Medications In Clinical Practice Research Articles

Isovaleryl Sucrose Esters from Atractylodes japonica and Their Cytotoxic Activity.

Cancer represents one of the most significant health challenges currently facing humanity, and plant-derived antitumour drugs represent a prominent class of anticancer medications in clinical practice. Isovaleryl sucrose esters, which are natural constituents, have been identified as having potential antitumour effects. However, the mechanism of action remains unclear. In this study, 12 isovaleryl sucrose ester components, including five new (1-5) and seven known compounds (6-12), were isolated from the roots of Atractylodes japonica. The structures of the compounds were elucidated using 1D and 2D-NMR spectroscopy, complemented by HR-ESI-MS mass spectrometry. The cytotoxic activities of all the compounds against human colon cancer cells (HCT-116) and human lung adenocarcinoma cells (A549) were also evaluated using the CCK8 assay. The results demonstrated that compounds 2, 4, and 6 were moderately inhibitory to HCT-116 cells, with IC50 values of 7.49 ± 0.48, 9.03 ± 0.21, and 13.49 ± 1.45 μM, respectively. Compounds 1 and 6 were moderately inhibitory to A549, with IC50 values of 8.36 ± 0.77 and 7.10 ± 0.52 μM, respectively. Molecular docking revealed that compounds 1-9 exhibited a stronger affinity for FGFR3 and BRAF, with binding energies below -7 kcal/mol. Compound 2 exhibited the lowest binding energy of -10.63 kcal/mol to FGFR3. We screened the compounds with lower binding energies, and the protein-ligand complexes already obtained after molecular docking were subjected to exhaustive molecular dynamics simulation experiments, which simulated the dynamic behaviour of the molecules in close proximity to the actual biological environment, thus providing a deeper understanding of their functions and interaction mechanisms. The present study provides a reference for the development and use of iso-valeryl sucrose esters in the antitumour field.

An algorithm for pharmacological treatment of mania during hospitalisation.

Current evidence for pharmacological treatment of mania during hospitalisation is insufficient as there are no larger well-designed randomised trials of comparative medical treatments of mania during inpatient stays. Moreover, there is considerable variation in pharmacological medication in clinical practice during hospitalisation for mania. Based on a hospital data overview, a systematic search of the literature and a three-day consensus meeting, this narrative review proposed an algorithm for optimised pharmacological treatment of mania during hospitalisation and its subsequent scientific evaluation.

Research Progress on Anti-Inflammatory Effects and Related Mechanisms of Astragalin.

Chronic inflammation is a significant contributor to the development of cancer, cardiovascular disease, diabetes, obesity, autoimmune disease, inflammatory bowel disease, and other illnesses. In the academic field, there is a constant demand for effective methods to alleviate inflammation. Astragalin (AST), a type of flavonoid glycoside that is the primary component in several widely used traditional Chinese anti-inflammatory medications in clinical practice, has garnered attention from numerous experts and scholars. This article focuses on the anti-inflammatory effects of AST and conducts research on relevant literature from 2003 to 2023. The findings indicate that AST demonstrates promising anti-inflammatory potential in various models of inflammatory diseases. Specifically, AST is believed to possess inhibitory effects on inflammation-related factors and protein levels in various in vitro cell models, such as macrophages, microglia, and epithelial cells. In vivo studies have shown that AST effectively alleviates neuroinflammation and brain damage while also exhibiting potential for treating moderate diseases such as depression and stroke; it also demonstrates significant anti-inflammatory effects on both large and small intestinal epithelial cells. Animal experiments have further demonstrated that AST exerts therapeutic effects on colitis mice. Molecular biology studies have revealed that AST regulates complex signaling networks, including NF-κB, MAPK, JAK/STAT pathways, etc. In conclusion, this review will provide insights and references for the development of AST as an anti-inflammatory agent as well as for related drug development.

The Medical Student Guide to Pharmacy: Piloting an Interactive Textbook on Basic Pharmacology Principles and Clinical Correlations.

Despite the wide use of medications in clinical practice, graduating medical students often feel unprepared for the task of prescribing upon starting residency. With recent educational initiatives aiming to transform learning modalities, we sought to pilot an interactive textbook on basic pharmacology principles at our institution as a supplement to first-year lectures and assess its subjective impact on students' knowledge of content as well as confidence to apply material in the real world through pre- and post-intervention surveys. First-year medical students were invited to complete non-validated, voluntary, anonymous, emailed, online surveys consisting of Likert scale and free-text response questions. Our investigation served as a pilot test for future iterations of this research. Response rates for the pre- and post-intervention surveys were 73/145 (50%) and 38/145 (26%), respectively, with the post-intervention survey further reduced to 13 individuals who indicated use of the interactive textbook. Questions regarding interactive textbook chapters that overlapped with course content were excluded from data analysis due to an inability to separate learning gains from lectures versus the interactive textbook. Post-intervention survey responses all showed significant changes in mean Likert scale scores on student-perceived knowledge and confidence to apply material with P < .001. Free-text response questions revealed limited exposure to the field of pharmacy and interactions with pharmacists prior to medical school. Our pilot study on the initial use of an interactive textbook titled The Medical Student Guide to Pharmacy presented us with valuable insight into providing first-year medical students with a clinically oriented supplemental resource within coursework on basic pharmacology. Challenges for the future include better integrating the interactive textbook into class lectures to facilitate increased use by students as well as developing more targeted, validated assessments of the impact it has on students' learning.

A cross sectional study to analyse the ADR reported in a hospital during the past three years

Introduction: Cross sectional study is a type of observational study that analyzes data from apopulation, or a representative subset, at a specific point in time-that is, cross sectional data. The causality appraisal is assessment of the probability that the detected adverse event is produced by a specific medication. The most commonly used causality assessment scales are Naranjo Probability Scale and the World Health Organization-Uppsala Monitoring Centre (WHO-UMC) causality scales. The study is to analyze the adverse drug reaction reported in a hospital for the past three years. Aim: A cross sectional study to analyze the ADR reported in a hospital during the past three years. Methodology: A cross sectional observational study was conducted at Nirmala medical centre, Muvattupuzha. ADR reported in the past three years in this hospital were analyzed. Drug leading to ADR, department .gender, observed reaction, severity, Naranjo probability scale and WHO UMC causality assessment were done. Classification of drugs according to their drug class, classification of ADR according to the system, based on severity, sex, Naranjo score, WHO UMC criteria were done. The datas were analysed and represented into graphs. Result: A total of 342 ADR reports were analyzed in this study. The key findings of this study include: Skin-related ADRs were the most frequently reported, affecting 27.83% of cases. The majority of reported ADRs were of moderate severity (56.7%).Naranjo probability scale and WHO-UMC causality assessment indicated that most cases were in the probable category, with 63% and 76%, respectively. The general medicine department had the highest number of reported ADRs. Males accounted for the majority of reported ADRs (57.18%).Cardiovascular agents and antibiotics were the drug classes most commonly associated with reported ADRs, at 25.6% and 22.28%, respectively. Among cardiovascular agents, diuretics were found to be the primary culprits, causing 38.66% of reported ADRs. Conclusion: This study highlights the importance of monitoring, assessing, and documenting ADRs in healthcare facilities, as it provides valuable insights into the prevalence, severity, and causality of adverse drug reactions. This information can contribute to improving patient safety and the rational use of medications in clinical practice.

Radiation-induced intestinal fibrosis: pathological assessment and pharmacological prevention

Although radiotherapy can improve the local control rate of tumors and prolong the survival period of patients, it can also lead to long-term adverse effects such as radiation-induced intestinal fibrosis. Radiation-induced intestinal fibrosis has a high incidence and poses significant challenges to treatment, severely impacting the quality of life of patients. Combining findings from domestic and international research, along with experiences of our center, this article mainly discusses the pathological changes of radiation-induced intestinal fibrosis, as well as the current status and challenges of pathological assessment and pharmacological prevention of this condition. At present, there is no definitive method to reverse the fibrotic pathological changes. Thus, the prevention of fibrosis is a crucial issue to be resolved. In the meantime, there is a lack of ideal assessment methods and effective preventive medications in clinical practice. It is necessary to enhance both basic and clinical research, thoroughly investigate the pathogenesis of the disease, and identify effective intervention targets to promote the diagnosis and treatment of radiation-induced intestinal fibrosis.

Real world outcomes of trilaciclib in ES-SCLC.

e20637 Background: Carboplatin, etoposide, and atezolizumab (PEA) is the most widely used combination for first-line treatment of extensive-stage small cell lung cancer (ES-SCLC). Chemotherapy-induced myelosuppression is a common sequalae that is traditionally managed with lineage-specific supportive care modalities. Studies that evaluated trilaciclib versus placebo in combination with chemotherapy demonstrated statistically significant improvements in the duration of severe neutropenia (SN), defined as ANC &lt; 500 cells/µL, in cycle 1 and incidence of SN as a result of its transient myeloprotective effects. There remains considerable controversy in the adoption of trilaciclib as a supportive medication in clinical practice. The objective of this quality assessment study was to assess utility of trilaciclib in real-world ES-SCLC patients. Methods: This was a single center study with quasi-experimental design comparing patients with confirmed ES-SCLC who received trilaciclib + PEA (PEAT) from April 2021 to July 2022 versus those who received PEA without trilaciclib (PEA) from February 2020 to February 2021. Patients with limited-stage SCLC, prior treatment with immunotherapies, carboplatin dose AUC &lt; 3.5 with cycle 1, and active clinical trial enrollment were excluded. The primary endpoint evaluated was incidence of SN after cycle 1 and during treatment period. Additional measures related to myelopreservation and patient outcomes were assessed as secondary endpoints. Demographic data was analyzed using descriptive statistics. Dichotomous and continuous variables were compared by Mann-Whitney U or one-sided Fisher’s exact test. Progression-free survival (PFS) and overall survival (OS) were evaluated by Kaplan-Meier (KM) estimate. Results: 34 patients received PEAT and 44 patients received PEA. Demographic and baseline clinical characteristics were similar between both cohorts except for older median age of patients (69 years old vs 64 years old) and higher proportion of male patients (65% vs 39%) in the trilaciclib cohort. Even though there was a numerically lower rate of SN (3%) and hospitalization due to febrile neutropenia (FN) or infection (6%) in the PEAT versus the PEA (18%;11%) cohort, statistical significance was not met (p = 0.07;p = 0.065). Likewise, incidence of FN, platelet transfusion requirements, all-cause chemotherapy reductions, and treatment delays were not statistically different. However, the PEAT cohort as compared to PEA experienced a statistically significant reduction in red blood cell transfusion requirements (3% vs 23%; p = 0.02) and grade 3-4 anemia (6% vs 25%; p = 0.03). PFS and OS between the two cohorts were not statistically different. Conclusions: Based on this single center retrospective study, use of trilaciclib appears to confer improvement in the safety profile of PEA without negatively impacting survival outcomes. Therefore, results of this study support the integration of trilaciclib with PEA for ES-SCLC.

LDE-paclitaxel in second or later lines in advanced pancreatic cancer: A phase I trial.

e16298 Background: Nanoparticles have been studied in association with chemotherapy, with objective of increasing the concentration of the drug in neoplastic cells and, thus, increasing its antitumor action. Nab-paclitaxel is a well-known nanotechnology association between paclitaxel and albumin and can be used in the treatment of advanced pancreatic cancer. LDE-Paclitaxel is a combination of paclitaxel and a synthetic molecule of low-density lipoprotein (LDE). It was previously evaluated in patients with gynaecological malignancies undergoing third-line treatment and showed higher rates of disease control than conventional regimens described in the literature. Our objective was to evaluate the efficacy of LDE-paclitaxel in the treatment of advanced pancreatic cancer (stage III and IV) in second or third line of therapy. Methods: This was a prospective phase I/II, single-arm study, in which we delivered LDE-Paclitaxel at a weekly dose of 85mg/m² to patients with pancreatic adenocarcinoma in second or third-line. The patients must had been through treatment of at least one standard chemotherapy scheme. Results: From October 2020 to November 2021, nine patients with advanced pancreatic adenocarcinoma were enrolled in this prospective, single-arm, phase 1/2 study in which we offered LDE-Paclitaxel at a dose of 85mg/m² intravenously, after progression to gemcitabine. During this period, patients underwent a maximum of 5 cycles, with no need to reduce the medication dose in any of the cycles, for any of the patients. LDE-paclitaxel presented mostly grade 1 and 2 toxicities, mainly anaemia and neuropathy; Grade 3 toxicity was presented by only 1 patient, which was acute kidney injury. Median overall patient survival was 20.14 months, and patient survival after enrolment in the study and initiation of LDE-paclitaxel use was close to 5 months, with no decline in the assessed quality of life indices. Conclusions: LDE-paclitaxel appears to be more tolerable, viable and less toxic than other standard chemotherapy in this setting. Our results suggest that LDE-paclitaxel could be a therapeutic possibility for patients with metastatic pancreatic cancer. For a better evaluation, further studies would be necessary, to obtain more data on the use of this medication in clinical practice and for a better understanding of other important outcomes. Clinical trial information: 4237198 .

Joint population pharmacokinetic modeling of venlafaxine and O-desmethyl venlafaxine in healthy volunteers and patients to evaluate the impact of morbidity and concomitant medication.

Introduction: Venlafaxine (VEN) is a widely used dual selective serotonin/noradrenaline reuptake inhibitor indicated for depression and anxiety. It undergoes first-pass metabolism to its active metabolite, O-desmethyl venlafaxine (ODV). The aim of the present study was to develop a joint population pharmacokinetic (PPK) model to characterize their pharmacokinetic characters simultaneously. Methods: Plasma concentrations with demographic and clinical data were derived from a bioequivalence study in 24 healthy subjects and a naturalistic TDM setting containing 127 psychiatric patients. A parent-metabolite PPK modeling was performed with NONMEM software using a non-linear mixed effect modeling approach. Goodness of fit plots and normalized prediction distribution error method were used for model validation. Results and conclusion: Concentrations of VEN and ODV were well described with a one-compartment model incorporating first-pass metabolism. The first-pass metabolism was modeled as a first-order conversion. The morbid state and concomitant amisulpride were identified as two significant covariates affecting the clearance of VEN and ODV, which may account for some of the variations in exposure. This model may contribute to the precision medication in clinical practice and may inspire other drugs with pre-system metabolism.

Updated Insights on Cardiac and Vascular Risks of Proton Pump Inhibitors: A Real-World Pharmacovigilance Study.

BackgroundProton pump inhibitors (PPIs) are among the most widely prescribed medications in clinical practice. However, there are also concerns about the potential risks of long-term PPI use. The present study aimed to examine the safety of PPIs and summarize their potential cardiac and vascular risks in a real-world setting.MethodsThis pharmacovigilance study extracted records between January 2015 and December 2019 from the FDA Adverse Event Reporting System (FAERS) database. The association of seven PPI medications with cardiac and vascular events (CVEs) were evaluated. Two established pharmacovigilance methods, reporting odds ratio (ROR) and information components (IC) based statistical shrinkage, were used to measure disproportionality.ResultsIn total 62,140 CVE records associated with PPI use were investigated. Women showed a higher proportion (54.37%) of PPI-associated CVEs. The median time from PPI initiation to CVE onset was 97 [interquartile range (IQR): 8–491] days, with the shortest median time of 42 days (IQR: 2–277 days) for esomeprazole, and the longest time of 389 days (IQR: 0–525 days) for dexlansoprazole. Although PPIs were not associated with elevated CVE risks compared those of the whole database (IC025/ROR025 = −0.39/0.74), various signals emerged. Despite some similarities exist between the PPIs, their cardiac and vascular safety profiles varied significantly. Pantoprazole showed the broadest spectrum of signals, from thrombotic thrombocytopenic purpura (IC025/ROR025 = 0.01/1.08) to renal haemangioma (IC025/ROR025 = 3.14/9.58). Esomeprazole showed the second-broadest spectrum of toxicities, ranging from duodenal ulcer hemorrhage (IC025/ROR025 = 0.07/1.28) to hypertensive nephropathy (IC025/ROR025 = 4.09/18.72). Vascular signals were more dominant than cardiac signals, suggesting that vascular function was more heavily affected. Hypertensive nephropathy, renal haemangioma, renal artery stenosis, and renal infarct had strong signals across most PPI regimens and merited further attention.ConclusionsPPIs may inflict various CVEs, particularly those involving the vascular system, on the users. Given the wide range of onset times and different toxicity profiles for various PPI medications, they should be prescribed with caution.

Primary care physicians\u2019 approaches to low-value prescribing in older adults: a qualitative study

BackgroundLow-value prescribing may result in adverse patient outcomes and increased medical expenditures. Clinicians’ baseline strategies for navigating patient encounters involving low-value prescribing remain poorly understood, making it challenging to develop acceptable deprescribing interventions. Our objective was to characterize primary care physicians’ (PCPs) approaches to reduce low-value prescribing in older adults through qualitative analysis of clinical scenarios.MethodsAs part of an overarching qualitative study on low-value prescribing, we presented two clinical scenarios involving potential low-value prescribing during semi-structured interviews of 16 academic and community PCPs from general internal medicine, family medicine and geriatrics who care for patients aged greater than or equal to 65. We conducted a qualitative analysis of their responses to identify salient themes related to their approaches to prescribing, deprescribing, and meeting patients’ expectations surrounding low-value prescribing.ResultsWe identified three key themes. First, when deprescribing, PCPs were motivated by their desire to mitigate patient harms and follow medication safety and deprescribing guidelines. Second, PCPs emphasized good communication with patients when navigating patient encounters related to low-value prescribing; and third, while physicians emphasized the importance of shared decision-making, they prioritized patients’ well-being over satisfying their expectations.ConclusionsWhen presented with real-life clinical scenarios, PCPs in our cohort sought to reduce low-value prescribing in a guideline-concordant fashion while maintaining good communication with their patients. This was driven primarily by a desire to minimize the potential for harm. This suggests that barriers other than clinician knowledge may be driving ongoing use of low-value medications in clinical practice.

An AI-based Prediction Model for Drug-drug Interactions in Osteoporosis and Paget's Diseases from SMILES.

The skeleton is one of the most important organs in the human body in assisting our motion and activities; however, bone density attenuates gradually as we age. Among common bone diseases are osteoporosis and Paget's, two of the most frequently found diseases in the elderly. Nowadays, a combination of multiple drugs is the optimal therapy to decelerate osteoporosis and Paget's pathologic process, which comes with various underlying adverse effects due to drug-drug interactions (DDIs). Artificial intelligence (AI) has the potential to evaluate the interaction, pharmacodynamics, and possible side effects between drugs. In this research, we created an AI-based machine-learning model to predict the outcomes of interactions between drugs used for osteoporosis and Paget's treatment, which helps mitigate the cost and time to implement the best combination of medications in clinical practice. In this study, a DDI dataset was collected from the DrugBank database within the osteoporosis and Paget diseases. We then extracted a variety of chemical features from the simplified molecular-input line-entry system (SMILES) of defined drug pairs that interact with each other. Finally, machine-learning algorithms were implemented to learn the extracted features. Our stack ensemble model from Random Forest and XGBoost reached an average accuracy of 74 % in predicting DDIs. It was superior to individual models as well as previous methods in terms of most measurement metrics. This study showed the potential of AI models in predicting DDIs of Osteoporosis-Paget's disease in particular, and other diseases in general.

Aspirin desensitization – how and when?

Aspirin is one of the most commonly used medication in clinical practice, ranking highest among NSAIDs involved in hypersensitivity reactions. Despite the abundance of several therapeutic options, the administration of aspirin is essential both in severe cardiovascular pathology and in pregnancy, particularly in high-risk pregnant women, significantly boosting the survival rate and the quality of life of impacted patients. Desensitization to aspirin may be effective in certain situations. The desensitization approach is tailored to the kind of previous hypersensitivity reaction, the patient's individual risks, and the therapeutic purpose for aspirin therapy.

New and Off-Label Uses of Tranexamic Acid.

New and Off-Label Uses of Tranexamic Acid.

Differences in Antipsychotic Treatment Discontinuation Among Veterans With Schizophrenia in the U.S. Department of Veterans Affairs.

Effectiveness of antipsychotic drugs is inferred from relatively small randomized clinical trials conducted with carefully selected and monitored participants. This evidence is not necessarily generalizable to individuals treated in daily clinical practice. The authors compared the clinical effectiveness between all oral and long-acting injectable (LAI) antipsychotic medications used in the treatment of schizophrenia in the U.S. Department of Veterans Affairs (VA) health care system. This was an observational study utilizing VA pharmacy data from 37,368 outpatient veterans with schizophrenia. Outcome measures were all-cause antipsychotic discontinuation and psychiatric hospitalizations. Oral olanzapine was used as the reference group. In multivariable analysis, clozapine (hazard ratio=0.43), aripiprazole long-acting injectable (LAI) (hazard ratio=0.71), paliperidone LAI (hazard ratio=0.76), antipsychotic polypharmacy (hazard ratio=0.77), and risperidone LAI (hazard ratio=0.91) were associated with reduced hazard of discontinuation compared with oral olanzapine. Oral first-generation antipsychotics (hazard ratio=1.16), oral risperidone (hazard ratio=1.15), oral aripiprazole (hazard ratio=1.14), oral ziprasidone (hazard ratio=1.13), and oral quetiapine (hazard ratio=1.11) were significantly associated with an increased risk of discontinuation compared with oral olanzapine. No treatment showed reduced risk of psychiatric hospitalization compared with oral olanzapine; quetiapine was associated with a 36% worse outcome in terms of hospitalizations compared with olanzapine. In a national sample of veterans with schizophrenia, those treated with clozapine, two of the LAI second-generation antipsychotics, and antipsychotic polypharmacy continued the same antipsychotic therapy for a longer period of time compared with the reference drug. This may reflect greater overall acceptability of these medications in clinical practice.

Use of Medications for the Treatment of Alcohol Dependence: A Retrospective Study Conducted in 2011-2012.

Pharmacotherapy for Alcohol Dependence (AD) is underutilized. Barriers preventing the use of AD medications include high prices, lack of access to prescribing physicians, and a limited number of available medications. The study evaluated the use of AD medications in a sample of Italian outpatients who received these medications free of charge, had access to physicians during office hours, and for whom substitution therapy [gamma-hydroxybutyrate (GHB)] was available. We also evaluated the rate of patients who received a combination of non-pharmacological and pharmacological treatments among participants who were still drinking. SCID for AD and questionnaire were filled by to AD outpatients during a face-to-face interview. 345 AD outpatients were interviewed: 58.8% were currently receiving at least one AD medication (GHB: 34.3%, disulfiram: 29.6%, acamprosate: 5.9%; naltrexone: 2.5%; more than one medication: 16.7%). Less than 30% of participants who were still drinking, received a combination of non-pharmacological and pharmacological treatments. Nonetheless, we found higher use of AD medications compared to previous studies conducted in other countries. This higher use of AD medications may be due to access to free medications, prescribing physicians' style, and a larger number of available medications. Our results confirm the underutilization of AD medications, as less than 60% of AD outpatients received medications, and less than 30% of those who were still drinking, received a combination of non-pharmacological and pharmacological treatments. These findings may be useful in improving our knowledge of the barriers that prevent the use of AD medications in clinical practice.

Progression and future of CDK4/6 inhibitors in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer

With the progress of tumor molecular biology research, the clinical treatment concept of advanced breast cancer gradually tends to be accurate. Hormone receptor (HR) positive and human epidermal growth factor receptor 2 (HER-2) negative breast cancer accounts for more than 70% of all breast cancers, and it is of great significance to explore new treatment strategies to break through the bottleneck of traditional treatment faced by the patient population. Targeted therapy for this type of breast cancer started relatively late. After the first cyclin-dependent kinase (CDK) 4/6 inhibitor Palbociclib entered the clinical application for HR positive and HER-2 negative advanced breast cancer patients in 2015, the clinical treatment pattern of HR positive and HER-2 negative advanced breast cancer has been changed significantly, with a consequent breakthrough improvement in patients' survival prognosis. Based on the basic pharmacological mechanism, the author analyzes the existing research data and puts forward opinions on how to achieve precise medication in clinical practice and wider application prospects in the future.

A Pharmacovigilance Study of Adverse Drug Reactions Reported for Cardiovascular Disease Medications Approved Between 2012 and 2017 in the United States Food and Drug Administration Adverse Event Reporting System (FAERS) Database.

Between 2012 and 2017, the FDA approved 29 therapies for a cardiovascular disease (CVD) indication. Due to the limited literature on patient safety outcomes for recently approved CVD medications, this study investigated adverse drug reports (ADRs) reported in the FDA Adverse Event Reporting System (FAERS). A disproportionality analysis of spontaneously reported ADR was conducted. Reports in FAERS from Quarter 1, 2012, through Quarter 1, 2019, were compiled, allowing a 2-year buffer following drug approval in 2017. Top 10 reported ADRs and reporting odds ratios (ROR; confidence interval (CI)), a measure of disproportionality, were analyzed and compared to drugs available prior to 2012 as appropriate. Of 7,952,147 ADR reports, 95,016 (1.19%) consisted of reports for newly approved CVD medications. For oral anticoagulants, apixaban had significantly lower reports for anemia and renal failure compared to dabigatran and rivaroxaban but greater reports for neurological signs/symptoms, and arrhythmias. Evaluating heart failure drugs, sacubitril/valsartan had greater reports for acute kidney injury, coughing, potassium imbalances, and renal impairment but notably, lower for angioedema compared to lisinopril. Assessing familial hypercholesterolemia drugs, alirocumab had greater reports for joint-related-signs/symptoms compared to other agents in this category. A newer pulmonary arterial hypertension treatment, selexipag, had greater reports of reporting for bone/joint-related-signs/symptoms but riociguat had greater reports for hemorrhages and vascular hypotension. Pharmacovigilance studies allow an essential opportunity to evaluate the safety profile of CVD medications in clinical practice. Additional research is needed to evaluate these reported safety concerns for recently approved CVD medications.

Patient harm from cardiovascular medications.

BackgroundMedication harm can lead to hospital admission, prolonged hospital stay and poor patient outcomes. Reducing medication harm is a priority for healthcare organisations worldwide. Recent Australian studies demonstrate cardiovascular (CV) medications are a leading cause of harm. However, they appear to receive less recognition as ‘high risk’ medications compared with those classified by the medication safety acronym, ‘APINCH’ (antimicrobials, potassium, insulin, narcotics, chemotherapeutics, heparin). Our aim was to determine the scale and type of medication harm caused by CV medications in healthcare.MethodsA narrative review of adult (>16 years) medication harm literature identified from PubMed and CINAHL databases was undertaken. Studies with the primary outcome of measuring the incidence of medication harm were included. Harm caused by CV medications was described and ranked against other medication classes at four key stages of a patient’s healthcare journey. Where specified, the implicated medications and type of harm were investigated.ResultsA total of 75 studies were identified, including seven systematic reviews and three meta-analyses, with most focussing on harm causing hospital admission. CV medications were responsible for approximately 20% of medication harm; however, this proportion increased to 50% in older populations. CV medications were consistently ranked in the top five medication categories causing harm and were often listed as the leading cause.ConclusionCV medications are a leading cause of medication harm, particularly in older adults, and should be the focus of harm mitigation strategies. A practical approach to generate awareness among health professionals is to incorporate ‘C’ (for CV medications) into the ‘APINCH’ acronym.Plain language summaryPatient harm from cardiovascular medicationsBackground• Harm from medications can cause poor patient outcomes.• Certain medications have been identified as ‘high risk’ and are known to cause high rates of harm.• ‘High risk’ medications are included in medication guidelines used by health professionals.• Cardiovascular medications (e.g. blood pressure and cholesterol medications) are important and have many benefits.• Recent studies have found cardiovascular medications to cause high rates of harm.• Cardiovascular medication harm is often under-recognised in clinical practice.• Some guidelines do not consider cardiovascular medications to be ‘high risk’.Method• This review investigated the extent of harm caused by cardiovascular medications in adults across four healthcare settings:(1) at the time of hospital admission;(2) during hospital admission;(3) after hospital; and(4) readmission to hospital.• Harm caused by cardiovascular medications was ranked against other medication classes.• We investigated the type of cardiovascular medications to cause harm and the type of harm caused.Results• Seventy-five studies were reviewed across 41 countries.• Cardiovascular medications were ranked within the top five medications to cause harm.• Cardiovascular medications were a leading cause of harm in each healthcare setting investigated.• Harm caused by cardiovascular medications was common in older adults (>65 years).• Cardiovascular medications often caused preventable harm.• Medications to treat high blood pressure and abnormal heart rhythms were the most common causes of harm.• We reported kidney injury, electrolyte changes and low blood pressure as common types of harm.Conclusion• Increased focus on cardiovascular medications in clinical practice is needed.• Health professionals need to carefully prescribe and frequently review cardiovascular medications, especially in older adults.• Patient and health professional discussions should be based on both the benefits and harms of cardiovascular medications.• Cardiovascular medications should be included in all ‘high risk’ medication guidelines.

Prevention of Non-steroidal Anti-inflammatory Drug-induced Peptic Ulcers.

Nonsteroidal anti-inflammatory drugs (NSAID) are some of the most commonly prescribed medications in clinical practice. The long-term use of NSAIDs is one of the main causes of peptic ulcers and the increased risk of upper gastrointestinal tract complications, such as perforation and bleeding. Thus, the prevention of NSAID-induced peptic ulcers is an important clinical issue. Previous studies have evaluated various strategies for preventing ulcers in patients requiring prolonged NSAID use. The Korean clinical practice guidelines have been published recently based on the evidence of the currently available data. This review describes the strategies for the prevention of peptic ulcers due to NSAID. An assessment of the risk factors for peptic ulcers from NSAID is recommended to identify patients who should be considered for primary prophylaxis. The risk of NSAID-induced peptic ulcers can be reduced by the concomitant use of proton pump inhibitors (PPI), misoprostol, and histamine-2 receptor antagonists. Selective cyclooxygenase-2 inhibitors can be used with caution due to concerns regarding cardiovascular toxicity. Attempts should be made to use the lowest dose and shortest duration of the NSAID.