Implementation of a virtual community of practice to promote the empowerment of middle-aged people with multimorbidity: study protocol of a randomised controlled trial.

INTRODUCTION: Empowering people living with multimorbidity (multiple chronic conditions) to gain greater confidence in managing their health can enhance their quality of life. Education focused on self-management is a key tool for fostering patient empowerment and is mostly provided on an individual basis. Virtual communities of practice (VCoP) present a unique opportunity for online education in chronic condition self-management within a social context. This research aims to evaluate the effectiveness/cost-effectiveness of individualised, online self-management education compared with VCoP among middle-aged individuals living with multiple chronic conditions. METHODS AND ANALYSIS: People aged 30-60, living with ≥2 chronic conditions and receiving care in primary care (PC) centres and outpatient hospital-based clinics in Madrid and Canary Islands will enrol in an 18-month parallel-design, blinded (intervention assessment and data analysts), pragmatic (adhering to the intention-to-treat principle), individually randomised trial. The trial will compare two 12-month web-based educational offers of identical content; one delivered individually (control) and the other with online social interaction (VCoP, intervention). Using repeated measures mixed linear models, with the patient as random effect and allocation groups and time per group as fixed effects, we will estimate between-arm differences in the change in Patient Activation Measure from baseline to 12 months (primary endpoint), including measurements at 6-month and 18-month follow-up. Other outcomes will include measures of depression and anxiety, treatment burden, quality of life. In addition to a process evaluation of the VCoP, we will conduct an economic evaluation estimating the relative cost-effectiveness of the VCoP from the perspectives of both the National Health System and the Community. ETHICS AND DISSEMINATION: The trial was approved by Clinical Research Ethics Committees of Gregorio Marañón University Hospital in Madrid/Nuestra Señora Candelaria University Hospital in Santa Cruz de Tenerife. The results will be disseminated through workshops, policy briefs, peer-reviewed publications and local/international conferences. TRIAL REGISTRATION NUMBER: NCT06046326.

Informational continuity of medication management in transitions of care: Qualitative interviews with stakeholders from the HYPERION-TransCare study.

BACKGROUND: The transition of patients between inpatient and outpatient care can lead to adverse events and medication-related problems due to medication and communication errors, such as medication discontinuation, the frequency of (re-)hospitalizations, and increased morbidity and mortality. Older patients with multimorbidity and polypharmacy are particularly at high risk during transitions of care. Previous research highlighted the need for interventions to improve transitions of care in order to support information continuity, coordination, and communication. The HYPERION-TransCare project aims to improve the continuity of medication management for older patients during transitions of care. METHODS AND FINDINGS: Using a qualitative design, 32 expert interviews were conducted to explore the perspectives of key stakeholders, which included healthcare professionals, patients and one informal caregiver, on transitions of care. Interviews were conducted between October 2020 and January 2021, transcribed verbatim and analyzed using content analysis. We narratively summarized four main topics (stakeholders' tasks, challenges, ideas for solutions and best practice examples, and patient-related factors) and mapped them in a patient journey map. Lacking or incomplete information on patients' medication and health conditions, inappropriate communication and collaboration between healthcare providers within and across settings, and insufficient digital support limit the continuity of medication management. CONCLUSIONS: The study confirms that medication management during transitions of care is a complex process that can be compromised by a variety of factors. Legal requirements and standardized processes are urgently needed to ensure adequate exchange of information and organization of medication management before, during and after hospital admissions. Despite the numerous barriers identified, the findings indicate that involved healthcare professionals from both the inpatient and outpatient care settings have a common understanding.

Digital Medication Management in Polypharmacy­Findings of a Cluster-Randomized, Controlled Trial With a Stepped-Wedge Design in Primary Care Practices (AdAM).

BACKGROUND: Inappropriate drug prescriptions for patients with polypharmacy can have avoidable adverse consequences. We studied the effects of a clinical decision-support system (CDSS) for medication management on hospitalizations and mortality. METHODS: This stepped-wedge, cluster-randomized, controlled trial involved an open cohort of adult patients with polypharmacy in primary care practices (=clusters) in Westphalia-Lippe, Germany. During the period of the intervention, their medication lists were checked annually using the CDSS. The CDSS warns against inappropriate prescriptions on the basis of patient-related health insurance data. The combined primary endpoint consisted of overall mortality and hospitalization for any reason. The secondary endpoints were mortality, hospitalizations, and high-risk prescription. We analyzed the quarterly health insurance data of the intention-to-treat population with a mixed logistic model taking account of clustering and repeated measurements. Sensitivity analyses addressed effects of the COVID-19 pandemic and other effects. RESULTS: 688 primary care practices were randomized, and data were obtained on 42 700 patients over 391 994 quarter years. No significant reduction was found in either the primary endpoint (odds ratio [OR] 1.00; 95% confidence interval [0.95; 1.04]; p = 0.8716) or the secondary endpoints (hospitalizations: OR 1.00 [0.95; 1.05]; mortality: OR 1.04 [0.92; 1.17]; high-risk prescription: OR 0.98 [0.92; 1.04]). CONCLUSION: The planned analyses did not reveal any significant effect of the intervention. Pandemic-adjusted analyses yielded evidence that the mortality of adult patients with polypharmacy might potentially be lowered by the CDSS. Controlled trials with appropriate follow-up are needed to prove that a CDSS has significant effects on mortality in patients with polypharmacy.

Recommendations for the primary prevention of atherosclerotic cardiovascular disease in primary care: study protocol for a systematic guideline review.

INTRODUCTION: Atherosclerotic cardiovascular disease (ASCVD) was the main cause of death in Germany in 2021, with major risk factors (ie, hypertension, diabetes, dyslipidaemia, obesity and certain lifestyle factors) being highly prevalent. Preventing ASCVD by assessment and modification of these risk factors is an important challenge for general practitioners. This study aims to systematically review and synthesise recent recommendations of national and international guidelines regarding the primary prevention of ASCVD in adults in primary care. METHODS AND ANALYSIS: We will conduct a systematic review of clinical practice guidelines (CPGs) to evaluate primary prevention strategies for ASCVD. CPGs will be retrieved from MEDLINE and the Turning Research Into Practice database, guideline-specific databases and websites of guidelines-producing societies, with searches limited to publications from 2016 onwards. We will include CPGs in English, Spanish, German or Dutch languages that provide evidence-based recommendations for ASCVD prevention. The study population will include adults without diagnosed ASCVD. Two independent reviewers will assess guideline eligibility and quality by means of the mini-checklist MiChe, and extract study characteristics and relevant recommendations for further consistency analysis. A third reviewer will resolve disagreements. Findings will be presented as a narrative synthesis and in tabular form. ETHICS AND DISSEMINATION: This review does not require ethical approval. Our systematic review will inform the CPG of the German College of General Practitioners and Family Physicians on the primary prevention of ASCVD. The review results will also be disseminated through publications in peer-reviewed journals and presentations at local, national and international conferences. PROSPERO REGISTRATION NUMBER: CRD42023394605.

Factors facilitating the implementation of a clinical decision support system in primary care practices: a fuzzy set qualitative comparative analysis.

BACKGROUND: Understanding how to implement innovations in primary care practices is key to improve primary health care. Aiming to contribute to this understanding, we investigate the implementation of a clinical decision support system (CDSS) as part of the innovation fund project AdAM (01NVF16006). Originating from complexity theory, the practice change and development model (PCD) proposes several interdependent factors that enable organizational-level change and thus accounts for the complex settings of primary care practices. Leveraging the PCD, we seek to answer the following research questions: Which combinations of internal and external factors based on the PCD contribute to successful implementation in primary care practices? Given these results, how can implementation in the primary care setting be improved? METHODS: We analyzed the joint contributions of internal and external factors on implementation success using qualitative comparative analysis (QCA). QCA is a set-theoretic approach that allows to identify configurations of multiple factors that lead to one outcome (here: successful implementation of a CDSS in primary care practices). Using survey data, we conducted our analysis based on a sample of 224 primary care practices. RESULTS: We identified two configurations of internal and external factors that likewise enable successful implementation. The first configuration enables implementation based on a combination of Strong Inside Motivation, High Capability for Development, and Strong Outside Motivation; the second configuration based on a combination of Strong Inside Motivators, Many Options for Development and the absence of High Capability for Development. CONCLUSION: In line with the PCD, our results demonstrate the importance of the combination of internal and external factors for implementation outcomes. Moreover, the two identified configurations show that different ways exist to achieve successful implementation in primary care practices. TRIAL REGISTRATION: AdAM was registered on ClinicalTrials.gov ( NCT03430336 ) on February 6, 2018.

Amitriptyline's anticholinergic adverse drug reactions-A systematic multiple-indication review and meta-analysis.

BACKGROUND: Half the US population uses drugs with anticholinergic properties. Their potential harms may outweigh their benefits. Amitriptyline is among the most frequently prescribed anticholinergic medicinal products, is used for multiple indications, and rated as strongly anticholinergic. Our objective was to explore and quantify (anticholinergic) adverse drug reactions (ADRs) in patients taking amitriptyline vs. placebo in randomized controlled trials (RCTs) involving adults and healthy individuals. METHODS: We searched electronic databases from their inception until 09/2022, and clinical trial registries from their inception until 09/2022. We also performed manual reference searches. Two independent reviewers selected RCTs with ≥100 participants of ≥18 years, that compared amitriptyline (taken orally) versus placebo for all indications. No language restrictions were applied. One reviewer extracted study data, ADRs, and assessed study quality, which two others verified. The primary outcome was frequency of anticholinergic ADRs as a binary outcome (absolute number of patients with/without anticholinergic ADRs) in amitriptyline vs. placebo groups. RESULTS: Twenty-three RCTs (mean dosage 5mg to 300mg amitriptyline/day) and 4217 patients (mean age 40.3 years) were included. The most frequently reported anticholinergic ADRs were dry mouth, drowsiness, somnolence, sedation, fatigue, constitutional, and unspecific anticholinergic ADRs. Random-effects meta-analyses showed anticholinergic ADRs had a higher odd's ratio for amitriptyline versus placebo (OR = 7.41; [95% CI, 4.54 to 12.12]). Non-anticholinergic ADRs were as frequent for amitriptyline as placebo. Meta-regression analysis showed anticholinergic ADRs were not dose-dependent. DISCUSSION: The large OR in our analysis shows that ADRs indicative of anticholinergic activities can be attributed to amitriptyline. The low average age of participants in our study may limit the generalizability of the frequency of anticholinergic ADRs in older patients. A lack of dose-dependency may reflect limited reporting of the daily dosage when the ADRs occurred. The exclusion of small studies (<100 participants) decreased heterogeneity between studies, but may also have reduced our ability to detect rare events. Future studies should focus on older people, as they are more susceptible to anticholinergic ADRs. REGISTRATION: PROSPERO: CRD42020111970.

The Relationship of Continuity of Care, Polypharmacy and Medication Appropriateness: A Systematic Review of Observational Studies.

INTRODUCTION: Worldwide, polypharmacy and medication appropriateness-related outcomes (MARO) are growing public health concerns associated with potentially inappropriate prescribing, adverse health effects, and avoidable costs to health systems. Continuity of care (COC) is a cornerstone of high-quality care that has been shown to improve patient-relevant outcomes. However, the relationship between COC and polypharmacy/MARO has not been systematically explored. OBJECTIVE: The aim of this systematic review was to investigate the operationalization of COC, polypharmacy, and MARO as well as the relationship between COC and polypharmacy/MARO. METHODS: We performed a systematic literature search in PubMed, Embase, and CINAHL. Quantitative observational studies investigating the associations between COC and polypharmacy and/or COC and MARO by applying multivariate regression analysis techniques were eligible. Qualitative or experimental studies were not included. Information on the definition and operationalization of COC, polypharmacy, and MARO and reported associations was extracted. COC measures were assigned to the relational, informational, or management dimension of COC and further classified as objective standard, objective non-standard, or subjective. Risk of bias was assessed by using the NIH Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. RESULTS: Twenty-seven studies were included. Overall, substantial differences existed in terms of the COC dimensions and related COC measures. Relational COC was investigated in each study, while informational and management COC were only covered among three studies. The most frequent type of COC measure was objective non-standard (n = 16), followed by objective standard (n = 11) and subjective measures (n = 3). The majority of studies indicated that COC is strongly associated with both polypharmacy and MARO, such as potentially inappropriate medication (PIM), potentially inappropriate drug combination (PIDC), drug-drug interaction (DDI), adverse drug events (ADE), unnecessary drug use, duplicated medication, and overdose. More than half of the included studies (n = 15) had a low risk of bias, while five studies had an intermediate and seven studies a high risk of bias. CONCLUSIONS: Differences regarding the methodological quality of included studies as well as the heterogeneity in terms of the operationalization and measurement of COC, polypharmacy, and MARO need to be considered when interpreting the results. Yet, our findings suggest that optimizing COC may be helpful in reducing polypharmacy and MARO. Therefore, COC should be acknowledged as an important risk factor for polypharmacy and MARO, and the importance of COC should be considered when designing future interventions targeting these outcomes.

Anticholinergic burden measures, symptoms, and fall-associated risk in older adults with polypharmacy: Development and validation of a prognostic model.

BACKGROUND: Anticholinergic burden has been associated with adverse outcomes such as falls. To date, no gold standard measure has been identified to assess anticholinergic burden, and no conclusion has been drawn on which of the different measure algorithms best predicts falls in older patients from general practice. This study compared the ability of five measures of anticholinergic burden to predict falls. To account for patients' individual susceptibility to medications, the added predictive value of typical anticholinergic symptoms was further quantified in this context. METHODS AND FINDINGS: To predict falls, models were developed and validated based on logistic regression models created using data from two German cluster-randomized controlled trials. The outcome was defined as "≥ 1 fall" vs. "no fall" within a 6-month follow-up period. Data from the RIME study (n = 1,197) were used in model development, and from PRIMUM (n = 502) for external validation. The models were developed step-wise in order to quantify the predictive ability of anticholinergic burden measures, and anticholinergic symptoms. In the development set, 1,015 patients had complete data and 188 (18.5%) experienced ≥ 1 fall within the 6-month follow-up period. The overall predictive value of the five anticholinergic measures was limited, with neither the employed anticholinergic variable (binary / count / burden), nor dose-dependent or dose-independent measures differing significantly in their ability to predict falls. The highest c-statistic was obtained using the German Anticholinergic Burden Score (0.73), whereby the optimism-corrected c-statistic was 0.71 after interval validation using bootstrapping and 0.63 in the external validation. Previous falls and dizziness / vertigo had the strongest prognostic value in all models. CONCLUSIONS: The ability of anticholinergic burden measures to predict falls does not appear to differ significantly, and the added value they contribute to risk classification in fall-prediction models is limited. Previous falls and dizziness / vertigo contributed most to model performance.

Prescribing Cascades: How to Detect Them, Prevent Them, and Use Them Appropriately.

BACKGROUND: A prescribing cascade is the treatment of an adverse drug reaction (ADR) with another drug. In this review, we discuss (a) the different types of prescribing cascade and (b) the measures that can be taken so that they will be recognized and dealt with appropriately, both in the hospital and in the outpatient setting. METHODS: This review is based on pertinent publications retrieved by a selective literature search. RESULTS: The literature distinguishes intentional from unintentional prescribing cascades, and appropriate from inappropriate ones. We further distinguish prophylactic from therapeutic prescribing cascades and draw a line between those that are necessary and those that are merely appropriate. The following main questions are essential for dealing with prescribing cascades appropriately: (1) Did the precipitating drug cause a clinically relevant ADR or risk of an ADR? (2) Is the precipitating drug still indicated? (3) Can an ADR be avoided by altering the treatment with the precipitating drug, or by (4) switching to another drug instead? (5) Can the drug used to treat the ADR actually affect it beneficially? (6) Do the benefits of the prescribing cascade outweigh its risks? CONCLUSION: Prescribing cascades are not problematic in themselves; on the contrary, they are sometimes a necessary part of good prescribing practice. There is still a lack of practically implementable instruments to help physicians detect prescribing cascades reliably, assess them properly, and put them to appropriate use.

Digital participatory workshops with patients and health professionals to develop an intervention for the management of polypharmacy: results from a mixed-methods evaluation and methodological conclusions.

BACKGROUND: In the COVID-19 pandemic, numerous researchers postponed their patient and public involvement (PPI) activities. This was mainly due to assumptions on patients' willingness and skills to participate digitally. In fact, digital PPI workshops differ from in-person meetings as some forms of non-verbal cues and body language may be missing and technical barriers may exist. Within our project HYPERION-TransCare we adapted our PPI workshop series for intervention development to a digital format and assessed whether these digital workshops were feasible for patients, health care professionals and researchers. METHODS: We used a digital meeting tool that included communication via audio, video and chat. Discussions were documented simultaneously on a digital white board. Technical support was provided via phone and chat during the workshops and with a technical introduction workshop in advance. The workshop evaluation encompassed observation protocols, participants' feedback via chat after each workshop on their chance to speak and the usability of the digital tools, and telephone interviews on patients' and health professionals' experiences after the end of the workshop series. RESULTS: Observation protocols showed an active role of moderators in verbally encouraging every participant to get involved. Technical challenges occurred, but were in most cases immediately addressed and solved. Participants median rating of their chance to speak and the usability of the digital tool was "very good". In the evaluation interviews participants reported a change of perspective and mutual understanding as a main benefit from the PPI workshops and described the atmosphere as inclusive and on equal footing. Benefits of the digital format such as overcoming geographical distance, saving time and combining workshop participation with professional or childcare obligations were reported. Technical support was stressed as a pre-condition for getting actively involved in digital PPI. CONCLUSIONS: Digital formats using different didactic and documentation techniques, accompanied by technical support, can foster active patient and public involvement. The advantages of digital PPI formats such as geographical flexibility and saving time for participants as well as the opportunity to prepare and hold workshops in geographically stretched research teams persists beyond the pandemic and may in some cases outweigh the advantages of in-person communication.

Digital patient and public involvement (PPI) activities differ from in-person meetings. For example, some forms of non-verbal cues and body language are limited and technical barriers may exist. Therefore, some research teams were hesitant to switch to a digital PPI format during the COVID-19 pandemic and postponed their PPI activities.In this paper, we aim to describe, how we adapted a PPI workshop series to a digital format, how patients and health care professionals experienced these digital workshops, and which conclusions we have drawn for future digital PPI activities. The workshop evaluation encompassed workshop observation protocols, participants' feedback via chat on their chance to speak and the feasibility of the digital tools, and telephone interviews on participants' experiences.The study results showed that moderators had an active role in verbally encouraging every participant to get involved. Technical challenges occurred, but were in most cases immediately addressed and solved. Most participants rated their chance to speak and the feasibility of the digital format as "very good". They described the atmosphere as inclusive and on equal footing without hierarchy between different stakeholder groups. Participants reported benefits of the digital format such as overcoming geographical distance, saving time and combining workshop participation with professional or childcare obligations. They stressed technical support as a condition for getting actively involved in digital PPI.We conclude that some advantages of digital PPI may persist beyond the pandemic. Therefore, we encourage research teams to discuss the question of digital or in-person PPI with the involved patients and health professionals and decide on a case-by-case basis.

Stakeholder Perspectives on the Development and Implementation of a Polypharmacy Management Program in Germany: Results of a Qualitative Study.

Structured management programs have been developed for single diseases but rarely for patients with multiple medications. We conducted a qualitative study to investigate the views of stakeholders on the development and implementation of a polypharmacy management program in Germany. Overall, we interviewed ten experts in the fields of health policy and clinical practice. Using content analysis, we identified inclusion criteria for the selection of suitable patients, the individual elements that should make up such a program, healthcare providers and stakeholders that should be involved, and factors that may support or hinder the program's implementation. All stakeholders were well aware of polypharmacy-related risks and challenges, as well as the urgent need for change. Intervention strategies should address all levels of care and include all concerned patients, caregivers, healthcare providers and stakeholders, and involved parties should agree on a joint approach.

Children and adolescents are not small adults: toward a better understanding of multimorbidity in younger populations.

Multimorbidity is of an increasing importance for the health of both children and adults but research has hitherto focused on adult multimorbidity. Hence, public awareness, practice, and policy lack vital information about multimorbidity in childhood and adolescence. We convened an international and interdisciplinary group of experts from six nations to identify key priorities supported by published evidence to strengthen research for children and adolescent with multimorbidity. Future research is encouraged (1) to develop a conceptual framework to capture unique aspects of child and adolescent multimorbidity-including definitions, characteristic patterns of conditions for different age groups, its dynamic nature through childhood and adolescence, and understanding of severity and trajectories for different clusters of multiple chronic conditions, (2) to define new indices to classify the presence of multimorbidity in children and adolescents, (3) to improve the availability and linkage of data across countries, (4) to synthesize evidence on the global phenomenon of multimorbidity in childhood and adolescence and health inequalities, and (5) to involve children and adolescents in research relevant to their health.

Use of an Electronic Medication Management Support System in Patients with Polypharmacy in General Practice: A Quantitative Process Evaluation of the AdAM Trial.

Polypharmacy is associated with a risk of negative health outcomes. Potentially inappropriate medications, interactions resulting from contradicting medical guidelines, and inappropriate monitoring, all increase the risk. This process evaluation (PE) of the AdAM study investigates implementation and use of a computerized decision-support system (CDSS). The CDSS analyzes medication appropriateness by including claims data, and hence provides general practitioners (GPs) with full access to patients' medical treatments. We based our PE on pseudonymized logbook entries into the CDSS and used the four dimensions of the Medical Research Council PE framework. Reach, which examines the extent to which the intended study population was included, and Dose, Fidelity, and Tailoring, which examine how the software was actually used by GPs. The PE was explorative and descriptive. Study participants were representative of the target population, except for patients receiving a high level of nursing care, as they were treated less frequently. GPs identified and corrected inappropriate prescriptions flagged by the CDSS. The frequency and intensity of interventions documented in the form of logbook entries lagged behind expectations, raising questions about implementation barriers to the intervention and the limitations of the PE. Impossibility to connect the CDSS to GPs' electronic medical records (EMR) of GPs due to technical conditions in the German healthcare system may have hindered the implementation of the intervention. Data logged in the CDSS may underestimate medication changes in patients, as documentation was voluntary and already included in EMR.

Effectiveness of the MULTIPAP Plus intervention in youngest-old patients with multimorbidity and polypharmacy aimed at improving prescribing practices in primary care: study protocol of a cluster randomized trial.

BACKGROUND: The progressive ageing of the population is leading to an increase in multimorbidity and polypharmacy, which in turn may increase the risk of hospitalization and mortality. The enhancement of care with information and communications technology (ICT) can facilitate the use of prescription evaluation tools and support system for decision-making (DSS) with the potential of optimizing the healthcare delivery process. OBJECTIVE: To assess the effectiveness and cost-effectiveness of the complex intervention MULTIPAP Plus, compared to usual care, in improving prescriptions for young-old patients (65-74 years old) with multimorbidity and polypharmacy in primary care. METHODS/DESIGN: This is a pragmatic cluster-randomized clinical trial with a follow-up of 18 months in health centres of the Spanish National Health System. Unit of randomization: family physician. Unit of analysis: patient. POPULATION: Patients aged 65-74 years with multimorbidity (≥ 3 chronic diseases) and polypharmacy (≥ 5 drugs) during the previous 3 months were included. SAMPLE SIZE: n = 1148 patients (574 per study arm). INTERVENTION: Complex intervention based on the ARIADNE principles with three components: (1) family physician (FP) training, (2) FP-patient interview, and (3) decision-making support system. OUTCOMES: The primary outcome is a composite endpoint of hospital admission or death during the observation period measured as a binary outcome, and the secondary outcomes are number of hospital admission, all-cause mortality, use of health services, quality of life (EQ-5D-5L), functionality (WHODAS), falls, hip fractures, prescriptions and adherence to treatment. Clinical and sociodemographic factors will be explanatory variables. STATISTICAL ANALYSIS: The main result is the difference in percentages in the final composite endpoint variable at 18 months, with its corresponding 95% CI. Adjustments by the main confounding and prognostic factors will be performed through a multilevel analysis. All analyses will be carried out in accordance to the intention-to-treat principle. DISCUSSION: It is important to prevent the cascade of negative health and health care impacts attributable to the multimorbidity-polypharmacy binomial. ICT-enhanced routine clinical practice could improve the prescription process in patient care. TRIAL REGISTRATION: ClinicalTrials.gov NCT04147130 . Registered on 22 October 2019.

How to Improve Healthcare for Patients with Multimorbidity and Polypharmacy in Primary Care: A Pragmatic Cluster-Randomized Clinical Trial of the MULTIPAP Intervention.

(1) Purpose: To investigate a complex MULTIPAP intervention that implements the Ariadne principles in a primary care population of young-elderly patients with multimorbidity and polypharmacy and to evaluate its effectiveness for improving the appropriateness of prescriptions. (2) Methods: A pragmatic cluster-randomized clinical trial was conducted involving 38 family practices in Spain. Patients aged 65-74 years with multimorbidity and polypharmacy were recruited. Family physicians (FPs) were randomly allocated to continue usual care or to provide the MULTIPAP intervention based on the Ariadne principles with two components: FP training (eMULTIPAP) and FP patient interviews. The primary outcome was the appropriateness of prescribing, measured as the between-group difference in the mean Medication Appropriateness Index (MAI) score change from the baseline to the 6-month follow-up. The secondary outcomes were quality of life (EQ-5D-5 L), patient perceptions of shared decision making (collaboRATE), use of health services, treatment adherence, and incidence of drug adverse events (all at 1 year), using multi-level regression models, with FP as a random effect. (3) Results: We recruited 117 FPs and 593 of their patients. In the intention-to-treat analysis, the between-group difference for the mean MAI score change after a 6-month follow-up was -2.42 (95% CI from -4.27 to -0.59) and, between baseline and a 12-month follow-up was -3.40 (95% CI from -5.45 to -1.34). There were no significant differences in any other secondary outcomes. (4) Conclusions: The MULTIPAP intervention improved medication appropriateness sustainably over the follow-up time. The small magnitude of the effect, however, advises caution in the interpretation of the results given the paucity of evidence for the clinical benefit of the observed change in the MAI. Trial registration: Clinicaltrials.gov NCT02866799.

Development of an intervention to improve informational continuity of care in older patients with polypharmacy at the interface between general practice and hospital care: protocol for a participatory qualitative study in Germany.

INTRODUCTION: Older patients with multimorbidity, polypharmacy and related complex care needs represent a growing proportion of the population and a challenge for healthcare systems. Particularly in transitional care (hospital admission and hospital discharge), medical errors, inappropriate treatment, patient concerns and lack of confidence in healthcare are major problems that may arise from a lack of information continuity. The aim of this study is to develop an intervention to improve informational continuity of care at the interface between general practice and hospital care. METHODS AND ANALYSIS: A qualitative approach will be used to develop our participatory intervention. Overall, 32 semistructured interviews with relevant stakeholders will be conducted and analysed. The stakeholders will include healthcare professionals from the outpatient setting (general practitioners, healthcare assistants, ambulatory care nurses) and the inpatient setting (clinical doctors, nurses, pharmacists, clinical information scientists) as well as patients and informal caregivers. At a series of workshops based on the results of the stakeholder analyses, we aim to develop a participatory intervention that will then be implemented in a subsequent pilot study. The same stakeholder groups will be invited for participation in the workshops. ETHICS AND DISSEMINATION: Ethical approval for this study was waived by the Ethics Committee of Goethe University Frankfurt because of the nature of the proposed study. Written informed consent will be obtained from all study participants prior to participation. Results will be tested in a pilot study and disseminated at (inter)national conferences and via publication in peer-reviewed journals. TRIAL REGISTATION NUMBER: Clinical Trials Register: registration number DRKS00027649.

Use of an electronic medication management support system in patients with polypharmacy in general practice: study protocol of a quantitative process evaluation of the AdAM trial.

BACKGROUND: Interventional studies on polypharmacy often fail to significantly improve patient-relevant outcomes, or confine themselves to measuring surrogate parameters. Interventions and settings are complex, with many factors affecting results. The AdAM study's aim is to reduce hospitalization and death by requiring general practitioners (GPs) to use a computerized decision-support system (CDSS). The study will undergo a process evaluation to identify factors for successful implementation and to assess whether the intervention was implemented as intended. OBJECTIVE: To evaluate our complex intervention, based on the Medical Research Council's guideline dimensions. RESEARCH QUESTIONS: We will assess implementation (reach, fidelity, dose, tailoring) by asking: (1) Who took part in the intervention (proportion of GPs using the CDSS, proportion of patients enrolled in them)? Information on GPs' and patients' characteristics will also be collected. (2) How many and which medication alerts were dealt with? (3) Was the intervention implemented as intended? (4) On what days did GPs use the intervention tool? METHODS: The process evaluation is part of a stepped-wedge cluster-randomized controlled trial. Characteristics of practices, GPs and patients using the CDSS will be compared with the non-participating population. CDSS log data will be analyzed to evaluate how the number of medication alerts changed between baseline and 2 months later, and to identify the kind of alerts that were dealt with. Comparison of enrolled patients on weekdays versus weekends will shed light on GPs' use of the CDSS in the absence or presence of patients. Outcomes will be presented using descriptive statistics, and significance tests will be used to identify associations between them. We will conduct subgroup analyses, including time effects to account for software improvements. DISCUSSION: This study protocol is the basis for conducting analyses of the quantitative process evaluation. By providing insight into how GPs conduct medication reviews, the evaluation will provide context to the trial results and support their interpretation. The evaluation relies on the proper documentation by GPs, potentially limiting its explanatory power.

Evidence-Based Decision Support for a Structured Care Program on Polypharmacy in Multimorbidity: A Guideline Upgrade Based on a Realist Synthesis.

Evidence-based clinical guidelines generally consider single conditions, and rarely multimorbidity. We developed an evidence-based guideline for a structured care program to manage polypharmacy in multimorbidity by using a realist synthesis to update the German polypharmacy guideline including the following five methods: formal prioritization in focus groups; systematic guideline review of evidence-based multimorbidity/polypharmacy guidelines; evidence search/synthesis and recommendation development; multidisciplinary consent of recommendations; feasibility test of updated guideline. We identified the need for a better description of the target group, decision support, prioritization of medication, consideration of patient preferences and anticholinergic properties, and of healthcare interfaces. We conducted a systematic guideline review of eight guidelines and extracted and synthesized recommendations using the Ariadne principles. We also included 48 systematic reviews. We formulated and agreed upon 34 recommendations for the revised guideline. During the feasibility test, guideline use enabled 57% of GPs to identify problems, leading to medication changes in 49% and self-assessed improvement in 56% of patients. Although 58% of GPs felt that it was too long, 92% recommended it. Polypharmacy should be systematically reviewed at least annually. Patients, family members, and healthcare professionals should monitor and adjust it using prospective process validation, taking into account patient preferences and agreed treatment goals.

Effectiveness of the application of an electronic medication management support system in patients with polypharmacy in general practice: a study protocol of cluster-randomised controlled trial (AdAM).

INTRODUCTION: Clinically complex patients often require multiple medications. Polypharmacy is associated with inappropriate prescriptions, which may lead to negative outcomes. Few effective tools are available to help physicians optimise patient medication. This study assesses whether an electronic medication management support system (eMMa) reduces hospitalisation and mortality and improves prescription quality/safety in patients with polypharmacy. METHODS AND ANALYSIS: Planned design: pragmatic, parallel cluster-randomised controlled trial; general practices as randomisation unit; patients as analysis unit. As practice recruitment was poor, we included additional data to our primary endpoint analysis for practices and quarters from October 2017 to March 2021. Since randomisation was performed in waves, final study design corresponds to a stepped-wedge design with open cohort and step-length of one quarter. SCOPE: general practices, Westphalia-Lippe (Germany), caring for BARMER health fund-covered patients. POPULATION: patients (≥18 years) with polypharmacy (≥5 prescriptions). SAMPLE SIZE: initially, 32 patients from each of 539 practices were required for each study arm (17 200 patients/arm), but only 688 practices were randomised after 2 years of recruitment. Design change ensures that 80% power is nonetheless achieved. INTERVENTION: complex intervention eMMa. FOLLOW-UP: at least five quarters/cluster (practice). recruitment: practices recruited/randomised at different times; after follow-up, control group practices may access eMMa. OUTCOMES: primary endpoint is all-cause mortality and hospitalisation; secondary endpoints are number of potentially inappropriate medications, cause-specific hospitalisation preceded by high-risk prescribing and medication underuse. STATISTICAL ANALYSIS: primary and secondary outcomes are measured quarterly at patient level. A generalised linear mixed-effect model and repeated patient measurements are used to consider patient clusters within practices. Time and intervention group are considered fixed factors; variation between practices and patients is fitted as random effects. Intention-to-treat principle is used to analyse primary and key secondary endpoints. ETHICS AND DISSEMINATION: Trial approved by Ethics Commission of North-Rhine Medical Association. Results will be disseminated through workshops, peer-reviewed publications, local and international conferences. TRIAL REGISTRATION: NCT03430336. ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT03430336).

Predicting hospital admissions from individual patient data (IPD): an applied example to explore key elements driving external validity.

OBJECTIVE: To explore factors that potentially impact external validation performance while developing and validating a prognostic model for hospital admissions (HAs) in complex older general practice patients. STUDY DESIGN AND SETTING: Using individual participant data from four cluster-randomised trials conducted in the Netherlands and Germany, we used logistic regression to develop a prognostic model to predict all-cause HAs within a 6-month follow-up period. A stratified intercept was used to account for heterogeneity in baseline risk between the studies. The model was validated both internally and by using internal-external cross-validation (IECV). RESULTS: Prior HAs, physical components of the health-related quality of life comorbidity index, and medication-related variables were used in the final model. While achieving moderate discriminatory performance, internal bootstrap validation revealed a pronounced risk of overfitting. The results of the IECV, in which calibration was highly variable even after accounting for between-study heterogeneity, agreed with this finding. Heterogeneity was equally reflected in differing baseline risk, predictor effects and absolute risk predictions. CONCLUSIONS: Predictor effect heterogeneity and differing baseline risk can explain the limited external performance of HA prediction models. With such drivers known, model adjustments in external validation settings (eg, intercept recalibration, complete updating) can be applied more purposefully. TRIAL REGISTRATION NUMBER: PROSPERO id: CRD42018088129.