibitors compared to placebo, no treatment, other drugs to treat type 2 diabetes or a non-pharmacological intervention. RESULTS: Thirty studies (reported in 33 publications) were included: 1 meta-analysis, 17 intervention studies and 12 observational studies. Sixteen studies were focused on older adults and 14 studies reported subgroup analyses in participants ≥65, ≥70, or ≥75 years. Comorbidities were reported by 26 studies and frailty or functional status by one study. There were conflicting findings regarding the effectiveness of DPP-4 inhibitors in older adults. In general, DPP-4 inhibitors showed similar or better safety than placebo and other antidiabetic drugs. However, these safety data are mainly based on short-term outcomes like hypoglycaemia in studies with HbA1c control levels recommended for younger people. One recommendation was developed advising clinicians to reconsider the use of DPP-4 inhibitors for the management of type 2 diabetes in older adults with HbA1c

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. The PRIMA-eDS study was supported by a grant from the European Commission within the 7th Framework Programme (Grant No. 305388–2). The work of YVM was also supported by a grant from the NIHR Greater Manchester Primary Care Patient Safety Translational Research Centre. Publication of this article was funded by the UK National Institute for Health Research School for Primary Care Research, University of Manchester.

BACKGROUND: The benefit from a blood pressure lowering therapy with beta blockers may not outweigh its risks, especially in older populations. The aim of this study was to look for evidence on risks and benefits of beta blockers in older adults and to use this evidence to develop recommendations for the electronic decision support tool of the PRIMA-eDS project. METHODS: Systematic review of the literature using a stage approach with searches for systematic reviews and meta-analyses first, and individual studies only if the previous searches are inconclusive. The target population were older adults (≥65 years old) with hypertension. We included studies reporting on the effectiveness and/or safety of beta blockers on clinically relevant endpoints (e.g. mortality, cardiovascular events, and stroke) in the management of hypertension. The recommendations were developed according to the GRADE methodology. RESULTS: Fifteen studies were included, comprising one meta-analysis, four randomized controlled trials, six secondary analyses of randomized controlled trials and four observational studies. Seven studies involved only older adults and eight studies reported subgroup analyses by age. With regard to a composite endpoint (death, stroke or myocardial infarction) beta blockers were associated with a higher risk of events then were other antihypertensive agents. Further, beta blockers showed no benefit compared to other antihypertensive agents or placebo regarding mortality. They appear to be less effective than other antihypertensive agents in reducing cardiovascular events. Contradictory results were found regarding the effect of beta blockers on stroke. None of the studies explored the effect on quality of life, hospitalisation, functional impairment/status, safety endpoints or renal failure. CONCLUSION: The quality of current evidence to interpret the benefits of beta blockers in hypertension is rather weak. It cannot be recommended to use beta blockers in older adults as first line agent for hypertension. The PRIMA-eDS study was supported by a grant from the European Commission within the 7th Framework Programme (Grant No. 305388–2). The work of YVM was also supported by a grant from the NIHR Greater Manchester Primary Care Patient Safety Translational Research Centre. The publication charge was funded by the University of Witten/Herdecke.

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 The PRIMA-eDS study was supported by a grant from the European Commission within the 7th Framework Programme (Grant No. 305388–2). The work of YVM was also supported by a grant from the NIHR Greater Manchester Primary Care Patient Safety Translational Research Centre. Publication of this article was funded by the UK National Institute for Health Research School for Primary Care Research, University of Manchester

We evaluated the disease management programme (DMP) “Therapie Aktiv” for diabetes mellitus type 2 during the first year of implementation in a cluster-randomised controlled trial (RCT), which revealed an improvement of process quality, but only insignificant effects on HbA1c. To further analyse the effects of the DMP we followed up participants of the RCT for another year. After completion of the RCT, the study was continued as an open observational trial. By patient’s choice, three groups were formed. Group 1 (DMP/DMP): interventions of the RCT (DMP), who remained in the DMP; group 2 (Control/DMP): controls of the RCT (usual care), who participated in the DMP during the second year; group 3 (Control/Control): controls of the RCT (usual care), who remained as controls. Primary outcome measure: HbA1c. Secondary outcome measures: BMI, lipids, blood pressure and measures of process quality. Only 801 of 1,489 RCT participants completed the study (53.8 %). Group 1: n = 355; group 2: n = 335; group 3: n = 111. After 2 years, pre-post-analysis revealed a significant reduction of HbA1c (0.37 %, p

Preoperative evaluation is aimed at prevention of complications and risk stratification. Routine testing should be abandoned in favour of selective ordering according to contemporary guidelines. This study was conducted to calculate the possible economic impact of a Web-based preoperative diagnostic guideline prior to its implementation in the state of Salzburg, Austria.Prospective observational cohort study.The study was carried out in a secondary care hospital in Salzburg (Schwarzach).Data from 1363 consecutive patients scheduled for elective surgery from 1 September to 30 November 2007 were collected: demographic data, medical history, surgical procedure, preoperative tests and findings. The data were entered into the preoperative diagnostic guideline software and the guideline-adherent recommendations were compared with the investigations performed, with special attention to duplicate examinations.A total of 5879 tests were documented and analysed. In 65.6% of patients, guideline-adherent evaluation would have indicated only basic requirements, but 3380 additional tests were carried out. In all, 81.7% of tests were identified as nonadherent based on the preoperative diagnostic guideline software and 226 duplicate tests were performed. Possible savings per 1000 patients would be €26 287 if preoperative diagnostic guideline recommendations were followed exactly and €1076 if duplicated tests were avoided. According to a generalised linear model (Gamma model), an increase of 1 year of age leads to an increase of costs by a factor of 1.020.These data indicate a considerable potential for improvement in process quality and cost reduction by using structured preoperative assessment with computer-assisted implementation of a guideline.

Objective: Most medications are prescribed, dispensed, and administered in ambulatory care settings, yet little information exists on the adverse effects of drugs in this setting. This review was conducted to estimate the prevalence of adverse drug events (ADEs) and the proportion of preventable ADEs in ambulatory care settings; compare data for different age groups including children, adults, and elderly patients; and review drug classes most commonly associated with ADEs. Data Sources: Four electronic databases–PubMed (1966-March 2011), International Pharmaceutical Abstracts (1970-March 2011), EMBASE (1980-March 2011), and the Cochrane Database of Systematic Reviews (1993-March 2011)—were systematically searched for published data. Bibliographies of retrieved articles were searched individually for additional relevant studies. Study Selection: A standardized definition of an ADE was used to select studies in populations living in the community, with medical visits to primary care facilities, nonspecialty ambulatory care facilities, and/or admissions to a hospital for medication-related adverse events. Data Extraction: Data were extracted using a standardized table. Forty-three studies met our inclusion criteria. Data Synthesis: The median ADE prevalence rate for retrospective studies was 3.3% (interquartile range [IQR] 2.3-7.1%) vs 9.65% (IQR 3.3-17.35%) for prospective studies. Median preventable ADE rates in ambulatory care–based studies were 16.5%, and 52.9% for hospital-based studies. Median prevalence rates by age group ranged from 2.45% for children to 5.27% for adults, 16.1% for elderly patients, and 3.45% for studies including all ages. Conclusions: Despite a recent increase in publications on ADEs in the ambulatory care setting, most studies remain hospital based. Notable differences in prevalence rates by age groups and by responsible drug categories provide guidance on how to direct attention toward effective targets for improvement of medication safety in ambulatory care settings.

Aim To estimate how accurately general practitioners’ (GP) assessed the probability of coronary heart disease in patients presenting with chest pain and analyze the patient management decisions taken as a result. Methods During 2005 and 2006, the cross-sectional diagnostic study with a delayed-type reference standard included 74 GPs in the German state of Hesse, who enrolled 1249 consecutive patients presenting with chest pain. GPs recorded symptoms and findings for each patient on a report form. Patients and GPs were contacted 6 weeks and 6 months after the patients’ visit to the GP. Data on chest complaints, investigations, hospitalization, and medication were reviewed by an independent panel, with coronary heart disease being the reference condition. Diagnostic properties (sensitivity, specificity, and predictive values) of the GPs’ diagnoses were calculated. Results GPs diagnosed coronary heart disease with the sensitivity of 69% (95% confidence interval [CI], 62-75) and specificity of 89% (95% CI, 87-91), and acute coronary syndrome with the sensitivity of 50% (95% CI, 36-64) and specificity of 98% (95% CI, 97-99). They assumed coronary heart disease in 245 patients, 41 (17%) of whom were referred to the hospital, 77 (31%) to a cardiologist, and 162 (66%) to electrocardiogram testing. Conclusions GPs’ evaluation of chest pain patients, based on symptoms and signs alone, was not sufficiently accurate for diagnosing or excluding coronary heart disease or acute coronary syndrome.

Background Diagnosing the aetiology of chest pain is challenging. There is still a lack of data on the diagnostic accuracy of signs and symptoms for acute coronary events in low-prevalence settings. Aim To evaluate the diagnostic accuracy of symptoms and signs in patients presenting to general practice with chest pain. Design of study Cross-sectional diagnostic study with delayed-type reference standard. Setting Seventy-four general practices in Germany. Method The study included 1249 consecutive patients presenting with chest pain. Data were reviewed by an independent reference panel, with coronary heart disease (CHD) and an indication for urgent hospital admission as reference conditions. Main outcome measures were sensitivity, specificity, likelihood ratio, predictive value, and odds ratio (OR) for non-trauma patients with a reference diagnosis. Results Several signs and symptoms showed strong associations with CHD, including known vascular disease (OR = 5.13; 95% confidence interval [CI] = 2.83 to 9.30), pain worse on exercise (OR = 4.27; 95% CI = 2.31 to 7.88), patient assumes cardiac origin of pain (OR = 3.20; 95% CI = 1.53 to 6.60), cough present (OR = 0.08; 95% CI = 0.01 to 0.77), and pain reproducible on palpation (OR = 0.27; 95% CI = 0.13 to 0.56). For urgent hospital admission, effective criteria included pain radiating to the left arm (OR = 8.81; 95% CI = 2.58 to 30.05), known clinical vascular disease (OR = 7.50; 95% CI = 2.88 to 19.55), home visit requested (OR = 7.31; 95% CI = 2.27 to 23.57), and known heart failure (OR = 3.53; 95% CI = 1.14 to 10.96). Conclusion Although individual criteria were only moderately effective, in combination they can help to decide about further management of patients with chest pain in primary care.

Chest wall syndrome (CWS) is the most frequent aetiology of chest pain in a primary care setting.The aims of the study are to describe the epidemiology, clinical characteristics and prognosis of CWS and to provide a simple decision rule for diagnosis.We included 1212 consecutive patients with chest pain aged 35 years and older attending 74 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 the diagnosis of CWS.GPs diagnosed pain originating from the chest wall in 46.6% of all patients. In most patients, pain was localized retrosternal (52.0%) and/or on the left side (69.2%). In total, 28.0% of CWS patients showed persistent pain and most patients reported no temporal association of pain (72.3%). In total, 55.4% of patients still had chest pain after 6 months. A simple score containing four determinants (localized muscle tension, stinging pain, pain reproducible by palpation and absence of cough) shows an area under the receiver operating characteristic curve of 0.78 (95% confidence interval: 0.75-0.81).This study broadens the knowledge about pain characteristics and the diagnostic accuracy of selected signs and symptoms for CWS. A simple four-point score can help the GP in the diagnostic workup of chest pain patients.

Aim. Testing the effectiveness of peer support additionally to a disease management programme (DMP) for type 2 diabetes patients.Methods. Unblinded cluster-randomised controlled trial (RCT) involving 49 general practices, province of Salzburg, Austria. All patients enrolled in the DMP were eligible,n=337participated (intervention: 148 in 19 clusters; control: 189 in 20 clusters). The peer support intervention ran over 24 months and consisted of peer supporter recruitment and training, and group meetings weekly for physical exercise and monthly for discussion of diabetes related topics.Results. At two-year follow-up, adjusted analysis revealed a nonsignificant difference inHbA1cchange of 0.14% (21.97 mmol/mol) in favour of the intervention (95% CI −0.08 to 0.36%,p=0.22). Baseline values were 7.02 ± 1.25% in the intervention and 7.08 ± 1.25 in the control group. None of the secondary outcome measures showed significant differences except for improved quality of life (EQ-5D-VAS) in controls (4.3 points on a scale of 100; 95% CI 0.08 to 8.53,p=0.046) compared to the intervention group.Conclusion. Our peer support intervention as an additional DMP component showed no significant effect onHbA1cand secondary outcome measures. Further RTCs with a longer follow-up are needed to reveal whether peer support will have clinically relevant effects.Trial Registration. This trial has been registered with Current Controlled Trials Ltd. (ISRCTN10291077).

Background: Evidence on the effectiveness of educational interventions on prescribing behaviour modification in prevention of cardiovascular disease is still insufficient. We evaluated the effects of a brief educational intervention on prescription of hydroxymethylglutaryl-CoA reductase inhibitors (statins), inhibitors of platelet aggregation (IPA), and antihypertensive agents (AH). Design: Cluster randomised controlled trial with continuous medical education (CME) groups of general practitioners (GPs). Methods: Prescription of statins, IPA, and AH were verified prior to study start (BL), immediately after index consultation (IC), and at follow-up after 6 months (FU). Prescription in patients at high risk (>15% risk of a cardiovascular event in 10 years, based on the Framingham equation) and no prescription in low-risk patients (≤ 15%) were considered appropriate. Results: An intervention effect on prescribing could only be found for IPA. Generally, changes in prescription over time were all directed towards higher prescription rates and persisted to FU, independent of risk status and group allocation. Conclusions: The active implementation of a brief evidence-based educational intervention on global risk in CVD did not lead directly to risk-adjusted changes in prescription. Investigations on an extended time scale would capture whether decision support of this kind would improve prescribing risk-adjusted sustainably.

INTRODUCTION: Diabetes mellitus type 2 plays an important role in population health worldwide, and diabetes care has been shown to be insufficient. Disease management programmes (DMPs) have been designed to overcome these deficiencies, but data on their effectiveness are inconclusive. One reason for the inconsistent extent of effects may be selection bias. Voluntary programmes might recruit preferably highly motivated patients who are already quite successful in managing diabetes. Other programmes enrol primarily patients with poor metabolic control which may lead to the demonstration of fairly large effects due to regression to the mean. We therefore investigated the baseline characteristics of patients willing to enrol in the Austrian DMP for diabetes mellitus type 2 ("Therapie aktiv"), and their quality of care. METHODS: We offered the study to all GPs and internists in the province of Salzburg. The physicians were asked to recruit all patients with type 2 diabetes according to WHO/ADA-criteria willing to participate in the Austrian DMP "Therapie aktiv". For all patients, data regarding metabolic control, medication, cardiovascular risk factors and diabetes complications were recorded and then analysed to detect deficiencies in care. RESULTS: One thousand Four hundred and eighty-nine patients (mean age 65.4 ± 10.4 years; 47.8% women) were recruited by 92 physicians. 24.3% of all participants (28.3% of the men and 20.1% of the women) had at least one diabetes-related complication with a significantly higher rate of cardiovascular complications in the male study population. 80.7% of all patients were treated with oral antidiabetics, insulin or both. With regards to quality of care 5% of all patients with an HbA1c above 7.5% did not receive any antidiabetic medication at all. 15.3% of the study population with high blood pressure was not supplied with any antihypertensive medication and 36.6% of the study participants with cardiovascular disease were not treated with a statin. CONCLUSION: Our results indicate that the majority of the patients receive treatment in adherence to current guidelines. Nevertheless there are deficits in care and hence room for improvement by implementation of the DMP.

Background: Chest pain can be caused by various conditions, with life-threatening cardiac disease being of greatest concern. Prediction scores to rule out coronary artery disease have been developed for use in emergency settings. We developed and validated a simple prediction rule for use in primary care. Methods: We conducted a cross-sectional diagnostic study in 74 primary care practices in Germany. Primary care physicians recruited all consecutive patients who presented with chest pain ( n = 1249) and recorded symptoms and findings for each patient (derivation cohort). An independent expert panel reviewed follow-up data obtained at six weeks and six months on symptoms, investigations, hospital admissions and medications to determine the presence or absence of coronary artery disease. Adjusted odds ratios of relevant variables were used to develop a prediction rule. We calculated measures of diagnostic accuracy for different cut-off values for the prediction scores using data derived from another prospective primary care study (validation cohort). Results: The prediction rule contained five determinants (age/sex, known vascular disease, patient assumes pain is of cardiac origin, pain is worse during exercise, and pain is not reproducible by palpation), with the score ranging from 0 to 5 points. The area under the curve (receiver operating characteristic curve) was 0.87 (95% confidence interval [CI] 0.83–0.91) for the derivation cohort and 0.90 (95% CI 0.87–0.93) for the validation cohort. The best overall discrimination was with a cut-off value of 3 (positive result 3–5 points; negative result ≤ 2 points), which had a sensitivity of 87.1% (95% CI 79.9%–94.2%) and a specificity of 80.8% (77.6%–83.9%). Interpretation: The prediction rule for coronary artery disease in primary care proved to be robust in the validation cohort. It can help to rule out coronary artery disease in patients presenting with chest pain in primary care.

Chest pain is a common complaint and reason for consultation. We aimed to study the epidemiology of chest pain with respect to underlying aetiologies and to establish pre-work-up probabilities for the primary care setting.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 on the aetiology of chest pain at the time of patient recruitment.The prevalence of chest pain among all attending patients was 0.7%. The majority (55.9%) of patients were women. Mean age was 59 (35-93) years. Of these patients, 53.2% had chest pains at the time of consultation and 29.6% presented with acute (48 hours' duration) chest pain. Pain originating from the chest wall was diagnosed in 46.6% of all patients, stable ischaemic heart disease (IHD) in 11.1%, and psychogenic disorders in 9.5%; 3.6% had acute coronary syndrome (ACS).The study adds important information about the epidemiology of chest pain as a frequent reason for consulting primary care practitioners. We provide updated pre-work-up probabilities for IHD for each age and sex category.

Background. Among patients presenting with low back pain (LBP), GPs have to identify those with serious, treatable conditions. However, excluding these conditions in every patient with LPB is time consuming and of low yield. We have suggested that identifying those patients where these serious conditions need to be considered can be made more efficient through asking patient if they feel their LBP is new or unfamiliar in some way. Objective. To evaluate the diagnostic validity of a simple heuristic based on the patient’s view of the familiarity of LBP. Methods. Cross-sectional diagnostic study with delayed-type reference standard, nested within a three-arm randomized trial of quality improvement for LBP. A total of 1378 patients presenting, with LBP, to one of 126 participating GPs were included. They were asked whether their LBP was familiar or not (index test). At 1 year, patients were interviewed with regard to relevant conditions that in hindsight might explain their LBP. Reviewers deciding on disease status (reference standard) were blinded to the results of the index test. Results. Totally 1190 patients answered the index test question and were available for interview at 1 year. Only four of these had a serious cause of their LBP. Two of these were identified by the familiarity heuristic, resulting in low sensitivity. Conclusion. The number of diseased patients was too small to obtain a reliable estimate of sensitivity. Low prevalence of serious disease in primary care poses difficulties for diagnostic research. In hindsight we would question whether an RCT-setting emphasizing non-specific LBP is suitable for this kind of research. At present, the familiarity heuristic cannot be recommended for patients presenting with LBP.

Cardiovascular risk factors depend decisively on living conditions and nutrition. The aim of the present study was to establish whether the different living conditions in the eastern and western parts of Germany were associated with differences in the frequency and severity of these risk factors.In Leipzig, 15,291 people (9,600 women and 5,691 men), in Nuremberg 8,387 (4,559 women and 3,828 men) were examined either after responding to a public appeal, or in the factory, etc.Clearly elevated cholesterol levels (250 mg/dl) were found in 33.8% of the men, and 35.9% of the women in Leipzig, and in 39.1% of the men and 50.7% of the women in Nuremberg. This larger incidence of treatment-requiring hypercholesterolemia in Nuremberg was distributed throughout all age groups up to the age of 60. Hypertension was significantly more common among the 30 to 80-year-old women, and the 20 to 40-year-old and 50 to 80-year-old men in Leipzig. the frequency of cigarette smoking, diabetes mellitus and overweight did not differ significantly between the two cities. In cases with known dyslipoproteinemia, drug treatment was rarely applied, and the therapeutic aim of a cholesterol level200 mg/dl, was achieved in only 2-6% of those treated. The most significant difference with respect to cardiovascular risk factors was serum cholesterol. It is possible that a higher ingestion of monounsaturated fatty acids and more physical activity may be responsible for the lower cholesterol levels in Leipzig.

The connection of body fat distribution (BFD) and the risk of developing mammary, cervical, endometrial or ovarian carcinoma was ascertained for 163 patients with carcinoma (mean age 49.9 [19-78] years) and 489 controls of comparable age and body-mass index. BFD was expressed as the ratio of waist and hip circumference (T/H ratio of 0.822 vs 0.781 and 0.826 vs 0.789, respectively; P less than 0.01). In premenopausal women with mammary or cervical carcinoma and in all postmenopausal women BFD was similar to that in the control subjects. A common cause of android obesity and ovarian or endometrial carcinoma may be a reduction of sex-hormone-binding globulins with an elevated serum level of free androgens and oestrogens.

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). Electronic supplementary material The online version of this article (doi:10.1186/s13063-016-1177-8) contains supplementary material, which is available to authorized users.

Background: Patients do not always receive guideline-adherent therapy, yet little is known about the underlying causes on the patients’ side. We quantified non-guideline-adherent treatment of chronic diseases (diabetes mellitus, hypertension, cardiovascular disease, heart failure, atrial fibrillation) in primary care and analysed the causes from the physician’s as well as the patient’s view. Methods: With the intention to analyze the frequency and causes of non-guideline-adherent treatment of patients with chronic diseases, we drew a random sample of 124 general practitioners (GP) in Salzburg, Austria, of which 58 (46.8%) participated. In the participating GP surgeries, we consecutively recruited 501 patients with at least one of the target-diseases and checked the guideline conformity of treatment using 9 quality indicators. We then interviewed the patients as well as the general practitioners regarding factors affecting deviation from guideline recommendations. Results: Of the 501 patients, a total of 1224 quality indicators could be analysed. Non-adherence to guideline recommendations were present in 16.8% (n = 205, 95% CI 14.7 to 18.8%) of all quality indicators. In 61.5% of these cases (n = 126, 95% CI 53.0 to 70.0%) the treatment was wrongly judged as not recommended by the physicians. In 10.2% (n = 21, 95% CI 0 to 23.2%) physicians attributed non-adherence to patient’s non-compliance, and in 10.7% (n = 22, 95% CI 0 to 23.7%) to an adverse drug event, whereas only 5.4% (n = 11, 95% CI 0 to 18.7%) of nonadherence was related to an adverse drug event reported by the patients. Patients were unaware regarding the reason for non-adherent therapy in 64.4% (n = 132, 95% CI 56.2 to 72.6%) of the quality indicators. In 20.0% (n = 41, 95% CI 7.8 to 32.2%) patients regarded a drug as not needed. Conclusions: Guideline adherence in chronic care was relatively good in our study sample, but still leaving room for improvement. Physicians’ lack of knowledge and patients’ lack of awareness account for about 70% of non-adherence, indicating the necessity to improve physician education, and patient involvement. In about 30% of the quality indicators not fulfilled, non-adherence is due to other reasons like adverse drug events or patients not willing to take a recommended drug.

Background Chronic diseases affect more than half of the population ≥75 years of age in developed countries. Prescription medication use increases with age. Depending on definition, 25-80% of elderly are exposed to polypharmacy. Polypharmacy increases the risk of hospitalization, interactions and adverse drug reactions. Objective To examine the frequency of medication errors in patients with polypharmacy treated in general practice. Methods The medications of 169 patients with polypharmacy treated in 22 GP surgeries in Austria were analysed. The analysis identified (i) medication errors, including non-evidence-based medications, dosing errors and potentially dangerous interactions in all patients and (ii) potentially inappropriate medications (PIMs) in the subgroup of elderly patients (≥65 years). Results The patients took on average 9.1±3.0 medications per day. The maximum, in one patient, was 20 medications per day. Some 93.5% had at least one non-evidence-based medication. On average, 2.7±1.66 medications per patient were found to be not indicated. At least one dosing error was found in 56.2% of all patients. One potential interaction of the most severe degree (category X interaction) was detected in 1.8% (n = 3) and two such interactions in 0.6% (n = 1). These combinations should have been avoided. Of the 169 patients, 158 were elderly (≥65 years). Of these seniors, 37.3% (n = 59) had at least one PIM according to the PRISCUS list for the elderly. Conclusion The frequency of medication errors is high in patients with polypharmacy in primary care. Development of strategies (e.g. external medication review) is required to counteract medication errors.

Background: Disease Management Programmes (DMPs) are proposed to enhance the quality of care, to improve health outcomes and to reduce costs. Yet, the evidence regarding the effectiveness of such structured approaches remains uncertain. Randomized controlled trials (RCTs) represent the gold standard of evaluation for complex interventions. However, most of the evidence derives from non-randomized or even uncontrolled trials. We therefore tried to assess the impact of a randomized control group on the interpretation of DMP effectiveness. Methods: We analyzed the data of a RCT on a DMP for diabetes type 2 by creating two scenarios. The first solely includes data of the intervention group ( n = 649), representing an ‘uncontrolled pre-test–post-test analysis’. The second comprehends all data ( n = 1489) of the ‘randomized controlled analysis’. HbA1c was used as the primary outcome measure for metabolic control in diabetes. Depending on either scenario, we calculated relative and absolute risk reduction regarding clinically relevant endpoints and estimated costs by extrapolating our results according to the UK Prospective Diabetes Study (UKPDS) findings. Results: The HbA1c reduction attributed to the DMP was 0.41% (uncontrolled analysis) vs. 0.13% (controlled comparison). Estimations of relative risk reduction for cardiovascular disease were 4.6% vs. 1.4%. The estimated numbers needed to treat (NNT) to avoid one myocardial infarction within 10 years differed from 125 (uncontrolled analysis) to 417 patients (controlled comparison), which led to a substantial scenario-dependent difference in cost estimations. Conclusion: Uncontrolled pre-test–post-test evaluation might lead to crucial overestimation of DMP effectiveness. We therefore recommend randomized controlled evaluations prior to long-term implementation.