Efficacy Of Medications Research Articles

Exploring the Efficacy of Herbal Medications in the Treatment of Parkinsonism: A Mini Review

Background: Over 10 million people worldwide are affected by the chronic neurodegenerative condition of Parkinson's disease. Dopaminergic neurons in the Substantia Nigra area of the brain are gradually lost as a result. Herbal medicine, which have its roots in ancient cultures, uses medicinal herbs to treat illnesses and advance general health. There is considerable interest in researching the possibilities of herbal medicine for treating neurodegenerative diseases like Parkinson's disease because they are thought to be safer than synthetic medications. Objective: The objective of this article is to investigate the potential of herbal medications as a treatment option for Parkinsonism, and to provide a clear understanding of the current state of research on this topic. Conclusion: This review focuses on herbal treatments and components that have demonstrated promise in Parkinson's disease in vitro and animal models. This information can be used to identify prospective traditional medicine prescription therapies. New therapeutic treatments for Parkinson's disease may result from further study of pharmaceutical components with well-established therapeutic potential.

Influence of oncology nurses' decision-making and personality traits on missed nursing care and related factors: a correlational study.

ObjectivesTo identify Missed Nursing Care (MNC) and related factors, as well as analyze the influence of nurses’ decision-making and personality traits on MNC in two Portuguese hospitals dedicated to cancer care. MethodsA cross-sectional, multicentric, descriptive-correlational study was conducted using a convenience sample of 298 nurses working in two hospitals dedicated to cancer care. Data were collected in the first semester of 2023 using a questionnaire that included sociodemographic and professional questions and the Portuguese versions of the MISSCARE Survey, the Nursing Decision-Making Instrument (NDMI-PT), and the Ten-Item Personality Inventory (TIPI-P). ResultsNurses missed care occasionally, namely in the dimensions related to Patient empowerment/autonomy care and Efficacy of feeding and medication. Staffing, Patient volume and acuity, and Management and organization were moderate to significant reasons for MNC. The flexible decision-making style was predominant (81.5%). The most prevalent personality traits were Conscientiousness, Agreeableness, and Openness to experience. Significant correlations were found between the four stages of the decision-making process and the personality traits and several dimensions of MNC. Data collection to assess a patient’s condition was negatively correlated with Team communication and Material resources. Similarly, the Emotional stability trait was negatively correlated with Team communication and Patient volume and acuity. ConclusionsThis study identified MNC and factors that can influence the quality of care. It is crucial to promote nurses’ training and specialization within healthcare teams, with a particular focus on enhancing some of their personality traits to make them more effective and efficient therapeutic agents.

Pencil Graphite Electrode Decorated with Gold Nanoparticles for Therapeutic Monitoring of Meropenem in Human Plasma

Abstract A fast, reliable, and cost-effective electrochemical voltammetric sensor has been developed for the ultrasensitive detection of Meropenem (MER), a non-classical β-lactam antibiotic, for therapeutic monitoring purposes in the evolution of personalized medicine. Enhanced voltammetric response was attained at a disposable pencil graphite electrode (PGE) decorated with electro-deposited gold nanoparticles (Au-NPs/PGE). Under optimized conditions, the modified sensor demonstrated a marked increase in the anodic peak current of meropenem compared to bare PGE. Differential pulse voltammetry (DPV) enabled the successful determination of MER across a linear concentration range of 1.0 ×10^(-8) and 7.0 ×10^(-5) M MER, with a detection limit of 3.31 ×10^(-9) M in Britton–Robinson buffer pH 2.0. The high sensitivity and reproducibility of the proposed sensor provided an effective sensing platform for MER in pharmaceutical formulations and spiked human plasma. The suggested sensor is capable of MER determination in human plasma as low as 5.0 ×10-7 M. It displayed a great potential for its point-of-care applicability for monitoring MER levels in human plasma, ensuring medication safety and efficacy for patients in critical care units. The proposed methodology was further assessed confirming the alliance with green and white analytical chemistry strategies.

P-1152. Cefepime, Meropenem, and Piperacillin Therapeutic Drug Monitoring in Neonatal and Pediatric Patients

Abstract Background Pharmacokinetics of beta-lactams vary widely in neonatal and pediatric patients due to developmental biology and critical illness. Cefepime (FEP), meropenem (MEM), and piperacillin/tazobactam (TZP) are highly susceptible to pharmacokinetic changes as hydrophilic, small molecules with renal clearance. Subtherapeutic levels are associated with clinical and microbiologic failure, and supratherapeutic levels associated with toxicity. Beta-lactam therapeutic drug monitoring (TDM) may optimize the effectiveness and safety of these agents. The purpose of this investigation is to describe the % of pediatric and neonatal patients with beta-lactam serum levels within target range. Methods In August 2023, TDM launched at the Mayo Clinic Children’s Center for select patients treated with FEP, MEM, or TZP with expected durations ≥ 48 hours, or who were on kidney replacement therapy (KRT), extracorporeal membrane oxygenation (ECMO), weighed > 120 kg, had a BMI > 95th percentile, or at the discretion of pediatric ID team. Validated drug assays were performed daily, Monday through Friday. A two-level sampling strategy was preferred with a peak 1 hour after the end of the infusion and a trough 30 minutes before the next dose. Empiric trough target ranges were set at FEP 8-50 mg/L, MEM 2-30 mg/L, and piperacillin 16-150 mg/L. These target ranges were adjusted with confirmed microbiology to a time above the minimum inhibitory concentration of the organism for 100% of the dosing interval (100%T > MIC). Results From August 2023 to April 2024, 74 episodes of TDM were performed on 45 patients. Thirty-seven (82%) patients were in an intensive care unit (ICU) at the time of TDM, 8/45 (22%) of whom were in the neonatal ICU. Target range was achieved in 67% of patients on FEP, 50% on MEM, and 52% on TZP. Median (IQR) trough values were 22.1 (8.6, 44.2) mg/L for FEP, 0.6 (0, 4.1) mg/L for MEM, and 15.5 (3.8, 27.1) mg/L for TZP. Seven levels were above target for FEP and 0 for MEM and TZP. Seven levels were below target for FEP, 4 for MEM, and 11 for TZP. Conclusion Implementation of a TDM program for FEP, MEM and TZP in pediatric and neonatal patients revealed drug levels frequently outside target range. TDM may facilitate dose individualization to optimize medication efficacy and minimize toxicity. Disclosures Raymond Stetson, MD, MS, Moderna: Grant/Research Support Christina G. Rivera (O'Connor), Pharm.D, Gilead Sciences: Board Member Erin F. Barreto, PharmD, MSc, Baxter Health: Advisor/Consultant|Wolters Kluwer: Advisor/Consultant

Comparative Efficacy of Nonsteroid Immunosuppressive Medications in Childhood Nephrotic Syndrome

Cyclophosphamide and calcineurin inhibitors are the most used nonsteroid immunosuppressive medications globally for children with various chronic inflammatory conditions. Their comparative effectiveness remains uncertain, leading to worldwide practice variation. Nephrotic syndrome is the most common kidney disease managed by pediatricians globally and suboptimal treatment is associated with high morbidity. To evaluate the comparative effectiveness of cyclophosphamide vs calcineurin inhibitors (tacrolimus or cyclosporine) for childhood nephrotic syndrome relapse prevention. Using target trial emulation methods, the study team emulated a pragmatic, open-label clinical trial using available data from the Insight Into Nephrotic Syndrome: Investigating Genes, Health, and Therapeutics (INSIGHT) study. INSIGHT is a multicenter, prospective cohort study in the Greater Toronto Area, Canada. Participants included children (1 to 18 years) with steroid-sensitive nephrotic syndrome diagnosed between 1996 and 2019 from the Greater Toronto Area, who initiated cyclophosphamide or a calcineurin inhibitor treatment. Data analysis was performed in 2024. Incident cyclophosphamide or calcineurin inhibitor treatment. Randomization was emulated by overlap weighting of propensity scores for treatment assignment. The primary outcome was time to relapse, analyzed by weighted Kaplan-Meier and Cox proportional hazards models. Secondary outcomes included relapse rates, subsequent immunosuppression, kidney function, hypertension, adverse events, and quality of life. Of 578 children (median age at diagnosis, 3.7 [IQR, 2.8-6.0] years; 371 male [64%] and 207 female [36%]), 252 initiated cyclophosphamide, 131 initiated calcineurin inhibitors, and 87 sequentially initiated both medications. Baseline characteristics were well balanced after propensity score weighting. During median 5.5-year (quarter 1 to quarter 3, 2.5-9.2) follow-up, there was no significant difference in time to relapse between calcineurin inhibitor vs cyclophosphamide treatment (hazard ratio [HR], 1.25; 95% CI, 0.84-1.87). Relapses were more common after calcineurin inhibitor treatment than cyclophosphamide (85% vs 73%) in the weighted cohorts, but not statistically significant. There were also no significant differences in subsequent relapse rates, nonsteroid immunosuppression use, or kidney function between medications. Calcineurin inhibitor treatment was associated with more hospitalizations (HR, 1.83; 95% CI, 1.14-2.92) and intravenous albumin use (HR, 2.81; 95% CI, 1.65-4.81). In this study, there was no evidence of difference in time to relapse after cyclophosphamide and calcineurin inhibitor treatment in children with nephrotic syndrome. Cyclophosphamide treatment is shorter in duration and more accessible globally than calcineurin inhibitors.

P0577 Influence of Pregnancy on Outcomes of Inflammatory Bowel Disease and Medication Adherence

Abstract Background Treatment of inflammatory bowel disease (IBD) is challenging due to the maintenance of remission and associated fetal safety concerns during pregnancy. While existing literature emphasizes the importance of achieving remission prior to conception, optimal management of IBD during pregnancy remains underexplored, especially regarding medication continuation and efficacy. Methods This cross-sectional study was performed in pregnant patients with IBD between March 2019 and June 2023. Clinical features, treatment details, disease activation and outcomes were collected and analyzed. Results A total of 57 pregnant were included, of those 37 (64.9%) had UC, and 20 (35.1%) had CD. The overall median disease duration was 9.1 (6-12.8) years (8.2 years for UC and 9.9 years for CD). The disease location was 19 (51.4%) left-sided colitis, 15 (40.5%) extensive, and 3 (8.1%) proctitis in UC, while in CD 8 (40%) patients were ileal involvement, 8 (40%) ileocolonic and 4 (20%) colonic. 4 (20%) had stricturing disease and 4 (20%) had penetrating disease in CD. Before pregnancy, medical treatments for UC patients were mesalazine in 29 (78.4%) patients, thiopurine in 20 (54.1%), biologic therapy in 6 (16.2%), while it was 13 (65%) patients biologic therapy and 7 (35%) thiopurine in CD patients. The most prescribed biologic agent was infliximab in both diseases. During pregnancy, 16 (28.1%) patients [6 (18.8%) with UC and 10 (50%) with CD] had a history of drug withdrawal. 13 (%81) medications were withdrawn by the patient's wish. Disease activation occurred in 25 (43.9%) patients, 10 (50%) with CD, and 15 (40.5%) with UC. 12 (48%) patients required steroids due to activation. There were 54 (94.7%) live births when compared based on whether disease activation developed or not, there was no statistically significant difference in live birth rate 23, 92% vs. 31, 96.9%, p=0.576. There was no statistically significant difference between normal birth and cesarean section rates with activation development. 3 (5%) abortions occurred. Abortion rate was not associated with disease activation (p>0.05). No serious infection occurred during the first month following birth. Conclusion In this study, the disease activation was seen in 43.9% of pregnant patients with IBD. Consistent medication management of IBD during pregnancy enhances patient adherence, reduces risks, and promotes positive maternal outcomes. Proactive counseling and careful selection of medications are crucial for disease control and optimizing pregnancy outcomes in IBD patients.

P0859 Handgrip Strength and Physical Activity in Children with IBD: Insights into Sarcopenia Risk

Abstract Background Approximately 15-20% of patients with inflammatory bowel disease (IBD) are diagnosed in childhood. Sarcopenia is known to be a poor prognostic factor, contributing to prolonged hospital stays, increased surgical complications, and reduced medication efficacy. While about one-third of adult IBD patients are affected by sarcopenia, data on its prevalence and impact in pediatric IBD are limited. Our aim was to assess and compare the physical activity and handgrip strength of healthy children and paediatric patients with IBD. Methods Single-centre, non-interventional case-control study. Anthropometric data, sex and age of healthy and sick children were recorded. Hand grip strength and physical activity were assessed using the JAMAR hydraulic hand dynamometer and PAQ-C questionnaire. Based on handgrip strength, the risk of sarcopenia was categorized into three groups using the Hungarian NETFIT database: ‘high risk’ (significant development needed), ‘some risk’ (improvement needed), and ‘healthy’. Results We analyzed data from 75 children with IBD (33 with Crohn’s disease, 40 with ulcerative colitis, and 2 with IBD-U) and 75 healthy controls. Girls comprised 42.5% of the cohort. The mean age was 15.5 ± 1.9 years in both groups. Most IBD patients (82.7%) were in remission, with a BMI z-score of 0.17 ± 1.6 kg/m² compared to -0.16 ± 0.8 kg/m² in healthy controls. Based on handgrip strength, 24% of IBD patients were at ‘some risk’ and 39% at ‘high risk’ for sarcopenia, while none of the healthy children were in the ‘high risk’ group and 33% were in the ‘some risk’ group. Physical activity (PAQ-C score) was significantly higher in healthy children compared to those with IBD (2.4 ± 0.61 vs. 2.1 ± 0.6, p < 0.05). Conclusion Compared to healthy peers, children with IBD exhibit a higher prevalence of muscle strength requiring improvement and lower physical activity levels, even though the majority were in remission. Our findings highlight the importance of assessing physical activity and sarcopenia in children with IBD.

The interplay between gut microbiota composition and dementia.

Recently, researchers have been interested in the potential connection between gut microbiota composition and various neuropsychological disorders. Dementia significantly affects the socioeconomics of families. Gut microbiota is considered as a probable factor in its pathogenesis. Multiplebacterial metabolites such as short-chain fatty acids, lipopolysaccharides, and various neurotransmitters that are responsible for the incidence and progression of dementia can be produced by gut microbiota. Various bacterial species such as Bifidobacterium breve, Akkermansia muciniphila, Streptococcus thermophilus, Escherichia coli, Blautia hydrogenotrophica, etc. are implicated in the pathogenesis of dementia. Gut microbiota can be a great target for imitating orinhibiting their metabolites as an adjunctive therapy based on their role in its pathogenesis. Therefore, some diets can prevent or decelerate dementia byaltering the gut microbiota composition. Moreover, probiotics can modulate gut microbiota composition by increasing beneficial bacteria and reducing detrimental species. These therapeutic modalities are considered novel methods that are probably safe and effective. They can enhance the efficacy of traditional medications and improve cognitive function.

Review Article: Pathways to Precision: Advancing the Understanding of Drug Administration Methods

This review explores various routes of drug administration, discussing their advantages, limitations, and applications. It emphasizes the importance of choosing the appropriate route based on pharmacokinetics, patient condition, and the nature of the drug, aiming to provide an in-depth understanding of the current landscape in drug delivery. The route of drug administration plays a pivotal role in determining the efficacy, onset, and overall therapeutic outcome of medications. This review comprehensively explores the diverse pathways through which drugs are introduced into the human body, highlighting their mechanisms, advantages, limitations, and applications. Broadly categorized into enteral, parenteral, and topical routes, each method is tailored to specific clinical needs based on factors such as the physicochemical properties of the drug, patient condition, and desired therapeutic goals. Innovations in drug delivery, including transdermal systems, inhalation devices, and targeted delivery techniques, have further expanded the scope of administration, enhancing precision and minimizing adverse effects. The review also emphasizes the importance of patient compliance, bioavailability considerations, and the impact of administration routes on pharmacokinetics and pharmacodynamics. By delving into traditional methods such as oral and intravenous routes alongside emerging technologies like nanocarriers and implantable devices, this paper aims to provide a holistic understanding of drug administration. The insights presented herein offer valuable perspectives for clinicians, researchers, and pharmaceutical developers, fostering advancements in drug delivery systems to optimize therapeutic outcomes and improve patient care.

Study on the Efficacy of a Novel Sedative Medication Based on Wilcoxon Rank-Sum Test and Multiple Machine Learning Models

This study investigates the efficacy of a novel sedative medication compared to an existing drug using the Wilcoxon Rank-Sum test and multiple machine learning models. The Wilcoxon Rank-Sum test revealed statistically significant differences in petco200, petco2005, IPI005, and moaas005 indicators, primarily within the first 1 to 3 minutes post-induction. Basic information between the novel and existing drug groups was comparable, suggesting effective variable control and attributing differences to the novel sedative. Subsequently, various evaluation metrics including MSE, RMSE, MAE, MAPE, and R² were employed. Exploratory predictions using the Random Forest (RF) model yielded suboptimal results. After comparing the performance of RF, XGBoost, CatBoost, LightGBM, and SVR, a combination of the RF model and logistic regression was selected for regression predictions based on data type. Visualization of results demonstrated good predictive performance and mitigated overfitting.

Optimizing the Efficacy of Anti-Obesity Medications: A Practical Guide to Personalizing Incretin-Based Therapies

Optimizing the Efficacy of Anti-Obesity Medications: A Practical Guide to Personalizing Incretin-Based Therapies

Exploring the Therapeutic Efficacy of Ethanolic Extract of Benincasa hispida in Alloxan Induced Diabetic Rats

Since the dawn of civilization, humans have used herbal medicine to treat medical ailments. This study seeks to evaluate the efficacy of Benincasa hispida as an anti-diabetic agent and its impact on lipid profiles. We assessed the efficacy of the anti-diabetes medication using the alloxan-induced diabetic model. Only the 900 mg/kg dosage exhibited statistically significant antidiabetic effects (p < 0.05) when compared to the 300 and 600 mg/kg dosages. Notwithstanding a slight reduction in these parameters, no groups demonstrated statistically significant results regarding HDL, LDL, and total cholesterol. The triglyceride value of 97.70 ± 7.50* yielded statistically significant results (p < 0.05). Conversely, SGPT and SGOT exhibited no statistically significant effects at dosages of 300, 600, or 900 mg/kg. Group 5 exhibited statistically significant results (p < 0.05) in the kidney function test in case of urea, with a value of 93.24 ± 9.23* after the administration of an extract at a dose of 600 mg/kg. No statistically significant results were seen in any groups concerning creatinine levels.

A Narrative Review of the Interplay Between Carbohydrate Intake and Diabetes Medications: Unexplored Connections and Clinical Implications.

This narrative review examines the dynamic interplay between carbohydrate intake and diabetes medications, highlighting their combined molecular and clinical effects on glycemic control. Carbohydrates, a primary energy source, significantly influence postprandial glucose regulation and necessitate careful coordination with pharmacological therapies, including insulin, metformin, glucagon-like peptide (GLP-1) receptor agonists, and sodium-glucose cotransporter-2 (SGLT2) inhibitors. Low-glycemic-index (GI) foods enhance insulin sensitivity, stabilize glycemic variability, and optimize medication efficacy, while high-GI foods exacerbate glycemic excursions and insulin resistance. Continuous glucose monitoring (CGM) offers real-time insights to tailor dietary and pharmacological interventions, improving glycemic outcomes and reducing complications. Despite advancements, gaps persist in understanding nutrient-drug interactions, particularly with emerging antidiabetic agents. This review underscores the need for integrating carbohydrate-focused dietary strategies with pharmacotherapy to enhance diabetes management. Future research should prioritize clinical trials leveraging CGM technology to explore how glycemic index, glycemic load, and carbohydrate quality interact with newer diabetes medications. Such studies can refine evidence-based recommendations, support individualized care plans, and improve long-term outcomes. Addressing systemic barriers, such as limited access to dietitians and CGM technology in underserved regions, is critical for equitable care. Expanding the roles of community health workers and training healthcare providers in basic nutrition counseling can bridge gaps, promoting sustainable and inclusive diabetes management strategies. These efforts are essential for advancing personalized, effective, and equitable care for individuals with diabetes.

Intraventricular Medication with or without Ventricular Shunt for Leptomeningeal Metastases with Different Intracranial Pressure: A Single-Center, Large-Scale Retrospective Study.

To evaluate the efficacy and prognosis of intraventricular medication (IVM) administered via the reservoir of Ommaya or ventricular shunt (VS) system to control leptomeningeal metastases, with or without VS based on intracranial pressure, in combination with postoperative systemic therapy. Between April 2021 and December 2022, 125 patients with leptomeningeal metastases were managed in our department who underwent Ommaya reservoir placement and/or VS and subsequently received IVM postoperatively. The extent of symptom amelioration and survival, as well as the determinants influencing prognosis, were evaluated. The 3-, 6-month, and 1-year survival rates and mOS of the patients were calculated by the Kaplan‒Meier method, and survival and prognostic analyses were performed using the log-rank test, one-way analysis of variance, and the Cox proportional hazards model. Symptoms were significantly alleviated among the 113 leptomeningeal metastases with intracranial hypertension who underwent VS placement. The median survival time of 112（89.6%）cases who received medication regularly was 9.0months, and significantly prolonged by 2-4months compared with that of other studies not involving IVM in the literature. Cox multifactorial analysis revealed that postoperative administration of IVM and the number of IVM times independently influenced the efficacy of leptomeningeal metastases treatment. For leptomeningeal metastases, VS not only significantly alleviates symptoms caused by intracranial hypertension but also avoids sudden death for those with severe intracranial hypertension. However, VS placement only does not improve overall survival. IVMs controls effectively leptomeningeal metastases, significantly prolongs survival, enhances quality of life.

Exploring Predictors of Treatment Response to GLP-1 Receptor Agonists for Smoking Cessation.

Understanding predictors of smoking cessation medication efficacy facilitates the ability to enhance treatment effectiveness. In our pilot trial, exenatide, a glucagon-like peptide-1 receptor agonist, adjunct to nicotine patch improved smoking abstinence compared to nicotine patch alone. This secondary analysis explores potential baseline characteristics associated with differential treatment response to exenatide. The parent trial randomized (1:1) 84 smokers with prediabetes and/or overweight to once-weekly placebo or exenatide, 2mg, subcutaneously. All participants received nicotine patch (21mg) and brief smoking cessation counseling, with biologically confirmed 7-day point prevalence abstinence at week 6 (end-of-treatment) deemed the primary outcome. Bayesian generalized linear modeling explored differential response to treatment as a function of baseline patient characteristics, including demographic, psychosocial, clinical, smoking related, and genetic factors. Posterior probability (PP)≥75% that an effect exists was taken as a minimum threshold of evidence in favor of model effects. Exenatide showed stronger benefit versus placebo in participants that smoked >20 cigarettes per day (PP=81.7%) and in those without prediabetes (PP=76.0%) or obesity (PP=94.4%). Exenatide's efficacy was observed only in individuals with no/minimal depression symptoms but not in those with symptoms (PP=91.2%). Finally, exenatide was more efficacious than placebo only in those with the CHRNA rs16969968 GG genotype (PP=88.6%). The effect of exenatide on abstinence may be moderated by the number of cigarettes smoked daily, metabolic, psychological, and genetic factors. Larger prospective investigations are needed to confirm and extend these findings. Understanding predictors of smoking cessation medication efficacy enhances the ability to improve treatment effectiveness. In our pilot trial, extended-release exenatide, a GLP-1 receptor agonist, adjunct to nicotine patch, improved smoking abstinence in smokers with prediabetes and/or overweight. The current post-hoc analysis found that the effect of exenatide on smoking abstinence may be moderated by the number of cigarettes smoked daily, metabolic, psychological, and genetic factors. Larger investigations are needed to confirm and extend these findings.

Pharmacogenetics of opioid medications for relief of labor pain and post-cesarean pain: a systematic review and meta-analysis.

Several studies have attempted to identify genetic determinants of clinical response to opioids administered during labor or after cesarean section. However, their results were often contrasting. A systematic review and meta-analysis was conducted to quantitatively assess the association between gene polymorphisms and clinical outcomes of opioid administration in the treatment of labor pain and post-cesarean pain. A comprehensive search was performed up to December 2023 using PubMed, Web of Knowledge, Cochrane Library, and OpenGrey databases. The clinical endpoints of interest were pain score after opioid treatment, total opioid consumption, patient's analgesic satisfaction, and incidence of opioid side effects. Random-effects meta-analyses were conducted when data were available in at least three studies. Twenty-six studies enrolling 7765 patients were included in the systematic review. Overall, a total of 12 candidate polymorphic genes (OPRM1, COMT, CYP2D6, CYP3A4, ABCB1, ABCC3, UGT2B7, CGRP, OPRK1, OPRD1, KCNJ6, KCNJ9) were considered by the included studies, among which the most investigated variant was OPRM1 rs1799971. Overall pooled results indicated that individuals carrying the G allele of OPRM1 rs1799971 required higher opioid doses for pain management in comparison to rs1799971 AA subjects (standardized mean difference: 0.26; 95% CI: 0.09-0.44; P = 0.003). Such an association was confirmed in the subgroups of patients with labor pain and post-cesarean pain. The present meta-analysis provides strong evidence of an association between OPRM1 rs1799971 and opioid dose requirement for relief of labor pain or post-cesarean pain. However, given the insufficient evidence for other polymorphic gene variants, large studies are still needed to investigate the impact of genetic variability on the efficacy and safety of opioid medications for relief of labor pain and post-cesarean pain (INPLASY Registration No. 202410040).

The Efficacy and Safety of Non-Biologic and Biologic Treatments in Palmoplantar Pustular Psoriasis and Palmoplantar Pustulosis: A Systematic Review and Network Meta-Analysis.

Palmoplantar pustular psoriasis (PPPP), or palmoplantar pustulosis (PPP), is a type of psoriasis that affects the skin on the palms and soles. It is characterised by dermatosis and small sterile pustules and is considered a significant burden on patients' quality of life, as there is currently no gold standard treatment or cure. This network meta-analysis (NMA) compares the efficacy and safety of biologic and non-biologic medications for PPPP and PPP. Medline, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched. The efficacy and safety of all medications were assessed through a frequentist NMA using a random-effects model. Treatments were ranked using the net rank function, yielding P scores. Fourteen RCTs with 1056 participants were included. Guselkumab 100 mg was the most effective for improving PPPGA scores (p = 0.72, RR = 1.31, CI: 0.31-5.57). Guselkumab 100 mg was ranked the highest for achieving PPPASI-75 (RR = 5.4, CI: 1.26-23.2, p = 0.023). Oral cyclosporine 1 mg/kg/day was ranked the highest for PPPASI-50 (RR = 2.10, CI: 0.65-6.82). Etretinate 1 mg/kg/day had the highest rate of adverse events (RR = 1.78, CI: 0.92-3.44). Secukinumab 300 mg was associated with the highest rate of serious adverse events (RR = 1.58, CI: 0.21-12.02). Based on the P-scores from our NMA, guselkumab 100 mg was the most effective for PPPGA improvement, guselkumab 100 mg for PPPASI-75, oral cyclosporine 1 mg/kg/day for PPPASI-50, etretinate 1 mg/kg/day had the most adverse events, and secukinumab 300 mg was associated with the highest rate of serious adverse events. TRIAL REGISTRATION: PROSPERO registration number: CRD42023460842.

Exploring perceived barriers and attitudes in young adults towards antidepressant pharmacotherapy, including the implementation of pharmacogenetic testing to optimize prescription practices.

The field of pharmacogenetics (PGx) is experiencing significant growth, with increasing evidence to support its application in psychiatric care, suggesting its potential to personalize treatment plans, optimize medication efficacy, and reduce adverse drug reactions. However, the perceived utility and practicability of PGx for psychiatric treatment in youth remains underexplored. This study investigated perceived barriers and attitudes in Australian young adults towards the implementation of PGx testing to guide antidepressant treatment in primary care. Semi-structured focus groups and interviews were conducted with 17 participants aged between 18 and 24years. These sessions were recorded and transcribed before thematic analysis was used to identify collective themes. Three key themes were identified, including attitudes towards the medication prescription process, concerns and attitudes towards PGx testing, and perceived barriers to its clinical implementation. Although PGx testing was positively perceived by most participants, all participants shared concerns about PGx testing. Participants voiced concerns about the financial impact of PGx testing, the potential for treatment delays, and the accuracy of PGx testing in guiding antidepressant treatment. Additionally, participants noted that the low awareness and willingness of general practitioners to incorporate PGx testing into routine practice could hinder successful clinical implementation. Prior to the implementation of PGx testing into Australian primary practices, it is essential to acknowledge patient perspectives and ensure that clinical practices remain patient-focused. This study highlights important considerations for integrating PGx testing into antidepressant pharmacotherapy and emphasizes the need for future research to address and mitigate the perceived barriers of young adults.

Cost-Effectiveness of Semaglutide in Patients With Obesity and Cardiovascular Disease.

Randomized clinical trials have shown that semaglutide is associated with a clinically relevant reduction in body weight and a lower risk of adverse cardiovascular events in those who are overweight or obese with a history of cardiovascular disease but no diabetes. The objective of this study was to assess the cost-effectiveness of semaglutide for this indication. A decision analytic Markov model was used to compare the lifetime benefits and costs of semaglutide 2.4-mg subcutaneous weekly vs standard care in a hypothetical cohort of patients who were overweight or obese with preexisting cardiovascular disease (and no diabetes) from the health care payer perspective. Our model included ischemic stroke, heart failure hospitalization and/or urgent visit or myocardial infarction, and death over monthly transition cycles. Model outcomes included costs (2023 CAD$), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios. Base case analysis showed that the incremental cost-effectiveness ratio for semaglutide compared with standard care was $72,962 per QALY gained with a 14% likelihood of cost-effectiveness adopting a $50,000 per QALY gained willingness to pay threshold. Factors with the greatest influence on cost-effectiveness were medication efficacy on mortality and medication cost. When the price of semaglutide was reduced by 50%, it was economically attractive at $37,190 per QALY gained with an 80% likelihood of cost-effectiveness at a $50,000 per QALY threshold. Semaglutide might be a cost-effective option for the publicly funded health care system contingent on initial pricing. Considering the candidate population-patients who are overweight or obese with preexisting cardiovascular disease-policymakers should consider the budget effect of funding semaglutide and weigh it against other ways scarce health care dollars might be used.

SiRNA-based therapy for overcoming drug resistance in human solid tumours; molecular and immunological approaches.

RNA interference (RNAi) is a primordial biological process that protects against external intrusion. SiRNA has the potential to selectively silence disease-related genes in a sequence-specific way, thus offering a promising therapeutic approach. The efficacy of siRNA-based therapies in cancer treatment has gained significant recognition due to multiple studies demonstrating its ability to effectively suppress cancer cells' growth and multiplication. Moreover, siRNA-based medicines have shown considerable promise in enhancing the sensitivity of cancer cells to chemotherapy and other treatment methods by suppressing genes that play a role in the development of drug resistance. Exploring and identifying functional genes linked to cancer cell characteristics and drug resistance is crucial for developing effective siRNAs for cancer treatment and advancing targeted and personalized therapeutics. Targeting and silencing genes in charge of resistance mechanisms, such as those involved in drug efflux, cell survival, or DNA repair, is possible with siRNA therapy in the context of drug resistance, especially cancer. Through inhibiting these genes, siRNA therapy can prevent resistance and restore the efficacy of traditional medications. This review addresses the potential of siRNAs in addressing drug resistance in human tumours, opening up new possibilities in cancer therapy. This review article offers a non-systematic summary of how different siRNA types contribute to cancer cells' treatment resistance. Using pertinent keywords, sources were chosen from reliable databases, including PubMed, Scopus, and Google Scholar. The review covered essential papers in this area and those that mainly addressed the function of siRNA in drug resistance. The articles examined in connection with the title of this review were primarily published from 2020 onward and are based on in vitro studies. Furthermore, this article examines the potential barriers and prospective perspectives of siRNA therapies.