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Statins, widely used cardiovascular drugs that lower cholesterol by inhibiting HMG-CoA reductase, have been increasingly recognized for their potential anticancer properties. This study elucidates the underlying mechanism, revealing that statins exploit Synthetic Lethality, a principle where the co-occurrence of two non-lethal events leads to cell death. Our computational analysis of approximately 37,000 SL pairs identified statins as potential drugs targeting genes involved in SL pairs with metastatic genes. In vitro validation on various cancer cell lines confirmed the anticancer efficacy of statins. This data-driven drug repurposing strategy provides a molecular basis for the anticancer effects of statins, offering translational opportunities in oncology. [ABSTRACT FROM AUTHOR]

Introduction: Clinical trials, essential for medical advancement, vary significantly in methodology and regulatory pathways depending on the type of therapeutic intervention (i.e., drugs or devices). This study aimed to determine whether the drug or device intervention types influence the impact of randomized trials in cardiovascular medicine. Methods: We analyzed late-breaking randomized controlled trials presented at major cardiology conferences from 2015 to 2021. The primary endpoint was the total number of citations obtained. Secondary endpoints included the number of citations at 1 and 2 years, number of total and 1-year mentions, and several metrics of study conduct and publication. Statistical analysis included tests for comparisons of continuous or categorical variables, based on their distribution, as appropriate. To adjust the results for potential confounders, univariable and multivariable regression models were utilized. Additionally, sensitivity analyses were conducted to explore both the effect of neutral or positive study outcomes on the comparative impact of drug versus device trials and the impact of the coronavirus disease 2019 (COVID-19) pandemic on the primary endpoint. Results: Of 382 eligible randomized trials, 227 (59.4%) were trials of drugs and 155 (40.6%) were trials of devices. Drug trials had a higher median number of total citations compared to device studies (93 [interquartile range {IQR} 48–137] vs. 82 [IQR 39–192]; p = 0.025). This difference was consistent at 1 and 2 years and was also observed in the number of total mentions and mentions at 1 year. All the metrics of study conduct and publication were similar, except for drug studies being more often stopped prematurely (8.8 vs. 1.9%; p = 0.006). After adjusting for multiple potential confounders, the difference in citations and mentions was no longer statistically significant. However, drug trials remained more likely to be stopped prematurely (adjusted odds ratio = 1.15; 95% confidence interval 1.03–1.28; p = 0.009). Positive study outcomes significantly influenced the number of citations and the likelihood of a trial being stopped prematurely. Conclusions: Drug trials are often stopped early and receive more citations and mentions than device trials. However, these differences are mainly due to factors other than the treatment itself. Studies published simultaneously tend to get more attention, and drug trials with positive results are cited more often than those with neutral results. [ABSTRACT FROM AUTHOR]

Objective: To investigate the prevalence of diabetes retinopathy and evaluate the factors influencing its occurrence both at the onset of type 2 diabetes (T2D) and three years into its duration. Design: Retrospective population-based study. Setting: Data was retrieved from Regional Healthcare Information Platform in Region Halland 2016–2020. Subjects: Patients 35-75 years old in Region Halland receiving first-time diabetes diagnosis according to ICD-code E11-14 in 2016–17. The total cohort consisted of 1659 patients. Main outcome measures: The main outcome measure of the study was the occurrence of diabetes retinopathy at onset and within three years from the diabetes diagnosis. Multivariate logistic regression analysis was conducted for diabetes retinopathy at onset and within three years, adjusted for age, gender, comorbidities, levels of HbA1c, cholesterol, kidney functional and blood pressure. Results: At onset, there were 12% with diabetes retinopathy and after three years, 32% of the patients had developed diabetes retinopathy. In the study cohort, 71 of patients who were examined with fundus photography within three years after onset, and 8% had had dietary recommendation without pharmacotherapy. High HbA1c levels, blood pressure values and impaired renal function already at onset were associated with development of diabetes retinopathy at onset and this association persisted after three years. The odds ratio for diabetes retinopathy was increased adjusted for HbA1c elevations, renal impairment, and increased blood pressure at index and when adjusted for these variables three years from index. Conclusion: These findings indicate that the risk of developing diabetes retinopathy is present early on at onset and within the first three years of diabetes diagnosis. This highlights the importance of promptly regulating glucose- and blood-pressure levels and follow up kidney dysfunction to mitigate the risk of diabetes retinopathy. KEY POINTS: Among patients with type 2 diabetes, 12% had developed diabetes retinopathy already at onset. Among patients with type 2 diabetes, one-third had developed diabetes retinopathy after three years from onset. The presence of diabetes retinopathy already at diabetes onset, was associated with elevated HbA1c levels, renal impairment and elevated blood pressure. Diabetes retinopathy three years after the onset of the disease, was associated with increased HbA1c levels, high blood pressure, and renal dysfunction. [ABSTRACT FROM AUTHOR]

Intracerebral hemorrhage (ICH) is a major health problem. It is one of the most common types of stroke and results in mortality in approximately half of patients. More than half of the fatalities occur in the first 2 days. In addition to the mass effect after ICH hemorrhage, complex pathophysiological mechanisms such as intracranial vessel vasospasm, microthrombosis, and inflammatory immune reaction also increase brain damage. Both resident (including microglia and astrocytes) and circulating immune cells (including neutrophils, macrophages, and lymphocytes) involved in the inflammatory process. The inflammatory response is especially harmful in the acute phase due to harmful substances secreted by infiltrating immune cells. The inflammatory response also has beneficial effects, especially in the later stages. Their role in pathophysiology makes immune cells important therapeutic targets. General immunosuppressive approaches and depleting cell groups such as neutrophils or keeping them away from the lesion site may not be sufficient to prevent poor outcomes after ICH. This is most likely because they suppress anti-inflammatory activities and pro-inflammatory effects. Instead, directing immune cells to the beneficial subpopulation seems like a more rational solution. The pro-inflammatory N1 subpopulation of neutrophils damages the tissue surrounding ICH. In contrast, the N2 subpopulation is associated with anti-inflammatory reactions and tissue repair. Studies show that when neutrophils are polarized toward the N2 subpopulation, clinical outcomes improve and the volume of the infarct decreases. However, more research is still needed. This study aims to evaluate the role of neutrophils as immunotherapeutic targets in ICH in light of current knowledge. [ABSTRACT FROM AUTHOR]

This study investigates the implications of increased internet penetration on demand in the context of pharmaceutical prescribing. The internet has changed the information and tools available to make decisions in complex tasks such as those made by physicians, and any impact on prescribing patterns has implications for the marketing activities of drug manufacturers, necessitating a strategic rethink of business practices. This study conceptualizes the prescription decision‐making process through the lens of expectancy value theory. The unique research design allows for the observation of contrasting internet penetration rates of geographically distributed physicians over an extended time period in multiple drug categories. Modeling physician behavior as a combination of learning, peer effects, and face‐to‐face detailing by pharmaceutical firms, the study finds that the growth of the internet has a significant moderating impact on detailing efforts. Interestingly, the study also documents the interaction between learning and peer effects, as well as how the internet ultimately reduces reliance on prior prescription behavior (prescribing inertia) for the four Cardiovascular drug categories under consideration. We discuss the implications of these findings for R&D managers, marketers, and policymakers. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to describe a population of very old people with heart failure (HF), to analyse the use of cardiovascular drugs over time, and to explore factors influencing cardiovascular drug treatment for this group. Methods: All participants with information regarding HF diagnosis were selected from the Umeå 85+/Gerontological Regional Database (GERDA). The people in GERDA are all ≥85 years old. Trained investigators performed structured interviews and assessments. Information regarding medications and diagnoses was obtained from the participants and from medical records. Medical diagnoses were reviewed and confirmed by an experienced geriatrician. Results: In this very old population, the prevalence of HF was 29.6% among women and 30.7% among men. Between 2000 and 2017, there was an increase in the use of renin-angiotensin (RAS) inhibitors (odds ratio [OR] 1.107, 95% confidence interval [CI] 1.072–1.144) and beta-blockers (BBs) (OR 1.123, 95% CI 1.086–1.161) among persons with HF, whereas the prevalence of loop diuretics (OR 0.899, 95% CI 0.868–0.931) and digitalis (OR 0.864, 95% CI 0.828–0.901) decreased (p < 0.001 for all drug classes). Higher age was associated with lower use of RAS inhibitors and BBs. Conclusion: In this HF population, the use of evidence-based medications for HF increased over time. This may be a sign of better awareness among prescribers regarding the under-prescribing of guidelines-recommended treatment to old people. Higher age associated with a lower prevalence of RAS inhibitors and BBs. This might indicate that further improvement is possible but could also represent a more cautious prescribing among frail very old individuals. [ABSTRACT FROM AUTHOR]

This research letter examines the use of semaglutide, a glucose-lowering drug, in adults with type 2 diabetes in Scandinavia. The study analyzes nationwide data on filled prescriptions in Denmark, Norway, and Sweden to compare the characteristics of semaglutide initiators with those of initiators of other glucose-lowering drugs. The findings show that semaglutide is being widely used in Scandinavia and that initiators of semaglutide are typically younger and have different medication usage patterns compared to initiators of other drugs. The study suggests that semaglutide may be used for indications other than type 2 diabetes, such as weight loss. However, the study acknowledges limitations, such as the lack of data on indications for use and the use of filled prescriptions as a proxy for drug use. [Extracted from the article]

Purpose: While patients with cardiovascular comorbidities are at a higher risk for the occurrence of non-arteritic anterior ischemic optic neuropathy (NAION), it is unclear whether adherence to medication results in risk reduction. The purpose of this study was to investigate whether nonadherence to medical therapy for cardiovascular morbidity correlates with a higher risk for NAION when compared to patients with strict adherence. Methods: A retrospective case-control study was conducted among members of Clalit Health Services in Israel from 2001 to 2022. For each of the 757 NAION cases, three controls (totaling 2271 patients) were matched based on birth year and sex, with a propensity score analysis employed to adjust for a range of comorbidities. A patient was deemed nonadherent with medical treatment if their purchased quantity of medication was less than 60% of the prescribed annual dosage. Mixed models were used to evaluate exposure differences, and conditional logistic regression was applied, incorporating adjustments for socioeconomic status and ethnicity, to examine the impact of medication nonadherence on NAION risk. Results: A total of 3028 patients were included in the study; 757 patients with the diagnosis of NAION and 2271 in the matched control group. The average age of NAION patients was 69 ± 9 years and 55% were male. After adjustments for socioeconomic status and ethnicity, nonadherence to calcium channel blockers (CCBs) (odds ratio [OR]: 1.33, 95% confidence interval [CI]: 1.03–1.71) and anti-arrhythmic (OR: 5.67, 95% CI: 1.89–21.2) medications emerged as significant risk factors. Similarly, nonadherence to cardioprotective medications (OR: 1.46, 95% CI: 1.23–1.74) was also identified as a significant risk factor. Conclusions: Nonadherence to treatments for cardiovascular disease, specifically to medications known to improve prognosis, is associated with a higher risk for NAION. [ABSTRACT FROM AUTHOR]

From its inception as a two-dimensional snapshot of the beating heart, echocardiography has become an indelible part of cardiovascular diagnostics. The integration of ultrasound enhancing agents (UEAs) marks a pivotal transition, enhancing its diagnostic acumen beyond myocardial perfusion. These agents have refined echocardiography's capacity to visualize complex cardiac anatomy and pathology with unprecedented clarity, especially in non-coronary artery disease contexts. UEAs aid in detailed assessments of myocardial viability, endocardial border delineation in left ventricular opacification, and identification of intracardiac masses. Recent innovations in UEAs, accompanied by advancements in echocardiographic technology, offer clinicians a more nuanced view of cardiac function and blood flow dynamics. This review explores recent developments in these applications and future contemplated studies. [ABSTRACT FROM AUTHOR]

Cardioprotective Unani drug, Saad Kufi (Cyperus scariosus R.Br.), mentioned by the intellectual colossus Ibn Sina (Avicenna) a thousand years back in his book, "Kitab al-Adviya al-Qalbia" and still widely used by Unani physicians, was selected for experimental study. The main objective of the study was to explore the trial drug ex vivo for validation, hemodynamic elucidation, and molecular mechanism identification for the improvement of Unani therapeutics and to identify a safe and effective novel cardiovascular drug for mainstream medicine. Five doses of 50% ethanolic extract of the physiochemically standardized root were studied in a normal rat heart, on a semi-automated Langendorff apparatus supported with an advanced data acquisition system, perfused with carbogenated non-recirculating Kreb's-Hensleit solution, at constant flow mode, by continuous recording. The effect of 6 repetitions (n = 6) of each dose was studied with the following parameters on the Lab chart pro version: heart rate, left ventricular developed pressure, cardiac work, and coronary pressure. The significance of the difference was determined by the student's "t" test. Results of all doses of Saad Kufi showed a significant increase in the above parameters. The maximum increase was observed by Dose III. It could be concluded that Unani's clinical use of Saad Kufi (C. scariosus R.Br) as cardioprotective was validated and higher doses were indicated to be clinically optimal. Hemodynamically and molecular mechanism-wise, it is indicated to be a sympathomimetic or inotropic-like agent and possibly a direct vasodilator. Since existing long-term treatment of heart failure is not done by cardiac stimulants or positive inotropic and chronotropic agents, the possible future clinical demonstration of therapeutic improvement in heart failure will bring Saad Kufi as a novel drug in mainstream medicine. [ABSTRACT FROM AUTHOR]

AbstractPhenolic acids derived from plants have beneficial effects on cardiovascular diseases (CVD). Cinnamic acid (CA) is a crucial phenolic acid that can form numerous hydroxycinnamic derivate found in many food groups. We review current data on the cardiovascular pharmacology of CA with a focus on CVD and their risk factors including hyperlipidaemia, obesity, hyperglycaemia, cardiomyopathy and myocardial ischaemia, vascular dysfunction, oxidative stress and inflammation. Both in vivo and in vitro laboratory studies demonstrate the lipid-lowering, anti-obesity, anti-hyperglycemic, cardio-protective and vasorelaxant activities of CA. The protective impacts of CA against CVD occur by inhibiting inflammatory, oxidative, and apoptotic pathways, regulating the genes and enzymes involved in glucose and lipid metabolisms, and promoting vasodilation. This review showed that the most studied and prominent effects of CA are anti-hyperlipidemic and anti-diabetic properties. In conclusion, intake of plant foods rich in CA may reduce CVD risk especially through regulating blood glucose and lipids levels. [ABSTRACT FROM AUTHOR]

This study investigates the current situation and possible health risks due to pharmaceutically active compounds (PhACs) including analgesics, antibiotics, antifungals, anti-inflammatories, psychiatric and cardiovascular drugs, and metabolites, in indoor environments. To achieve this objective, a total of 85 dust samples were collected in 2022 from three different Spanish indoor environments: homes, classrooms, and offices. The analytical method was validated meeting SANTE/2020/12830 and SANTE/12682/2019 performance criteria. All indoor dust samples except one presented at least one PhAC. Although concentration levels ranged from < LOQ to 18 µg/g, only acetaminophen, thiabendazole, clotrimazole, and anhydroerythromycin showed quantification frequencies (Qf %) above 19% with median concentrations of 166 ng/g, 74 ng/g, 25 ng/g and 14 ng/g, respectively. The PhAC distribution between dust deposited on the floor and settled on elevated (> 0.5 m) surfaces was assessed but no significant differences (p > 0.05, Mann–Whitney U-test) were found. However, concentrations quantified at the three types of locations showed significant differences (p < 0.05, Kruskal–Wallis H-test). Homes turned out to be the indoor environment with higher pharmaceutical concentrations, especially acetaminophen (678 ng/g, median). The use of these medicines and their subsequent removal from the body were identified as the main PhAC sources in indoor dust. Relationships between occupant habits, building characteristics, and/or medicine consumption and PhAC concentrations were studied. Finally, on account of concentration differences, estimated daily intakes (EDIs) for inhalation, ingestion and dermal adsorption exposure pathways were calculated for toddlers, adolescents and adults in homes, classrooms and offices separately. Results proved that dust ingestion is the main route of exposure, contributing more than 99% in all indoor environments. Moreover, PhAC intakes for all studied groups, at occupational locations (classrooms and offices) are much lower than that obtained for homes, where hazard indexes (HIs) obtained for acetaminophen (7%—12%) and clotrimazole (4%-7%) at the worst scenario (P95) highlight the need for continuous monitoring. [ABSTRACT FROM AUTHOR]

Background: Drug-drug interactions (DDIs) increase the incidence of adverse drug reactions (ADRs). In a previous report, we revealed that the incidence of potential DDIs due to the same CYP molecular species in one prescription exceeds 90% among patients taking six or more drugs and that CYP3A4 markedly influences the increase in the number of potential DDIs in clinical practice. However, the factors contributing to an increased number of potential DDIs in prescriptions from multiple clinical departments remain poorly clarified. Methods: This observational study was performed at five pharmacies in Okayama Prefecture, Japan. Patients who visited these pharmacies from 11 April 2022 to 24 April 2022 were included, except those who had prescriptions only from a single clinical department. A stratified analysis was performed to determine the incidence of CYP3A4-related potential DDIs according to the number of drugs taken. Additionally, factors associated with an increase in the number of drugs involved in CYP3A4-related potential DDIs were identified using multiple linear regression analysis. In this study, potential DDIs for the prescription data subdivided by clinical department, containing two or more drugs, were used as control data. Results: Overall, 372 outpatients who received prescriptions from multiple clinical departments were included in the current study. The number of drugs contributing to CYP3A4-related potential DDIs increased with an increase in the number of clinical departments. Notably, in cases taking fewer than six drugs, prescriptions from multiple clinical departments had a higher frequency of CYP3A4-related potential DDIs than those in prescriptions subdivided by clinical department. Multiple regression analysis identified "Cardiovascular agents", "Agents affecting central nervous system", and "Urogenital and anal organ agents" as the top three drug classes that increase CYP3A4-related potential DDIs. Conclusion: Collectively, these results highlight the importance of a unified management strategy for prescribed drugs and continuous monitoring of ADRs in outpatients receiving prescriptions from multiple clinical departments even if the number of drugs taken is less than six. [ABSTRACT FROM AUTHOR]

Clinical annotations for the actionable pharmacogenetic variants affecting the efficacy of cardiovascular drugs have been collected, yet their impacts on elderly patients with coronary artery disease (CAD) undergoing polypharmacy remain uncertain. We consecutively enrolled 892 elderly patients (mean age 80.7 ± 5.2) with CAD and polypharmacy. All the included patients underwent genotyping for 13 variants in 10 pharmacogenes (CYP2C19, CYP2C9, CYP4F2, CYP2D6, VKORC1, SLCO1B1, APOE, ACE, ADRB1, and MTHFR), which have the clinical annotations for 12 drugs that are commonly prescribed for patients with CAD. We found that 80.3% of the elderly CAD patients had at least one drug–gene pair associated with a therapeutical drug change. After adjusting for covariates, the number of drug–gene pairs was independently associated with a decreased risk of both major cardiovascular events (MACEs) (adjusted hazard ratio [HR]: 0.803, 95% confidence interval [CI]: 0.683–0.945, p = 0.008) and all-cause mortality (adjusted HR: 0.848, 95% CI: 0.722–0.996, p = 0.045), but also with an increased risk of adverse drug reactions (ADRs) (adjusted HR: 1.170, 95% CI: 1.030–1.329, p = 0.016). The Kaplan–Meier survival curves showed that compared to patients without a drug–gene pair, a significantly lower risk of MACEs could be observed in patients with a drug–gene pair during a 4-year follow-up (HR: 0.556, 95% CI: 0.325–0.951, p = 0.013). In conclusion, the carrier status of the actionable drug–gene pair is predictive for the clinical outcomes in elderly patients with CAD and polypharmacy. Implementing early or preemptive pharmacogenetic panel-guided polypharmacy holds the potential to enhance clinical outcomes for these patients. [ABSTRACT FROM AUTHOR]

To understand the large inter-species variations in drug effects on repolarization, the properties of the rapid (IKr) and the slow (IKs) components of the delayed rectifier potassium currents were compared in myocytes isolated from undiseased human donor (HM), dog (DM), rabbit (RM) and guinea pig (GM) ventricles by applying the patch clamp and conventional microelectrode techniques at 37 °C. The amplitude of the E-4031-sensitive IKr tail current measured at −40 mV after a 1 s long test pulse of 20 mV, which was very similar in HM and DM but significant larger in RM and GM. The L-735,821-sensitive IKs tail current was considerably larger in GM than in RM. In HM, the IKs tail was even smaller than in DM. At 30 mV, the IKr component was activated extremely rapidly and monoexponentially in each studied species. The deactivation of the IKr component in HM, DM, and RM measured at −40 mV. After a 30 mV pulse, it was slow and biexponential, while in GM, the IKr tail current was best fitted triexponentially. At 30 mV, the IKs component activated slowly and had an apparent monoxponential time course in HM, DM, and RM. In contrast, in GM, the activation was clearly biexponential. In HM, DM, and RM, IKs component deactivation measured at −40 mV was fast and monoexponential, while in GM, in addition to the fast component, another slower component was also revealed. These results suggest that the IK in HM resembles that measured in DM and RM and considerably differs from that observed in GM. These findings suggest that the dog and rabbit are more appropriate species than the guinea pig for preclinical evaluation of new potential drugs expected to affect cardiac repolarization. [ABSTRACT FROM AUTHOR]

The Finnish web-based Meds75+ database supports rational, safe and appropriate prescribing to older adults in primary care. This article describes the content and updating process of Meds75+ and demonstrates its applicability in everyday clinical practice. Meds75+ contains a classification (A–D) and recommendation texts for 450–500 drug substances when used in the treatment of older adults aged 75 years or older. The content of Meds75+ is continually updated. Each assessment of a drug substance begins with a structured collection of available information and research evidence. After that, an interdisciplinary expert panel discusses the classification and recommendation using a consensus method. A rolling 3-year updating cycle guarantees that all drug substances are reviewed regularly. Most drug substances are classified as class A (41%) (suitable, e.g. bisoprolol) or as class C (37%) (suitable with specific precautions, e.g. ibuprofen). One-fifth (20%) of the substances are in class D (avoid use, e.g. diazepam). Most commonly, older adults have purchased substances affecting the alimentary tract and metabolism (17%), the nervous system (16%) and the cardiovascular system (15%). In Finland, the proportion of older adults using class D substances (37%) has not changed between the years 2019 and 2022. Meds75+ has potential to support safer and more effective use of medications for older adults, since it offers up-to-date information on drug substances for healthcare professionals. [ABSTRACT FROM AUTHOR]

Background and Objectives: Saliva is a patient-friendly matrix for therapeutic drug monitoring (TDM) but is infrequently used in routine care. This is due to the uncertainty of saliva-based TDM results to inform dosing. This study aimed to retrieve data on saliva–plasma concentration and subsequently determine the physicochemical properties that influence the excretion of drugs into saliva to increase the foundational knowledge underpinning saliva-based TDM. Methods: Medline, Web of Science and Embase (1974–2023) were searched for human clinical studies, which determined drug pharmacokinetics in both saliva and plasma. Studies with at least ten subjects and five paired saliva–plasma concentrations per subject were included. For each study, the ratio of the area under the concentration–time curve between saliva and plasma was determined to assess excretion into saliva. Physicochemical properties of each drug (e.g. pKa, lipophilicity, molecular weight, polar surface area, rotatable bonds and fraction of drug unbound to plasma proteins) were obtained from PubChem and Drugbank. Drugs were categorised by their ionisability, after which saliva-to-plasma ratios were predicted with adjustment for protein binding and physiological pH via the Henderson–Hasselbalch equation. Spearman correlation analyses were performed for each drug category to identify factors predicting saliva excretion (α = 5%). Study quality was assessed by the risk of bias in non-randomised studies of interventions tool. Results: Overall, 42 studies including 40 drugs (anti-psychotics, anti-microbials, immunosuppressants, anti-thrombotic, anti-cancer and cardiac drugs) were included. The median saliva-to-plasma ratios were similar for drugs in the amphoteric (0.59), basic (0.43) and acidic (0.41) groups and lowest for drugs in the neutral group (0.21). Higher excretion of acidic drugs (n = 5) into saliva was associated with lower ionisation and protein binding (correlation between predicted versus observed saliva-to-plasma ratios: R2 = 0.85, p = 0.02). For basic drugs (n = 21), pKa predicted saliva excretion (Spearman correlation coefficient: R = 0.53, p = 0.02). For amphoteric drugs (n = 10), hydrogen bond donor (R = − 0.76, p = 0.01) and polar surface area (R = − 0.69, p = 0.02) were predictors. For neutral drugs (n = 10), protein binding (R = 0.84, p = 0.004), lipophilicity (R = − 0.65, p = 0.04) and hydrogen bond donor count (R = − 0.68, p = 0.03) were predictors. Drugs considered potentially suitable for saliva-based TDM are phenytoin, tacrolimus, voriconazole and lamotrigine. The studies had a low-to-moderate risk of bias. Conclusions: Many commonly used drugs are excreted into saliva, which can be partly predicted by a drug's ionisation state, protein binding, lipophilicity, hydrogen bond donor count and polar surface area. The contribution of drug transporters and physiological factors to the excretion needs to be evaluated. Continued research on drugs potentially suitable for saliva-based TDM will aid in adopting this person-centred TDM approach to improve patient outcomes. [ABSTRACT FROM AUTHOR]

A 15‐month‐old female Ragdoll cat was evaluated for progressive lethargy, tachypnoea and increased respiratory effort for 1 week after routine ovariohysterectomy. Thoracic radiographs and an echocardiogram showed evidence of congestive heart failure and a hypertrophic cardiomyopathy phenotype, respectively. The maximum left ventricular wall thickness in end diastole was 6.2 mm. The serum cardiac troponin I concentration was 20.86 ng/mL. The cat was treated with furosemide and clopidogrel and discharged after 3 days. A repeat echocardiogram 2 weeks later showed complete resolution of the hypertrophic cardiomyopathy phenotype (maximum left ventricular wall thickness: 5.0 mm). A repeat cardiac troponin I concentration was 0.041 ng/mL. All cardiac medications were discontinued. A final recheck 4 weeks later revealed stable normal echocardiogram and further reduction in cardiac troponin I concentration to 0.004 ng/mL. This case report demonstrates that resolution of transient myocardial thickening can take 2 weeks after the echocardiographic diagnosis of left ventricular thickening. [ABSTRACT FROM AUTHOR]

Acute coronary syndrome (ACS) remains a major cause of morbidity and mortality worldwide, requiring ongoing efforts to identify novel therapeutic targets to improve patient outcomes. This manuscript reviews promising therapeutic targets for ACS identified through preclinical research, including novel antiplatelet agents, anti-inflammatory drugs, and agents targeting plaque stabilization. Preclinical studies have expounded these agents' efficacy and safety profiles in mitigating key pathophysiological processes underlying ACS, such as platelet activation, inflammation, and plaque instability. Furthermore, ongoing clinical trials are evaluating the efficacy and safety of these agents in ACS patients, with potential implications for optimizing ACS management. Challenges associated with translating preclinical findings into clinical practice, including patient heterogeneity and trial design considerations, are also discussed. Overall, the exploration of emerging therapeutic targets offers promising avenues for advancing ACS treatment strategies and improving patient outcomes. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study is to explore and analyze the FDA Adverse Event Reporting System (FAERS) database to identify drug adverse reaction signals associated with angioedema. The findings aim to provide valuable insights for clinical drug safety considerations. Methods: The Open Vigil 2.1 data platform was utilized to collect adverse event reports related to angioedema from the first quarter of 2004 to the fourth quarter of 2023. The reporting odds ratio (ROR) and proportional reporting ratio (PRR) were employed as disproportionality measures to detect adverse reaction signals Sof drugs associated with angioedema. Results: A total of 38,921 reports were retrieved, with the majority being reported by healthcare professionals. The analysis included predominantly adult patients (=18 years of age), with slightly higher representation of females compared tomales. Among the top 30 drugs associated with the occurrence of angioedema, 24 drugs showed positive signals in the risk analysis. Based on the individual drug reporting odds ratio (95% confidence interval) as ameasure of risk signal strength, the top five drugs are as follows: lisinopril [ROR (95% CI): 46.43 (42.59-50.62)], enalapril [ROR (95% CI): 43.51 (39.88-47.46)], perindopril [ROR (95% CI): 31.17 (27.5-35.32)], alteplase [ROR (95% CI): 29.3 (26.95-31.85)], ramipril [ROR (95% CI): 20.93 (19.66-22.28)]. After categorizing the drugs, the strongest positive signal was observed in the antithrombotic agents [ROR (95% CI): 22.53 (21.16-23.99)], following that, cardiovascular drugs [ROR (95% CI): 9.17 (8.87-9.48)], antibiotics [ROR (95% CI): 6.42 (5.91-6.96)], immunosuppressors [ROR (95% CI): 5.95 (5.55-6.39)], anti-inflammatory analgesics [ROR (95% CI): 4.65 (4.45-4.86)], antiallergic drugs [ROR (95% CI): 4.47 (3.99-5)], antiasthmatics [ROR (95% CI): 2.49 (2.14-2.89)], blood sugar control drugs [ROR (95% CI): 1.65 (1.38-1.97)], and digestive system drugs [ROR (95% CI): 1.59 (1.45-1.74)] exhibited progressively decreasing ROR values. Conclusion: Many medications are associated with a high risk of angioedema. These medications play a crucial and potentially preventable role in controlling the occurrence of angioedema. It is essential to consider the risk level of druginduced angioedema in clinical practice to optimize medication therapy. [ABSTRACT FROM AUTHOR]

Background: Despite significant progress in cardiovascular disease (CVD) management, it remains a public health priority and a global challenge. Within the disease process, health care after a cardiovascular event (secondary prevention) is essential to prevent recurrences. Nonetheless, evidence has suggested the existence of gender disparities in CVD management, leaving women in a vulnerable situation. The objective of this study is to identify all available evidence on the existence of gender differences in health care attention after a major adverse cardiovascular event. Methods: A scoping review following the structure of PRISMA-ScR was conducted. To define the inclusion criteria, we used Joanna Briggs Institute (JBI) population, concept, context framework for scoping reviews. A systematic search was performed in MEDLINE (PubMed), EMBASE and Cochrane. The methods of this review are registered in the International Platform of Registered Systematic Review and Meta-Analysis Protocols (INPLASY) (INPLASY202350084). Results: The initial search retrieved 3,322 studies. 26 articles were identified manually. After the reviewing process, 93 articles were finally included. The main intervention studied was the pharmacological treatment received (n = 61, 66%), distantly followed by guideline-recommended care (n = 26, 28%) and cardiac rehabilitation (CR) referral (n = 16)". Literature described gender differences in care and management of secondary prevention of CVD. Women were less frequently treated with guideline-recommended medications and seem more likely to be non-adherent. When analysing guideline recommendations, women were more likely to make dietary changes, however, men were more likely to increase physical activity. Studies also showed that women had lower rates of risk factor testing and cholesterol goals attainment. Female sex was associated with lower rates of cardiac rehabilitation referral and participation. Conclusions: This review allowed us to compile knowledge on the existence of gender inequalities on the secondary prevention of CVD. Additional research is required to delve into various factors influencing therapeutic disparities, referral and non-participation in CR programs, among other aspects, in order to improve existing knowledge about the management and treatment of CVD in men and women. This approach is crucial to ensure the most equitable and effective attention to this issue. [ABSTRACT FROM AUTHOR]

Background: Adverse drug reactions (ADRs) represent a significant barrier to achieve optimal treatment outcomes. Cardiovascular drugs, including antihypertensive drugs, lipid-lowering drugs, and antithrombotic drugs, are among the most prescribed medications in the primary care setting. Objectives: To estimate the prevalence of cardiovascular drug-related ADRs consultations in United Kingdom (UK) primary care and identify risk factors of these ADRs. Methods: This was a cross-sectional study of cardiovascular drug users between 2000–2019 using UK IQVIA Medical Research Data. ADRs consultations were identified using database screening method employing standardised designated codes. The overall and annual age-standardised prevalence was estimated using direct standardisation method using 2019 mid-year UK population. Risk factors of ADRs consultations were estimated using logistic regression model stratified by therapeutic areas. Results: The standardised prevalence of consultations related to cardiovascular drugs ADRs was 10.60 (95% CI. 10.46, 10.75) per 1000 patients. Patients aged 70–79 years had the highest occurrence of ADRs consultations. The most frequently drug classes implicated in the ADRs consultations were statins (n = 9,993 events, 27.09%), beta-blockers (n = 8,538 events, 23.15%), ACEIs/ARBs (n = 8,345 events, 22.62%), and aspirin (n = 6,482 events, 17.57%). Risk factors of ADRs consultations were previous history of cardiovascular diseases, e.g., myocardial infarction and stroke; advanced age, comorbidities; diabetes and dyslipidaemia; and polypharmacy. Conclusions: The burden of cardiovascular drug-related ADRs consultations in primary care was considerable. Statins, beta-blockers, ACEIs/ARBs, and aspirin were the most frequently implicated drug classes. Closer clinical monitoring should be performed for patients affected by the ADRs to mitigate the risk of suboptimal treatment outcomes. [ABSTRACT FROM AUTHOR]

Recurrent events, including cardiovascular events, are commonly observed in biomedical studies. Understanding the effects of various treatments on recurrent events and investigating the underlying mediation mechanisms by which treatments may reduce the frequency of recurrent events are crucial tasks for researchers. Although causal inference methods for recurrent event data have been proposed, they cannot be used to assess mediation. This study proposed a novel methodology of causal mediation analysis that accommodates recurrent outcomes of interest in a given individual. A formal definition of causal estimands (direct and indirect effects) within a counterfactual framework is given, and empirical expressions for these effects are identified. To estimate these effects, a semiparametric estimator with triple robustness against model misspecification was developed. The proposed methodology was demonstrated in a real‐world application. The method was applied to measure the effects of two diabetes drugs on the recurrence of cardiovascular disease and to examine the mediating role of kidney function in this process. [ABSTRACT FROM AUTHOR]

AbstractObjectivesDesignSettingParticipantsMain Outcome MeasuresResultsConclusionThis study compares the demographics, diagnoses, re-admission rates, sick leaves, and prescribed medications of patients accessing digital general practitioner (GP) visits with those of patients opting for traditional face-to-face appointments in a primary health care setting.The study adopted a retrospective analysis of patient record data collected in 2019, comparing visits to a digital primary health center with traditional health center visits.Primary health care.The data encompassed patients who utilized the digital clinic and those who visited public health centers for primary health care services.The study assessed demographics, health diagnoses, prescribed medications, sick leave recommendations, re-admission rates, and differences in costs between digital clinic and face-to-face visits. Secondary outcomes included a comparative analysis of medication categories, resolution rates for health problems, and potential impacts on health care utilization.Digital clinic users were typically younger, more educated, and predominantly female compared with health centre users. Digital visits were well-suited for uncomplicated infections, while health centre appointments were associated with a higher prevalence of chronic conditions. Medication patterns differed between the two modalities, with digital clinic users receiving generic over-the-counter drugs and antibiotics, whereas health centre visits commonly involved cardiac and antihypertensive medications. Sick leave recommendations were slightly higher in the digital clinic, but the difference was not significant. Approximately 70% of health problems addressed in the digital clinic were successfully resolved, and the cost of digital visits was about 50,3% of face-to-face appointments.Digital health care services offer a cost-efficient alternative for specific health problems, appealing to younger, educated individuals, when compared to the users of public health center, and may enable improvement of cost-effectiveness combined with acceptable demand management and patient segmentation practices. The results highlight the potential benefits of digital clinics, particularly for uncomplicated cases, while also emphasizing the importance of suitable referral mechanisms for in-person consultations. [ABSTRACT FROM AUTHOR]

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have emerged as a promising tool for studying cardiac physiology and drug responses. However, their use is largely limited by an immature phenotype and lack of high-throughput analytical methodology. In this study, we developed a high-throughput testing platform utilizing hPSC-CMs to assess the cardiotoxicity and effectiveness of drugs. Following an optimized differentiation and maturation protocol, hPSC-CMs exhibited mature CM morphology, phenotype, and functionality, making them suitable for drug testing applications. We monitored intracellular calcium dynamics using calcium imaging techniques to measure spontaneous calcium oscillations in hPSC-CMs in the presence or absence of test compounds. For the cardiotoxicity test, hPSC-CMs were treated with various compounds, and calcium flux was measured to evaluate their effects on calcium dynamics. We found that cardiotoxic drugs withdrawn due to adverse drug reactions, including encainide, mibefradil, and cetirizine, exhibited toxicity in hPSC-CMs but not in HEK293-hERG cells. Additionally, in the effectiveness test, hPSC-CMs were exposed to ATX-II, a sodium current inducer for mimicking long QT syndrome type 3, followed by exposure to test compounds. The observed changes in calcium dynamics following drug exposure demonstrated the utility of hPSC-CMs as a versatile model system for assessing both cardiotoxicity and drug efficacy. Overall, our findings highlight the potential of hPSC-CMs in advancing drug discovery and development, which offer a physiologically relevant platform for the preclinical screening of novel therapeutics. [ABSTRACT FROM AUTHOR]

With the increase in life expectancy, aging has emerged as a significant health concern. Due to its various mechanisms of action, cardiometabolic drugs are often repurposed for other indications, including aging. This systematic review analyzed and highlighted the repositioning potential of cardiometabolic drugs to increase lifespan as an aging parameter in animal studies and supplemented by information from current clinical trial registries. Systematic searching in animal studies was performed based on PICO: "animal," "cardiometabolic drug," and "lifespan." All clinical trial registries were also searched from the WHO International Clinical Trial Registry Platform (ICTRP). Analysis of 49 animal trials and 10 clinical trial registries show that various cardiovascular and metabolic drugs have the potential to target lifespan. Metformin, acarbose, and aspirin are the three most studied drugs in animal trials. Aspirin and acarbose are the promising ones, whereas metformin exhibits various results. In clinical trial registries, metformin, omega-3 fatty acid, acarbose, and atorvastatin are currently cardiometabolic drugs that are repurposed to target aging. Published clinical trial results show great potential for omega-3 and metformin in healthspan. Systematic Review Registration: crd.york.ac.uk/prospero/display_record.php?RecordID=457358, identifier: CRD42023457358. [ABSTRACT FROM AUTHOR]

Background: Zolpidem is a non-benzodiazepine hypnotic widely used to manage insomnia. Zolpidem-triggered atrial fibrillation (AF) in patients with cardiomyopathy has never been reported before. Case presentation: A 40-year-old man with Duchenne muscular dystrophy-related cardiomyopathy attempted suicide and developed new-onset AF after zolpidem overdose. One year before admission, the patient visited our clinic due to chest discomfort and fatigue after daily walks for 1 month; both electrocardiography (ECG) and 24-hour Holter ECG results did not detect AF. After administration of cardiac medication (digoxin 0.125 mg/day, spironolactone 40 mg/day, furosemide 20 mg/day, bisoprolol 5 mg/day, sacubitril/valsartan 12/13 mg/day), he felt better. AF had never been observed before this admission via continuous monitoring during follow-up. Sixteen days before admission, the patient saw a sleep specialist and started zolpidem tartrate tablets (10 mg/day) due to insomnia for 6 months; ECG results revealed no significant change. The night before admission, the patient attempted suicide by overdosing on 40 mg of zolpidem after an argument, which resulted in severe lethargy. Upon admission, his ECG revealed new-onset AF, necessitating immediate cessation of zolpidem. Nine hours into admission, AF spontaneously terminated into normal sinus rhythm. Results from the ECG on the following days and the 24-hour Holter ECG at 1-month follow-up showed that AF was not detected. Conclusions: This study provides valuable clinical evidence indicating that zolpidem overdose may induce AF in patients with cardiomyopathy. It serves as a critical warning for clinicians when prescribing zolpidem, particularly for patients with existing heart conditions. Further large-scale studies are needed to validate this finding and to explore the mechanisms between zolpidem and AF. [ABSTRACT FROM AUTHOR]

Aims: Data on diuretic use in pregnancy are limited and inconsistent, and consequently it remains unclear whether they can be used safely. Our study aims to evaluate the perinatal outcomes after in‐utero diuretic exposure. Methods and results: The Registry Of Pregnancy And Cardiac disease (ROPAC) is a prospective, global registry of pregnancies in women with heart disease. Outcomes were compared between women who used diuretics during pregnancy versus those who did not. Multivariable regression analysis was used to assess the impact of diuretic use on the occurrence of congenital anomalies and foetal growth. Diuretics were used in 382 (6.7%) of the 5739 ROPAC pregnancies, most often furosemide (86%). Age >35 years (odds ratio [OR] 1.5, 95% confidence interval [CI] 1.2–2.0), other cardiac medication use (OR 5.4, 95% CI 4.2–6.9), signs of heart failure (OR 1.7, 95% CI 1.2–2.2), estimated left ventricular ejection fraction <40% (OR 2.9, 95% CI 2.0–4.2), New York Heart Association class >II (OR 3.4, 95% CI 2.3–5.1), valvular heart disease (OR 6.3, 95% CI 4.7–8.3) and cardiomyopathy (OR 3.9, 95% CI 2.6–5.7) were associated with diuretic use during pregnancy. In multivariable analysis, diuretic use during the first trimester was not significantly associated with foetal or neonatal congenital anomalies (OR 1.3, 95% CI 0.7–2.6), and diuretic use during pregnancy was also not significantly associated with small for gestational age (OR 1.4, 95% CI 1.0–1.9). Conclusions: Our study does not conclusively establish an association between diuretic use during pregnancy and adverse foetal outcomes. Given these findings, it is essential to assess the risk–benefit ratio on an individual basis to guide clinical decisions. [ABSTRACT FROM AUTHOR]

Background: Adverse drug reactions (ADRs) refer to an unintended harmful reaction that occurs after the administration of a medication for therapeutic purposes, which is unrelated to the intended pharmacological action of the drug. In the United States, ADRs account for 6% of all hospital admissions annually. The cost of ADR-related illnesses in 2016 was estimated at USD 528.4 billion. Increasing the awareness of ADRs is an effective measure to prevent them. Assessing suspected drugs in adverse events helps to enhance the awareness of ADRs. Methods: In this study, a suspect drug assisted judgment model (SDAJM) is designed to identify suspected drugs in adverse events. This framework utilizes the graph isomorphism network (GIN) and an attention mechanism to extract features based on patients' demographic information, drug information, and ADR information. Results: By comparing it with other models, the results of various tests show that this model performs well in predicting the suspected drugs in adverse reaction events. ADR signal detection was conducted on a group of cardiovascular system drugs, and case analyses were performed on two classic drugs, Mexiletine and Captopril, as well as on two classic antithyroid drugs. The results indicate that the model can accomplish the task of predicting drug ADRs. Validation using benchmark datasets from ten drug discovery domains shows that the model is applicable to classification tasks on the Tox21 and SIDER datasets. Conclusions: This study applies deep learning methods to construct the SDAJM model for three purposes: (1) identifying drugs suspected to cause adverse drug events (ADEs), (2) predicting the ADRs of drugs, and (3) other drug discovery tasks. The results indicate that this method can offer new directions for research in the field of ADRs. [ABSTRACT FROM AUTHOR]

Increasing knowledge of the processes leading to heart failure (HF) has allowed significant developments in therapies for HF over the past few decades. Despite the evolution of HF treatment, it still places a large burden on patients and health care systems across the world. We used clinicaltrials.gov to gather information about clinical trials as of August 2023 studying pharmacotherapy for HF. We included interventional trials that were "active, not recruiting", "recruiting", or looking for participants but "not yet recruiting". In total, 119 studies met our criteria of ongoing clinical trials studying novel as well as currently approved HF pharmacotherapies. The major interventions were novel medications/already approved medications for other diseases 29 % (34 trials), sodium-glucose co-transporter inhibitors 21 % (25 trials), angiotensin receptor blocker-neprilysin inhibitors 10 % (12 trials), diuretics 14 % (17 trials) and mineralocorticoid receptor antagonists 5 % (6 trials). Ongoing research will aid in reducing the impact of HF and we summarize clinical trials leading the way to better HF treatment in this review. [ABSTRACT FROM AUTHOR]

Background: Friedreich ataxia is a rare genetic disorder associated with progressive mitochondrial dysfunction leading to widespread sequelae including ataxia, muscle weakness, hypertrophic cardiomyopathy, diabetes mellitus, and neuromuscular scoliosis. Children with Friedreich ataxia are at high risk for periprocedural complications during posterior spinal fusion due to their comorbidities. Aim: To describe our single‐center perioperative management of patients with Friedreich ataxia undergoing posterior spinal fusion. Methods: Adolescent patients with Friedreich ataxia presenting for spinal deformity surgery between 2007 and 2023 were included in this retrospective case series performed at the Children's Hospital of Philadelphia. Perioperative outcomes were reviewed along with preoperative characteristics, intraoperative anesthetic management, and postoperative medical management. Results: Seventeen patients were included in the final analysis. The mean age was 15 ± 2 years old and 47% were female. Preoperatively, 35% were wheelchair dependent, 100% had mild‐to‐moderate hypertrophic cardiomyopathy with preserved systolic function and no left ventricular outflow tract obstruction, 29% were on cardiac medications, and 29% were on pain medications. Intraoperatively, 53% had transesophageal echocardiography monitoring; 12% had changes in volume status on echo but no changes in function. Numerous combinations of total intravenous anesthetic agents were used, most commonly propofol, remifentanil, and ketamine. Baseline neuromonitoring signals were poor in four patients and one patient lost signals, resulting in 4 (24%) wake‐up tests. The majority (75%) were extubated in the operating room. Postoperative complications were high (88%) and ranged from minor complications like nausea/vomiting (18%) to major complications like hypotension/tachycardia (29%) and need for extracorporeal membrane oxygenation support in one patient (6%). Conclusions: Patients with Friedreich ataxia are at high risk for perioperative complications when undergoing posterior spinal fusion and coordinated multidisciplinary care is required at each stage. Future research should focus on the utility of intraoperative echocardiography, optimal anesthetic agent selection, and targeted fluid management to reduce postoperative cardiac complications. [ABSTRACT FROM AUTHOR]

Pharmaceuticals and drugs of abuse are organic micropollutants of emerging concern in both surface and groundwater worldwide. These compounds are considered to be pseudo‐persistent because of their continuous release into water systems. The presence of these compounds in the environment at any concentration poses a potential risk to nontarget organisms. The main sources of these contaminants are wastewater treatment plants (WWTPs) and combined sewer overflows (CSOs). The primary goal of our study was to identify and quantify a panel of 28 commonly prescribed pharmaceuticals (mood‐altering drugs, cardiovascular drugs, antacids, antibiotics) and high‐prevalence drugs of abuse (cocaine, amphetamines, opioids, cannabis) in river water samples collected from 19 locations in the Hudson and East rivers in New York City. The second goal was to investigate the possible source (WWTP or CSOs) of these micropollutants. Samples were collected weekly from May to August 2021 (n = 224) and May to August 2022 (n = 232), and placed at −20 °C until analysis by liquid chromatography–tandem mass spectrometry. The most frequently detected analytes in 2021 were metoprolol (n = 206, 92%), benzoylecgonine (n = 151, 67%), atenolol (n = 142, 63%), and methamphetamine (n = 118, 53%), and in 2022 the most frequently detected were methamphetamine (n = 194, 84%), atenolol (n = 177, 76%), metoprolol (n = 177, 76%), and 2‐ethylene‐1,5‐dimethyl‐3,3‐diphenylpyrrolidine (n = 159, 69%). Measured concentrations ranged from the limit of detection (0.50–5.00 ng/L) to 103 ng/L. More drugs and higher concentrations were detected in water contaminated by Enterococci (>60 most probably number) and after rainfall, indicating the influence of CSOs. The presence of drugs in samples with little to no Enterococci and after dry weather events indicates that WWTPs contribute to the presence of these substances in the river, probably due to a low removal rate. Environ Toxicol Chem 2024;43:1592–1603. © 2024 SETAC [ABSTRACT FROM AUTHOR]

Pharmacogenetics can improve clinical outcomes by reducing adverse drug effects and enhancing therapeutic efficacy for commonly used drugs that treat a wide range of cardiovascular diseases. One of the major barriers to the clinical implementation of cardiovascular pharmacogenetics is limited education on this field for current healthcare providers and students. The abundance of pharmacogenetic literature underscores its promise, but it can also be challenging to learn such a wealth of information. Moreover, current clinical recommendations for cardiovascular pharmacogenetics can be confusing because they are outdated, incomplete, or inconsistent. A myriad of misconceptions about the promise and feasibility of cardiovascular pharmacogenetics among healthcare providers also has halted clinical implementation. Therefore, the main goal of this tutorial is to provide introductory education on the use of cardiovascular pharmacogenetics in clinical practice. The target audience is any healthcare provider (or student) with patients that use or have indications for cardiovascular drugs. This tutorial is organized into the following 6 steps: (1) understand basic concepts in pharmacogenetics; (2) gain foundational knowledge of cardiovascular pharmacogenetics; (3) learn the different organizations that release cardiovascular pharmacogenetic guidelines and recommendations; (4) know the current cardiovascular drugs/drug classes to focus on clinically and the supporting evidence; (5) discuss an example patient case of cardiovascular pharmacogenetics; and (6) develop an appreciation for emerging areas in cardiovascular pharmacogenetics. Ultimately, improved education among healthcare providers on cardiovascular pharmacogenetics will lead to a greater understanding for its potential in improving outcomes for a leading cause of morbidity and mortality.

Background Time-domain parameters are less reliable in children due to increased arterial and chest wall compliance. We assessed the ability of indices derived from frequency analysis of photoplethysmography (PPG) and arterial blood pressure (ABP) waveforms to predict the hemodynamic state in children undergoing congenital heart surgery. Methods We analyzed waveforms after cardiopulmonary bypass period in 76 children who underwent total repair of congenital heart disease. Amplitude density of baseline and amplitude modulation in PPG and ABP by respiratory frequency were obtained using fast Fourier transform analysis and normalized by cardiac pulse height (representing respiratory modulations in venous blood [PPG-DC%] and in amplitude [PPG-AC%] at respiratory frequency). The ratio of amplitude density of PPG at the cardiac frequency (CF) to ABP-CF was used to assess vascular compliance. We assessed volume replacement (ml/kg) and vasoactive inotropic score (VIS). Results Children requiring volume replacement > 10 ml/kg (15.8%) showed higher PPG-DC% than those not requiring it (median: 52.4%, 95% CI [24.8, 295.1] vs. 36.7% [10.7, 125.7], P = 0.017). In addition, children with a VIS > 7 (22.4%) showed higher PPG-CF/ABP-CF (3.6 [0.91, 10.8] vs. 1.2 [0.27, 5.5], P = 0.008). On receiver operating characteristic curve analysis, PPG-DC% predicted a higher fluid requirement (area under the curve: 0.71, 95% CI [0.604, 0.816], P = 0.009), while PPG-CF/ABP-CF predicted a higher VIS (0.714, [0.599, 0.812], P = 0.004). Conclusions Frequency domain analysis of PPG and ABP may assess hemodynamic status requiring fluid or vasoactive inotropic therapy after congenital heart surgery.

Introduction: Antihypertensive drugs are used preventatively to lower the risk of cardiovascular disease events. Comparative effectiveness studies on angiotensinconverting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), beta-blockers (BBs), calcium channel blockers (CCBs), and thiazides have yielded inconsistent results and given little consideration to patient adherence. Using a longitudinal cohort and considering time-varying adherence and confounding factors, we aimed to estimate the real-world effectiveness of five major antihypertensive drug monotherapies in the primary prevention of cardiovascular events. Methods: Eligible patients for a retrospective inception cohort study were selected using information obtained from the University of Groningen IADB.nl pharmacy prescription database. Cohort 1 comprised adherent patients with a follow-up time exceeding 1 year, and cohort 2 comprised all patients independent of adherence. The exposures were ACEIs, ARBs, BBs, CCBs, and thiazides. The primary outcome was the time to the first prescription for an acute cardiac drug therapy (CDT) measured using valid drug proxies to identify the first major cardiovascular event. A per-protocol analytical approach was adopted with inverse probability of treatment weighted (IPTW), time-varying Cox regression analysis to obtain the hazard ratios (HRs) and 95% confidence intervals (CIs). Results: In cohort 1 (n = 22,441), 1,294 patients (5.8%) were prescribed an acute CDT with an average follow-up time of 4.2 ± 2.8 years. Following IPTW, the hazard measures of ARBs and thiazides were lower than those of BBs (HRs: 0.79 and 0.80, respectively; 95% CIs: 0.64-0.97 and 0.69-0.94, respectively). Among drug-treated diabetic patients, the hazard measures were even lower, with HR point estimates of 0.43 (CI: 0.19-0.98) for ARBs and 0.32 (CI: 0.13-0.82) for thiazides. In cohort 2 (n = 33,427) and sensitivity analysis, the comparative effectiveness results for thiazides and BBs were similar to those for cohort 1. Conclusion: The findings of this real-world analysis suggest that the incidence of CDT associated with long-term thiazide or ARB monotherapy is lower than the incidence of CDTwith BBs, notably among high-risk patients. Incidences of CDT associated with ACEIs and CCBs were comparable relative to those associated with BBs. [ABSTRACT FROM AUTHOR]

Background: Emulation of the "target trial" (TT), a hypothetical pragmatic randomized controlled trial (RCT), using observational data can be used to mitigate issues commonly encountered in comparative effectiveness research (CER) when randomized trials are not logistically, ethically, or financially feasible. However, cardiovascular (CV) health research has been slow to adopt TT emulation. Here, we demonstrate the design and analysis of a TT emulation using electronic health records to study the comparative effectiveness of the addition of a disease-modifying anti-rheumatic drug (DMARD) to a regimen of methotrexate on CV events among rheumatoid arthritis (RA) patients. Methods: We used data from an electronic medical records-based cohort of RA patients from Northwestern Medicine to emulate the TT. Follow-up began 3 months after initial prescription of MTX (2000–2020) and included all available follow-up through June 30, 2020. Weighted pooled logistic regression was used to estimate differences in CVD risk and survival. Cloning was used to handle immortal time bias and weights to improve baseline and time-varying covariate imbalance. Results: We identified 659 eligible people with RA with average follow-up of 46 months and 31 MACE events. The month 24 adjusted risk difference for MACE comparing initiation vs non-initiation of a DMARD was -1.47% (95% confidence interval [CI]: -4.74, 1.95%), and the marginal hazard ratio (HR) was 0.72 (95% CI: 0.71, 1.23). In analyses subject to immortal time bias, the HR was 0.62 (95% CI: 0.29–1.44). Conclusion: In this sample, we did not observe evidence of differences in risk of MACE, a finding that is compatible with previously published meta-analyses of RCTs. Thoughtful application of the TT framework provides opportunities to conduct CER in observational data. Benchmarking results of observational analyses to previously published RCTs can lend credibility to interpretation. [ABSTRACT FROM AUTHOR]

Chronic wound treatments pose a challenge for healthcare worldwide, particularly for the people in developed countries. Chronic wounds significantly impair quality of life, especially among the elderly. Current research is devoted to novel approaches to wound care by repositioning cardiovascular agents for topical wound treatment. The emerging field of medicinal products' repurposing, which involves redirecting existing pharmaceuticals to new therapeutic uses, is a promising strategy. Recent studies suggest that medicinal products such as sartans, beta-blockers, and statins have unexplored potential, exhibiting multifaceted pharmacological properties that extend beyond their primary indications. The purpose of this review is to analyze the current state of knowledge on the repositioning of cardiovascular agents' use and their molecular mechanisms in the context of wound healing. [ABSTRACT FROM AUTHOR]

OBJECTIVE It is perceived by many pharmacists that inadequate training and the resulting lack of confidence hinder participation in medical emergencies. There is insufficient information detailing training programs for pharmacists responding to pediatric medical emergencies. The primary objective of this study was to compare competency scores pre and post participation in the pediatric medical emergency training (PedMET) program. The secondary objectives included comparing confidence and knowledge for participation in pediatric medical emergencies, knowledge of resources and error prevention tools, description of the median time to prepare medications, and the most common errors that occurred during simulation. METHODS A comprehensive didactic lecture and simulation-based training were designed and contained pre- and post-competencies to assess pharmacists' knowledge related to pediatric medical emergencies. Self-assessments were included to determine pharmacists' confidence levels in knowledge and preparation of medications. Feedback was solicited from participants to identify areas of improvement for the program. Standards for QUality Improvement Reporting Excellence (SQUIRE) 2.0 was used to report findings. RESULTS Twenty-nine pharmacists of diverse training (e.g., residency vs nonresidency) and experience levels completed the program between July 2021 and March 2023. Competency scores improved from a median of 86% to 97% (p value < 0.001). Significant improvement was detected in pharmacists' confidence in their ability to prepare complex medications during medical emergencies (p value = 0.001). CONCLUSIONS Following the implementation of didactic and simulation-based training, pharmacists' knowledge and confidence increased. Departments of pharmacy should consider implementing pharmacist-specific training programs for all pharmacists who respond to pediatric medical emergencies. [ABSTRACT FROM AUTHOR]

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been shown to improve outcomes in patients with heart failure (HF) and are now included in guideline-directed medical therapy. Trials reporting the change in loop diuretic dose following SGLT2i initiation have indicated conflicting results. There is no clear guidance on whether reducing loop diuretic doses following SGLT2i initiation is appropriate. Objective: The purpose of this study is to assess the impact of SGLT2i initiation on diuretic adjustment in hospitalized patients with known or new HF. Methods: This was a retrospective, single health-system study assessing the change in loop diuretic dose in the 60 days following discharge for patients with HF initiated on SGLT2i therapy during a hospital admission or upon discharge. Secondary outcomes assessed effect on renal function and discontinuation of SGLT2i within the 60 day follow up period. Results: Forty percent of patients required loop diuretic dose adjustment, with 29% requiring a dose reduction within the 60 days following discharge. There was minimal change in serum creatinine or blood urea nitrogen. The SGLT2i was discontinued in 6 patients. Conclusions: After inpatient initiation of SGLT2is, approximately one-third of patients required a reduction in loop diuretic dose within 60 days following hospital discharge. Further study is recommended to confirm if empiric diuretic dose adjustments are appropriate in this HF population. [ABSTRACT FROM AUTHOR]

Safety pharmacology examines the potential for new drugs to have unusual, rare side effects such as torsade de pointes (TdP). Recently, as a part of the Comprehensive in vitro Proarrhythmia Assay (CiPA) project, techniques for predicting the development of druginduced TdP through computer simulations have been proposed and verified. However, CiPA assessment generally does not consider the effect of cardiac cell inter-individual variability, especially related to metabolic status. The study aimed to explore whether rare proarrhythmic effects may be linked to the inter-individual variability of cardiac cells and whether incorporating this variability into computational models could alter the prediction of drugs' TdP risks. This study evaluated the contribution of two biological characteristics to the proarrhythmic effects. The first was spermine concentration, which varies with metabolic status; the second was L-type calcium permeability that could occur due to mutations. Twenty-eight drugs were examined throughout this study, and qNet was analyzed as an essential feature. Even though there were some discrepancies of TdP risk predictions from the baseline model, we found that considering the inter-individual variability might change the TdP risk of drugs. Several drugs in the high-risk drugs group were predicted to affect as intermediate and low-risk drugs in some individuals and vice versa. Also, most intermediaterisk drugs were expected to act as low-risk drugs. When compared, the effects of interindividual variability of L-type calcium were more significant than spermine in altering the TdP risk of compounds. These results emphasize the importance of considering interindividual variability to assess drugs. [ABSTRACT FROM AUTHOR]

Background: There are numerous publications on inpatient medication errors. However, little focus is given to medication errors that occur at home. Aims: To describe and analyse the types of medication errors among community-dwelling patients following their discharge from an acute care hospital in Singapore. Method: This is a retrospective review of a 'good catch' reporting system from December 2018 to March 2022. Medication-related errors were extracted and analysed. Findings: A total of 73 reported medication-related error incidents were reviewed. The mean age of the patients was 78 years old (SD=9). Most patients managed their medications independently at home (45.2%, n=33). The majority of medications involved were cardiovascular medications (51.5%, n=50). Incorrect dosing (41.1%, n=39) was the most common medication error reported. Poor understanding of medication usage (35.6%, n=26) and lack of awareness of medication changes after discharge (24.7%, n=18) were the primary causes of the errors. Conclusion: This study's findings provide valuable insights into reducing medication errors at home. More attention must be given to post-discharge care, especially to preventable medication errors. Medication administration and management education can be emphasised using teach-back methods. [ABSTRACT FROM AUTHOR]

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Purpose: Warfarin plays an important role in anticoagulation therapy despite the availability of the newest oral anticoagulants, and achieving optimal anticoagulation is challenging due to its narrow therapeutic range and variable dose. This study aimed to highlight polypharmacy and drug interactions in patients receiving warfarin therapy at Medani Heart Centre, Sudan. Methods: This retrospective hospital-based study was conducted from May 2017 to October 2018. Each concurrent medication prescribed for 104 patients was collected and checked for drug-drug interactions using Medscape Reference-Drug Interaction Checker. The data were analysed by using SPSS 20, and descriptive statistics were used. Results: The results revealed that 95.2% of patients had more than three medications in their profile, (3– 5), (6– 9) and more than 10 medications were prescribed for 40.4%, 44.2% and 10.6% of patients, respectively. A total of 93.3% of patients had drug-drug interactions, as follows: (1– 5), (6– 10), (11– 15), (16– 20) and more than 20 drug-drug interactions were found in 31.7%, 32.7%, 19.2%, 5.8% and 3.8% of patients, respectively. A total of 178 warfarin-drug interactions were identified in 88.5% of the patients. The INR ranged between 2 and 2.99 in 13.4% of patients, and INR values below 2 and above 5 were found in 44.2% and 21.2% of patients, respectively. Analgesics (n=54; 30.3%), cardiovascular drugs (n=51; 28.6%), and anticoagulants (n=46; 25.8%) were the most common drug classes that interact with warfarin. Significant and serious types of interactions with warfarin were found in 51% and 37.5% of patients, respectively. Conclusion: This study highlights the complexity of managing warfarin therapy amid prevalent polypharmacy. A substantial majority of patients experienced multiple drug interactions. The identification of significant and serious interactions emphasizes the need for vigilant management strategies, including improved communication among healthcare professionals and targeted education for both providers and patients, to enhance the safety and efficacy of warfarin therapy. [ABSTRACT FROM AUTHOR]

Objectives: (1) To investigate the prevalence of frailty defined by the Hospital Frailty Risk Score (HFRS), a new scale for assessing frailty, in older patients with acute coronary syndrome (ACS); (2) To identify associations between frailty and the prescriptions of cardiovascular medications, percutaneous coronary intervention (PCI) and in‐hospital adverse outcomes. Methods: An observational study was conducted in patients aged older than 60 years with ACS at Thong Nhat Hospital from August to December 2022. The Hospital Frailty Risk Score is retrospectively calculated for all participants based on ICD‐10 codes, and those with HFRS scores ≥5 were defined as frail. Logistic regression models were applied to examine the relationship between frailty and the study outcomes. Results: There were 511 participants in the study. The median age was 72.7, 60% were male and 29% were frail. Frailty was associated with lower odds of beta‐blocker use at admission (OR.49 95% CI.25–.94), treatment with PCI during hospitalisation (OR.48, 95% CI.30–.75), but did not show an association with prescriptions of cardiovascular drugs at discharge. Frailty was significantly associated with increased odds of adverse outcomes, including major bleeding (OR 4.07, 95% CI1.73–9.54), hospital‐acquired pneumonia (OR 2.55, 95% CI 1.20–5.42), all‐cause in‐hospital mortality (OR 3.14, 95% CI 1.37–7.20) and non‐cardiovascular in‐hospital mortality (OR 10.73, 95% CI 1.93–59.55). Conclusions: The HFRS was an effective tool for stratifying frailty and predicting adverse health outcomes in older patients with ACS. Further research is needed to compare the HFRS with other frailty assessment tools in this population. [ABSTRACT FROM AUTHOR]

Recently FDA-approved drugs for cardiovascular disease (CVD) require robust post-marketing surveillance. The objective of this study was to assess their safety using a large pharmacovigilance database. We analyzed adverse event (AE) reports for 17 drugs approved from 2014 to 2021, utilizing the FDA Adverse Event Reporting System (FAERS). Descriptive and disproportionality analyses were conducted by estimating the reporting odds ratio (ROR) and its 95% confidence interval. Among the 43,664,773 AE reports 97,702 (0.22%) were related to newly approved CVD drugs. No AEs were reported for finerenone and evinacumab. The results from the disproportionality analyses revealed potential risks of acute kidney injury (ROR = 8.24, 95% CI: 6.05–11.22), cardiac failure (ROR = 4.80, 95% CI: 3.82–6.05), and hypotension (ROR = 3.98, 95% CI: 3.44–4.61) among sacubitril/valsartan users. Additionally, ivabradine was found to be associated with tachycardia (ROR = 11.94, 95% CI: 8.35–17.08), abnormal feeling (ROR = 4.40, 95% CI: 2.70–7.18), and dizziness (ROR = 2.56, 95% CI: 1.68–3.90). This study identified specific safety concerns related to recently approved CVD drugs. Further research is required to understand the underlying mechanisms and clinical implications of these findings. [ABSTRACT FROM AUTHOR]

The article discusses the evolving field of cardiac safety in drug discovery and the need for integration with immunology. It highlights the historical evolution of cardiac safety assessments and the increasing attention given to hemodynamic and structural alterations. The article also discusses the emergence of novel models, such as in silico predictions and 3D tissue-based systems, and the importance of incorporating immune components in these models. It specifically focuses on the risk of immune-mediated myocarditis and the need for more complex human-based in vitro models. The article concludes by discussing the potential of advanced cellular models, such as organ-on-chip systems, in improving cardiac safety assessments and reducing animal testing. [Extracted from the article]

Objective: As a novel drug formulation, antibody drug conjugates (ADCs) are widely used in various types of cancer. However, clinically, there is a lack of attention to the CVD produced by them, as well as a lack of research on the real-world situation. Using the Food and Drug Administration Adverse Event Reporting System (FAERS) database, to ensure its clinical safety application, we analyzed post-marketing data on antitumor ADCs to identify risk factors and drugs associated with the risk of cardiovascular events. Research design and methods: We used OpenVigil 2.1 to conduct a database query for adverse events (AEs) reported to the FAERS database between the time the drug was launched and the second quarter of 2023. Cardiovascular adverse events (AEs) were grouped into fourteen narrow categories using the Standardized Medical Dictionary for Regulatory Activities (MedDRA) Queries (SMQs), and the reporting odds ratio (ROR) and the proportional reporting ratio (PRR) for reporting the association between different drugs and cardiovascular disease (CVD) risk were calculated. Results: In the FAERS database, 1863 AEs associated with CVD we studied were identified in patients receiving ADC therapy. Most reports came from people aged ≥65, but a significant number of cases were found to be unknown. The number of patients with antibody-drug conjugates (ADCs)-related CVD cases aged <18 years, 18–64 years, and≥ 65 years was 52 (2.79%), 586 (31.45%), and 613 (32.90%), respectively. The proportion of female patients (834, 44.77%) was higher than that of male patients (752, 40.37%). Death (770 reports), disability (9 reports), Hospitalization initial or prolonged (407 reports), and life-threatening reactions (187 reports). Of the 770 deaths reported, 103 (31.7%) were associated with brentuximab vedotin, 10 (24.4%) with sacituzumab govitecan, 22 (19.3%) with enfortumab vedotin, and 35 (34.7%) with trastuzumab emtansine.49 (41.2%) cases were associated with polatuzumab vedotin, 62 (29%) with trastuzumab deruxtecan, 423 (54.3%) with gemtuzumab ozogamicin, and 66 (38.8%) with inotuzumab ozogamicin. In a disproportionate number of SMQS, cardiac failure (n = 277) and embolic and thrombotic events, venous (n = 446) were the most frequently reported CVD-related AEs in ADCs. Conclusion: By mining the FAERS database, we provided relevant information on the association between ADC use and cardiovascular-associated AEs. ADCs were associated with increased cardiovascular toxicity, deserving distinct monitoring and appropriate management. Further research is needed to confirm these findings and assess causality. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate the recovery rate of the left ventricular systolic function of women diagnosed with peripartum cardiomyopathy receiving specialized care in rural Tanzania. Methods: In this observational study, women diagnosed with peripartum cardiomyopathy at a referral center in rural Tanzania between December 2015 and September 2021 were included. Women diagnosed between February and September 2021 were followed prospectively, those diagnosed between December 2015 and January 2021 were tracked back for a follow-up echocardiography. All participants received a clinical examination, a comprehensive echocardiogram, and a prescription of guideline-directed medical therapy. The primary outcome was recovery of the left ventricular systolic function (left ventricular ejection fraction > 50%). Results: Median age of the 110 participants was 28.5 years (range 17–45). At enrolment, 49 (45%) participants were already on cardiac medication, 50 (45%) had severe eccentric hypertrophy of the left ventricle, and the median left ventricular ejection fraction was 30% (range 15–46). After a median follow-up of 8.98 months (IQR 5.72–29.37), 61 (55%) participants were still on cardiac medication. Full recovery of the left ventricular systolic function was diagnosed in 76 (69%, 95% CI 59.6–77.6%) participants. In the multivariate analysis, a higher left ventricular ejection fraction at baseline was positively associated with full recovery (each 5% increase; OR 1.7, 95% CI 1.10–2.62, p = 0.012), while higher age was inversely associated (each 10 years increase; OR 0.40, 95% CI 0.19–0.82, p = 0.012). Conclusion: Left ventricular systolic function recovered completely in 69% of study participants with peripartum cardiomyopathy from rural Tanzania under specialized care. [ABSTRACT FROM AUTHOR]

Background: Healthcare costs are a major burden on the society of developing countries like India. Countries like India try to limit healthcare costs in support of generic medicine. So, the Indian government initiated the Jan Aushadhi scheme in 2008 to provide high-quality generic medication at a low cost. Aim: The aim of the study was to compare the cost difference between Jan Aushadhi generic pharmaceutical formulations and branded medications in Tamil Nadu. Settings and Design: Pharmaco economic - Cost minimization observational study. Methods and Material: Study Duration: Five months, from February 2023 to June 2023. Study Place: 10 Jan Aushadhi outlets from various districts of Tamil Nadu. Sampling technique: Convenience sampling technique Statistical analysis used: Mean median, mode and Percentage. Results: A total of 729 medications were available in 10 Jan Aushadhi outlets. The Jan Aushadhi outlet has the most cardiovascular medications and the fewest antimalarial medications among different categories of drugs. Erythropoietin has the biggest cost difference between the average cost of branded medications and Jan Aushadhi drug costs, while Digoxin has the lowest cost difference. Antitubercular drugs, Oxytocics, Antileprosy drugs, Antiparkinsonism categories of drugs also delisted in Jan Aushadhi outlet. Conclusions: Compared to branded drugs, Jan Aushadhi's generic drugs are 64.65 % less costly on an average as observed in our study. The manufacturer of Jan Aushadhi shops is a WHO and GMO-certified company, and they manufacture branded drugs. So, there will be no quality compromise in Jan Aushadhi's generic drugs. [ABSTRACT FROM AUTHOR]

To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury (DILI) caused by different drugs and their correlation with clinical indicators. The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests (RUCAM) scoring criteria and clinically diagnosed with DILI. Based on Chinese herbal medicine, cardiovascular drugs, non-steroidal anti-inflammatory drugs (NSAIDs), anti-infective drugs, and other drugs, patients were divided into five groups. Cytokines were measured by Luminex technology. Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. 73 patients were enrolled. Age among five groups was statistically different (P = 0.032). Alanine aminotransferase (ALT) (P = 0.033) and aspartate aminotransferase (AST) (P = 0.007) in NSAIDs group were higher than those in chinese herbal medicine group. Interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in patients with Chinese herbal medicine (IL-6: P < 0.001; TNF-α: P < 0.001) and cardiovascular medicine (IL-6: P = 0.020; TNF-α: P = 0.001) were lower than those in NSAIDs group. There was a positive correlation between ALT (r = 0.697, P = 0.025), AST (r = 0.721, P = 0.019), and IL-6 in NSAIDs group. Older age may be more prone to DILI. Patients with NSAIDs have more severe liver damage in early stages of DILI, TNF-α and IL-6 may partake the inflammatory process of DILI. [ABSTRACT FROM AUTHOR]