Efficacy In Clinical Trials Research Articles

Qualitative In-trial Interviews: Methods, Challenges, and Best Practice.

Qualitative in-trial interviews with clinical trial participants are a means of providing rich, in-depth patient experience data to supplement and complement data captured by clinical outcome assessments and other clinical trial efficacy endpoints. Such in-trial interview data can be used to build understanding of disease and treatment experiences, evaluate content validity of clinical outcome assessments, aid interpretation of scores and meaningful changes, inform trial design feasibility and operational considerations, and provide supportive evidence regarding safety, efficacy, and effectiveness. Despite the rapid growth of in-trial interviews as part of clinical development programs in the pharmaceutical industry in recent years, published guidelines regarding the methods, conduct, and implementation of in-trial interviews are scarce. Drawing on published examples and the authors' experiences of conducting in-trial interview studies, this article provides an overview of best practice methods for implementing this methodology (including considerations for study design, sample size, interview conduct, and analysis) and the value of in-trial interview data to answer specific research questions. Operational and logistical considerations are outlined, including recommendations for country selection, site selection, training and communication, adverse event safety reporting, and data management and handling. Well-designed and carefully implemented in-trial interviews can lead to generation of insightful patient experience data that are truly of value to inform regulators, health technology agencies, clinicians, patients, and caregivers about product attributes and the impact of diseases and treatments on patients' lives.

High dose of ascorbic acid induces selective cell growth inhibition and cell death in human gastric signet-ring cell carcinoma-derived NUGC-4 cells.

Anticancer effects of high-dose vitamin C (VC) have been evaluated on many cancer cell lines, and its efficacy in clinical trials and in combination with anticancer drugs or radiation have been reported; however, its effect on gastric cancer and its mechanisms remain unclear. In the present study, the cell growth inhibitory/lethal effects of high-dose ascorbic acid (AsA), a reduced form of VC was examined on three gastric cancer cell lines. Of these, signet ring cell carcinoma NUGC-4 cells were the most sensitive, but the effects were small and limited in normal cells. Second, high-dose AsA was effective in NUGC-4 cells, whereas dehydroascorbic acid, an oxidized form of VC, was less effective. Third, high-dose AsA showed stronger cell growth inhibitory/lethal effects on floating cells than on adherent cells, and was effective even under hypoxic microenvironment conditions. A single 1-h treatment of high-dose AsA strongly inhibited cell growth, causing apoptosis-like cell death over 72h after treatment, triggered by hydrogen peroxide generation, actin abnormality, DNA synthesis suppression, DNA damage induction, and ATP level decrease. The effects of high-dose AsA were inhibited either by adding or chelating iron ions, but was not affected via inhibiting AsA transport. Inhibition of glutathione synthesis enhanced the anticancer effects of high-dose AsA. These results indicate that a single high-dose of AsA induces cancer cell-selective, sustained cell growth inhibition and cell death, and these effects may be regulated by iron ion and/or intracellular oxidative stress levels in human gastric signet-ring cell carcinoma-derived NUGC-4 cells.

Using clinical outcome assessments for rare disease clinical trial efficacy endpoints: Regulatory considerations and case studies

Using clinical outcome assessments for rare disease clinical trial efficacy endpoints: Regulatory considerations and case studies

Dengue Vaccination: A Practical Guide for Clinicians

Dengue is a growing global public health challenge, with rising incidence and case fatality rates fueled by urbanization and climate change. The substantial mortality, morbidity, and economic burden associated with the disease underscore the need for effective prevention strategies, including vector control, personal protective measures, and vaccination. This narrative review provides a practical guide for clinicians to ensure the appropriate administration of dengue vaccines to at-risk groups, such as individuals in endemic regions and travelers to these areas. Live-attenuated tetravalent dengue vaccines, including Dengvaxia®, Qdenga®, and Butantan-DV, have demonstrated efficacy in clinical trials but require careful use due to the risk of antibody-dependent enhancement (ADE). To mitigate this risk, guidelines recommend vaccination primarily for individuals with prior confirmed dengue infection, emphasizing the importance of accessible and affordable point-of-care rapid testing. Co-administration of dengue vaccines with other live-attenuated or inactivated vaccines has been shown to be safe and immunogenic, broadening their potential application. However, live-attenuated vaccines are contraindicated for immunocompromised individuals and pregnant women. Enhancing clinician awareness, expanding diagnostic capabilities, and prioritizing high-risk populations are critical steps to optimize vaccination strategies. Combined with robust prevention programs, these efforts are essential to reducing the global burden of dengue and mitigating its impact.

Willingness to Use Long-Acting Injectable Pre-Exposure Prophylaxis among Adolescent Girls and Young Women in Kampala, Uganda.

Pre-exposure prophylaxis (PrEP) has proven to be a powerful tool in preventing HIV infection. There is limited information about the factors associated with willingness to use different PrEP modalities among adolescent girls and young women (AGYW) in Africa. We assessed willingness to use long-acting injectable PrEP (LAI-PrEP) among 14-24-year-old AGYW at high risk of HIV in Uganda, and associated factors determined using multivariable complementary log-log regression. Of the 285 participants, 69.8% of participants showed willingness to use LAI-PrEP despite only 3.9% having knowledge about it before enrolment. Report of recent transactional sex was high (92.6%). Participants that were divorced/separated (aOR = 1.74, 95% CI 1.03-2.92) and those with multiple sexual partners (aOR = 2.11, 95% CI 1.46-3.06) compared to those with one partner were more likely to be willing to use LAI-PrEP while those that were screened as heavy episodic drinkers (consuming 6 or more drinks on an occasion as per the AUDIT tool) were less likely to be willing to use LAI-PrEP (aOR = 0.61, 95% CI 0.42-0.87). LAI PrEP has shown efficacy in clinical trials; the product is approved for use by the Government of Uganda (MoH) and should be expedited for use by AGYW engaged in paid sex and those with multiple sexual partnerships. As it becomes available, we recommend PrEP education and counseling to increase awareness of LAI PrEP as an alternative HIV prevention method.

Targeting the Menin-KMT2A interaction in leukemia: Lessons learned and future directions.

Chromosomal rearrangements involving the Mixed Lineage Leukemia gene (MLL1, KMT2A) are defining a genetically distinct subset in about 10% of human acute leukemias. Translocations involving the KMT2A-locus at chromosome 11q23 are resulting in the formation of a chimeric oncogene, where the N-terminal part of KMT2A is fused to a variety of translocation partners. The most frequently found fusion partners of KMT2A in acute leukemia are the C-terminal parts of AFF1, MLLT3, MLLT1 and MLLT10. Unfortunately, the presence of an KMT2A-rearrangements is associated with adverse outcomes in leukemia patients. Moreover, non-rearranged KMT2A-complexes have been demonstrated to be crucial for disease development and maintenance in NPM1-mutated and NUP98-rearranged leukemia, expanding the spectrum of genetic disease subtypes that are dependent on KMT2A. Recent advances in the development of targeted therapy strategies to disrupt the function of KMT2A-complexes in leukemia have led to the establishment of Menin-KMT2A interaction inhibitors that effectively eradicate leukemia in preclinical model systems and show favorable tolerability and significant efficacy in early-phase clinical trials. Indeed, one Menin inhibitor, Revumenib, was recently approved for the treatment of patients with relapsed or refractory KMT2A-rearranged acute leukemia. However, single agent therapy can lead to resistance. In this Review article we summarize our current understanding about the biology of pathogenic KMT2A-complex function in cancer, specifically leukemia, and give a systematic overview of lessons learned from recent clinical and preclinical studies using Menin inhibitors.

C-28 linker length modulates the activity of second-generation HIV-1 maturation inhibitors

Maturation inhibitors (MIs) block HIV-1 maturation by preventing the cleavage of the capsid protein and spacer peptide 1 (CA-SP1). Bevirimat (BVM), a first-in-class MI, displayed sub-optimal efficacy in clinical trials due to presence of SP1:V7A polymorphism in the Gag protein.This polymorphism is inherently present in HIV-1 subtype C and conferred resistance to BVM. Second generation BVM analogs with modifications at C-28 position gained potent activity against HIV-1 subtype C. In this study, we have evaluated the efficacy of nine second-generation MIs (BVM analogs) with varying length of C28 carbon linker against HIV-1 subtype B and C. Increasing the length of carbon linker decreased their activity against both subtypes. These MIs were also active against integrase inhibitor-resistant viruses and protease inhibitor-resistant viruses. Our data has provided vital information that in addition to the nature of the functional group at C28 position of the MI, the length of linker contributes significantly to its activity. The shorter the length, the better the activity of MIs. These results will further pave way for design of novel and potent MIs.

Efficacy of LaAg Vaccine Associated with Saponin Against Leishmania amazonensis Infection

Background/Objectives: The total lysate of Leishmania amazonensis (LaAg) is one of the most extensively studied vaccine formulations against leishmaniasis. Despite demonstrating safety and immunogenicity when administered intramuscularly, LaAg has failed to show efficacy in clinical trials and, in some cases, has even been associated with an enhanced susceptibility to infection. Adjuvants, which are molecules or compounds added to antigens to enhance the immunogenicity or modulate the immune response, are frequently employed in vaccine studies. This study aimed to evaluate different adjuvants to improve the protective efficacy of LaAg in L.amazonensis infection using a BALB/c mouse model. Methods: BALB/c mice were immunized with LaAg in combination with various adjuvants. The delayed-type hypersensitivity (DTH) test was assessed by measuring the infected paw and was used to evaluate the immunogenicity and to determine the most effective adjuvant. The immune response was analyzed through flow cytometry, focusing on cytokine production, immune cell recruitment and lesion size, alongside the control of parasite load at the infection site. The expression levels of iNOS and TGF-β were quantified using RT-qPCR, while IgG1, IgG2a and IgE antibody levels were determined via ELISA. Results: Among the adjuvants tested, only saponin (SAP) elicited a significant DTH response following LaAg challenge. SAP enhanced the immunogenicity of LaAg, as evidenced by increased IFN-γ-producing CD4+ and CD8+ T cells in the draining lymph nodes at 18 h post-challenge. Additionally, SAP facilitated the recruitment of lymphocytes, macrophages, neutrophils and eosinophils to the infection site. Conclusions: The LaAg + SAP combination conferred partial protection, as demonstrated by a reduction in lesion size and the partial control of parasite load. In conclusion, the addition of SAP as an adjuvant to LaAg effectively modulates the immune response, enhancing the vaccine’s protective efficacy. These findings provide valuable insights into the development of improved vaccines against L.amazonensis infection.

Crossing the blood-brain barrier: emerging therapeutic strategies for neurological disease.

The blood-brain barrier is a physiological barrier that can prevent both small and complex drugs from reaching the brain to exert a pharmacological effect. For treatment of neurological diseases, drug concentrations at the target site are a fundamental parameter for therapeutic effect; thus, the blood-brain barrier is a major obstacle to overcome. Novel strategies have been developed to circumvent the blood-brain barrier, including CSF delivery, intracranial delivery, ultrasound-based methods, membrane transporters, receptor-mediated transcytosis, and nanotherapeutics. These approaches each have their advantages and disadvantages. CSF delivery and intracranial delivery are direct but invasive techniques that have not yet shown efficacy in clinical trials, although development of novel delivery devices might improve these approaches. Ultrasound-based disruption has shown some efficacy in clinical trials, but it can require invasive procedures. Approaches using membrane transporters and receptor-mediated transcytosis are less invasive than are other techniques, but they can have off-target effects. Nanotherapeutics have shown promise, but these strategies are in early stages of development. Advancements in drug delivery across the blood-brain barrier will require appropriately designed and powered clinical studies, with a focus on the timing of treatment, demographic and genetic considerations, head-to-head comparison with other treatment strategies (rather than a placebo), and relevant primary and secondary outcome measures.

P0661 Effectiveness of upadacitinib for induction of remission in moderate-to-severe ulcerative colitis: real-world clinical outcomes appear independent of prior tofacitinib exposure

Abstract Background Upadacitinib (UPA), a selective JAK1 inhibitor, has shown efficacy in clinical trials for moderate-to-severe ulcerative colitis (UC), but real-world data remain limited, particularly on outcomes related to prior exposure to other JAK inhibitors, such as tofacitinib (TOFA). This study evaluates real-world outcomes of UPA induction therapy in UC, focusing on clinical remission and differences by prior TOFA exposure. Methods This retrospective, observational study was conducted at a tertiary care centre in Spain, including adult patients with moderate-to-severe UC who initiated UPA in routine clinical practice. Data were retrospectively collected from electronic records, capturing baseline characteristics, TOFA exposure, disease duration, and concomitant treatments. The primary outcome was clinical remission at end of induction, assessed via the Physician Global Assessment (PGA) based on symptoms and laboratory data. Secondary outcomes included changes in faecal biomarkers, adverse events, treatment discontinuation, and maintenance dosing. Results Twenty-six patients were included, with a mean age of 50.5 years, 61.5% female, and a median disease duration of 10 years. All patients had prior exposure to advanced therapies, with 53.8% treated with at least three different lines of therapy. TOFA-exposed patients had a higher rate of pancolitis (84.6% vs. 30.8%; p=0.013), though endoscopic severity was similar between groups. All patients began with 45 mg UPA once daily; 23% had concomitant treatments, including vedolizumab (n=1), apheresis (n=3), and prednisone tapering (n=2). Following induction, 65.4% achieved clinical remission and 88.5% at least a partial response based on PGA. Among TOFA-naïve patients, 76.9% achieved remission and 100% partial response, compared to 53.8% and 76.9%, respectively, in TOFA-exposed patients (p=0.9). Faecal calprotectin levels decreased, with reductions of 96.7% in TOFA-naïve patients (from median 4002 µg/g to 132 µg/g) and 97.9% in TOFA-exposed patients (from 3556 µg/g to 76 µg/g). Extended induction was needed in 38.4% of patients, with no difference based on prior TOFA exposure (46.2% vs. 30.8%, p=0.6). Discontinuation during induction occurred in 23%, due to lack of effectiveness in 50%, adverse events in 33%, and transition to vedolizumab monotherapy in 17%. Post-induction, 88.4% continued on 30 mg as maintenance, consistent across both groups. Conclusion UPA induction therapy shows promise in achieving clinical remission in moderate-to-severe UC, with comparable outcomes independent of prior TOFA exposure. Our data suggests UPA may be a valuable option in real-world, treatment-experienced UC populations. Further studies could help clarify its role in complex cases and refine treatment strategies

P0777 Sonographic transmural induction outcomes across advanced therapies in Crohn’s Disease

Abstract Background Intestinal ultrasound (IUS) is increasingly being used to evaluate induction efficacy in both clinical practice and clinical trials. The differential healing rates across advanced therapies (AT) remains unknown. We aimed to quantify the rates of early post induction IUS transmural (TM) remission and response across AT in Crohn’s Disease (CD). Methods Single center retrospective review of patients with CD initiating AT who underwent IUS pre and post induction and had disease activity and biomarker data available. Patients with normal pre-AT IUS or post op were excluded. Primary outcome was post-induction TM response of the most affected segment (segmental response compared to baseline: >25% decrease in bowel wall thickness (BWT), absolute BWT decrease >2mm, or absolute decrease >1mm with ≥1-point improvement in Modified Limberg Score (MLS)). Secondary outcomes were segmental and complete (all bowel segments) TM remission (BWT ≤ 3.0mm and MLS 0). Descriptive statistics summarized data (median [IQR]), univariate and multivariate analysis tested associations. Results 101 patients (53% female, age 17.4 [15.0-21.1] years); disease duration 0.80 years [0.17-3.96]; post induction IUS performed 78 days [56-102] on AT (44% anti-TNF, 53% AT naïve). Segmental TM induction response across all AT was 63%. Segmental and complete TM remission was 36% and 35%, respectively (figure). Complete TM remission was seen at a higher rate with upadacitinib (UPA) than ustekinumab (UST) (p=0.009) and risankizumab (RZB) (p=0.032) but not anti-TNF (NS). Patients with severe IUS inflammation (MLS 3) at baseline were less likely to achieve TM remission independent of AT (aOR 0.21 [0.059-0.76]). Complete TM remission was independently associated with infliximab (IFX) (aOR 11.7 [2.2-62.4]) and UPA (aOR 5.22 [1.0-27.2]). Rates of segmental TM response were greater for colonic than ileal disease in UST/RZB (88% vs 47%, p=0.038), but no different in TNF/UPA. Patients started on UST/RZB after >1 failed prior AT had a trend for lower rates of TM outcomes (NS), while number of prior therapies had no impact on UPA response or remission rates. Conclusion Post-induction TM outcomes are achievable across AT: 2/3 of patients achieve segmental TM response and 1/3 achieve complete TM remission. This data, combined with the high correlation between IUS and endoscopy, suggests that IUS response could be considered as a clinical trial endpoint.

Identification of putative Indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO) dual inhibitors for triple-negative breast cancer therapy

Tryptophan catabolism is a central pathway in many cancers, serving to sustain an immunosuppressive microenvironment. The key enzymes involved in this tryptophan metabolism such as indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO) are reported as promising novel targets in cancer immunotherapy. IDO1 and TDO overexpression in TNBC cells promote resistance to cell death, proliferation, invasion, and metastasis. To date, there are no clinically available small-molecule inhibitors that target these enzymes. Navoximod, a reliable dual-specific inhibitor, resulted in poor bioavailability and modest efficacy in clinical trials restricts its utility. This situation urges the development of a potent drug-like candidate against these key enzymes. A total of 1574 natural compounds were proclaimed and subjected to ADME screening. Subsequently, the resultant compounds were attributed to hierarchical molecular docking and MM-GBSA validation. Ultimately, re-scoring with the aid of combined machine learning algorithms resulted six lead compounds. Captivatingly, NPACT00380 exhibited maximum interaction among the lead compounds. In addition, the scaffold analysis also highlighted that the chromanone moiety of the hit compound boasts anti-cancer activity against breast cancer cell lines. The reliability of the results was corroborated through a rigorous 100 ns molecular dynamics simulation using the parameters including RMSD, PCA and FEL analysis. In light of these findings, it is presumed that the proposed compound exhibits significant inhibitory activity. As a result, we speculate that further optimisation of NPACT00380 could be beneficial for the treatment and management of TNBC.

The Stability-Indicating Ultra High-Performance Liquid Chromatography with Diode Array Detector and Tandem Mass Spectrometry Method Applied for the Forced Degradation Study of Ritlecitinib: An Appraisal of Green and Blue Metrics.

Janus kinase inhibitors open new horizons for small-molecule drugs in treating inflammatory bowel disease, with ritlecitinib demonstrating significant efficacy in clinical trials for ulcerative colitis and Crohn's disease. Ritlecitinib, a second-generation JAK3 inhibitor, is a novel therapeutic agent for alopecia areata and other autoimmune conditions. A new stability-indicating UHPLC-DAD-MS/MS method was developed, validated, and applied for a forced degradation study of ritlecitinib under ICH guidelines. The method demonstrated high specificity, sensitivity (LOD: 0.04 µg/mL; LOQ: 0.14 µg/mL), precision (RSD ≤ 0.15%), and accuracy (99.9-100.3%). Forced degradation studies under acidic, basic, oxidative, thermal, and photolytic conditions revealed four novel degradation products. Basic degradation followed second-order kinetics, while oxidative degradation followed zero-order kinetics. The validated method reliably characterized ritlecitinib's stability and degradation products, providing essential data for optimizing formulation, determining proper storage conditions, anticipating drug-excipient interactions, and ensuring quality control. The eco-friendliness and applicability of the developed forced degradation procedure were evaluated using various green and blue metric tools. Incorporating green analytical principles underscores its potential for sustainable pharmaceutical analysis.

A real-world Pharmacovigilance study of brodalumab based on the FDA adverse event reporting system

Brodalumab, a humanized monoclonal antibody that targets the interleukin-17 receptor A, is primarily used to manage moderate-to-severe plaque psoriasis. Although it has demonstrated favorable efficacy and safety in clinical trials, the strict inclusion and exclusion criteria may not fully reflect its safety profile in real-world settings. As its use becomes more widespread in clinical practice, understanding its safety in real-world applications is crucial.This study employed disproportionality analysis to assess the safety of brodalumab by examining all adverse event reports that identified brodalumab as the primary suspected drug in the FDA Adverse Event Reporting System database since 2017. Techniques such as the Reporting Odds Ratio, Proportional Reporting Ratio, Multi-item Gamma Poisson Shrinker, and Bayesian Confidence Propagation Neural Network were utilized to analyze the adverse events associated with brodalumab. Additionally, the Weibull distribution was used to model the temporal risk of adverse events.The study identified several adverse reactions already listed on the drug’s label that showed positive signals, including arthralgia, headache, myalgia, suicidal ideation, oropharyngeal pain, injection site mass, and infections. Additionally, we found potential adverse reactions not noted on the drug’s label that exhibited positive signals, including depression, increased blood pressure, peripheral swelling, gait disturbance, inability to walk, stress, myocardial infarction, sepsis, uveitis, nephrolithiasis, and interstitial lung disease. Moreover, this analysis highlighted the critical need for vigilant monitoring of adverse events, especially during the first month following the initiation of treatment.This study provides initial insights into the real-world safety of brodalumab, confirming known adverse reactions and uncovering additional potential risks. The results deliver vital information that can assist clinicians in making informed decisions when prescribing brodalumab for psoriasis treatment.

The evolving therapeutic landscape in atopic dermatitis

Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disorder affecting millions worldwide, with significant variations in clinical presentation influenced by socioeconomic, racial, and environmental factors. This review explores the current understanding of AD pathophysiology, emphasizing immune dysregulation, epithelial barrier dysfunction, and the role of cytokines, particularly interleukin (IL)-4 and IL-13, in disease progression. Safety and efficacy concerns limit traditional corticosteroids, phototherapy, and systemic immunosuppressants, prompting interest in innovative therapies. New biologic agents, including monoclonal antibodies (mAbs) and Janus kinase (JAK) inhibitors (JAKis), target specific immune pathways, promising outcomes in moderate-to-severe AD cases. Biologics like dupilumab and emerging JAKis have shown substantial efficacy and safety in clinical trials, with notable reductions in inflammation and pruritus. However, these advancements present challenges, including hypersensitivity risks and the high costs of biologics, underscoring the need for further research on long-term safety and accessibility. The shift toward precision medicine in AD management marks a significant evolution, with future approaches likely to integrate targeted therapies alongside multidisciplinary care to enhance patient outcomes and quality of life (QoL).

Current understanding and prospects for targeting neurogenesis in the treatment of cognitive impairment.

Adult hippocampal neurogenesis is linked to memory formation In the adult brain, with new neurons in the hippocampus exhibiting greater plasticity during their immature stages compared to mature neurons. Abnormal adult hippocampal neurogenesis is closely associated with cognitive impairment in central nervous system diseases. Targeting and regulating adult hippocampal neurogenesis have been shown to improve cognitive deficits. This review aims to expand the current understanding and prospects of targeting neurogenesis in the treatment of cognitive impairment. Recent research indicates the presence of abnormalities in AHN in several diseases associated with cognitive impairment, including cerebrovascular diseases, Alzheimer's disease, aging-related conditions, and issues related to anesthesia and surgery. The role of these abnormalities in the cognitive deficits caused by these diseases has been widely recognized, and targeting AHN is considered a promising approach for treating cognitive impairment. However, the underlying mechanisms of this role are not yet fully understood, and the effectiveness of targeting abnormal adult hippocampal neurogenesis for treatment remains limited, with a need for further development of treatment methods and detection techniques.By reviewing recent studies, we classify the potential mechanisms of adult hippocampal neurogenesis abnormalities into four categories: immunity, energy metabolism, aging, and pathological states. In immunity-related mechanisms, abnormalities in meningeal, brain, and peripheral immunity can disrupt normal adult hippocampal neurogenesis.Lipid metabolism and mitochondrial function disorders are significant energy metabolism factors that lead to abnormal adult hippocampal neurogenesis. During aging, the inflammatory state of the neurogenic niche and the expression of aging-related microRNAs contribute to reduced adult hippocampal neurogenesis and cognitive impairment in older adult patients. Pathological states of the body and emotional disorders may also result in abnormal adult hippocampal neurogenesis. Among the current strategies used to enhance this form of neurogenesis, physical therapies such as exercise, transcutaneous electrical nerve stimulation, and enriched environments have proven effective. Dietary interventions, including energy intake restriction and nutrient optimization, have shown efficacy in both basic research and clinical trials. However, drug treatments, such as antidepressants and stem cell therapy, are primarily reported in basic research, with limited clinical application. The relationship between abnormal adult hippocampal neurogenesis and cognitive impairment has garnered widespread attention, and targeting the former may be an important strategy for treating the latter. However, the mechanisms underlying abnormal adult hippocampal neurogenesis remain unclear, and treatments are lacking. This highlights the need for greater focus on translating research findings into clinical practice.

Real-world effectiveness and safety of sodium-glucose co-transporter 2 inhibitors in chronic kidney disease

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have shown efficacy in clinical trials for slowing chronic kidney disease (CKD) progression, but real-world data in diverse populations are limited. This retrospective study evaluated the effectiveness and safety of SGLT2i versus renin-angiotensin-aldosterone system (RAAS) blockade in CKD patients. Data from Ramathibodi Hospital (2010–2022) were analyzed, including 6,946 adults with CKD stages 2–4, with and without diabetes, who received SGLT2i (n = 1,405) or RAAS blockade (n = 5,541) for at least three months. Patients were matched 1:4 by CKD stage and treatment initiation date. A weighted Cox proportional hazards model with inverse probability weighting assessed the effect on composite major adverse kidney events (MAKEs), including eGFR decline ≥ 40%, progression to CKD stage 5, dialysis initiation, and cardiovascular or kidney death. SGLT2i therapy was associated with a lower risk of composite MAKEs (HR: 0.59; 95% CI: 0.36–0.98; P = 0.041) and less frequent progression to CKD stage 5 (HR: 0.52; 95% CI: 0.34–0.80; P < 0.003). Adverse event rates were similar between groups, with lower urinary tract infection incidence in the SGLT2i group. These findings suggest SGLT2i therapy might reduce adverse kidney outcomes in CKD patients, regardless of diabetic status, with a favorable safety profile.

Identifying novel response markers for spinal muscular atrophy revealed by targeted proteomics following gene therapy.

Spinal muscular atrophy (SMA) is a progressive disease that affects motor neurons, with symptoms usually starting in infancy or early childhood. Recent breakthroughs in treatments targeting SMA have improved both lifespan and quality of life for infants and children with the disease. Given the impact of these treatments, it is essential to develop methods for managing treatment-induced changes in disease characteristics. Zolgensma® is the first effective and approved gene therapy for SMA caused by biallelic mutation in the SMN1 gene. In three children with SMA treated with Zolgensma®, neuronal, glial, inflammation, and vascular markers in the plasma exhibited a quicker response, emphasizing their potential as valuable biomarkers of treatment efficacy in clinical trials. We chose the novel Nucleic acid Linked Immuno-Sandwich Assay, to investigate a predefined panel of neuroinflammatory markers in plasma samples collected from SMA patients at baseline and six months after Zolgensma® treatment. We identified a set of novel targets whose levels differed between pre and post Zolgensma® treatment group and that were responsive to treatment. Even though our results warrant validation in larger SMA cohorts and longer follow-up time, they may pave the way for a panel of responsive proteins solidifying biomarker endpoints in SMA clinical trials.

Evolving Strategies for Respiratory Syncytial Virus (RSV): A Review Article of Preventive Agents and Vaccines for RSV.

The objective was to describe the pharmacology, efficacy, safety, and recommendations for the use of newly approved preventive agents and vaccines for respiratory syncytial virus (RSV) and discuss their uptake during the 2023 to 2024 RSV season. A literature search of PubMed was performed (January 2020 to February 2024) with the search terms RSV vaccine, preventive antibody, and RSV prevention. Utilization data were collected from TriNetX using the US Collaborative Network (May 2024) using the terms palivizumab, nirsevimab, and RSV prefusion F protein. Relevant English-language studies assessing the use of Food and Drug Administration (FDA)-approved preventive agents and vaccines for RSV in humans were considered. Population-level utilization data were extracted from TriNetX. Nirsevimab was observed to have noninferior efficacy and safety compared with palivizumab with less frequent administration. Nirsevimab is recommended to replace palivizumab for RSV prophylaxis in all eligible infants. Arexvy and Abrysvo are effective at reducing the risk of RSV infection in adults aged ≥60 years, and Arexvy is indicated in adults aged ≥50 years. These vaccines are equally recommended for use in the elderly adult population, but only Abrysvo is indicated and recommended for maternal administration. Most infants only require prophylaxis through either maternal RSV vaccination or nirsevimab administration. This review compares the indications for use, guideline recommendations, and clinical trial efficacy and safety data for palivizumab, nirsevimab, Abrysvo, and Arexvy to guide clinical decision-making. Novel RSV preventive agents, including Abrysvo, Arexvy, and nirsevimab, offer less burdensome dosing and administration compared with palivizumab, show promising efficacy and safety data, and expand the populations eligible for RSV prevention. Updated clinical guidance supports immediate adoption of these agents in practice, and population-level data suggest these agents were used during the 2023 to 2024 RSV season.

In-vivo implementation of the HPTLC methodology to rat plasma for the concurrent determination of a novel combination therapy for the management of COVID-19 (favipiravir and nitazoxanide).

The 2019 coronavirus outbreak has prompted scientists to investigate pharmaceuticals to prevent the spread of the disease. Favipiravir (FAV) has received Food and Drug Administration FDA approval for the treatment of various viral infections with notable efficacy in clinical trials for COVID-19. Nitazoxanide (NTZ) is a broad-spectrum antiparasitic and antiviral agent used for the treatment of parasitic illnesses. Recently, the antiviral medications FAV and NTZ have been utilized therapeutically as early antiviral combination therapy for COVID-19, highlighting their safety, efficacy, and immunomodulatory effects. Despite several clinical studies on both FAV and NTZ, no analytical method has been developed for their concurrent detection. The objective of this study is to develop a TLC-densitometric method for their assessment and application to rat plasma. FAV, NTZ, and tizoxanide (the active metabolite of nitazoxanide (TZM)) were simultaneously determined using an HPTLC method embracing sulfasalazine as an internal standard (IS). Silica gel 60 F254 used as the stationary phase for chromatographic separation, the mobile phase consisted of chloroform-methanol-formic acid (9.5:0.5:0.2, v/v/v), with UV detection at 230 nm demonstrating linearity within the range of 0.5-5 μg/band. The proposed methodology has been shown to effectively measure the analyzed elements in both pure form and in-vivo rat plasma.