Potential Multidrug Interactions in Elderly Ambulatory Patients

Aim. Polypharmacy may increase the prevalence of potential multidrug interactions (pMDIs), where one drug interacts with two or more other drugs, possibly amplifying the risk of a potential adverse drug event (pADE). The major goal of this study was to estimate the prevalence of amplifying pMDIs in an ambulatory cohort of older patients. Methods. Current medication lists of 22033 randomly chosen outpatients ≥50 years old were extracted from the New York Presbyterian Hospital (NYP) data warehouse. Network analysis identified patients prescribed three or more interacting drugs from their current medication lists. Potentially harmful interactions were identified from the NYP drug-drug interaction alerting system. pMDIs were considered amplifying if the interactions increased the probability of a pADE through pharmacokinetic, pharmacodynamic or conditional mechanisms. Results. pMDIs were identified in 5.1% of the medication lists; 3.4% were three-drug and 1.1% were four-drug pMDIs. The most common drugs involved were psychotropic, comprising 23.3% of the total drugs. The most common pADEs associated with the interactions were serotonin syndrome (17.2%), seizures (14.4%), prolonged QT interval (15.8%) and bleeding (14.4%). pADE amplification risk was identified in 71.8% of three-drug pMDIs when one drug interacted with two others, 97.8% when all three interacted with each other, and 93% for four-drug pMDIs. Conclusion. Our data suggest that approximately 5% of elderly ambulatory patients may be exposed to pMDIs which amplify the probability of associated adverse drug events. The recent and persistent rise in polypharmacy will likely increase the prevalence of pMDIs and potential exposure to serious adverse events.

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Prevalence of potentially harmful multidrug interactions on medication lists of elderly ambulatory patients

BMC Geriatrics ◽

10.1186/s12877-021-02594-z ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Tara V. Anand ◽

Brendan K. Wallace ◽

Herbert S. Chase

Keyword(s):

Drug Interactions ◽

Serotonin Syndrome ◽

Adverse Drug Events ◽

Pharmacodynamic Interactions ◽

Potential Ades ◽

Ambulatory Patients ◽

Alerting System ◽

Prolonged Qt Interval ◽

Prolonged Qt ◽

Enterprise Data Warehouse

Abstract Background It has been hypothesized that polypharmacy may increase the frequency of multidrug interactions (MDIs) where one drug interacts with two or more other drugs, amplifying the risk of associated adverse drug events (ADEs). The main objective of this study was to determine the prevalence of MDIs in medication lists of elderly ambulatory patients and to identify the medications most commonly involved in MDIs that amplify the risk of ADEs. Methods Medication lists stored in the electronic health record (EHR) of 6,545 outpatients ≥60 years old were extracted from the enterprise data warehouse. Network analysis identified patients with three or more interacting medications from their medication lists. Potentially harmful interactions were identified from the enterprise drug-drug interaction alerting system. MDIs were considered to amplify the risk if interactions could increase the probability of ADEs. Results MDIs were identified in 1.3 % of the medication lists, the majority of which involved three interacting drugs (75.6 %) while the remainder involved four (15.6 %) or five or more (8.9 %) interacting drugs. The average number of medications on the lists was 3.1 ± 2.3 in patients with no drug interactions and 8.6 ± 3.4 in patients with MDIs. The prevalence of MDIs on medication lists was greater than 10 % in patients prescribed bupropion, tramadol, trazodone, cyclobenzaprine, fluoxetine, ondansetron, or quetiapine and greater than 20 % in patients prescribed amiodarone or methotrexate. All MDIs were potentially risk-amplifying due to pharmacodynamic interactions, where three or more medications were associated with the same ADE, or pharmacokinetic, where two or more drugs reduced the metabolism of a third drug. The most common drugs involved in MDIs were psychotropic, comprising 35.1 % of all drugs involved. The most common serious potential ADEs associated with the interactions were serotonin syndrome, seizures, prolonged QT interval and bleeding. Conclusions An identifiable number of medications, the majority of which are psychotropic, may be involved in MDIs in elderly ambulatory patients which may amplify the risk of serious ADEs. To mitigate the risk, providers will need to pay special attention to the overlapping drug-drug interactions which result in MDIs.

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Using ActionADE to create information continuity to reduce re-exposures to harmful medications: study protocol for a randomized controlled trial

Trials ◽

10.1186/s13063-021-05061-7 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Jeffrey P. Hau ◽

Penelope M. A. Brasher ◽

Amber Cragg ◽

Serena Small ◽

Maeve Wickham ◽

...

Keyword(s):

Health Information ◽

Adverse Drug Event ◽

Primary Outcome ◽

Adverse Drug Events ◽

Primary Objective ◽

Drug Event ◽

Controlled Trials ◽

Drug Reactions ◽

Main Trial ◽

Randomized Controlled

Abstract Background Repeat exposures to culprit medications are a common cause of preventable adverse drug events. Health information technologies have the potential to reduce repeat adverse drug events by improving information continuity. However, they rarely interoperate to ensure providers can view adverse drug events documented in other systems. We designed ActionADE to enable rapid documentation of adverse drug events and communication of standardized information across health sectors by integrating with legacy systems. We will leverage ActionADE’s implementation to conduct two parallel, randomized trials: patients with adverse drug reactions in the main trial and those diagnosed with non-adherence in a secondary trial. Primary objective of the main trial is to evaluate the effects of providing information continuity about adverse drug reactions on culprit medication re-dispensations over 12 months. Primary objective of the secondary trial is to evaluate the effect of providing information continuity on adherence over 12 months. Methods We will conduct two parallel group, triple-blind randomized controlled trials in participating hospitals in British Columbia, Canada. We will enroll adults presenting to hospital with an adverse drug event to prescribed outpatient medication. Clinicians will document the adverse drug event in ActionADE. The software will use an algorithm to determine patient eligibility and allocate eligible patients to experimental or control. In the experimental arm, ActionADE will transmit information to PharmaNet, where adverse drug event information will be displayed in community pharmacies when re-dispensations are attempted. In the control arm, ActionADE will retain information in the local record. We will enroll 3600 adults with an adverse drug reaction into the main trial. The main trial’s primary outcome is re-dispensation of a culprit or same-class medication within 12 months; the secondary trial’s primary outcome will be adherence to culprit medication. Secondary outcomes include health services utilization and mortality. Discussion These studies have the potential to guide policy decisions and investments needed to drive health information technology integrations to prevent repeat adverse drug events. We present an example of how a health information technology implementation can be leveraged to conduct pragmatic randomized controlled trials. Trial registration ClinicalTrials.gov NCT04568668, NCT04574648. Registered on 1 October 2020.

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JADE: A tool for medical researchers to explore adverse drug events using health claims data

Applied Clinical Informatics ◽

10.4338/aci-2014-04-ra-0036 ◽

2014 ◽

Vol 05 (03) ◽

pp. 621-629 ◽

Cited By ~ 4

Author(s):

S.K. Sauter ◽

C. Rinner ◽

L.M. Neuhofer ◽

M. Wolzt ◽

W. Grossmann ◽

...

Keyword(s):

Adverse Drug Events ◽

Claims Data ◽

Age Groups ◽

Rule Learning ◽

Health Claims ◽

Drug Event ◽

Study Cohort ◽

Defined Daily Doses ◽

Health Claims Data ◽

Medical Researchers

SummaryObjective: The objective of our project was to create a tool for physicians to explore health claims data with regard to adverse drug reactions. The Java Adverse Drug Event (JADE) tool should enable the analysis of prescribed drugs in connection with diagnoses from hospital stays.Methods: We calculated the number of days drugs were taken by using the defined daily doses and estimated possible interactions between dispensed drugs using the Austria Codex, a database including drug-drug interactions. The JADE tool was implemented using Java, R and a PostgreSQL database.Results: Beside an overview of the study cohort which includes selection of gender and age groups, selected statistical methods like association rule learning, logistic regression model and the number needed to harm have been implemented.Conclusion: The JADE tool can support physicians during their planning of clinical trials by showing the occurrences of adverse drug events with population based information.Citation: Edlinger D, Sauter SK, Rinner C, Neuhofer LM, Wolzt M, Grossmann W, Endel G, Gall W. JADE: A tool for medical researchers to explore adverse drug events using health claims data. Appl Clin Inf 2014; 5: 621–629http://dx.doi.org/10.4338/ACI-2014-04-RA-0036

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US Emergency Department Visits for Adverse Drug Events From Antibiotics in Children, 2011–2015

Journal of the Pediatric Infectious Diseases Society ◽

10.1093/jpids/piy066 ◽

2018 ◽

Vol 8 (5) ◽

pp. 384-391 ◽

Cited By ~ 8

Author(s):

Maribeth C Lovegrove ◽

Andrew I Geller ◽

Katherine E Fleming-Dutra ◽

Nadine Shehab ◽

Mathew R P Sapiano ◽

...

Keyword(s):

Emergency Department ◽

Adverse Drug Events ◽

Emergency Department Visits ◽

Drug Event ◽

Injury Surveillance System ◽

Adverse Event Data ◽

Systemic Medication ◽

Ed Visits ◽

Pharmacy Dispensing Data

Abstract Background Antibiotics are among the most commonly prescribed medications for children; however, at least one-third of pediatric antibiotic prescriptions are unnecessary. National data on short-term antibiotic-related harms could inform efforts to reduce overprescribing and to supplement interventions that focus on the long-term benefits of reducing antibiotic resistance. Methods Frequencies and rates of emergency department (ED) visits for antibiotic adverse drug events (ADEs) in children were estimated using adverse event data from the National Electronic Injury Surveillance System–Cooperative Adverse Drug Event Surveillance project and retail pharmacy dispensing data from QuintilesIMS (2011–2015). Results On the basis of 6542 surveillance cases, an estimated 69464 ED visits (95% confidence interval, 53488–85441) were made annually for antibiotic ADEs among children aged ≤19 years from 2011 to 2015, which accounts for 46.2% of ED visits for ADEs that results from systemic medication. Two-fifths (40.7%) of ED visits for antibiotic ADEs involved a child aged ≤2 years, and 86.1% involved an allergic reaction. Amoxicillin was the most commonly implicated antibiotic among children aged ≤9 years. When we accounted for dispensed prescriptions, the rates of ED visits for antibiotic ADEs declined with increasing age for all antibiotics except sulfamethoxazole-trimethoprim. Amoxicillin had the highest rate of ED visits for antibiotic ADEs among children aged ≤2 years, whereas sulfamethoxazole-trimethoprim resulted in the highest rate among children aged 10 to 19 years (29.9 and 24.2 ED visits per 10000 dispensed prescriptions, respectively). Conclusions Antibiotic ADEs lead to many ED visits, particularly among young children. Communicating the risks of antibiotic ADEs could help reduce unnecessary prescribing. Prevention efforts could target pediatric patients who are at the greatest risk of harm.

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Adverse Drug Event of Rheumatoid Arthritis and Osteoarthritis Ambulatory Patients in a Large Teaching Hospital in Thailand

Drug Safety ◽

10.2165/00002018-200730100-00085 ◽

2007 ◽

Vol 30 (10) ◽

pp. 919-990

Author(s):

P Tragulpiankit ◽

S Chulavatnatol ◽

T Limsuwan ◽

U Sirikhedgon ◽

S Somjarit

Keyword(s):

Rheumatoid Arthritis ◽

Teaching Hospital ◽

Adverse Drug Event ◽

Drug Event ◽

Large Teaching Hospital ◽

Ambulatory Patients

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Utility of Different Data Standards to Document Adverse Drug Event Symptoms and Diagnoses: A Mixed Methods Study (Preprint)

10.2196/preprints.27188 ◽

2021 ◽

Author(s):

Erina Chan ◽

Serena S Small ◽

Maeve E Wickham ◽

Vicki Cheng ◽

Ellen Balka ◽

...

Keyword(s):

Mixed Methods ◽

Adverse Drug Event ◽

Adverse Drug Events ◽

Retrospective Chart Review ◽

Drug Event ◽

Free Text ◽

Snomed Ct ◽

Data Standards ◽

Data Standard ◽

Research Assistants

BACKGROUND Existing systems to document adverse drug events often use free text data entry, producing non-standardized, unstructured data prone to misinterpretation. Standardized terminology may improve data quality, but it is unclear which data standard is most appropriate to document adverse drug event symptoms and diagnoses. OBJECTIVE Our objective was to compare the utility, strengths, and weaknesses of different data standards for documenting adverse drug event symptoms and diagnoses. METHODS We performed a mixed-methods sub-study of a multicenter retrospective chart review. We reviewed research records of prospectively diagnosed adverse drug events at 5 Canadian hospitals. Two pharmacy research assistants independently entered symptoms and/or diagnoses for adverse drug events using 4 standards: MedDRA, SNOMED CT, SNOMED Adverse Reaction, and ICD-11. Disagreements between research assistants regarding case-specific utility of data standards were discussed until reaching consensus. We used consensus ratings to determine proportion of adverse drug events covered by a data standard, and coded and analyzed field notes from consensus sessions. RESULTS We reviewed 573 adverse drug events and found MedDRA and ICD-11 had excellent coverage of adverse drug event symptoms and/or diagnoses. While MedDRA had the highest number of matches between the research assistants, ICD-11 had the fewest. SNOMED ADR had the lowest proportion of adverse drug event coverage. Research assistants were most likely to encounter terminological challenges with SNOMED ADR and usability challenges with ICD-11, and least likely with MedDRA. CONCLUSIONS Usability, comprehensiveness, and accuracy are important features of data standards for documenting ADE symptoms and diagnoses. Based on our results, we would recommend the use of MedDRA.

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Pharmacovigilance Assessment of Drug-Induced Acute Pancreatitis Using a Spontaneous Reporting Database

International Journal of Toxicology ◽

10.1177/1091581819870717 ◽

2019 ◽

Vol 38 (6) ◽

pp. 487-492 ◽

Cited By ~ 3

Author(s):

Iku Niinomi ◽

Keiko Hosohata ◽

Saki Oyama ◽

Ayaka Inada ◽

Tomohito Wakabayashi ◽

...

Keyword(s):

Acute Pancreatitis ◽

Odds Ratio ◽

Spontaneous Reporting ◽

Adverse Drug Events ◽

Drug Event ◽

Reporting Odds Ratio ◽

Event Report ◽

Disproportionality Analysis ◽

Drug Induced ◽

Spontaneous Reporting Database

Background: Acute pancreatitis (AP) is associated with risks of morbidity and mortality. The incidence of AP recently increased compared to that traditionally reported in the literature. Objective: The purpose of this study was to evaluate the possible association between AP and drugs using the Japanese Adverse Drug Event Report (JADER) database, which is a spontaneous reporting database of adverse drug events. Methods: Adverse event reports submitted to the JADER database between 2004 and 2017 were analyzed. Disproportionality analysis was performed by calculating the reporting odds ratio (ROR) with 95% confidence intervals for signal detection. Results: A total of 3,443 reports (0.17% of all adverse events) were identified as drug-induced AP, in which 431 different drugs were involved. Acute pancreatitis was frequently reported in men (58.5%) in their 60s (19.1%); 40.6% developed AP within 4 weeks after the treatment. Among the most frequently reported drugs, signals were detected for prednisolone, ribavirin, sitagliptin, mesalazine, tacrolimus, and l-asparaginase, which are well-known causes of AP. Telaprevir, donepezil, and ustekinumab also generated signals. As for drugs with high RORs, l-asparaginase and alogliptin were noteworthy. Conclusion: Most of the identified drugs were already known to induce AP, but the likelihood of the reporting of AP varied among the drugs. Our results should raise physicians’ awareness of drugs associated with AP, but further investigation of these medications is warranted.

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Preventing Adverse Drug Events in Hospitalized Patients

Annals of Pharmacotherapy ◽

10.1177/106002809402800417 ◽

1994 ◽

Vol 28 (4) ◽

pp. 523-527 ◽

Cited By ~ 88

Author(s):

R. Scott Evans ◽

Stanley L. Pestotnik ◽

David C. Classen ◽

Susan D. Horn ◽

Sheron B. Bass ◽

...

Keyword(s):

Adverse Drug Events ◽

Salt Lake ◽

Care Center ◽

Tertiary Care ◽

Salt Lake City ◽

Hospitalized Patients ◽

Drug Event ◽

Antibiotic Administration ◽

Type B ◽

Lake City

OBJECTIVE: To use computerized adverse drug event (ADE) surveillance to help identify methods to reduce the number of ADEs in hospitalized patients. DESIGN: Prospective study of 79 719 hospitalized patients during a 44-month period. SETTING: LDS Hospital, a 520-bed tertiary care center affiliated with the University of Utah School of Medicine, Salt Lake City. INTERVENTION: Sequential study periods of at least one year each were compared. In the first period, data were collected but not reported to physicians, pharmacists, or nurses. In the subsequent study periods, three interventions (computerized alerts of drug allergies, standardized antibiotic administration rates, and timely physician notification of all ADEs) were made to reduce the number of type B (allergic or idiosyncratic reactions) and severe ADEs. RESULTS: In the first study period, we identified 56 type B ADEs during 120 213 patient days. During two subsequent study periods that included alerts to physicians of known drug allergies and standardized antibiotic administration rates, 8 type B events were identified during 113 237 patient days and 18 during 107 868 patient days, respectively (p<0.OO2). Early notification of physicians of all confirmed ADEs regardless of severity was associated with asignificant reduction of ADEs classified as severe from 41 during 113 859 patient days in the first study period to 12 during 103 071 patient days and 15 during 108 320 patient days in two subsequent study periods, respectively (p<0.00 1). CONCLUSIONS: Prospective surveillance of computer-based medical records for known drug allergies and appropriate drug administration rates can reduce the number of type B ADEs. Early ADE detection and notification of physicians permit drug and dosage changes that reduce the progression of mild and moderate ADEs to more severe conditions.

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Monitoring adverse events in older hospitalized patients: A retrospective cross-sectional study using validated screening criteria with administrative data

Journal of Hospital Administration ◽

10.5430/jha.v7n6p7 ◽

2018 ◽

Vol 7 (5) ◽

pp. 7

Author(s):

Stacy A. Ackroyd-Stolarz ◽

Susan K. Bowles ◽

Lorri Giffin

Keyword(s):

Administrative Data ◽

Older Patients ◽

Adverse Drug Events ◽

Pressure Ulcers ◽

Cross Sectional Study ◽

System Level ◽

Drug Event ◽

Sectional Study ◽

Cross Sectional ◽

Screening Criteria

Objective: Older patients are at higher risk of experiencing an adverse event (AE) during an acute hospitalization. The objective of the current study was to use routinely collected administrative data to characterize AEs and their system-level impact for older patients hospitalized in one Canadian health authority.Methods: This retrospective cross-sectional study occurred in the Capital District Health Authority in Nova Scotia, Canada between April 1, 2012 and March 31, 2013. The primary outcome was identification of pressure ulcers, fall-related injuries and adverse drug events in patients 65 years of age and older admitted to an acute inpatient service. AEs were identified using validated screening criteria. Data were analyzed using standard descriptive statistics.Results: There were 11,747 hospitalizations during the study period. A total of 330 (2.8%) AEs in 325 patients were identified using the screening criteria. This included 55 (16.7% of 330) pressure ulcers, 25 (7.6%) fall-related injuries and 250 (75.8%) adverse drug events. The average length of stay was significantly higher in patients with a pressure ulcer (35.8 ± 47.3 vs. 9.0 ± 14.8 days, p < .0001), fall-related injury (30.3 ± 23.2 vs. 9.0 ± 15.2 days, p < .0001), or adverse drug event (14.6 ± 14.4 vs. 9.0 ± 15.2 days, p < .0001) during their acute hospitalization.Conclusions:Use of validated screening criteria with administrative hospitalization data provides important information for monitoring the system-level impact of common AEs in older patients. Significant and clinically important differences in healthcare utilization underscore the value in monitoring these AEs in this growing patient population.

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Drug-related problems with targeted/immunotherapies at an oncology outpatient clinic

Journal of Oncology Pharmacy Practice ◽

10.1177/1078155219861679 ◽

2019 ◽

Vol 26 (3) ◽

pp. 595-602

Author(s):

Esra Kucuk ◽

Aygin Bayraktar-Ekincioglu ◽

Mustafa Erman ◽

Saadettin Kilickap

Keyword(s):

Adverse Drug Event ◽

Clinical Pharmacist ◽

Adverse Drug Events ◽

Drug Event ◽

Targeted Chemotherapy ◽

Drug Related Problems ◽

Patients With Cancer ◽

Common Drug ◽

Oncology Care ◽

The Impact

Background Some studies in the literature describe drug-related problems in patients with cancer, although few studies focused on patients receiving targeted chemotherapy and/or immunotherapy. To identify the incidence of drug-related problems in patients receiving targeted chemotherapy and/or immunotherapy, and demonstrate the impact of a clinical pharmacist in an outpatient oncology care setting. Methods Prospective study was conducted in a hospital outpatient oncology clinic between October 2015 and March 2016. Patients greater than 18 years old receiving cetuximab, nivolumab, ipilimumab, or pembrolizumab were included in the study and monitored over a three-month period by a clinical pharmacist. Drug-related problems were analyzed using the Pharmaceutical Care Network Europe classification system. The main outcome measures were the frequency and causes of drug-related problems and the degree of resolution achieved through the involvement of a clinical pharmacist. Results A total of 54 patients (mean age: 57 ± 12 years) were included. There were 105 drug-related problems and 159 associated causes. Among the planned interventions (n = 149), 92 interventions were at the patient-level with 88 (96%) being accepted by the doctors. This resulted in 68 (65%) drug-related problems being completely resolved and 9 (8.6%) being partially resolved. The most common drug-related problem identified was “adverse drug event” (n = 38, 36%). Of the 105 drug-related problems, 63 (60%) related to targeted chemotherapy and/or immunotherapy with 34 (54%) classified as an “adverse drug event.” Conclusion Adverse drug events were the most common drug-related problems in patients with cancer. The involvement of a clinical pharmacist improved the identification of drug-related problems and helped optimize treatment outcomes in patients receiving targeted chemotherapy/immunotherapy.

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