Adverse Drug Events In Patients Research Articles

Predictors of olaparib discontinuation owing to adverse drug events in patients with ovarian, peritoneal, or fallopian tube cancer: a retrospective observational study

We investigated predictors of olaparib discontinuation owing to adverse effects. Patients with ovarian, peritoneal, or fallopian tube cancers treated with olaparib at Osaka Medical and Pharmaceutical University Hospital between April 2018 and September 2022 were included in this study. The exclusion criteria were as follows: discontinuation of treatment due to disease progression, use of anaemia medications, and use of cytochrome P450 (CYP3A4) inhibitors. The follow-up period was 90 d. Of the 46 eligible patients, 21 patients discontinued olaparib, including 15 patients with grade 3 or higher anaemia, eight patients with grade 3 or higher neutropenia, and four patients with non-haematological toxicity (including multiple onset). Multivariate logistic regression analysis showed that grade 4 neutropenia and anaemia progression to grades 2–3 due to chemotherapy administered before olaparib administration were predictors of olaparib discontinuation. The severity of neutropenia and anaemia due to chemotherapy before olaparib administration may be a potential marker for its discontinuation.

Serious adverse drug events associated with psychotropic treatment of bipolar or schizoaffective disorder: a 17-year follow-up on the LiSIE retrospective cohort study.

Mood stabilisers and other psychotropic drugs can lead to serious adverse drug events (ADEs). However, the incidence remains unknown. We aimed to (a) determine the incidence of serious ADEs in patients with bipolar or schizoaffective disorders, (b) explore the role of lithium exposure, and (c) describe the aetiology. This study is part of the LiSIE (Lithium-Study into Effects and Side Effects) retrospective cohort study. Between 2001 and 2017, patients in the Swedish region of Norrbotten, with a diagnosis of bipolar or schizoaffective disorder, were screened for serious ADEs to psychotropic drugs, having resulted in critical, post-anaesthesia, or intensive care. We determined the incidence rate of serious ADEs/1,000 person-years (PY). In 1,521 patients, we identified 41 serious ADEs, yielding an incidence rate of 1.9 events per 1,000 PY. The incidence rate ratio (IRR) between ADEs with lithium present and causally implicated and ADEs without lithium exposure was significant at 2.59 (95% CI 1.20-5.51; p = 0.0094). The IRR of ADEs in patients <65 and ≥65 years was significant at 3.36 (95% CI 1.63-6.63; p = 0.0007). The most common ADEs were chronic lithium intoxication, oversedation, and cardiac/blood pressure-related events. Serious ADEs related to treatment of bipolar (BD) or schizoaffective disorder (SZD) were uncommon but not rare. Older individuals were particularly at risk. The risk was higher in individuals exposed to lithium. Serum lithium concentration should always be checked when patients present with new or unclear somatic symptoms. However, severe ADEs also occurred with other mood stabilisers and other psychotropic drugs.

Renal drug dosage adjustments and adverse drug events in patients with chronic kidney disease admitted to the hospital: a cross-sectional study

ABSTRACT Background The study aimed to evaluate the agreement of prescribed drug dosages with renal dosing recommendations and describe adverse drug events (ADEs) contributing to hospital admissions of patients with chronic kidney disease (CKD). Methods This cross-sectional study focused on CKD patients admitted to University Hospital Hradec Králové, with an estimated glomerular filtration rate below 60 ml/min. The necessity for renal dosage adjustments was determined using the Summary of Product Characteristics (SmPC). For medications requiring renal dosage adjustment according to SmPC, agreement between the prescribed and recommended renal dosage was assessed. ADEs were adjudicated using the OPERAM drug-related hospital admissions adjudication guide. Results Of 375 CKD patients, 112 (30%, 95% CI 25–34) were prescribed drug dosages in disagreement with SmPC renal dosage recommendations. Perindopril, metformin, and ramipril were most frequently dosed in disagreement with SmPC. ADE-related hospital admissions occurred in 20% (95% CI 16–24) of CKD patients. Conclusion CKD patients are often prescribed medication dosages in disagreement with SmPC renal dosing recommendations. Besides explicit factors, treatment goals, feasibility of monitoring and alternative treatment must be weighed when assessing drug and dosage appropriateness. Gastrointestinal bleeding was the most frequent ADE that contributed to hospital admissions of CKD patients.

Evaluation of Adverse Drug Events in Patients on Anti-Retroviral Therapy Regimen at Omdurman Voluntary Counselling and Testing and Anti-Retroviral Therapy Center in Sudan - A Cross-Sectional Study.

Anti-retroviral therapy-related adverse drug events are accounted as a main cause of anti-retroviral therapy non-adherence. In Sudan, pharmacovigilance studies are relatively rare and obstructed by the problem of under-reporting. It is a well-defined issue worldwide and is highly reported in developing countries. This study aimed to evaluate the prevalence of adverse events associated with anti-retroviral therapy among adult patients with immunodeficiency virus at Omdurman Voluntary Counselling and Testing and Anti-retroviral Therapy Center. The study was a descriptive cross-sectional study conducted through direct interviews with 429 patients at the selected center using the Adverse Drug Events (ADEs) reporting form. The collected data were analyzed by The Statistical Package for Social Sciences. More than half (55.5%) of the participants experienced adverse events, with 48.7% having experienced them at the beginning of treatment. Central nervous system manifestations were the most common adverse events. By using the Naranjo scale, most adverse events showed a "probable" relationship to anti-retroviral medicines. Based on the chi-square test, medication regimen was significantly associated with the presence of ADEs (namely abdominal pain and jaundice) (p values = 0.03 and 0.001), respectively. This study clearly stated that ART-related ADEs are common among Sudanese PLHIV and with central nervous system being the main adverse events. More pharmacovigilance studies and efforts by healthcare providers should be applied targeting ART-related ADEs under-reporting in Sudanese healthcare facilities.

Impact of pharmacist-led admission medication reconciliation on patient outcomes in a large health system

Objective Performing accurate medication history and reconciliation is recognized to reduce medication discrepancies and errors resulting in improved patient safety. This quality improvement project retrospectively evaluated the impact of a newly implemented pharmacy-led admission medication reconciliation program for several hospitals. Methods In 2020, a pharmacy-led admission medication reconciliation program was implemented in 16 hospitals across a large health system. The program targeted high-risk, complex inpatients admitted through the emergency department and directly to the hospital. Medication history technicians captured the best possible medication list and medication reconciliation pharmacists reviewed the list, collaborating with providers to complete reconciliation, and intervening to optimize drug therapy. A retrospective, pre-post analysis was performed comparing the preimplementation time period of June to November 2019 to the postimplementation time period of June to November 2020. Outcomes evaluated included pharmacy staff productivity, adverse drug events (ADEs), complications, and healthcare professional satisfaction. Results A total of 311,473 patients were admitted to the 16 hospitals during the pre- and postimplementation time periods. During the six-month postimplementation period, nearly 80,000 medication histories and reconciliations were completed, with 39.9% of those histories requiring medication clarification. Both the ADE rate and complication rate decreased significantly after program implementation, 12% decrease ( p &lt; 0.017) and 14% decrease ( p &lt; 0.001), respectively. Healthcare professional survey results from nurse, physician, and pharmacist respondents indicated a statistically significant improvement in satisfaction. Conclusion After implementation of pharmacy-led admission medication reconciliation, patient ADEs and complications decreased during hospitalization, and physician, nurse, and pharmacist satisfaction significantly improved.

Update of triggers for detection of adverse drug events in hematologic patients

The use of triggers for the active search and detection of adverse drug events (ADEs) has been gaining ground within pharmacovigilance services. Thus, the main objective of the study was to propose a new list of triggers to be used in a center specialized in hematology in Rio de Janeiro, Brazil. The update of the list of triggers consisted of revising the current list, with the exclusion and inclusion of new triggers. To verify the performance of the new list of triggers, a cross-sectional study was conducted in which the new triggers were used to investigate the occurrence of ADEs in patients attended in the emergency unit or hospitalized from January to March 2022. For each suspected ADEs, the patient's profile and adverse drug reactions (ADRs) were characterized regarding causality and severity. The performance of the triggers and their ability to capture ADEs were estimated using the following indicators: frequency of the trigger per 100 medical records, frequency of ADEs per 100 records, and positive predictive value (PPV). To evaluate the overall performance of the proposed new list, the PPV was estimated. A total of 374 prescriptions for triggers were identified in 186 medical records. The most efficient in the detection of possible ADEs were: lidocaine, loperamide, bisacodyl, filgrastim and glycerin clyster. The overall PPV of the new suggested list was 48% versus 10% of the previous list. This study demonstrated the importance of an updated list of triggers for the monitoring of ADEs and improvement of the care provided.

Analysis of adverse drug events in patients with bipolar disorders using the Japanese Adverse Drug Event Report database.

The aim of the present study was to survey adverse drug events (ADEs) in patients with bipolar disorders and identify risk factors using the Japanese Adverse Drug Event Report (JADER) database, a spontaneous reporting system. Data on patients with bipolar disorders were extracted from the JADER database. The Medical Dictionary for Regulatory Activities (MedDRA) preferred terms (PT) and standardized MedDRA queries (SMQ) were used to define ADEs. A multiple logistic regression analysis was performed to identify risk factors for ADEs. A total of 8653 reports of 1108 types of ADEs (PT) were registered in data collected on 3521 patients with bipolar disorders. Rash (PT) was the most frequently reported in 549 patients, followed by drug eruption (PT) in 387, fever (PT) in 364, toxicity to various agents (PT) in 291, and Stevens-Johnson syndrome (PT) in 261. Among 24 ADEs (PT) that were reported in more than 50 patients, lamotrigine was associated with increased risks of 13 ADEs (PT), followed by carbamazepine with increased risks of 8 ADEs (PT). The majority of these ADEs belonged to hypersensitivity (SMQ) or hepatic disorder (SMQ). Lithium carbonate was associated with increased risks of rash (PT), drug interaction (PT), and tubulointerstitial diseases (SMQ). All antipsychotics increased the adjusted odds ratio for neuroleptic malignant syndrome (PT). The risk of hyperglycemia/new onset diabetes mellitus (SMQ) was increased by olanzapine, quetiapine fumarate, and risperidone. We are presenting the profiles of ADEs in patients with bipolar disorders using the JADER database, and propose risk factors for 19 ADEs (PT) and 4 ADEs (SMQ).

COVID-19 impact on the prevalence of PIMS in elderly patients according to STOPP/ START criteria: a record base study

Background: Polypharmacy, contribute to an increased risk of adverse drug reaction morbidity, and mortality, and increases the length of hospital stay, hospital revisits and readmissions. We aimed to evaluate the prevalence and trends of polypharmacy and potentially inappropriate medications in elderly patients with version 2. STOPP/START criteria, and assess the severity of adverse drug events in patients with PIMs.Methods: This is a retrospective, record-based study of over-the-counter, and potentially inappropriate medications in the prescriptions of patients (&gt;60 years). PIMs have been identified and further investigated to determine any adverse effects. If harm occurred, the severity of an adverse effect was rated using a modified Hartwig and Siegel scale. The causality of the events was assessed by using Naranjo's scale.Results: Out of 583 patients polypharmacy and excessive polypharmacy were found in 36.0%, and 42.8% of pre-admission medications. The most common over-the-counter (OTC) drugs were hydrocortisone (39.86%), ranitidine (21.62%), bisacodyl (14.86%), and diphenhydramine (12.84%). A statistically significant positive correlation was seen between age and the number of drugs prescribed (r2=0.16), while a non-significant positive correlation was found between sex, length of stay (LOS), and the number of drugs prescribed (r2 =0.0002, r2 =0.001). Common PIMs related incidence reported include Insulin (regular) 31.25% (N=20), Trihexyphenidyl (THP) 18.75%, zolpidem 12.5%, acetylsalicylic acid 9.3%, pantoprazole 52 7.81%, furosemide 7.8%, hydrocortisone 6.25%, and glimepiride 6.25%. Total of 130 ADRs 50% were mild, 28.4% were moderate, and 21.5% were severe. Out of 130 incidents, 64.6% were preventable, 22.3% were probably preventable, and 13.0% were not preventable. A total of 50.0% recovered completely from the ADRs, 33.0% had been recovering, 12.3% recovered with a squeal, 2.3% could not recover and 2.3% had been fatal.Conclusions: The study shows high uses of OTC and PIMs and PGx in elderly patients; which encourage intent need to develop awareness and action plans.

Incidence of adverse drug events in patients hospitalized in the medical wards of a teaching referral hospital in Ethiopia: a prospective observational study

BackgroundAdverse drug events (ADEs) are an important public health problem with considerable clinical and economic costs. However there are limited studies of ADE incidence in adult inpatients in low-income countries, particularly in Ethiopia. Hence, this study aimed to assess the incidence of adverse drug events and associated factors in patients hospitalized in the medical wards of Wolaita Sodo University teaching referral hospital (WSUTRH).MethodsA prospective observational study was conducted involving 240 patients admitted to the medical wards of WSUTRH. A checklist was used for data collection, while standard tools were employed for assessing the probability and characterization of ADEs. A multifaceted approach involving daily chart review, patient interview, attendance at ward rounds and/or meetings, and staff reports were employed to collect the data. To identify factors independently associated with ADEs, logistic regression analysis was conducted using Stata version 15.ResultsPatients were followed from ward admission to discharge, accounting for 2200 patient-days of hospital stay. Overall, 976 medications were ordered during the hospital stay. Sixty-four ADEs were identified with an incidence of approximately 27 per 100 admissions and 29 per 1000 patient days. Of the total ADEs, 59% were preventable. Regarding the severity, 2% of the ADEs were severe, while 54% were moderate. The risk of ADEs increased with longer hospital stay (LOHS) (p = 0.021), in patients with blood and immune disease diagnosis (p = 0.001), use of cardiovascular medicines (p = 0.028), and an increase in the number of medications prescribed (p = 0.021).ConclusionsIn this study, ADEs were identified in about one-quarter of the participants. Longer hospital stays, blood and immune diseases, cardiovascular medicines use, and multiple medication use had increased the likelihood of ADE occurrences. The majority of the ADEs were preventable, indicating the existence of a window of opportunity to ensure patient safety.

Identifying adverse drug events in patients at a pediatric ward in a Brazilian hospital: application and performance of the triggers

Abstract Objectives: to evaluate the performance of a trigger tool in identifying adverse drug events (ADE) in hospitalized children. Methods: a retrospective cohort study review on 133 medical records at a federal maternal and child reference hospital in Rio de Janeiro in 2016. A list of 14 triggers was developed to detect ADE in the pediatric population. Three steps were performed: (1) search for triggers; (2) selection of suspected cases of ADE and (3) final determination of ADE by experts’ consensus. Results: 360 triggers were identified in 100 hospitalizations (75.2%), with an average of 2.7 triggers/ hospitalization. The most frequent triggers were “abrupt medication stop” (79.7%); “antiemetics use” (8.9%) and “laxatives use” (7.2%); while the “diphenhydramine use”, “phytomenadione use” and “excessive sedation/lethargy/fall/hypotension” obtained the highest performance indicating ADE every time they occurred. Thirty-one ADE were identified in 12.8% of the hospitalizations; 11 (35.5%) ADE were detected without the aid of the triggers thus, pruritus and diarrhea were the most frequent. Conclusion: the trigger tool proved to be useful in identifying ADE in hospitalized children, especially if high performance and high frequency triggers are used in identifying the events. The inclusion of the triggers “diarrhea” and “pruritus”, may favor the identification of ADE in patients at pediatric wards.

Pharmacogenetic markers of chemotherapy toxicity in gastrointestinal tumors: a preliminary analysis

Aim. To assess the association between the carriage of minor allelic variants of 8 genes that encode key enzymes involved in the metabolism of anticancer drugs (DPYD, GSTP1, MTHFR, UGT1A1) and cell repair (XPC, ERCC1, TYMP, NQO1) and the severity of adverse drug events in patients with common gastrointestinal tumors. Tasks. To study the frequency of minor allelic variants of the DPYD, GSTP1, MTHFR, UGT1A1, XPC, ERCC1, TYMP, NQO1 genes; to assess the frequency and severity of adverse drug events of chemotherapy treatment in the study population. Materials and methods. For the period from October 2020 to April 2021, 56 patients (women 29, men 27) with verified malignant tumors of the gastrointestinal tract were included in a prospective clinical study as a part of the RSF grant No. 20-75-10158. The mean age was 62.311.4 years. Colon cancer was detected in 24 patients, tumors of the esophagus and stomach in 19 patients, tumors of pancreas and biliary tract in 13 patients. First-line palliative chemotherapy was given to 27 patients, adjuvant 19 patients, neoadjuvant 10 patients. All patients had not previously received cytotoxic or radiation treatment. Point nucleotide variants of genes DPYD, XPC, GSTP1, MTHFR, ERCC1, UGT1A1, TYMPS, NQO1 were determined by hybridization analysis on biological microchips. Differences in the tolerance of cytotoxic therapy (5-fluorouracil, platinum preparations, irinotecan) depending on the genotype were assessed using Fishers exact test. Results. The average number of chemotherapy courses received was 4.22.6 (112). There was a statistically significant difference in the tolerability of chemotherapy in patients with minor allelic variants of the GSTP1 rs1695 (p=0.03), ERCC1 rs11615 (p=0.01), and UGT1A1 rs8175347 (p=0.003) genes. Conclusion. The use of hybridization analysis on biological microchips to assess allelic variants responsible for the tolerability of cytotoxic therapy is reasonable and requires further prospective assessment.

The impact of diabetes mellitus on the anti-tuberculosis treatment outcome: a series of cases from the Republic of Moldova.

The Republic of Moldova ranks among the European Region countries with the highest global incidence of tuberculosis. Almost 5% of the cases with pulmonary TB had been diagnosed with DM in 2017. The aim of this study was to assess the impact of diabetes mellitus on the anti-tuberculosis treatment effectiveness for the improvement of the disease outcome. A retrospective, longitudinal and case-control study, which included a total number of 252 patients diagnosed with pulmonary tuberculosis and distributed into a study group of 93 patients diagnosed with diabetes mellitus and a control group of 159 patients without glycemic disorders was performed. The statistical analysis was performed using EpiInfo software. The statistical analysis of the differences between normally distributed continuous variables was tested with the Student T-test. Based on the collected data we established that the majority of the patients with glycemic disorders were diagnosed with the type 2 diabetes, associated with hyperglycemia and in half of them complications of diabetes were revealed. The age older 55 years and the low economical state were common characteristics of the diabetic patients. Tuberculosis was detected in every second diabetic patient through the radiological screening compared with the passive detection of most of the non-diabetic patients. The anti-tuberculosis treatment outcome was endangered by a higher rate of the adverse drug events in patients with diabetes, which contributed to death in 15%, lost to follow-up 7%, and therapeutic failure in 6%. The anti-tuberculous treatment outcome in patients diagnosed with tuberculosis and diabetes mellitus was significantly diminished by glycemic disorders, history of the previous anti-tuberculous treatment and adverse drug reactions. Individualized therapeutic approach to tuberculosis could improve the treatment effectiveness.

Clinical outcomes and adverse events in patients hospitalised with COVID-19, treated with off-label hydroxychloroquine and azithromycin.

To assess clinical outcomes and adverse drug events in patients hospitalised with COVID-19 treated with off-label hydroxychloroquine (HCQ) and azithromycin (Az). We performed a retrospective analysis of hospitalised patients who had a positive polymerase chain reaction test for SARS-CoV-2 and received HCQ plus Az or no targeted therapy. The primary end point was clinical improvement on day 7 defined as either hospital discharge or an improvement of 2 points on a 6-category ordinal scale. Secondary outcomes included mortality at day 28, intensive care admission, requirement for mechanical ventilation and incidence of adverse events. Data from a total of 134 patients were evaluated; 82 patients received HCQ/Az and 52 patients received no targeted therapy. Clinical improvement was seen in 26.8% of patients who received HCQ/Az but this was not significant. The rates of intensive care transfer and mechanical ventilation were higher in the treatment group, but these differences were not significant. Mortality at day 28 was significantly higher in the treatment group (P = .03). Hypoglycaemia elevated liver function tests and QT prolongation were monitored in both groups. The risk of QT prolongation was significantly higher in the treatment group. Treatment was stopped early in 6 (7.3%) patients due to adverse events. Although patients who received HCQ/Az were more severely ill the administration of these repurposed drugs did not result in clinical improvement and was associated with a significant increase in toxicity. This descriptive study highlights the importance of monitoring all repurposed agents for adverse events.

Adverse Drug Events in Patients with Chronic Kidney Disease Associated with Multiple Drug Interactions and Polypharmacy.

Chronic kidney disease (CKD) is associated with adverse drug events due to medication errors and the risks of polypharmacy. The aim of this study was to investigate whether multiple pharmacodynamic interactions are a significant problem in CKD patients to improve medication safety. The discharge medication of 200 elderly patients with stage 3, 4 and 5/5D CKD was analysed in a retrospective observational study with respect to kidney-related medication errors and multiple pharmacodynamic interactions. The clinical relevance of the most common and hazardous multiple interactions was assessed by evaluating adverse events at the primary or the subsequent hospital stay. Findings showed that 29.5% of the study cohort were at risk of QTc-interval prolongation in association with their medication combinations and half of them exhibited QTc-interval prolongation. The QTc interval was extended among all patients receiving a combination of two or more drugs with 'known' risk of Torsades de pointes. Amiodarone, citalopram and ciprofloxacin turned out to be the most hazardous drugs in this context. Eight percent of the patient population received a regimen of 4-6 potassium-enhancing drugs during their hospital stay, which was not de-escalated in 75.0% in the ambulatory setting. Despite close monitoring in the clinical setting, 37.5% of these patients developed hyperkalaemic episodes during their primary stay and 66.7% during rehospitalization. Of the study cohort, 8.5% received a combination of three drugs with antithrombotic or antiplatelet effects. Of these, 64.7% developed haemorrhagic events with two of them proving fatal. Multiple pharmacodynamic interactions related to QTc prolongation, hyperkalaemia and haemorrhage are frequently associated with a negative outcome in older adults with CKD and often require recurrent medical treatment or rehospitalization.

Utilization profile of enoxaparin in hospitalized patients with Chronic Kidney Disease in southern Brazil

Chronic Kidney Disease (CKD) patients usually require the use of anticoagulants for treatment or prevention of thromboembolic diseases. One such commonly used anticoagulant is enoxaparin. However, special attention is advised when using this drug for CKD patients because dosage adjustments may be needed. This prospective observational study was conducted in adult patients (> 18 years) with CKD stages 3 to 5 who were followed-up daily via prescriptions, medical records and laboratory tests. Enoxaparin doses, renal function and adverse drug events (ADEs) were thus monitored. Of the 87 ADEs identified in this study, 56 (64.3%) occurred in patients requiring enoxaparin prescription adjustment. Out of the 9 patients who had severe ADEs, 8 (88.9%) needed enoxaparin prescription adjustment. The results of this study suggest an overall increased risk of major bleeding and ADEs in patients requiring enoxaparin prescription adjustment. Further investigation of alternative dosing regimens in patients with CKD to maintain efficacy while reducing risks is imperative, as are studies on the utility of monitoring anti-factor Xa activity to guide dosing of enoxaparin. In addition, the role of clinical pharmacists in the management of CKD patients is crucial, as dose adjustments are often necessary.

Development of a Computer-Assisted Adverse Drug Events Alarm and Assessment System for Hospital Inpatients in China.

Computerized detection is a promising method for monitoring adverse drug events (ADEs); however, this method is currently in its infancy and is a new area of exploration in China. This study aimed to develop a computerized ADE alarm and assessment system to help pharmacists effectively detect, assess, and analyze possible ADEs in patients in China. Based on the clinical characteristics of these adverse drug events, we designed combined multiparameters as ADE alert rules to be assembled into detection configurations. We also developed system function modules by extracting data from the People's Liberation Army (PLA) general hospital information system (electronic medical records). Positive predictive values were calculated for the alert. Five function modules were created in this platform: automatic screening, assisted evaluation, risk characteristic analysis, report generation into SRS (spontaneous reporting system), and a dictionary database. Four ADE alert configurations were set in our ADE alarm and assessment system: drug-related thrombocytopenia, anemia, liver injury, and kidney injury. The positive predictive values of the 4 monitored ADEs were approximately 44.4% to 95.8%. An automatic ADE screening system was established for hospitalized patients in Chinese medical institutions. Compared with previous studies, combined drug-event alerts and a system-assisted assessment interface performed better than alerts based only on laboratory values. Furthermore, this platform's assisted-layered evaluation and risk factor analysis functions could save considerable time for professionals and improve early prevention of potentially serious ADEs. To date, this system has been applied in 10 large-scale medical institutions.

Evaluation of Clinical Factors Associated with Adverse Drug Events in Patients Receiving Sub-Anesthetic Ketamine Infusions.

IntroductionSub-anesthetic ketamine is frequently used as an analgesic to reduce perioperative opioid consumption and has also been shown to have antidepressant effects. Side effects of ketamine include dizziness, diplopia, nystagmus, and psychomimetic effects. It is unclear what clinical factors may be associated with ketamine-related adverse drug events (ADEs).MethodsWe performed a retrospective review of 95 patients who received sub-anesthetic ketamine infusions at our institution. Data examined associations between ketamine-related ADEs and various clinical characteristics including chronic pain, depression, or psychiatric disorder, patient physical characteristics, chronic opioid use, perioperative opioid use, dose and duration of ketamine infusions, pain scores, and perioperative medications such as serotonergic agents, central nervous system (CNS) depressants, and analgesics.ResultsOverall incidence of ketamine-related ADEs was 29.5% and the incidence of psychomimetic effects was 14.8%. We observed that patients with a history of depression have a lower incidence of ketamine-related ADEs compared to patients without a history of depression (10.3% vs 37.3%; p value = 0.007).ConclusionPatients with depression were found to have a statistically significant reduction in the incidence of ketamine-related ADEs. We found no statistically significant positive associations between ketamine-related ADEs and other clinical factors such as a history of chronic pain, psychiatric disease, patient physical characteristics, perioperative opioid use, dose of ketamine infusion, or co-administration of other CNS depressants.

HLADQA1*05 genotype predicts anti-drug antibody formation and loss of response during infliximab therapy for inflammatory bowel disease.

Anti-drug antibodies (ADAs) are a leading contributor to infliximab loss of response and adverse drug events. It is not feasible to identify patients at risk of antibody formation before initiating infliximab. The genetic variation HLADQA1*05 (rs2097432) has been linked to infliximab antibody formation in Crohn's disease (CD). To evaluate the association between HLADQA1*05 and infliximab antibody formation, infliximab loss of response, treatment discontinuation and adverse drug events in patients with inflammatory bowel disease (IBD) METHODS: In a retrospective cohort study, infliximab-exposed patients with IBD (n=262) were screened for the genetic variation, HLADQA1*05A>G (rs2097432). Risk of infliximab ADA formation, infliximab loss of response, adverse events and discontinuation were assessed in wild-type (GG) and variant-carrying (AG or AA) individuals. Forty per cent of all participants were HLADQA1*05A>G variant carriers, with 79% of participants with infliximab antibodies carrying at least one variant allele. The risk of infliximab antibody formation was higher in HLADQA1*05A>G variant carriers (adjusted HR=7.29, 95% confidence interval (CI)=2.97-17.191, P=1.46×10-5 ) independent of age, sex, weight, dose and co-immunosuppression with an immunomodulator. Variant carrier status was associated with an increased risk of infliximab loss of response (adjusted HR=2.34, 95% CI=1.41-3.88, P=.001) and discontinuation (adjusted HR=2.27, 95% CI=1.46-3.43, P=2.53×10-4 ) although not with infliximab-associated adverse drug events. HLADQA1*05 is independently associated with a high risk of infliximab antibody formation in addition to infliximab loss of response and treatment discontinuation. There may be a role for genotype-guided application of combination therapy in IBD.

Effect of pharmacy‐led medication reconciliation in emergency departments: A systematic review and meta‐analysis

Medication reconciliation is recommended to be performed at every transition of medical care to prevent medication errors or adverse drug events. This study investigated the impact of pharmacy-led medication reconciliation on medication discrepancies and potential adverse drug events in the ED to assess the benefits of pharmacy services. The systematic review and meta-analysis was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. The PubMed, Ovid Embase and Cochrane library databases were searched up from inception to 1 July 2018. Studies comparing the effectiveness of the medication reconciliation service performed by pharmacy personnel to usual care (nurses or physicians) in the ED were included. Duplicated studies, non-clinical studies, studies with ineligible comparators or study designs were excluded. Eleven studies were eligible for qualitative analysis, and 8 studies were included in meta-analysis. Pharmacy-led medication reconciliation substantially reduced medication discrepancies in the ED. The most common medication discrepancies included medication omission and incorrect/omitted dose or frequency. Unlike usual care, pharmacy-led medication reconciliation significantly reduced the proportion of patients with medication discrepancies by 68% (response rate 0.32; 95% confidence interval (CI): 0.19-0.53, P<.0001) and the number of medication discrepancy events by 88% (response rate 0.12; 95% CI 0.06-0.26, P<.00001). Intervention decreased the number of discrepancies per patient by 3.08 (mean difference -3.08; 95% CI: -4.76 to -1.39, P=.0003). Subgroup analysis revealed no differences between pharmacists and pharmacy technicians in medication reconciliation performance pertaining to medication discrepancies. The patients with several comorbidities or those administered numerous medications received marked benefits related to reduced medication discrepancies from pharmacy-led medication reconciliation. Moreover, a randomized controlled trial revealed decreased risk of potential adverse drug events by pharmacy-led medication reconciliation in patients receiving care in the ED. Pharmacy-led medication reconciliation significantly decreased the number of medication discrepancies. However, only one study investigated potential adverse drug events in patients receiving care in the ED. Therefore, further studies investigating the direct clinical impact of decreased medication discrepancies are required.

Association of Adverse Drug Events with Broad-spectrum Antibiotic Use in Hospitalized Patients: A Single-center Study.

Objective The importance of antimicrobial stewardship is increasingly highlighted in this age of antimicrobial resistance. A better comprehension of adverse drug events (ADEs) can promote the appropriate use of antibiotics. We aimed to quantify the incidence of ADEs associated with broad-spectrum systemic antibiotics in a hospital setting. Methods We conducted a six-month prospective, observational study at Osaka University Hospital to describe the incidence of ADEs in patients hospitalized in general wards undergoing treatment with broad-spectrum antibiotics [carbapenems, piperacillin/tazobactam (PIPC/TAZ), and anti-methicillin-resistant Staphylococcus aureus agents]. The occurrence of ADE was defined as any cardiac, gastrointestinal, hepatobiliary, renal, neurologic, hematologic, dermatologic, or musculoskeletal manifestation after 48 hours or more of systemic antibiotic therapy. Results The 3 most frequently prescribed antibiotics were PIPC/TAZ (242 cases), meropenem (181 cases), and vancomycin (92 cases). Of 689 patients, 118 (17.1%) experienced ADEs, including gastrointestinal (6.4%), hepatobiliary (4.2%), dermatologic (2.5%), and renal (2.3%) manifestations. Patients treated with PIPC/TAZ, meropenem, doripenem, vancomycin, daptomycin, and teicoplanin developed ADEs at rates of 20.7%, 16.0%, 15.4%, 19.6%, 11.8%, and 10.9%, respectively. Conclusion Our study provides a quantitative value for the incidence of ADEs associated with broad-spectrum antibiotics in clinical practice. To optimize patient safety, clinicians need to be aware of the risks associated with antibiotic administration.