Specific Drug Classes Research Articles

NCOG-38. LAMOTRIGINE MONOTHERAPY ASSOCIATES WITH IMPROVED PROGRESSION-FREE AND OVERALL SURVIVAL IN HIGH-GRADE GLIOMA

Abstract BACKGROUND High-grade gliomas (HGG) are aggressive brain tumors with notoriously poor prognoses and high symptomatic burden, including seizures in 30-60% of HGG cases. Despite negative impacts to quality of life, positive seizure history at presentation and during the disease course has been shown to associate with improved overall survival. Further, recent preclinical studies have suggested a link between neuronal hyperexcitation and more rapid glioma progression. We hypothesized anti-seizure medication (ASM) therapy may suppress neuronal excitation and therefore help prolong survival. To this aim, we characterized the association of various ASM therapies with survival and seizure control. METHODS Retrospective review of 413 patients with co-occurring HGG and clinically diagnosed epileptic activity. Multivariable linear regression was used to assess the impact of ASM quantity (monotherapy versus polytherapy) and type (specific ASMs as well as ASM class) on progression-free survival (PFS) and overall survival (OS). Logistic regression was used to assess the impact of ASM quantity and type on likelihood of achieving seizure remission. Additional variables in the regressions included age, treatment exposure (radiation therapy, cytotoxic chemotherapy, or targeted chemotherapy), and extent of surgical resection (gross total resection versus all other surgeries). Kruskal-Wallis tests were used to compare median survival between multiple groups. RESULTS ASM monotherapy and polytherapy demonstrated comparable survival outcomes. Among patients who received ASM monotherapy, only lamotrigine demonstrated a significant association with improved survival with PFS and OS (P = <0.001 for both). No specific drug or drug class demonstrated greater likelihood of achieving seizure remission. CONCLUSION Lamotrigine demonstrates a unique association with improved outcomes that is neither shared by other ASMs nor explained by ASM drug class, without any decline in likelihood of achieving seizure remission. Optimization of ASM therapy may enhance survival outcomes without compromising seizure control.

Serum creatine kinase elevation following tyrosine kinase inhibitor treatment in cancer patients: Symptoms, mechanism, and clinical management.

Molecular targeted tyrosine kinase inhibitors (TKIs) have produced unprecedented treatment response in cancer therapy for patients harboring specific oncogenic mutations. While the TKIs are mostly well tolerated, they were reported to increase serum levels of creatine kinase (CK) and cause muscle metabolism-related toxicity. CK is an essential enzyme involved in cellular energy metabolism and muscle function. Elevated serum CK levels can arise from both physiological and pathological factors, as well as triggered by specific drug classes. The incidence of serum CK elevation induced by a few approved TKIs (brigatinib, binimetinib, cobimetinib-vemurafenib combination [Food and Drug Administration, United States]; aumolertinib, and sunvozertinib [only approved by National Medical Products Administration, China]) were over 35%. CK elevation-related symptoms include myopathy, myositis, inclusion body myositis (IBM), cardiotoxicity, rhabdomyolysis, rash, and acneiform dermatitis. High-level or severe symptomatic CK elevation may necessitate dose reduction and indirectly dampen TKI efficacy. This review presents an updated summary about the prevalence rate and recent research about mechanisms leading to TKI-induced serum CK elevation in cancer patients. The utility of monitoring serum CK levels for predicting TKI-induced adverse effects and their management will also be discussed.

Efficacy of specific drug class therapy in pulmonary arterial hypertension associated with HIV, portal hypertension or both: a single Center experience

Abstract Background Pulmonary arterial hypertension (PAH) is a rare complication of both HIV infection (HIV-PAH) and portal hypertension (Po-PAH); it can occur in patients with both diseases (HIV/Po-PAH). The use of the PAH-specific drug classes (prostanoids, endothelin-1 receptor antagonists [ERA] and phosphodiesterase-5 inhibitors [PDE5-i]) is largely justified by retrospective and observational case reports since, to date, there are no randomized clinical trials except for the PORTICO trial which demonstrated the efficacy of macitentan in Po-PAH. Purpose the aim of the study was to evaluate the efficacy of PAH-specific drugs, both monotherapy and dual oral upfront therapy (ERA + PDE5i started within 1 month apart), in patients with Po-PAH, HIV/Po-PAH and HIV-PAH. Methods Between 1998 and 2023 we enrolled patients with Po-PAH, HIV-PAH and HIV/Po-PAH referred to our Center and undergoing monotherapy with prostanoid, ERA and PDE5-I or dual upfront oral therapy. The efficacy of the drugs was assessed by comparing clinical parameters (NYHA functional class), exercise capacity (six-minute walking test) and hemodynamic parameters at baseline and after a treatment period of 3-6 months. The data are expressed as mean and standard deviation and were compared with Student's t-test for paired data. Results 128 patients were enrolled (83 Po-PAH, 23 HIV/Po-PAH and 22 HIV-PAH). 20 were treated with ERA monotherapy, 90 with PDE5-I, 13 with prostanoids and 5 treated with dual oral upfront therapy. Conclusions Prostanoids, ERAs and PDE5-Is, both in monotherapy and as dual upfront oral therapy, are associated with a significant improvement in functional class, exercise capacity and hemodynamic parameters. The effect of such drugs is similar to patients suffering from other forms of PAH.

Antimicrobial Resistance Gene Carriage is not Associated with Uremic Toxin Levels in Chronic Kidney Disease Patients

In chronic kidney disease (CKD), uremic toxin molecules build up and risk of infection increase overtime, making the presence of antimicrobial resistant (AMR) bacteria in the gut more problematic with advancing disease. This study assessed if serum levels of uremic toxins and gut carriage of AMR genes are correlated in individuals with CKD. Whole metagenomic sequencing of stool samples and measured levels of 4 uremic toxins from 21 individuals with CKD were obtained. Multivariable, multivariate linear regression was performed with total abundance of AMR genes and abundance of specific drug classes of AMR genes as outcome variables and serum levels of four uremic toxins as predictor variables. Beta diversity differences of AMR genes were visualized using non-metric multidimensional scaling (NMDS) based on robust Aitchison distances and tested using PERMANOVA. There were no significant associations between uremic toxin levels and AMR gene abundance, or with any of the drug classes of AMR genes. There were no significant differences in beta diversity of AMR genes. These null findings suggest that increased uremic toxin levels are not associated with an increase in AMR carriage, and therefore uremia does not appear to be a direct cause of increased resistant bacteria in patients with more severe CKD.

Vaginal Tritrichomonas foetus infection in mice as an in vivo model for drug development against Trichomonas vaginalis.

Trichomonas vaginalis is the causative agent of the common sexually transmitted disease, trichomoniasis, which affects more than a hundred million people worldwide. Metronidazole and tinidazole, agents belonging to the 5-nitroheterocyclic class of antimicrobials, are most often used to treat infection, but increased resistance has been reported and adverse effects of these drugs can be significant. Consequently, an urgent need exists for the development of novel drug entities against trichomoniasis. Critical for antimicrobial drug development is the demonstration of in vivo efficacy. Murine models of vaginal T. vaginalis infection are unreliable for unknown reasons. Meanwhile, murine infections with the related bovine pathogen, Tritrichomonas foetus, tend to be more robust, although susceptibility to different antimicrobials might differ from T. vaginalis. Here, we explored the utility of T. foetus infection as a surrogate model for drug development against T. vaginalis. Four different T. foetus strains caused robust vaginal infection in young mice, while none of four diverse T. vaginalis strains did. Comparison of drug susceptibility profiles revealed that T. foetus and T. vaginalis were similarly susceptible to a range of 5-nitroheterocyclic and gold(I) compounds. By comparison, proteasome inhibitors were 10- to 15-fold less active against T. foetus than T. vaginalis, although one of the proteasome inhibitors, bortezomib, had low micromolar activity or better against multiple strains of both trichomonads. Different strains of T. foetus were used to demonstrate the utility of the murine vaginal infection models for in vivo efficacy testing, including for bortezomib and a gold(I) compound. The differences in susceptibility to proteasome inhibitors may be partially explained by differences in the proteasome subunit sequences between the two trichomonads, although the functional relevance of the proteasome was similar in both organisms. These findings indicate that T. foetus can serve as a reliable surrogate model for T. vaginalis in vitro and in murine infections in vivo, but caution must be exercised for specific drug classes with targets, such as the proteasome, that may display genetic divergence between the trichomonads.

Prenatal antidepressant use and risk of congenital malformations: A population-based cohort study

Previous studies examining antidepressants and congenital-malformations were primarily conducted in western countries, and many were constrained by important methodological limitations. This population-based study identified 465,069 women (including 1,705 redeemed ≥1 prescription of antidepressants during first-trimester) aged 15–50 years who delivered their first and singleton child between 2003 and 2018 in a predominantly-Chinese population in Hong Kong, using territory-wide medical-record database of public-healthcare services, and employed propensity-score fine-stratification-weighted logistic-regression analyses to evaluate risk of any major and organ/system-specific congenital-malformations following first-trimester exposure to antidepressants. Major malformation overall was not associated with any antidepressant (weighted-odds-ratio wOR, 0.88 [95 %CI, 0.44–1.76]), specific drug-class, or individual antidepressants. Exposure to any antidepressant was associated with increased risk of cardiac (wOR, 1.82 [95 %CI, 1.07–3.12]) and respiratory anomalies (wOR,4.11 [95 %CI, 1.61–10.45]). Exposure to selective-serotonin-reuptake-inhibitors (SSRI) and multiple-AD-classes were associated with respiratory and cardiac anomalies, respectively. However, these identified associations were not consistently affirmed across sensitivity analyses, precluding firm conclusion. Observed associations of specific cardiac defects with serotonin-norepinephrine-reuptake-inhibitors (SNRI), tricyclic-antidepressants (TCA) and multiple-AD-classes were noted with wide confidence-intervals, suggesting imprecise estimation. Overall, our findings suggest that first-trimester antidepressant exposure was not robustly associated with increased risk of congenital-malformations. Further research clarifying comparative safety of individual antidepressants on specific malformations is warranted.

Knowledge, Attitudes, and Practices about Hyperuricemia and Gout in Community Health Workers and Patients with Diabetes.

Hyperuricemia exhibits a high incidence among individuals with diabetes; however, the significance of hyperuricemia and gout is often underestimated. This study aimed to assess the knowledge, attitude, and practice of hyperuricemia and gout among community health workers and patients with diabetes. Two questionnaires were designed to investigate knowledge, attitudes, and practices of hyperuricemia and gout among community health workers and patients with diabetes in Chenghua District, Chengdu, from August 2021 to January 2022. A total of 709 community health workers were included, whose average score was 17.74/30. Approximately half of general practitioners (GPs) demonstrated knowledge regarding the target serum uric acid levels for hyperuricemia and gout. Only 11.2% of GPs were fully aware of the preferred medicine for acute gout. The majority of GPs (86.7%) demonstrated limited awareness regarding the contraindications associated with colchicine, while a significant proportion (65.1%) lacked knowledge about the specific classes of drugs that inhibit uric acid synthesis. Among the 508 patients with diabetes included in this survey, 32.3% demonstrated awareness of hyperuricemia, while 60.8% exhibited knowledge regarding gout. The average score attained by these individuals was recorded at 7.21 out of a total of 26 points. The majority of patients with diabetes (87.8%) held the mistaken belief that hyperuricemia definitely led to the development of gout. Almost 66% agreed that a massage or a hot compress could be used when acute gouty arthritis attacks. The knowledge rate of hyperuricemia and gout among community health workers was moderate, while it was low in patients with diabetes.

Are There Sex-Related Differences in the Effectiveness of Janus Kinase Inhibitors in Rheumatoid Arthritis Patients?

Background: There is evidence suggesting the existence of sex differences in the effectiveness of specific drug classes for rheumatoid arthritis (RA). Our study stands as the first to elucidate sex-related differences in the effectiveness of Janus kinase (JAK) inhibitors. Methods: The study involved 150 RA patients treated with tofacitinib, baricitinib, upadacitinib, or filgotinib between September 2017 and October 2023. Sex differences in achieving remission and low disease activity (LDA) were identified through logistic regression analyses. Sex disparities in treatment effectiveness survival were evaluated through the Kaplan-Meier estimate, employing the log-rank test for comparison. The Cox model was applied to analyze the variable sex as a potential factor that could influence the maintenance of the JAK inhibitor treatment effectiveness. Results: Concerning the achievement of remission and LDA, no differences were observed between sexes in terms of the 28-joint Disease Activity Score (DAS28) C-reactive protein (CRP), the Clinical Disease Activity Index (CDAI), and the Simplified Disease Activity Index (SDAI). With respect to the DAS28-erythrocyte sedimentation rate (ESR), female patients, compared to males, possessed 70% lower odds of achieving remission (p = 0.018) and 66% lower odds of achieving LDA (p = 0.023). No differences were observed in treatment effectiveness survival between sexes (p = 0.703). Sex was not found to influence the survival of JAK inhibitor treatment effectiveness (p = 0.704). Conclusions: Being a female or male patient does not entail differences in the effectiveness of the JAK inhibitor treatment. Our findings encourage the consideration of a global pool of composite indices (DAS28-ESR/CRP, CDAI, SDAI) to measure RA disease activity, thus individualizing the target value as advocated by the treat-to-target strategy.

Likelihood of Antimicrobial Resistance in Urinary E. coli Isolates Among US Female Patients with Recurrent Versus Non-Recurrent uUTI

ObjectivesTo assess the relative likelihood of antimicrobial resistance (AMR) and multi-drug resistance (MDR) among E. coli isolates from outpatients with recurrent versus non-recurrent uncomplicated urinary tract infection (uUTI). MethodsIn this retrospective observational US cohort study, female outpatients (≥12 years) with uUTI, positive E. coli culture, and treated with ≥1 oral antibiotic within ±5 days of diagnosis were grouped into recurrent and non-recurrent uUTI cohorts per their UTI history (past 12 months). AMR to specific drug classes was evaluated at index. Univariable and multivariable logistic regression models estimated the likelihood of not-susceptible E. coli isolates (AMR/MDR) among patients with recurrent uUTI versus non-recurrent uUTI. ResultsRecurrent (N=12,234) and non-recurrent (N=68,033) uUTI cohorts had similar distributions (race, ethnicity, region). Patients with recurrent uUTI had a higher prevalence of E. coli resistance to trimethoprim-sulfamethoxazole (21.8% vs 18.7%) and fluoroquinolones (14.2% vs 8.6%), and more isolates were extended-spectrum β-lactamase-producing (5.9% vs 4.1%) compared to non-recurrent uUTI patients. Patients with recurrent uUTI had a higher likelihood (odds ratio [95% confidence interval]) of any AMR (1.28 [1.22–1.34]), single drug-class resistance (1.18 [1.12–1.24]), and resistance to 2 (1.53 [1.41–1.67]) or ≥ 3 drug classes (1.70 [1.48–1.96]) (all P<0.001). ConclusionsThis study delineated the likelihood of AMR and MDR among E. coli isolates from patients with recurrent versus non-recurrent uUTI. While some treatment guidelines support empiric therapy in recurrent uUTI, the increased likelihood of resistance among these patients suggests that culture and susceptibility testing should be undertaken to inform recurrent uUTI treatment.

Targeting vascular senescence in cardiovascular disease with aging.

Aging is a major risk factor for atherosclerosis and cardiovascular disease (CVD). Two major age-associated arterial phenotypes, endothelial dysfunction and large elastic arterial stiffness, are autonomous predictors of future CVD diagnosis and contribute to the progression of CVD in older adults. Senescent cells lose the capacity to proliferate but remain metabolically active and secrete inflammatory factors termed senescence-associated secretory phenotype (SASP), leading to an increase in inflammation and oxidative stress. Accumulation of senescent cells is linked with the progression of age-related diseases and has been known to play a role in cardiovascular disease. In this brief review, we describe the characteristics and mechanisms of senescent cell accumulation and how senescent cells promote endothelial dysfunction and arterial stiffness. We focus on a range of novel therapeutic strategies aimed at reducing the burden of endothelial dysfunction leading to atherosclerosis through targeting senescent cells. Studies have begun to investigate a specific class of drugs that are able to selectively eliminate senescent cells, termed senolytics, which have shown great promise in reversing the aging phenotype and ameliorating pathologies in age-related disorders, creating a new opportunity for aging research. Generating therapies targeting the elimination of senescent cells would improve health span and increase longevity, making senolytics a promising therapy for cardiovascular diseases.

Drug-induced autoimmune-like liver injury

Drug-induced liver injury (DILI) is arare yet potentially life-threatening disease. Besides intrinsic DILI, which is mainly caused by paracetamol overdosing and which is dose-dependent and predictable, there is idiosyncratic DILI-an unpredictable and dose-independent injury of the liver caused by certain medications that only occurs in aminority of patients taking this drug. The reason why some patients react with DILI towards aspecific drug is still unknown. However, the immune system plays acentral role, which is underlined by the association of certain human leukocyte antigen (HLA) polymorphisms and DILI caused by specific drug classes. Due to the immunological processes that lead to the liver injury in DILI, there are great overlaps regarding laboratory and histological parameters between DILI and autoimmune hepatitis (AIH). Differentiating DILI and AIH can therefore be challenging, especially at the time of presentation. In addition, there are other immunologically mediated DILI phenotypes, in particular the newly defined drug-induced autoimmune-like hepatitis (DI-ALH) and liver injuries caused by checkpoint inhibitors (CPI). DI-ALH is characterized by autoimmune features and good responses towards corticosteroids, with the difference that DI-ALH mostly does not relapse after discontinuation of corticosteroids. CPI-induced liver injury has become more frequent with the rising use of those drugs and is characterized by adistinct histopathological pattern with granulomatous hepatitis and infiltration dominated by cytotoxic Tcells. Similarly, the recently recognized liver injury following vaccinations also shows an autoimmune phenotype; however, in contrast to AIH, cytotoxic Tcells seem to dominate the inflammatory infiltrates in the liver.

Sub-clustering based recommendation system for stroke patient: Identification of a specific drug class for a given patient

Stroke is one of the leading causes of death worldwide. Previous studies have explored machine learning techniques for early detection of stroke patients using content-based recommendation systems. However, these models often struggle with timely detection of medications, which can be critical for patient management and decision-making regarding the prescription of new drugs. In this study, we developed a content-based recommendation model using three machine learning algorithms: Gaussian Mixture Model (GMM), Affinity Propagation (AP), and K-Nearest Neighbors (KNN), to aid Healthcare Professionals (HCP) in quickly detecting medications based on the symptoms of a patient with stroke. Our model focused on three classes of drugs: antihypertensive, anticoagulant, and fibrate. Each machine learning algorithm was used to accomplish specific tasks, thereby reducing the partial search space, computational cost, and accurately detecting a primary drug class without loss of precision and accuracy. Our proposed model, called CRGANNC (Clustering Recommendation Gaussian Affinity Nearest Neighbors Classifier), effectively addresses the sparsity and scalability issues faced by content-based recommendation models. The CRGANNC model dynamically partition clusters into sub-clusters with variable numbers based on the group, and can diagnose healthy, sick, and at-risk patients, and recommend drugs to the HCP. In addition to our analysis, we developed a semi-artificial dataset with new features such as weakness, dizziness, headache, nausea, and vomiting, using a pipeline. This dataset serves as a valuable resource for researchers in the sensitive domain of stroke, providing a starting point for building and testing models when real data is often restricted. Our work not only contributes to the development of predictive models for stroke but also establishes a framework for creating similar datasets in other sensitive domains, accelerating research efforts and improving patient care. Our experiments were conducted on our dataset consisting of 9691 patient records, with 1206 records for stroke attacks and 8485 healthy patients. The CRGANNC model achieved an average precision of 0.98, recall of 0.95 and F1-score of 0.96 across all three drugs classes. Furthermore, our model demonstrated significant improvement in computational efficiency compared to existing content-based recommendation models, reducing the processing time by 25.80% . This results indicate the effectiveness of our model in accurately detecting medications for stroke patients based on their symptoms.

A Study Using The Defined Daily Dose Method To Evaluate The Use Of Antihypertensive Medications

The DDD concept is a method for quantifying a drug. Drug use in terms of DDD aids in converting the number of pharmaceuticals readily available into medically significant units and in estimating the number of people who have been exposed to a specific drug or class of drugs. In a hospital setting, the unit DDD per 100 bed-days suggests the proportion of inpatients that may receive a DDD. DDD in anti-hypertensive medications helps to track down prescription drug usage and examine drug usage trends. A 6-month prospective and observational study was conducted to assess the drug utilisation of antihypertensives. In this study we found that Diuretics were commonly prescribed antihypertensives. Furosemide and Spironolactone were mostly prescribed antihypertensives as single therapy, while Telmisartan+Hydrochlorothiazide was commonly prescribed as combination therapy. Propranolol was over utilised antihypertensives with 187.82 DDD/100bed-days and 1.74 PDD:DDD ratio.

Prescribing Pattern of Antimicrobial Agents in Patients with Pelvic Inflammatory Disease in a Tertiary Care Hospital at Rural Part of Western Nepal

Introduction: Antibiotics are the most frequently prescribed drugs in patients with Pelvic Inflammatory Diseases. Appropriate antibiotic prescriptions in health care institutions are an important element in quality of care, infection management and cost control.&#x0D; Aims: To analyze prescription pattern of antimicrobial agents in patients with pelvic inflammatory diseases.&#x0D; Methods: This quantitative cross-sectional study was conducted including 300 patients' prescriptions, at Karnali Academy of Health Sciences Jumla Nepal for period of six months during August 2021 to January 2022. This study was based on medication utilization form, which was designed on basis of World Health Organization core drug use indicator format.&#x0D; Results: Females were in ages from 12 to 69 years, with mean of 30.46 ± 18.71 years. Chronic Pelvic inflammatory Disease was most prevalent in 20–29 age group (47%) while, lowest in 60–69 age group (1.67%). The total number of prescribed drugs was 796 averaging 2.65 drugs per prescription. The most commonly prescribed antimicrobials were azithromycin (30.15%), tinidazoles (25.25%) and ofloxacin (8.16%). Only 15.5% of drugs were prescribed with generic names and all were from essential list of medicines. 92.8% of prescriptions were administered orally, while 7.8% parenteral. However 76.34% of prescriptions were considered irrational.&#x0D; Conclusion: The high prevalence of irrational prescriptions suggests need for interventions to improve healthcare provider's adherence to established treatment guidelines. Dominance of specific drug classes underscores importance of tailoring treatments to the specific pathogens involved in Pelvic Inflammatory Disease. Suggesting potential room for improvement inadherence to evidence-based guidelines.

Critical review of the current and future prospects of VEGF-TKIs in the management of squamous cell carcinoma of head and neck.

As the prognosis for squamous cell carcinoma of the head and neck remains unsatisfactory when compared to other malignancies, novel therapies targeting specific biomarkers are a critical emerging area of great promise. One particular class of drugs that has been developed to impede tumor angiogenesis is vascular endothelial growth factor-tyrosine kinase inhibitors. As current data is primarily limited to preclinical and phase I/II trials, this review summarizes the current and future prospects of these agents in squamous cell carcinoma of the head and neck. In particular, the combination of these agents with immunotherapy is an exciting area that may be a promising option for patients with recurrent or metastatic disease, evidenced in recent trials such as the combination immune checkpoint inhibitors with lenvatinib and cabozantinib. In addition, the use of such combination therapy preoperatively in locally advanced disease is another area of interest.

Preparation, characterization, in-vitro and toxicological evaluation of carbopol based nanogels for solubility enhancement of Valsartan

Solubility is an essential criterion for attaining desired concentration of the drug within the systemic circulation to ensure intended pharmacological action. The main setback for the formulation development of new chemical entities and generic drugs is their lower aqueous solubility. Therefore, a drug carrier system is needed which not only enhances the solubility of low aqueous soluble drugs but also maintains a constant pharmacological action of drugs within predetermined intervals of time. For this purpose, authors prepared carbopol 934-co-poly(itaconic acid) (CPcPIA) nanogels by the free radical polymerization technique for the solubility enhancement of Valsartan. The polymeric nanogels were characterized and studied for further evaluation. FTIR studies indicated no interactions between the drug and nanogel contents. SEM showed a porous and sponged structure of particles without any agglomeration. Similarly, higher thermal stability was detected for the fabricated nanogel compared to its constituents, while reduction in crystallinity of the drug and excipients was shown by XRD analysis, indicating the amorphous nature of the polymeric nanogels. Average particle size and zeta potential of prepared nanogels were found 290.32 nm and –8.32 mV, respectively. Furthermore, various studies such as sol-gel fraction, dynamic swelling, drug loading, in-vitro drug release studies, solubility, and toxicity study were conducted for the developed nanogels. A significant increase in the solubility of Valsartan (2.002, 2.976, and 3.543 mg/mL) was observed by polymeric nanogels in pH 1.2, deionized distilled water, and pH 7.4 as compared to reference product. Toxicity study indicated no toxic effect of prepared nanogels on rabbit's species. Thus, it can be demonstrated from the results that synthesized nanogels are not only limited to a specific class of drug but the solubility of all low aqueous soluble drugs can be enhanced by the prepared networks of nanogels.

Associations of antihypertensive medication (AHM) consumption and drug‐drug interaction with Statin and Metformin with reduced Alzheimer’s disease and related dementias (ADRD) risk among hypertensive patients with mild cognitive impairment (MCI) using high volume claims data

AbstractBackgroundWhile hypertension is a modifiable risk factor of Alzheimer’s disease and related dementias (ADRD), limited studies have been conducted on drug effectiveness of antihypertensive medications (AHMs) on ADRD progression from mild cognitive impairment (MCI) or on drug‐drug interactions of AHMs with drugs for other risk factors such as type 2 diabetes and hypercholesterolemia.Method128,683 unique hypertensive patients with MCI on US‐based Optum claims data were identified. Diuretics, beta blockers (BBs), calcium channel blockers (CCBs), angiotensin‐converting enzyme inhibitors (ACE inhibitors), and angiotensin II receptor antagonists (ARBs) were identified as five major AHM classes. Baseline characteristics were compared. Cox proportional hazards (PH) models were used to study the association between specific AHM exposure and the progression from MCI to ADRD while controlling for demographic variables, comorbidities, and use of Statin and Metformin. To examine the association of AHM‐Statin or AHM‐Metformin interaction with ADRD progression, we also investigated models controlling for aforementioned confounders, as well as drug‐drug interaction terms.ResultThe study included 100,678 patients who were taking at least one class of AHM and 28,005 who were not taking any AHMs. AHM users had higher ratios for the comorbidities (all P≤0.039) and consumption of Metformin and Statin (both P&lt;0.001) compared to non‐users. Users of each major AHM class showed significantly lower risk of developing ADRD compared to non‐users of that specific drug class (adjusted hazard ratio (aHR): 0.96‐0.98; all P≤0.048). Within patients on monotherapy (using only one AHM drug), no specific AHM class had significantly lower risk of ADRD diagnosis compared to other AHM drug classes (aHR: 0.97‐1.11; all P≥0.053). Use of Diuretics or CCBs in combination with Metformin consumption (aHR: 0.89, 0.91, respectively) showed lower risk of MCI to ADRD progression than that under Metformin non‐consumption (aHR: 0.97, 0.98), whereas use of any of the five major AHMs under Statin consumption (aHR: 0.91‐0.94) all showed lower risk than that under Statin non‐consumption (aHR: 0.98‐1.04).ConclusionAll five major AHM classes show a protective effect against ADRD progression among hypertensive patients with MCI. Also, AHMs combined with consumption of Metformin or Statin showed a stronger protective effect compared to non‐consumption.

Adverse drug reactions as cause of nonspecific symptoms in patients in the emergency department

In alarge proportion of patients admitted to the emergency department (ED), the initial main symptom is nonspecific. One possible reason for this, especially in older patients, may be adverse drug reactions (ADR) due to their frequent polypharmacy. To illustrate the incidence of ADRs, the affected patient population including risk factors, and drug classes with ADRs leading to nonspecific symptoms. To provide practice recommendations for the management of ADRs in the ED. Presentation of the pharmacological principles on ADRs, statistics of pharmacovigilance centers as well as original literature including experiences from clinical practice and own projects. In 10% of patients with nonspecific symptoms an ADR is responsible for presentation in the ED. In 60% of cases these ADRs are not correctly identified in the ED setting. Asmall number of drug classes are responsible for most of these referrals. Databases, risk stratification, clinical pharmacists, or clinical decision support systems are available to improve ADR identification and management. As these options are partly associated with considerable costs or the validation for German EDs is missing, awidespread application does not take place. Correct identification of ADRs in patients with nonspecific symptoms in the ED is necessary to initiate adequate treatment. These ADRs are often overlooked because processes and tools for identification and management are not applied in the ED, leading to a lack of awareness. For high-risk patients in the ED, the focus should be on drug history, ideally considering patient-specific risk factors and specific drug classes.

Abstract 16795: Blood Pressure Lowering Therapeutical Strategies Have Different Impact on Brain Functional Connectivity

Hypertension is a major risk factor for cognitive impairment and dementia. Using functional MRI, researchers have been able to study the brain’s functional connectivity in hypertensive patients. This has revealed that even before showing signs of vascular dementia, hypertensive patients have altered brain connections compared to normotensive patients. Our aim is now to characterize whether different classes of antihypertensive drugs, which vary in their mechanism of action and ability to cross the blood-brain barrier, have different effects on the brain’s functional organization. In this study, 42 hypertensive patients with controlled blood pressure underwent resting-state functional MRI. The data was analyzed using CONN to build functional connectivity network matrices and analyze the amplitude of spontaneous brain activity fluctuations (fALFF). These results were then evaluated using general linear models to identify connections that were modulated by specific classes of antihypertensive drugs. We applied regression models taking into account age, sex, BMI, alcohol, smoke and BP levels as covariates. Our results show that treatment with diuretics was associated with a large connectivity network among several brain networks (A). Treatment with ACE inhibitors (B), ARBs (C), and beta-blockers (D) was also associated with significant modulation of specific connections (all highlighted connections p&lt;0.05, statistics in figure). Overall, diuretics had the greatest impact on brain function, possibly due to their effect on blood volume and cerebral circulation, with the effect further confirmed by fALFF analyses, showing a widespread reduction of the BOLD-signal intensity of spontaneous cerebral activity (all highlighted clusters p&lt;0.05, statistics in figure E). These findings may help inform the choice of antihypertensive treatment for individual patients, taking into account the potential cognitive and functional impact of different drugs.

Precision Medicine in Type 2 Diabetes Mellitus: Utility and Limitations.

Type 2 diabetes mellitus (T2DM) is one of the most widespread diseases in Western countries, and its incidence is constantly increasing. Epidemiological studies have shown that in the next 20 years. The number of subjects affected by T2DM will double. In recent years, owing to the development and improvement in methods for studying the genome, several authors have evaluated the association between monogenic or polygenic genetic alterations and the development of metabolic diseases and complications. In addition, sedentary lifestyle and socio-economic and pandemic factors have a great impact on the habits of the population and have significantly contributed to the increase in the incidence of metabolic disorders, obesity, T2DM, metabolic syndrome, and liver steatosis. Moreover, patients with type 2 diabetes appear to respond to antihyperglycemic drugs. Only a minority of patients could be considered true non-responders. Thus, it appears clear that the main aim of precision medicine in T2DM is to identify patients who can benefit most from a specific drug class more than from the others. Precision medicine is a discipline that evaluates the applicability of genetic, lifestyle, and environmental factors to disease development. In particular, it evaluated whether these factors could affect the development of diseases and their complications, response to diet, lifestyle, and use of drugs. Thus, the objective is to find prevention models aimed at reducing the incidence of pathology and mortality and therapeutic personalized approaches, to obtain a greater probability of response and efficacy. This review aims to evaluate the applicability of precision medicine for T2DM, a healthcare burden in many countries.