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Zusammenfassung Hintergrund Real World Evidence (RWE) gewinnt in der Bewertung medizinischer Maßnahmen zunehmend an Bedeutung und ergänzt Befunde von kontrollierten klinischen Studien. Gleichzeitig sieht sich der RWE-Ansatz erheblichen methodischen und ethischen Herausforderungen gegenüber. Phytopharmaka haben ihren Platz in der Therapie durch Heilberufe und in der Selbstmedikation bei leichteren Beschwerden sowie Symptomen, die nachhaltig die Lebensqualität beeinflussen. Die aktuell geforderten Schlüsselstudien für die Arzneimittelzulassung bilden die Folgen einer ärztlichen Verordnung und/oder der Selbstmedikation jedoch nur unzureichend ab. Im Rahmen eines Workshops werden daher die Nutzbarkeit von RWE für die Forschung im Bereich Phytopharmaka sowie methodische Grundlagen zum Aufbau eines Phytoregisters diskutiert. Methoden Der Workshop bestand aus 2 Teilen: Impulsreferate zu den Themen RWE und Phytotherapie und die Erarbeitung der Basis eines Positionspapiers mithilfe der Methodik des nominalen Gruppenprozesses. Ergebnisse Die Impulsreferate umfassten interdisziplinäre Argumente aus den Bereichen Forschung und Praxis der Phytotherapie, Registererstellung, Versorgungsforschung, künstliche Intelligenz und Telemedizin. Im nominalen Gruppenprozess wurden die Chancen und Risiken der Phytotherapie sowie inhaltliche, methodische und praktische Aspekte eines Phytoregisters diskutiert (Fokus, Mehrwert und methodische Standards des Registers, Finanzierung, erwartete Kritik, Analysemethoden und Stellenwert im Vergleich zu anderen medizinischen Bereichen). Schlussfolgerungen Register sind ein zunehmend akzeptierter Weg, um Evidenz in Ergänzung zu klinischen Studien zu generieren. Der schrittweise Aufbau eines Registers für Phytopharmaka mit klar definierten methodischen Kriterien und der Erfassung von patientenzentrierten Endpunkten bietet die Chance, die wissenschaftliche Fundierung der Anwendung und des klinischen Nutzens von Phytopharmaka zu erweitern.

Background: Proton pump inhibitors (PPIs) are well tolerated in the short term but have recently been associated with increased long-term cardiovascular risk in observational studies. Aims: To evaluate long-term risks of myocardial infarction (MI) and ischaemic stroke (IS) associated with PPI vs H2-receptor antagonist (H2RA) therapy in adults without pre-existing cardiovascular or cerebrovascular disease. Methods: Using administrative claims data (2008–2018), we emulated a target trial comparing MI and IS risks in new users of PPIs vs H2RAs. Treatment was identified using dispensed prescriptions. MI and IS were defined using hospital discharge codes. Inverse probability weighting was used to adjust for confounding, and Cox models to estimate hazard ratios (HRs). Survival curves were estimated using weighted Kaplan-Meier estimators. Results: We identified 1143948 new users of PPIs and 36229 new users of H2RAs who were free of prevalent cardiovascular or cerebrovascular disease. The mean follow-up time was 6.2years for PPI initiators and 5.3years for H2RA initiators. After 10years, the HRs for MI and IS were 0.96 (95% confidence interval (CI): 0.80-1.16) and 0.98 (95% CI: 0.89-1.08), respectively. Conclusions: This analysis of claims data of a large German health insurer did not provide evidence that PPI therapy increased the risk of MI or IS in the first decade after treatment initiation.

(1) Adverse drug events (ADEs) are a common cause of emergency department visits and occur frequently during hospitalisation. Instruments that facilitate the detection of the most relevant ADEs could lead to a more targeted and efficient use of limited resources in research and practice. (2) We conducted two consensus processes based on the RAND/UCLA appropriateness method, in order to prioritise ADEs leading to hospital admission (panel 1) and occurring during hospital stay (panel 2) for inclusion in future ADE measurement instruments. In each panel, the experts were asked to assess the “overall importance” of each ADE on a four-point Likert scale (1 = not important to 4 = very important). ADEs with a median rating of ≥3 without disagreement were defined as “prioritised“. (3) The 13 experts in panel 1 prioritised 38 out of 65 ADEs, while the 12 experts in panel 2 prioritised 34 out of 63 ADEs. The highest rated events were acute kidney injury and hypoglycaemia (both panels), as well as Stevens–Johnson syndrome in panel 1 and rhabdomyolysis in panel 2. (4) The survey led to a set of ADEs for which there was consensus that they were of particular importance as presentations of acute medication-related harm, thereby providing a focus for further medication safety research and clinical practice.

BACKGROUND The treatment of elderly patients with dizziness/vertigo/balance disorders (VDB) can be challenging for their general practitioner. Patient-centered care with a focus on self-management support could be a possible approach. Primary objective of this study was to investigate the correlations between quality of primary care and health-related quality of life (HRQOL) from the patient's perspective. METHOD Data had been collected in the area of Munich and in the area of Dresden between 2017 and 2019. Questionnaires of n = 157 elderly patients from primary care practices in Munich and Dresden were evaluated. Multiple linear regression was used to analyse quality of care, physical activity, depression, and their correlations with HRQOL. RESULTS In this cohort of patients aged 65 to 94 no significant correlation between quality of care and HRQOL could be detected. Depression correlated negatively with HRQOL, whereas physical activity showed a positive correlation with HRQOL. CONCLUSIONS Physical activity can be beneficial for elderly dizzy patients' HRQOL. Additionally, a potential depression should be taken into account when treating patients with dizziness to improve their HRQOL. The results can be well transferred to elderly patients with VDB. Analysing more patients however, could increase the significance of the results. ZUSAMMENFASSUNG Hintergrund: Die Behandlung von alteren Patienten mit Schwindelbeschwerden kann eine Herausforderung fur den Hausarzt darstellen. Ein moglicher Ansatz ist eine patientenzentrierte Versorgung mit Fokus auf der Unterstutzung des Selbstmanagements. Die Untersuchung des Zusammenhangs zwischen der Versorgungsqualitat durch den Hausarzt und der gesundheitsbezogenen Lebensqualitat (HRQOL) aus der Patientenperspektive war primares Ziel dieser Analyse. Methode: Die Datenerhebung fand zwischen 2017 und 2019 im Raum Munchen und im Raum Dresden statt. Insgesamt wurden Fragebogen von n = 157 Patienten mit Schwindel aus der hausarztlichen Versorgung analysiert. Die Versorgungsqualitat, korperliche Aktivitat, Depressivitat und deren Zusammenhang mit der HRQOL wurden mithilfe multipler linearer Regressionsmodelle im Quer- und Langsschnitt (nach 6 Monaten) betrachtet. Ergebnisse: In der beobachteten Kohorte von Patienten zwischen 65-94 Jahren ergaben sich keine signifikanten Zusammenhange zwischen der Versorgungsqualitat und der HRQOL. Es zeigte sich ein negativer Zusammenhang zwischen Depressivitat und HRQOL und ein positiver Zusammenhang zwischen korperlicher Aktivitat und HRQOL. Schlussfolgerungen: Fur die HRQOL alterer Patienten mit Schwindel kann korperliche Aktivitat von Vorteil sein. Auch sollte zur Verbesserung der HRQOL eine mogliche Depressivitat bei der Behandlung von Patienten mit Schwindel berucksichtigt werden. Die Ergebnisse lassen sich sehr gut auf altere hausarztliche Patienten mit Schwindel ubertragen. Die Untersuchung einer groseren Kohorte konnte die Aussagekraft der Ergebnisse noch erhohen. Schlusselworter: Schwindel, gesundheitsbezogene Lebensqualitat, Versorgungsqualitat, korperliche Aktivitat, DepressivitatEingereicht am 1.12.2020 - Revision akzeptiert am 2.2.2021.

IntroductionPeople in need of care or support are severely affected by the COVID-19 pandemic. We lack valid data of long-term assessments. We present a register study to detect the physical and psychosocial impact of the COVID-19 pandemic on people in need of care or support in Bavaria, Germany. To describe the persons’ life conditions comprehensively, we assess the perspectives and needs of the respective care teams too. Results will serve as evidence-based source to manage the pandemic and long-term prevention strategies.Methods and analysisThe ‘Bavarian ambulatory COVID-19 Monitor’ is a multicentre registry including a purposive sample of up to 1000 patient–participants across three study sites in Bavaria. The study group consists of 600 people in need of care with a positive SARS-CoV-2 PCR test. Control group 1 comprises 200 people in need of care with a negative SARS-CoV-2 PCR test, while control group 2 comprises 200 people with a positive SARS-CoV-2 PCR test but are not in need of care. We assess the clinical course of infection, psychosocial aspects and care needs using validated measures. Follow-up is every 6 months for up to 3 years. Additionally, we assess up to 400 people linked to these patient–participants (caregivers, general practitioners (GPs)) for their health and needs. Main analyses are stratified by level of care I–V (I=minor/V=most severe impairment of independence), inpatient/outpatient care setting, sex and age. We use descriptive and inferential statistics to analyse cross-sectional data and changes over time. In qualitative interviews with 60 stakeholders (people in need of care, caregivers, GPs, politicians), we explore interface problems of different functional logics, of everyday and professional perspectives.Ethics and disseminationThe Institutional Review Board of the University Hospital LMU Munich (#20-860) and the study sites (Universities of Wurzburg and Erlangen) approved the protocol. We disseminate the results by peer-reviewed publications, international conferences, governmental reports, etc.

BACKGROUND Shared decision making (SDM) is a promising approach, to bridge major barriers concerning vaccination by patient education and personal interaction of health care provider (HCP) and patient. SDM affects patient adherence, enhances patient knowledge, decreases decisional conflict and improves trust in the physician in most areas of health care. The shared decision making process (SDM process) is characterised by three key components: patient activation, bi-directional exchange of information and bi-directional deliberation of options. OBJECTIVES To assess the impact of SDM processes on influenza vaccination rates in outpatient care patients. METHODS A systematic literature search in MEDLINE, CENTRAL, EMBASE, PsycINFO and ERIC was conducted (2020-02-05). Randomized controlled trials (RCTs) and cluster RCTs, that aimed to improve influenza vaccination rates in adult patients in outpatient care were included. We examined effects of SDM processes on influenza vaccination rates by meta-analysis, and considered the extent of SDM processes in the analysed interventions and possible effect modifiers in subgroup analyses. RESULTS We included 21 studies, with interventions including face-to-face sessions, telephone outreach, home visits, Health Care Practitioner (HCP) trainings and supporting educational material. In 12 studies, interventions included all elements of a SDM process. A meta-analysis of 15 studies showed a positive effect on vaccination rates (OR of 1.96 (95% CI: 1.31 to 2.95)). Findings further suggest that interventions are effective across different patients groups and could increase effectiveness when the interaction is facilitated by multidisciplinary teams of HCP in comparison to interventions delivered by individual HCP. DISCUSSION This systematic review and meta-analysis provide evidence that SDM processes can be an effective strategy to increase influenza vaccination rates. Further research with more detailed descriptions of SDM implementation modalities is necessary to better understand which components of SDM are most effective. TRIAL REGISTRATION PROSPERO: CRD42020175555.

Background: The misattribution of an adverse drug reaction (ADR) as a symptom or illness can lead to the prescribing of additional medication, referred to as a prescribing cascade. The aim of this systematic review is to identify published prescribing cascades in community-dwelling adults. Methods: Systematic review reported in line with the PRISMA guidelines and pre-registered with PROSPERO. Electronic databases (Medline (Ovid), EMBASE, PsycINFO, CINAHL, Cochrane Library) and grey literature sources were searched. Inclusion criteria: Community-dwelling adults; Risk-prescription medication; Outcomes-initiation of new medicine to ‘treat’ or reduce ADR risk; Study type-cohort, cross-sectional, case-control and case-series studies. Title/abstract screening, full-text screening, data extraction and methodological quality assessment was conducted independently in duplicate. A narrative synthesis was conducted. Results: A total of 101 studies (reported in 103 publications) were included. Study sample sizes ranged from 126 to 11,593,989 participants and 15 studies examined older adults specifically (≥60 years). Seventy-eight of 101 studies reported a potential prescribing cascade including calcium channel blockers to loop diuretic (n=5), amiodarone to levothyroxine (n=5), inhaled corticosteroid to topical antifungal (n=4), antipsychotic to anti-Parkinson drug (n=4), and acetylcholinesterase inhibitor to urinary incontinence drugs (n=4). Identified prescribing cascades occurred within three months to one year following initial medication. Methodological quality varied across included studies. Conclusion and implications: Prescribing cascades occur for a broad range of medications. ADRs should be included in the differential diagnosis for patients presenting with new symptoms, particularly older adults and those who started a new medication in the preceding 12 months. Word count: 245

BackgroundAlthough there are several efficacious vaccines against COVID-19, vaccination rates in many regions around the world remain insufficient to prevent continued high disease burden and emergence of viral variants. Repurposing of existing therapeutics that prevent or mitigate severe COVID-19 could help to address these challenges. The objective of this study was to determine whether prior use of bisphosphonates is associated with reduced incidence and/or severity of COVID-19.MethodsA retrospective cohort study utilizing payer-complete health insurance claims data from 8,239,790 patients with continuous medical and prescription insurance from 1-1-2019 to 6-30-2020 was performed. The primary exposure of interest was use of any bisphosphonate from 1-1-2019 to 2-29-2020. Outcomes of interest included: (a) testing for SARS-CoV-2 infection; (b) COVID-19 diagnosis; and (c) hospitalization with COVID-19 diagnosis between 3-1-2020 and 6-30-2020.Results7,906,603 patients for whom continuous medical and prescription insurance information was available were selected. 450,366 bisphosphonate users were identified and 1:1 propensity score-matched to bisphosphonate non-users by age, gender, insurance type, primary-care-provider visit in 2019, and comorbidity burden. Bisphosphonate users had lower odds ratios (OR) of testing for SARS-CoV-2 infection (OR=0.22; 95%CI:0.21-0.23; pConclusionsPrior bisphosphonate-use was associated with dramatically reduced odds of SARS-CoV-2 testing, COVID-19 diagnosis, and COVID-19-related hospitalizations. Prospective clinical trials will be required to establish a causal role for bisphosphonate-use in COVID-19-related outcomes.

BACKGROUND AND AIMS: Observational research has indicated that proton pump inhibitors (PPIs) might increase the long-term risk of cardiovascular events. This study evaluated the evidence from observational studies for an effect of PPI monotherapy on the risk of incident cardiovascular events and cardiovascular mortality. METHODS: The databases MEDLINE, EMBASE, and Scopus were systematically searched up to September 2021. The primary outcome was first cardiovascular event, i.e. first myocardial infarction or first ischaemic stroke. The secondary outcome was cardiovascular mortality. Studies were included following a detailed risk of bias assessment with the ROBINS-I tool. Sensitivity and bias analyses adjusted for potential publication bias, immortal time bias, and unmeasured confounding. RESULTS: We included ten studies with 75,371 first cardiovascular events, as well as seven studies on cardiovascular mortality with 50,329 cardiovascular deaths in total. The pooled hazard ratios (HRs) for PPI use and cardiovascular events were 1.05 with a 95% confidence interval of (0.96; 1.15) before and 0.99 (0.93; 1.04) after adjusting for observational study design bias. The pooled HRs for PPI use and cardiovascular mortality were 1.27 (1.11; 1.44) before and 1.06 (0.96; 1.16) after adjusting for publication bias and observational study design bias. CONCLUSION: It is questionable, whether PPI monotherapy constitutes a cardiovascular risk factor.

Adverse drug events (ADEs) and adverse drug reactions (ADRs) are leading causes of iatrogenic injury, which can result in emergency department (ED) visits or admissions to inpatient wards. The aim of this systematic review and meta-analysis was to provide up-to-date estimates of the prevalence of (preventable) drug-related ED visits and hospital admissions, as well as the type and prevalence of implicated ADRs/ADEs and drugs. A literature search of studies published between January 2012 and December 2021 was performed in PubMed, Medline, EMBASE, Cochrane Library, and Web of Science. Retrospective and prospective observational studies investigating acute admissions to EDs or inpatient wards due to ADRs or ADEs in the general population were included. Meta-analyses of prevalence rates were conducted using generalized linear mixed models (GLMM) with the random-effect method. Seventeen studies reporting ADRs and/or ADEs were eligible for inclusion. The prevalence rates of ADR- and ADE-related admissions to EDs or inpatient wards were estimated at 8.3% ([95% CI, 6.4–10.7%]) and 13.9% ([95% CI, 8.1–22.8%]), respectively, of which almost half (ADRs: 44.7% [95% CI: 28.1; 62.4]) and more than two thirds (ADEs: 71.0% [95% CI, 65.9–75.6%]) had been classified as at least possibly preventable. The ADR categories most frequently implicated in ADR-related admissions were gastrointestinal disorders, electrolyte disturbances, bleeding events, and renal and urinary disorders. Nervous system drugs were found to be the most commonly implicated drug groups, followed by cardiovascular and antithrombotic agents. Our findings demonstrate that ADR-related admissions to EDs and inpatient wards still represent a major and often preventable health care problem. In comparison to previous systematic reviews, cardiovascular and antithrombotic drugs remain common causes of drug-related admissions, while nervous system drugs appear to have become more commonly implicated. These developments may be considered in future efforts to improve medication safety in primary care.

Hepatic impairment (HI) is a known risk factor for drug safety. The MELD score (Model-for-endstage-liver-disease), calculated from serum creatinine, bilirubin and International Normalized Ratio (INR), is a promising screening tool corresponding to Child-Pugh Score (CPS) for drug adjustment. We tested the feasibility of MELD as an automatic screening tool accounting for correct calculation, interfering factors (IF) and detection of patients corresponding to CPS-B/C potentially requiring drug adjustment.We retrospectively calculated MELD for a 3-month cohort of surgical patients and assessed need for adjustment of MELD parameters to standard values. IF for INR (oral anticoagulants) and serum creatinine (renal insufficiency (RI; eGFR60 ml/min/1.73m²); as well as drugs elevating creatinine levels (DECL)) and the number of patients with MELD scores corresponding to CPS-B/C were analysed. For MELD ≥7.5, liver and bile diagnoses were recorded.Of 1183 patients, MELD was calculable for 761 (64%; median 7.5, range 6.4-36.8). Parameters had to be adjusted for 690 (91%) patients. IF of parameters were RI in 172 (23%), INR-elevating drugs in 105 (14%) and DECL in 33 (4%) patients. Of 335 (44%) patients with MELD ≥7.5, 122 (36%) had documented liver or bile diagnoses. MELD 10-15 (corresponding to CPS-B) was found for 105 (14%), MELD ≥15 (corresponding to CPS-C) for 66 (9%) of the 761 patients with a calculated MELD. Referred to all patients, drug adjustments due to possible HI were recommendable for 14% of patients with suspected CPS-B/C.MELD is a feasible screening tool for HI as a risk factor for drug safety at hospital admission when appropriately considering correct parameter adjustment and RI and INR-elevating drugs as IF. Further evaluation of sensitivity and specificity is needed.

Introduction: Polypharmacy is increasingly common, and associated with undesirable consequences. Polypharmacy management necessitates balancing therapeutic benefits and risks, and varying clinical and patient priorities. Current guidance for managing polypharmacy is not supported by high quality evidence. The aim of the Improving Medicines use in People with Polypharmacy in Primary Care (IMPPP) trial is to evaluate the effectiveness of an intervention to optimise medication use for patients with polypharmacy in a general practice setting. Methods: This trial will use a multicentre, open-label, cluster-randomised controlled approach, with two parallel groups. Practices will be randomised to a complex intervention comprising structured medication review (including interprofessional GP/pharmacist treatment planning and patient-facing review) supported by performance feedback, financial incentivisation, clinician training and clinical informatics (intervention), or usual care (control). Patients with polypharmacy and triggering potentially inappropriate prescribing (PIP) indicators will be recruited in each practice using a computerised search of health records. 37 practices will recruit 50 patients, and review them over a 26-week intervention delivery period. The primary outcome is the mean number of PIP indicators triggered per patient at 26 weeks follow-up, determined objectively from coded GP electronic health records. Secondary outcomes will include patient reported outcome measures, and health and care service use. The main intention-to-treat analysis will use linear mixed effects regression to compare number of PIP indicators triggered at 26 weeks post-review between groups, adjusted for baseline (pre-randomisation) values. A nested process evaluation will explore implementation of the intervention in primary care. Ethics and dissemination: The protocol and associated study materials have been approved by the Wales REC 6, NHS Research Ethics Committee (REC reference 19/WA/0090), host institution and Health Research Authority. Research outputs will be published in peer-reviewed journals and relevant conferences, and additionally disseminated to patients and the public, clinicians, commissioners and policy makers. ISRCTN Registration: 90146150 (28/03/2019)

While studies have reported pharmacists' perspectives of research involvement, almost all are limited by sector, have little focus on research translation and have not incorporated behavior change theory. The objective of this research was to determine pharmacists' views and experiences of research conduct, dissemination and translation. This was an electronic cross-sectional survey of pharmacists across six Scottish health board areas. Survey items were: demographics; research activities (e.g. conduct, dissemination) in the last two years; research interests, experience and confidence in research tasks (e.g. proposal writing, data collection); and Likert statements on research conduct, dissemination and the translation of research findings into practice. Conduct/dissemination and translation items were based on the Theoretical Domains Framework (TDF). Data were analysed using descriptive and inferential statistics, and principal component analysis (PCA) of TDF items. Following determination of internal consistency, scores for each component were calculated. The response rate was 19.4% (136/701), with 17 (12.5%) currently involved in research. Responses were more positive for interest in research than experience or confidence. PCA of research conduct/dissemination items identified three internally-reliable components of support/opportunities, motivation/outcomes, and roles/characteristics. Component scores for support/opportunities to participate in research were most negative. PCA of translation items identified three internally-reliable components of current practices/abilities, consequences and support. Scores for all three components were positive, being most positive for consequences of research translation. Those in secondary care, with a postgraduate qualification and prescription responsibilities scored higher for interest, experience, confidence and for most components (p < 0.05). In conclusion, a minority of pharmacists are involved in research conduct/dissemination and these are more likely to be highly-qualified individuals, based in secondary care. Given the need to develop and evaluate new models of pharmaceutical care, involvement should be extended to all practice settings. Study findings could be used to develop behavior change interventions targeting individuals and organizations.

Funding: The workshop was cofunded by National Institute of Health Research Health Technology Assessment Programme, Clinical Practice Research Datalink and Health Data Research UK; MRC grant MC_UU_12023/24 funded the salary of Matthew Sydes. Rationale Clinical trials are the gold standard for testing interventions. COVID-19 has further raised their public profile and emphasised the need to deliver better, faster, more efficient trials for patient benefit. Considerable overlap exists between data required for trials and data already collected routinely in electronic healthcare records (EHRs). Opportunities exist to use these in innovative ways to decrease duplication of effort and speed trial recruitment, conduct and follow-up. Approach The National Institute of Health Research (NIHR), Health Data Research UK and Clinical Practice Research Datalink co-organised a national workshop to accelerate the agenda for ‘data-enabled clinical trials’. Showcasing successful examples and imagining future possibilities, the plenary talks, panel discussions, group discussions and case studies covered: design/feasibility; recruitment; conduct/follow-up; collecting benefits/harms; and analysis/interpretation. Reflection Some notable studies have successfully accessed and used EHR to identify potential recruits, support randomised trials, deliver interventions and supplement/replace trial-specific follow-up. Some outcome measures are already reliably collected; others, like safety, need detailed work to meet regulatory reporting requirements. There is a clear need for system interoperability and a ‘route map’ to identify and access the necessary datasets. Researchers running regulatory-facing trials must carefully consider how data quality and integrity would be assessed. An experience-sharing forum could stimulate wider adoption of EHR-based methods in trial design and execution. Discussion EHR offer opportunities to better plan clinical trials, assess patients and capture data more efficiently, reducing research waste and increasing focus on each trial’s specific challenges. The short-term emphasis should be on facilitating patient recruitment and for postmarketing authorisation trials where research-relevant outcome measures are readily collectable. Sharing of case studies is encouraged. The workshop directly informed NIHR’s funding call for ambitious data-enabled trials at scale. There is the opportunity for the UK to build upon existing data science capabilities to identify, recruit and monitor patients in trials at scale. Publisher PDF

The treatment of elderly patients with dizziness/vertigo/balance disorders (VDB) can be challenging for their general practitioner. Patient-centered care with a focus on self-management support could be a possible approach. Primary objective of this study was to investigate the correlations between quality of primary care and health-related quality of life (HRQOL) from the patient's perspective.Data had been collected in the area of Munich and in the area of Dresden between 2017 and 2019. Questionnaires of n = 157 elderly patients from primary care practices in Munich and Dresden were evaluated. Multiple linear regression was used to analyse quality of care, physical activity, depression, and their correlations with HRQOL.In this cohort of patients aged 65 to 94 no significant correlation between quality of care and HRQOL could be detected. Depression correlated negatively with HRQOL, whereas physical activity showed a positive correlation with HRQOL.Physical activity can be beneficial for elderly dizzy patients' HRQOL. Additionally, a potential depression should be taken into account when treating patients with dizziness to improve their HRQOL. The results can be well transferred to elderly patients with VDB. Analysing more patients however, could increase the significance of the results.Hintergrund: Die Behandlung von älteren Patienten mit Schwindelbeschwerden kann eine Herausforderung für den Hausarzt darstellen. Ein möglicher Ansatz ist eine patientenzentrierte Versorgung mit Fokus auf der Unterstützung des Selbstmanagements. Die Untersuchung des Zusammenhangs zwischen der Versorgungsqualität durch den Hausarzt und der gesundheitsbezogenen Lebensqualität (HRQOL) aus der Patientenperspektive war primäres Ziel dieser Analyse. Methode: Die Datenerhebung fand zwischen 2017 und 2019 im Raum München und im Raum Dresden statt. Insgesamt wurden Fragebögen von n = 157 Patienten mit Schwindel aus der hausärztlichen Versorgung analysiert. Die Versorgungsqualität, körperliche Aktivität, Depressivität und deren Zusammenhang mit der HRQOL wurden mithilfe multipler linearer Regressionsmodelle im Quer- und Längsschnitt (nach 6 Monaten) betrachtet. Ergebnisse: In der beobachteten Kohorte von Patienten zwischen 65-94 Jahren ergaben sich keine signifikanten Zusammenhänge zwischen der Versorgungsqualität und der HRQOL. Es zeigte sich ein negativer Zusammenhang zwischen Depressivität und HRQOL und ein positiver Zusammenhang zwischen körperlicher Aktivität und HRQOL. Schlussfolgerungen: Für die HRQOL älterer Patienten mit Schwindel kann körperliche Aktivität von Vorteil sein. Auch sollte zur Verbesserung der HRQOL eine mögliche Depressivität bei der Behandlung von Patienten mit Schwindel berücksichtigt werden. Die Ergebnisse lassen sich sehr gut auf ältere hausärztliche Patienten mit Schwindel übertragen. Die Untersuchung einer größeren Kohorte könnte die Aussagekraft der Ergebnisse noch erhöhen. Schlüsselwörter: Schwindel, gesundheitsbezogene Lebensqualität, Versorgungsqualität, körperliche Aktivität, DepressivitätEingereicht am 1.12.2020 - Revision akzeptiert am 2.2.2021.

Study Objective Long‐term intake of proton pump inhibitors (PPIs) might increase the risk of cardiovascular events. One suggested mechanism is that PPIs inhibit the enzyme dimethylarginine dimethylaminohydrolase (DDAH) and thereby block the degradation of endothelial asymmetrical dimethylarginine (ADMA). Excess ADMA in turn leads to impaired endothelial nitric oxide (NO) generation. So far, this mechanism has only been established in human cell cultures. Previous studies that examined this pathway in human populations measured circulating ADMA and found no association with PPI use and excess plasma ADMA. But in a recent study, plasma ADMA was not correlated with intracellular ADMA. We therefore focused on changes in plasma citrulline as an indicator for potential DDAH inhibition. Design We analyzed the association between regular daily PPI intake and flow‐mediated dilation (FMD) of the brachial artery as well as plasma concentrations of citrulline, arginine, ADMA, and symmetric dimethylarginine using inverse probability weighting to adjust for confounding and censoring. Data Source Data of 1298 participants from two independent cohorts of the population‐based Study of Health in Pomerania were used. Participants Participants of the population‐based Study of Health in Pomerania are a stratified random sample of the study region. Exposure Regular daily intake of PPIs. Measurements FMD of the brachial artery and plasma concentrations of citrulline, arginine, ADMA, and symmetric dimethylarginine. Main Results Eighty‐seven participants (57.5% female) were regular daily users of PPIs. In the fully adjusted models, associations were identified for FMD and plasma citrulline concentrations. PPI users revealed a 0.99% (95% CI: −1.96 to −0.02) lower FMD and 3.03 µmol/L (95% CI: −4.96 to −1.10) lower plasma citrulline levels as compared to non‐users. Conclusion Our data provide evidence that long‐term intake of PPIs might inhibit human DDAH activity, resulting in impaired endothelial NO production and reduced vascular function. In the long run, this might explain an increased risk for cardiovascular diseases associated with long‐term PPI use.

Insufficient vaccination rates against pneumococcal disease are a major problem in primary health care, especially in adult patients. Shared decision-making (SDM) may address major barriers to vaccination. The objective of this review was to assess the impact of SDM on pneumococcal vaccination rates in adult patients. We conducted a systematic literature search in MEDLINE, EMBASE, CENTRAL, PsycINFO, and ERIC. RCTs and cluster RCTs were included, if they aimed to enhance pneumococcal vaccination rates in adult patients and comprised a personal interaction between health care provider (HCP) and patient. Three further aspects of the SDM process (patient activation, bi-directional exchange of information and bi-directional deliberation) were assessed. A meta-analysis was conducted for the effects of interventions on vaccination rates. We identified eight studies meeting the inclusion criteria. The pooled effect size was OR (95% CI): 2.26 (1.60–3.18) comparing intervention and control groups. Our findings demonstrate the efficacy of interventions that enable a SDM process to enhance pneumococcal vaccination rates; although, the quality of evidence was low. In exploratory subgroup analyses, we concluded that an impersonal patient activation and an exchange of information facilitated by nurses are sufficient to increase vaccination rates against pneumococcal disease in adult patients. However, the deliberation of options between physicians and patients seemed to be more effective than deliberation of options between nurses and patients.

Background Development of acute kidney injury (AKI) following the use of antibiotics such as sulphonamides, trimethoprim and aminoglycosides is a frequently described phenomenon. More recently, an association between fluoroquinolone use and AKI has been suggested. The aim of this study was to evaluate the risk of AKI as an unintended consequence of commonly prescribed antibiotics in a large community cohort using a method that fully adjusts for underlying patient characteristics, including potential unmeasured confounders. Methods A self-controlled case study was conducted and included all individuals aged 18 years and over in the Tayside region of Scotland who had a serum creatinine measured between 1 January 2004 and 31 December 2012. AKI episodes were defined using the Kidney Disease: Improving Global Outcomes definition. Data on oral community-prescribed antibiotics (penicillins, cephalosporins, fluoroquinolones, sulphonamides and trimethoprim, macrolides and nitrofurantoin) were collected for all individuals. Incidence rate ratios (IRRs) for AKI associated with antibiotic exposure versus time periods without antibiotic exposure were calculated. Results Combined use of sulphonamides, trimethoprim and nitrofurantoin rose by 47% and incidence of community-acquired AKI rose by 16% between 2008 and 2012. During the study period 12 777 individuals developed 14 900 episodes of AKI in the community, of which 68% was AKI Stage 1, 16% Stage 2 and 16% Stage 3. The IRR of AKI during any antibiotic use was 1.16 [95% confidence interval (CI) 1.10—1.23], and this was highest during sulphonamides or trimethoprim use; IRR 3.07 (95% CI 2.81–3.35). Fluoroquinolone and nitrofurantoin use was not associated with a significantly increased rate of AKI; IRR 1.13 (95% CI 0.94–1.35) and 1.16 (95% CI 0.91–1.50), respectively. Conclusions Incidence of AKI rose by 16% between 2008 and 2012. In the same period the use of sulphonamides, trimethoprim and nitrofurantoin increased by 47%. A significant increased risk of AKI was seen with the use of sulphonamides and trimethoprim, but not with fluoroquinolones or nitrofurantoin.

Polypharmacy describes the concomitant use of multiple medicines and represents a growing global challenge attributable to aging populations with an increasing prevalence of multimorbidity. Polypharmacy can be appropriate but is problematic when the increased risk of harm from interactions between drugs or between drugs and diseases or the burden of administering and monitoring medicines outweighs plausible benefits. Polypharmacy has a substantial economic impact in service demand and hospitalization as well as a detrimental impact on patients’ quality of life. Apart from causing avoidable harm, polypharmacy can also lead to therapeutic failure, with up to 50% of patients who take four or more medications not taking them as prescribed. Guidance is needed to support patients and clinicians in defining and achieving realistic goals of drug treatment, and system change is necessary to aid implementation. This article outlines lessons from two programs that aim to address these challenges: the Scottish polypharmacy guidance on realistic prescribing and the European Union SIMPATHY project.

Aims Regulatory risk communications are important to ensure medication safety, but their impact is poorly understood. The aim was to quantify the impact of UK risk communications on medication use and other outcomes. Methods We conducted a systematic review of studies reporting prescribing/health outcome data relevant to UK regulatory risk communication. Data were reanalysed using interrupted time series regression 12 months after each regulatory intervention. Mean changes were pooled using random-effects generic inverse variance examining the following subgroups: drug withdrawals; restrictions/changes in indications; be aware messages without specific recommendations for action; communication via direct healthcare practitioner communications; communication via drug bulletins. Results Of 11 466 articles screened, 40 studies examining 25 UK regulatory risk communications were included. Product withdrawals, restriction in indications and be aware communications were associated with relative mean changes of -78% (95% confidence interval [CI] -60 to -96%), -34% (95% confidence interval [CI] -12 to -55%) and -11% (95%CI -8 to -15%) in targeted drug prescribing respectively. Direct healthcare professional communications were associated with relative mean changes of -47% (95%CI -27 to -68%) compared to -13% (95%CI -6 to -20%) for drug bulletins. Of 7 studies examining unique health outcomes related to the safety concern, risk communications were associated with a mean -10% (95%CI -3 to -16%) decrease in intended and a 7% (95%CI 4 to 10%) increase in unintended health outcomes. Discussion UK regulatory risk communications were associated with significant changes in targeted prescribing and potential changes in clinical outcomes. Further research is needed to systematically study the impact of regulatory interventions.

ObjectivesHealthcare is a complex system, so quality improvement will commonly lead to unintended consequences which are rarely evaluated. In previous qualitative work, we proposed a framework for considering the range of these potential consequences, in terms of their desirability and the extent to which they were predictable or expected during planning. This paper elaborates on the previous findings, using consensus methods to examine what consequences should be identified, why and how to prioritise, evaluate and interpret all identified consequences, and what stakeholders should be involved throughout this process.DesignTwo-round modified Delphi consensus study.Setting and participantsBoth rounds were completed by 60 panellists from an academic, clinical or management background and experience in designing, implementing or evaluating quality improvement programmes.ResultsPanellists agreed that trade-offs (expected undesirable consequences) and unpleasant surprises (unexpected undesirable consequences) should be actively considered. Measurement of harmful consequences for patients, and those with high workload or financial impact was prioritised, and their evaluation could also involve the use of qualitative methods. Clinical teams were agreed as important to involve at all stages, from identifying potential consequences, prioritising which of those to systematically evaluate, undertaking appropriate evaluation and interpreting the findings. Patients were necessary in identifying consequences, managers in identifying and prioritising, and improvement advisors in interpreting the data.ConclusionThere was consensus that a balanced approach to considering all the consequences of improvement can be achieved by carefully considering predictable trade-offs from the outset and deliberately pausing after implementation to identify any unexpected surprises and make an informed decision as to whether quantitative or qualitative evaluation is needed and feasible. Stakeholders’ roles in in the process of identifying, prioritising, evaluating and interpreting potential consequences should be explicitly addressed within planning and revisited during and after implementation.

Background The definitions that are being used for the terms 'clinical pharmacy' and 'pharmaceutical care' seem to have a certain overlap. Responsibility for therapy outcomes seems to be especially linked to the latter term. Both terms need clarification before a proper definition of clinical pharmacy can be drafted. Objective To identify current disagreements regarding the term 'Clinical Pharmacy' and its relationship to 'Pharmaceutical Care' and to assess to which extent pharmacists with an interest in Clinical Pharmacy are willing to accept responsibility for drug therapy outcomes. Setting The membership of the European Society of Clinical Pharmacy. Methods A total of 1,285 individuals affiliated with the European Society of Clinical Pharmacy were invited by email to participate in an online survey asking participants to state whether certain professional activities, providers, settings, aims and general descriptors constituted (a) 'Clinical Pharmacy only', (b) 'Pharmaceutical Care only', (c) 'both' or (d) 'neither'. Further questions examined pharmacists' willingness to accept ethical or legal responsibility for drug therapy outcomes, under current and ideal working conditions. Main outcome measures Level of agreement with a number of statements. Results There was disagreement (

ObjectivesThe quality and safety of drug therapy in primary care are global concerns. The Pharmacist and Data-Driven Quality Improvement in Primary Care (P-DQIP) intervention aims to improve prescribing safety via an informatics tool, which facilitates proactive management of drug therapy risks (DTRs) by health-board employed pharmacists with established roles in general practices. Study objectives were (1) to identify and prioritise factors that could influence P-DQIP implementation from the perspective of practice pharmacists and (2) to identify potentially effective, acceptable and feasible strategies to support P-DQIP implementation.DesignSemistructured face-to-face interviews using a Theoretical Domains Framework informed topic guide. The framework method was used for data analysis. Identified implementation factors were prioritised for intervention based on research team consensus. Candidate intervention functions, behavioural change techniques (BCTs) and policies targeting these were identified from the behavioural change wheel. The final intervention content and modes of delivery were agreed with local senior pharmacists.SettingGeneral practices from three Health and Social Care Partnerships in National Health Service (NHS) Tayside.Participants14 NHS employed practice pharmacists.ResultsIdentified implementation factors were linked to thirteen theoretical domains (all except intentions) and six (skill, memory/attention/decision making, behavioural regulation, reinforcement, environmental context/resources, social influences) were prioritised. Three intervention functions (training, enablement and environmental restructuring) were relevant and were served by two policy categories (guidelines, communication/marketing) and eight BCTs (instructions on how to perform a behaviour, problem solving, action planning, prompt/cues, goal setting, self-monitoring, feedback and restructuring the social environment). Intervention components encompass an informatics tool, written educational material, a workshop for pharmacists, promotional activities and small financial incentives.ConclusionsThis study explored pharmacists’ perceptions of implementation factors which could influence management of DTRs in general practices to inform implementation of P-DQIP, which will initially be implemented in one Scottish health board with parallel evaluation of effectiveness and implementation.

Objectives The cluster randomised trial of the Data-driven Quality Improvement in Primary Care (DQIP) intervention showed that education, informatics and financial incentives for general medical practices to review patients with ongoing high-risk prescribing of non-steroidal anti-inflammatory drugs and antiplatelets reduced the primary end point of high-risk prescribing by 37%, where both ongoing and new high-risk prescribing were significantly reduced. This quantitative process evaluation examined practice factors associated with (1) participation in the DQIP trial, (2) review activity (extent and nature of documented reviews) and (3) practice level effectiveness (relative reductions in the primary end point). Setting/participants Invited practices recruited (n=33) and not recruited (n=32) to the DQIP trial in Scotland, UK. Outcome measures (1) Characteristics of recruited versus non-recruited practices. Associations of (2) practice characteristics and ‘adoption’ (self-reported implementation work done by practices) with documented review activity and (3) of practice characteristics, DQIP adoption and review activity with effectiveness. Results (1) Recruited practices had lower performance in the quality and outcomes framework than those declining participation. (2) Not being an approved general practitioner training practice and higher self-reported adoption were significantly associated with higher review activity. (3) Effectiveness ranged from a relative increase in high-risk prescribing of 24.1% to a relative reduction of 77.2%. High-risk prescribing and DQIP adoption (but not documented review activity) were significantly associated with greater effectiveness in the final multivariate model, explaining 64.0% of variation in effectiveness. Conclusions Intervention implementation and effectiveness of the DQIP intervention varied substantially between practices. Although the DQIP intervention primarily targeted review of ongoing high-risk prescribing, the finding that self-reported DQIP adoption was a stronger predictor of effectiveness than documented review activity supports that reducing initiation and/or re-initiation of high-risk prescribing is key to its effectiveness. Trial registration number NCT01425502; Post-results.