Adverse drug reactions (ADRs) are associated with greater healthcare costs; drug-drug interactions (DDIs) are a common cause of ADRs.

To estimate the risk and cost of ADR-related hospital admission associated with DDI-exposure versus no DDI-exposure in an older community-dwelling population.

This is a secondary analysis of a cohort study among 798 older individuals admitted acutely to hospital in Ireland (2016-2017). Full medication-history (pre-admission) was used to measure severe DDIs. Hospital costs were derived from unit costs. Logistic regression and propensity score weighting was used to examine the association between DDI-exposure and ADR-related hospital admission. Quantile regression was used to examine median costs associated with DDI-exposure. Adjusted odds-ratios (aORs), adjusted median costs, and 95% confidence intervals (CIs) are reported.

N = 782 (98%) individuals using ≥ 2 drugs were included. Mean age: 80.9(SD ± 7.5) years; 52.2% female; 45.1% with an ADR-related admission. Pre-admission, n = 316 (40.4%) patients had any severe DDI, n = 466 unexposed; n = 113 (14.5%) had a DDI which increases bleeding risk, n = 669 unexposed. The risk of ADR-related hospital admission associated with any severe DDI was aOR = 1.02 [95% CI: 0.82, 1.28]), and aOR = 1.83 [95% CI: 1.35, 2.44]) for DDIs which increase bleeding risk. The median cost of ADR-related hospital admission associated with any severe DDI versus none, was €880 [- 1205, 3055]; and €3,520 [- 934, 7974] for a DDI which increases bleeding risk versus none.

DDIs which increase bleeding risk were associated with greatest ADR-related hospital admission risk and highest costs for the healthcare system. Further research examining these DDIs is needed.

As people get older, they tend to take more preventive medication such as statins, beta-blockers and anti-coagulants to help prolong their lives. The risks of taking medication can start to outweigh the benefits in older people, and whether those with comorbidities want to extend these years of poor health is another consideration. One-third of older people will develop dementia, and they may not have the mental capacity to decide whether to continue or withdraw preventive medication. In these cases, deprescribing is left to advocates, such as healthcare professionals and family members. This systematic review will look at the views of stakeholders, including advocates, people living with dementia and any other people involved in the decision-making process for deprescribing preventive medication in dementia.

A systematic review of qualitative evidence using thematic synthesis and an inductive approach will be conducted. The following databases and platforms will be searched: Embase, HMIC, MEDLINE, PsycINFO, CINAHL, PubMed, Cochrane Central Library, OATD, ProQuest, Scopus and the Web of Science, along with manual searches through citation mining and grey literature. Only primary qualitative studies (or the qualitative elements of mixed method studies) will be used. There will be no date limit, and the search will be completed by April 2025. Only English-language articles will be used. The included studies will present views and experiences about deprescribing specifically preventive medication in dementia cases. Principles identified by Cochrane for qualitative studies will be used as guidance. Covidence will facilitate two independent reviewers to identify relevant studies, and the Critical Appraisal Skills Programme and Mixed Methods Appraisal Tool will be used to assess quality. NVivo will be used to manage the extracted findings from the included studies.

Ethical approval is not applicable for this study as no original data is going to be collected as it is a systematic review. The findings will be disseminated in a peer-reviewed open-access publication and at conference presentations.

CRD42023476394. Any changes made to the protocol will be reported on PROSPERO.

Pulmonary fibrosis (PF) is a slow and irreparable damage of the lung caused by the accumulation of scar tissue, which eventually results in organ dysfunction and fatality from gas exchange failure. One of the extensively studied inflammatory pathways in PF is the NF-κB signalling pathway, which is reportedly involved in epithelial-mesenchymal transition, myofibroblast differentiation, and other cellular processes. Additionally, studies have evidence that NF-κB signalling pathways can be employed as a potential target for developing therapeutic agents against PF. In the current scenario, FDA-approved drugs, nintedanib and pirfenidone, have been used for the treatment of PF with potential side effects. Recently, the usage of bioactive compounds has attracted attention in the treatment of PF. This review focuses on the involvement of the NF-κB signalling pathway in PF and the significance of phytocompounds in regulating the NF-κB pathway. Both the in vitro and in vivo studies reveal that NF-κB-targeted plant-based bioactive compounds significantly ameliorate the PF condition as well as improve the health condition. Databases such as Scopus, PubMed, and Web of Science were used to conduct literature surveys and compile data on all the bioactive compounds. In conclusion, the plant-derived bioactive compounds are potent enough to target the NF-κB with its biological properties, and this could be a highly effective therapeutic strategy for PF in the future.

Background/Objectives: Polymorbidity and polypharmacy are major challenges in geriatric care, resulting in a reduced quality of life and increased health care costs. Methods: We evaluated the proactive medication management of nursing home residents through personal visits and the use of a clinical decision support system (CDSS) with an integrated Beers Criteria list. Results: Among 56 nursing home residents, we observed a high prevalence of polypharmacy with an average of 7.9 regular and 5.1 on-demand prescriptions. Proactive medication management led to persistent medication changes in 87.5% of patients. Regular prescriptions were reduced in 21 residents and increased in 18 residents, resulting in a reduced use of cardiovascular drugs and antacids (p < 0.05), but no significant overall reduction in polypharmacy. CDSS alerts based on Beers Criteria made no clinically relevant contribution to medication reduction. Conclusions: Proactive geriatric medication management led to persistent medication changes and no reduction in overall polypharmacy but reduced the use of selected drug classes that are associated with an increased risk of adverse reactions and costs. The clinical relevance and implementability of Beers Criteria were low, revealing major limitations of algorithm-based alerts for older patients, who require additional personalized evaluations of their individual complex healthcare needs.

Adverse drug reactions (ADRs) harm patients and are costly for healthcare systems. Genetic variation contributes to variability in medication response and prospective knowledge of these variants can decrease risk of ADRs, as shown in the PREPARE trial. Reduction in ADRs would affect only those reactions to drugs contained in well-validated pharmacogene-drug pairs. The scope of ADRs represented by these drugs on a population scale is unclear. The objective of this study was to characterize the pharmacogene-drug-associated ADR reporting landscape from a national regulatory pharmacovigilance dataset to elucidate the scale of potential ADR mitigation by pharmacogenomics (PGx) implementation.

All publicly available Yellow Card ADR reports to the United Kingdom Medicines and Healthcare Products Regulatory Agency, from 1963 to 2024, were compiled using programmatic data extraction. The ADRs were analysed with descriptive statistics, stratified by PGx status and by associated genes. Prescribing prevalence from the literature was compared with age range matched ADR reports for PGx-associated drugs. There were 1,345,712 ADR reports, attributed to 2,499 different substances. 115,789 adverse drug reports (9%) were associated with drugs for which ADR risk can be modified based on pharmacogenomic prescribing guidance. Seventy-five percent of these (n = 87,339) were due to medicines which interact with only three pharmacokinetic pharmacogenes (CYP2C19, CYP2D6, SLCO1B1). Forty-seven percent of all the PGx mitigatable ADRs identified were attributed to psychiatric medications (n = 54,846), followed by 24% attributed to cardiovascular medications (n = 28,279). Those experiencing PGx mitigatable ADRs, as compared with non-PGx mitigatable ADRs, were older and the ADRs more often consisted of severe non-fatal reactions. Many PGx-associated psychiatric drug ADRs were overrepresented as compared with prescribing prevalence, but fatal cardiac arrhythmias were uncommon consequences, comprising only 0.4% of these ADRs (n = 172 of n = 48,315 total ADRs). Limitations of this data source include under reporting of ADRs and reporting bias. These findings are based on analysis of the Yellow Card dataset described and may not represent all ADRs from a generalised patient population.

Nine percent of all reported ADRs are associated with drugs where a genetic variant can cause heightened risk of an ADR and inform prescribing. A panel of only three pharmacogenes could potentially mitigate three in every four PGx modifiable ADRs. Based on our findings, Psychiatry may be the single highest impact specialty to pilot PGx to reduce ADRs and associated morbidity, mortality and costs.

Evaluating a patient's medication list is critical to reduce prescribing errors (PEs), but is a labour- and time-intensive process. Identification of patients at risk of PEs could improve the allocation of scarce time and resources, but currently available prediction tools are not effective.

To investigate whether ward doctors can identify patients at risk of PEs.

This prospective matched case-control study was conducted on three clinical wards in an academic hospital. Otolaryngology and oncology ward doctors used clinical intuition to select patients requiring a clinical medication review (CMR) (cases). These patients were then matched 1:1 on age (±10 years) and number (±1) of prescriptions with patients not selected for CMRs on the internal medicine and upper gastrointestinal surgery ward (controls). A multidisciplinary in-hospital pharmacotherapeutic stewardship team assessed the prevalence of PEs.

A total of 387 patients with 5191 prescriptions were included. Overall, 799 PEs affecting 279 patients (72.1%) were identified. Most PEs (58.8%) occurred during hospitalization. There were no significant differences in age, number of prescriptions, sex, renal function or documented allergies or intolerances between the cases and controls or between controls and other patients who did not receive a CMR. The incidence of PEs was higher in cases than in controls (97.5% vs 72.5%, odds ratio = 14.8, 95% confidence interval [CI] 1.8-121.1, P = .002)). The rate of PEs was three times higher in cases than in controls (incidence rate ratio = 3.0, 95% CI 2.3-4.0, P < .001).

Ward doctors can effectively identify patients with PEs, and thus at risk of medication-related harm, using clinical intuition.

Potential drug-drug interactions (pDDIs) pose substantial risks in clinical practice, leading to increased morbidity, mortality, and healthcare costs. Tools like Micromedex drug-drug interaction checker are commonly used to screen for pDDIs, yet emerging AI models, such as ChatGPT, offer the potential for supplementary pDDI prediction. However, the accuracy and reliability of these AI tools in a clinical context remain largely untested.

This study evaluates pDDIs in discharge prescriptions for medical ward patients and assesses ChatGPT-4.0's effectiveness in predicting these interactions compared to Micromedex drug-drug interaction checker.

A cross-sectional study was conducted over three months with 301 discharged patients. pDDIs were identified using Micromedex drug-drug interaction checker, detailing each interaction's occurrence, severity, onset, and documentation. ChatGPT-4.0 predictions were then analyzed against Micromedex data. Binary logistic regression analysis was applied to assess the influence of predictor variables in the occurrence of pDDIs.

1551 drugs were prescribed to 301 patients, averaging 5.15 per patient. pDDIs were detected in 60.13 % of patients, averaging 3.17 pDDIs per patient, ChatGPT-4.0 accurately identified pDDIs (100 % for occurrence) but had limited accuracy for severity (37.3 %) and moderate accuracy for onset (65.2 %). The most frequent major interaction was between Cefuroxime Axetil and Pantoprazole Sodium. Polypharmacy significantly increased the risk of pDDIs (OR: 3.960, p < 0.001).

pDDIs are prevalent in internal medicine discharge prescriptions, with polypharmacy heightening the risk. While ChatGPT 4.0 accurately identifies pDDI occurrence, its limitations in predicting severity, onset, and documentation underscore healthcare professionals' need for careful oversight.

Nonsteroidal anti-inflammatory drug use is prevalent in sport however the risk associated with their use in athletes is not well-understood. This review discusses the pharmacology of nonsteroidal anti-inflammatory drugs and the prevalence of their use in different sports and factors driving this. Use is very high in sports such as professional football and is sometimes by routine without indication and without medical supervision. However there is a paucity of evidence in other sports. There is good evidence for use of nonsteroidal anti-inflammatory drugs following an acute injury but they may prevent normal tissue healing and remodelling if used longer term for musculoskeletal injuries. There are well-known risks of cardiac, gastrointestinal and renal side effects but little specific data for athletes. Renal events are discussed in detail including the cumulative effect that nonsteroidal anti-inflammatory drug use, dehydration and concurrent illness can have to produce significant renal and systemic insult. We then discuss a pragmatic prescribing model enabling clinicians to utilise the beneficial effects of these medications whilst minimising risks.

Predicting accurately the mechanisms of drug-drug interaction (DDI) events is crucial in drug research and development. Existing methods used to predict these events are primarily based on deep learning and have achieved satisfactory results. However, they rarely consider the presence of redundant co-information between the multimodal data of a drug and the need for consistency in the predicted features of each drug modality. Herein, we propose a new method for drug interaction event prediction based on multimodal mutual orthogonal projection and intermodal consistency loss. Our method obtains the features of each modality through a multimodal mutual orthogonal projection module, which eliminates redundant common information with other modalities. In addition, we use the consistency loss between modalities and make the predicted features of each modality more similar. In comparative experiments, our proposed method achieves a prediction accuracy of 0.9500, and an area under the precision-recall (AUPR) curve is 0.9833 for known DDIs. This method outperforms existing methods. The results show that the proposed method is capable of accurately predicting DDIs.

The interactions of drugs with the host's immune cells determine the drug's efficacy and adverse effects in patients. Nonsteroidal Anti-Inflammatory Drugs (NSAID), such as corticosteroids, NSAIDs, and immunosuppressants, affect the immune cells and alter the immune response. Molecularly, drugs can interact with immune cells via cell surface receptors, changing the antigen presentation by modifying the co-stimulatory molecules and interacting with the signaling pathways of T cells, B cells, Natural killer (NK) cells, mast cells, basophils, and macrophages. Immunotoxicity, resulting from drug-induced changes in redox status, generation of Reactive Oxygen Species (ROS)/Reactive Nitrogen Species (RNS), and alterations in antioxidant enzymes within immune cells, leads to immunodeficiency. This, in turn, causes allergic reactions, autoimmune diseases, and cytokine release syndrome (CRS). The treatment options should include the evaluation of immune status and utilization of the concept of pharmacogenomics to minimize the chances of immunotoxicity. Many strategies in redox, like targeting the redox pathway or using redox-active agents, are available for the modulation of the immune system and developing drugs. Case studies highlight significant drug-immune cell interactions and patient outcomes, underscoring the importance of understanding these complexities. The future direction focuses on the drugs to deliver antiviral therapy, new approaches to immunomodulation, and modern technologies for increasing antidote effects with reduced toxicity. In conclusion, in-depth knowledge of the interaction between drugs and immune cells is critical to protect the patient from the adverse effects of the drug and improve therapeutic outcomes of the treatment process. This review focuses on the multifaceted interactions of drugs and their consequences at the cellular levels of immune cells.

As the population ages, the prevalence of chronic diseases increases, leading to greater reliance on multiple medications that are conducted to increase the risk of adverse drug reactions (ADR) that may cause higher morbidity and mortality rates. This study aims to evaluate medication prescribing patterns in the older adults and assess compliance with the World Health Organization (WHO) guidelines and Beers Criteria.

A cross-sectional study was conducted over six months in 2022, collecting prescriptions for patients aged 65 and above from a 24-hour community pharmacy in Iran. The prescriptions were analyzed according to the WHO prescribing guidelines, including the mean number of prescribed drugs, the number of injectable drugs and antibiotics per prescription, and also the prescription of drugs with generic names and from the list of Essential Drug List (EDL). In addition, the prescriptions were assessed according to the Beers Criteria for the frequency of prescription of potentially inappropriate medications (PIMs). Also, polypharmacy, which is defined as the prescription of more than five drugs per prescription, has been investigated based on the number of drugs prescribed per prescription.

1,053 older patient prescriptions were assessed, whose average age was 72.3 ± 6.7 years, with 36.2% of prescriptions involving polypharmacy (five or more drugs). The most frequent medical discipline of prescribers was general practice (30.3%). The average number of drugs per prescription was 4.1 ± 2.1, which exceeded the WHO recommendation. Additionally, 47.3% of prescriptions contained at least one PIM according to the Beers Criteria, with non-steroidal anti-inflammatory drugs (NSAIDs) being the most common (17.9%). The relative frequency of injectable drugs and antibiotics used per prescription was 20.8 and 18.9%, respectively, while 7.6% of prescriptions did not use generic names.

The study highlights concern about levels of polypharmacy and PIM use in older patients. While the low rate of antibiotic prescribing and relatively high use of generic drugs indicate some positive adherence to WHO guidelines, the frequent prescription of PIMs and the high average number of drugs per prescription point to substantial room for improvement.

Prescribing errors (PEs) in hospital care lead to patient harm, prolonged hospital stays, readmissions, and mortality. Despite interventions that successfully target 'high risk' populations in trials, PE rates remain largely unchanged in real-world settings. Existing studies often focus narrowly on specific populations, overlooking the wider complexities of hospital-wide prescribing. This scoping review evaluates interventions for adult inpatients to identify knowledge gaps in how to reduce in-hospital PEs.

A systematic search of PubMed, EMBASE.com, and the Cochrane Library (inception to 13 December 2024) was conducted following PRISMA-ScR guidelines. Studies prospectively evaluating interventions reducing in-hospital PEs were eligible for inclusion; those focusing on specific drugs, wards or populations or lacking original data were excluded.

Fourteen studies met the inclusion criteria. Technological interventions, such as computerized order entry systems, accounted for 35.7% of the studies. Half addressed prescriber-related factors, such as inadequate drug knowledge and prescribing skills, while organizational factors were underexplored.

Current interventions fail to address the underlying complexities, leaving critical gaps to decrease in-hospital PEs. To achieve sustainable PE reductions and improve patient safety, a multidisciplinary approach, standardized reporting, organizational reform, and a Safety-II perspective are essential.

Phenoconversion, a genotype-phenotype mismatch, challenges a successful implementation of personalized medicine. The aim of this study was to detect and determine phenoconversion using the solanidine metabolites 3,4-seco-solanidine-3,4-dioic acid (SSDA) and 4-OH-solanidine as diet-derived cytochrome P450 2D6 (CYP2D6) biomarkers in a geriatric, multimorbid cohort with high levels of polypharmacy.

Blood samples and data of geriatric, multimedicated patients were collected during physician counsel (CT: NCT05247814). Solanidine and its metabolites were determined via liquid chromatography/tandem mass spectrometry and used for CYP2D6 phenotyping. CYP2D6 genotyping was performed and activity scores (AS) were assigned. Complete medication intake was assessed. A shift of the AS predicted via genotyping as measured by phenotyping was calculated.

Solanidine and its metabolites were measured in 88 patients with complete documentation of drug use. Patients had a median age of 83 years (interquartile range [IQR] 77-87) and the majority (70.5%, n = 62) were female. Patients took a median of 15 (IQR 12-17) medications. The SSDA/solanidine metabolic ratio correlated significantly with the genotyping-derived AS (P < .001) and clearly detected poor metabolizers. In the model adjusted for age, sex, Charlson Comorbidity Index and estimated glomerular filtration rate each additional CYP2D6 substrate/inhibitor significantly lowered the expected AS by 0.53 (95% confidence interval 0.85-0.21) points in patients encoding functional CYP2D6 variants (R2 = 0.242).

Phenotyping of CYP2D6 activity by measurement of diet-derived biomarkers elucidates phenoconversion in geriatric patients. These results might serve as a prerequisite for the validation and establishment of a bedside method to measure CYP2D6 activity in multimorbid patients for successful application of personalized drug prescribing.

The aim of this study was to identify potentially applicable pharmacovigilance (PV) indicators for health services available in the literature.

We searched MEDLINE, EMBASE, LILACS, IBECS, CUMED, SciELO, and Google Scholar bibliographic between January 1, 2004 and January 23, 2023, and 25 websites from different organizations for studies describing specific PV indicators in health services. The methodological quality of the included studies was assessed using the Appraisal of Indicators through the Research and Evaluation (AIRE) tool. The indicators were differentiated into structure, process and outcome, and also grouped according to the applicability of the PV activities carried out in health services, based on the domains proposed by the Centers for Disease Control and Prevention.

We identified 14 studies and 100 PV indicators classified as structural (51%), process (32%), and outcome (17%). The indicators classified according to the aspect of the PV activities they measure cover "Results of PV/ External impact" (45%); "How does the PV unit works/Management of their information" (32%); "The PV unit and team" (23%). According to AIRE, the methodological quality of the included studies varied considerably. In consensus, we selected 55 indicators that could potentially be useful to health services.

This systematic review made it possible to identify a considerable number of indicators. Many of them aim to evaluate different aspects of PV activities that can be valuable from a public health and health system perspective. Therefore, we propose a new classification and a set of indicators useful for health services.

The corticosteroid dexamethasone, which is used to treat numerous health conditions, remains the first-line treatment for patients hospitalized with COVID-19 requiring oxygen. Current British National Formulary prescribing advice warns of a "severe theoretical" or "severe anecdotal" risk of drug-drug interactions between dexamethasone and 138 different medications. In humans, dexamethasone is eliminated via the cytochrome P450 monooxygenase system, particularly CYP3A4. It is also described as a human cytochrome P450-inducing agent. To establish factors that affect concomitant therapy and dexamethasone efficacy in the treatment of COVID-19, we used a unique mouse model humanized for cytochrome P450s and the transcription factors that regulate their expression, the pregnane X receptor, and the constitutive androstane receptor. We found that induction of CYP3A4 with the anticancer drug dabrafenib or the herbal medicine St John's wort profoundly reduced dexamethasone exposure. These data suggest that comedications that induce cytochrome P450 expression can have a marked effect on dexamethasone exposure and, potentially, clinical efficacy. We also observed that rather than increasing CYP3A4 expression, dexamethasone at doses equivalent to or higher than those used in the treatment of COVID-19 reduced CYP3A4 expression and increased exposure to dabrafenib. These data indicate the need for a clinical trial to establish the risk of overexposure to comedications during dexamethasone treatment, including the treatment of COVID-19. SIGNIFICANCE STATEMENT: Current prescribing advice identifies a potential theoretical risk of severe side effects when dexamethasone, one of the most widely used drugs in clinical practice, is coadministered with many other drugs; it is, however, difficult to define the magnitude of this risk for specific drug combinations. We describe the use of cytochrome P450-humanized 8HUM mice to predict drug-drug interactions in patients on polypharmacy, a means of generating data that could better inform clinicians regarding foreseeable drug-drug interactions involving dexamethasone.

Adverse drug reactions (ADRs) account for a large proportion of hospitalizations among adults and are more common in multimorbid patients, worsening clinical outcomes and burdening healthcare resources. Over the past decade, pharmacogenomics has been developed as a practical tool for optimizing treatment outcomes by mitigating the risk of ADRs. Some single-gene reactive tests are already used in clinical practice, including the DPYD test for fluoropyrimidines, which demonstrates how integrating pharmacogenomic data into routine care can improve patient safety in a cost-effective manner. The evolution from reactive single-gene testing to comprehensive pre-emptive genotyping panels holds great potential for refining drug prescribing practices. Several implementation projects have been conducted to test the feasibility of applying different genetic panels in clinical practice. Recently, the results of a large prospective randomized trial in Europe (the PREPARE study by Ubiquitous Pharmacogenomics consortium) have provided the first evidence that prospective application of a pre-emptive pharmacogenomic test panel in clinical practice, in seven European healthcare systems, is feasible and yielded a 30% reduction in the risk of developing clinically relevant toxicities. Nevertheless, some important questions remain unanswered and will hopefully be addressed by future dedicated studies. These issues include the cost-effectiveness of applying a pre-emptive genotyping panel, the role of multiple co-medications, the transferability of currently tested pharmacogenetic guidelines among patients of non-European origin and the impact of rare pharmacogenetic variants that are not detected by currently used genotyping approaches.

Severe cutaneous adverse reactions (SCARs) are life-threatening and often linked to antiepileptic drugs (AEDs). Common types of SCARs include Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS). Immune-mediated mechanisms involving human leukocyte antigen (HLA) alleles have been implicated in the pathogenesis of this reaction. This study examines the association between specific HLA alleles (HLA-A, -B, and -DRB1) and AED-induced SCARs in the Iraqi population.

A total of 50 patients diagnosed with SCARs and 90 tolerant controls were recruited from Dr. Saad Al-Wattari Hospital for Neurological Sciences and Baghdad Hospital - Medical City. HLA genotyping was performed using PCR-SSO method from peripheral blood samples. Statistical comparisons were made using the t-test or chi-square test, while univariate logistic regression with Bonferroni's correction (p < 0.05) were used to assess associations between HLA alleles and SCARs.

Among the patients, SJS was the most prevalent type of SCARs observed. Analysis of HLA allele frequencies revealed significant associations between specific alleles. HLA-A∗02:01 was found to be significantly associated with a lower risk of AED-induced SJS (OR = 0.36; 95 % CI: 0.13-0.97), while HLA-A∗24:02 and HLA-B∗15:02 were associated with an increased risk of AED-induced SJS (OR = 3.60; 95 % CI: 1.21-10.72 and OR = 4.41; 95 % CI: 1.18-16.47, respectively). For AED-induced TEN, HLA-A∗01:02, HLA-B∗15:02, and HLA-B∗52:01 showed significant associations (OR = 6.92; 95 % CI: 1.39-34.37 and OR = 6.55; 95 % CI: 1.62-26.52, respectively), with HLA-DRB1∗03:01 being highly significant (OR = 5.09; 95 % CI: 1.72-15.00). Additionally, HLA-B∗40:02 was strongly associated with AED-induced DRESS (OR = 29.33; 95 % CI: 3.50-245.32).

This study identifies key HLA alleles associated with AED-induced SCARs in the Iraqi population. These findings could facilitate personalized medicine approaches, aiding in better prediction and prevention of SCARs in AED therapy.

Multimorbidity is associated with significant out-of-pocket expenditures (OOPE) and catastrophic health expenditure (CHE), especially in low- and middle-income countries like India. Despite this, there is limited research on the financial burden of multimorbidity in outpatient and inpatient care, and cross-state comparisons of CHE are underexplored.

We conducted a cross-sectional analysis using nationally representative data from the National Sample Survey 75th Round 'Social Consumption in India: Health (2017-18)', focusing on patients aged 30 and above in outpatient and inpatient care in India. We assessed multimorbidity prevalence, OOPE, CHE incidence, and CHE intensity. Statistical models, including linear, log-linear, and logistic regressions, were used to examine the financial risk, with a focus on non-communicable diseases (NCDs), healthcare facility choice, and socioeconomic status and Epidemiological Transition Levels (ETLs).

Multimorbidity prevalence in outpatient care (6.1%) was six times higher than in inpatient care (1.1%). It was most prevalent among older adults, higher MPCE quintiles, urban patients, and those with NCDs. Multimorbidity was associated with higher OOPE, particularly in the rich quintile, patients seeking care from private providers, low ETL states, and rural areas. CHE incidence was highest in low ETL states, private healthcare users, poorest quintile, males, and patients aged 70 + years. CHE intensity, measured by mean positive overshoot, was greatest among the poorest quintile, low ETL states, rural, and male patients. Log-linear and logistic regressions indicated that multimorbidity patients with NCDs, those seeking private care, and those in low ETL states had higher OOPE and CHE risk. The poorest rural multimorbidity patients had the greatest likelihood of experiencing CHE. Furthermore, CHE intensity was significantly elevated among multimorbidity patients with NCDs (95% CI: 19.29-45.79), patients seeking care in private, poorest, and from low ETL states (95% CI: 7.36-35.79).

The high financial burden of OOPE and CHE among multimorbidity patients, particularly those with NCDs, highlight the urgent need for comprehensive health policies that address financial risk at the primary care level. To alleviate the financial burden among multimorbidity patients, especially in low-resource settings, it is crucial to expand public healthcare coverage, incorporate outpatient care into financial protection schemes, advocate for integrated care models and preventive strategies, establish standardized treatment protocols for reducing unnecessary medications linked to polypharmacy, and leverage the support of digital health technologies.

Intravenous non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used in healthcare settings, but their comparative safety and resource utilization impacts remain understudied. This study aimed to compare adverse drug reactions (ADRs) and healthcare resource utilization (HCRU) between patients receiving IV-ibuprofen versus IV/IM ketorolac.

A retrospective, longitudinal analysis was conducted using an all-payer database, examining records from January 1, 2014, to June 3, 2023. The study included both adult (≥18 years) and pediatric (<18 years) populations who received one or more doses of either medication. Propensity score matching was applied to both populations, and HCRU was tracked for 29 days post-final dose. The adult cohort included 31,046 IV-ibuprofen and 124,184 ketorolac records, while the pediatric cohort had 5,579 patients per treatment arm.

Both adult and pediatric patients receiving IV-ibuprofen demonstrated lower ADR incidence and reduced HCRU compared to those receiving ketorolac.

The findings suggest IV-ibuprofen may be a safer alternative to ketorolac, potentially improving patient care outcomes while reducing healthcare system burden. These results have implications for clinical practice and healthcare resource management.

Community pharmacists are most accessible to patients. Hence, they have a crucial role in ensuring drug safety by detecting and reporting adverse drug reactions (ADRs). However, there may be gaps in their knowledge of ADR reporting systems and barriers they face in reporting.

This study aims to assess community pharmacists' knowledge of ADR reporting systems in the Kingdom of Jordan, identify the barriers they face in reporting ADRs, and explore the broader factors that influence their involvement in pharmacovigilance activities.

In-depth, semi-structured, face-to-face interviews were held with 20 community pharmacists from different regions of Jordan to evaluate their understanding of ADR reporting, the obstacles they encountered, and the elements that could motivate them to report ADRs. The interviews were transcribed and subjected to thematic analysis to find recurrent themes and insights. The thematic analysis highlighted opportunities for continuing education and an absence of formal training as the main barriers to ADR reporting.

Pharmacists reported dissatisfaction with time limits in their hectic work situations and the complexity of reporting procedures, especially the length and information demanded by ADR reporting forms. Another factor influencing low reporting rates was a perceived lack of acknowledgment and feedback. Participants proposed that encouraging ADR reporting with professional recognition or compensation and improving and digitizing the reporting process would promote increased participation.

ADR reporting presents considerable difficulties for community pharmacists in Jordan, mostly because of administrative obstacles and an absence of official support and training. Enhancing pharmacovigilance efforts in Jordan could be achieved by providing incentives, simplifying the reporting procedure, and incorporating reporting into the current pharmacy management software.

Drug-drug interactions (DDIs), highly prevalent amongst the elderly, can lead to avoidable medication-related harm. Cardiovascular and central nervous system (CNS) drugs are commonly implicated. To date, there is no consensus on how to measure DDIs, making comparisons across countries challenging.

To (i) establish a common data model (CDM) to measure DDI prevalence in the older (aged ≥ 70 years) community-dwelling population of three European countries and (ii) compare and describe cardiovascular and CNS DDI prevalence rates across these countries.

This cross-country study will apply a harmonised method of DDI identification and analysis using the WHO ATC classification system and national pharmacy claims data from three European countries (Ireland, Italy, Spain). Patients aged ≥ 70 years dispensed ≥ 2 medications during 2016 will be identified from each country's national database. 'Severe' cardiovascular and CNS DDIs (i.e., may result in a life-threatening event/permanent detrimental effect) will be identified using the British National Formulary and Stockley's Drug Interactions. Two separate lists of 'severe' DDIs, per medications reimbursed, will be applied to each database: (i) DDIs relevant to each individual country and (ii) DDIs relevant to all three countries. DDIs will be defined as co-dispensed (same day) and concomitantly (±7 days) dispensed.

Descriptive statistics, including DDI prevalence and 95% confidence intervals, will be reported for each country. Prevalence will be pooled and compared across countries using random effects models and meta-regression, where feasible.

The EuroDDI study will develop a harmonised method to measure and compare DDI prevalence across health-related databases in Europe.

Adverse drug reaction (ADR) monitoring is crucial in ensuring patient and pharmaceutical safety. However, there is a lack of evidence regarding ADR reporting trend pattern in Ghana. This study, therefore, aimed to analyse and characterise trends in ADRs reported in Ghana over 16 years.

We retrospectively analysed individual case safety retorts (ICSRs) received by the Ghana National Pharmacovigilance Centre from 2005 to 2021. Jointpoint regression was used to estimate age-adjusted ADR rates, stratified by sex and patient characteristics, suspected medication groups, clinical indications, and the manifestation of ADRs. To evaluate trends over time, the percentage annualised estimator was used.

We identified a total of 6853 ICSRs from 2005 to 2021. The age-adjusted ICSR rates increased significantly from 2005 to 2019, with an annual increase of 18.6%; however, there was a downward trend from 2019 to 2021, although not statistically significant. Males accounted for the majority (64.3%) of ICSRs compared to females (35.7%). The suspected medication group most frequently associated with ADRs were antiprotozoals accounting for 35.6% of all ICSRs, while vascular disorders (21.0%) were the most commonly observed clinical indication in relation to ADRs. An increase in ICSR rates was noted for gastrointestinal disorders with an annual increase of 32.5% (95% CI, 20.6-45.6%; p < 0.001). Amodiaquine was the most commonly suspected medication (8.9%) associated with ADRs, while pruritus (7.2%) was the most frequently reported preferred term.

The study provides a detailed overview of ICSRs received by the Ghana National Pharmacovigilance Centre over the past 16 years and demonstrates an increasing trend of ADR-related medication use as well as clinical indications over time. The findings of this study call for multifaceted strategies aimed at reducing the risks associated with inappropriate drug use, and enhancing knowledge of medication safety, thus improving healthcare service delivery and patient safety.

The prevalence of harms in healthcare related to drug treatment is often quantified using terms developed for pharmacovigilance and pharmaceutical care. In this overview, we guide through the definitions and the settings for which they were developed, with the underlying intention to facilitate the interpretation of hitherto available research intended to contribute information regarding the magnitude of the problem in healthcare and to provide guidance for future research. To start, the regulatory/academic definitions of an adverse drug reaction (ADR) and a drug-related problem (DRP) are considerably broader than a literal interpretation would suggest. ADRs are defined for the pharmacovigilance setting, and for drug safety reasons the opposite of the benefit of the doubt rules; if it cannot be excluded that the medication has caused or contributed to an event, it will be a suspected ADR. DRPs represent the pharmaceutical care setting where every aspect is included that could potentially be problematic; a manifested problem is not required. When quantifying the prevalence of harms related to drug treatment in the healthcare setting, however, it may not be considered reasonable to count every circumstance that could possibly be an ADR or everything that could potentially be problematic. Therefore, definitions developed for the pharmacovigilance and the pharmaceutical care settings are not fully applicable to estimate the magnitude of drug treatment problems in healthcare. Proposed guidance for the future includes cautious interpretation of research results, as well as a conscious choice of definitions according to purpose and tempered reporting in research.

Multiple trigger tools have been developed to identify medication-related hospital (re)admissions (MRRs); however, the accuracy of these tools in real-world clinical practice is uncertain. The objective of this study was to compare the accuracy of four different trigger tools (OPERAM, STOPP/START criteria, ADR-tool, and QUADRAT) to identify MRRs compared with clinical adjudication.

We conducted a secondary analysis of patients readmitted within 30 days to seven departments of a teaching hospital. In the primary study, which involved a retrospective chart review of 1111 readmissions, MRRs and their potential preventability were clinically adjudicated by physicians and pharmacists. In the current study, four trigger tools were applied by a different physician and pharmacist panel. Patients of all ages were included. Trigger tools included both explicit items specifying the event and the associated medication and implicit items requiring clinical knowledge. The accuracy of each trigger tool was assessed by calculating the proportion of clinically adjudicated MRRs each tool identified overall as well as according to explicit and implicit triggers separately. The accuracy of each tool to identify potentially preventable MRRs was also calculated.

Of 1111 readmissions, 181 were adjudicated as medication-related (mean age 69 years, 56% male); 72 (40%) MRRs were potentially preventable. The original OPERAM tool identified 166 (92%) MRRs (62% through explicit triggers). The STOPP/START criteria identified 23 (13%, 7% through explicit triggers), the ADR tool identified 51 (28%, all explicit triggers), and the QUADRAT tool identified 76 (42%; all explicit triggers) MRRs. Of the 72 potentially preventable MRRs, OPERAM identified 59 (82%), STOPP/START identified 18 (25%), ADR identified 20 (28%), and QUADRAT identified 21 (29%).

The original OPERAM tool identified the highest proportion of (preventable) MRRs. However, this tool includes many implicit triggers requiring expert clinical knowledge. Future studies should assess the practicality of implementing this tool in daily practice.

Pharmacogenetics (PGx) aims to optimize drug treatment outcomes by using a patient's genetic profile for individualized drug and dose selection. Currently, reactive and pretherapeutic single-gene PGx tests are increasingly applied in clinical practice in several countries and institutions. With over 95% of the population carrying at least one actionable PGx variant, and with drugs impacted by these genetic variants being in common use, pretherapeutic or preemptive PGx panel testing appears to be an attractive option for better-informed drug prescribing. Here, we discuss the current state of PGx panel testing and explore the potential for clinical implementation. We conclude that available evidence supports the implementation of pretherapeutic PGx panel testing for drugs covered in the PGx guidelines, yet identification of specific patient populations that benefit most and cost-effectiveness data are necessary to support large-scale implementation.

Polypharmacy-related drug-drug interactions (DDIs) are a significant and growing healthcare concern. An increasing number of therapeutic drugs on the market underscores the necessity to accurately assess new drug combinations during preclinical evaluation for DDIs. In vitro primary human hepatocytes (PHH) models are only applicable for short-term induction studies because of their rapid loss of metabolic function. Though coculturing nonhuman stromal cells with PHH has been shown to stabilize metabolic activity long-term, there are concerns about human specificity for accurate clinical assessment. In this study, we demonstrated a PHH-only liver microphysiological system in the Liver Tissue Chip is capable of maintaining long-term functional and metabolic activity of PHH from 3 individual donors and thus a suitable platform for long-term DDI induction studies. The responses to rifampicin induction of 3 PHH donors were assessed using cytochrome P450 activity and mRNA changes. Additionally, victim pharmacokinetic studies were conducted with midazolam (high clearance) and alprazolam (low clearance) following perpetrator drug treatment, rifampicin-mediated induction, which resulted in a 2-fold and a 2.6-fold increase in midazolam and alprazolam intrinsic clearance values, respectively, compared with the untreated liver microphysiological system. We also investigated the induction effects of different dosing regimens of the perpetrator drug (rifampicin) on cytochrome P450 activity levels, showing minimal variation in the intrinsic clearance of the victim drug (midazolam). This study illustrates the utility of the Liver Tissue Chip for in vitro liver-specific DDI induction studies, providing a translational experimental system to predict clinical clearance values of both perpetrator and victim drugs. SIGNIFICANCE STATEMENT: This study demonstrated the utility of the Liver Tissue Chip with a primary human hepatocyte-only liver microphysiological system for drug-drug interaction induction studies. This unique in vitro system with continuous recirculation maintains long-term functionality and metabolic activity for up to 4 weeks, enabling the study of perpetrator and victim drug pharmacokinetics, quantification of drug-induced cytochrome P450 mRNA and activity levels, investigation of patient variability, and ultimately clinical predictions.

We aimed to assess the characteristics of adverse drug reactions (ADRs) collected in a university hospital.

A retrospective analysis of ADRs spontaneously reported in the Hospital Pharmacovigilance Program database (RutiRAM) over a 13-year period was conducted. The analysis included a description of ADRs [System Organ Class (SOC)] and their seriousness, the drugs involved [level 1 of the Anatomical Therapeutic Chemical (ATC) Classification System], drug-drug interactions, medication errors, drugs 'under additional monitoring', positive rechallenge, and the 'pharmacovigilance interest' of ADRs. An ADR was considered of 'pharmacovigilance interest' when it was serious, and/or produced sequelae, and/or affected the paediatric population, and/or when the suspected drug was 'under additional monitoring'. Additionally, an exploratory analysis for bivariate associations through an automated method was performed.

A total of 2,148 spontaneous ADRs were registered in the RutiRAM database, with 92.5% recorded by medical doctors. The mean age of cases was 59.2 years (SD 20.9), range 1 day-99 years; 5.7% were paediatric, 46.2% adults, and 48.1% elderly. The drugs most often involved were anti-infectives (ATC group J), mainly amoxicillin-clavulanic acid. 'Blood system disorders' were the most frequent SOC ADRs, and skin rashes were the most frequent ADRs. The 63.2% of ADRs were considered of 'pharmacovigilance interest'. Almost half of ADRs were hospital-acquired, and these were related to medication error; serious ADRs were related to drug-drug interactions and elderly patients, and involved drugs 'under additional monitoring' were related to younger ones.

This is the first study to overview of ADRs reported in an HPVP over more than a decade. Almost two-thirds of the ADRs collected in the RutiRAM database are of sufficient quality to be classified as 'pharmacovigilance interest', and thus can contribute to signal detection and the issuing of drug alerts by pharmacovigilance systems. Analysing ADRs in hospitals contributes to patient safety by implementing relevant actions to prevent medication errors or ADRs, some of which can be applied to other centres.

Patient engagement in pharmacovigilance (PEP) has been shown to improve information on adverse drug reactions (ADRs), which may not be found in reports from healthcare professionals. This review shows that there is paucity of information on PEP in lower-middle-income countries (LMICs), particularly Africa. It provides insights into PEP in high-income countries (HICs) compared with Africa to help identify the disparities and system challenges in Africa.

We discussed the impact of PEP in HICs in comparison with Africa and incorporated two case studies: PEP in Ghana and medication error reporting in Africa using a scoping review. Recommendations were made to improve medication safety in Africa based on the identified disparities and system challenges.

PEP is at an early stage in LMICs, particularly in Africa, with limited information available regarding patients' contributions to the safety of medicines. There should be further research into patients' roles in pharmacovigilance accompanied by advocacy efforts with policymakers, the development of sustainable funding strategies, benchmarking against experienced pharmacovigilance centers, and the use of technology to improve patient reporting.

Objective: Upper gastrointestinal bleeding (UGIB) has been identified as a potential adverse drug reaction associated with the use of low-dose aspirin (LDA). This study aimed to investigate the relationship between variants in the TBXA2R gene, which is involved in platelet aggregation, and the risk of UGIB in patients with cardiovascular diseases treated with LDA. Methods: A case-control study was conducted at a Brazilian hospital complex. Three groups were defined: (1) case group (n = 50): patients with cardiovascular disease who used LDA and were diagnosed with UGIB of non-variceal etiology, (2) LDA control group (n = 50): patients with cardiovascular disease who used LDA without developing UGIB, and (3) healthy control group (n = 189). Data were collected through face-to-face interviews, and blood samples were collected for the analysis of Helicobacter pylori infection and genotyping of 3 genetic variants [rs2238631 (C > T), rs4807491 (A > G), and rs1131882 (A > G)]. Results: The case group had a significantly higher frequency of carriers of the rs4807491.G allele compared to the control group of LDA users (P-value = .004). No significant difference was observed in the proportion of carriers of the rs2238631.T and 1131882.G variants between the studied groups. Carriers of rs2238631.T (OR: 4.515, 95% CI: 1.37-14.89) and rs4807491.G allele (OR: 3.232, 95% CI: 1.12-9.37) exhibited a higher risk of UGIB. Conclusion: These findings suggest that the presence of the rs2238631 and rs4807491 variant alleles is associates with a 3- to 4-fold increased risk of UGIB in patients with cardiovascular diseases treated with LDA. Future studies with larger sample sizes should confirm these results and to better identify individuals who may benefit from chronic LDA use.

Cutaneous adverse drug reactions (CADRs) remain a challenge for non-dermatologists. Medical-related applications to assist in learning about and managing patients with CADRs are scarce. We aimed to evaluate the efficacy of a web application for non-dermatologists in managing CADRs by comparing the knowledge scores of users and non-users.

A multicenter randomized controlled trial was conducted between January 2023 and May 2023. Clinician participants were randomized (1:1) into the application and control groups using a simple randomization method. Knowledge scores between the groups were compared to evaluate the efficacy of the web application, and participants' perspectives on the application were also collected.

A total of 44 clinician participants were included in the final analysis. The median age was 33.0 years (95% confidence interval (CI) 27.5-35.0) and predominantly female (56.8%). The score in the application group (median, 27.0; 95% CI, 25.0-28.0) was significantly higher than that in the control group (median, 14.0; 95% CI 13.0-17.0) (p < 0.001). There were no differences in scores between the sex groups (p = 0.695), between general practitioners (GPs) and non-GPs (p = 0.93), or among groups with different frequencies of evaluation of patients with CADRs (p = 0.266). In addition, the participants in the application group rated a high level of overall satisfaction.

The web application for CADRs is an effective and convenient tool for assisting non-dermatologist physicians in learning and providing initial management with a high level of satisfaction. However, prospective long-term randomized controlled studies are required to confirm the efficacy of this tool.

To describe the use of non-steroidal anti-inflammatory drugs (NSAID), opioids, and physiotherapy (PT) among persons with newly diagnosed knee or hip osteoarthritis (OA) with and without NSAID contraindications or precautions.

We used population-based register data to identify adults aged ≥35 as of January 1, 2014, residing in Skåne region (Sweden) between 2004 and 2013, without a previous knee or hip OA diagnosis. Among this cohort, we identified people with incident knee or hip OA diagnosis between 2014 and 2018 and the presence of contraindications to or precautions for oral NSAIDs at the time of OA diagnosis. We estimated the risk of 1) regular oral NSAID use, 2) regular opioid use, and 3) PT during the first year after diagnosis among those with vs. without contraindications or precautions using confounder-adjusted logistic regression with standardization.

We identified 35,173 persons with newly diagnosed OA, of whom 3257 and 8351 had ≥1 contraindication to oral NSAIDs and ≥1 precaution, respectively. Overall, 27% of individuals used oral NSAIDs (with or without opioids or PT), 10% used opioids, and 57% attended PT. Among patients with contraindications, 21% used oral NSAIDs compared to 31% without (absolute adjusted difference -0.06 (95% CIs: -0.08, -0.05)), 53% vs 59% used PT (adjusted difference -0.03 (-0.05, -0.01)), while 14% vs. 8% had prescribed dispensed opioids (adjusted difference 0.02 (0.01, 0.03)). Similar results were observed for those with precautions.

We highlight the need for safer treatment options. People with OA and contraindications/precautions to NSAIDs have a higher risk of opioid use, slightly lower risk of PT use, and continue to be prescribed NSAIDs.

The risk-benefit balance of statin use in healthy older people is uncertain. We describe the baseline characteristics of the STAREE (Statins in Reducing Events in the Elderly) trial, which is a randomized, double-blind, placebo-controlled trial among community-dwelling older people; the trial evaluated the effect of atorvastatin 40 mg for the prevention of major cardiovascular events (cardiovascular death, nonfatal myocardial infarction or stroke), and on disability-free survival (survival free of both dementia and persistent physical disability).

STAREE enrolled people aged ≥70 years from 1583 general practices across Australia with no history of clinical cardiovascular disease, diabetes, or dementia. Baseline data collected included demographic, clinical, cognitive (Modified Mini-Mental State Examination), psychological (Center for Epidemiologic Studies Short Depression Scale), lifestyle, medical, physical, blood and urine measures, and quality of life. Demographic and clinical characteristics of study participants were then compared with publicly available landmark statin trials. A total of 9971 participants were recruited (mean±SD age 74.7±4.5 years, 4023 (40%) ≥75 years, 52% women) between July 2015 and March 2023. The mean low-density lipoprotein cholesterol was 3.27 mmol/L (SD=0.72; 126 mg/dL). Hypertension was reported by 43% of participants and the mean blood pressure was 136/80 mm Hg. Compared with previous landmark statin trials that included primary prevention cohorts, STAREE is unique in including such a large number of older (≥75 years) independent-living people.

STAREE is the largest primary prevention trial of statins powered to address the important clinical outcomes of major cardiovascular events, disability-free survival, and cognition in older people.

https://www.clinicaltrials.gov; Unique identifier: NCT02099123.

Hypothetical strategy is a common strategy for handling intercurrent events (IEs). No current guideline or study considers treatment-IE interaction to target the estimand in any one IE-handling strategy. Based on the hypothetical strategy, we aimed to (1) assess the performance of three estimators with different considerations for the treatment-IE interaction in a simulation and (2) compare the estimation of these estimators in a real trial. Simulation data were generalized based on realistic clinical trials of Alzheimer's disease. The estimand of interest was the effect of treatment with no IE occurring under the hypothetical strategy. Three estimators, namely, G-estimation with and without interaction and IE-ignored estimation, were compared in scenarios where the treatment-IE interaction effect was set as -50% to 50% of the main effect. Bias was the key performance measure. The real case was derived from a randomized trial of methadone maintenance treatment. Only G-estimation with interaction exhibited unbiased estimations regardless of the existence, direction or magnitude of the treatment-IE interaction in those scenarios. Neglecting the interaction and ignoring the IE would introduce a bias as large as 0.093 and 0.241 (true value, -1.561) if the interaction effect existed. In the real case, compared with G-estimation with interaction, G-estimation without interaction and IE-ignored estimation increased the estimand of interest by 33.55% and 34.36%, respectively. This study highlights the importance of considering treatment-IE interaction in the estimand framework. In practice, it would be better to include the interaction in the estimator by default.

Statins are the primary therapeutic approach for treating hypercholesterolemia in hyperlipidemic high cardiovascular-risk patients, as stated by the recent European and American guidelines. However, in some patients, statin treatment is not sufficient to achieve the recommended plasma LDL-C levels, and the addition of a second hypolipidemic drug becomes mandatory. Concomitant administration of multiple medications may increase the risk of adverse events, potentially leading to statin-associated muscle or liver symptoms and non-adherence or discontinuation of statin therapy, such as in women. The addition of a second hypolipidemic drug (such as ezetimibe, anti-PCSK9 monoclonal antibodies, bempedoic acid, and inclisiran) may lead to drug-drug interactions (DDIs). The evaluation of the different pharmacokinetic profiles may improve and personalize the treatment.

We aimed to give an update on the potential DDIs between statins and other hypolipidemic drugs currently used to treat high-risk hyperlipidemic patients.

It is fundamental to understand the risk associated with DDIs to manage better the addition of a concomitant hyperlipidemic drug to a statin-treated patient. Many health agencies have published specific guidelines for assessing DDIs, but these mainly apply to in vitro studies. New predictive approaches are being proposed and may help evaluate and manage DDIs.

The recognition of adverse drug reactions (ADRs) is an important part of daily clinical work. However, medical education in this field is mostly drug-based and does not address adequately the complexity of this field regarding individual risk factors and polypharmacy. This study investigates the potential of the web-based serious game SeeMe (side-effect exposure-medical education) in pharmacological education of medical students to improve the recognition of relevant ADRs.

One hundred fifty-seven medical students were recruited to evaluate the serious game SeeMe. SeeMe was developed to improve knowledge and recognition of ADRs in clinical practice. Players take on the role of a physician trying to understand fictional patients with ADRs. Before and after an 8-week playing period, an evaluation was carried out through a pre- and post-questionnaire and a pre- and post- knowledge test.

The students achieved significantly better results in the knowledge test, as almost twice as many exam-relevant questions were answered correctly (p < 0.001). The serious game had a positive effect on the students' perception of the importance of ADRs.

This study demonstrates the potential of web- and case-based fictional serious games in medical education. The improved recognition of side effects represents a crucial step for education and training in clinical pharmacology. Future versions of the serious game may take this further and focus on training in the treatment of ADRs and their relevance in various healthcare professions.

Adverse drug events, encompassing both adverse drug reactions and medication errors, pose a significant threat to health, leading to illness and, in severe cases, death. Timely and voluntary reporting of adverse drug events by healthcare professionals plays a crucial role in mitigating the morbidity and mortality linked to unexpected reactions and improper medication usage.

To assess the effectiveness of different interventions aimed at healthcare professionals to improve the reporting of adverse drug events.

We searched CENTRAL, Embase, MEDLINE and several other electronic databases and trials registers, including ClinicalTrials.gov and WHO ICTRP, from inception until 14 October 2022. We also screened reference lists in the included studies and relevant systematic reviews.

We included randomised trials, non-randomised controlled studies, controlled before-after studies, interrupted time series studies (ITS) and repeated measures studies, assessing the effect of any intervention aimed at healthcare professionals and designed to increase adverse drug event reporting. Eligible comparators were healthcare professionals' usual reporting practice or a different intervention or interventions designed to improve adverse drug event reporting rate. We excluded studies of interventions targeted at adverse event reporting following immunisation. Our primary outcome measures were the total number of adverse drug event reports (including both adverse drug reaction reports and medication error reports) and the number of false adverse drug event reports (encompassing both adverse drug reaction reports and medication error reports) submitted by healthcare professionals. Secondary outcomes were the number of serious, high-causality, unexpected or previously unknown, and new drug-related adverse drug event reports submitted by healthcare professionals. We used GRADE to assess the certainty of evidence.

We followed standard methods recommended by Cochrane and the Cochrane Effective Practice and Organisation of Care (EPOC) Group. We extracted and reanalysed ITS study data and imputed treatment effect estimates (including standard errors or confidence intervals) for the randomised studies.

We included 15 studies (eight RCTs, six ITS, and one non-randomised cross-over study) with approximately 62,389 participants. All studies were conducted in high-income countries in large tertiary care hospitals. There was a high risk of performance bias in the controlled studies due to the nature of the interventions. None of the ITS studies had a control arm, so we could not be sure of the detected effects being independent of other changes. None of the studies reported on the number of false adverse drug event reports submitted. There is low-certainty evidence suggesting that an education session, together with reminder card and adverse drug reaction (ADR) report form, may substantially improve the rate of ADR reporting by healthcare professionals when compared to usual practice (i.e. spontaneous reporting with or without some training provided by regional pharmacosurveillance units). These educational interventions increased the number of ADR reports in total (RR 3.00, 95% CI 1.53 to 5.90; 5 studies, 21,655 participants), serious ADR reports (RR 3.30, 95% CI 1.51 to 7.21; 5 studies, 21,655 participants), high-causality ADR reports (RR 2.48, 95% CI 1.11 to 5.57; 5 studies, 21,655 participants), unexpected ADR reports (RR 4.72, 95% CI 1.75 to 12.76; 4 studies, 15,085 participants) and new drug-related ADR reports (RR 8.68, 95% CI 3.40 to 22.13; 2 studies, 7884 participants). Additionally, low-certainty evidence suggests that, compared to usual practice (i.e. spontaneous reporting), making it easier to report ADRs by using a standardised discharge form with added ADR items may slightly improve the total number of ADR reports submitted (RR 2.06, 95% CI 1.11 to 3.83; 1 study, 5967 participants). The discharge form tested was based on the 'Diagnosis Related Groups' (DRG) system for recording patient diagnoses, and the medical and surgical procedures received during their hospital stay. Due to very low-certainty evidence, we do not know if the following interventions have any effect on the total number of adverse drug event reports (including both ADR and ME reports) submitted by healthcare professionals: - sending informational letters or emails to GPs and nurses; - multifaceted interventions, including financial and non-financial incentives, fines, education and reminder cards; - implementing government regulations together with financial incentives; - including ADR report forms in quarterly bulletins and prescription pads; - providing a hyperlink to the reporting form in hospitals' electronic patient records; - improving the reporting method by re-engineering a web-based electronic error reporting system; - the presence of a clinical pharmacist in a hospital setting actively identifying adverse drug events and advocating for the identification and reporting of adverse drug events.

Compared to usual practice (i.e. spontaneous reporting with or without some training from regional pharmacosurveillance units), low-certainty evidence suggests that the number of ADR reports submitted may substantially increase following an education session, paired with reminder card and ADR report form, and may slightly increase with the use of a standardised discharge form method that makes it easier for healthcare professionals to report ADRs. The evidence for other interventions identified in this review, such as informational letters or emails and financial incentives, is uncertain. Future studies need to assess the benefits (increase in the number of adverse drug event reports) and harms (increase in the number of false adverse drug event reports) of any intervention designed to improve healthcare professionals' reporting of adverse drug events. Interventions to increase the number of submitted adverse drug event reports that are suitable for use in low- and middle-income countries should be developed and rigorously evaluated.

Patients with Alzheimer's disease (AD) and other dementias are more frequently exposed to polymedication, mainly due to the presence of comorbidities, are particularly vulnerable to drug-related problems, and present greater risk of adverse effects due to drug-drug interactions (DDIs).

To assess the prevalence of clinically relevant interactions in dementia patients using a routine database, we describe the most frequent interactions and risk factors associated with them to facilitate specific interventions and programs to prevent and minimize them.

An observational, descriptive, and cross-sectional study that included patients with AD and other types of dementia (n = 100, 64% female) was conducted to identify potential DDI in their treatment using the Lexi-Interact/Lexicomp® database.

A total of 769 drugs were prescribed, involving 190 different active ingredients; 83% of the treatments included five or more drugs. DDI occurred in 87% of the patients, of which 63.2% were female. A total of 689 DDIs were found, grouped in 448 drug pairs, with a mean of 6.9 ± 7.1 (range, 0-31) DDIs per patient, and 680 DDIs were considered clinically relevant. It was observed that 89.8% of the DDIs had a moderate level of severity, 23.5% had a good level of relevance, and pharmacodynamic-based DDIs accounted for 89.5%. The drugs most frequently involved in DDIs were quetiapine (24.5%) and acetylsalicylic acid (10%). A total of 97 DDIs were detected between the acetylcholinesterase inhibitors (AChEIs), and the remaining drugs were administered concomitantly. One of the most frequent DDIs was between AChEIs and beta-blocking agents (n = 29, 4.3%). The most important factors that showed the strongest association with the presence of drug interactions were the use of AChEIs (p = 0.01) and the total number of drugs (p = 0.014) taken by the patient.

Patients with dementia present increased risk of DDIs. Among the most common drugs are psychotropic drugs, which are involved in pharmacodynamic interactions caused by the concomitant use of CNS-targeted drugs. The results highlight the difficulty to evaluate DDIs in clinical practice due to polymedication and variety of comorbidities. Therefore, it is important to review their treatment and consider metabolism inhibition or induction, and potentially P450 substrate overlapping.

Heart failure (HF) is not included in atrial fibrillation (AF) bleeding risk prediction scores, reflecting uncertainty regarding its importance as a risk factor for major haemorrhage. We aimed to report the relative risk of first major haemorrhage in people with HF and AF compared with people with AF without HF ('AF only').

English primary care cohort study of 2 178 162 people aged ≥45 years in the Clinical Practice Research Datalink from January 2000 to December 2018, linked to secondary care and mortality databases. We used traditional survival analysis and competing risks methods, accounting for all-cause mortality and anticoagulation.

Over 7.56 years median follow-up, 60 270 people were diagnosed with HF and AF of whom 4996 (8.3%) had a major haemorrhage and 36 170 died (60.0%), compared with 8256 (6.4%) and 34 375 (27.2%), respectively, among 126 251 people with AF only. Less than half those with AF were prescribed an anticoagulant (45.6% from 2014 onwards), although 75.7% were prescribed an antiplatelet or anticoagulant. In a fully adjusted Cox model, the HR for major haemorrhage was higher among people with HF and AF (2.52, 95% CI 2.44 to 2.61) than AF only (1.87, 95% CI 1.82 to 1.92), even in a subgroup analysis of people prescribed anticoagulation. However, in a Fine and Gray competing risk model, the HR of major haemorrhage was similar for people with AF only (1.82, 95% CI 1.77 to 1.87) or HF and AF (1.71, 95% CI 1.66 to 1.78).

People with HF and AF are at increased risk of major haemorrhage compared with those with AF only and current prediction scores may underestimate the risk of haemorrhage in HF and AF. However, people with HF and AF are more likely to die than have a major haemorrhage and therefore an individual's expected prognosis should be carefully considered when predicting future bleeding risk.

Objective: This study explores the frequency of human leukocyte antigen (HLA) genes, particularly HLA-B alleles, within the Kuwaiti population. We aim to identify alleles with known associations to adverse drug reactions (ADRs) based on existing literature. We focus on the HLA-B gene due to its well-documented associations with severe cutaneous adverse reactions and the extensive pharmacogenetic research supporting its clinical relevance.

We utilized the HLA-HD tool to extract, annotate, and analyse HLA-B alleles from the exome data of 561 Kuwaiti individuals, sequenced on the Illumina HiSeq platform. HLA typing was conducted using the HLA-HD tool with a reference panel from the IPD-IMGT/HLA database. The major HLA-B pharmacogenetic markers were obtained from the HLA Adverse Drug Reaction Database, focusing on alleles with significant ADR associations in published literature.

The distribution of HLA-B alleles in the Kuwaiti population revealed that the most frequent alleles were HLA-B*50:01 (10.52%), HLA-B*51:01 (9.89%), HLA-B*08:01 (6.06%), HLA-B*52:01 (4.55%), HLA-B*18:01 (3.92%), and HLA-B*41:01 (3.65%). Notably, alleles HLA-B*13:01, HLA-B*13:02, HLA-B*15:02, HLA-B*15:13, HLA-B*35:02, HLA-B*35:05, HLA-B*38:01, HLA-B*40:02, HLA-B*44:03, HLA-B*51:01, HLA-B*57:01 and HLA-B*58:01 were identified with known associations to various ADRs. For example, HLA-B*51:01 was associated with clindamycin, phenobarbital, and phenytoin, and was found in 18% of individuals.

Our study enriches the regional genetic landscape by delineating HLA-B allele variations within Kuwait and across the Arabian Peninsula. This genetic insight, along with the identification of markers previously linked to drug hypersensitivity, provides a foundation for future pharmacogenetic research and potential personalized medicine strategies in the region.

Hemophilia type A and B is associated with spontaneous bleeding in muscle tissues and joints. Acute hemarthrosis, representing 70-80% of all bleedings in severe hemophilia patients, is extremely painful. When surgical procedures are needed in hemophiliac patients, perioperative management should be planned with a multidisciplinary team. Our narrative review, through a rigorous analysis of the current literature, focuses on pain management in hemophiliac patients.

The report synthesizes a literature review on hemophilia, adapting PRISMA guidelines. It identifies a research question on surgical procedures and perioperative pain management. Various sources, including electronic databases, are utilized. Study inclusion criteria are defined based on the research question. Forty studies are included. A detailed study selection is illustrated.

Guidelines for managing acute postoperative pain in the general population advocate for a multimodal analgesic administration to enhance synergistic benefits, reduce opioid requirements, and minimize side effects. Recent recommendations from the World Federation of Hemophilia (WFH) for postoperative pain management in hemophilia patients suggest tailoring treatment based on pain levels, in coordination with anesthesiologists.

Pain management in hemophiliac patients undergoing orthopedic interventions requires a multidisciplinary approach, with further research needed to define a reliable global standard of treatment.

Adverse events following immunization (AEFIs), especially if serious, may impact vaccine recipients' quality of life and financial well-being and fuel vaccine hesitancy. Nigeria rolled out COVID-19 vaccination in 2021 with little known about the impact of AEFIs on an individual's quality of life. No study in Africa has explored the health and financial impact of AEFIs. We explored patient-reported outcomes (PROs) of adverse events after COVID-19 vaccination and documented the lived experiences of those with serious AEFIs to understand the effect on their health, financial well-being, and attitude to future vaccinations.

We conducted a convergent mixed-methods study using the RAND 36-item health survey and in-depth interviews to collect PROs on vaccine recipients in Nigeria. Eight health scale scores and two summary composite scores were used to measure the health-related quality of life outcomes from the survey and inductive analysis was used to identify themes from the interview scripts. The results of both studies were integrated in a joint display to highlight areas of concordance.

In total, 785 survey responses were analyzed (53% females, 68% aged 18-30 years). Responders reporting an AEFI were 58%, of whom 62% received the first dose only. Younger age and first vaccine dose (p < .001 respectively) were associated with experiencing an AEFI. Not reporting an AEFI was associated with better quality of life, measured as higher scores on all eight SF-36 Health scales and the physical and mental component summary scores. All six interviewees with serious AEFIs experienced physical, mental, and financial distress. Some expressed a strong negative attitude toward future COVID-19 vaccinations but not toward vaccines for routine immunization.

AEFIs negatively impact the health and financial well-being of affected individuals and their attitude to future vaccinations, especially if serious. Understanding the impact of AEFIs on people is important and should inform future policies and interventions. The results of our study can inform policy and planning for future mass vaccination campaigns in LMICs.