Total Adverse Drug Events Research Articles

Comparative analysis of semaglutide induced adverse reactions: Insights from FAERS database and social media reviews with a focus on oral vs subcutaneous administration

BackgroundCompared to alternative weight-loss strategies and medications, semaglutide stands out for its convenience and efficacy, resulting in a significant increase in prescriptions and raising public safety concerns. Furthermore, the safety profiles of its oral and subcutaneous formulations require further examination.ObjectiveOur goal is to investigate the potential safety risks associated with semaglutide by analyzing data from the FAERS database and social media. Additionally, we aim to compare the adverse drug reaction (ADR) signals between the oral and subcutaneous administration routes of semaglutide.MethodsWe collected semaglutide-related reports from the FAERS database spanning Q1 2018 to Q2 2023, and patient reviews on WebMD and AskaPatient up to 20 July 2023. Following data extraction and cleansing, we conducted descriptive analyses of demographic characteristics. Subsequently, we calculated adverse drug reaction (ADR) signals using the reporting odds ratio (ROR).ResultsWe identified 19,289 and 422 semaglutide-related adverse drug events (ADEs) reported in the FAERS database and online patient reviews, respectively. Gastrointestinal disorders emerged as the most commonly reported System Organ Class (SOC) in both datasets. Predominant Preferred Terms (PTs) included nausea, vomiting, and diarrhea. Serious outcomes constituted 3.07% and 2.25% of all cases for oral and subcutaneous semaglutide, respectively. At the SOC level, gastrointestinal disorders accounted for 30.19% of total ADEs in oral semaglutide, slightly surpassing the 27.76% in subcutaneous semaglutide. The median onset for gastrointestinal PTs was 4 days in both oral (Q1: 1, Q3: 32) and subcutaneous (Q1: 1, Q3: 35) formulations. Noteworthy, new serious adverse event (AE) signals were identified, including hemorrhagic diarrhea (ROR: 3.69), hepatic pain (ROR: 4.20), abnormal hormone levels (ROR: 6.51), and pancreatic failure (ROR: 36.34) in subcutaneous semaglutide, and Dupuytren’s contracture (ROR: 46.85) in oral semaglutide.ConclusionOur study delineates the safety profile of semaglutide using data from the FAERS database and social media. And identified novel ADR signals specific to oral and subcutaneous forms of semaglutide.

Adherence to Antibiotic Stewardship Program Associated with Shorter Course of Treatment and Fewer Adverse Events

Group Name: NorthShore University HealthSystemBackground: Prolonged antibiotic use has been attributed to an increased incidence of adverse drug events (ADEs). Cessation of unnecessary antibiotics would decrease length of treatment and may help prevent these adverse events. We evaluated whether an antibiotic stewardship intervention aimed at stopping unnecessary antibiotic usage would both shorten the duration of treatment and reduce ADEs. Methods: At NorthShore University HealthSystem, a 4-hospital, 832-bed system, we identified patients who were started on empiric antibiotics during a hospital admission between May 2, 2016, and June 30, 2018. Within 24 hours of antibiotic initiation, an infectious disease (ID) physician reviewed each patient chart. If the patient was unlikely to have a symptomatic bacterial infection, the ID physician left a note in the electronic medical record (EMR) recommending antibiotic cessation. Two physician reviewers retrospectively reviewed whether the treatment team accepted these recommendations and assessed potential ADEs for 30 days after the recommendation through inpatient and outpatient notes in the EMR. These ADEs were defined using previously published criteria. If the 2 reviewers disagreed on the presence of an ADE, an ID physician acted as the tie breaker. We compared the number of antibiotic days and the number of ADEs between cases in which the recommendations were followed and cases in which they were not. Results: We reviewed 168 cases: 78 (46.43%) followed recommendations and 90 (53.57%) did not. There were no significant differences in baseline patient characteristics between the 2 groups. There was a significant difference in total ADEs between the 2 groups: in 6 cases (7.69%) the recommendations were followed, and 21 (23.33%) they were not followed (P = .011). There was also a significant difference in antibiotic days between cases in which recommendations were followed (1.40 days) versus those in which they were not followed (1.99 days) (p < 0.001). Conclusions: Antibiotic-associated adverse events can cause harm to patients and increase healthcare costs, particularly when used for patients who are unlikely to have a bacterial infection. An antibiotic stewardship program to identify patients in an EMR who are unlikely to benefit from antibiotic use can decrease the length of total antibiotic usage and help prevent adverse events.Funding: NoDisclosures: None

Computerized prescription order entry and adverse drug events in pediatrics: a systematic review

Abstract Background Potentially harmful errors occur in pediatric patients at a rate three times higher than in adults, mainly due to dosage calculations. Objective. To evaluate the effect of Computerized Prescription Order Entry (CPOE) and Decision Support Systems (DSS) on Adverse Drug Events (ADE) in pediatrics. Method. Systematic review updated up to December 2019 in the PubMed, Scopus, Web of Science and Embase, Lilacs and cross-references, recorded in Prospero CRD 42019126590. Observational and pre- and post-implementation CPOE studies were included. in any language. A scale was used for methodological evaluation of the studies. Relative risk (RR), attributable risk (AR) or number needed to treat (NNT) with 95% CIs were computed for comparing the incidence of total, actual, preventable and potentially harmful ADE. Results Starting with 203 retrieved abstracts, 12 articles were included - eight interventional and four observational studies. Five articles evaluated CPOE and seven CPOE plus DSS. Settings for eleven studies were hospitals and one an outpatient facility. Sample sizes ranged from 514 to 45,615 totaling 112,187 patients. The number of prescriptions ranged from 724 to 92,398, totaling 182,803. A reduction in total ADE was observed in two studies. The risk reduction of preventable ADE ranged from 24% RR 0.76 (0.59 - 0.97) to 47% RR 0.53 (0.29-0.91) in four articles. Potentially harmful ADE (ADE ph) in five studies were reduced from 76% RR = 0.24 (0.09-0.68) to 44% (RR 0.56 (0.46 - 0.70), with an AR variyng from 1.8 to 0.9%. One of the articles stated that 64 (95% CI 25-100) patients would need to be using CPOE in order to avoid one potentially harmful ADE. Studies identified reductions in ADE in various settings- two in wards, one in wards and Pediatric Intensive Care Unit (PICU), the others in PICU and Neonatal Intensive Care Units. Conclusions Implementation of CPOE plus DSS reduces EADs in pediatric settings. Key messages Accumulated evidence favors implementation of CPOE plus DSS as important for prevention of ADE in pediatric settings. Potentially harmful and preventable errors can be avoided by implementing electronic prescribing systems in pediatrics. Its use should be encouraged in countries in low-income countries.

Use of a Bioinformatics-Based Toxicity Scoring System to Assess Serotonin Burden and Predict Population-Level Adverse Drug Events from Concomitant Serotonergic Drug Therapy.

Numerous medications interact at serotonin (5-hydroxytryptamine [5-HT]) receptors directly or through off-target interactions, causing mild to severe serotonergic adverse drug events (ADEs), particularly among older adults. Our objective was to develop a novel molecular-based toxicity scoring system to assess serotonergic burden resulting from concurrently administered drugs. Quantitative methods to assess serotonergic burden may provide a useful clinical tool for improving pharmacotherapy. Retrospective cohort study. PharMetrics Legacy health claims database (January 2001-December 2013) and ChEMBL bioactivity database. A 2-serotonergic drug exposure cohort (78,172 patients) and a 3-serotonergic drug exposure cohort (19,900 patients) were generated, and population-level statistics were collected. Nonexposure cohorts were created for each drug exposure cohort and matched in a 4:1 ratio for age, sex, and length of enrollment. Eight 5-HT medications were screened against multiple bioactivity databases to identify their off-target interactions at 5-HT receptors and serotonin reuptake transporter protein. A computational serotonin burden score (SBS) was derived from the receptor-specific interaction propensities reported from the comprehensive bioactivity screen. Linear regression was used to characterize associations between SBSs and combined total ADE incidence rate detected by International Classification of Diseases, Ninth Revision, Clinical Modification, diagnosis codes. A significantly greater incidence of 17 potential 5-HT-related ADEs was seen in exposed serotonergic drug cohorts (p<0.05). A positive correlation between SBS and overall ADE incidence rate in the 2-serotonergic drug exposure cohort (R2 =0.69, p<0.34) and 3-drug cohort (R2 =0.85, p<0.01) was observed. When both drug cohorts were combined, total drug SBSs strongly correlated with the composite 5-HT adverse event rate (R2 =0.92, p<0.0001). Despite an increasing burden of illness, these data suggest that drug combinations with higher SBSs are associated with a higher rate of potential serotonergic ADEs. In this test of concept, positive associations between SBSs and serotonin-related ADEs suggest that it may offer a pharmacologic-based foundation for developing risk assessment tools to assist in optimizing pharmacotherapy.

Comparison of Quetiapine Abuse and Misuse Reports to the FDA Adverse Event Reporting System With Other Second-Generation Antipsychotics.

Background:Second-generation antipsychotics (SGAs) are assumed to have little abuse potential. However, reports of quetiapine abuse have emerged as prescribing has increased in recent years. The US Food and Drug Administration’s (FDA) Adverse Event Reporting System (FAERS) provides postmarketing information regarding adverse drug events (ADEs). This is the first study to analyze quetiapine abuse-related ADEs reported to FAERS to determine whether a disproportionate rate of such events have been reported when compared with other commonly used SGAs.Methods:A cross-sectional analysis of FAERS data from January 1, 2015, to December 31, 2017, was performed. The total number of all-cause and abuse-related ADEs reported to FAERS regarding quetiapine, olanzapine, aripiprazole, and risperidone were identified, along with demographic and mortality data. The proportional reporting ratio (PRR) was calculated to assess disproportionate reporting of abuse-related adverse drug reactions between quetiapine and each of three alternative SGA medications.Results:Abuse-related ADEs represented 11% (3144/27 962) of total ADEs reported for quetiapine, 8% for olanzapine (1548/19 228), 5% (1380/29 699) for aripiprazole, and 3% (1168/45 518) for risperidone. The PRRs (95% confidence interval) for quetiapine versus olanzapine, aripiprazole, and risperidone were 1.40 (1.32-1.48), 2.42 (2.28-2.57), and 4.38 (4.10-4.68), respectively, indicating that abuse-related events were significantly more likely to be reported with quetiapine than each comparator drug. In addition, more deaths were reported among the abuse-related events regarding quetiapine (673) than olanzapine (200), aripiprazole (88), and risperidone (143).Conclusion:This study corroborates recent evidence indicating that quetiapine might possess a significantly higher abuse potential than other commonly used SGAs. Although prospective studies are needed to better understand the abuse potential of quetiapine, increased vigilance in monitoring for signs of substance abuse might be warranted when prescribing quetiapine.

Implications of Off-Target Serotoninergic Drug Activity: An Analysis of Serotonin Syndrome Reports Using a Systematic Bioinformatics Approach.

Study ObjectiveSerotonergic adverse drug events (ADEs) are caused by enhanced intrasynaptic concentrations of 5‐hydroxytryptamine (5‐HT). No systematic process currently exists for evaluating cumulative 5‐HT and off‐target toxicity of serotonergic drugs. The primary study aim was to create a Serotonergic Expanded Bioactivity Matrix (SEBM) by using a molecular bioinformatics, polypharmacologic approach for assessment of the participation of individual 5‐HT drugs in serotonin syndrome (SS) reports.Data SourcesPublicly available databases including the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS), ChEMBL, DrugBank, PubChem, and Kyoto Encyclopedia of Genes and Genomes (KEGG) were queried for computational and pharmacologic data.DesignAn in‐house bioinformatics TargetSearch program ( http://dxulab.org/software) was used to characterize 71 serotonergic drugs interacting at 13 serotonin receptor subtypes and serotonin reuptake transporter protein (SERT). In addition, off‐target interactions at norepinephrine transporter (NET), monoamine oxidase (MAO), and muscarinic receptors were included to define seven polypharmacological drug cohorts. Serotonin syndrome reports for each serotonergic drug were extracted from FAERS by using the Sternbach and Hunter criteria.Measurements and Main ResultsA proportional reporting adverse drug reaction (ADR) ratio (PRR) was calculated from each drug's total ADEs and SS case reports and aggregated by drug bioactivity cohorts. Triple‐receptor interactions had a disproportionately higher number of SS cases using both the Hunter criteria (mean PRR 1.72, 95% CI 1.05–2.39) and Sternbach (mean PRR 1.54, 95% CI 1.29–1.79). 5‐Hydroxytryptamine agonists were associated with a significantly lower proportion of SS cases using the Hunter and Sternbach criteria, respectively (mean PRR 0.49, 95% CI 0.17–0.81 and mean PRR 0.49, 95% CI 0.15–0.83). Drugs with disproportionately higher participation in SS vary considerably between the two diagnostic criteria.ConclusionThe SEBM model suggests a possible polypharmacological role in SS. Although further research is needed, off‐target receptor activity may help explain differences in severity of toxicity and clinical presentation.

Efficiency of an interactive program for enhancing patient reporting of adverse drug events in primary care

Introduction Adverse drug events (ADE) are frequents in primary care. They could often be prevented and their complications avoided. One of the main causes is that patients rarely know how to detect ADE. Another cause is inadequate communication between patients and physicians. If patients were effectively trained in identifying and reporting ADE, this should enhance ADE management (and avoid consequences on patient's health). The aim of the InPAct study was to assess an interactive program promoting patients to be active in ADE identification and their reporting to their general practitioners (GP), in order to enhance ADE management in primary care. We focused on patients treated by anti-hypertensive drugs, mainly prescribed in primary care and known to be often responsible for ADE. Methods/design We conducted a cluster randomized controlled stepped wedge trial, with eight clusters of GP. The InPAct program was implemented in the clusters in random order along five successive three-month periods. The program featured: – a patient booklet including information on cardiovascular risks and management of antihypertensive drugs, care plans and patient ADE report forms; – standardized training of physicians in how to present the booklet to the patient. The primary outcome was the active reporting of ADE by patients to their GP within three months of inclusion, after the identification of the ADE by the patients themselves. Total ADE identification (i.e. ADE identified by physician or patient, independently of patient active reporting to their practitioner), knowledge of patient about cardiovascular risks and management of antihypertensive treatments and patient satisfaction about their care management by their general practitioner were evaluated as secondary outcomes. The effect of the intervention was quantified and tested using a mixed logistic model to integrate cluster and time effects. Results We analyzed data for 1095 patients included by 60 different GP belonging to the 8 clusters. Multivariate analyses showed that InPAct program efficiently enhanced active reporting of ADE by patients to their GP (OR = 3.5, 95 CI [1.2–10.1], P = 0.02), but also total ADE identification (OR = 2.6, 95 CI [1.3–5.1], P = 0.01). The anti-hypertensive prescription status (initiation, modification or renewal) was strongly associated with patient active ADE reporting and total ADE identification. Moreover, patient satisfaction about their care management by their GP was higher in the intervention group, as the communication or the given information by the practitioner were concerned. Conclusion The InPAct intervention constituted an original program that was intended to improve ADE management in primary care by enhancing patient involvement in their own care. Finally, the InPAct intervention was efficient not only to enhance patient ADE identification associated with an active reporting, but also total ADE identification and communication between patients and their practitioners. Our study suggests that a better communication between patients and GP could improve patient safety in primary care.

Sustaining and Spreading the Reduction of Adverse Drug Events in a Multicenter Collaborative

Adverse drug events (ADEs) occur more frequently in pediatric patients than adults. ADEs frequently cause serious harm to children and increase the cost of care. The purpose of this study was to decrease ADEs by targeting the entire medication-delivery system for all high-risk medications. Thirteen freestanding children's hospitals participated in this ADE collaborative. An advisory panel developed a change package of interventions that consisted of standardization of medication-ordering (eg, consensus-based protocols and order sets and high-alert medication protocols), reliable medication-dispensing processes (eg, automated dispensing cabinets and redesign of floor stock procedures), reliable medication-administration processes (eg, safe pump use and reducing interruptions), improvement of patient safety culture (eg, safety-culture changes and reduction of staff intimidation), and clinical decision support (eg, increase ADE detection and redesign care systems). ADE rates were compared from the 3-month baseline period to quarters of the 12-month intervention phase. ADE rates were categorized further as opioid related and other medication related. From baseline to the final quarter, the collaborative resulted in a 42% decrease in total ADEs, a 51% decrease in opioid-related ADEs, and a 41% decrease in other medication ADEs. A pediatric collaborative that targeted the medication-delivery system decreased the rate of ADEs at participating institutions.

Análisis retrospectivo de los acontecimientos adversos por medicamentos en pacientes ancianos en un centro de salud de atención primaria

To describe the adverse drug events (ADEs) reported by doctors of a primary health care centre in the patient's medical record.A retrospective, descriptive study.Burriana Health Centre (Castellón), Spain.All patients over 75 with a clinical history held on paper at the health centre, ie non-institutionalized patients seen on an out-patient basis, were checked.A total of 2044 paper-based medical records were analysed, in which 832 histories describing 1893 ADEs (90.4% unforeseen and 9.6% preventable) were found. This means that 41% of the patients experienced one or more adverse events, with an average of 2.28 ADEs per patient.Most ADEs (85.3%) were light, but 6% were classified as serious, with high digestive haemorrhage caused by NSAIDs standing out as the most common serious problem (37.3%). The pharmaco-therapeutic groups most involved in ADEs were cardiovascular therapy (29.4%), anti-infectious drugs (21.2%) and nervous system drugs (20.1%). Seventeen cases of intoxication were detected (0.9% total ADEs), with digoxin responsible for 67% of the serious intoxications. It was observed that ADEs occur with statistical significance most frequently in women (OR, 1.73; 95% CI, 1.42-2.10). After an age-stratified analysis, it was concluded that the only sub-group where the increase in risk was not significant was the group of people over 85 years old.ADEs create a serious public health problem, with negative effects on patients. Although most ADEs are unforeseen (90.4%), it is still worrying that 9.6% of the ADEs identified are preventable.

Medication safety messages for patients via the web portal: The MedCheck intervention

Objective Communication failures account for many adverse drug events (ADEs) in adult primary care. Improving patient–physician communication may improve medication safety. Accordingly, the goal of this study was to learn whether electronic medication safety messages directed to patients can improve communication about medications and identify ADEs. Design We studied adult patients enrolled in a patient Internet portal at three primary care practices affiliated with a teaching hospital. MedCheck, a medication safety application, sent patients a secure electronic message 10 days after they received a new or changed prescription. MedCheck asked if the patient had filled the prescription or experienced medication-related problems, and then forwarded the patient's response to their primary care physician. Measurements We selected a stratified random sample of 267 subjects from 1821 patients who received and opened a MedCheck message from April 2001 to June 2002. We reviewed subjects’ medical records for three months following their first MedCheck message. We analyzed patient and clinician response rates and times, examined patient–clinician communication about medications, and identified ADEs. Results Patients opened 79% of MedCheck messages and responded to 12%; 77% responded within 1 day. Patients often identified problems filling their prescriptions (48%), problems with drug effectiveness (12%), and medication symptoms (10%). Clinicians responded to 68% of patients’ messages; 93% answered within 1 week. Clinicians often supplied or requested information (19%), or made multiple recommendations (15%). Patients experienced 21 total ADEs; they reported 17 electronically. Conclusion Patients and physicians responded promptly to patient-directed electronic medication messages, identifying and addressing medication-related problems including ADEs.

Role of Pharmacist Counseling in Preventing Adverse Drug Events After Hospitalization

Hospitalization and subsequent discharge home often involve discontinuity of care, multiple changes in medication regimens, and inadequate patient education, which can lead to adverse drug events (ADEs) and avoidable health care utilization. Our objectives were to identify drug-related problems during and after hospitalization and to determine the effect of patient counseling and follow-up by pharmacists on preventable ADEs. We conducted a randomized trial of 178 patients being discharged home from the general medicine service at a large teaching hospital. Patients in the intervention group received pharmacist counseling at discharge and a follow-up telephone call 3 to 5 days later. Interventions focused on clarifying medication regimens; reviewing indications, directions, and potential side effects of medications; screening for barriers to adherence and early side effects; and providing patient counseling and/or physician feedback when appropriate. The primary outcome was rate of preventable ADEs. Pharmacists observed the following drug-related problems in the intervention group: unexplained discrepancies between patients' preadmission medication regimens and discharge medication orders in 49% of patients, unexplained discrepancies between discharge medication lists and postdischarge regimens in 29% of patients, and medication nonadherence in 23%. Comparing trial outcomes 30 days after discharge, preventable ADEs were detected in 11% of patients in the control group and 1% of patients in the intervention group (P = .01). No differences were found between groups in total ADEs or total health care utilization. Pharmacist medication review, patient counseling, and telephone follow-up were associated with a lower rate of preventable ADEs 30 days after hospital discharge. Medication discrepancies before and after discharge were common targets of intervention.

Adverse drug events in emergency department population: a prospective Italian study

There is little evidence concerning adverse drug events (ADEs) in outpatients and related hospital admissions. In Italy, only one investigation was conducted on this important health issue. We therefore carried out a study to determine ADE incidence and ADE-related hospital admissions among emergency department (ED) visits, and to identify the risk factors for serious ADE leading to ED visit. During the year 2000, we performed a prospective study in two observational periods of 10 days each in 22 Italian EDs. Demographic, clinical and pharmacological data about all patients admitted to ED were collected by trained and qualified monitors. Records related to ADE were analysed and validated by a specific scientific committee. On 18,854 enrolled patients, 629 (3.3%) were affected by ADE. Among these, 244 (38.8% of ADE patients) reported a serious event. Patients with ADE, accounting for 4.3% (193 cases) of total hospitalisations, were significantly more likely to be hospitalised (30.7% vs. 23.7%; p<0.0001), females (57.2% vs. 46.3%; p<0.0001) and elders, compared with the total sample. Serious ADE resulted significantly associated with male gender and old age. NSAIDs (16.5% of total ADE visits) and antibiotics (12.9%) were the drugs mostly involved in ADE occurrence. ADE affected mostly skin (213 ADE visits) and gastrointestinal system (211). Old age and male gender resulted risk factors involved in the development of serious ADE. The high ADE-related hospitalisation incidence highlights the need for prevention strategies targeted to reduce the impact of ADE in the general population.