Pharmacological Treatment Research Articles

Management of open globe injury: a narrative review.

Open globe injuries are a significant global cause of visual loss, including unilateral and bilateral blindness. Prognosis is predicted by injury severity, with lower presenting visual acuity and more posterior injuries associated with poor visual outcomes, although even the most severely injured eyes with no perception of light vision may regain some visual function. In addition to severity of the primary injury, the secondary injuries and complications causing poor outcomes include proliferative vitreoretinopathy (PVR) and endophthalmitis. Endophthalmitis is common after open globe injury, affecting up to 16.5% of patients. Systemic antibiotic prophylaxis is commonly used, with a limited evidence base, while intraocular antibiotics are less commonly used but have stronger supporting evidence of efficacy. Endophthalmitis rates are also reduced by prompt primary repair, which may also support recovery of visual acuity. PVR is not prevented or treated by any pharmacologic interventions in current clinical practice, but the incidence of post-traumatic PVR may be reduced by early vitrectomy within the first 4-7 days after injury. Ocular trauma training is often limited in Western ophthalmic surgical training programmes, and patients with ocular trauma often require the input of multiple subspecialists. In this context, it is important that patients have an overview and coordination of the different aspects of their care, with ownership by one lead clinician.

Physiological Features of the Neural Stem Cells Obtained from an Animal Model of Spinal Muscular Atrophy and Their Response to Antioxidant Curcumin

The most prevalent rare genetic disease affecting young individuals is spinal muscular atrophy (SMA), which is caused by a loss-of-function mutation in the telomeric gene survival motor neuron (SMN) 1. The high heterogeneity of the SMA pathophysiology is determined by the number of copies of SMN2, a separate centromeric gene that can transcribe for the same protein, although it is expressed at a slower rate. SMA affects motor neurons. However, a variety of different tissues and organs may also be affected depending on the severity of the condition. Novel pharmacological treatments, such as Spinraza, Onasemnogene abeparvovec-xioi, and Evrysdi, are considered to be disease modifiers because their use can change the phenotypes of the patients. Since oxidative stress has been reported in SMA-affected cells, we studied the impact of antioxidant therapy on neural stem cells (NSCs) that have the potential to differentiate into motor neurons. Antioxidants can act through various pathways; for example, some of them exert their function through nuclear factor (erythroid-derived 2)-like 2 (NRF2). We found that curcumin is able to induce positive effects in healthy and SMA-affected NSCs by activating the nuclear translocation of NRF2, which may use a different mechanism than canonical redox regulation through the antioxidant-response elements and the production of antioxidant molecules.

Clinical and economic burden of acute exacerbations of idiopathic pulmonary fibrosis: a prospective observational study in Spain (OASIS study)

BackgroundIdiopathic pulmonary fibrosis (IPF) is a fatal progressive lung disease entailing significant impairment in health-related quality of life (HRQoL) and high socioeconomic burden. The course of IPF includes episodes of acute exacerbations (AE-IPF) leading to poor outcomes. This study aimed to compare management, costs and HRQoL of patients with AE-IPF to patients without AE-IPF during one year in Spain.Materials and methodsIn a 12-month, prospective, observational, multicenter study of IPF patients, healthcare resource use was recorded and costs related to AE-IPF were estimated and compared between patients with and without AE-IPF. HRQoL was measured with the St. George’s Respiratory Questionnaire (SGRQ), EuroQoL 5 dimensions 5 levels questionnaire (EQ-5D-5L), EQ-5D visual analogue scale (EQ-VAS) and the Barthel Index.Results204 IPF patients were included: 22 (10.8%) experienced ≥ 1 acute exacerbation, and 182 (89.2%) did not. Patients with exacerbations required more primary care visits, nursing home visits, emergency visits, hospital admissions, pharmacological treatments and transport use (p < 0.05 for all comparisons). Likewise, patients with exacerbations showed higher annual direct health AE-IPF-related costs. In particular, specialized visits, emergency visits, days of hospitalization, tests, palliative care, transport in ambulance and economic aid (p < 0.05 for all comparisons). Exploratory results showed that patients with AE-IPF reported a non-significant but substantial decline of HRQoL compared with patients without AE-IPF, although causality can be inferred.ConclusionWe observed significantly higher resource use and cost consumption and lower HRQoL among patients suffering exacerbations during the study. Thus, preventing or avoiding AE-IPF is key in IPF management.

High myopia: Reviews of myopia control strategies and myopia complications.

Myopia and especially high myopia are recognised as major public health concerns. Although the prevalence of high myopia in young children is low, 10-20% of high school children in Asia have high myopia, with many still progressing, and one in three patients with high myopia develop visual impairment with age. Most participants in myopia control studies have low and moderate myopia; relatively little is known about myopia control in high myopia. Literature searches were undertaken in MEDLINE and EMBASE to identify publications in English, investigating (Aim 1) the efficacy of myopia control strategies (environmental, pharmacological and optical) in high myopia (≤-6.00 D) and (Aim 2) the complications of high myopia using keywords. Outcomes included change in spherical equivalent refractive error (SE) and/or axial length (AL) to evaluate progression in high myopia. Aim 1: Twelve studies were identified that reported the efficacy of optical and pharmacological (none on environmental) interventions on AL and SE for high myopia control. A statistically significant reduction in progression of SE and AL in high myopes was reported with 1% and 0.5% atropine. Defocus Incorporated Multiple Segment spectacle lenses had lower efficacy in slowing high myopia progression compared to moderate and low myopia. Ortho-K lenses were equally effective in reducing myopia progression in low, moderate and high myopia. Aim 2: Myopic patients have an increased risk of myopic macular degeneration, retinal detachment, cataract and glaucoma, with the risk increasing with the level of myopia. High myopia has significant effects on quality of life, risk of pathological complications and vision impairment. Young children, excluding those with some syndromic associations, who are fast progressing moderate and high myopes require early intervention and close monitoring. Further research investigating the efficacy of myopia control strategies in highly myopic patients, both independently and through combination treatments, are necessary.

Non-Ergot Dopamine Agonists and the Risk of Heart Failure and Other Adverse Cardiovascular Reactions in Parkinson’s Disease

Reports suggest possible risks of adverse cardiovascular reactions, including heart failure, associated with non-ergot dopamine agonist (DA) use in Parkinson’s disease (PD). The objectives of our review were to evaluate the risk of heart failure and other adverse cardiovascular reactions in PD patients who received a non-ergot DA compared with other anti-PD pharmacological interventions, placebo, or no intervention. Studies were identified via searches of six bibliographic databases. Randomized controlled trials (RCTs) and non-randomized studies (NRS) were eligible for study inclusion. Random-effect meta-analyses were performed to estimate adverse cardiovascular reaction risks. Quality of evidence was assessed using GRADE. In total, forty-four studies (thirty-six RCTs and eight NRS) satisfied our inclusion criteria. A single RCT found no significant difference in the risk of heart failure with ropinirole compared with bromocriptine (odds ratio (OR) 0.39, 95% confidence interval (CI) 0.07 to 2.04; low certainty). Conversely, three case–control studies reported a risk of heart failure with non-ergot DA treatment. The quality of evidence for the risk of heart failure was judged as low or very low. Findings suggest that non-ergot DA use may be associated with adverse cardiovascular outcomes, including heart failure. Studies are needed to better understand cardiovascular risks associated with PD treatment.

Outcomes of Mitral Valve Regurgitation Management after Expert Multidisciplinary Valve Team Evaluation

Background/Objectives: Mitral regurgitation (MR) affects millions worldwide, necessitating timely intervention. There are significant clinical challenges in the conservative management of MR, leaving a knowledge gap regarding the impact of multidisciplinary decision-making on treatment outcomes. This study aimed to provide insights into the impact of multidisciplinary decision-making on the survival outcomes of MR patients, focusing on conservative approaches. Methods: This study retrospectively analyzes 1365 patients evaluated by an expert multidisciplinary heart team (MDT) in a single center from 2015 to 2022. Treatments included surgery, catheter-based interventions, and conservative management. Propensity matching was utilized to compare surgery and conservative approaches. Results: Surgical intervention was associated with superior long-term survival outcomes compared to conservative and catheter-based treatments, particularly for degenerative MR (DMR). Survival rates of patients deemed by the MDT to have non-severe DMR were comparable to surgical patients (HR 1.07, 95% CI: 0.37–3.12, p = 0.90). However, non-severe functional MR (FMR) patients trended towards elevated mortality risk (HR 1.77, 95% CI: 0.94–3.31, p = 0.07). Pharmacological treatment for DMR was associated with significantly higher mortality compared to surgery (HR 8.0, 95% CI: 1.78–36.03, p = 0.001). Functional MR patients treated pharmacologically exhibited a non-significantly higher mortality risk compared to surgical intervention (HR 1.93, 95% CI: 0.77–4.77, p = 0.20). Conclusions: Survival analysis revealed significant benefits for surgical intervention, contrasting with elevated mortality risks associated with conservative management. “Watchful waiting” may be appropriate for non-severe DMR, while FMR may require closer monitoring. Further research is needed to assess the impact of regular follow-up or delayed surgery on survival rates, as pharmacological therapy has limited long-term efficacy for DMR.

Conservative versus Invasive Approaches in Temporomandibular Disc Displacement: A Systematic Review of Randomized Controlled Clinical Trials

Background: Temporomandibular disorders (TMDs) frequently cause orofacial pain and dysfunction, with treatment options spanning from conservative therapies to invasive surgical procedures. The aim of this systematic review was to analyze and compare the efficacy and safety profiles of conservative, minimally invasive interventions and surgical procedures in patients diagnosed with TMDs and disc displacement. Methods: Following PRISMA recommendations, PubMed, Scopus, and Web of Science databases were searched for randomized clinical trials (RCT). Data were synthesized in a table and evaluated through the Cochrane risk of bias 2 (RoB 2) tool. Results: Thirty-eight RCTs, most with moderate RoB, were selected. Conservative approaches, including physical therapy and occlusal devices, led to an improvement in symptoms and function. Pharmacological treatments demonstrated effectiveness in reducing pain and improving function; however, they can have undesirable side effects. Minimally invasive and invasive treatments also demonstrated efficacy, although most trials did not show their superiority to conservative treatments. Conclusion: The primary approach to TMDs should be a conservative, multimodal treatment plan tailored to patient complaints and characteristics. Treatment goals should focus on symptom control and functional recovery. Surgical treatment should be reserved for cases with a precise diagnosis and a clear etiology.

Delivery of Synthetic Interleukin-22 mRNA to Hepatocytes via Lipid Nanoparticles Alleviates Liver Injury.

Hepatocellular injury, a pivotal contributor to liver diseases, particularly hepatitis, lacks effective pharmacological treatments. Interleukin-22 (IL-22), crucial for liver cell survival, shows potential in treating liver diseases by regulating repair and regeneration through signal transducer and activator of transcription 3 (STAT3) activation. However, the short half-life and off-target effects limit its clinical applications. To address these issues, lipid nanoparticles are employed to deliver synthetic IL-22 mRNA (IL-22/NP) for in situ IL-22 expression in hepatocytes. The study reveals that IL-22/NP exhibits liver-targeted IL-22 expression, with increased IL-22 levels detected in the liver as early as 3h postintravenous injection, lasting up to 96h. Furthermore, IL-22/NP activates STAT3signaling in an autocrine or paracrine manner to upregulate downstream factors Bcl-xL and CyclinD1, inhibiting hepatocyte apoptosis and promoting cell proliferation. The therapeutic efficacy of IL-22/NP is demonstrated in both chronic and acute liver injury models, suggesting IL-22 mRNA delivery as a promising treatment strategy for hepatitis and liver diseases involving hepatocellular injury.

A Systematic Review of Economic Evidence of Cardiovascular Interventions in India.

Cardiovascular diseases (CVDs) continue to be the primary cause of mortality globally and invariably in India as well. The rapid upsurge in the prevalence of CVDs in India has created a pressing need to promote contemporary, sustainable, and cost-effective interventions to tackle the CVD burden. This systematic review integrates the research-based evidence of the cost-effectiveness of various interventions that can be adapted to control CVDs in India. Databases, namely, PubMed, Cochrane Library, Embase, and Google Scholar, were searched for data on the economic evaluation of interventions targeting CVD based on the Indian population for a period of 30 years (1991-2021). Two reviewers assessed the articles for eligibility, and data were extracted from the shortlisted articles as per a predefined template, including the quantification of methodological aspects. In total, 1249 studies were examined, out of which 23 completely met the inclusion criteria for full-text review. A total of 16 studies were based solely on the Indian population, while the rest (7) included South Asia/Asia for the intervention, of which India was a participant nation. Most of the economic evaluations targeted treatment-based or pharmacological interventions (14) for CVDs. The evaluations were based on Decision-based models (10), Randomized controlled Trials (RCTs) (9), and Observational studies (4). The cost-effectiveness ratio for the included studies exhibited a diverse range due to variations in methodological approaches, such as differences in study settings, populations, and inconsistencies in study design. The mean ICER (Incremental Cost-effectiveness ratio) for primordial and primary preventions was found to be 3073.8 (US $2022) and 17489.9 (US $2022), respectively. Moreover, the combined mean value for secondary and tertiary prevention was 2029.6 (US$2022). The economic evidence of public health interventions are expanding, but their focus is restricted towards pharmacological interventions. There is an urgency to emphasize primordial and primary prevention for better outcomes in health economics decision-making. Technology- based avenues for intervention need more exploration in order to cater to a large population like India.

The Effect of Endorphin Massage on the Intensity of Dysmenorrhea in Adolescent Girls

Dysmenorrhea is often experienced by young women, this can disturb your sense of comfort and interfere with daily activities, generally it is not dangerous but must be treated immediately. Dysmenorrhea usually occurs before or during menstruation, starting from one to two days before menstruation or during menstruation. Dysmenorrhea treatment can be divided into two categories, namely pharmacological and non-pharmacological. Pharmacological treatment such as consuming non-steroidal anti-inflammatory drugs (NSAIDs), while non-pharmacological treatment can be done with Endorphin Massage. Endorphin Massage has the effect of stimulating the body to release endorphin compounds which are pain relievers and can create a feeling of comfort, which is a therapeutic action that is useful for improving physical and psychological conditions. The aim of the research was to determine the effect of giving endorphin massage on reducing dysmenorrhea in young women. The research design used was Quasi Experimental with a pre-experimental design, with one group pretest-posttest. to see the effect of Endorphin Massage before and after the intervention. The sample size was 30 respondents. The sampling technique used consecutive sampling which had been adjusted to the inclusion criteria and exclusion criteria. This study used the Wilcoxon statistical test with a significance level of α = 0.05. The results of this study showed a value of ρ = 0.000, where the value of ρ

The Effect of Intra-Articular Injections of Hyaluronic Acid for the Treatment of Trapezio-Metacarpal Joint Osteoarthritis

Background: Osteoarthritis of the basal thumb joint is a debilitating disease with a high prevalence. Among pharmacological treatments, intra-articular injections of hyaluronic acid have been clinically applied. This study aimed to investigate the effectiveness and safety of intra-articular injections of hyaluronic acid for the treatment of trapezio-metacarpal joint osteoarthritis (TMOA), over a one-year period. Methods: Patients with TMOA were enrolled and treated with five consecutive intra-articular injections of hyaluronic acid (20 mg/2 mL, 500–750 KDa, HyalganBio) at weekly intervals. Primary outcomes were pain during different activities (changes in numerical rating scale) and function (pinch and grip strength), and secondary outcomes were safety (adverse events) and patient-reported outcomes (quick-DASH and SF-12). The outcomes were evaluated at baseline and 1-, 3-, 6-, and 12- months after the last injection. Results: A total of 29 patients were included. All participants completed the five injective sessions and the first follow-up. A total of 15 patients completed the study. During the follow-up period, intra-articular injections of hyaluronic acid have significantly reduced spontaneous and provoked pain and improved disability. No severe systemic adverse events were reported. Conclusions: At a follow-up of up to 12 months, patients with TMOA treated with intra-articular hyaluronic acid injections reported improvements in pain relief and quality of life.

Community pharmacists’ comfort levels with and barriers to application of an expanded scope of practice in Québec

Background: In recent years, community pharmacists have seen their profession transition from a dispensing-focused role to a rapidly evolving clinically oriented practice. In Québec, Bill 31, adopted in 2020, increased the clinical opportunities for pharmacists with independent prescribing privileges in various defined clinical situations. As this expanded role can lead to different barriers, it is crucial to explore pharmacists’ comfort levels with implementing such changes in their practice. Methods: A web-based survey was conducted from March 25 to May 28, 2021, among community pharmacists in Québec. We collected data with a questionnaire developed for this study. Questions were grouped into 4 domains: (1) characteristics of the respondents; (2) workload and work setting; (3) comfort level with, and barriers to, adjusting medications and following up pharmacologic treatments (86 clinical situations evaluated); and (4) general barriers and facilitators to implementation. Results: A total of 146 community pharmacists completed the questionnaire. Most were women (71.9%), younger than 50 years of age (86.2%), had a bachelor’s degree (64.4%) as their highest academic level and had more than 10 years of experience as pharmacists (56.8%). Most of them worked exclusively in a community pharmacy (86.3%). Among the 86 clinical situations evaluated, there were 16 in which at least 80% of respondents felt comfortable. The main barriers identified were a lack of knowledge, experience and dedicated time and difficulties integrating these activities into the workflow; facilitators were having an adequate environment and resources. Conclusion: This study shows community pharmacists can confidently adjust pharmacotherapy for several conditions. However, they must have adequate time and resources. Also, the more complex the clinical situations were, the less comfortable community pharmacists felt adjusting pharmacotherapy. This study identified several areas where continuing education, training and mentoring could be offered and where the work environment and organization could be improved.

Advancements in Alzheimer's Disease: Emerging Therapies, Lifestyle Modifications, and Early Intervention Strategies

Alzheimer’s disease (AD), the most prevalent form of dementia, represents a major global health challenge, affecting over 45 million people worldwide with projections to triple by 2050 [1]. This progressive, irreversible neurodegenerative disease leads to cognitive decline, behavioural changes, and a significant socioeconomic burden [2]. Despite extensive research into its complex pathophysiology, involving beta-amyloid plaques and tau protein tangles, the exact causes remain a mix of genetic, environmental, and lifestyle factors [3]. Current treatments primarily focus on symptom management, as no cure exists [4]. This literature review synthesises recent advancements in Alzheimer’s research, exploring new pharmacological treatments, emerging therapies, and the efficacy of prevention strategies. It particularly examines how lifestyle modifications and risk factor management influence disease progression. The review highlights the potential of early intervention in at-risk individuals, aiming to prevent significant neuronal damage before clinical symptoms appear. It discusses the impact of various lifestyle factors such as diet, exercise, mental and social engagement, and cardiovascular health on AD risk. Understanding these connections is crucial, given the ageing population and rising prevalence of AD. This review aims to inform better clinical practices and health policies, potentially reducing Alzheimer’s impact and guiding healthcare professionals, researchers, and policymakers in effective interventions. Ultimately, these insights could substantially alleviate the socioeconomic burden of Alzheimer’s disease and improve public health outcomes.

The Analysis Study of Efficacy and Safety of Topical Anesthetic Agent for Treatment of Premature Ejaculation: A Comprehensive Systematic Review

Background: Premature ejaculation (PE) affects 20-30% of men globally, with lifelong and acquired types requiring diverse behavioral and pharmacological treatments. This systematic review aims to analyze current evidence on the efficacy and safety of topical anesthetic agent for treatment of premature ejaculation based on literatures of the last 10 years. Methods: The study adhered to PRISMA 2020 standards, examining English literature from 2014 to 2024. PubMed, SagePub, SpringerLink, and Google Scholar were utilized as literature sources. Result: Initially retrieving 360 articles from online databases (PubMed, SagePub, SpringerLink and Google Scholar) six relevant papers were selected after three rounds of screening for full-text analysis. Conclusion: Overall, the evidence suggests that topical anesthetic agents are effective in treating PE. These agents consistently improve IELT and patient satisfaction, with a favorable safety profile. The findings also highlight the importance of individualized treatment approaches, considering patient preferences, sexual habits, and the specific characteristics of PE.

HUBUNGAN TUGAS KESEHATAN KELUARGA DENGAN MANAJEMEN DIRI KLIEN HIPERTENSI DI PUSKESMAS SILO 1 KABUPATEN JEMBER

The role of the family is very important in carrying out family health duties for family members who carry out hypertension self-management. Apart from the family, the role of health workers is to carry out strategies for pharmacological and non-pharmacological treatment. The Health Promotion model is a non-pharmacological strategy that must be implemented by health workers. This research is to determine the relationship between family health tasks and self-management of hypertensive clients at the Silo 1 Health Center, Jember Regency. This research design uses a correlational cross sectional approach, the population is 454 hypertensive clients, the size used is 213 hypertensive clients, the sampling technique uses simple random sampling, data analysis uses the Spearman Rank test. Tested using the family health task questionnaire and HSMBQ. Based on the research results, most of the family health tasks were in the quite good category, numbering 159 people (74.7%) while hypertensive clients who had quite good self-management were 172 respondents (80%). Analysis of the relationship between family health tasks and self-management resulted in a p value = 0.012 with r = 0.172 so that H0 was rejected, which means there is a significant relationship between family health tasks and self-management of hypertensive clients. The results of this study can be a basis for health workers, especially those who focus on hypertension health problems, to make efforts to improve health promotion.

Effectiveness of deep brain stimulation on refractory aggression in pediatric patients with autism and severe intellectual disability: meta-analytic review

Some patients with autism and severe intellectual disability may experience uncontrolled aggression, causing serious injury or harm to others, and the therapeutic ineffectiveness of traditional pharmacological and behavioral treatment may aggravate symptoms. Deep brain stimulation (DBS) has been tested in patients with little evidence in children and adolescents. Therefore, we analyzed the efficacy and safety of DBS in refractory aggression in pediatric subjects with autism (ASD) and severe intelligence deficit (ID).Methods A meta-analytic review of Web of Science (WOS) and Scopus articles, following Prisma criteria. A total of 555 articles were identified, but after applying the inclusion criteria, only 18 were analyzed. The review of the registries and the extraction of information was performed by 2 independent groups, to reduce the evaluator’s bias. For the description of the results, pediatric patients with ASD or ID present in each registry, with an application of specialized scales (Overt aggression scale, OAS, and THE modified version of the OAS, MOAS) pre and post-DBS, with a clinical follow-up of at least 12 months, were considered valid. Clinical improvement was calculated using tests of aggressiveness. In each registry with available data and then pooling the means of all patients in the OAS and MOAS, the effect size of DBS (overall and per study) was estimated. Finally, the adapted NOS scale was applied to rate the studies’ quality and level of bias.Results In the studies analyzed, 65/100 were pediatric patients, with a mean age of 16.8 years. Most of the studies were conducted in South America and Europe. In all teams, aggressive behavior was intractable, but only 9 groups (53/65) applied specialized scales to measure aggressiveness, and of these, only 51 subjects had a follow-up of at least 12 months. Thus, in 48/51 a clinical improvement of patients was estimated (94.2%), with a considerable overall effect size (OAS: d = 4.32; MOAS: d = 1.46). However, adverse effects and complications were found in 13/65 subjects undergoing DBS. The brain target with the most evidence and the fewest side effects was the posteromedial hypothalamic nuclei (pHypN). Finally, applying the adapted NOS scale, quality, and bias, only 9 studies show the best indicators.Conclusion An optimal level of efficacy was found in only half of the publications. This is mainly due to design errors and irrelevant information in the reports. We believe that DBS in intractable aggressiveness in children and adolescents with ASD and severe ID can be safe and effective if working groups apply rigorous criteria for patient selection, interdisciplinary assessments, objective scales for aggressiveness, and known surgical targets.

The role of pharmacological interventions in managing hyperlipidemia: A closer look at different drugs

Hyperlipidemia is a medical condition characterized by an increase in plasma lipids, including triglycerides, cholesterol, cholesterol esters, phospholipids, and plasma lipoproteins, which is a leading risk factor for cardiovascular diseases. The pathophysiology of hyperlipidemia is influenced by endothelial damage to blood vessels, leading to a loss of nitric oxide, increased inflammation, and lipid accumulation in the deepest layer of the endothelial wall. Lipid-lowering drugs like statins can reduce LDL levels by 25-60%, but they have negative impacts on clinical outcomes. Lipoprotein metabolism involves various enzymes, and atherosclerosis accumulates fat, cholesterol, and calcium in artery linings, creating fibrous plaques that reduce blood flow and oxygen supply, leading to heart damage and death. Lipoprotein metabolism involves various enzymes, including lipoprotein lipase (LPL), hepatic lipase (HL), lecithin cholesterol acyl transferase (LCAT), cholesterol ester transfer protein (CETP), microsomal triglyceride protein (MTP), and acyl Co-A transferase (ACAT). Atherosclerosis accumulates fat, cholesterol, and calcium in artery linings, creating fibrous plaques. This leads to reduced blood flow and oxygen supply, causing heart damage and death. Reducing LDL and total cholesterol can significantly lower the incidence of strokes. Reducing LDL and total cholesterol can significantly lower the incidence of strokes. Traditional antihyperlipidemic medicines have negative effects, and herbal treatments like onion, garlic, guggul, and Asparagus racemosus have been shown to have anti-diabetic and antihyperlipidemic properties.

Screening Targets and Therapeutic Drugs for Alzheimer's Disease Based on Deep Learning Model and Molecular Docking.

Alzheimer's disease (AD) is a neurodegenerative disorder caused by a complex interplay of various factors. However, a satisfactory cure for AD remains elusive. Pharmacological interventions based on drug targets are considered the most cost-effective therapeutic strategy. Therefore, it is paramount to search potential drug targets and drugs for AD. We aimed to provide novel targets and drugs for the treatment of AD employing transcriptomic data of AD and normal control brain tissues from a new perspective. Our study combined the use of a multi-layer perceptron (MLP) with differential expression analysis, variance assessment and molecular docking to screen targets and drugs for AD. We identified the seven differentially expressed genes (DEGs) with the most significant variation (ANKRD39, CPLX1, FABP3, GABBR2, GNG3, PPM1E, and WDR49) in transcriptomic data from AD brain. A newly built MLP was used to confirm the association between the seven DEGs and AD, establishing these DEGs as potential drug targets. Drug databases and molecular docking results indicated that arbaclofen, baclofen, clozapine, arbaclofen placarbil, BML-259, BRD-K72883421, and YC-1 had high affinity for GABBR2, and FABP3 bound with oleic, palmitic, and stearic acids. Arbaclofen and YC-1 activated GABAB receptor through PI3K/AKT and PKA/CREB pathways, respectively, thereby promoting neuronal anti-apoptotic effect and inhibiting p-tau and Aβ formation. This study provided a new strategy for the identification of targets and drugs for the treatment of AD using deep learning. Seven therapeutic targets and ten drugs were selected by using this method, providing new insight for AD treatment.

What Is the Link between Attention-Deficit/Hyperactivity Disorder (ADHD) and Dyslipidemia in Adults? A German Retrospective Cohort Study

Background: Alterations in the serum lipid profile have been suspected in many psychiatric disorders, such as schizophrenia and depression. However, studies on lipid status in attention-deficit/hyperactivity disorder (ADHD) are sparse and inconsistent. Methods: Using the nationwide, population-based IQVIA Disease Analyzer database, this retrospective cohort study included 5367 outpatients from general practices in Germany aged ≥18 years with a documented first diagnosis of ADHD between January 2005 and December 2021 and 26,835 propensity score-matched individuals without ADHD. Study outcomes were the first diagnosis of lipid metabolism disorders as a function of ADHD within up to 10 years of the index date. The cumulative 10-year incidence was analyzed using Kaplan–Meier curves and compared using the log-rank test. In addition, univariate Cox regression analyses were performed. Results: In the regression analysis, there was no significant association between ADHD and subsequent lipid metabolism disorders in the total population (HR: 0.94; 95% CI: 0.83–1.08), among women (HR: 1.04; 95% CI: 0.84–1.28), and among men (HR: 0.89; 95% CI: 0.74–1.06). In addition, no significant association was observed in the disease-stratified analyses. Conclusions: The findings of this study indicate that ADHD does not exert an influence on lipid metabolism. However, further investigation is warranted, particularly with respect to pharmacological interventions.

Accelerating evidence synthesis for safety assessment through ClinicalTrials.gov platform: a feasibility study

BackgroundStandard systematic review can be labor-intensive and time-consuming meaning that it can be difficult to provide timely evidence when there is an urgent public health emergency such as a pandemic. The ClinicalTrials.gov provides a promising way to accelerate evidence production.MethodsWe conducted a search on PubMed to gather systematic reviews containing a minimum of 5 studies focused on safety aspects derived from randomized controlled trials (RCTs) of pharmacological interventions, aiming to establish a real-world dataset. The registration information of each trial from eligible reviews was further collected and verified. The meta-analytic data were then re-analyzed by using 1) the full meta-analytic data with all trials and 2) emulated rapid data with trials that had been registered and posted results on ClinicalTrials.gov, under the same synthesis methods. The effect estimates of the full meta-analysis and rapid meta-analysis were then compared.ResultsThe real-world dataset comprises 558 meta-analyses. Among them, 56 (10.0%) meta-analyses included RCTs that were not registered in ClinicalTrials.gov. For the remaining 502 meta-analyses, the median percentage of RCTs registered within each meta-analysis is 70.1% (interquartile range: 33.3% to 88.9%). Under a 20% bias threshold, rapid meta-analyses conducted through ClinicalTrials.gov achieved accurate point estimates ranging from 77.4% (using the MH model) to 83.1% (using the GLMM model); 91.0% to 95.3% of these analyses accurately predicted the direction of effects.ConclusionsUtilizing the ClinicalTrials.gov platform for safety assessment with a minimum of 5 RCTs holds significant potential for accelerating evidence synthesis to support urgent decision-making.