Current Medications Research Articles

Potential drug targets for myocardial infarction identified through Mendelian randomization analysis and Genetic colocalization.

Myocardial infarction (MI) is a major cause of death and disability worldwide, but current treatments are limited by their invasiveness, side effects, and lack of efficacy. Novel drug targets for MI prevention are urgently needed. In this study, we used Mendelian randomization to identify potential therapeutic targets for MI using plasma protein quantitative trait loci as exposure variables and MI as the outcome variable. We further validated our findings using reverse causation analysis, Bayesian co-localization analysis, and external datasets. We also constructed a protein-protein interaction network to explore the relationships between the identified proteins and known MI targets. Our analysis revealed 2 proteins, LPA and APOA5, as potential drug targets for MI, with causal effects on MI risk confirmed by multiple lines of evidence. LPA and APOA5 are involved in lipid metabolism and interact with target proteins of current MI medications. We also found 4 other proteins, IL1RN, FN1, NT5C, and SEMA3C, that may have potential as drug targets but require further confirmation. Our study demonstrates the utility of Mendelian randomization and protein quantitative trait loci in discovering novel drug targets for complex diseases such as MI. It provides insights into the underlying mechanisms of MI pathology and treatment.

Efficacy of fecal microbiota transplantation in patients with Parkinson’s disease: clinical trial results from a randomized, placebo-controlled design

ABSTRACT The occurrence and development of Parkinson’s disease (PD) have been demonstrated to be related to gut dysbiosis, however, the impact of fecal microbiota transplantation (FMT) on microbiota engraftment in PD patients is uncertain. We performed a randomized, placebo-controlled trial at the Department of Neurology, Army Medical University Southwest Hospital in China (ChiCTR1900021405) from February 2019 to December 2019. Fifty-six participants with mild to moderate PD (Hoehn-Yahr stage 1–3) were randomly assigned to the FMT and placebo group, 27 patients in the FMT group and 27 in the placebo group completed the whole trial. During the follow-up, no severe adverse effect was observed, and patients with FMT treatment showed significant improvement in PD-related autonomic symptoms compared with the placebo group at the end of this trial (MDS-UPDRS total score, group×time effect, B = -6.56 [−12.98, −0.13], P < 0.05). Additionally, FMT improved gastrointestinal disorders and a marked increase in the complexity of the microecological system in patients. This study demonstrated that FMT through oral administration is clinically feasible and has the potential to improve the effectiveness of current medications in the clinical symptoms of PD patients.

Saururus chinensis water-extract effectively controls asthma by ameliorating of Th1/Th2 imbalance and suppressing of NF-κB/COX-2/PGE2-related inflammation

Asthma is an incurable chronic inflammatory pulmonary hyperresponsiveness. As current medications have many adverse effects, the development of new drugs is required. To define the anti-asthmatic effect of Saururus chinensis, animal and RAW264.7 cell models were used. Histopathological evaluation such as H&E and PAS staining; inflammatory cell analysis, such as cell count using equipment and Diff-Quick staining; serum IgE measurement; and asthma/inflammation-related proteins evaluation via RT-PCR, immunofluorescence, ELISA, immunohistochemistry, and western blotting were conducted. In animal study, S. chinensis prevented asthmatic pulmonary changes, such as epithelial cells hyperplasia, inflammatory cells increment, and mucous hypersecretion; controlled Th2 cell-related cytokines (IL-4 and IL-5) including GATA-3 and blocked inflammation occurrence via NF-κB/COX-2/PGE2 pathway. The anti-inflammatory effects and pathways of S. chinensis were confirmed in a cell-based study. Asthma is caused by both Th1/Th2 imbalance and inflammation and as S. chinensis effectively prevents the occurrence of asthma, it should be considered an anti-asthmatic candidate.

Protective efficacy of the oral vaccine Tc24:Co1 produced in Schizochytrium sp. against Trypanosoma cruzi infection in a mouse model

Trypanosoma cruzi parasite – causal Chagas disease agent - affects about 7 million people; no vaccine is available, and current medications have not been entirely effective. Multidisciplinary efforts are necessary for developing clinical vaccine prototypes. Thus, this research study aims to assess the expressed and whole-cell administration protection of the oral vaccine prototype Tc24:Co1 using Schizochytrium sp. microalga. High recombinant protein expression yields (675 μg/L) of algal culture were obtained. Additionally, Schizochytrium sp.-Tc24:Co1 resulted stable at 4 °C for up to six months and at 25 °C for three months. After receiving four oral doses of the vaccine, the mice showed a significant humoral immune response and a parasitemia reduction associated with a lack of heart inflammatory damage compared with the unvaccinated controls. The Schizochytrium sp.-Tc24:Co1 vaccine demonstrates to be promising as a prototype for further development showing protective effects against a T. cruzi challenge in a mouse model.

Formulation development and evaluation of fluvastatin loaded transethosomes: Characterization, stability, in vitro dermal penetration, cytotoxicity and antipsoriatic activity studies

Psoriasis, a common immune-mediated chronic inflammatory disease, may arise from genetic, epigenetic, and immune system factors. Current medications focus on symptom relief, presenting a challenge in discovering new compounds or methods for safe and effective psoriasis management while ensuring patient adherence. Statin drugs like fluvastatin, initially for dyslipidemia, were considered beneficial for treating psoriasis. Thus the objective of this study was to formulate novel topical transethosomes as drug delivery systems for dermal administration of fluvastatin sodium (fluvastatin) in psoriasis treatment. The thin film hydration method was exploited to prepare fluvastatin loaded transethosomes consisted of Phospholipon 90 as the phospholipid, along with Tween 20 or Tween 80 as the edge activators. The physicochemical properties of the transethosomes, including particle size and size distribution, zeta potential, encapsulation efficiency, pH, and conductivity, were evaluated. Attenuated Total Reflectance Fourier Transformed Infrared (ATR-FTIR) analysis was conducted to determine the structural characteristics, while Transmission Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM) analyses were employed to examine the morphological properties. Additionally, the stability of the transethosomes was monitored. Transfersome-type delivery systems were also developed for comparison with the transethosome formulations. The in vitro skin penetration and deposition behavior of fluvastatin transethosomes were assessed using sequential tape stripping, ATR-FTIR Spectroscopy, and Confocal Laser Scanning Microscopy (CLSM) and compared to fluvastatin-loaded transfersomes. Furthermore, in vitro cell culture studies were conducted to evaluate the cytotoxicity and antipsoriatic activities of the fluvastatin-loaded transethosomal carrier systems that exhibited the highest dermal accumulation. The results suggest that fluvastatin-loaded transethosomes inhibit the IL6 and IL8 production in HaCaT cells compared to free fluvastatin. Overall, the aim of this research is to develop innovative, skin-compatible, and stable drug delivery systems that improve the effectiveness of psoriasis treatment. This would be achieved by targeting the active substance, fluvastatin, which is believed to have potential antipsoriatic effects, specifically to the affected area of the skin.

Effect of Bacille-Calmette-Guerin vaccine against rotenone-induced Parkinson's disease: Role of neuroinflammation and neurotransmitters.

Parkinson's disease (PD) is an extrapyramidal movement disorder associated with a hypokinetic condition generated by impairment in dopaminergic neuronal viability in the nigrostriatal region of the brain. Current medications can only provide symptomatic management; to date, no permanent cure is available. To compensate for this lacuna, researchers are gaining interest in antigen-based therapy, and Bacille-Calmette-Guerin (BCG) is one of the vaccineswith a high safety margin that acts by stimulating immunoreactive T-cells in the CNS and reducing expression of pro-inflammatory cytokines including interleukin (IL)-1β and tumor necrotic factor (TNF-α) to produce neuroprotection. A previous study reported that BCG exerts a neuroprotective effect against several neurodegenerative disorders, such as Alzheimer's disease. The objective of this study is to explore the neuroprotective effect of the BCG vaccine against the rotenone model of PD. Rotenone (1.5 mg/kg, s.c) for 28 days, and BCG vaccine (2 × 107 cfu, i.p) single dose was injected to rats, and behavioral assessments were performed on the 21st and 28th day. On the 29th day, rats were sacrificed, and brains were isolated for biochemical and neurochemical estimation. BCG vaccine significantly restored rotenone-induced motor deficits (open field test, narrow beam walk, and rotarod), biochemical levels (GSH, SOD, catalase, MDA, and nitrite), neurotransmitters (dopamine, 5-hydroxy tryptamine, norepinephrine, 3,4-dihydroxyphenylacetic acid, hemovanillic acid, and 5-hydroxy indoleacetic acid), and levels of inflammatory cytokines (IL-1β and TNF-α) in the striatum. It also prevents histopathological changes by reducing eosinophilic lesions in the striatum. From the results, we conclude that BCG vaccine showed neuroprotection through antioxidant and anti-inflammatory effect. Thus, in the future, it can be used as a neuroprotective agent for other neurological disorders, including PD.

Prescription patterns of antidiabetic and cardiovascular preventive medications in community-dwelling older adults with type 2 diabetes mellitus: a cross-sectional study.

To describe trends in antidiabetics drug prescription patterns in community-dwelling older adults with type 2 diabetes mellitus (T2DM) and to evaluate the use of cardiovascular preventive medications among those diagnosed with atherosclerotic cardiovascular disease (ASCVD). This cross-sectional, face-to-face interview study that comprised community-dwelling older adults (≥ 65 years) diagnosed with T2DM. The study questionnaire included the patients' demographics, clinical data, and current medication use. Patients with established ASCVD were further classified into low (i.e., not receiving evidence-based therapy or only one) and high (i.e., receiving at least two evidence-based therapies) composite score groups. Bivariate analysis followed by multivariable logistic regression analysis were performed to evaluate the demographic/clinical characteristics associated with the use of antidiabetic monotherapy/polytherapy and evidence-based pharmacotherapy. A total of 500 older adults were enrolled. The mean age of included participants was 73 ± 7 years, 310 participants (62%) were males, and 385 participants (77.0%) had established ASCVD. Antidiabetic monotherapy was reported in 251 participants (50.2%), with metformin followed by sulfonylureas being the most commonly prescribed drugs as monotherapy. The results of the multivariable analysis showed that age [odds ratio (OR) = 0.89, 95% CI: 0.85-0.94, P < 0.001], obesity (OR = 4.18, 95% CI: 1.63-10.36, P = 0.003), hypertension (OR = 4.2, 95% CI: 1.22-7.66, P = 0.04), and dyslipidemia (OR = 4.1, 95% CI: 1.28-8.30, P = 0.01), were significantly associated with the prescription of cardiovascular preventive medications. Only one in twenty-one participant with T2DM and ASCVD collectively received three guideline-recommended therapies, indicating a deficiency of utilization of cardiovascular preventive drugs.

Clinical variables associated with late-onset thrombotic and cardiovascular events, after SARS-CoV-2 infection, in a cohort of patients from the first epidemic wave: an 18-month analysis on the “Surviving-COVID” cohort from Bergamo, Italy

ImportancePopulation studies have recorded an increased, unexplained risk of post-acute cardiovascular and thrombotic events, up to 1 year after acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.ObjectivesTo search for clinical variables and biomarkers associated with late post-acute thrombotic and cardiovascular events after SARS-CoV-2 infection.DesignRetrospective cohort study.SettingThird-level referral hospital in Bergamo (Italy).ParticipantsAnalysis of an existing database of adult patients, who received care for SARS-CoV-2 infection at our institution between 20 February and 30 September 2020, followed up on a single date (“entry date”) at 3–6 months.ExposureInitial infection by SARS-CoV-2.Main outcomes and measuresPrimary outcome: occurrence, in the 18 months after entry date, of a composite endpoint, defined by the International Classification of Diseases—9th edition (ICD-9) codes for at least one of: cerebral/cardiac ischemia, venous/arterial thrombosis (any site), pulmonary embolism, cardiac arrhythmia, heart failure. Measures (as recorded on entry date): history of initial infection, symptoms, current medications, pulmonary function test, blood tests results, and semi-quantitative radiographic lung damage (BRIXIA score). Individual clinical data were matched to hospitalizations, voluntary vaccination against SARS-CoV-2 (according to regulations and product availability), and documented reinfections in the following 18 months, as recorded in the provincial Health Authority database. A multivariable Cox proportional hazard model (including vaccine doses as a time-dependent variable) was fitted, adjusting for potential confounders. We report associations as hazard ratios (HR) and 95% confidence intervals (CI).ResultsAmong 1,515 patients (948 men, 62.6%, median age 59; interquartile range: 50–69), we identified 84 endpoint events, occurring to 75 patients (5%): 30 arterial thromboses, 11 venous thromboses, 28 arrhythmic and 24 heart failure events. From a multivariable Cox model, we found the following significant associations with the outcome: previous occurrence of any outcome event, in the 18 months before infection (HR: 2.38; 95% CI: 1.23–4.62); BRIXIA score ≥ 3 (HR: 2.43; 95% CI: 1.30–4.55); neutrophils-to-lymphocytes ratio ≥ 3.3 (HR: 2.60; 95% CI: 1.43–4.72), and estimated glomerular filtration rate &amp;lt; 45 ml/min/1.73 m2 (HR: 3.84; 95% CI: 1.49–9.91).Conclusions and relevanceWe identified four clinical variables, associated with the occurrence of post-acute thrombotic and cardiovascular events, after SARS-CoV-2 infection. Further research is needed, to confirm these results.

Evaluation of Anti-Inflammatory and Analgesic Property of Methanolic Extract of Momordica Dioica in Wistar Rat Model

Background: Since current medications frequently cause potentially serious side effects, countless individuals continued to have pain and inflammation despite the accessibility of treatments. Ancient practitioners have used a variety of herbal remedies with analgesic and anti-inflammatory properties extensively. Momordica Dioica is one of them, but no experimental research has been done in support of this traditional use. Objective: The purpose of the research was to assess the analgesic and anti-inflammatory properties of methanolic Momordica Dioica fruit extracts. Methods: Dryed by air According to OECD guideline the version eighteen, the fruit of Momordica Dioica is extracted with the solvent methanol as well as an acute oral toxicity study was done for the methanol-based extract of Momordica Dioica. The Active Constituent responsible for the Activity was confirmed by HPTLC method. The hot plate method was employed to assess the analgesic efficacy of centrally mediated analgesia.The ability to reduce inflammation was assessed using a carrageenan-induced paw oedema test. Results: Momordica dioica's methanolic extract inhibits the ceiling result during activity. The Methanolic Extract of Momordica dioica (MEMD) extract demonstrated a significant (p 0.0001) analgesic effect in the hot plate method at doses of 100mg/kg and in all combinations with standard. Maximum anti-inflammatory effects were seen in carrageenan-induced paw edema starting 2-4 hours after induction, and all tested doses of the extract significantly inhibited the carrageenan-induced inflammation (p 0.0001, p 0.001). The presence of a pentacyclic terpenoid i.e Ursolic acid present in the extract had potential analgesic and anti-inflammatory activity which supports the traditional claim.

Screening of Natural Compounds for CYP11A1 Stimulation Against Cell Renal Cell Carcinoma

BackgroundRenal cancer therapies are challenging owing to the extensive spreading of this cancer to other organs and its ability to pose resistance to current medications. Therefore, drugs targeting novel targets are urgently required to overcome these challenges. The cholesterol side-chain cleavage enzyme (CYP11A1) is closely associated with steroidogenesis, and its downregulation is linked to adrenal dysfunction and several types of carcinoma. We previously found that overexpression of CYP11A1 inhibited epithelial-mesenchymal transition and induced G2/M arrest in the kidney cancer Caki-1 cell line. In this context, natural compounds that exhibit potent CYP11A1 stimulation activity can be promising therpaeutic agents for kidney cancer.MethodsWe screened a panel of 1374 natural compounds in a wound-healing assay using CYP11A1-transfected Caki-1 cells. Of these, 167 promising biologically active compounds that inhibited cancer cell migration by more than 75% were selected, and their half-maximal inhibitory concentrations (IC50) were determined. The IC50 of 159 compounds was determined and 38 compounds with IC50 values less than 50 µM were selected for further analysis. Steroid hormones (cholesterol and pregnenolone) levels in cells treated with the selected compounds were quantitated using LC–MS/MS to determine their effect on CYP11A1 activity. Western blotting for CYP11A1, autophagy signaling proteins, and ferroptosis regulators were performed to ivestigate the mechanisms underlying the action of the selected compounds.ResultsWe screened five promising natural lead compounds that inhibited cancer cell proliferation after three screening steps. The IC50 of these compounds was determined to be between 5.9 and 14.6 μM. These candidate compounds increased the expression of CYP11A1 and suppressed cholesterol levels while increasing pregnenolone levels, which is consistent with the activation of CYP11A1. Our results showed that CYP11A1 activation inhibited the migration of cancer cells, promoted ferroptosis, and triggered autophagy signaling.ConclusionsThis study indicates that the CYP11A1-overexpressing Caki-1 cell line is useful for screening drugs against kidney cancer. The two selected compounds could be utilized as lead compounds for anticancer drug discovery, and specifically for the development of antirenal cancer medication.

The Lack of Tolerable Treatments Options That Can Induce Durable Responses without Fear of Relapse after Discontinuation Represents a Significant Unmet Need for Patients (Pts) with Immune Thrombocytopenia (ITP): Results from the ITP World Impact Survey (I-WISh) 2.0

Background: ITP is an acquired autoimmune disease characterized by transient or persistent thrombocytopenia. ITP substantially impairs pts' quality of life (QoL), including daily activities, social interactions, work and emotional wellbeing, with fatigue being the most common symptom reported by pts. Corticosteroids are the standard first-line treatment for ITP, while thrombopoietin receptor agonists (TPO-RAs), rituximab and fostamatinib are recommended for later lines; however, these treatments have limited sustained efficacy and may be associated with short- and long-term side effects that impact QoL. Aim: To assess pt and physician (MD) perceptions of current ITP treatment and treatment goals using data from I-WISh 2.0. Methods: I-WISh 2.0 was developed using findings from I-WISh 1.0 and surveyed 1018 pts with ITP aged &amp;gt;18 years and 431 MDs who managed ≥3 pts with ITP. I-WISh 2.0 was conducted from February to July 2022 in 15 countries. The surveys, developed by a steering committee (supported by Novartis) comprising expert ITP MDs and pt advocates, included questionnaires about prescribed ITP treatments, their impact on QoL and treatment satisfaction and goals. Results: Of 1018 pts (median age: 46 years), 67% were female and 48% reported ≥1 comorbidity. 97% (956/987) of pts had received ≥1 treatment for ITP and 12% (126/1018) had a splenectomy; 80% (811/1018) were receiving ITP treatment at survey completion and median time on most recent treatment was 30 weeks (n=608). Corticosteroids and TPO-RAs were the most common first- and second-line treatments prescribed by MDs, respectively (Figure 1); MDs estimated that 15% of their pts have opted against receiving ITP treatment (n=431). 73% of MDs (313/431) considered their pts' perception of medications when making treatment decisions. Pts reported a significant burden due to their current ITP medication: 34% (202/597) experienced daily disruption, 37% (214/576) were bothered by needing to plan meals, and 22% (204/939) had difficulty keeping up with daily medications. 19% (172/897) of pts were dissatisfied with their treatment's platelet level control, and 18% (155/843) disagreed that their medication effectively controlled their symptoms. Pts worried about their treatment's short- (48%; 400/833) and long-term (62%; 527/844) side effects. 38% (162/431) of MDs were neutral toward current ITP treatment options and 9% (37/431) were dissatisfied. Of the 37 dissatisfied MDs, limited options (68%), inability to achieve deep/stable remission (54%), lack of efficacy (43%) and inability to reach treatment goals (43%) were the most common reasons. 32% (327/1016) and 13% (127/1016) of pts believed they were not or did not know if they were in sustained remission, respectively. A treatment offering a sustained remission or cure for ITP was an important goal for 82% (823/1007) of pts. Of treatment goals mentioned in their top 3, the most common were healthy blood counts (56%), improving QoL (44%) and increasing energy levels (43%) for pts (n=1018), and reducing spontaneous bleeds (79%), healthy blood counts (60%) and improving QoL (52%) for MDs (n=431). Limiting time on treatment would substantially affect the treatment preference of 66% (668/1009) of pts. 38% (294/775) of pts did not want to take their ITP treatment for the foreseeable future; however, 67% (680/1013) were concerned about relapse if they stopped. Immunosuppression due to ITP treatment worried 414/787 (53%) pts, with 679/1007 (67%) considering it important when discussing treatment decisions. MDs considered corticosteroids and other immunosuppressants to have the most negative impact on fatigue (Figure 2), yet only 12% (52/431) strongly agreed they aimed to limit immunosuppressive effects. Conclusions: Pts with ITP are dissatisfied with current treatment options because of a perceived lack of efficacy, the burden of short- and long-term side effects, and the need for daily, life-long administration. Additionally, some commonly prescribed treatments for ITP are associated with fatigue. Pts and MDs would like new ITP treatments to offer a sustained period of remission or cure, and pts wish to be able to discontinue them without fear of relapse. There is an unmet need for well-tolerated therapies with disease-modifying potential that can safely achieve these goals.

Omega-3 polyunsaturated fatty acids in the prevention of relapse in patients with stable bipolar disorder: A 6-month pilot randomized controlled trial

This study investigated the efficacy and safety of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in relapse prevention of bipolar disorder (BD), addressing the shortcomings of current medications. Thirty-one stable BD patients were randomized to receive n-3 PUFAs or placebo for 6 months and intergroup differences in the incidence of the recurrence of bipolar depression were assessed. Differences in depression severity, manic symptoms, and routine biochemical parameters were also assessed. Interestingly, n-3 PUFAs demonstrated a favorable preventive effect on bipolar depression recurrence (p=0.005; Log-Rank) and reduced depression severity compared to placebo, and were well-tolerated, suggesting their potential as a safe prophylactic therapy for BD.

Predicting best treatment in rheumatoid arthritis

BackgroundAlthough targeted biological treatments have transformed the outlook for patients with rheumatoid arthritis (RA), 40% of patients show poor clinical response, and there is an imperative to unravel the molecular pathways and mechanisms underlying non-response and disease progression. 5–20% of RA individuals do not respond to all current medications including biologic and targeted therapies, which suggests that distinct pathogenic processes underlie multi-drug refractoriness. ObjectivesIn this brief review we discuss advances from recent studies in precision medicine in rheumatoid arthritis. MethodsBulk RNA-Sequencing of synovial biopsies from RA individuals combined with histology and deep clinical phenotyping has revealed substantial insights into divergent pathogenic pathways which lead to disease progression and illuminated mechanisms underlying failure to response to specific treatments. Biopsy-driven randomised controlled trials, such as R4RA and the forthcoming STRAP trial, have enabled the development of machine learning predictive models for predicting response to different therapies. ResultsIn the Pathobiology of Early Arthritis Cohort (PEAC), gene expression analysis showed that individuals could be classified into three gene expression subgroups which correlated with histopathotypes defined by histological markers: pauci-immune fibroid pathotype characterised by fibroblasts and an absence of immune inflammatory cells; diffuse-myeloid pathotype characterised by macrophage influx; and the lympho-myeloid pathotype delineated by the presence of B cells, but typically containing a complex inflammatory infiltrate with ectopic lymphoid structure formation. In the R4RA biopsy-driven randomised controlled trial, patients were randomised to either rituximab or tocilizumab. Comprehensive analysis of synovial biopsies pre/post-treatment identified gene signatures of response associated with pathogenic pathways which could be tracked over time. A group of true refractory patients were identified who had failed anti-TNF prior to the study (it was an entry criterion) and then subsequently failed both trial biologics during the trial. RNA-Seq analysis and digital spatial profiling identified specific cell types including DKK3+ fibroblasts as being associated with the refractory state. We identified machine learning predictive models based on specific gene signatures which were able to predict future response to therapy as well as the refractory state. ConclusionsRNA-sequencing of synovial biopsies has enabled substantial progress in understanding disease endotypes in RA and identifying synovial gene signatures which predict prognosis and future response to treatment.

Adherence to antiseizure medications in an underserved population with epilepsy

Background and purposeAntiseizure medications (ASM) effectively prevent seizures in about 70% of adult epilepsy patients, but nonadherence to medication is the primary cause of breakthrough seizures, accounting for 26% to 79% of cases. Factors such as age, education, dosing frequency, forgetfulness, fear of side effects, and socioeconomic status contribute to poor adherence, especially among underserved populations. This study aimed to assess medication adherence during routine follow-up visits and identify the role of education in reducing non adherence in an underserved patient population. MethodsThe study involved a retrospective chart review of adult epilepsy patients seen at the University of Illinois Hospital between December 2016 and April 2020. Data on patient demographics, epilepsy and seizure classification, medication details, emergency visits, and adherence were collected from electronic medical records using the RedCap system. Descriptive statistics and statistical tests were conducted using STATA 17.0 for data analysis, including chi-squared analysis for categorical data and t-tests for continuous data. ResultsThe study enrolled a total of 286 adult epilepsy patients who met the eligibility criteria. Among them, 111 patients (38.81 %) were classified as nonadherent based on ASM levels. Caucasian/white race and income > $50,000 per year, were significantly associated with adherence (p = 0.009 and p = 0.006 respectively). Moreover, patients with weekly seizures were more likely to be adherent (p = 0.042). No significant differences were found regarding medication adherence and sex, education, employment, epilepsy type, age at diagnosis, seizure type or number of current ASM medications. Even though not significant, a trend towards college educated patients being more adherent was observed (70.37 %). Of self-reported adherent patients, 33.33 % were found to be nonadherent based on ASM levels. Nurse phone calls reminding 70 non adherent patients about adherence increased the chances of becoming adherent by 80.39 %. Finally, although not statistically significant, the majority of adherent patients had no history of hospitalizations for breakthrough seizures (73.89 %). ConclusionMore than a third of our patients were found to be non-adherent during routine follow-up visits. Lower socio-economic status and lower education were associated with increased chances of being non adherent. Rates of adherence were improved by nurse’s phone calls discussing the importance of adherence and risks of SUDEP. The findings emphasize the importance of education in improving medication adherence among these populations, suggesting the need for social interventions, community outreach programs, and targeted educational initiatives.

Nanoparticle therapy for antibiotic-resistant bacteria: current methods and prospects

Emerging diseases due to antibiotic-resistant bacteria cause severe health concerns while increasing their negative effects on human health. The overuse or misuse of antimicrobial agents has contributed to the evolution of bacterial resistance to current medications. Bacteria can develop resistance by altering drugs, changing their target sites, forming biofilms and spending more time in the intracellular environment. Due to this, efforts are being made to create novel, alternative nanoantibiotics as a promising strategy to treat bacteria that cause disease and have developed resistance to a variety of drugs. Utilizing their biocidal properties, nanoparticles can be directed for medication delivery to particular tissues and employed as antibacterial agents against a range of illnesses. Targeted medication delivery-related toxicity problems may be solved with the aid of nanoencapsulation technology. This review paper generally provides a conceptual foundation for understanding the complexity of the problem of the development of antibiotic-resistant bacteria, particularly for brand-new synthetic antibiotics. This information will allow researchers to explore the use of nanoparticles in the treatment of multidrug-resistant bacteria.

Polypharmacy and the In Silico Prediction of Potential Body Proteins Targeted by These Drugs Among Hospitalized COVID-19 Patients With Cytokine Storm.

Background and objective Polypharmacy is prevalent in coronavirus disease 2019 (COVID-19) patients with severe disease. However, information on polypharmacyamong COVID-19patients who also suffer fromcytokine storm is scarce. In light of this, the purpose of the present study was to assess the incidence of polypharmacy and in silico prediction of potential body proteins targeted by these drugs among hospitalized COVID-19 patients who were identified to have the additional burden of cytokine storm in the city of Duhok, Kurdistan Region, Iraq. Methods This was a cross-sectional observational study conducted from June 2021 to April 2022; the phenomena of major polypharmacy (six to nine medications) and excessive polypharmacy (≥10 medications)were documented among 33 (15 males and 18 females) COVID-19 patients with cytokine storm during their hospital stay (8-45 days) in Duhok, Kurdistan Region, Iraq. The SwissTargetPrediction program was utilized in silico to predict and identify human body proteins that could be potentially targeted by selected medications involved in polypharmacy. Results All patients had tested positive forCOVID-19 via PCR testing, and they showed different signs and symptoms of the disease. None of the patients recovered and all of them deceased. All 33 patients received many therapeutic agents that ranged in number from eight to 20/patient during their hospital stay. The mean number ofmedications was 15 ± 3. We identified 2/33 (6%) patients with major polypharmacy (eight and nine) and 31/33 (94%) withexcessive polypharmacy(15.5 ± 2.7). The total number of medications identified inpolypharmacy was 37, excluding vitamins, minerals, and intravenous solutions. The frequency of medications administered was as follows: antibiotics (67, 13.7%), mucolytic agents (56, 11.5%), corticosteroids (54, 11%), anticoagulants (48, 9.8%), antiviral agents (41, 8.4%), antihypertensive agents (32, 6.5%), analgesics (28, 5.7%), antifungal drugs (27, 5.5%), antidiabetics (26, 5.3%), and other medications (2-19, 0.41-3.9%). Using the SwissTargetPrediction program, various drugs including antiviral agents involved in polypharmacy were found to target, in silico, body proteins at a prediction percentagethat ranged from 6.7% to 40%. Conclusions Major and extensive polypharmacy conditions were identified in hospitalized COVID-19 patients suffering fromcytokine storm.The severity of COVID-19 with cytokine storm, comorbidities, and hospitalization were key factors associated with polypharmacy in the patients.The SwissTargetPrediction web server is useful for predicting in silico potential human body protein targets that could possibly be sources of additional information on theadverse/toxic effects of polypharmacy medications administered concurrently. Further research in current medication protocols prescribed for advanced COVID-19 illness with cytokine storm is warranted to gain deeper insights into the topic.

Preoperative tamsulosin effect on postoperative urinary retention following spinal surgery: A randomized controlled trial

BackgroundCurrent study aims to investigate pre-surgical medical intervention on the reduction of POUR incidence in patients undergoing spine surgery. MethodThe study was a single center double-blind randomized placebo clinical trial. Participants were individuals over 18 years old who underwent spinal surgery at the Educational and Therapeutic Hospital between 2020 and 2023. Inclusion criteria included the ability to provide informed consent and follow the study schedule, while exclusion criteria included certain medical conditions, current medication use, and inability to take oral medication after surgery. ResultsThe study enrolled 100 patients. There was no significant difference in age or gender distribution between the tamsulosin and placebo groups, but the tamsulosin group had a lower prevalence of diabetes. The duration of surgery was shorter in the tamsulosin group, and there was no significant difference in the surgical site. The tamsulosin group had significantly less post-void residual volume on the eighth day of the study, but there were no significant differences in urine output volume during surgery or residual urine volume before or after surgery. ConclusionTamsulosin may be effective in preventing postoperative urinary retention (POUR), but its effectiveness in treating established POUR is uncertain. The Tamsulosin group had significantly lower post-void residual volume after spine surgery. Considering the low risk of adverse effects, Tamsulosin could be considered for high-risk patients. However, patients should be aware of potential risks and seek medical attention if they experience adverse effects. Further research is needed to determine the best dosage and duration of treatment.

Abstract 18388: Hypertension Identification and Management in the USA: Adherence of the 2017 ACC/AHA High Blood Pressure Guidelines

Background: The 2017 ACC/AHA Guideline for the Prevention, Detection, Evaluation and Management of High Blood Pressure in Adults changed the criteria for a diagnosis of hypertension and provided new recommendations goals and management. We aimed to investigate the prevalence of hypertension identification, treatment, and adherence in the US population. Methods: We analyzed the 2017-2020 pre-pandemic National Health and Nutrition Examination Survey for participants between 18 and 79 years of age. Participant data was used to assess for a hypertension diagnosis and eligibility for AHA/ACC’s primary or secondary prevention hypertension strategies. Current hypertension medication usage was stratified if prescribed for hypertension management or a non-hypertension indication. Participants with a current hypertension-indicated medication were identified as “Undergoing Treatment”; all other participants were stratified into “No Indication”, “Primary Prevention”, or “Secondary Prevention”, based on the AHA/ACC guideline. Complex survey methodology with weighting was utilized for national estimates. Results: Our study included 236,621,712 participants, of which 22.4% (n=53,064,773) were undergoing treatment for hypertension, 67.0% (n=158,613,605) had no indication for management, 8.9% (n=21,158,544) qualified for primary prevention, and 1.6% (n=3,784,790) qualified for secondary prevention. A known hypertension diagnosis was reported in 26.0% of the primary prevention group, 45.0% of secondary prevention, and 94.8% of those undergoing treatment. In patients undergoing treatment, 57.9% of participants had mean blood pressure readings above goal. Conclusion: One in ten adults under 80 qualify for hypertension management but may not be undergoing treatment. Of patients qualifying without current treatment, most did not know they would qualify for a hypertension diagnosis. More than half of treated patients did not meet blood pressure goals.

Abstract 16304: Contemporary Practice Patterns and Opportunities to Improve Type 2 Diabetes (T2D) Therapy in Patients at Elevated Cardiovascular and/or Kidney Risk

Background: Evidence-based SGLT2 inhibitors (SGLT2i) and GLP-1 receptor agonists (GLP-1 RA) reduce cardiovascular (CV) events and improve kidney outcomes in patients with type 2 diabetes (T2D) who are at elevated cardiac or renal risk; however, prescription rates are low despite guidelines recommending their use. We aimed to evaluate the eligibility for, and utilization of, SGLT2i and GLP-1 RA in real-world practice in a large, integrated, multicenter health system. Aim: To determine the prevalence of CV and kidney comorbidities in patients with T2D and current medication use patterns within a large, urban healthcare system. Methods: In this cross-sectional analysis of the Mass General Brigham healthcare system from 2020-2023, we identified all patients with T2D meeting current guideline eligibility criteria for SGLT2i and/or GLP-1 RA. Indications for therapy included ASCVD, heart failure, kidney disease, or high risk for developing ASCVD - determined by EHR data. High risk for developing ASCVD and ASCVD were mutually exclusive, however other indications were reported as identified comorbidities by patient. Demographics, medications, laboratory values, and comorbidities were assessed. Results: There were 304,105 people with T2D and an HbA1c within 3 years: mean age 70 years, HbA1c 7.1%, 52% male, 30% non-white, 11% non-English language preferred. 186,885 (62%) patients had &gt; 1 CV or kidney comorbidity: 82,245 (44%) high risk for developing ASCVD, 90,408 (48%) ASCVD, 29,766 (16%) HF, 46,801 (25%) kidney disease, and 50,825 (27%) with &gt; 2 comorbidities. Of the 186,885 patients with an indication, 21,997 (12%) were prescribed an SGLT2i, 28,620 (15%) a GLP-1 RA, and 7,544 (4%) both ( Figure 1 .) Conclusion: Ongoing limited use of agents with proven CV and kidney benefit exists among commonly encountered patients with T2D despite guideline recommendations; novel strategies are needed to overcome the barriers that keep patients from improved outcomes.

Generalized anxiety symptoms and life satisfaction

This study examines the mediating role of repetitive negative thinking in the relationship between generalized anxiety symptoms and life satisfaction. A web survey was administered to 857 participants (365 men) who filled out a sociodemographic questionnaire, the Generalized Anxiety Disorder-7, the Persistent and Intrusive Negative Thoughts Scale, and the Satisfaction with Life Scale. Then, participants were divided into four groups according to levels of symptomatology. The results showed that scores for repetitive negative thinking increased due to the severity of generalized anxiety symptoms. For life satisfaction, individuals without generalized anxiety symptoms scored significantly higher than individuals with generalized anxiety symptoms. Furthermore, repetitive negative thinking mediates and explains over 54% of the relationship between generalized anxiety symptoms and life satisfaction when controlling for age, sex, clinical diagnosis, and current psychiatric medication. Overall, the current findings highlight the central role of repetitive negative thinking in the relationship between generalized anxiety symptoms and life satisfaction and reinforce a transdiagnostic process in the maintenance of anxiety symptomatology and well-being impairment.