Potential Adverse Drug Events Research Articles

Financial impact of medication reviews by clinical pharmacists to reduce in-hospital adverse drug events: a return-on-investment analysis

BackgroundAdverse drug events contribute to rising health care costs. Clinical pharmacists can reduce their risks by identifying and solving drug-related problems (DRPs) through medication review.AimTo develop an economic model to determine whether medication reviews performed by clinical pharmacists could lead to a reduction in health care costs associated with the prevention of potential adverse drug events.MethodTwo pharmacists performed medication reviews during ward rounds in an internal medicine setting over one year. Avoided costs were estimated by monetizing five categories of DRPs (improper drug selection, drug interactions, untreated indications, inadequate dosages, and drug use without an indication). An expert panel assessed potential adverse drug events and their probabilities of occurrence for 20 randomly selected DRPs in each category. The costs of adverse drug events were extracted from internal hospital financial data. A partial economic study from a hospital perspective then estimated the annual costs avoided by resolving DRPs identified by 3 part-time clinical pharmacists (0.9 full-time equivalent) from 2019 to 2020. The return on investment (ROI) of medication review was calculated.ResultsThe estimated annual avoided costs associated with the potential adverse drug events induced by 676 DRPs detected was € 304,170. The cost of a 0.9 full-time equivalent clinical pharmacist was € 112,408. Extrapolated to 1 full-time equivalent, the annual net savings was € 213,069 or an ROI of 1–1.71. Sensitivity analyses showed that the economic model was robust.ConclusionThis economic model revealed the positive financial impact and favorable return on investment of a medication review intervention performed by clinical pharmacists. These findings should encourage the future deployment of a pharmacist-led adverse drug events prevention program.

Adherence to stewardship recommendations for antibiotic discontinuation reduces antibiotic-associated adverse drug events.

Inappropriate antibiotic use may lead to increased adverse drug events (ADEs). This study assessed whether an antimicrobial stewardship recommendation to discontinue antibiotics in patients with low likelihood for bacterial infection reduced antibiotic duration and antibiotic-associated ADEs. At a 4-hospital system, hospitalized adult patients receiving empiric antibiotics for suspected infection were identified between May 2, 2016 and June 30, 2018. For those patients who were deemed unlikely to have a bacterial infection, a note was left by an infectious diseases physician recommending antibiotic discontinuation. Patient cases were considered "adherent" to recommendations if antibiotics were discontinued within 48 hours of the note and "non-adherent" to recommendations if antibiotics were continued beyond this. Duration of antibiotics and potential antibiotic-associated ADEs were collected retrospectively. Attribution of the adverse event to the antibiotic was decided upon by the investigators. The incidence of ADEs and duration of antibiotics between the adherent and non-adherent groups were compared. Of 253 patients deemed unlikely to have a bacterial infection, 114 (45%) treatment teams stopped antibiotics within 48 hours of the recommendation, and 139 (55%) continued antibiotics. The total number of ADEs was significantly higher in the non-adherent group compared to the adherent group (34 ADEs vs 9 ADEs, P = .001). The median number of total prescribed antibiotic days was higher in the non-adherent group than in the adherent group (5 days vs 1 day, P < .001). This study demonstrates that stewardship programs may prevent ADEs by recommending antibiotic discontinuation in patients with low suspicion for bacterial infection.

Usability Analysis of a Medication Visualization Tool for Decision Support.

In Germany, patients are entitled to a medication plan. While the overview is useful, it does not contain explicit information on various potential adverse drug events (ADEs). Therefore, physicians must continue to seek information from various sources to ensure medication safety. In this project a first functional prototype of a medication therapy tool was developed that focuses on visualizing and highlighting potential ADEs. A usability analysis about the tool's functionality, design and usability was conducted. A web application tool was developed using the MMI Pharmindex as database. ADEs are color coded and can be displayed in three different ways - as a list, a table, or a graph. To test the tool, an online survey was conducted amongst healthcare professionals (n = 9). The test included two real medication plans to check ADEs through the tool. The survey results indicated that the web tool was clear and self-explanatory. It scored overall "good" (score: 76.5) on the System Usability Scale questionnaire. Due to the free-text information of the database used, there were some inconsistencies in the visualized ADEs. There is a demand for a visualization tool for medications. The high quality of the database is crucial in order to correctly visualize all necessary information, such as drug-drug interactions and inclusion of patient data. This is essential to provide a trustworthy tool for medical professionals.

Prolonged use of linezolid in bone and joint infections: a retrospective analysis of adverse effects.

Antibiotic treatment for bone and joint infections generally lasts for 6 weeks or longer. Linezolid may be a good option for treating bone and joint infections, but there is an increased risk of potential serious adverse drug events (ADEs) when used for more than 28 days. The aim of this study was to obtain detailed information on the type and time to occurrence of the patient-reported ADEs, the dynamics of haematopoiesis over time, and the reasons for early discontinuation of linezolid when used for an intended maximum duration of 12 weeks. This single-centre retrospective study was conducted at the Sint Maartenskliniek in The Netherlands. Patients were included if they were planned to use linezolid for more than 28 days. The main reason for discontinuation of linezolid, the ADE according to the Naranjo score, and the time to occurrence of ADEs were analysed. Among 78 patients, drug toxicity led to early discontinuation of linezolid in 11 (14%) patients before and nine (12%) after 28 days of therapy. The median treatment duration was 42 days. Gastrointestinal intolerance (42%) and malaise (32%) were the most common ADEs. In 75% of the cases the ADE occurred within 28 days of therapy. Sixty-seven patients were able to continue linezolid beyond 28 days, 87% of whom completed therapy as scheduled. Severe cytopenia, according to the Common Terminology Criteria for Adverse events (CTCA), was observed in four patients and was reversible after discontinuation of linezolid. One patient suffered optic neuropathy related to linezolid use. Linezolid could be considered an alternative option to the current standard of IV glycopeptides for the treatment of bone and joint infection for up to 12 weeks. If patients pass the first 28 days of therapy, the likelihood of successful completion of therapy is high with a low risk of serious ADEs.

Signal detection of adverse events associated with gabapentinoid use for chronic pain.

Gabapentinoids (GABA) prescribing as a potential and conceivably safer substitute for opioids has substantially increased. Understanding all potential adverse drug events (ADEs) associated with GABA will guide clinical decision-making for pain management. A 20% sample of Medicare enrollees with new chronic pain diagnoses in 2017-2018 was selected. GABA users were those with >=30 consecutive days prescription in a year without opioid prescription. Opioid users were similarly defined. The control group used neither of these drugs. Propensity score match across three groups based on demographics and comorbidity was performed. We used proportional reporting ratio (PRR), Gamma Poisson Shrinker, and tree-based scan statistic (TBSS) to detect ADEs within 3, 6, and 12 months of follow-up. Immunity disorder was detected within 3 months of follow-up by PRR compared to opioid use (PRR:2.33), and by all three methods compared to controls. Complications of transplanted organs/tissues and schizophrenia spectrum/other psychotic disorders were consistently detected by PRR and TBSS within 3 months. Skin disorders were detected by TBSS; and stroke was detected by PRR within 3 months compared to opioid use (PRR:4.74). Some malignancies were detected by PRR within 12 months. Other signals detected in GABA users were neuropathy and nerve disorders. Our study identified expected and unexpected ADE signals in GABA users. Neurological signals likely related to indications for GABA use. Signals for immunity, mental/behavior, and skin disorders were found in the FDA adverse event reporting system database. Unexpected signals of stroke and cancer require further confirmatory analyses to verify.

Identification of Medication Prescription Errors and Factors of Clinical Relevance in 314 Hospitalized Patients for Improved Multidimensional Clinical Decision Support Algorithms.

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.

Neutralizing Monoclonal Antibody Use and COVID-19 Infection Outcomes

Evidence on the effectiveness and safety of COVID-19 therapies across a diverse population with varied risk factors is needed to inform clinical practice. To assess the safety of neutralizing monoclonal antibodies (nMAbs) for the treatment of COVID-19 and their association with adverse outcomes. This retrospective cohort study included 167 183 patients from a consortium of 4 health care systems based in California, Minnesota, Texas, and Utah. The study included nonhospitalized patients 12 years and older with a positive COVID-19 laboratory test collected between November 9, 2020, and January 31, 2022, who met at least 1 emergency use authorization criterion for risk of a poor outcome. Four nMAb products (bamlanivimab, bamlanivimab-etesevimab, casirivimab-imdevimab, and sotrovimab) administered in the outpatient setting. Clinical and SARS-CoV-2 genomic sequence data and propensity-adjusted marginal structural models were used to assess the association between treatment with nMAbs and 4 outcomes: all-cause emergency department (ED) visits, hospitalization, death, and a composite of hospitalization or death within 14 days and 30 days of the index date (defined as the date of the first positive COVID-19 test or the date of referral). Patient index dates were categorized into 4 variant epochs: pre-Delta (November 9, 2020, to June 30, 2021), Delta (July 1 to November 30, 2021), Delta and Omicron BA.1 (December 1 to 31, 2021), and Omicron BA.1 (January 1 to 31, 2022). Among 167 183 patients, the mean (SD) age was 47.0 (18.5) years; 95 669 patients (57.2%) were female at birth, 139 379 (83.4%) were White, and 138 900 (83.1%) were non-Hispanic. A total of 25 241 patients received treatment with nMAbs. Treatment with nMAbs was associated with lower odds of ED visits within 14 days (odds ratio [OR], 0.76; 95% CI, 0.68-0.85), hospitalization within 14 days (OR, 0.52; 95% CI, 0.45-0.59), and death within 30 days (OR, 0.14; 95% CI, 0.10-0.20). The association between nMAbs and reduced risk of hospitalization was stronger in unvaccinated patients (14-day hospitalization: OR, 0.51; 95% CI, 0.44-0.59), and the associations with hospitalization and death were stronger in immunocompromised patients (hospitalization within 14 days: OR, 0.31 [95% CI, 0.24-0.41]; death within 30 days: OR, 0.13 [95% CI, 0.06-0.27]). The strength of associations of nMAbs increased incrementally among patients with a greater probability of poor outcomes; for example, the ORs for hospitalization within 14 days were 0.58 (95% CI, 0.48-0.72) among those in the third (moderate) risk stratum and 0.41 (95% CI, 0.32-0.53) among those in the fifth (highest) risk stratum. The association of nMAb treatment with reduced risk of hospitalizations within 14 days was strongest during the Delta variant epoch (OR, 0.37; 95% CI, 0.31-0.43) but not during the Omicron BA.1 epoch (OR, 1.29; 95% CI, 0.68-2.47). These findings were corroborated in the subset of patients with viral genomic data. Treatment with nMAbs was associated with a significant mortality benefit in all variant epochs (pre-Delta: OR, 0.16 [95% CI, 0.08-0.33]; Delta: OR, 0.14 [95% CI, 0.09-0.22]; Delta and Omicron BA.1: OR, 0.10 [95% CI, 0.03-0.35]; and Omicron BA.1: OR, 0.13 [95% CI, 0.02-0.93]). Potential adverse drug events were identified in 38 treated patients (0.2%). In this study, nMAb treatment for COVID-19 was safe and associated with reductions in ED visits, hospitalization, and death, although it was not associated with reduced risk of hospitalization during the Omicron BA.1 epoch. These findings suggest that targeted risk stratification strategies may help optimize future nMAb treatment decisions.

Short- and long-term effects of an electronic medication management system on paediatric prescribing errors

Electronic medication management (eMM) systems are designed to improve safety, but there is little evidence of their effectiveness in paediatrics. This study assesses the short-term (first 70 days of eMM use) and long-term (one-year) effectiveness of an eMM system to reduce prescribing errors, and their potential and actual harm. We use a stepped-wedge cluster randomised controlled trial (SWCRCT) at a paediatric referral hospital, with eight clusters randomised for eMM implementation. We assess long-term effects from an additional random sample of medication orders one-year post-eMM. In the SWCRCT, errors that are potential adverse drug events (ADEs) are assessed for actual harm. The study comprises 35,260 medication orders for 4821 patients. Results show no significant change in overall prescribing error rates in the first 70 days of eMM use (incident rate ratio [IRR] 1.05 [95%CI 0.92–1.21], but a 62% increase (IRR 1.62 [95%CI 1.28–2.04]) in potential ADEs suggesting immediate risks to safety. One-year post-eMM, errors decline by 36% (IRR 0.64 [95%CI 0.56–0.72]) and high-risk medication errors decrease by 33% (IRR 0.67 [95%CI 0.51–0.88]) compared to pre-eMM. In all periods, dose error rates are more than double that of other error types. Few errors are associated with actual harm, but 71% [95%CI 50–86%] of patients with harm experienced a dose error. In the short-term, eMM implementation shows no improvement in error rates, and an increase in some errors. A year after eMM error rates significantly decline suggesting long-term benefits. eMM optimisation should focus on reducing dose errors due to their high frequency and capacity to cause harm.

Adverse drug events in the prevention and treatment of COVID-19: A data mining study on the FDA adverse event reporting system.

Background: In the emergent situation of COVID-19, off-label therapies and newly developed vaccines may bring the patients more adverse drug event (ADE) risks. Data mining based on spontaneous reporting systems (SRSs) is a promising and efficient way to detect potential ADEs to help health professionals and patients get rid of the risk. Objective: This pharmacovigilance study aimed to investigate the ADEs of some attractive drugs (i.e., "hot drugs" in this study) in COVID-19 prevention and treatment based on the data from the US Food and Drug Administration (FDA) adverse event reporting system (FAERS). Methods: The FAERS ADE reports associated with COVID-19 from the 2nd quarter of 2020 to the 2nd quarter of 2022 were retrieved with hot drugs and frequent ADEs were recognized. A combination of support, lower bound of 95% confidence interval (CI) of the proportional reporting ratio (PRR) was applied to detect significant hot drug and ADE signals by the Python programming language on the Jupyter notebook. Results: A total of 66,879 COVID-19 associated cases were retrieved with 22 hot drugs and 1,109 frequent ADEs on the "preferred term" (PT) level. The algorithm finally produced 992 significant ADE signals on the PT level among which unexpected signals such as "hypofibrinogenemia" of tocilizumab and "disease recurrence" of nirmatrelvir\ritonavir stood out. A picture of signals on the "system organ class" (SOC) level was also provided for a comprehensive understanding of these ADEs. Conclusion: Data mining is a promising and efficient way to assist pharmacovigilance work, and the result of this study could help timely recognize ADEs in the prevention and treatment of COVID-19.

Evaluation of Factors Associated with Adverse Drug Events in South Korea Using a Population-Based Database.

This retrospective study aims to investigate the factors associated with the occurrence of ADEs using nationally representative claims data. All patients with at least one claim with diagnosis codes denoting potential ADE between 1 July 2015 and 31 December 2015 were included. Potential ADE was defined as ADE identified in the claims data, because it was not verified. The index date was defined as the date of the first claim with potential ADEs. Demographic data were collected at the index date, while data on comorbidities and number of medications used were collected six months before the index date. Multivariate logistic regression was used to explore the association between potential ADEs and several factors, including sex, age group, insurance type, comorbidities, and number of prescribed medications. Patients with potential ADEs were older, had more chronic diseases, and used more medications than those without potential ADEs. In the multivariate analysis, occurrence of potential ADEs was associated with age (≥65 years, odds ratio [OR] 1.15, 95% confidence interval [CI] 1.08-1.21), Medical Aid program (OR 1.37, 95% CI 1.27-1.47), Charlson Comorbidity Index scores (≥5, OR 2.87, 95% CI 2.56-3.20), and use of six or more medications (6-10 medications, OR 1.89, 95% CI 1.79-1.99). Age, Medical Aid program, comorbidities, and number of medications were associated with occurrence of potential ADEs.

Adverse drug event trigger tool: construction and application of a readyto-use tool at Hue University of Medicine and Pharmacy Hospital

Background: Adverse drug event (ADE) is one of the most common causes of injury to patients, accounting for 19% of adverse events (AEs), particularly among the elderly due to their sensitivity to ADE. Thus, taking ADE detection is the first vital step in improving medication safety. Objective: This study aimed to develop an appropriate modified triggers tool based on Institute for Healthcare Improvement (IHI) Global Trigger tool for Adverse Events detecting potential ADEs in patients at Hue University Hospital. Materials and methods: Using a retrospective study on the medical records of inpatients treated in Hue University of Medicine and Pharmacy Hospital in 2020. Results: The modified ADE trigger tool encompassed 13 triggers. In the screening stage, the ADEs were found in 18 medical records (1.9% of total screening records), and 22 ADEs were identified, in which 19 ADEs were determined as adverse drug reactions (ADRs). The study also found that 17/19 ADRs had not been reported via a spontaneous reporting system (89.5%). The modified ADE Trigger tool’s positive predictive value (PPV) was 0.06. Conclusion: A modified ADE Trigger tool for detecting ADE has been constructed and applied at Hue University of Medicine and Pharmacy Hospital. This study would be the first motivation for further studies that attempt to apply this tool into daily clinical pharmacy activities and emphasize the role of Clinical Pharmacists at the hospital. Key words: Adverse Drug Event, adverse event, geriatrics, clinical pharmacy.

Behavioural side effects of inhaled corticosteroids among children and adolescents with asthma

BackgroundInhalation corticosteroids (ICS) are prescribed for treatment of asthma in approximately 3% of all children in Denmark. Despite limited evidence, case reports suggest that ICS-related behavioural adverse drug events (ADEs) may be frequent. In general, underreporting of ADEs to official databases is common, and little is known about doctor’s clinical experiences with behavioural ADEs when prescribing ICS for children with asthma. The objective was to investigate the extent of behavioural ADEs in children with asthma treated with ICS by comparing database findings to experiences of specialist doctors.MethodsFirst, databases of the European Medicines Agency (EMA) and the Danish Medicines Agency (DKMA) were searched for reports made by healthcare professionals about behavioural ADEs in children from 2009 to 2018. Second, questionnaire data on behavioural ADEs were collected from eight of the 11 specialist doctors responsible for treating children with asthma at the six paediatric departments in Central Denmark Region and North Denmark Region.ResultsEMA and DKMA had registered 104 and 3 reports, respectively, on behavioural ADEs during the 10-year study period. In contrast, five of the eight specialist doctors (45.5%) had experienced patients who had developed behavioural changes during ICS treatment. However, none of the five specialist doctors had filed reports on these events to DKMA.ConclusionBehaviour-related ADEs to ICS in children with asthma are likely to be highly underreported in official databases and doctors treating children with ICS should be aware of potential ADEs and consider submitting ADE reports whenever appropriate.

Prevalence of Potential Drug-Drug Interactions in Neonatal Intensive Care Unit of a Tertiary Care Hospital: A Prospective Observational Study

Hospitalized neonates in neonatal intensive care unit (NICU) are usually exposed to great number of drugs and they are susceptible to adverse outcomes due to their immature functioning organs and reasons like inappropriate dosing or choice of medicines. We aimed to assess the prevalence and characteristics of potential drug- drug interactions (pDDIs) in the NICU. In this prospective observational study, case sheets of neonates who were in the NICU for more than 24 hours and were administered with at least two drugs were analysed for pDDIs by using Lexicomp database. All pDDIs were classified according to their severity, reliability, risk level and their underlying mechanisms. Potential predictors and potential outcomes of pDDIs were also evaluated. We found that 66.2% of neonates were exposed to at least one pDDI. Total of 902 pDDIs comprising of 70 distinct pDDIs were identified of which 88% were moderate in severity. 11.8% and 0.2% of them were major and minor respectively. Most of pDDIs belonged to category C (61.4%) and category D (30%) of risk level. Majority of interactions had pharmacodynamic mechanism (65.7%) and fair scientific evidences (68.6%). The most common potential adverse drug events included increased sympathomimetic effects, nephrotoxicity and alteration of serum concentration of drugs. Systemic anti-infective were involved in majority of interactions. pDDIs were more prevalent in neonates with gestational age of &lt;32 weeks, &gt;11 days of hospital stay and those who received &gt;11 concomitant drugs. Identification of pDDIs and monitoring the neonates for potential adverse outcomes is mandatory especially in high risk conditions to avoid or minimize the actual harm.

The Impact of Medication Reconciliation on Continuityof Drug Therapy during Perioperative Period

Background. Medication errors and resultant adverse drug events (ADEs) often occur during transitions of care. Up to 67% of in-patients prescriptions have at least one unintentional medication discrepancy with previously prescribed therapy. The proportion of clinically significant medication discrepancies is 1159%. Studies from the developed countries demonstrated the effectiveness of medication reconciliation in reducing medication errors, ADEs and healthcare resource utilization. There is a necessity to conduct medication reconciliation studies within Russian current clinical practice to develop effective medical care quality and patients safety programs. Aims to evaluate the impact of pharmacologist-led medication reconciliation on the frequency and structure of unintentional medication discrepancies and potential ADEs at hospital admission and discharge. Methods. Standard care was compared to medication reconciliation led by a clinical pharmacologist in a prospective randomized trial of 410 elective surgical patients. Medication discrepancies at hospital admission and discharge were identified and reconciled. Clinical outcomes were evaluated by reviewing electronic health records. Results. In the intervention group the frequency of unintentional discrepancies at hospital admission decreased from 32.68 to 16.86%, the proportion of patients with at least one unintentional discrepancy decreased from 64.9 to 44.9%, the number of discrepancies per patient decreased from 1.5 to 0.66. The incidence of discrepancies at hospital discharge decreased from 82.90 to 43.29%, the proportion of patients with discrepancies decreased from 95.61 to 52.68%, the average number of discrepancies per patient decreased from 2.79 to 1.67. Medication reconciliation led by clinical pharmacologist decreased the frequency of unscheduled out-patient visits after discharge from 7.32 to 2.93%. The determined risk factors for unintentional discrepancies at hospital admission were: prescribing of cardiovascular, endocrine drugs and those affecting the central nervous system. Both at admission and discharge medication reconciliation was the significant factor reducing the risk of unintentional discrepancies. Conclusions. Medication reconciliation at hospital admission and discharge reduces the frequency of unintentional discrepancies in drug prescriptions by 16 and 40%, respectively. The implementation of medication reconciliation into clinical practice reduces unscheduled out-patient visits after hospital discharge.

Efficacy of a Bariatric Surgery Clinic-Based Pharmacist

PurposeTo evaluate the impact of a bariatric clinic-based pharmacist on inpatient length of stay, medication errors, and patient experience.Materials and MethodsThis was a retrospective cohort study comparing patients who received a pre-operative pharmacist consultation to historical cases without pre-operative pharmacist consultation prior to admission for bariatric surgery. A patient experience survey was administered post-operatively to the intervention group. The primary outcome was hospital length of stay (LOS). Secondary outcomes included corrected medication errors on reconciliation, pharmacist interventions, adverse drug event (ADE) prevention, and patient satisfaction.ResultsWith 68 patients in the intervention group and 67 patients in the control group, the majority were female (76%) and received either laparoscopic Roux-en-Y gastric bypass (53%) or sleeve gastrectomy (47%). The median LOS in the intervention group was 55.5 h, which did not significantly differ from the median 57.9 h in the control group (p = 0.56). The clinic-based pharmacist made an average of 13 interventions per patient. Surveys were distributed to 73 patients with a 60% response rate. High overall satisfaction with the pre-operative pharmacist consultation was reported by 97% of patients.ConclusionAlthough hospital LOS did not significantly differ between groups, pre-operative pharmacist consultation prevented potential ADEs, and provided strong patient satisfaction. Having pharmacists as part of a multidisciplinary approach to bariatric surgery patient care can prevent medication-related adverse events and improve patient satisfaction.Graphic

Evaluating the Impact of Medication Risk Mitigation Services in Medically Complex Older Adults.

Adverse drug events (ADEs) represent an expensive societal burden that disproportionally affects older adults. Therefore, value-based organizations that provide care to older adults—such as the Program of All-Inclusive Care for the Elderly (PACE)—should be highly motivated to identify actual or potential ADEs to mitigate risks and avoid downstream costs. We sought to determine whether PACE participants receiving medication risk mitigation (MRM) services exhibit improvements in total healthcare costs and other outcomes compared to participants not receiving structured MRM. Data from 2545 PACE participants from 19 centers were obtained for the years 2018 and 2019. We compared the year-over-year changes in outcomes between patients not receiving (control) or receiving structured MRM services. Data were adjusted based on participant multimorbidity and geographic location. Our analyses demonstrate that costs in the MRM cohort exhibited a significantly smaller year-to-year increase compared to the control (MRM: USD 4386/participant/year [95% CI, USD 3040–5732] vs. no MRM: USD 9410/participant/year [95% CI, USD 7737–11,084]). Therefore, receipt of structured MRM services reduced total healthcare costs (p < 0.001) by USD 5024 per participant from 2018 to 2019. The large majority (75.8%) of the reduction involved facility-related expenditures (e.g., hospital admission, emergency department visits, skilled nursing). In sum, our findings suggest that structured MRM services can curb growing year-over-year healthcare costs for PACE participants.

A Data-Driven Medical Decision Framework for Associating Adverse Drug Events with Drug-Drug Interaction Mechanisms.

Adverse drug events (ADEs) occur when multiple drugs interact within an individual, thus causing effects that were not initially predicted. Such toxic interactions lead to morbidity and mortality. Contemporary research surrounding ADEs has tended to focus on the detection of potential ADEs without great concern for elucidating the associations of drug-drug interaction (DDI) mechanisms that can predict potential adverse drug reactions (ADRs). Such associations are of great practical importance for everyday pharmacovigilance efforts. This study presents a data-driven framework for conducting knowledge-driven data analysis that combines a semantic inference system and enrichment analysis in order to identify potential ADE mechanisms. The framework was used to rank mechanisms according to their relevance for DDIs and also to categorize ADEs based on the number of DDI mechanism associations identified through enrichment analysis. Its validity is demonstrated through using both commercial and publicly available DDI resources. The results of this study solidly prove the framework's effectiveness and highlight potential for future research by way of incorporating additional and broader data to deepen and expand its capabilities.

ADENet: a novel network-based inference method for prediction of drug adverse events.

Identification of adverse drug events (ADEs) is crucial to reduce human health risks and improve drug safety assessment. With an increasing number of biological and medical data, computational methods such as network-based methods were proposed for ADE prediction with high efficiency and low cost. However, previous network-based methods rely on the topological information of known drug-ADE networks, and hence cannot make predictions for novel compounds without any known ADE. In this study, we introduced chemical substructures to bridge the gap between the drug-ADE network and novel compounds, and developed a novel network-based method named ADENet, which can predict potential ADEs for not only drugs within the drug-ADE network, but also novel compounds outside the network. To show the performance of ADENet, we collected drug-ADE associations from a comprehensive database named MetaADEDB and constructed a series of network-based prediction models. These models obtained high area under the receiver operating characteristic curve values ranging from 0.871 to 0.947 in 10-fold cross-validation. The best model further showed high performance in external validation, which outperformed a previous network-based and a recent deep learning-based method. Using several approved drugs as case studies, we found that 32-54% of the predicted ADEs can be validated by the literature, indicating the practical value of ADENet. Moreover, ADENet is freely available at our web server named NetInfer (http://lmmd.ecust.edu.cn/netinfer). In summary, our method would provide a promising tool for ADE prediction and drug safety assessment in drug discovery and development.

Combining a Pharmacological Network Model with a Bayesian Signal Detection Algorithm to Improve the Detection of Adverse Drug Events.

Introduction: Improving adverse drug event (ADE) detection is important for post-marketing drug safety surveillance. Existing statistical approaches can be further optimized owing to their high efficiency and low cost. Objective: The objective of this study was to evaluate the proposed approach for use in pharmacovigilance, the early detection of potential ADEs, and the improvement of drug safety. Methods: We developed a novel integrated approach, the Bayesian signal detection algorithm, based on the pharmacological network model (ICPNM) using the FDA Adverse Event Reporting System (FAERS) data published from 2004 to 2009 and from 2014 to 2019Q2, PubChem, and DrugBank database. First, we used a pharmacological network model to generate the probabilities for drug-ADE associations, which comprised the proper prior information component (IC). We then defined the probability of the propensity score adjustment based on a logistic regression model to control for the confounding bias. Finally, we chose the Side Effect Resource (SIDER) and the Observational Medical Outcomes Partnership (OMOP) data to evaluate the detection performance and robustness of the ICPNM compared with the statistical approaches [disproportionality analysis (DPA)] by using the area under the receiver operator characteristics curve (AUC) and Youden’s index. Results: Of the statistical approaches implemented, the ICPNM showed the best performance (AUC, 0.8291; Youden’s index, 0.5836). Meanwhile, the AUCs of the IC, EBGM, ROR, and PRR were 0.7343, 0.7231, 0.6828, and 0.6721, respectively. Conclusion: The proposed ICPNM combined the strengths of the pharmacological network model and the Bayesian signal detection algorithm and performed better in detecting true drug-ADE associations. It also detected newer ADE signals than a DPA and may be complementary to the existing statistical approaches.

Retrospective study of the prevalence and characteristics of adverse drug events in adults who present to an Australian emergency department.

To determine the burden, on the ED, of harm from unintentional adverse drug events (ADEs) in the community. A retrospective, observational study of 936 randomly selected presentations to a level 6 ED at a principal referral hospital in Brisbane, Australia, in November 2017. Clinical records were screened by a pharmacist, who identified suspected ADEs. All suspected ADEs and a random selection of presentations without ADEs were reviewed by an expert panel, which classified, by consensus: occurrence and type of ADE, contribution of ADE to presentation, severity of harm and preventability of presentation. Medication-related ED presentations (ADE-Ps) and potential ADEs were, respectively, defined as presentations directly attributable to an ADE, and medication events that occurred but did not cause the ED presentation. Descriptive data analysis was performed. The median (interquartile range) age of patients was 40 (27-58) years, with 49.7% (95% confidence interval [CI] 46.5-52.9) being male. The prevalences of ADE-Ps and potential ADEs were 9.2% (95% CI 7.5-11.3) and 5.0% (95% CI 3.8-6.6), respectively. The severity of harm was classified as 'death or likely permanent harm' in 4.7% (95% CI 0.2-9.1) of ADE-Ps, 'temporary harm' (89.5%, 95% CI 83.1-96.0) and 'minimal or no harm' (5.8%, 95% CI 0.9-10.8). Most (79.1%, 95% CI 70.5-87.7) ADE-Ps were preventable. There is a high burden on emergency care because of unintended medication harm in the community. Interventions to reduce such harm are likely to require a co-ordinated primary, acute and public healthcare response. The high proportion of presentations with potential ADEs indicates opportunity for harm mitigation in the ED.