Occurrence Of Adverse Drug Events Research Articles

A real-world pharmacovigilance study of drug-induced QT interval prolongation: analysis of spontaneous reports submitted to FAERS.

To identify the most commonly reported drugs associated with QT interval prolongation in the FDA Adverse Event Reporting System (FAERS) and evaluate their risk for QT interval prolongation. We employed the preferred term (PT) "electrocardiogram QT prolonged" from the Medical Dictionary for Regulatory Activities (MedDRA) 26.0 to identify adverse drug events (ADEs) of QT interval prolongation in the FAERS database from the period 2004-2022. Reporting odds ratio (ROR) was performed to quantify the signals of ADEs. We listed the top 40 drugs that caused QT interval prolongation. Among them, the 3 drugs with the highest number of cases were quetiapine (1,151 cases, ROR = 7.62), olanzapine (754 cases, ROR = 7.92), and citalopram (720 cases, ROR = 13.63). The two most frequently reported first-level Anatomical Therapeutic Chemical (ATC) groups were the drugs for the nervous system (n = 19, 47.50%) and antiinfectives for systemic use (n = 7, 17.50%). Patients with missing gender (n = 3,482, 23.68%) aside, there were more females (7,536, 51.24%) than males (5,158, 35.07%) were involved. 3,720 patients (25.29%) suffered serious clinical outcomes resulting in deaths or life-threatening conditions. Overall, most drugs that caused QT interval prolongation had early failure types according to the assessment of the Weibull's shape parameter (WSP) analysis. Our study offered a list of drugs that frequently caused QT interval prolongation based on the FAERS system, along with a description of some risk profiles for QT interval prolongation brought on by these drugs. When prescribing these drugs in clinical practice, we should closely monitor the occurrence of ADE for QT interval prolongation.

The application of Global Trigger Tool in monitoring antineoplastic adverse drug events: a retrospective study.

This study aimed to establish an antineoplastic drugs trigger tool based on Global Trigger Tool (GTT), to examine the performance by detecting adverse drug events (ADEs) in patients with cancer in a Chinese hospital (a retrospective review), and to investigate the factors associating with the occurrence of antineoplastic ADEs. Based on the triggers recommended by the GTT and those used in domestic and foreign studies and taking into account the scope of biochemical indexes in our hospital, some of them were adjusted. A total of 37 triggers were finally developed. Five hundred medical records of oncology patients discharged in our hospital from 1 June 2020 to 31 May 2021 were randomly selected according to the inclusion and exclusion criteria. These records were reviewed retrospectively by antineoplastic drugs trigger tool. The sensitivity and specificity of the triggers were analyzed, as well as the characteristics and risk factors for the occurrence of ADEs. Thirty-three of the 37 triggers had positive trigger, and the sensitivity rate was 91.8% (459/500). For the specificity, the positive predictive value of overall ADEs was 46.0% (715/1556), the detection rate of ADEs was 63.0% (315/500), the rate of ADEs per 100 admissions was 136.0 (95% CI, 124.1-147.9), and the rate of ADEs per 1,000 patient days was 208.33 (95% CI, 201.2-215.5). The top three antineoplastic drugs related to ADEs were antimetabolic drugs (29.1%), plant sources and derivatives (27.1%), and metal platinum drugs (26.3%). The hematologic system was most frequently involved (507 cases, 74.6%), followed by gastrointestinal system (89 cases, 13.1%). Multivariate logistic regression analysis showed that the number of combined drugs (OR = 1.14; 95% CI, 1.07-1.22; P < 0.001) and the previous history of adverse drug reaction (ADR) (OR = 0.38; 95% CI, 0.23-0.60; P < 0.001) were the risk factors for ADEs. The length of hospital stay (OR = 0.40; 95% CI, 0.14-1.12; P < 0.05) and the previous history of ADR (OR = 2.18; 95% CI, 1.07-4.45; P < 0.05) were the risk factors for serious adverse drug events (SAE). The established trigger tool could be used to monitor antineoplastic drugs adverse events in patients with tumor effectively but still needs to be optimized. This study may provide some references for further research in order to improve the rationality and safety of antineoplastic medications.

Realistic simulation in the preparation and administration of medications: a systematic review

Adverse drug events are multi-causal and interrelated, and it is important to know the causes and create prevention strategies. Realistic simulation is one of the methods widely used to discover the cause of these iatrogenies and as an effective method in the training of nursing professionals and students. The aim of this study is to identify and map how realistic simulations in the preparation and administration of medicines are being used in teaching and in the scientific community. This work is a bibliographical survey through a systematic review of online publications between 2012 and 2022. After selecting the articles, they were read and critically analysed. Of the 75 articles found, 52% were carried out in high-fidelity laboratories. As for the professional category, 29% had a multidisciplinary approach; as for the profile of the scenario used in the simulations, 43% involved scenarios for preventing iatrogenic events in adults. As for the aim of each study, 37% centred on simulation as a teaching resource. It was concluded that realistic simulation is an effective pedagogical tool for developing skills in students and professionals, it is a tool widely used to investigate the cause of adverse drug events and also to train professionals and students in the preparation and administration of medicines; it was shown that the lack of material resources is among the main causes for the occurrence of adverse drug events.

A221 AZATHIOPRINE DOSING THRESHOLD IN ANTI-TNF COMBINATION THERAPY FOR MINIMIZING IMMUNOGENICITY AND OPTIMIZING TREATMENT EFFICACY FOR PATIENTS WITH INFLAMMATORY BOWEL DISEASE. A RETROSPECTIVE COHORT STUDY

Abstract Background Reported rates of anti-drug antibody (ADA) formation to tumor necrosis factor-a antagonists (anti-TNF) range from 20-75%. One way to reduce the risk of ADA formation is to combine a second immune-suppressing agent such as azathioprine (AZA) with the anti-TNF agent, known as combination therapy. However, it is unknown if the risk of combination therapy, including the additive risk of AZA and anti-TNF side effects, could be reduced by exposing individuals with inflammatory bowel disease (IBD) to the lowest dose of azathioprine while still maintaining the beneficial effect of ADA prevention. Aims To identify the minimum dose of AZA needed to prevent ADA formation to anti-TNF agents in individuals with IBD receiving combination therapy. We also assessed the occurrence of adverse drug events, treatment loss of response, treatment discontinuation and the need for treatment dose escalation. Methods A retrospective cohort study is ongoing in adult participants with IBDreceiving either infliximab or adalimumab in combination with AZA. Patients are divided based on their AZA dosage (low dose group, AZA ampersand:003C2mg/kg/day versus standard dose group, AZA 2mg/kg/day). All participants will be followed for 1 year and observed for the occurrence of ADA formation, adverse drug events, treatment loss of response, treatment discontinuation and the need for treatment dose escalation. Results To date, 48 participants are currently included (low dose, n=29; standard dose, n=19). 42 are on Infliximab and 6 are on Adalimumab. The occurrence of ADA was 17.4% in the low dose group and 20% in the standard dose group (pampersand:003E0.99). More participants lost response to treatment and discontinued anti-TNF therapy in the standard dose group (n=7/19, 36.8%) versus the low-dose group (n=8/29, 27.6%, p=0.54). More participants in the low-dose group received anti-TNF dose escalation (n= 20/29,68.9%) compared to the standard dose group (n=6/19, 31.6%, p=0.017). Adverse events, to Anti-TNF was seen in (n=3/19, 15.7%) in the standard dose group, in comparison to (n=4/29, 13.79%, pampersand:003E0.99) in the low dose group. Adverse events to AZA were surprisingly higher in the low dose group (n=14/29, 48.3%) while in the standard dose, it was (n=5/19, 26.3%, p=0.14). Conclusions The preliminary result of the study suggests that there is no significant difference in anti-drug antibody formation between standard and low doses of azathioprine in combination with anti-TNF therapy, in addition, data showed significant lower rates of Anti-TNF discontinuation and loss of response to treatment in low Azathioprine dose group. Completion of the study will help further define if low-dose AZA can be used for ADA prevention in anti-TNF combination therapy without compromising important clinical outcomes. Funding Agencies None

Development of a multivariate predictive model for dapsone adverse drug events in people with leprosy under standard WHO multidrug therapy.

The occurrence of adverse drug events (ADEs) during dapsone (DDS) treatment in patients with leprosy can constitute a significant barrier to the successful completion of the standardized therapeutic regimen for this disease. Well-known DDS-ADEs are hemolytic anemia, methemoglobinemia, hepatotoxicity, agranulocytosis, and hypersensitivity reactions. Identifying risk factors for ADEs before starting World Health Organization recommended standard multidrug therapy (WHO/MDT) can guide therapeutic planning for the patient. The objective of this study was to develop a predictive model for DDS-ADEs in patients with leprosy receiving standard WHO/MDT. This is a case-control study that involved the review of medical records of adult (≥18 years) patients registered at a Leprosy Reference Center in Rio de Janeiro, Brazil. The cohort included individuals that received standard WHO/MDT between January 2000 to December 2021. A prediction nomogram was developed by means of multivariable logistic regression (LR) using variables. The Hosmer-Lemeshow test was used to determine the model fit. Odds ratios (ORs) and their respective 95% confidence intervals (CIs) were estimated. The predictive ability of the LRM was assessed by the area under the receiver operating characteristic curve (AUC). A total of 329 medical records were assessed, comprising 120 cases and 209 controls. Based on the final LRM analysis, female sex (OR = 3.61; 95% CI: 2.03-6.59), multibacillary classification (OR = 2.5; 95% CI: 1.39-4.66), and higher education level (completed primary education) (OR = 1.97; 95% CI: 1.14-3.47) were considered factors to predict ADEs that caused standard WHO/MDT discontinuation. The prediction model developed had an AUC of 0.7208, that is 72% capable of predicting DDS-ADEs. We propose a clinical model that could become a helpful tool for physicians in predicting ADEs in DDS-treated leprosy patients.

Ward-based clinical pharmacists in intensive care medicine: an economic evaluation

The positive impact of pharmaceutical care in improving medication safety is considered proven. Little is known about the economic benefit of clinical pharmaceutical services in Germany. In 2020, apilot project was started at the Ernst von Bergmann Hospital to introduce ward-based clinical pharmacists in intensive care medicine, also in order to determine the economic benefit of the medication management offered. By ateam of experienced intensive care physicians and clinical pharmacists on the basis of aconsensus principle, each pharmaceutical intervention (PI) was assigned aprobability score (Nesbit probability score) with which an adverse drug event (ADE) would have occurred. Assuming that each ADE results in an increased length of stay, the costs of intensive care treatment/day were used as potential savings. The model thereby combines the findings of two international publications to enable an economic analysis of pharmaceutical services. During the study period, 177pharmaceutical interventions were evaluated and corresponding probability scores for the occurrence of ADE were determined. From this, annual savings of € 80,000 through avoided costs were calculated. In this project, the economic benefit of pharmaceutical services in intensive care medicine was proven. Ward-based clinical pharmacists are now an integral part of the intensive care treatment team at the Ernst von Bergmann Hospital.

The FORTA (Fit fOR The Aged) List

Multimorbidity and the resulting polypharmacy are widespread in the very old and the evidence on the efficacy and safety of drugs in older people is sparse. Driven by guidelines, this often leads to inappropriate prescribing and drug-related problems. To improve this, numerous listing approaches were developed as tools to optimize medication. These approaches can be divided into drug-oriented listing approaches (DOLA), such as the Beers Criteria®, alist of potentially inappropriate medications for older people or patient-in-focus listing approaches (PILA), such as the Fit fOR The Aged (FORTA) list. The most recent version of the FORTA list was published in 2022 and contains 299 drugs or drug groups targeting 30age-related indications. In addition, several country-specific or region-specific FORTA lists, such as the EURO-FORTA list have been developed. Very few randomized controlled trials have demonstrated the utility of existing listing approaches for improving clinical outcomes, such as adverse drug events, falls or hospitalizations. In the VALFORTA study, the use of FORTA led to a significant improvement in medication treatment. In addition, important clinical endpoints, such as the occurrence of adverse drug events (number needed to treat = 5), activities of daily living (ADL) and the incidence of falls were significantly improved by the FORTA intervention in aclinically relevant manner. Based on these promising results, the use of the FORTA list for medication optimization in older patients is recommended; the prerequisite for application is the needs analysis for drugs according to diagnoses, severity, life expectancy, functional status, and patient wishes.

A pharmacovigilance study of etoposide in the FDA adverse event reporting system (FAERS) database, what does the real world say?

Introduction: Etoposide is a broad-spectrum antitumor drug that has been extensively studied in clinical trials. However, limited information is available regarding its real-world adverse reactions. Therefore, this study aimed to assess and evaluate etoposide-related adverse events in a real-world setting by using data mining method on the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database.Methods: Through the analysis of 16,134,686 reports in the FAERS database, a total of 9,892 reports of etoposide-related adverse drug events (ADEs) were identified. To determine the significance of these ADEs, various disproportionality analysis algorithms were applied, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) algorithms.Results: As a result, 478 significant disproportionality preferred terms (PTs) that were identified by all four algorithms were retained. These PTs included commonly reported adverse events such as thrombocytopenia, leukopenia, anemia, stomatitis, and pneumonitis, which align with those documented in the drug’s instructions and previous clinical trials. However, our analysis also uncovered unexpected and significant ADEs, including thrombotic microangiopathy, ototoxicity, second primary malignancy, nephropathy toxic, and ovarian failure. Furthermore, we examined the time-to-onset (TTO) of these ADEs using the Weibull distribution test and found that the median TTO for etoposide-associated ADEs was 10 days (interquartile range [IQR] 2–32 days). The majority of cases occurred within the first month (73.8%) after etoposide administration. Additionally, our analysis revealed specific high-risk signals for males, such as pneumonia and cardiac infarction, while females showed signals for drug resistance and ototoxicity.Discussion: These findings provide valuable insight into the occurrence of ADEs following etoposide initiation, which can potentially support clinical monitoring and risk identification efforts.

The INGENIOUS trial: Impact of pharmacogenetic testing on adverse events in a pragmatic clinical trial.

Adverse drug events (ADEs) account for a significant mortality, morbidity, and cost burden. Pharmacogenetic testing has the potential to reduce ADEs and inefficacy. The objective of this INGENIOUS trial (NCT02297126) analysis was to determine whether conducting and reporting pharmacogenetic panel testing impacts ADE frequency. The trial was a pragmatic, randomized controlled clinical trial, adapted as a propensity matched analysis in individuals (N = 2612) receiving a new prescription for one or more of 26 pharmacogenetic-actionable drugs across a community safety-net and academic health system. The intervention was a pharmacogenetic testing panel for 26 drugs with dosage and selection recommendations returned to the health record. The primary outcome was occurrence of ADEs within 1 year, according to modified Common Terminology Criteria for Adverse Events (CTCAE). In the propensity-matched analysis, 16.1% of individuals experienced any ADE within 1-year. Serious ADEs (CTCAE level ≥ 3) occurred in 3.2% of individuals. When combining all 26 drugs, no significant difference was observed between the pharmacogenetic testing and control arms for any ADE (Odds ratio 0.96, 95% CI: 0.78-1.18), serious ADEs (OR: 0.91, 95% CI: 0.58-1.40), or mortality (OR: 0.60, 95% CI: 0.28-1.21). However, sub-group analyses revealed a reduction in serious ADEs and death in individuals who underwent pharmacogenotyping for aripiprazole and serotonin or serotonin-norepinephrine reuptake inhibitors (OR 0.34, 95% CI: 0.12-0.85). In conclusion, no change in overall ADEs was observed after pharmacogenetic testing. However, limitations incurred during INGENIOUS likely affected the results. Future studies may consider preemptive, rather than reactive, pharmacogenetic panel testing.

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.

S-1 and 5-Fluorouracil-related adverse events in patients with advanced gastric cancer: A meta-analysis.

To assess S-1 and 5-fluorouracil (5-FU)-related adverse events in patients with advanced gastric cancer and provide focused health care approaches to improve patient compliance and quality of survival. The PubMed, Web of Science, Medline, Cochrane Library, EMbase, SinoMed, Wan Fang Data, CNKI, and VIP databases were searched, and relevant literature was screened from the database construction date through March 31, 2023. Review Manager 5.4.1 and Stata 12.0 were used to analyze the data and GRADEpro was used to assess the quality of the literature. Relative risk ratio (RR) and a 95% confidence interval (CI) were employed as markers to compare adverse events due to S-1 vs 5-FU. Eight randomized controlled trials (RCT) were included, which contained 3,455 patients. The S-1 group had 1,804 patients, and the 5-FU group had 1,651 patients. There were 17 recorded adverse events in total. Stomatitis, hypokalemia, mucosal inflammation, and hypophosphatemia were more common in the 5-FU group than in the S-1 group (P < 0.001). No significant difference was observed between S-1 and 5-FU for other adverse events. Although both S-1 and 5-FU cause a variety of side effects, 5-FU resulted in a higher incidence of stomatitis, hypokalemia, mucosal inflammation, and hypophosphatemia than S-1. Medical professionals should closely monitor the occurrence of adverse drug events and provide timely, rational guidance and nursing care to improve patient compliance and quality of life.

Safety and Efficacy of Low-Dose Versus High-Dose Parenteral Ketorolac for Acute Pain Relief in Patients 65 Years and Older in the Emergency Department.

Background There is limited data surrounding acute pain management in elderly ED patients. Ketorolac is a potent non-steroidal anti-inflammatory drug (NSAID) with dose/duration-dependent side effects. There is evidence that an analgesic ceiling effect exists for parenteral ketorolac doses greater than 10 milligrams (mg); however, this has not been studied in patients 65 years and older. Methods This was a retrospective chart review of ED patients 65 years and older who received at least one dose of parenteral ketorolac. Patients were separated into two cohorts based on the ketorolac dose received: 15 mg IV or 30 mg intramuscular (IM) and 30 mg IV or 60 mg IM. The primary objective was to evaluate the analgesic efficacy of parenteral ketorolac doses measured as needing rescue analgesia from 30 minutes to 2 hours after ketorolac administration. Secondary objectives included changes in pain scores and the occurrence of adverse drug events commonly associated with ketorolac. Results Two-hundred and sixty patients received ketorolac doses of 15 mg IV or 30 mg IM, and 52 received 30 mg IV or 60 mg IM. The primary outcome occurred in seven of 52 patients who received ketorolac 30 mg IV or 60 mg IM and 17 of 260 patients who received ketorolac 15 mg IV or 30 mg IM (13.5% vs. 6.5%, p=0094; OR: 2.22, 95% CI: 0.87-5.67). The average change in pain scores were 2.9 (±3.1) and 2.8 (±2.9) for patients who received doses 30 mg IV or 60 mg IM compared to doses 15 mg IV or 30 mg IM, respectively (p=0.154). The occurrence of adverse events was low in both groups. Conclusion Parenteral ketorolac doses of 15 mg IV or 30 mg IM did not demonstrate a greater need for rescue analgesia compared to doses of 30 mg IV or 60 mg IM.

Economic impact of clinical pharmacist interventions in a general tertiary hospital in Qatar.

With an increasingly strained health system budgets, healthcare services need to continually demonstrate evidence of economic benefits. This study sought to evaluate the economic impact of interventions initiated by clinical pharmacists in an adult general tertiary hospital. A retrospective review of clinical pharmacist interventions was carried out throughout follow-up durations in March 2018, July/August 2018, and January 2019 in Hamad General Hospital (HGH) at Hamad Medical Corporation (HMC) in Qatar. The study included clinical pharmacy interventions data of patients admitted to the internal medicine, critical care, and emergency wards. Included interventions were documented by clinical pharmacists or clinical pharmacy specialists, and approved by physicians. Interventions by non-clinical pharmacists or with missing data were excluded. Adopting the perspective of HMC, we calculated the total economic benefit, which is the sum of the cost savings and the cost avoidance associated with the interventions. Cost savings was defined as the reduced cost of therapy associated with therapy changes minus the cost of intervention and cost avoidance was the cost avoided by eliminating the occurrence of adverse drug events (ADEs). Sensitivity analyses were performed to assess the robustness of results against uncertainties. A total of 852 interventions, based on 340 patients, were included. The analysis projected an annual total benefit of QAR 2,267,036 (USD 621,106) based on a negative cost-savings of QAR-175,139 (USD-47,983) and a positive cost avoidance of QAR741,898 (USD203,260) over the 3-month follow-up period. The uncertainty analysis demonstrated the robustness of outcomes, including a 100% probability of positive economic benefit. The clinical pharmacist intervention was associated with an increased cost of resource use, which was overtaken by the cost avoidance generated. The pharmacy intervention, therefore, is an overall economically beneficial practice in HGH, reducing ADEs with considerable consequential positive economic savings.

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.

Barriers and facilitators to deprescribing of cardiovascular medications: a systematic review

ObjectiveTo synthesise the current knowledge on barriers and facilitators to deprescribing cardiovascular medications (CVMs) at the levels of patients, informal caregivers and healthcare providers (HCPs).Design/settingWe conducted a systematic review of...

Validation of Pharmacogenomic Interaction Probability (PIP) Scores in Predicting Drug-Gene, Drug-Drug-Gene, and Drug-Gene-Gene Interaction Risks in a Large Patient Population.

Utilizing pharmacogenomic (PGx) testing and integrating evidence-based guidance in drug therapy enables an improved treatment response and decreases the occurrence of adverse drug events. We conducted a retrospective analysis to validate the YouScript® PGx interaction probability (PIP) algorithm, which predicts patients for whom PGx testing would identify one or more evidence-based, actionable drug-gene, drug-drug-gene, or drug-gene-gene interactions (EADGIs). PIP scores generated for 36,511 patients were assessed according to the results of PGx multigene panel testing. PIP scores versus the proportion of patients in whom at least one EADGI was found were 22.4% vs. 22.4% (p = 1.000), 23.5% vs. 23.4% (p = 0.6895), 30.9% vs. 29.4% (p = 0.0667), and 27.3% vs. 26.4% (p = 0.3583) for patients tested with a minimum of 3-, 5-, 14-, and 25-gene panels, respectively. These data suggest a striking concordance between the PIP scores and the EAGDIs found by gene panel testing. The ability to identify patients most likely to benefit from PGx testing has the potential to reduce health care costs, enable patient access to personalized medicine, and ultimately improve drug efficacy and safety.

The safety of habits of food supplementation use in dyslipidemic patients

Transitional care programs (i.e. interventions delivered both in hospital and in primary care), could increase continuity and consequently quality of care. However, limited studies on the effect of these programs on Adverse Drug Events (ADEs) post-discharge are available. Therefore, the aim of this study was to investigate the effect of a transitional pharmaceutical care program on the occurrence of ADEs 4 weeks post-discharge.A multicentre prospective before-after study was performed in a general teaching hospital, a university hospital and 49 community pharmacies. The transitional pharmaceutical care program consisted of: teach-back to the patient at discharge, a pharmaceutical discharge letter, a home visit by a community pharmacist and a clinical medication review by both the community and the clinical pharmacist, on top of usual care. Usual care consisted of medication reconciliation at admission and discharge by pharmacy teams. The primary outcome was the proportion of patients who reported at least 1 ADE 4 weeks post-discharge. Multivariable logistic regression was used to adjust for potential confounders.In total, 369 patients were included (control: n = 195, intervention: n = 174). The proportion of patients with at least 1 ADE did not statistically significant differ between the intervention and control group (general teaching hospital: 59% vs. 67%, ORadj 0.70 [95% CI 0.38–1.31], university hospital: 63% vs 50%, OR adj 1.76 [95% CI 0.75–4.13]).The transitional pharmaceutical care program did not decrease the proportion of patients with ADEs after discharge. ADEs after discharge were common and more than 50% of patients reported at least 1 ADE. A process evaluation is needed to gain insight into how a transitional pharmaceutical care program could diminish those ADEs.

Psychosomatic or Psychotropic Polypharmacy? A Case Highlighting the Importance of Pharmacokinetics

<h3>Introduction</h3> Psychotropic drugs are among the most common medications prescribed to elderly patients. The number of psychotropic drugs has increased significantly over the past few decades with a proportional increase in adverse medication outcomes including drug-drug interactions. Advancing age is accompanied by changes in pharmacokinetics and pharmacodynamics that put older patients at greater risk for adverse medication outcomes. The majority of psychotropic agents are metabolized by hepatic enzymes with many drug-drug interactions of psychotropics involving the cytochrome P450 enzyme system. The activity of these enzymes can be inhibited or induced by several drugs resulting in clinically significant drug-drug interactions. This case highlights the importance of maintaining a comprehensive understanding of pharmacokinetics and considering the possibility of an adverse drug reaction when evaluating an older patient presenting with new and unexplained symptoms. <h3>Methods</h3> This case report focuses on a geriatric patient with depression and multiple medical comorbidities presenting with unexplained neurological symptoms thought to be psychosomatic in origin. Patient's clinical documents in our electronic medical records system were reviewed. A literature survey was performed on the topic of psychotropic polypharmacy, pharmacokinetics, and the increased risk of adverse medical outcomes in geriatric patients. <h3>Results</h3> A 69 year old female was referred by inpatient neurology to an outpatient geriatric psychiatry clinic for evaluation and management of psychogenic non-epileptic seizures/conversion disorder. She had been experiencing ongoing symptoms of dizziness, dysarthria, and gait instability with multiple serious falls requiring hospitalization. She underwent an extensive and uneventful medical and neurological workup. Immediately prior to onset of symptoms, the patient was taking the maximum dose of amitriptyline at 150mg when bupropion was added and increased to 300mg. Symptoms were suspected to be secondary to amitriptyline toxicity with bupropion (a potent CYP2D6 inhibitor) leading to supratherapeutic amitriptyline levels (a CYP2D6 substrate). Amitriptyline level was obtained and returned supratherapeutic at 362. Both amitriptyline and bupropion were discontinued with immediate resolution of the patient's neurological symptoms. <h3>Conclusions</h3> Polypharmacy is a disease simulator; patients may exhibit conditions caused by medications rather than organic illness. It is crucial for clinicians to be aware of drug interactions and consider whether the development of a new medical condition could be the presentation of an adverse drug event. Many drug interactions are the result of altered CYP450 metabolism, and therapeutic drug doses may cause adverse effects related to increased drug serum levels if a CYP450 enzyme inhibitor is added or if the patient is a genetically poor metabolizer. Knowledge of the most important drugs metabolized by cytochrome P450 enzymes, as well as the most potent inducers and inhibitors, can help to reduce the occurrence of adverse drug events and interactions.

Drug resistance patterns, treatment outcomes and factors affecting unfavourable treatment outcomes among extensively drug resistant tuberculosis patients in Pakistan; a multicentre record review

BackgroundExtensively drug resistant tuberculosis (XDR-TB) is considered as a major threat to global health. This study aimed to analyse the treatment outcomes and identify the factors significantly associated with unfavourable treatment outcomes among XDR-TB patients. MethodsWe conducted a retrospective observational study at 10 Programmatic Management Units of the National Tuberculosis Control Program of Pakistan. The Electronic Nominal Recording Reporting System records were used to collect data of all eligible XDR-TB patients registered at the study sites between March 2012 and August 2018. Treatment outcomes were analysed as per the standard criteria. Factors associated with unfavourable treatment outcomes were analysed by using multivariate binary logistic regression analysis. ResultsOut of the total 184 patients, 59 (32.1%) completed their treatment successfully. Whereby, 83 patients (45.1%) died, 24 (13%) had treatment failure, and 11 (6%) were lost to follow-up. Treatment outcomes were not evaluated in 7 (3.8%) patients. Factors significantly associated with unfavourable treatment outcomes included; conventional therapy with bedaquiline, unfavourable interim treatment outcomes and occurrence of adverse drug events (negative association). ConclusionTreatment success rate in the study cohort was sub-optimal (i.e., <75%). The poor success rate and high mortality are concerning, and requires immediate attention of the program managers and clinicians.

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.