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Quality indicators to assess the quality of primary care have only been applied on a national or regional level in European countries, and there have been no comparisons between regions of different countries. In the interventional pre-post-study "Improvement of Quality by Benchmarking - IQuaB" (level of evidence: 3), we aimed to improve and compare quality of process care in 57 participating general practices in Salzburg, Austria, and South Tyrol, Italy.The intervention consisted of self-audit, benchmarking and quality circles. Quality indicators for eight common chronic diseases (e. g., diabetes) were extracted from the electronic health records in 2012, 2013 and 2014. Based on 19 quality indicators, a supra-regional quality score was calculated and compared using Mann-Whitney U tests.A relatively weak baseline performance was identified in both regions. In all three assessments, the median quality score increased in both regions and was significantly higher in South Tyrol than in Salzburg. During the study period the median supra-regional quality score increased from 20.00 to 38.00 in the Salzburg sample and from 47.00 to 79.50 in the South Tyrolian sample. The differences between the two regions were significant at baseline and after intervention (2012: p=0.015, 2014: p=0.001).Despite data extraction challenges in Austria, we are convinced that our data highlight real differences in (processual) quality of care between the two regions.The reasons underlying the persisting differences between the two regions may include: (1) different functions in electronic health records, (2) benchmarking as an integral part of the electronic health record, (3) gate-keeping system and use of registration lists, (4) state-supported quality initiatives.

BACKGROUND: The term potentially inadequate medication (PIM) is used to describe substances that may be unsuitable for use in the elderly and should be avoided. The PRISCUS list, published in 2010, was the first catalog of PIM designed for the German drug market to become adopted in practice. While 24% of German patients aged ≥ 65 years were prescribed at least one PIM per year in 2009, the proportion in 2019 was only 14.5%. METHODS: In a three-round Delphi process, experts from clinical practice and research evaluated whether selected substances are PIM for the elderly. The participants were provided with dedicated literature including systematic reviews carried out for the particular purposes of this project. RESULTS: Fifty-nine persons took part in the Delphi process and, in addition, contributed comments and therapeutic alternatives. Altogether, 187 substances were classed as PIM. One hundred thirty-three of the substances now listed were not in the original PRISCUS list: these include some oral antidiabetics, all of the selective COX-2 inhibitors, and moderately long acting benzodiazepines such as oxazepam. For some other substances, e.g., proton pump inhibitors (PPI), the advisability of treatment for more than 8 weeks was considered as potentially inappropriate, as was the use of ibuprofen in doses >1200 mg/day and for more than 1 week without PPI. Risperidone for more than 6 weeks is also PIM. CONCLUSION: The new, greatly extended PRISCUS list must now be validated in epidemiological and prospective studies and its practicability in routine daily use must be verified.

Background: As face masks are a mandatory public health intervention during the COVID-19 pandemic, adverse effects require substantiated investigation. Methods: A systematic review of 2168 studies yielded 54 publications for synthesis and 37 studies for meta-analysis (on n=8641, m=2482, f=6159, age=34.8±12.5). The median trial duration was only 18 min (IQR=50) for our comprehensive evaluation of mask induced physio-metabolic and clinical outcomes. Results: We found significant effects in both medical masks with a greater impact regarding the N95. These effects included decreased SpO2 (overall SMD=-0.24, 95%CI=-0.38 to -0.11, p=0.0004) and minute ventilation (SMD=-0.72, 95%CI=-0.99 to -0.46, p2 (SMD=+0.64, 95%CI=0.31–0.96, p=0.0001), heart rate (N95: SMD=+0.22, 95%CI=0.03–0.41, p=0.02), systolic blood pressure (surgical: SMD=+0.21, 95%CI=0.03–0.39, p=0.02), skin temperature (overall SMD=+0.80 95%CI 0.23–1.38, p=0.006) and humidity (SMD +2.24, 95%CI=1.32–3.17, pDiscussion: Masks interfered with O2-uptake and CO2-release and compromised respiratory compensation. Though evaluated wearing durations do not represent daily/prolonged use, outcomes independently validate mask-induced exhaustion-syndrome (MIES). MIES can have long-term clinical consequences, especially for vulnerable groups. Conclusion: Face mask side-effects must be assessed (risk-benefit) against the available evidence of their effectiveness against viral transmissions.

Objective Due to the increasing concerns about polypharmacy, there is a growing need for clinical recommendations for drug discontinuation. This requires studies investigating the process on several levels. This paper addresses the methodological problems of drug discontinuation trials (DDTs). To that end, we offer a new typology of research aims and corresponding methodological recommendations for trials evaluating drug discontinuation. Study Design and Setting Multi-stage development process, including literature search and expert panels. Results Clinical trials are only required in cases of scientific uncertainty. We identified three situations of uncertainty associated with drug discontinuation from which we derived three study types: 1) Uncertainty regarding the effectiveness and/or safety of a drug; 2) Uncertainty regarding the procedure of discontinuing a previously taken drug; 3) Uncertainty regarding the effectiveness of complex strategies used to discontinue one or more drugs. We developed specific methodological recommendations for each study type. Conclusion We offer a comprehensive definition of research aims, study designs, and methodological recommendations regarding DDTs. The typology we propose can help investigators clarify their research aims and study design. The type-specific methodological recommendation should improve the quality of future drug discontinuation trials.

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.

The aim of the current study is to perform model calculations on the possible use of SARS-CoV-2-rapid point-of-care tests as mass tests, using the quality criteria extracted from evidence-based research as an example for the Federal Republic of Germany. In addition to illustrating the problem of false positive test results, these calculations are used to examine their possible influence on the 7-day incidence. For a substantial period of time, this parameter formed the decisive basis for decisions on measures to protect the population in the wake of the COVID pandemic, which were taken by the government. Primarily, model calculations were performed for a base model of 1,000,000 SARS-CoV-2-rapid point-of-care tests per week using various sensitivities and specificities reported in the literature, followed by sequential testing of the test positives obtained by a SARS-CoV-2 PCR test. Furthermore, a calculation was performed for an actual maximum model based on self-test contingents by the German Federal Ministry of Health. Assuming a number of 1,000,000 tests per week at a prevalence of 0.5%, a high number of false positive test results, a low positive predictive value, a high negative predictive value, and an increase in the 7-day incidence due to the additional antigen rapid tests of approx. 5/100,000 were obtained. A previous maximum calculation based on contingent numbers for self-tests given by the German Federal Ministry of Health even showed an additional possible influence on the 7-day incidence of 84.6/100,000. The model calculations refer in each case to representative population samples that would have to be drawn if the successive results were comparable which should be given, as far-reaching actions were based on this parameter. The additionally performed SARS-CoV-2-rapid point-of-care tests increase the 7-day incidence in a clear way depending on the number of tests and clearly show their dependence on the respective number of tests. SARS-CoV-2-rapid point-of-care tests as well as the SARS-CoV-2-PCR test method should both be used exclusively in the presence of corresponding respiratory symptoms and not in symptom-free persons.

Zusammenfassung Hintergrund Ziel dieser Arbeit ist die exemplarische methodische Uberprufung der Qualitat eingeschlossener Studien zur medikamentosen Therapie alterer Menschen anhand einer publizierten Reihe von sechs systematischen Reviews (SRs). Diese sechs SRs inkludierten 48 systematische Ubersichtsarbeiten, 65 Interventions- und 33 Beobachtungsstudien. Die Reihe der SRs wurde im Rahmen des PRIMA-eDS-Projekts ( www.prima-eds.eu ) erstellt, um Empfehlungen zur Behandlung von alteren Menschen mit Polypharmazie zu entwickeln. Methode Wir gehen mit dieser Qualitatsanalyse der Frage nach, inwieweit sich Empfehlungen zur medikamentosen Behandlung alterer Menschen auf belastbare Studienevidenz grunden. Hierzu erfolgte eine Qualitatsbewertung aller eingeschlossenen Studien mittels AMSTAR fur systematische Ubersichtsarbeiten, CASP fur Beobachtungsstudien und dem Cochrane „Risk of Bias“-Tool fur Interventionsstudien. Ergebnisse Die Evidenzbasis fur haufig verschriebene Medikamente bei alteren Menschen ist schwach. Die in der Reihe von SRs identifizierten Publikationen offenbarten sowohl einen deutlichen Mangel an hochwertigen Studien hinsichtlich der Zielpopulation als auch einen Mangel an Studienqualitat. Unter den 33 Beobachtungsstudien blieb bei fast der Halfte aller Veroffentlichungen unklar, ob das Follow-up ausreichend lang und vollstandig war. Bei einem Drittel passten die Schlussfolgerungen nicht zur beobachteten Evidenz. Das groste Verzerrungsrisiko der Interventionsstudien fand sich bei der korrekten Gruppenzuteilung und der korrekten Verblindung. Qualitatsmangel der systematischen Ubersichtsarbeiten bestanden hinsichtlich der Bereitstellung einer vollstandigen Studienliste und der fehlenden Berucksichtigung eines moglichen Publikationsbias. Diskussion Insgesamt zeigten sich viele methodische Mangel, wodurch die Ableitung belastbarer Empfehlungen erschwert oder fast unmoglich gemacht wurde. Schlussfolgerung Unsere Arbeit verdeutlich zum einen den immensen Forschungsbedarf in der Behandlung alterer und hochbetagter Patientinnen und Patienten und zum anderen die Wichtigkeit, sowohl bei der Durchfuhrung von Primarstudien als auch bei der Erstellung systematischer Ubersichtsarbeiten auf hochste Qualitatsstandards zu achten.

BackgroundAdrenergic 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.MethodsA comprehensive literature search was performed 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. ResultsFourteen studies were included: 3 meta-analyses, 6 randomised controlled trials and 5 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. One large observational study points at an increased risk of falls and fractures. The effects of long-term treatment remained unclear. All meta-analyses and 5 out of 6 interventional studies were downgraded in the quality appraisal. 4 out of 5 observational studies were of good quality.ConclusionsIt 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.

BackgroundSystematic reviews that synthesize safety outcomes pose challenges (e.g. rare events), which poses questions for grading the strength of the body of evidence. In this contribution, we suggest adaption of the GRADE system for grading the quality of evidence on safety outcomes for developing a potentially inappropriate medication list (PRISCUS).MethodsWe 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. Subsequently, we performed a proof-of-concept application using a convenience sample of systematic reviews. Results We adapted aspects of 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 for 19 clinical questions. 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.ConclusionThe adaptions 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.

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

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.

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.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.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.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.ClinicalTrials.gov identifier: NCT02295462 ; November 20, 2014.

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.

BackgroundWe aim to assess the safety of dipeptidylpeptidase-4 inhibitors (DPP4s) in older type 2 diabetes patients with inadequate glycaemic control. MethodsWe included RCTs in older (≥65 years) patients with type 2 diabetes. The intervention group was treated with any DPP4. A systematic search in MEDLINE and EMBASE was performed in December 2020. For assessing risk of bias, the RoB 2 tool was applied. The quality of evidence was assessed using GRADE. We pooled outcomes using random-effects meta-analyses. ResultsWe identified 16 RCTs that included 19,317 patients with a mean age >70 years. The mean HbA1c ranged between 7.1g/dl and 10.0g/dl.Adding DPP4s to standard alone care may increase mortality slightly (RR 1.04; 0.89-1.21). Adding DPP4s to standard care increases the risk for hypoglycaemia (RR 1.08; 95%CI 1.01-1.16), but difference in overall adverse events is negligible.DPP4s added to standard care likely reduce mortality compared to sulfonylureas (RR 0.88; 0.75-1.04). DPP4s probably reduce the risk for hypoglycaemia compared to sulfonylureas (magnitude of effect not quantifiable because of heterogeneity) but difference in overall adverse events is negligible.There is insufficient evidence on hospitalizations, falls, fractures, renal impairment, and pancreatitis. Conclusion There is no evidence that DPP4s in addition to standard care decrease mortality but DPP4s increase hypoglycaemia risk. Second-line therapy in older patients should be considered cautiously because even in drugs with a good safety profile like DPP4s. In the case second-line treatment is necessary, DPP4s appear to be superior to sulfonylureas. RegistrationPROSPERO: CRD42020210645

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.

Zusammenfassung Ziel der Studie In Anbetracht des prognostizierten Allgemeinmediziner-Mangels führten wir eine Online-Umfrage unter allen Medizinstudierenden Nordrhein-Westfalens durch, um Faktoren für die Entscheidung Medizinstudierender zur Fachrichtung Allgemeinmedizin (AM) zu identifizieren und die Stärke der Zusammenhänge zwischen Faktoren und Fachrichtungswahl zu quantifizieren. Methodik Um Beweggründe für und gegen die Fachrichtungswahl AM zu identifizieren wurde eine Faktorenanalyse mit den Angaben von 3976 Umfrageteilnehmern (22,6% aller eingeladenen Medizinstudierenden) durchgeführt. Die Stärke der Zusammenhänge zwischen extrahierten Faktoren und Fachrichtungswahl wurden mittels Regressionsanalysen für 2862 Teilnehmer ermittelt, die sich eher für oder gegen AM positioniert hatten. Adjustiert wurde für relevante Populationsmerkmale. Ergebnisse Fünf Faktoren wurden identifiziert. Signifikante Zusammenhänge zur Fachrichtungswahl AM zeigten 4 dieser Faktoren. „Umfassender Patientenkontakt“ (OR 4,02; 95% KI [3,5–4,6]), und „flexible Arbeitszeiten“ (OR 1,35; 95% KI [1,2–1,5]) stellen Beweggründe für die Fachrichtungswahl AM dar, obwohl „höhere(s) Karrierechancen, Einkommensmöglichkeiten & Ansehen in anderen Fachrichtungen“ (OR 1,14; 95% KI [1,0–1,3]) gesehen werden. Bessere Möglichkeiten der „Spezialisierung, Forschung und Teamarbeit in anderen Fachrichtungen“ stehen einer Wahl von AM als Fach entgegen (OR 0,55; 95% KI [0,5–0,6]). Schlussfolgerungen Der Nachwuchsgewinnung dienlich wären die strukturierte Förderung studentischen Interesses am Patientenkontakt in Lehrpraxen, mehr Spezialisierung, Forschung und Teamarbeit durch verbesserte allgemeinmedizinische Strukturen an Universitäten und eine weitere Flexibilisierung der Arbeitszeiten.

PurposeOur objective was to assess the safety of long-term intake of DOACs in older adults with atrial fibrillation (AF). MethodsWe included RCTs in elderly (≥65 years) patients with AF. A systematic search in MEDLINE and EMBASE was performed on 9/11/2020. For determination of risk of bias, the RoB-2 tool was applied. We pooled outcomes using random-effects meta-analyses. The quality of evidence was assessed using GRADE.ResultsTen RCTs with a total of 61,948 patients were identified. Seven RCTs included patients with AF-only and three with AF who received PCI and additional antiplatelet-therapy. Two RCTs compared apixaban with either warfarin or aspirin, three edoxaban with either placebo, aspirin, or Vitamin K antagonists (VKAs), two dabigatran with warfarin and three rivaroxaban with warfarin. DOACs probably reduce mortality in elderly patients with AF-only (HR 0.89 95%CI 0.78 to 1.02). We did not find any RCT that reported mortality in elderly AF-PCI patients. Low-dose DOACs likely reduce bleeding compared to VKAs (HR ranged from 0.47 to 1.01). High-dose edoxaban reduces major or clinically relevant bleeding (MCRB) compared to VKAs (HR 0.82 95%CI 0.73 to 0.93) but high-dose dabigatran or rivaroxaban increase MCRB (HR 1.15 95%CI 1.02 to 1.30).Conclusion We found that low-dose DOACs probably decrease mortality in AF-only patients. Moreover, apixaban and edoxaban are associated with fewer MCRB compared to VKAs. For dabigatran and rivaroxaban, the risk of MCRB varies depending on dose.

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.

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.

The objective was to assess the changes in quality of life (QoL) and patient satisfaction of chronically ill patients in general practices in Salzburg (Austria) and South Tyrol (Italy) after implementation of a combined intervention addressing quality of care of general practitioners (GPs). Furthermore, the correlation between QoL/patient satisfaction and quality of care provided by the GPs (measured by a quality score based on quality indicators [QIs]) was investigated. The non-controlled pre-post study involved GPs and patients with chronic conditions. The intervention consisted of self-audit, benchmarking and quality circles. QIs were extracted in the participating practices in 2012 (preintervention) and 2014 (postintervention). Before and after the intervention, a patient survey was conducted including EQ-5D (measuring health-related QoL), a patient participation scale and parts of the European Task Force on Patient Evaluations of General Practice questionnaire (measuring patient satisfaction). Mann-Whitney U-tests, chi-square tests and Spearman's rank correlation were applied for statistical analysis. Fifty-six GPs participated in the study. 1,710 patients returned the questionnaire in 2012, and 1,374 in 2014. Mean EQ-5D index (QoL) was similar in Salzburg and South Tyrol in both years: 2012 Salzburg 0.85 (95% CI 0.84-0.87), South Tyrol 0.85 (95% CI 0.84-0.86); 2014 Salzburg 0.84 (95% CI 0.83-0.86), South Tyrol 0.84 (95% CI 0.83-0.86). Patient satisfaction was higher in Salzburg than in South Tyrol at baseline (EUROPEP: mean percentage of best response 61.5% vs. 49.1%, p

Background Proton pump inhibitors (PPIs) are increasingly being prescribed, although long-term use is associated with multiple side effects. Therefore, an electronic decision support tool with the aim of reducing the long-term use of PPIs in a shared decision-making process between general practitioners (GPs) and their patients has been developed. The developed tool is a module that can be added to the so-called arriba decision support tool, which is already used by GPs in Germany in routine care. In this large-scale cluster-randomized controlled trial we evaluate the effectiveness of this arriba-PPI tool. Methods The arriba-PPI tool is an electronic decision support system that supports shared decision-making and evidence-based decisions around the long-term use of PPIs at the point of care. The tool will be evaluated in a cluster-randomized controlled trial involving 210 GP practices and 3150 patients in Germany. GP practices will be asked to recruit 20 patients aged ≥ 18 years regularly taking PPIs for ≥ 6 months. After completion of patient recruitment, each GP practice with enrolled patients will be cluster-randomized. Intervention GP practices will get access to the software arriba-PPI, whereas control GPs will treat their patients as usual. After an observation period of six months, GP practices will be compared regarding the reduction of cumulated defined daily doses of PPI prescriptions per patient. Discussion Our principal hypothesis is that the application of the arriba-PPI tool can reduce PPI prescribing in primary care by at least 15% compared to conventional strategies used by GPs. A positive result implies the implementation of the arriba-PPI tool in routine care. Trial registration German Clinical Trials Register, DRKS00016364. Registered on 31 January 2019.

Aim The aim of the present study was to explore the impact of strategies to reduce polypharmacy on mortality, hospitalization and change in number of drugs. Methods Systematic review and meta-analysis: a systematic literature search targeting patients ≥65 years with polypharmacy (≥4 drugs), focusing on patient-relevant outcome measures, was conducted. We included controlled studies aiming to reduce polypharmacy. Two reviewers independently assessed studies for eligibility, extracted data and evaluated study quality. Results Twenty-five studies, including 10 980 participants, were included, comprising 21 randomized controlled trials and four nonrandomized controlled trials. The majority of the included studies aimed at improving quality or the appropriateness of prescribing by eliminating inappropriate and non-evidence-based drugs. These strategies to reduce polypharmacy had no effect on all-cause mortality (odds ratio 1.02; 95% confidence interval 0.84, 1.23). Only single studies found improvements, in terms of reducing the number of hospital admissions, in favour of the intervention group. At baseline, patients were taking, on average, 7.4 drugs in both the intervention and the control groups. At follow-up, the weighted mean number of drugs was reduced (−0.2) in the intervention group but increased (+0.2) in controls. Conclusions There is no convincing evidence that the strategies assessed in the present review are effective in reducing polypharmacy or have an impact on clinically relevant endpoints. Interventions are complex; it is still unclear how best to organize and implement them to achieve a reduction in inappropriate polypharmacy. There is therefore a need to develop more effective strategies to reduce inappropriate polypharmacy and to test them in large, pragmatic randomized controlled trials on effectiveness and feasibility.

Background The treatment of upper respiratory tract infections (URTIs) accounts for the majority of antibiotic prescriptions in primary care, although an antibiotic therapy is rarely indicated. Non-clinical factors, such as time pressure and the perceived patient expectations are considered to be reasons for prescribing antibiotics in cases where they are not indicated. The improper use of antibiotics, however, can promote resistance and cause serious side effects. The aim of the study was to clarify whether the antibiotic prescription rate for infections of the upper respiratory tract can be lowered by means of a short (2 x 2.25h) communication training based on the MAAS-Global-D for primary care physicians. Methods In total, 1554 primary care physicians were invited to participate in the study. The control group was formed from observational data. To estimate intervention effects we applied a combination of difference-in-difference (DiD) and statistical matching based on entropy balancing. We estimated a corresponding multi-level logistic regression model for the antibiotic prescribing decision of German primary care physicians for URTIs. Results Univariate estimates detected an 11-percentage-point reduction of prescriptions for the intervention group after the training. For the control group, a reduction of 4.7% was detected. The difference between both groups in the difference between the periods was -6.5% and statistically significant. The estimated effects were nearly identical to the effects estimated for the multi-level logistic regression model with applied matching. Furthermore, for the treatment of young women, the impact of the training on the reduction of antibiotic prescription was significantly stronger. Conclusions Our results suggest that communication skills, implemented through a short communication training with the MAAS-Global-D-training, lead to a more prudent prescribing behavior of antibiotics for URTIs. Thereby, the MAAS-Global-D-training could not only avoid unnecessary side effects but could also help reducing the emergence of drug resistant bacteria. As a consequence of our study we suggest that communication training based on the MAAS-Global-D should be applied in the postgraduate training scheme of primary care physicians.

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 Type 2 diabetes is a chronic disease associated with poorer health outcomes and decreased health related quality of life (HRQoL). The aim of this analysis was to explore the impact of a disease management programme (DMP) in type 2 diabetes on HRQoL. A multilevel model was used to explain the variation in EQ-VAS. Methods A cluster-randomized controlled trial—analysis of the secondary endpoint HRQoL. Our study population were general practitioners and patients in the province of Salzburg. The DMP “Therapie-Aktiv” was implemented in the intervention group, and controls received usual care. Outcome measure was a change in EQ-VAS after 12 months. For comparison of rates, we used Fisher’s Exact test; for continuous variables the independent T test or Welch test were used. In the multilevel modeling, we examined various models, continuously adding variables to explain the variation in the dependent variable, starting with an empty model, including only the random intercept. We analysed random effects parameters in order to disentangle variation of the final EQ-VAS. Results The EQ-VAS significantly increased within the intervention group (mean difference 2.19, p = 0.005). There was no significant difference in EQ-VAS between groups (mean difference 1.00, p = 0.339). In the intervention group the improvement was more distinct in women (2.46, p = 0.036) compared to men (1.92, p = 0.063). In multilevel modeling, sex, age, family and work circumstances, any macrovascular diabetic complication, duration of diabetes, baseline body mass index and baseline EQ-VAS significantly influence final EQ-VAS, while DMP does not. The final model explains 28.9% (EQ-VAS) of the total variance. Most of the unexplained variance was found on patient-level (95%) and less on GP-level (5%). Conclusion DMP “Therapie-Aktiv” has no significant impact on final EQ-VAS. The impact of DMPs in type 2 diabetes on HRQoL is still unclear and future programmes should focus on patient specific needs and predictors in order to improve HRQoL. Trial registration Current Controlled trials Ltd., ISRCTN27414162

Contains fulltext : 153117.pdf (Publisher’s version ) (Open Access) BACKGROUND: Drug treatment is an important clinical process in primary care that is associated with risk of error and adverse events. OBJECTIVE: To review currently available research evidence on the topic and to develop a framework, which can help to guide improvement of medication safety. METHODS: Systematic reviews were performed on adverse drug events (ADE), their preventability, and on available tools and methods to improve medication safety with a particular focus on information technology. Consensus methods were used to develop a framework to guide the improvement of medication safety based on the findings of our literature review. RESULTS: The median prevalence rate of ADEs in primary care patients was 12.8%. Only a median of 16.5% of ADEs were preventable and thus could be classified as medication errors. Our review of information technology interventions found that only about half of the studies found a reduction of medication errors. In both reviews, the wide range between studies emphasizes the necessity of a validated medication error classification system. Another important aspect of medication safety appears to be a general lack of safety culture in primary care, which led us to the development of the Salzburg medication safety framework (SaMSaF), based on the MaPSaF tool to improve patient safety. The tool proved to be feasible and useful in a pilot study with several GP practices. CONCLUSION: A number of tools and interventions to investigate and enhance medication safety have been identified. Further research is necessary to implement and evaluate current concepts.

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

Introduction Medication safety incidents occur in all health care sectors and cause considerable morbidity and mortality, with 8.5% of all related incidents reported estimated to occur in primary care. A common incident classification system could facilitate collective learning from the analysis of medication-related errors and improve patient safety Objective The objective of this study was to assess the validity of a new classification system of medication safety incidents in primary care in Poland. Methods Analysis of data from a descriptive, cross-sectional, self-reported survey on the Learning from International Networks about Errors and Understanding Safety in Primary Care (LINNEAUS Euro-PC) medication safety incident classification for primary care with assessment of 10 case-based clinical scenarios done by doctors and pharmacists form community-based family medicine clinics and pharmacies in Lodz. Main outcome measures The percentages of overall agreement on judgements and a fixed-marginal multirater kappa (κ) coefficient as statistical measures of interrater agreement for categorical items. Results The overall agreement levels were: category 1 – 86.3%; category 2 – 85.6%; category 3 – 72.1%; category 4 – 71.8%; and category 5 – 70.4%. The interrater agreement between the 15 evaluators varied as follows: category 1 fixed-marginal κ = 0.144; category 5 fixed-marginal κ = 0.565; category 3 fixed-marginal κ = 0.607; category 4 fixed-marginal κ = 0.634; and category 2 fixed-marginal κ = 0.807. Conclusions This is the first known study on levels of agreement on the perception of medication safety incidents and assessment of the validity of a related classification system in primary health care in Poland. Interrater agreement in this study was surprisingly high, but still leaves room for improvement.