Adverse drug reactions associated with amitriptyline - protocol for a systematic multiple-indication review and meta-analysis

Background: Unwanted anticholinergic effects are both underestimated and frequently overlooked. Failure to identify adverse drug reactions (ADRs) can lead to prescribing cascades and the unnecessary use of over-thecounter products. The objective of this systematic review and meta-analysis is to explore and quantify the frequency and severity of ADRs associated with amitriptyline vs. placebo in randomized controlled trials (RCTs) involving adults with any indication, as well as healthy individuals. Methods: A systematic search in six electronic databases, forward/backward searches, manual searches, and searches for Food and Drug Administration (FDA) and European Medicines Agency (EMA) approval studies, will be performed. Placebo-controlled RCTs evaluating amitriptyline in any dosage, regardless of indication and without restrictions on the time and language of publication, will be included, as will healthy individuals. Studies of topical amitriptyline, combination therapies, or including <100 participants, will be excluded. Two investigators will screen the studies independently, assess methodological quality, and extract data on design, population, intervention, and outcomes ((non-)anticholinergic ADRs, e.g., symptoms, test results, and adverse drug events (ADEs) such as falls). The primary outcome will be the frequency of anticholinergic ADRs as a binary outcome (absolute number of patients with/without anticholinergic ADRs) in amitriptyline vs. placebo groups. Anticholinergic ADRs will be defined by an experienced clinical pharmacologist, based on literature and data from Martindale: The Complete Drug Reference. Secondary outcomes will be frequency and severity of (non-)anticholinergic ADRs and ADEs. The information will be synthesized in meta-analyses and narratives. We intend to assess heterogeneity using metaregression (for indication, outcome, and time points) and I2 statistics. Binary outcomes will be expressed as odds ratios, and continuous outcomes as standardized mean differences. Effect measures will be provided using 95% confidence intervals. We plan sensitivity analyses to assess methodological quality, outcome reporting etc., and subgroup analyses on age, dosage, and duration of treatment. Discussion: We will quantify the frequency of anticholinergic and other ADRs/ADEs in adults taking amitriptyline for any indication by comparing rates for amitriptyline vs. placebo, hence, preventing bias from disease symptoms and nocebo effects. As no standardized instrument exists to measure it, our overall estimate of anticholinergic ADRs may have limitations

Patient Safety and the COVID-19 Pandemic in Germany: A Repeated Population-Based Cross-Sectional Survey.

The coronavirus (COVID-19) has presented Germany with major challenges and has led to concerns about patient safety. We conducted an observational, population-based, nationwide, repeated cross-sectional survey on patient safety in Germany in 2019, 2020, and 2021. Each of the three samples consisted of 1000 randomly recruited adults. Self-reported data via computer-assisted telephone interviews were taken from TK Monitor of Patient Safety. Perceptions, experience, and knowledge relating to patient safety were assessed. The majority of respondents considered medical treatment to involve risks to patient safety. This proportion decreased during the pandemic. The majority also had a high degree of self-efficacy regarding the prevention of medical errors, whereby the percentage that felt well informed with regard to patient safety rose throughout the pandemic. The proportion of persons that suspected they had in the past experienced an error in their treatment remained steady at one third as well as the reported errors. In 2020, 65% of respondents thought health communication with service providers (e.g., extent and comprehensibility of information) remained unchanged during the pandemic, while 35% reported that medical appointments had been cancelled or postponed. This study is the first to assess patient safety from a general population perspective during the coronavirus pandemic in Germany. COVID-19 had a positive impact on perceived patient safety but no impact on suspected and reported errors. Self-efficacy with regard to medical error prevention steadily increased in the general population, and people considered themselves well informed

Multimedication in Family Doctor Practices: The German Evidence-Based Guidelines on Multimedication

Schubert I, Fessler J, Harder S, Dinh TS, Brueckle M-S, Muth C. Multimedication in Family Doctor Practices: The German Evidence-Based Guidelines on Multimedication. Pharmacoepidemiology. 2022;1(1):35-48.Patients with multimorbidity and multimedication require special attention from their treating physicians, as the risks of drug interactions and negative effects on adherence increase with the number of drugs. Most guidelines aim for the treatment of a single disease and do not take potential problems due to multimedication into account. In 2021, updates and evidence-based upgrades of the first version (2012) of the German Guidelines on Multimedication were issued. The aim of the article is to introduce the framework of these evidence-based guidelines, which follows the medication process in six steps: (1) inventory and medication assessment; (2) coordination with the patient; (3) prescription proposal and communication; (4) dispensing of medicines; (5) medication application and self-management; and (6) monitoring. For each step, recommendations and practice tips are presented. The central feature is a structured medication review. The target group is patients with multimorbidity and the concurrent use of five or more drugs. The Medication Appropriateness Index has been modified, and the guiding questions are recommended as guidance for the structured medication review. Overuse and undertreatment are taken into account. The guidelines were consented to in a formal process with 15 medical societies, a patient representative, and experts, as well as piloted in general practices

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

Engler J, Brosse F, Dinh TS, et al. 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. Research Involvement and Engagement . 2022;8(1): 52.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. © 2022. The Author(s)

Everyday Lives of Middle-Aged Persons with Multimorbidity:A Mixed Methods Systematic Review

The healthcare burden of patients with multimorbidity may negatively affect their family lives, leisure time and professional activities. This mixed methods systematic review synthesizes studies to assess how multimorbidity affects the everyday lives of middle-aged persons, and identifies skills and resources that may help them overcome that burden. Two independent reviewers screened title/abstracts/full texts in seven databases, extracted data and used the Mixed Methods Appraisal Tool (MMAT) to assess risk of bias (RoB). We synthesized findings from 44 studies (49,519 patients) narratively and, where possible, quantitatively. Over half the studies provided insufficient information to assess representativeness or response bias. Two studies assessed global functioning, 15 examined physical functioning, 18 psychosocial functioning and 28 work functioning. Nineteen studies explored skills and resources that help people cope with multimorbidity. Middle-aged persons with multimorbidity have greater impairment in global, physical and psychosocial functioning, as well as lower employment rates and work productivity, than those without. Certain skills and resources help them cope with their everyday lives. To provide holistic and dynamic health care plans that meet the needs of middle-aged persons, health professionals need greater understanding of the experience of coping with multimorbidity and the associated healthcare burden

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

BackgroundHalf 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.MethodsWe 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.ResultsTwenty-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.DiscussionThe 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 (RegistrationPROSPERO: CRD42020111970

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

Dinh TS, Brueckle M-S, Gonzalez-Gonzalez AI, et al. Stakeholder Perspectives on the Development and Implementation of a Polypharmacy Management Program in Germany: Results of a Qualitative Study. Journal of Personalized Medicine . 2022;12(7): 1115.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

Everyday lives of middle-aged persons living with multimorbidity: protocol of a mixed-methods systematic review.

INTRODUCTION: Multimorbidity is the simultaneous occurrence of several (chronic) diseases. Persons living with multimorbidity not only have complex care needs, but the burden of care often has a negative impact on their family lives, leisure time and professional activities. The aim of this project is to systematically review the literature to assess how multimorbidity affects the everyday lives of middle-aged persons, and to find out what abilities and resources help in the development of coping strategies to overcome the challenges of living with it. METHODS AND ANALYSIS: We will systematically search for studies reporting on the everyday life experiences of middle-aged persons (30–60 years) with multimorbidity (≥2 chronic conditions) in MEDLINE, CINAHL, PsycINFO, Social Sciences Citation Index, Social Sciences Citation Index Expanded, PSYNDEX and The Cochrane Library from inception. We will include all primary studies that use quantitative, qualitative and mixed methodologies, irrespective of publication date/study setting. Two independent reviewers will screen titles/abstracts/full texts, extract data from the selected studies and present evidence in terms of study/population characteristics, data collection method and the phenomenon of interest, that is, everyday life experiences of middle-aged persons with multimorbidity. Risk of bias will be independently assessed by two reviewers using the Mixed Methods Appraisal Tool. We will use a convergent integrated approach on qualitative/quantitative studies, whereby information will be synthesised narratively and, if possible, quantitatively. ETHICS AND DISSEMINATION: Ethical approval is not required due to the nature of the proposed systematic review. Results from this research will be disseminated at relevant (inter)national conferences and via publication in peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42021226699

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

Dinh TS, Hanf M, Klein A-A, et al. Informational continuity of medication management in transitions of care: Qualitative interviews with stakeholders from the HYPERION-TransCare study. PLoS ONE . 2024;19(4): e0300047.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. Copyright: © 2024 Dinh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited