Andrea Burden

Last Name

Burden

First Name

Andrea

ORCID

0000-0001-7082-8530

Organisational unit

01509 - Lehre Chemie u. Ang. Biowiss.

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Publications 1 - 10 of 85

Opioid sales and opioid-related poisonings in Switzerland: A descriptive population-based time-series analysis
Hooijman, Marit F.; Martinez de la Torre, Adrian; Weiler, Stefan; et al. (2022)
The Lancet Regional Health - Europe
Background: To examine time trends and characteristics of calls related to opioid poisonings reported to the National Poison Centre and opioid sales in Switzerland. Methods: We used population-level data from the Swiss National Poisons Information Centre on reported opioid-related poisonings and data provided by the Swiss Pharmacists’ Association (pharmaSuisse) based on IQVIA data to identify sold opioid packages. The rate of opioid-related poisoning calls and dispensed opioid packages per 100,000 Swiss inhabitants between 2000 and 2019 were plotted by year and annual trends were assessed. All analyses were stratified by individual opioid and potency (strong vs weak). Findings: There was a significant 177% increase in the rate of calls for opioid-related poisonings (1·4 to 3·9 per 100,000 inhabitants, p<0·001) and a 91·3% increase in opioid sales (from 14,364·0 to 27,477·6 per 100,000 inhabitants, p<0.001). The increase associated with strong opioids was higher when compared to weak opioids, in both poison centre calls and sales. In 2019, tramadol was the most frequently reported opioid in the poison centre data (35·7%, n=133) and sales (37·5%, n=8,863,377), followed by oxycodone calls (24·4%, n=91) and sales 23·4%, n= 552,751). Poisoning calls and sales related to oxycodone increased substantially between 2009 and 2016, as did the rate of poison centre calls requiring medical care. Interpretation: Calls to the Swiss National poison centre and sales for opioid have increased substantially in Switzerland in the last two-decades. Increases were primarily driven by oxycodone and tramadol; however, sales have attenuated since 2016. Our findings mirror other European countries and stress the importance of surveillance and monitoring. Funding: The research did not receive external funding. Translation of the abstract in German, French and Italian are available in the Supplementary section.
Identification of Medication Prescription Errors and Factors of Clinical Relevance in 314 Hospitalized Patients for Improved Multidimensional Clinical Decision Support Algorithms
Russmann, Stefan; Martinelli, Fabiana; Jakobs, Franziska; et al. (2023)
Journal of Clinical Medicine
Potential medication errors and related adverse drug events (ADE) pose major challenges in clinical medicine. Clinical decision support systems (CDSSs) help identify preventable prescription errors leading to ADEs but are typically characterized by high sensitivity and low specificity, resulting in poor acceptance and alert-overriding. With this cross-sectional study we aimed to analyze CDSS performance, and to identify factors that may increase CDSS specificity. Clinical pharmacology services evaluated current pharmacotherapy of 314 patients during hospitalization across three units of two Swiss tertiary care hospitals. We used two CDSSs (pharmaVISTA and MediQ), primarily for the evaluation of drug-drug interactions (DDI). Additionally, we evaluated potential drug-disease, drug-age, drug-food, and drug-gene interactions. Recommendations for change of therapy were forwarded without delay to treating physicians. Among 314 patients, automated analyses by both CDSSs produced an average of 15.5 alerts per patient. In contrast, additional expert evaluation resulted in only 0.8 recommendations per patient to change pharmacotherapy. For clinical pharmacology experts, co-factors such as comorbidities and laboratory results were decisive for the classification of CDSS alerts as clinically relevant in individual patients in about 70% of all decisions. Such co-factors should therefore be used for the development of multidimensional CDSS alert algorithms with improved specificity. In combination with local expert services, this poses a promising approach to improve drug safety in clinical practice.
Editorial: Shaping with data: Using pharmacoepidemiology to shape pharmaceutical policy and clinical decision-making
Tadrous, Mina; Burden, Andrea (2022)
Frontiers in Pharmacology
The relationship between osteoporosis treatment history and receipt of a second zoledronic acid dose
Konstantelos, Natalia; Kim, Sandra; Cheung, Angela M.; et al. (2025)
Osteoporosis International
Summary: We examined characteristics of patients in Ontario, Canada, initiating publicly funded zoledronic acid for osteoporosis from 2006 to 2021. Most patients had prior osteoporosis treatments, with those previously using oral bisphosphonates more likely to receive a second dose. Understanding treatment decisions and patient beliefs is key for future research. Purpose: Zoledronic acid is a once-yearly intravenous bisphosphonate and is considered a second-line osteoporosis therapy in Ontario, Canada. This regimen was approved using evidence from clinical trials of treatment-na ïve patients. However, many patients initiating zoledronic acid have used other osteoporosis medications prior, which may influence the frequency of dosing. We describe the characteristics of patients initiating zoledronic acid and identify if previous osteoporosis pharmacotherapy impacts the receipt of a second dose. Methods: Healthcare administrative data in Ontario were used to identify older patients initiating publicly funded zoledronic acid from 10/2006 to 10/2021 and followed until 10/2022. Patients were categorized based on 5-year osteoporosis treatment look back history in mutually exclusive groups: (1) no history, (2) denosumab, (3) oral bisphosphonates, and (4) other osteoporosis medications. Cox proportional hazards models were used to compare receipt of a second zoledronic acid infusion between patients in treatment history groups. Results: We identified 3308 patients initiating zoledronic acid; median age = 77, 81% female, 31% received a second infusion of zoledronic acid. Half (49%) had a history of oral bisphosphonates, 37% no history, 11% denosumab, and 3% other medications. Overall, patients having history of oral bisphosphonates were 1.5 times more likely to receive a second dose relative to no history (HR, 95%CI: 1.50 [1.31-1.71]). Conclusion: In contrast to patients in pivotal trials, most patients receiving zoledronic acid had prior osteoporosis pharmacotherapy. Patients with prior oral bisphosphonate use had higher rates of receiving a second dose. Better understanding of treatment decisions and patient beliefs around receiving a second infusion of zoledronic acid should be further investigated.
Comment on: Paradoxically protective effect of glucocorticoids on bone mass and fragility fracture in a large cohort: a cross-sectional study
Hayes, Kaleen N.; Burden, Andrea; Winter, Elizabeth M.; et al. (2022)
Rheumatology Advances in Practice
Implementation and management outcomes of pharmacogenetic CYP2C19 testing for clopidogrel therapy in clinical practice
Russmann, Stefan; Rahmany, Ali; Niedrig, David; et al. (2021)
European Journal of Clinical Pharmacology
Purpose The antiplatelet prodrug clopidogrel is bioactivated by the polymorphic enzyme CYP2C19. Prospective clinical studies demonstrated an association between CYP2C19 loss of function (LoF) variants and an increased risk of thrombotic events under clopidogrel, but pharmacogenetic (PGx) testing is not frequently implemented in clinical practice. We report our experience with PGx-guided clopidogrel therapy with particular regard to clinically relevant patient management changes. Methods We conducted an observational study analyzing patients that underwent PGx testing for clopidogrel therapy at two Swiss hospitals. Primary outcome was the proportion of patients with clinically relevant PGx-based management recommendations and their implementation. The association of recurrent ischemic events under clopidogrel with CYP2C19 LoF variants and other factors was explored in a multivariate case-control analysis. Results Among 56 patients undergoing PGx testing, 18 (32.1%) were classified as CYP2C19 intermediate or poor metabolizers. This resulted in 17 recommendations for a change of antiplatelet therapy, which were implemented in 12 patients (70.1%). In the remaining five patients, specific reasons for non-implementation could be identified. Recurrent ischemic events under clopidogrel were associated with LoF variants (OR 2.2, 95% CI 0.3–14.4) and several cardiovascular risk factors. Associations were not statistically significant in our small study, but plausible and in line with estimates from large prospective studies. Conclusion PGx-guided clopidogrel therapy can identify patients with an elevated risk of ischemic events and offer evidence-based alternative treatments. Successful implementation in clinical practice requires a personalized interdisciplinary service that evaluates indications and additional risk factors, provides specific recommendations, and proactively follows their implementation.
Concomitant use of oral glucocorticoids and proton pump inhibitors and risk of osteoporotic fractures among patients with rheumatoid arthritis: a population-based cohort study
Abtahi, Shahab; Driessen, Johanna H.M.; Burden, Andrea; et al. (2020)
Annals of the Rheumatic Diseases
Background Patients with rheumatoid arthritis (RA) commonly use oral glucocorticoids (GCs) and proton pump inhibitors (PPIs), both associated with osteoporotic fractures. We investigated the association between concomitant use of oral GCs and PPIs and the risk of osteoporotic fractures among patients with RA. Methods This was a cohort study including patients with RA aged 50+ years from the Clinical Practice Research Datalink between 1997 and 2017. Exposure to oral GCs and PPIs was stratified by the most recent prescription as current use (<6 months), recent use (7–12 months) and past use (>1 year); average daily and cumulative dose; and duration of use. The risk of incident osteoporotic fractures (including hip, vertebrae, humerus, forearm, pelvis and ribs) was estimated by time-dependent Cox proportional-hazards models, statistically adjusted for lifestyle parameters, comorbidities and comedications. Results Among 12 351 patients with RA (mean age of 68 years, 69% women), 1411 osteoporotic fractures occurred. Concomitant current use of oral GCs and PPIs was associated with a 1.6-fold increased risk of osteoporotic fractures compared with non-use (adjusted HR: 1.60, 95% CI: 1.35 to 1.89). This was statistically different from a 1.2-fold increased osteoporotic fracture risk associated with oral GC or PPI use alone. Most individual fracture sites were significantly associated with concomitant use of oral GCs and PPIs. Among concomitant users, fracture risk did not increase with higher daily dose or duration of PPI use. Conclusions There was an interaction in the risk of osteoporotic fractures with concomitant use of oral GCs and PPIs. Fracture risk assessment could be considered when a patient with RA is co-prescribed oral GCs and PPIs.
Antiplatelet therapy guided by CYP2C19 point-of-care pharmacogenetics plus multidimensional treatment decisions
Voicu, Victor; Diehm, Nicolas; Moarof, Igal; et al. (2024)
Pharmacogenomics
Aim: Implementation of CYP2C19 point-of-care (POC) pharmacogenetic (PGx) testing with personalized treatment recommendations. Methods: POC CYP2C19 genotyping plus expert evaluation of risk factors for ischemic and bleeding events. Results: 167 patients underwent PGx testing, 54 (32.3%) were CYP2C19 loss of function carriers, and POC versus standard PGx analysis results for *2 and *3 variants matched in 100%. Antiplatelet therapy was adjusted in 44 patients (26.3%), but always required consideration of patient-specific factors. Conclusion: CYP2C19 POC-PGx is reliable and offers clinically relevant advantages for immediate evidence-based adaptations of antiplatelet therapy, whereas in less acute cases conventional PGx testing can also have advantages. Antiplatelet therapy has become more complex, and implementation of PGx-based personalized antiplatelet therapy requires complementary expert knowledge.
Optimizing deprescribing of hospital-initiated opioids: a multi-level consensus study bridging evidence, expertise, and patient perspectives
Rainer , Marcel; Sebesta , Elin; Wertli , Maria Monika; et al. (2025)
Scientific Reports
Hospital-initiated opioid analgesics that extend beyond discharge can lead to long-term use and adverse outcomes. Despite a growing understanding of opioid-related harms, there is a lack of published protocols for structured deprescribing of hospital-initiated opioids in Europe. Opioid stewardship initiatives, which encompass coordinated approaches to optimize prescribing practices and reduce long-term use, require deprescribing frameworks that extend beyond medication discontinuation to include patient communication and systematic care coordination. We aimed to develop an actionable opioid deprescribing framework that builds on trialed reduction protocols with patient-centered determinants for systematic implementation in tertiary care. We conducted a multi-level consensus study to bridge evidence, clinician expertise, and patient perspectives. Initial framework development included focus group discussions with multidisciplinary clinicians (n = 5). The framework was validated for our institution via a two-round Delphi survey across six medical specialties (n = 11). An opioid reduction calculator was developed in Python, incorporating clinical parameters to determine reduction trajectories for prespecified starting and end doses. Final refinement included interviews with patients receiving opioid therapy (n = 11) to optimize understandability of the reduction plan as a patient handout and for developing a patient pamphlet on opioids with patients (n = 13). The framework identified four critical domains for successful deprescribing of hospital-initiated opioids: interventional reduction strategies, patient-specific physiological variables, environmental enablers, and procedural elements. Reduction strategies categorized patients into chronic and new users, incorporating grace periods for dose stabilization, with particular attention given to patients exhibiting pain catastrophizing behavior and frailty. Environmental and procedural factors included shared responsibility and interdisciplinarity, ensuring that follow-up is facilitated by a coordinated care team. These findings were operationalized into the reduction calculator, proposing initial individualized reduction plans (10–25%) based on key patient-specific variables with built-in stabilization periods. Delphi validation achieved full consensus (87.8% first-round agreement; 100% final consensus) on all framework components. Patient involvement refined the handout to improve understandability and actionability, and yielded comprehensive information on opioids. We developed an actionable opioid deprescribing framework that bridges published evidence with patient-centered care for our institution, providing other healthcare institutions with a practical blueprint for their own implementation. Our multi-level consensus identified critical patient-specific and environmental determinants, and established individualized reduction protocols, addressing a critical gap in transitional care while facilitating safe opioid deprescribing practices.
National Poison Center Calls Before vs After Availability of High-Dose Acetaminophen (Paracetamol) Tablets in Switzerland
Martinez de la Torre, Adrian; Weiler, Stefan; Bräm, Dominic S.; et al. (2020)
JAMA Network Open
Importance: Acetaminophen (paracetamol) is among the most widely used pain medications worldwide; while safe within the therapeutic range, intake exceeding 4000 mg/d can lead to hepatotoxicity. Prior evidence suggests that limiting the availability of large quantities of acetaminophen is associated with decreased acetaminophen-related poisonings and mortality; in Switzerland, 500-mg tablets are available over-the-counter (OTC) and, as of October 2003, 1000-mg tablets are available with prescription. Objective: To evaluate the association of adding 1000-mg acetaminophen tablets to the Swiss market with utilization and poisonings. Design, Setting, and Participants: This cross-sectional study used a quasi-experimental interrupted time series analysis to evaluate 15 790 acetaminophen poison records from January 1, 2000, to December 31, 2018. All calls for acetaminophen-related poisonings identified from the National Swiss Poisons Centre and all sales for oral acetaminophen tablets (prescription and OTC) dispensed between January 2000 and December 2018 were included. Exposure: October 3, 2003 (Q4 2003), was defined as the intervention date, corresponding to the date of market entry for 1000-mg acetaminophen tablets in Switzerland. Main Outcomes and Measures: The primary outcome was the number of quarterly acetaminophen-related poison calls to the National Poison Centre. Additional outcomes included quarterly sales for acetaminophen and change in poisoning circumstances, stratified by preintervention and postintervention periods and by formulation (ie, 500-mg and 1000-mg tablets). Results: Between 2000 and 2018, 15 790 acetaminophen-related poisoning calls were identified, of which 10 628 (67.3%) were regarding women, and the mean (SD) age of patients was 25.2 (18.2) years. The interrupted time series analysis identified a significant increase in the slope for the number of reported poisonings following the intervention point, particularly for accidental circumstances (z score, -3.62; P < .001). In the preintervention period, 120 of 961 poisonings (15.3%) involved a dose greater than 10 000 mg, while for the postintervention period, 1140 of 5696 (30.6%) had a dose larger than 10 000 mg (P < .001). There was a rapid uptake in 1000-mg acetaminophen sales, while sales of the 500-mg tablet decreased slightly. Since 2012, a mean (SD) of 20.7 million (1.4 million) 1000-mg tablets were dispensed quarterly compared with 2.7 million (0.5 million) 500-mg tablets. Conclusions and Relevance: This study found a significant increase in acetaminophen dispensing and acetaminophen-related poisonings in Switzerland following the approval of 1000-mg tablets in 2003. The availability of 1000-mg acetaminophen should be re-evaluated to minimize the potential for accidental poisonings.

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