Clinical Safety Research Articles

An Open-Labeled, Randomized Clinical Trial to Study the Performance and Safety of an Intravenous Line Organizer (IVO) in a Tertiary Care Hospital

Background: Medical line and tube entanglement poses a significant threat causing unintentional consequences to the patients. Objectives: To study the clinical performance and safety of the IVO (intravenous line organizer) for providing patient autonomy, mobility, and comfort. Methods: Patients aged <18 years (pediatrics) and >18 years (adults) who were admitted to the hospital for treatment were included in the study. Tools like the Global Scale, Ease of Operability Scale, Severity of Intravenous Line Entanglement by Medical Line Entanglement Scale, Subjective Presumption Questionnaire, and Skin Irritation Scale, and adverse and serious adverse events were assessed and analyzed. Results: A total of 120 subjects who participated in the study were randomized into Groups-A (with IVO) and B (without IVO). The majority of patients in Group-A demonstrated better autonomy toward lines and tubes compared to Group-B in both adult and pediatric populations (86.3% vs 20%: Pediatric, 83.3% vs 26.6%: Adult), p<0.0001. Also, on mobility the Group-A patients reported improved movements with reduced restriction compared to Group-B (76.3% vs 26.6%, p<0.0001). Further, on the design and usability of IVO, 73.3% of patients in Group-A showed greater interest in the operability and usability compared to 27% in Group-B. No entanglement was reported in Group-A compared to the 12 (10%) patients facing potential harm of levels 2 & 3 who were in the standard-of-care group (without IVO). No significant adverse events were reported in patients using IVO. Conclusion: The IVO provided patients with the safe organization of intravenous tubes with greater autonomy, mobility, and comfort in managing the IV lines. Keywords: Intravenous Line Organizer, Autonomy, Mobility, Comfort, Entanglement

Simulation in health profession education in Pakistan: Bridging gaps, building futures

Simulation-based education (SBE) has revolutionized health profession education (HPE) globally, addressing gaps in clinical training, patient safety, and competency-based learning.1 In Pakistan, the adoption of SBE reflects a growing acknowledgment of its potential to transform healthcare education in resource-constrained settings.2 However, landscape of SBE in Pakistan remains a dynamic interplay of opportunities and challenges.3

Critical Assessment of Effectiveness and Safety of Tramadol and Evaluation of its Market in Ukraine

Introduction. The article examines the role of tramadol in chronic pain (CP) treatment, focusing on its clinical effectiveness, safety profile, and market presence in Ukraine. Given the rising concerns surrounding opioid use, this manuscript seeks to provide a comprehensive assessment of the role of such medicine as Tramadol in pain management. The research aimed to the secondary and tertiary sources of clinical effectiveness, and safety of tramadol for the management of CP, and to analyze the Ukrainian market of this pharmaceutical in the sales data provided by PharmXplorer. Materials and Methods. This review thoroughly searched clinical trials, systematic reviews, and meta-analyses in various scientific databases, including PubMed, Scopus, Web of Science, Embase, ClinicalTrials.gov, and Google Scholar. It employed keywords such as "tramadol," "CP", "effectiveness," "safety," "adverse effects," "overdose," and "abuse" to identify relevant studies. Primary data from the analytical application for pharmaceutical market players - PharmXplorer were used as marketing research materials. Logical analysis, synthesis, generalization, graphic, and statistical methods were used in the research. Results and Conclusions. This study critically analyzed the clinical effectiveness of tramadol through a comprehensive evaluation of clinical trials, systematic reviews, and meta-analyses concerning its use for CP management in oncological patients, non-cancer pain management, and pediatric practice. The conducted analysis does not demonstrate the advantage of tramadol compared to other opioids in the treatment of chronic pain in cancer patients, or chronic pain of different origins, including in pediatric practice. The safety of tramadol in clinical settings does not exceed the safety of other narcotic analgesics, and in some cases is even inferior to it. 80% of tramadol drugs on the Ukrainian pharmaceutical market are produced in Ukraine. Nevertheless, tramadol is not recommended as a first-line therapy for CP management due to its limited efficacy and safety concerns.

Chinese Physicians’ Preference for Prescribing Brand-Name vs. Generic: A Discrete Choice Experiment

Background: Promoting the use of generic drugs is a viable strategy to control drug costs. As physicians have a critical role in deciding on what drugs to prescribe and thus whether certified generic drugs were actually used, this study aimed to analyze factors influencing whether physicians were willing to prescribe generic drugs versus brand-name drugs after the implementation of Consistency Evaluation Policy (CEP). Methods: A discrete choice experiment (DCE) was developed to explore factors influencing physicians’ preferences toward prescribing brand-name drugs versus its certified generic. There were four attributes in the model, namely prices, hospital-level cost control measures, information about clinical safety and efficacy of generic drugs, and reimbursement rate. In total, 1297 physicians from 101 hospitals participated in the study and 1047 questionnaires were retained. Results: We found that substantial disclosed information about the generic’s clinical safety and efficacy (Sufficient information, odds ratio [OR]=3.251, 95% CI=3.098-3.412), lower price of the certified generic (price ratio of generic drugs versus brand-name drugs=1: 10, OR=1.130, 95% CI=1.078-1.185), stringent hospital cost control measures (the brand-name drugs were affected by the national centralized drug procurement (NCDP) policy or a tight cost-control measure, OR=1.247, 95% CI=1.190-1.307), and lower reimbursement rates for brand-name drugs (reimbursement rate=20%, OR=1.283, 95% CI=1.224-1.346) all increased physicians’ propensity to prescribe certified generic drugs. Conclusion: When certified generic drugs were lower priced or disclosed more information about their clinical safety and efficacy or when brand-name drugs were subject to tighter hospital cost control measures, physicians were more inclined to prescribe certified generic drugs. The findings suggest that CEP, together with the NCDP to promote market competition and hospital cost control measures targeting brand-name drugs, promoted the use of generic drugs through influencing physician prescribing behavior. The widely use of generic drugs may further benefit from increased disclosure of the clinical safety and efficacy of generic drugs by their manufacturers.

Evaluation of the In Vivo Efficacy of the JAK Inhibitor AZD1480 in Uterine Leiomyomas Using a Patient-derived Xenograft Murine Model.

Uterine leiomyomas are common noncancerous hormonally-dependent neoplasms comprised of uterine smooth-muscle cells and fibroblasts. Despite their significant impact on morbidity, effective non-hormonal medical treatments are lacking. In vitro studies have identified the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway as a promising target in leiomyoma cells. Our objective was to evaluate the efficacy of AZD1480, a JAK 1/2 inhibitor, in treating uterine leiomyomas using a patient-derived xenograft murine model. Ovariectomized immunodeficient mice received an estrogen and progesterone pellet and were subsequently implanted with human leiomyoma tissue surgically resected from premenopausal women not on hormonal medication. Mice were divided into treatment (n = 6) and vehicle control (n = 6) groups receiving either 50mg/kg of AZD1480 or vehicle via oral gavage for 5days/week for 28days. Our results demonstrate a significant AZD1480-mediated reduction in both xenograft volume (59.5% vs. 0.3%; treated vs. control, p < .0001) and weight (56.0% vs. 31.2%; p = 0.03) compared to controls. Moreover, xenografts from the treated group exhibited a significant decrease in cell density(p = 0.01). Levels of pSTAT3-positive cells (4.1% vs. 10.3%), Ki67-positive cells (4.1% vs. 6.5%), and fibrillar collagen (19.8% vs. 29.5%) declined but did not reach statistical significance, whereas AZD1480 treatment significantly reduced blood vessel formation in the xenografts (20.1 vs 45.6 per FOV; p = 0.01). These findings suggest JAK inhibition as a potential treatment for uterine leiomyomas by targeting angiogenesis. However, further studies are warranted to explore alternative JAK inhibitors, examine downstream effects, optimize dosing, and establish clinical efficacy and safety.

Electroacupuncture treatment for sarcopenia: study protocol for a randomized controlled trial

IntroductionSarcopenia is a disease primarily characterized by age-related loss of skeletal muscle mass, muscle strength, and/or decline in physical performance. Sarcopenia has an insidious onset which can cause functional impairment in the body and increase the risk of falls and disability in the elderly. It significantly increases the likelihood of fractures and mortality, severely impairing the quality of life and health of the elderly people. This disease poses a heavy burden on the healthcare system and society in our country, and currently, there are limited clinical intervention strategies for sarcopenia. This study aims to explore the clinical efficacy and safety of electroacupuncture in treating sarcopenia.Methods and analysisIn this parallel-design, randomized, sham-controlled trial, a total of 168 elderly sarcopenia patients will be randomly assigned in a 1:1 ratio to receive either electroacupuncture (EA) or sham electroacupuncture (sEA) treatment. The acupuncture points used in the study are Hegu (LI4), Shousanli (LI10), Quchi (LI11), Binao (LI14), Futu (ST32), Liangqiu (ST34), Zusanli (ST36), and Jiexi (ST41). The participants will receive EA or sEA treatment three times per week for eight weeks. The primary outcome measure is the change in grip strength (GS) of the patients after the eight-week treatment. The secondary outcome measures include the changes in grip strength at the fourth and twentieth weeks, changes in appendicular skeletal muscle mass index (ASMI), the Short Physical Performance Battery (SPPB) score, the physical activity level (PAL) assessed by the International Physical Activity Questionnaire (IPAQ), assessment of expectations regarding the efficacy of acupuncture, patient subjective evaluation of efficacy, and evaluation of blinding efficacy of acupuncture. All statistical analyses will be conducted according to the intention-to-treat principle and as per the study protocol.Ethics and disseminationThis study protocol was reviewed and approved by the Institutional Review Board of West China Hospital of Sichuan University (permission number: 2023 − 525). The participants will provide written informed consent to participate in this study.Trial registrationChinese Clinical Trial Registry (http://www.chictr.org.cn), Registration number: ChiCTR2300079294. Date of Registration: 2023-12-29.

Therapeutic Potential of Ginger Ethanolic Extract, Ginger-Loaded Chitosan ‎Nanoparticles, and Chitosan Nanoparticles in Induced Type 2 Diabetes Mellitus in Dogss in Induced Type 2 Diabetes Mellitus in Dogs

Type 2 diabetes mellitus (T2DM) in dogs is a complex, multifactorial disease that is characterized by chronic hyperglycemia and insulin resistance. Current therapeutic options are often limited by side effects and variable efficacy, highlighting the need for more effective and safer treatments. This study assessed the therapeutic potential of ginger ethanolic extract (GEE), GEE-loaded chitosan nanoparticles (GEE-CNPs), and chitosan nanoparticles (CNPs) against T2DM in dogs. Twenty adult local breed mongrel dogs of both sexes, aged 7 to 13 months, with an average body weight of 10.4±0.76 kg, were included. The dogs were allocated into five groups (n=4 each): a non-diabetic, untreated Negative Control group, and four diabetic treatment groups, following T2DM induction via a single intravenous alloxan-nicotinamide injection. Each treatment group received daily oral administrations of either saline (Positive Control), GEE, GEE-CNPs, or CNPs at a dosage of 81.7 mg/kg BW over 45 days. Serum glycemic status (fasting serum glucose, insulin, and insulin resistance) was ‎recorded at baseline and on days 7, 14, 21, 28, 35, 42, and 45 post-treatments. ‎Additionally, on day 45, serum lipid profiles, liver function indicators (alanine aminotransferase [ALT], gamma-glutamyl transferase [GGT], and bilirubin), and ‎markers of antioxidant status (glutathione [GSH] and malondialdehyde [MDA]) were assessed.‎ The results showed that dogs in the diabetic Positive Control group ‎exhibited ‎hyperglycemia, dyslipidemia‎, liver ‎dysfunction, and elevated ‎oxidative stress markers, ‎‎underscoring the severe impact of T2DM. Compared to the diabetic Positive Control, oral GEE, GEE-CNPs, and CNPs ‎treatments significantly (P&lt;0.05) improved ‎fasting glucose levels, insulin sensitivity, lipid profiles (reduced total cholesterol, ‎triglycerides, and LDL-C), liver function markers, and antioxidant status, indicating ‎enhanced metabolic health and reduced oxidative stress. The findings suggest that GEE, GEE-CNPs, and CNPs offer potential as therapeutic agents for T2DM in dogs, demonstrating ‎significant benefits in glycemic control, lipid normalization, liver function, and oxidative ‎stress reduction. Further investigations with larger cohorts and longer durations are ‎recommended to confirm these results and ascertain the clinical applicability and safety of ‎these natural remedies in managing canine diabetes‎‎‎.

Efficacy of percutaneous vertebroplasty using cross-puncture in the treatment of Genant grade 0-1 osteoporotic vertebral compression fractures.

Percutaneous vertebroplasty (PVP) is a common surgical method for osteoporotic vertebral compression fracture (OVCFs). The puncture method and location of the puncture needle can directly affect bone cement distribution in the vertebra. This retrospective study aimed to compare the clinical efficacy and safety of PVP using the cross-puncture and bilateral conventional puncture for the treatment of Genant grade 0-1 OVCFs. We retrospectively analyzed 98 patients who underwent PVP in our department between January 2019 and April 2023, including 50 and 48 treated with the cross-puncture (group A) and bilateral conventional puncture (group B), respectively. Operation time (min), bone cement injection volume (mL), bone cement leakage rate, bone cement classification, and related complications were compared between the groups. The visual analog scale (VAS), Oswestry disability index (ODI), heights of the anterior and midline of the injured vertebrae, and Cobb angle were compared pre-operatively and at the follow-up. Excellent and good operation rates were evaluated using the modified Macnab criteria. The bone cement leakage rate in group B (25%) was higher than that in group A (8%) (P<0.05). However, the injection amount of bone cement in group A (5.47±0.72 mL) was significantly higher than that in group B (4.43±0.64 mL) (P<0.001). The bone cement distribution grades in group A (40 cases of grade 3) were significantly better than those in group B (0 cases of grade 3) (P<0.001). Compared with pre-operative values, the VAS and ODI scores at each follow-up significantly decreased, anterior and midline heights of the injured vertebrae significantly increased, and Cobb angle significantly decreased in both groups (P<0.001). The complication rate in group A (0%) was significantly lower than that in group B (10.42%) (P<0.05). According to the modified Macnab standard, the excellent and good ratings in group A (96%) were significantly higher than those in group B (62.5%) (P<0.001). Cross-puncture and bilateral conventional puncture were both effective methods for the treatment of Genant grade 0-1 OVCFs. However, the cross-puncture was more advantageous in terms of the bone cement leakage rate, amount of bone cement injected, bone cement distribution grade, and complications.

Assessment of Nurses' Patient Safety Culture in Primary Health Care Centers in Saudi Arabia

Purpose: Patient safety culture emphasizes strategies to prevent harm, learn from errors, and strengthen healthcare systems, nurses play a crucial role in maintaining patient safety within health facilities. Assessing patient safety culture (PSC) among nurses is essential for identifying gaps, fostering improvements, and strengthening overall care delivery. This study aims to explore nurses' perceptions of patient safety culture in the primary health care centers (PHCs) in Saudi Arabia. Materials and Methods: A cross-sectional study design was utilized to select 387 nurses employed in primary healthcare centers in Jeddah, using convenient sampling via an online survey. The Hospital Survey on Patient Safety Culture (HSOPSC) questionnaire was used to evaluate the perception of patient safety culture. Data were saved and examined utilizing SPSS Ver.26 software. Along with descriptive statistics, independent sample t-tests and ANOVA were employed to examine the significance of differences among subgroups. A p-value below 0.05 signifies statistical significance. Findings: The overall score representing nurse managers' perceptions of patient safety culture was a mean of 3.93 with a standard deviation of 0.44. Among the assessed domains, the teamwork support domain received the highest score, with a mean of 4.27 and a standard deviation of 0.587, while the nonpunitive response to error had the lowest score, with a mean of 2.44 and a standard deviation of 0.883. Nurses younger than 30 years reported a significantly lower overall score, with a mean of 3.74 and a standard deviation of 0.43. In contrast, nurses holding diplomas and those in clinical roles achieved higher scores, with means of 3.97 and 3.99, respectively, and standard deviations of 0.44 and 0.46. Scores increased notably with additional years of experience, particularly for nurses with ten or more years of experience, who achieved a mean score of 4.07 with a standard deviation of 0.62, compared to those with ten to less than fifteen years of experience, who achieved a mean score of 3.75 with a standard deviation of 0.33. The differences were statistically significant with a p-value of less than 0.001. Significant differences, also with a p-value of less than 0.001, were observed across departments. The WBC unit recorded the highest perception score, with a mean of 4.32 and a standard deviation of 0.50, followed by the X-ray unit, with a mean of 4.01 and a standard deviation of 0.33 Implications to Theory, Practice and Policy: Nurses viewed the safety culture positively in the primary health care centers. Less experienced and younger nurses indicated lower perceptions of PSC, whereas clinical nurses assessed it higher than non-clinical personnel. High-pressure areas such as the Operating Room encounter more significant PSC challenges than other departments. It is essential to create training programs that connect younger nurses with older professionals to boost their clinical confidence and safety skills, focusing on learning from errors instead of placing blame.

Efficacy and safety of aspirin in preventing venous thromboembolism after hip arthroplasty for femoral neck fracture: a noninferiority prospective cohort study

BackgroundVenous thromboembolism (VTE) is a common complication after hip arthroplasty. Here, we investigated the clinical efficacy and safety of prophylactic aspirin vs. conventional therapy in hip arthroplasty for femoral neck fracture.MethodsPatients who underwent total hip arthroplasty and hemiarthroplasty for femoral neck fractures between April 2021 and April 2024 were prospectively enrolled. Group A received oral aspirin (100 mg, once daily) as VTE prophylaxis; Group LR received low-molecular-weight heparin (4,250 U, once daily) sequentially followed by rivaroxaban (10 mg, once daily). The patients were followed up for 90 days postoperatively. Safety and efficacy were comprehensively evaluated based on postoperative VTE incidence, laboratory blood tests, bleeding events, and other complications.ResultsGroup A was noninferior to Group LR in preventing VTE (incidence rates of 11.6% and 10.1%, respectively, with a rate difference of 1.5%, 95% CI: 0.7–2.3%, P for non-inferiority test = 0.017). There was no significant difference between the groups in the incidence of bleeding events (3.3 vs. 8.4%; P = 0.092). Furthermore, the rates of other complications did not differ significantly between groups.ConclusionIn patients undergoing hip arthroplasty for femoral neck fractures, the efficacy and safety of oral aspirin for preventing VTE was similar to that of low-molecular-weight heparin followed by rivaroxaban.

Efficacy and Safety of Aerosol Inhalation of Colistin Sulfate for the Treatment of Carbapenem-Resistant Klebsiella pneumoniae Infection in the Peri-Operative Period of Liver Transplantation: A Single-Center Retrospective Study.

Objective: This study intended to evaluate the clinical efficacy and safety of colistin sulfate aerosol inhalation in combination with ceftazidime-avibactam for the treatment of pulmonary carbapenem-resistant Klebsiella pneumoniae (CRKP) infection during the peri-operative period of liver transplantation. Materials and Methods: A retrospective analysis was designed to investigate 52 patients who developed pulmonary CRKP infection after liver transplantation between December 1, 2019, and November 30, 2022. On the basis of whether they received colistin sulfate aerosol inhalation, the patients were divided into the treatment group (n = 29) and the control group (n = 23). The baseline information, infection status, CRKP enzyme type, inflammatory markers, liver and kidney function, and prognosis were compared and analyzed. Results: There were no significant differences in patient characteristics, infection status, and drug resistance enzyme type between the treatment group (treated with colistin sulfate aerosol inhalation and ceftazidime and avibactam sodium for injection) and the control group (treated with ceftazidime and avibactam sodium for injection alone). Colistin sulfate aerosol inhalation treatment reduced concentrations of inflammatory markers, with post-treatment white blood cell count, procalcitonin, and C-reactive protein significantly lower than pre-treatment levels (p < 0.05). Except for C-reactive protein at 14 days (p = 0.032), the two groups had no significant differences in other indicators. There were no significant differences in alanine aminotransferase, aspartate aminotransferase, total bilirubin, and glomerular filtration rate after treatment, indicating no discernible alteration in liver and kidney function. In addition, the treatment group took a significantly shorter time to normalize body temperature compared with the control group (p = 0.025), but there were no significant differences in the cure with no colonization rate and all-cause mortality rate between the two groups. Conclusions: The combination of colistin sulfate aerosol inhalation and ceftazidime and avibactam sodium for injection is effective in treating pulmonary CRKP infection during the peri-operative period of liver transplantation. It does not impose an additional burden on liver and kidney function, providing a new treatment option for this type of infection.

Evaluation of the attitudes, actions, and preferences of pharmacists about ongoing education

Background: Pharmaceutical care is a dynamic field that requires continuous education (CE) to ensure pharmacists remain proficient in addressing advancements in healthcare. Understanding pharmacists' attitudes, actions, and preferences toward CE is crucial for designing effective programs that align with their needs and overcome barriers to participation. Methods: A cross-sectional study was conducted among 500 licensed pharmacists using a structured, self-administered questionnaire. Participants were recruited from various practice settings, including community pharmacies, hospitals, academia, and medical representatives. The survey assessed demographic characteristics, attitudes toward CE, participation frequency, preferred learning methods, and barriers to engagement. Data were analyzed using descriptive and inferential statistics, including multivariate logistic regression to identify predictors of positive attitudes and high CE participation. Results: Of the participants, 78% strongly agreed or agreed that CE is essential for professional development. Common barriers to participation included time constraints (62%), lack of access to quality programs (45%), and financial limitations (30%). Preferred CE formats were online courses (65%) and workshops (50%), with high interest in clinical practice topics (82%), drug safety (58%), and pharmacy management (40%). A significant association was observed between professional roles and preferences for CE formats and topics (p &lt; 0.05). Conclusion: Pharmacists strongly value CE for professional growth, favoring flexible and workplace-relevant learning formats. Addressing barriers such as time, cost, and access to quality programs is critical to enhancing participation. Future CE initiatives should include routine needs assessments and offer diverse, cost-effective, and practical learning opportunities tailored to pharmacists’ professional roles and preferences.

Assessment of Oral Anticoagulant Reversal Strategies in Emergency Surgery: Insights from a Prospective Study

Introduction: The management of thrombotic risk in clinical medicine has been a longstanding challenge. Oral anticoagulants, specifically vitamin K antagonists (VKAs) like warfarin, have been used for over fifty years. However, VKAs present significant challenges such as frequent monitoring and dietary interactions. Direct oral anticoagulants (DOACs) were developed to address these limitations, offering simplified dosing and fewer interactions. Both VKAs and DOACs, however, pose challenges in managing major bleeding and urgent surgical interventions. Methods: This prospective study, conducted at Mohammed V Military Hospital in Rabat from January 2022 to January 2023, examined the clinical practice, efficacy, and safety of different treatment strategies in patients on oral anticoagulants (VKAs and DOACs) requiring emergency surgery within 24 hours of hospital admission. Inclusion criteria included being over 18 years of age, on anticoagulant therapy, and requiring emergency surgery. Patients were evaluated for bleeding before and after surgery, use of hemostatic agents, blood loss, transfusions, and adverse events. Results: A total of 69 patients were included, with 48 treated with VKAs and 21 with DOACs. The mean age was 63.8 years (range 36-78), with a mean age of 62.5 years (±10.2) for the VKA group and 66.7 years (±9.1) for the DOAC group (p = 0.44). There was no significant difference in delays to surgery between the VKA (68%) and DOAC (66.6%) groups for surgeries performed within 24 hours. Hemostatic treatment varied significantly, with more VKA patients receiving resh frozen plasma (77% vs. 52%) and more DOAC patients receiving prothrombin complex concentrates (48% vs. 23%). Bleeding complications were observed in 12.5% of VKA patients and 9.5% of DOAC patients. Thromboembolic events were observed in one patient within 30 days, specifically, a pulmonary embolism occurring on day 3 in a patient who underwent surgery for a hip fracture. The mortality rate ...

The Potential of PARP Inhibitors as Antitumor Drugs and the Perspective of Molecular Design.

PARP (poly-ADP ribose polymerase) has received widespread attention in cancer treatment. Research has shown that PARP plays a crucial role in DNA damage repair and has become a popular target for drug design. Based on the mechanism of "synthetic lethality", multiple PARPis (PARP inhibitors) have been launched for the treatment of BRCA deficient tumors. For example, the approved PARPis have shown significant potential in cancer treatment, particularly in breast cancer and cancers associated with BRCA1/BRCA2 deficiencies. However, the clinical efficacy and safety of PARP inhibitors in different cancers remain issues that cannot be overlooked. The design of PARPis aims to eliminate their resistance and broaden their application scope. Designing selective PARP-1 inhibitors is also a potential strategy. PROTACs (Proteolysis Targeting Chimeras) to degrade PARP have become a potential novel cancer treatment strategy.

Small-Molecular Drugs for Alzheimer's Disease

Alzheimer's disease (AD) is predominantly characterized by the accumulation of β-amyloid (Aβ) plaques and the formation of neurofibrillary tangles, which are induced by the hyperphosphorylation of the Tau protein. Furthermore, the pathology of AD extends to include the progressive loss of synapses and neurons, accompanied by reactive gliosis. Mannose sodium capsule is a low molecular weight acidic oligosaccharide compound prepared from Marine brown algae extract. It is an innovative drug independently researched and developed by China with independent intellectual property rights, and has been supported by the national Major Special Project of New Drug Creation and Technology. Among the myriads of pharmacological interventions, Mannatna has emerged as a novel therapeutic agent the drug is the first novel drug targeting the brain-gut axis for the treatment of Alzheimer's disease in China and the world. Behind its development logic is a new understanding of the pathogenesis of Alzheimer's disease. that has notably demonstrated both its clinical safety and efficacy in Phase III randomized controlled trials. Post-marketing clinical studies have convincingly corroborated its effectiveness and safety profile across a diverse range of real-world patient populations.

DREAMM-11, Part 2: Japanese phase I trial of belantamab mafodotin combination therapies in relapsed/refractory multiple myeloma

DREAMM-11 (NCT03828292) was a Phase 1, open-label, dose-escalation study of belantamab mafodotin in Japanese patients with relapsed/refractory multiple myeloma (RRMM). In Part 1, belantamab mafodotin monotherapy (2.5 or 3.4 mg/kg every 3 weeks) was tolerated and demonstrated clinical activity and a manageable safety profile. Part 2 investigated the tolerability, safety, clinical activity and pharmacokinetics of belantamab mafodotin (2.5 mg/kg on Day [D]1 of each 21-day cycle) plus bortezomib and dexamethasone (Arm A; N = 3) or belantamab mafodotin (2.5 mg/kg on D1 of the first 28-day cycle; 1.9 mg/kg on D1 of subsequent cycles) plus pomalidomide and dexamethasone (Arm B; N = 4) in Japanese patients with RRMM and ≥ 1 prior line of therapy. No dose-limiting toxicities were reported in Arm A; 1 (non-serious liver injury) was reported in Arm B. Safety profiles of each treatment combination were consistent with those of the individual agents and those in Western populations. An overall response was achieved by 3/3 (100%) patients in Arm A and 2/4 (50%) in Arm B. Pharmacokinetics were consistent between Japanese and Western populations. The clinical pharmacokinetics, safety, and efficacy data from this study can inform future use of belantamab mafodotin plus bortezomib/pomalidomide and dexamethasone in Japanese patients with RRMM.

Commentary on Clinical Safety and Efficacy of Dual Wavelength Low Level Light Therapy in Androgenetic Alopecia; A Double-Blind Randomized Controlled Study

Commentary on Clinical Safety and Efficacy of Dual Wavelength Low Level Light Therapy in Androgenetic Alopecia; A Double-Blind Randomized Controlled Study

The Significant Therapeutic Effects of Chinese Scorpion: Modern Scientific Exploration of Ion Channels.

Chinese scorpion (CS), a traditional animal-based medicine used for over a millennium, has been documented since AD 935-960. It is derived from the scorpion Buthus martensii Karsch and is used to treat various ailments such as stroke, epilepsy, rheumatism, and more. Modern research has identified the pharmacological mechanisms behind its traditional uses, with active components like venom and proteins showing analgesic, antitumor, antiepileptic, and antithrombotic effects. Studies reveal that CS affects ion channels, crucial for cellular functions, through interactions with sodium, potassium, and calcium channels, potentially explaining its therapeutic effects. Future research aims to elucidate the precise mechanisms, target specific ion channel subtypes, and validate clinical efficacy and safety, paving the way for novel therapies based on these natural compounds.

Targeting Refractory Triple-Negative Breast Cancer with Sacituzumab Govitecan: A New Era in Precision Medicine.

Advanced triple-negative breast cancer (TNBC) has poorer outcomes due to its aggressive behavior and restricted therapeutic options. While therapies like checkpoint inhibitors and PARP inhibitors offer some benefits, chemotherapy remains ineffective beyond the first line of treatment. Antibody-drug conjugates (ADCs) like sacituzumab govitecan-hziy (SG) represent a significant advancement. SG combines SN-38, an irinotecan derivative, with a Trop-2-targeting antibody via a pH-sensitive linking moiety, achieving a good drug:antibody ratio. In a phase I-II study involving metastatic TNBC (mTNBC) individuals, SG achieved an overall response rate of 33.3% and a median response period of 7.7 months. The phase III ASCENT trial demonstrated SG's efficacy in relapsed or refractory TNBC, improving median progression-free survival and median overall survival compared to chemotherapy. Common side effects include neutropenia, nausea, and fatigue. This article highlights the clinical potential, pharmacokinetics, safety profile, and resistance mechanisms of SG along with key ongoing clinical trials, emphasizing its role in managing refractory mTNBC, especially in third-line therapy. The review also discusses current strategies for managing adverse reactions and sequencing ADC treatments in clinical practice, along with the predicted basis of resistance. The optimal sequencing of SG relative to other ADCs, such as trastuzumab deruxtecan or T-DXd, remains an evolving question, especially as newer agents with distinct mechanisms of action and safety profiles enter the field. Further research is essential to establish evidence-based strategies for sequencing SG and addressing disease progression post-ADC therapy.

Population Pharmacokinetics of Epcoritamab Following Subcutaneous Administration in Relapsed or Refractory B Cell Non-Hodgkin Lymphoma.

Epcoritamab is a CD3xCD20 bispecific antibody approved for the treatment of adults with different types of relapsed or refractory (R/R) B cell non-Hodgkin lymphoma (B-NHL) after ≥ 2 lines of systemic therapy. Here we report the first results from a population pharmacokinetic model-based analysis using data from 2 phase 1/2 clinical trials (EPCORE® NHL-1, NCT03625037 and EPCORE NHL-3, NCT04542824) evaluating epcoritamab in patients with R/R B-NHL. Plasma concentration-time data included 6819 quantifiable pharmacokinetic samples from 327 patients with R/R B-NHL. A wide range of subcutaneous epcoritamab doses, 0.004-60 mg, was explored, with most patients (n = 298) following the approved dosing regimen: step-up dose (SUD) 1 of 0.16 mg on cycle 1 day 1 and SUD 2 of 0.8 mg on cycle 1 day 8, followed by a full dose of 48 mg administered weekly during cycles 1-3, biweekly in cycles 4-9, and every 4 weeks thereafter. Each cycle lasted 28 days. The data were analyzed using nonlinear mixed-effects modeling. Quasisteady-state approximation of a two-compartment target-mediated drug disposition model with first-order absorption adequately characterized pharmacokinetics of epcoritamab following subcutaneous administration. After the first full dose and at the end of the weekly dosing regimen (end of cycle 3), the estimated median time to maximum concentration (tmax) was 4 and 2.3 days, respectively. Age and body weight were significant covariates on the pharmacokinetics of epcoritamab. The geometric mean (coefficient of variation [CV], %) of the apparent total volume of distribution was 25.6 L (82%) for patients with R/R large B cell lymphoma in EPCORE NHL-1. Epcoritamab elimination exhibited nonlinear characteristics, with exposure increasing more than proportionally over 1.5-48 mg doses. The geometric mean (CV%) values of apparent total clearance and terminal half-life were 0.53 L/day (40%) and 22 days (58%), respectively, at the end of cycle 3 for the 48 mg full dose. Clinical data analyses did not identify any association between assessed characteristics, including body weight or age, and clinical efficacy or safety. After accounting for body weight, no clinically significant differences in epcoritamab pharmacokinetics were observed for sex, race, renal or hepatic function, or other disease characteristics. Age was not found to significantly affect epcoritamab pharmacokinetic exposure. Antidrug antibodies developed in 4 (2.6%) of 156 evaluable patients treated with the approved 0.16/0.8/48 mg regimen. Antidrug antibody status did not affect epcoritamab pharmacokinetics. Epcoritamab pharmacokinetics in R/R B-NHL were well characterized by the population pharmacokinetic model. No dosage adjustments are recommended in subpopulations based on body weight, age, sex, race, mild-to-moderate renal impairment, or mild hepatic impairment. The risk of immunogenicity was low. These are the first published results of population pharmacokinetic modeling for epcoritamab.