Investigation of adverse events (AEs) of immune checkpoint inhibitors (ICIs) is meaningful based on its rapid increase in the real-world utilization. We aimed to detect signals of adverse drug reaction (ADR) associated with ICIs plus chemotherapy as well as ICIs monotherapy compared to chemotherapy. We used individual case safety reports (ICSRs) between 2014 and 2022 using KIDS KAERS DB (2304A0076). We defined AEs and drug using MedDRA and the national drug code directory provided by the Ministry of Food and Drug Safety. Disproportionality analysis was performed with indices of reporting odds ratio (ROR) and information component (IC) to detect signals. The criteria for signal detection were established as follows: PRR and ROR value of 2 or more, χ2 value of 4 or more, an occurrence count of 3 or more, and lower bound of the 95% confidence interval greater than 0. We identified 206,959 ICSRs in the KIDS KAERS DB, of which 5,154 were associated with ICIs and 201,805 were associated with chemotherapy. Most reported cases were male (71.05%) and 60-69 years old (36.79%). A total of ICIs-AE combinations satisfied all three criteria of the signal: 146 were ICIs monotherapy and 63 were ICIs plus chemotherapy. Among the top 50 signals for ICIs monotherapy, the highest ROR was for radiation pneumonitis (ROR, 2313.58; IC, 5.38), vitiligo (ROR, 509.41; IC, 4.94), and thyroiditis (ROR, 356.79; IC, 5.03). The top 50 signals for ICIs plus chemotherapy were similar to ICIs monotherapy, with high RORs reported for bleeding varicose vein (ROR, 445.88; IC, 6.43) and macular oedema (ROR, 334.57; IC, 6.33) as adverse events not found in ICIs monotherapy. The study highlights an important signal of AEs associated with ICIs, both monotherapy and combination, with conditions such as radiation pneumonitis, thyroiditis, and vitiligo. These AEs should be monitored in clinical settings.

Introduction
Diabetic macular edema (DME) is a leading cause of vision impairment among diabetics. Evaluating the safety of treatments like aflibercept and ranibizumab, especially regarding renal side effects, is critical due to the high prevalence of kidney complications in diabetics.

Aims
This study compares the incidence of renal side effects—acute kidney injury (AKI) and end-stage renal disease (ESRD)—and all-cause mortality between DME patients treated with aflibercept versus ranibizumab.

Methods
We conducted a retrospective cohort analysis using the Global Collaborative Network's data on 12,628 DME patients. The groups analyzed included 9,206 patients receiving aflibercept and 3,422 on ranibizumab. Propensity score matching was used to equalize baseline characteristics across groups, including demographics and clinical profiles. The incidence of AKI, ESRD, and mortality were assessed through Kaplan-Meier survival analysis, and hazard ratios (HRs) with 95% confidence intervals (CIs) were computed to compare risks.

Results
Post-matching, each cohort consisted of 3,182 patients. The HR for ESRD was 1.032 (95% CI: 0.898-1.187, p = 0.653), indicating no significant difference between treatments. Similarly, the HRs for AKI and mortality were 0.979 (95% CI: 0.892-1.075, p = 0.660) and 0.987 (95% CI: 0.884-1.101, p = 0.811) respectively, showing no significant differences.

Conclusions
The study revealed no significant differences in the risk of renal side effects or mortality between aflibercept and ranibizumab treatments in DME patients. Both medications have comparable safety profiles regarding renal outcomes and survival. This supports flexible treatment choice based on other patient-specific factors. Further studies are recommended to investigate additional treatment efficacy and safety aspects.

Introduction: Continuing controller therapy is necessary for pregnant women with asthma to decrease the risk of asthma exacerbation during pregnancy. However, existing evidence regarding the effects of inhaled corticosteroids (ICS) and long-acting beta2-agonists (LABA) on adverse fetal outcomes was less and old.
Aims: This study was to update and comprehend safety evidence on ICS and LABA use among pregnant women with asthma. The ICS use, the ICS dose-response effects, and the add-on therapy with LABA during pregnancy were investigated.
Methods: A population-based retrospective cohort study was conducted. The Health and Welfare Database, Birth Certificate Application, and Maternal and Child Health Database in Taiwan were used as data sources. Pregnant women with asthma who delivered babies between 2009 and 2017 were enrolled. Three independent variables, ICS, ICS dose-response effects, and LABA use during pregnancy, were evaluated separately. Adverse fetal outcomes included low birth weight, small for gestational age, preterm birth, and congenital anomalies. Propensity scores matching (PSM) and inverse probability of treatment weighting (IPTW) were used to adjust confounders, including socio-demographics, comorbidities, comedications, and asthma severity. Logistic regression models were used to calculate the adjusted odds ratio (aOR).
Results: There were 4,538 pregnant women with asthma enrolled. After PSM and IPTW, neither ICS nor LABA was significantly associated with any adverse fetal outcome. However, high-dose ICS users had a significantly higher risk of congenital anomalies (aOR: 4.46; 95% CI: 1.45-13.71) within 90 days of delivery and congenital anomalies (aOR: 3.87; 95% CI: 1.29-11.60) within one year of delivery than low-to-moderate ICS users.
Discussion: This study did not identify the increased risk of adverse fetal outcomes among ICS or LABA users during pregnancy. Nonetheless, a higher risk of congenital anomalies was observed among high-dose ICS users. Pregnant women who need high-dose ICS should be closely monitored.
Keywords: corticosteroid, long-acting beta2-agonist, pregnancy, asthma

Introduction
Head and neck cancers (HNCs) are among the most prevalent malignancies in India, significantly contributing to cancer-related morbidity and mortality. Oral premalignant disorders (OPMDs) increase the risk of developing HNCs. Early detection of potential malignancies can improve prognosis; however, current diagnostic methods are expensive, invasive, and require highly skilled professionals. Micro-RNAs (miRNAs) play a fundamental role in oncogenesis pathways, and their elevated expression has been investigated as a potential early diagnostic tool.
Aim
This study aims to identify expression changes of miRNA-21 and miRNA-31 in patients with OPMDs.
Methods
The study involved testing the saliva of 25 patients with OPMDs (study group) and 25 healthy individuals (control group). miRNAs were isolated from saliva samples using miRNA isolation kits and quantified using reverse-transcriptase polymerase chain reaction (RT-PCR).
Results
Compared to the control group, patients with OPMDs showed significantly higher expression levels of miRNA-21 and miRNA-31. The mean expression levels of miRNA-21 were 3.5 times higher in the study group compared to the control group (p<0.001). Similarly, the mean expression levels of miRNA-31 were 4 times higher in the study group (p<0.001). These findings indicate a strong correlation between elevated miRNA expression and the presence of OPMDs.
Discussion/Conclusion
The elevated expression of miRNA-21 and miRNA-31 in patients with OPMDs suggests a higher likelihood of developing malignant conditions in the future. These miRNAs can serve as potential biomarkers for early detection of malignancies in patients with OPMDs. Further optimization and detailed research on this procedure can help identify individuals with OPMDs who are at higher risk of developing malignancies. Early detection of potential malignancies can significantly improve prognostic outcomes for these patients. Developing non-invasive early diagnostic techniques can revolutionize cancer detection and diagnosis, leading to better clinical management and reduced healthcare costs.

Introduction: Quinazolinone, characterized by its distinctive structural features, holds significant importance in contemporary drug research due to its capacity for high-affinity binding at various binding sites and effective promotion of drug activity. Medicinal chemists usually design specific pharmaceutical agent for clinical treatment needs via several strategies. The CADD (computer-aided drug design) approach utilizes multiple computational techniques to facilitate the process of new drug discovery in designing ligands that may effectively bind to a specific biotarget.

Aims: To develop safe and effective anticancer drugs remains a critical aspect of contemporary healthcare. From clinical observation, patients usually suffer from significant toxic side effects when receiving chemotherapy. Therefore, the aim of the study is to develop novel chemotherapeutic drugs with good anticancer activity but low toxicity to normal cells.

Methods: In this study, the CADD technique was used to design novel potent quinazoline analogues with low toxicity for cancer treatment. A series of quinazoline derivatives (HoLu-1~HoLu-10) aiming at tubulin as a biotarget was designed and synthesized. These compounds were then subjected to treatment of oral CAL27, metastatic CAL27, colorectal HCT116, and normal colon epithelial FHC cells at a concentration of 10 μM for 72 hours. Cell viability was determined utilizing the sulforhodamine B (SRB)-based in vitro toxicology assay as described previously.

Results: Some of the compounds demonstrated significant cytotoxicity against various cancer cell lines. Among these compounds, compound HoLu-7 demonstrated the most potent cytotoxicity against CAL27, metastatic CAL27, and HCT116 cells, while exhibiting relatively low toxicity towards normal colon epithelial FHC cells.

Discussion: These findings suggest that compound Holu-7, with the structure of quinazoline scaffold possessing 2,4-disubstituted phenyl moiety and displaying the best geometrical conformation, exhibited selectivity by demonstrating non-toxicity towards normal cells but enhanced cytotoxicity against various cancer cell lines, and may be a promising candidate for further development as anticancer drug.

Introduction. Psoriasis, a chronic inflammatory skin disorder affecting many globally, often requires systemic treatments such as biologics. The long-term safety of interleukin (IL) inhibitors like ustekinumab remains uncertain due to limited follow-up in existing studies. Comprehensive long-term safety data are essential for managing chronic conditions like psoriasis.
Aims. This 14-year cohort study, using Danish national register data, aimed to investigate the long-term safety profile of ustekinumab concerning malignancies, major adverse cardiovascular events (MACE), serious infections, and serious hypersensitivity reactions compared to other systemic psoriasis treatments.
Methods. Utilizing Danish national register data, this study examined patients diagnosed with psoriasis (PsO) or psoriatic arthritis (PsA) treated with ustekinumab. Comparators included non-biological systemic treatments (non-biologic), tumor necrosis factor α inhibitors (TNF-α), IL-17 inhibitors (IL-17), and IL-23 inhibitors (IL-23). Study periods were 2009-2022 for non-biologic and TNF-α, 2015-2022 for IL-17, and 2018-2022 for IL-23. Patients with prior malignancies or MACE were excluded. An active comparator new user (ACNU) design with propensity score matching was used, and Cox proportional hazards regression models analyzed intention-to-treat (ITT) and continuous-index-treatment (CIT) estimands.
Results. Ustekinumab users averaged 45.1 years in age, younger than other groups. Males constituted 57.3% of the ustekinumab group. Hazard ratios indicated no elevated risks for malignancies excluding non-melanoma skin cancer (NMSC) (HR 1.36, CI 0.95-1.94), NMSC (HR 0.97, CI 0.61-1.53), MACE (HR 1.32, CI 0.86-2.02), or serious infections (HR 0.69, CI 0.23-2.05) compared to other treatments. Subgroup analyses by PsA status showed similar safety outcomes across all groups.
Discussion. This study found ustekinumab to be safe regarding malignancies, MACE, serious infections, and serious hypersensitivities over a 14-year follow-up in Danish psoriasis patients. Strengths include extensive follow-up and comprehensive data, ensuring no loss to follow-up. However, reliance on hospital-based diagnoses and potential registration discrepancies may bias results, and limited follow-up for IL-23 restricted some analyses. Overall, ustekinumab showed a favorable safety profile compared to other treatments.

Introduction
Understanding prostate cancer progression and mortality risk is important for optimised patient management and informed medical decisions. Real-world data provide valuable evidence for model fitting and evaluation to predict mortality.
Aims
This study aims to develop a time-inhomogeneous Markov model using population-based real-world data to estimate prostate cancer progression and predict 10-year mortality risks utilizing baseline characteristics.
Methods
We developed time-inhomogeneous Markov model comprises seven health states related to prostate cancer progression (localized hormone-naive, localized castration resistance, metastasis hormone-sensitive, metastasis castration resistance, remission and death). Hong Kong territory-wide electronic medical database CDARS was the primary data source for real-world transition probability estimation, based on a 10-year follow-up of patients newly diagnosed with prostate cancer between 2011 and 2013. Age, Charlson Comorbidity Index (CCI) and Prostate-Specific Antigen (PSA) were considered for fitting the time-varying transition probability. Model performance was assessed using Mean Average Percentage Error (MAPE) by comparing expected and observed cumulative deaths in the validation cohort of patients diagnosed in 2014.
Results
We identified 3978 incident patients (mean [SD] age, 73.1 [8.80] years) with prostate cancer between 2011 and 2013 with 2037 death recorded during the 10-year follow-up. The MAPE of the 10-year cumulative death in the validation cohort was 0.17, indicating good prediction performance. The most frequently observed group of patients (aged <65, CCI 0, PSA 4-10 ng/mL) had one-year, five-year, and 10-year mortality risks of 3.4%, 22.6%, and 42.8%, respectively. In contrast, severe patients (aged >80 years at diagnosis, CCI >= 3, and PSA >= 100 ng/mL) faced significantly higher risks, with a death probability of 22.4% at year one, 64.3% at year five and 91.3% at year ten.
Discussion
The real-world time-varying Markov model can mimic the disease progression in actual clinical practice, estimate individual mortality risk, and guide early patient management plans for improved survival.

Introduction: Tissue damage is common during the surgical and Para surgical procedures because of which general post-operative complications like pain, inflammation, burning sensation, bleeding, etc. may occur. Ayurveda has explained about application of Liquorice (Glycyrrhiza glabra) Ghee preparation to reduce the pain, inflammation, burning sensation, bleeding pain caused by the surgery of haemorrhoids.
Aim: To evaluate and validate the suppositories of Liquorice preparation in Human subjects through an open labelled controlled randomized clinical study.
Methods: Total number of 40 Subjects suffering from Haemorrhoids were selected for the study and were randomly allotted into two groups namely Group-A and Group-B with 20 in each group. Subjects with Group-A were treated with Liquorice Ghee in the form of suppositories and Subjects of Group-B were treated with Diclofenac-sodium suppositories. Distribution of age gender, occupation, diet, appetite, age of haemorrhoids, bowel habit, nature and type of pain were recorded.
Results: Comparative analysis of effect of treatment on burning sensation, size, color and shape of wound, between Group A and Group B, the results of Group A (Liquorice treated) were statistically highly significant (P value <0.001). Further moderate improvement was observed on 4th day, marked improvement was seen after 5th day and maintained at follow up. Notably, Liquorice suppositories are on par with Diclofenac sodium suppositories in mitigating the pain. Whereas results of treatment on bleeding between Group A and Group B, was found to be statistically insignificant. It was found that Liquorice suppositories is the best line of treating post operative haemorrhoids. Group-A has better effects on the wound healing, burning sensation and bleeding.
Discussion: Group-A has better effect because of Liquorice suppositories which has analgesic, wound healing properties. It also contains phytochemicals which have anti-inflammatory properties. Most importantly, Liquorice preparation in Ghee increases the bioavailability of Liquorice extract.

Introduction: Impostor syndrome involves doubting one's accomplishments and feeling self-conscious about abilities, often rooted in low self-worth, upbringing, and aspirations for success. This condition affects both health and work performance and may lead to additional health issues.
Aim/Objective: To investigate the prevalence of impostor syndrome among undergraduate students and associated factors.
Method: Undergraduate students participate in this cross-sectional study design by completing an online self-report questionnaire between August and December of 2023. The Impostor syndrome was measured by the Clance Impostor Phenomenon Scale (CIPs) consists of twenty items, each of which is rated from 1 (not at all true) to 5 (extremely true) on a Likert scale. Total score of 60 or more shows the presence of impostor syndrome, whereas a score of less than 60 indicates the absence of impostor syndrome. Stata version 14 was used for data analysis; multivariable logistic regression was used to find association between impostor syndrome and the factors including gender, age, education year, income and satisfaction with GPA.
Results: Three hundred and twenty-two students completed the questionnaire; 66.7% were female; 52.5% were 20 years old; 33.5% were the second-year students. According to CIPs: 71.7% had impostor syndrome and 28.3% had no impostor syndrome. There was no statistically significant relationship between impostor syndrome and the variables including gender, age, years, income and satisfaction with GPA (p>0.05).
Conclusion: The prevalence of impostor syndrome was around 72%. Moreover, there was no significant association between associated factors and impostor syndrome.

Introduction: Acute paraquat poisoning is a global health concern due to high mortality rate. Absence of an antidote or treatment guideline, poorly understood regimens of newer extra-corporeal removal (ECR) techniques further complicate patient prognosis. Thus, there is a need to identify optimal management strategies in acute paraquat poisoning for improving patient outcomes.
Aims: To investigate the clinical characteristics, treatment efficacy and factors affecting clinical improvement in patients admitted with acute paraquat poisoning.
Methods: The medical records of 222 patients admitted with acute paraquat poisoning from 1st January, 2012 to 1st March, 2023 were retrospectively reviewed. Patients were classified into two treatment groups, ECR group and Non ECR group. Primary outcomes were clinical improvement and clinical non-improvement. Secondary outcomes were days of hospitalisation, intensive care and mechanical ventilation. Chi square test was used to compare categorical variables and binary logistic regression was used to assess association of factors with clinical non-improvement. Statistical analysis was performed using SPSS software.
Results: A total of 139 (62.6%) males and 83 (37.4%) females with a median (IQR) age of 25 (11) years were included. The clinical non-improvement rate was 60.4% (n = 134). There was no significant difference between the ECR and Non-ECR treatment groups in terms of clinical improvement (p=0.88). Variables significantly associated with clinical non-improvement were mechanical ventilation (OR: 0.003; p<0.001) and development of multi-organ dysfunction syndrome (MODS) (OR: 0.081; p=0.012).
Conclusion: There was a significantly higher incidence of clinical non-improvement in cases with acute paraquat poisoning. Management approaches including ECR techniques did not significantly improve clinical outcome. Mechanical ventilation and development of MODS were associated with clinical non-improvement.
Keywords: paraquat poisoning, improvement, extra-corporeal removal, treatment

Introduction: With a dramatic expansion in stem cell research, there is a conflict in the literature about whether stem cell therapy is effective and safe in muscular dystrophies.
Aims: We performed a systematic review to assess the efficacy and safety of stem cell therapy in muscular dystrophies and make recommendations for use in clinical settings.
Methods: An electronic search on Cochrane Library, Embase, PubMed, and Web of Science from inception to August 2023 to identify randomised controlled trials(RCTs) on the efficacy and safety of stem cell therapy compared to usual care in MD. Improvement in functional composite (using PUL), beyond 6-mo of treatment were the efficacy outcomes, while occurrence of treatment-emergent adverse events(TEAEs) were the safety outcomes. The Risk of Bias version 2 tool was applied for quality assessment of individual study, while GRADE for certainty assessment of individual outcome. The pooled estimates were reported as either as mean-difference(MD) or risk-ratio(RR) with 95% confidence interval(CI) and heterogeneity (I2).
Results: Three RCTs on Duchenne Muscular Dystrophy(DMD) with low risk of bias were included. The estimates of PUL 1.2 in HOPE-trial reported the overall unfavourable changes with intracoronary infusion of CAP-1002 as compared to usual care at 6(MD:-6.27; 95%CI:-14.15 to 1.61) and 12(-2.74; 95%CI:-7.68 to 2.20) month from baseline. However, the HOPE-2 trial reported the favourable changes with intravenous CAP-1002 in PUL 1.2(Least square mean(LSM):29.7; 95% CI:5.7 to 53.7; p=0.02) and PUL 2.0(LSM: 28.8; 95% CI: 1.5 to 56.1; p = 0.04 scores at 12-month from baseline. The pooled estimates of occurrence of serious AEs were not statistically significant(RR:3.22; 95%CI: 0.56-18.47; I2:0%).
Discussion: Considering a small number of RCTs, heterogeneity and low certainty of evidence, our systematic review suggests that stem cell therapy may have little to no difference in clinical improvement and quality of life in persons with muscular dystrophies.

Introduction: Rare diseases pose significant challenges to the global healthcare system due to criticality and lack of treatments. The quality of healthcare varies across countries making it difficult to undertake coherent approach to treatment management. Pharmacoepidemiological studies are crucial in understanding the real-world effectiveness and safety of rare disease treatments. This review explores the current landscape of these studies to identify key differences in treatment availability, health outcomes, and ways to improve healthcare for rare disease patients.

Aim
• Comparative assessment of orphan drug utilization studies in Japan and India
• Identifying best practices and areas of cross-adoption and collaboration to improve rare disease management
Methods: Literature focusing on pharmacoepidemiological studies in Japan and India were identified by searching scientific databases using combination of related keywords. Literature with information about orphan drugs and references to overall conduct, challenges, and best practices regarding pharmacoepidemiological studies were considered for the final review.

Results: Rare disease prevalence estimates vary between Japan and India. Japan’s disease registry system (RADAR-J) is well established with various data sources for pharmacoepidemiological data, whereas registry in India (NRROID) is under development. Japan’s orphan drug regulatory framework enables streamlined drug approval but available therapies are limited. A targeted orphan drug regulatory framework and classification system is absent in India and drug availability is limited. Pharmacoepidemiological data is widely incorporated in orphan drug development lifecycle in Japan, while in India focus is on case reports and small-scale observational studies.

Discussion: Understanding orphan drug utilization patterns and treatment outcomes based on pharmacoepidemiological data is key to identifying areas for improvement, and promoting adoption of best practices and collaboration. This will help in design and development of treatments to improve rare disease management and optimize orphan drug availability and usage across Japan and India.

Keyword: Registry, Comparative Assessment, Rare disease, India, Japan

Introduction
The development of CFTR modulators (correctors and potentiators) emerged as a promising approach, aiming to restore CFTR protein function. A lack of head-to-head randomized clinical trials (RCTs) comparing CFTR modulators leaves uncertainty regarding optimal treatment.

Aim
To estimate the relative efficacy and safety of CFTR modulators for patients with cystic fibrosis who have a phe508del CFTR mutation.

Methodology
We conducted an extensive literature search for randomized clinical trials (RCTs) in PubMed, EMBASE, Scopus, and Ovid from inception until December 2023. Eligible studies included any CFTR modulators for the treatment of children and adults with a confirmed diagnosis of cystic fibrosis with phe508del CFTR mutation. Two reviewers independently and in duplicate performed study selection, data extraction, and quality assessment. We performed a random effect Bayesian network meta-analysis (NMA) for each outcome using the gemtc package in R. Primary outcomes were change in ppFEV1, sweat chloride, CFQ-R score, and serious adverse events. The confidence in the NMA (CINEMA) framework was utilized to determine the certainty of evidence.

Results
23 studies involving 4296 patients examining 22 treatment strategies and placebo were included. Most studies were conducted for adults receiving 4 to 8 weeks of therapy. Vanzacaftor 10mg-Tezacaftor 100mg-Deutivacaftor 150mg combination therapy was superior to placebo (MD, 15.9; 95% CrI: 7.5-24.1; high certainty]) with SUCRA of 89.5% suggesting the highest probability of improving ppFEV1. Compared to placebo, Bamocaftor 400mg-Tezacaftor 100mg-Ivacaftor 150mg showed a significant reduction in sweat chloride (MD, -53.6-point reduction; 95% CrI: -64.8- -42.5; high certainty) and Vanzacaftor 20mg-Tezacaftor 100mg-Deuticaftor 150mg showed a significant improvement in CFQ-R score (MD, 27.9; 95% CrI: 15.9- 39.8; high certainty]. Safety analyses were limited by low event rates.

Conclusion
This NMA indicated that Bamocaftor-Tezacaftor-Ivacaftor and Vanzacaftor-Tezacaftor Deutivacaftor combination therapies were more effective for up to 4 to 8 weeks for treating adult patients with cystic fibrosis.

Introduction:
Osteoporosis is the most valued health issue in post-menopausal women. A new type of monoclonal antibody that binds and inhibits sclerostin, romosozumab, was approved by FDA. However, evidence about long-term utilization of romosozumab was limited in Asian population.
Aims:
This study aimed to analyze percentage change of bone marrow density (BMD) and prescription pattern of postmenopausal women receiving romosozumab.
Methods:
This was a retrospective observational study by using Chang Gung Research Database, which covers eight hospitals from different areas in Taiwan. Postmenopausal women with osteoporosis who received romosozumab for 12 months from November 2021 to March 2024 were included. The primary outcome was the percent change from baseline BMD of the spine and left hip. Paired-t test was applied to analyze the BMD change. Secondary outcomes were the prescribing pattern before and after using romosozumab. Baseline characteristics such as age, comorbidity, biochemical data, previous medication records and BMD were also collected.
Results:
A total of 397 patients were enrolled with the mean age of 75.6±9.6 and eGFR of 73.1±41.3. Baseline BMD of spine and left hip were 0.65±0.17 and 0.62±0.10, respectively. The percentage changes of BMD from baseline at the spine and left hip were both significantly increased (spine: 19.9%, 95% confidence interval [CI]: 10.0 – 29.9%; left hip: 2.5%, 95% CI: 0.1 – 5.1%). 33% of patients never use any medication before romosozumab and 30% of patients used denosumab as prior treatment. After receiving 12 months of romosozumab, 53% and 26% patients shifted their treatment to denosumab and bisphosphonate, respectively.
Discussion:
This study showed romosozumab was associated in increasing BMD at both spine and hip, and the percentage change from BMD baseline at spine was greater than hip. The results were also similar with previous pivotal trials and offered the effectiveness of real-world romosozumab utilization among Taiwanese patients.

Introduction: Osteoporosis is a significant cause and consequences of morbidity and mortality in the elderly and an important public health issue. Bisphosphonates are the primary treatment options for osteoporosis. The administration of bisphosphonates may show better treatment efficacy, but less is known about its impacts on health-related quality of life (HRQoL), and whether the anti-osteoporosis treatment can improve HRQoL of osteoporosis patient.
Aims: We have carried out a meta-analysis to evaluate the efficacy of Bisphosphonates treatment for osteoporosis and its impact on pain and HRQoL.
Methods: Randomized controlled trials with Bisphosphonates treatment for osteoporosis were retrieved from PubMed, EMBASE and clinicaltrials.gov. The risk ratio with 95% confidence interval (RR, 95% CI) was calculated to evaluate the effect of Bisphosphonates treatment on incidence of fracture. Data on changes in HRQoL following Bisphosphonates treatment was also extracted. SPSS software was used for all the statistical analyses.
Results: Effective anti-osteoporotic drugs could improve HRQoL. After receiving treatment, patients had a significant improvement in their health conditions. The mean increases in mental component scores were 2.43 (95% CI: 1.71–3.03) and 2.52 (95% CI: 1.75–3.07), respectively, with an increase of 4.48 (95% CI: 3.71–5.25) or 4.53 (95% CI: 3.74–5.19) in the physical component scores
Conclusion: Our meta-analysis showed that Bisphosphonates treatment is beneficial to improve HRQoL of osteoporosis.

Keywords: Bisphosphonates; Quality of Life; Osteoporosis.

Introduction: Effective pain management is crucial for improving the quality of life in cancer patients. Despite the availability of various analgesics, there is limited comprehensive data on their usage patterns, efficacy, and safety within the Indian population. This systematic review and meta-analysis aim to evaluate the utilization of analgesics among cancer patients in India, examining the types of analgesics used, their efficacy, and associated adverse effect.

Aim :
1) To assess the utilization patterns of analgesics in Indian cancer patients.
2) To evaluate the efficacy of different types of analgesics used in this population.
3)To analyze the prevalence and types of adverse effects associated with analgesic use in Indian cancer patients.

Methods: A systematic search is being conducted across multiple databases including PubMed, Scopus, and Cochrane Library, covering studies from January 2000 to December 2023. Inclusion criteria comprise studies reporting on the use of analgesics in cancer patients in India. Data are being extracted on study characteristics, patient demographics, types of analgesics used, efficacy outcomes, and adverse effects. Meta-analysis will be performed using random-effects models to synthesize the data.

Preliminary Results: Preliminary findings indicate that opioids are the most commonly used analgesics, followed by non-opioid analgesics and adjuvant analgesics. Early analysis suggests that opioids are highly effective in pain relief. Non-opioid analgesics show moderate efficacy, particularly in managing mild to moderate pain, while adjuvant analgesics appear effective in treating neuropathic pain. Common adverse effects noted include constipation, nausea, and sedation.

Conclusion: The ongoing systematic review aims to provide a comprehensive understanding of analgesic use in cancer patients in India. Preliminary results underscore the importance of opioid analgesics in pain management, although they are associated with significant adverse effects. The final results will inform better pain management strategies and highlight the need for improved palliative care services.

Introduction: The opioid crisis in the US has led to a significant increase in overdose incidents, necessitating effective emergency interventions. Naloxone, an opioid antagonist, is commonly administered in emergency departments (EDs) to counteract life-threatening overdoses. Understanding the characteristics and trends of naloxone use in these settings is crucial for improving response strategies and patient outcomes.

Aims: To determine the rate of naloxone use in EDs in the US.

Methods: This cross-sectional study used the National Hospital Ambulatory Medical Care Survey from 2017 to 2021. The data includes a national sample of visits to EDs in the US, focusing on visits where one or more naloxone orders were made for patients aged 15 and older. Sampling weights were applied to estimate national rates and 95% confidence intervals (95% CIs). The naloxone order rate, patient demographics, and the primary source of payment for the visit were examined.

Results: In 2017-2021, 0.5 per 100 ED visits included naloxone (95% CI 0.4 – 0.6 per 100). From 2017 to 2018, the rate decreased from 0.5 to 0.3, then increased to 0.6 and remained until 2021. Of all ED visits including naloxone, 55% were by male patients. Non-Hispanic White patients accounted for 63%, followed by non-Hispanic Black (19%), Hispanic (11%), and non-Hispanic other (7%). The average age was 45.4 years (42.5 – 48.3); however, those aged 25-34 comprised the largest proportion of naloxone use (25%). Medicaid (35%) and unknown (19%) were the most common sources of payment.

Conclusion: According to the CDC, drug overdose deaths increased by 30% from 2019 to 2020 and by 15% from 2020 to 2021. Our analysis indicates that naloxone use in EDs did not rise during this period, possibly due to the impact of COVID-19 measures. Naloxone use was more prevalent among relatively young adults and individuals with low incomes.

Introduction:
Morphine and Tapentadol are using for the management of cancer pain and the study was designed to determine the comparative effectiveness of the both drugs.

Aim:
To assess the effectiveness of Morphine and Tapentadol in patients with cancer pain in outpatient settings.

Methods:
A longitudinal observational study was carried out after institutional ethics committee’s approval. Patients, aged 18 years and above visiting outpatient department of palliative medicine of a tertiary care center in India and receiving oral Tapentadol 50mg or oral Morphine 10mg were recruited in the study. The severity of pain was assessed using the numerical rating scale (0-10). Categorical data in demographic parameters at baseline was analyzed by using ‘Z’ test for difference between two proportions. Continuous variables between the two treatment groups were analyzed by unpaired t-test.

Results:
A total of 390 patients participated in the study among whom, 161 patients received oral Tapentadol and 229 received oral Morphine. The mean age of the participants were 51.9 (±9.7) years in the Morphine group and 60.3 (±10.8) in the Tapentadol group. Morphine group consisted of 38% male whereas, Tapentadol included 22% male. The median duration of follow-up in days was 16 and 20 in Morphine and Tapentadol group respectively. Both the drugs were effective in reducing the intensity of pain during the end of follow-up with a mean difference of -0.68 [95% CI (-1.03, -0.32), p>0.001] in the Morphine group and -0.69 [95%CI (-1.10, -0.27), p>0.05] in Tapentadol group.

Discussion/Conclusion:
The study showed that Morphine was effective in cancer pain in routine clinical practice in outpatient patient department. Larger studies are needed for exploring the predictors and factors affecting pain.

Keywords: Pain, NRS, Tapentadol, Morphine, Outpatient

Background
The opioid use is restricted in children due to possible adverse drug reactions. Fentanyl is used in pediatric cancer for disease-related or therapy-related pain. During the drug administration, the child is kept under strict monitoring. The field of research is sparse, and the need to understand the ongoing research in the sector is important.

Aim
To identify the areas of research for Fentanyl use in pediatric oncology and the extent to which each area has been explored to date.

Methodology
A scoping review was performed using articles published till 31st December 2023. Keywords like “Fentanyl”, “Pediatrics”, and “Cancer” were used to identify the studies from PubMed, Embase, Scopus and Cochrane databases. A systematic two-step approach was used in the screening processes. Only research articles published in the English language were included. The extracted data from the studies included demographics, research country, aims and outcomes. The review followed the five-step methodological approach detailed by Arksey and O'Malley and the Joanna Briggs Institute updated methodological guidance.

Result
Of the 5701 articles screened, 24 (0.42%) articles were included. Cross-referencing further included one study. The major findings of the review were: 1) The research on Fentanyl use in pediatric oncology is limited. 2) The included publications were from 15 countries, of which the United States of America had the most (20%). 3) Intravenous/Intrathecal dosage forms (76%) were the most studied 4) Majority of the studies were themed on the efficacy (44%), safety (28%) and tolerability (12%) of Fentanyl in the population.

Discussion/Conclusion
The review highlighted the areas of research in pediatric oncology. Studies on areas like blood level estimation and genomic variability of the patients are needed to identify the possible relation between the variations of efficacy and safety profiles.

Keywords: Fentanyl; Pediatrics; Cancer; Scoping review.

Introduction: The growth in the number of medications available to consumers world-wide has increased medication use in children. Research conducted worldwide opined that children in general had a negative attitude towards medication. To date, there has been limited data on explored knowledge, attitudes and practices of school going children in India.
Aim: To assess the Knowledge, Attitude & Practice regarding the appropriate use of medication amongst the school going children.
Methodology: The study was a questionnaire based cross sectional observational study, carried out among the high school students in 3 urban & rural schools across Mysore. Students who met the study criteria were enrolled into the study after obtaining the informed consent. The questionnaires were administered and students were briefed about the purpose of the study before filling. Finally the collected questionnaires were evaluated to assess the KAP students.
Results: A total of 715 students were enrolled from three urban and three rural schools in our study. Higher KAP scores were observed in Females (74.4%) than Males (73.1%). In class-wise distribution, Class 8 shows higher KAP score (74.8%) than Class 9 (74.2%) and Class10 (72.1%). Urban schools show a better KAP score of 75.3% compared to rural schools (71.3%). Further assessment was performed to find out the influence of age, gender and geographical location of the school children on individual parameters of KAP.
Discussion: Geographical distribution of participants based on class and gender suggests that Class 9 was found to have maximum number of students (35%) compared to the other classes (31%, 34%). Gender-wise analysis of the data showed that female students enrolled in each school were comparatively lesser than males. children had a satisfactory knowledge about medicines and their use. Results are surprisingly good for the school curriculum which does not formally include education about rational use of medicines.

Introduction
The application of regenerative medicine (RM) to meet clinical needs is a highly sophisticated process requiring healthcare professionals (HCPs) to acquire specialized skillset. Currently, the evidence about HCP capacity building concerning RM and its effectiveness is still unfolding.

Aims
The study aimed to summarize the current practices of developing HCP capacity in RM and to identify the effectiveness of capacity-building actions.

Methods
Four databases (PubMed, ScienceDirect, Web of Science, Scopus) were searched following PRISMA guidelines to retrieve related articles dated since 2005 till now.

Results
Twenty-seven publications were included from the 3534 records initially retrieved. HCP capacity building in RM mainly occurred through formal undergraduate/graduate education (n=15) and continuing professional development training (n=16). The training content encompassed RM-related disease knowledge (n=7), therapies (n=14), manufacturing (n=10), laboratory skills (n=11), clinical translation (n=12), research ethics (n=10), regulatory affairs (n=17) and data science (n=5). The main training approaches were face-to-face, network events, and workshops. Nine of the 27 studies were empirical studies which either surveyed 1,308 HCPs such as physicians (n=670), laboratory staff (n=182), interdisciplinary students (n=150), industry professionals (n=149), academic fellows (n=90), physician trainees (n=71), clinical scientists (n=23), or interviewed 27 stem cell network trainees investigating the availability, equity, and accessibility of training and education. Only 2 studies reported the training effectiveness among medical students in terms of improved self-perceived knowledge of translational process and patient care, increased interest in attending education activities and willingness to work in interdisciplinary teams. No study reported the RM training outcomes among practicing HCPs. Capacity building was expected to focus more on cell science, manufacturing operation management, and regulatory issues.

Conclusion
RM education has been increasingly used to enhance HCPs' knowledge, confidence, and practice in developing and using RM, but the evidence about the impact of capacity-building on clinical practice among HCPs warrants further investigation.

Introduction:
Evidence has shown an increased risk of endometrial cancer associated with tamoxifen use in women with breast cancer, but data for premenopausal women are scarce.
Aims:
To investigate the association between Tamoxifen treatment and risk of developing uterine diseases in women with breast cancer aged 20 to 50 years.
Methods:
We conducted a retrospective cohort study using a target trial emulation framework. Women aged 20 to 50 years, diagnosed with estrogen receptor–positive breast cancer, and who had undergone mastectomy from 2010 to 2019, were identified using Taiwan’s National Health Insurance claims data linked to the cancer registry. Those with a history of hysterectomy, neoadjuvant therapy, and diagnosis of postmenopausal status and uterine diseases were excluded. Tamoxifen use was defined as receipt tamoxifen treatment only as adjuvant hormone treatment within one year after surgery. Inverse probability of treatment weighting controlled baseline confounding between the Tamoxifen treatment and non-treatment groups. Observational analogs of the intention-to-treat and per-protocol effects were estimated using pooled logistic regression models.
Results:
A total of 23,062 Tamoxifen users and 3,000 non-users were included. The mean age was 43.1 years (SD 5.2) and 42.4 years (SD 5.8), respectively. During the follow-up period, 3,888 users and 109 non-users developed uterine diseases, with 106 and 5 cases of endometrial cancer, respectively. In the intention to treat analysis, the estimated hazard ratio (95% confidence interval) was 4.15 (2.65-6.50) for endometrial polyps, 5.42 (4.09-7.18) for endometrial hyperplasia, and 2.41 (0.86-6.72) for endometrial cancer. Corresponding estimates in per-protocol analysis was 4.75 (2.55-8.86), 8.37 (5.24-13.35), and 4.20 (1.20-14.63), respectively.
Discussion:
Among women of premenopausal age with breast cancer in Taiwan, tamoxifen as adjuvant hormone therapy was associated with increased risk of uterine diseases including endometrial cancer. These findings highlight the importance of monitoring uterine diseases among tamoxifen users in this age.

Aim/Objective:To evaluate the possibility of artery dissection as a class effect of vascular endothelial growth factor pathway inhibitors (VPIs). Methods: We conducted a nationwide cohort study using the National Database of Health Insurance Claims of Japan (NDB), which covers over 100 million individuals. Patients prescribed any VPIs from April 1, 2012, to March 31, 2020, were included and patients without any medical records after the inclusion or patients prescribed same VPIs were excluded. The incidence rate (IR) of artery dissection in patients prescribed each VPI and the adjusted IR ratio (aIRR) compared to bevacizumab were examined. Results:In total, 503,342 patients were identified and the most prescribed VPI was bevacizumab (n=278,722) among 12 VPIs. The IR of artery dissection for bevacizumab, only VPI with artery dissection listed in the package insert in Japan, was 44.4 /100,000 person-years. The aIRR of artery dissection for each VPI compared to bevacizumab was consistently similar to or greater than 1.0. An additional analysis was conducted to compare the IR of each VPI with the natural IR of artery dissection in the general population from NDB. The natural IR was 1.66 /100,000 person-years in entire Japanese population, and the standardized IR (sex and age were standardized to the bevacizumab prescribed patient population) was 2.18 /100,000 person-years. Conclusion:Our findings indicated a possibility of a class effect of VPIs on the risk of artery dissection. The Pharmaceuticals and Medical Devices Agency conducted a safety assessment on the risk of artery dissection by VPIs based on this study as major evidence for review and other available data including adverse drug reaction reports, literature and pharmacological mechanism of action. The package inserts of all VPIs included in this study were revised on February 15, 2024 to add a precaution about the risk of artery dissection as "Clinically Significant Adverse Reactions".

Introduction: Rituximab biosimilar products (RTX-BS) have been introduced in Japan, but their safety in the real world has not been fully evaluated.
Aims: We compared incidences of adverse events (AE) by RTX-BS with RTX reference drug (RTX-R) using real-world data in Japan.
Methods: Using a medical information database (Medical Data Vision Co., Ltd.), a total of 46,726 patients with malignant lymphoma were selected who were RTX-naïve and treated with either RTX-R (n= 21,583), RTX-BS1 (n= 23,208) or RTX-BS2 (n= 1,938), without switching, during April 2014 to December 2023. Outcomes were defined as new records of AEs (infection, febrile neutropenia, heart and lung diseases, anaphylaxis) based on ICD-10, and leucopenia (grade 2 and higher) based on laboratory data which were available from 6,155 patients. Evaluation periods were up to 14 days after the first and the last RTX-treatment. Adjusted odds ratios (aOR) and 95% confidence intervals of each RTX-BS to the RTX-R were determined by multivariate logistic regression models using patient characteristics (age, sex, medical history, comorbidities, co-administered drugs, etc.) as covariates.
Results: Treatment durations of RTX were similar among three RTX-groups (median: 110 to 118 days). In the first RTX-treatment, slightly but significantly higher aORs (1.1 to 1.8) were observed for infection, febrile neutropenia, heart and lung diseases for RTX-BS1 and grade 4 leucopenia for RTX-BS2. Regarding the AEs in the last RTX-treatment, no significantly higher aORs were observed, except for anaphylaxis by RTX-BS1 in which significant association of history of anaphylaxis was identified.
Discussion/Conclusion: Although higher aOR of some AEs were observed in the first RTX-treatment, safety of RTX-BS seemed to be overall managed during RTX-treatment cycles to complete RTX-therapy as well as RTX-R. Consideration on risk factors identified in this study, such as history of AEs, would be important for safety management of either of RTX-therapy.

- Introduction
Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with aromatase inhibitors have become the first-line treatment for hormone-positive(HR+)/ human epidermal growth factor receptor 2-negative(HER2-) advanced breast cancer. However, high proportion of patients required dose modification due to adverse effects such as severe neutropenia in clinical trials. As a result, the relationship between the dose and effectiveness of CDK4/6i is an important issue.

- Aims
To compare the effectiveness between low relative dose intensity (RDI) and high RDI of CDK4/6i as first-line treatment for HR+/HER2- advanced breast cancer.

- Methods
We conducted a retrospective cohort study including HR+/HER2- advanced breast cancer patients who initiated CDK4/6i as first-line therapy from September 2016 to December 2022 at our hospital. Patients were categorized into two groups based on their first 12-week dose intensity: low-RDI group(≤0.8 for palbociclib or ≤0.667 for ribociclib and abemaciclib) or high-RDI group(>0.8 for palbociclib or >0.667 for ribociclib and abemaciclib). The outcome was progression-free survival (PFS), defined as the time from initiating CDK4/6i to disease progression or death. We used Kaplan–Meier method to estimated PFS and Cox regression model to analyze hazard ratio (HR) and 95% confidence interval (CI) between groups.

- Results
Total 607 patients were enrolled and all were females. The mean age was 58 years old and body surface area was 1.58m². 278(46%) patients received palbociclib, 264(43%) received ribociclib, and 65(11%) received abemaciclib. There were 227(37%) in low-RDI group and 380(63%) in high-RDI group. PFS was similar in both groups, with median of 18.5 months in low-RDI group and 22.3 months in high-RDI group, adjusted HR(95%CI): 1.04(0.84-1.28).

- Conclusion
Dose intensity of CDK4/6i in the first 12 week had no impact on PFS in HR+/HER2- advanced breast cancer. This finding provided an evidence that dose adjustment had no negative impact on effectiveness.

Introduction: While the importance of utilizing real-world data in epidemiological research is being emphasized, existing studies have rarely addressed the availability of real-world databases in the field of cancer.
Aims: To compare the latest operational availability of population-based cancer registries in the United States, Europe, and South Korea, providing foundational information for epidemiological research on cancer.
Methods: Criteria for selection included registries covering over 40% of the national population, operated by governmental institutions, and documenting more than two types of cancer. Consequently, the NPCR (National Program of Cancer Registries) and SEER (Surveillance, Epidemiology, and End Results), the ENCR (European Network of Cancer Registries) and the K-CURE (Korea-Clinical Data Utilization Network for Research Excellence) were identified. Each registry was reviewed based on topics discussed in prior study related to cancer registry design.
Results: Most registries were based on Electronic Medical Records (EMR), but the K-CURE distinctively integrates claims data. The NPCR focuses solely on cancer occurrence, whereas the others included information on cancer incidence, treatment, and prognosis. All registries, except for the recently established K-CURE, covered all cancer types. Each registry had an independent systematic quality assessment system. Access procedures were most straightforward for SEER, whereas others are more complex or restrictive. In terms of flexibility and timeliness, all registries were updated annually, maintaining consistency. Regarding terminology standardization, all of those registries utilize ICD-O-3, with K-CURE additionally using KCD.
Discussion: In conducting epidemiological research on cancer, it is crucial to consider the features, advantages, and limitations of these databases to select the most suitable registry based on the research objective and methods. This comparative analysis provides insights into the status of population-based cancer registries across various regions, laying the groundwork for advancements in cancer epidemiology research.

Introduction: Paliperidone, an antipsychotic used for schizophrenia and schizoaffective disorder, presents challenges in patients on multiple medications (polypharmacy). Real-world data on its use in this group is limited. This pharmacist-led study addresses this gap by investigating paliperidone utilization patterns in polypharmacy patients, aiming to optimize medication use and improve patient outcomes.
Aim: To investigate the utilization patterns of paliperidone and identify factors associated with polypharmacy among patients receiving paliperidone in a tertiary care hospital setting.
Methods: This was a pharmacist-led, retrospective study conducted in the department of psychiatry at a tertiary care hospital over 6 months. The data on utilization patterns of paliperidone was obtained using medical health records of psychiatric patients dispensed with paliperidone. Data on demographics, comorbidities, medications, and prescriptions of paliperidone were collected. Descriptive statistics were used to find the association between prescribing patterns and demographic characteristics.
Results: A total of 110 patients dispensed with paliperidone were observed in the study. Demographic characteristics used in the study were age, gender, and co-morbid conditions. Among 110 patients majority were male (70, 63.6%) and had a mean age of 25.6±4.6 years. Out of 110 patients, 45 (40.9%) patients were on polypharmacy with a higher prevalence of males (29, 64.4%). Among 45 patients dispensed with paliperidone were associated with the following co-morbid conditions 14 depression (31.1%), 31 bipolar disorder (68.8%), and 17 generalized anxiety disorder (37.7%) conditions.
Discussion: These findings underscore the importance of further research on paliperidone use in a population with schizophrenia. The high prevalence of polypharmacy and the dominance of bipolar disorder as a comorbidity necessitate further investigation to refine treatment strategies and improve patient outcomes in the population.
Keywords: Paliperidone, Patterns, Patients, Polypharmacy

Introduction:
Most individuals with increased cardiovascular (CVD) risk require concurrent treatment with multiple medications, which may lead to polypharmacy.

Aim:
This study aimed to identify CVD risk factors associated with CVD-related polypharmacy and to investigate the association between CVD-related polypharmacy and the presence of liver and kidney dysfunction among patients receiving lipid-lowering therapy within the Australian primary care setting.

Methods:
Electronic medical records for adults prescribed lipid lowering therapy between January 2013 and December 2022 were utilised. A multi-logistic regression adjusted for risk factors (age, sex, smoking, diabetes, hyperlipidaemia, hypertension and chronic kidney disease (CKD)) was used to identify factors associated with CVD-related polypharmacy and with liver and kidney dysfunction. Liver dysfunction was defined as exceeding established reference ranges for alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin levels, while kidney dysfunction was defined based on the estimated glomerular filtration rate (eGFR) as per the Australian guidelines.

Results:
Of 13,568 study participants (median age: 63 years, 54% males), 33.73% had CVD-related polypharmacy. Risk factors associated with CVD-related polypharmacy included diabetes (Odd ratio (OR)=5.40, 95% CI: 4.96-5.93), CKD (OR=2.39, 95% CI: 2.00-2.86) and hypertension (OR=1.91, 95% CI: 1.75-2.07). Compared to the 18-35 age group, individuals aged ≥80 years demonstrated a significantly higher association of CVD-related polypharmacy (OR=8.17, 95% CI: 5.47-12.21). CVD-related polypharmacy was not significantly associated with liver dysfunction (OR=1.19, 95% CI: 0.59-2.37) but was significantly associated with kidney dysfunction (OR=1.45, 95% CI: 1.30-1.62).

Conclusion:
Findings indicate a potentially heightened risk of polypharmacy which may lead to medication-related complications and adversely affect renal function. Comprehensive medication management and multidisciplinary-care are essential for the prevention of potential polypharmacy-related harm.

Introduction: Previous studies have shown that polypharmacy may influence the composition of the gut microbiota. However, the potential impact of drug interactions with the oral microbiome remains uncertain.
Aims: The aim of this study was to investigate the potential association between polypharmacy and the oral microbiome.
Methods: Participants who were 55-79 years old and took at least one prescription medication from the National Health and Nutrition Examination (2009-2010, 2011-2012) were included in the cross-sectional study. The concurrent use of 5 or more medications was defined as polypharmacy. Alpha diversity (within-sample richness and phylogenetic diversity) was measured with metrics including observed OTUs, Faith’s Phylogenetic Diversity, the Shannon-Weiner index, and the Simpson index. Beta diversity (heterogeneous dispersion of oral microbiome community) was measured between all pairs of samples with metrics including unweighted UniFrac, weighted UniFrac, and Bray-Curtis dissimilarity. Weighted multivariable linear regression, principal coordinate analyses (PCoA) and multivariate analysis of variance (PERMANOVA) were employed to examine the association between polypharmacy and oral microbiome composition.
Results: Of 1,658 participants assessed, 562 were taking 5 or more medications (weighted percentage, 29.5%). After adjustment for covariates, multivariable linear regression revealed a significant negative correlation between polypharmacy and alpha diversity. The weighted β-coefficient and 95% confidence interval of polypharmacy were -8. 342(-12.487, -4.197), 0.566(-0.944, -0.189), and -0.126(-0.221, -0.030) for observed OTUs, Faith’s Phylogenetic Diversity, and the Shannon-Weiner index, respectively. PCoA analysis showed a significant differentiation of oral microbiome community based on the prevalence of polypharmacy as measured by Bray-Curtis dissimilarity (R2=0.299%, P<.001), unweighted UniFrac distance (R2=0.247%, P<.001), and weighted UniFrac distance (R2=0.215%, P<.001).
Conclusion: In the middle-aged and older Americans adults, polypharmacy is associated with both oral microbiome alpha diversity and beta diversity. Further longitudinal studies are required to substantiate the impact of polypharmacy on the dynamics of the oral microbiome.

Introduction:
Japan population is aging at the highest rate in the world. Elderly patients often have multiple comorbidities, leading to polypharmacy. Polypharmacy seems to be associated with various problems such as increased risk of adverse events, decreased adherence, and cognitive impairment.
Aims
This study aimed to analyze the correlation between polypharmacy and dementia using National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) Open Data in 2020.
Methods
The NDB, Japan’s national health insurance claims database, covers most reimbursement claims. In this study, aggregate data by gender, age, or prefecture of NDB and data from the patient survey by the Ministry of Health, Labour and Welfare were used. Polypharmacy was defined as the number of prescriptions for seven or more medications per prescription in the NDB open data. Dementia was defined as the estimated number of patients with “vascular and unspecified dementia” and “Alzheimer’s disease” in the patient survey. We conducted a correlation analysis between polypharmacy and the number of patients with dementia adjusted for gender and age. Additionally, we stratified the analysis by the median prescription amount of lifestyle-related disease (hypertension, dyslipidemia, and diabetes) medications.
Results
Polypharmacy was significantly associated with a higher prevalence of inpatients with dementia (r = 0.644; p < 0.001). There was no correlation between polypharmacy and outpatients with dementia (r = -0.010; p = 0.947). A positive correlation between polypharmacy and inpatients with dementia was shown in each region stratified by lifestyle-related disease medications (r = 0.646; p < 0.001, r = 0.711; p < 0.001 for high and low prescription regions, respectively).
Discussion/Conclusion
A positive correlation was found between polypharmacy and inpatients with dementia, suggesting polypharmacy is associated with the risk of developing more severe dementia. Appropriate intervention is required for medication therapy in the elderly.

Introduction: Trastuzumab deruxtecan (T-DXd) has emerged as a promising therapy for breast cancer, yet data on its utilization among Chinese patients remain limited.

Aims: This study aimed to investigate the real-world treatment patterns of T-DXd among Chinese breast cancer patients, particularly focusing on treatment duration and dosing considerations.

Methods: A retrospective observational study was conducted among 2055 Chinese female breast cancer patients who received T-DXd treatment between 2023 and 2024. Patient demographics, treatment duration, tumor staging, medication patterns, and dosing details were analyzed.

Results: The age distribution showed a mean age of 54.8 years (SD 10.8), with a median of 55 years (IQR 47-61), and the majority of patients (71.1%) were aged between 41 and 64 years. The mean treatment duration of 5.4 cycles (SD 2.3) and a median of 4.0 cycles (IQR 4.0-8.0). Notably, 70.2% of patients received only 4 cycles, while 24.9% received 8 cycles, 4.7% received 12 cycles, and 0.1% received 16 cycles. The mean number of doses per cycle was 2.7 (SD 0.6), with a median of 3.0 doses (IQR 2.0-3.0). The majority of patients received 3 doses per cycle (59.0%), followed by 2 doses (33.7%), 4 doses (5.8%), and 1 dose (1.3%). The mean interval between medication refills was 85.1 days (SD 27.8), with a median of 86 days (IQR 67-102). Additionally, the mean dose per cycle was 4.9 mg/kg (SD 0.9), with a median of 5.0 mg/kg (IQR 4.3-5.5). Factors influencing dosage and treatment interval included age at diagnosis, cancer stage, body weight and geographic regions.

Discussion: These findings highlight suboptimal dosing of T-DXd among Chinese breast cancer patients, potentially influenced by lower-than-average patient weight and dosing practices. Understanding the factors contributing to these deviations from recommended treatment regimens is crucial for optimizing therapeutic outcomes in this population.

Introduction: The Status Epilepticus in Pediatric patients Severity Score (STEPSS) has been utilized to assess treatment outcomes in children with status epilepticus (SE).
Aims: This study aims to investigate the diagnostic value of STEPSS in predicting the survival outcomes in SE patients.
Methods: A comprehensive meta-analysis was conducted to address this objective. Pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), area under the curve (AUC), Relative Risk (RR) and corresponding 95% confidence intervals (95% CI) were calculated. Subgroup analysis, meta-regression analysis and the Deek’s plot were used to evaluate heterogeneity.
Results: Eight articles, comprising 918 SE patients, conformed to the inclusion criteria. The literature exhibited non-threshold effect-caused heterogeneity. Pooled sensitivity and specificity, calculated by a random-effects model, were 0.82 (95% CI: 0.71,0.90, Q = 0.12, I2 = 23.21) and 0.78 (95% CI: 0.70,0.85, Q = 60.71, I2 = 88.47), respectively. The DOR was 18 (95% CI: 8,43), and the Summary Receiver Operating Characteristic Area Under the Curve (SROC-AUC) was 0.85. The pooled result of RR showed that the accuracy of using STEPSS for SE diagnosis was 10.74 times higher than without using it (RR = 10.74, 95% CI: 6.12,18.86, I2 = 35.6). Subgroup and meta-regression analysis pinpointed geographical location (specifically, China) as a potential heterogeneity source. Deek’s funnel plot did not reveal any obvious asymmetry. Discussion: Our evidence suggests moderate support for the efficiency of STEPSS in diagnosing the condition in pediatric patients with SE.

Introduction
Multiple medicine use is common in Australia but little is known about its extent in people with cancer. There are concerns for people with colorectal cancer (CRC) as they receive treatment from multiple specialists, increasing risks of medication errors and inappropriate prescribing.
Aims
To estimate the prevalence of multiple medicine use amongst adults (>18 years) with CRC and detail how medicine use evolves from the year preceding diagnosis, through active cancer treatment, and into the post-treatment survivorship period.
Methods
We used dispensing claims for residents of New South Wales diagnosed with CRC between 2013 and 2017. We used group-based trajectory modelling to explore changes in the quarterly number and type of medicines used during the year preceding and five years following CRC diagnosis. We stratified our cohort by extent of cancer spread at diagnosis (local, regional, or metastatic disease).
Results
There were 7,088, 8,632, and 3,826 people diagnosed with localised, regional, and metastatic CRC, respectively, during the study period. The proportions of people dispensed five or more medicines during each year around diagnosis ranged between 35% and 65%, peaking near 75% during the first year following diagnosis for each sub-cohort. Medicine use trajectories were similarly stable for localised and regional CRC sub-cohorts, averaging 0–10 unique medicines dispensed/quarter over the study period. Metastatic patients showed more variation across six trajectory groups with half stable, averaging 2–8 medicines dispensed/quarter, and half declining as patients discontinued medicines prior to death.
Discussion
Multiple medicine use is common and more prevalent in CRC patients than in the general Australian population . Patients in all disease sub-cohorts experienced an increase in the number of dispensed medicines during the year following diagnosis, reflecting initiation of cancer therapies, however, medicine use trajectories were otherwise largely stable over the study period.

Introduction: In head and neck cancer (HNC), docetaxel, cisplatin, & 5-fluorouracil (TPF) is widely accepted regimen in neoadjuvant settings. However, administration of this regimen is resource-consuming, and not feasible for many patients with low socioeconomic status. Oral metronomic chemotherapy (OMCT), typically utilized in palliative setup, when combined with a paclitaxel-carboplatin regimen provides synergistic effects owing to the continuous exposure of cytotoxic drugs to the tumor environment.
Aim: To compare the efficacy of P+C+OMCT vs. TPF as neoadjuvant chemotherapy (NACT) in patients with locally advanced HNCs.
Methods: This prospective, observational study included 46 patients undergoing NACT. The patients were assessed for efficacy after a minimum of 2 cycles of chemotherapy using RECIST 1.1 criteria.
Results: Out of 46 included patients, 25 and 21 patients received TPF and P+C+OMCT, respectively. Overall response rate (ORR) was 52% for TPF and 57.14% for P+C+OMCT (p=0.727). 2 patients in the TPF arm had complete response (CR). Disease control rate (DCR) was 92% and 95.23% for TPF and P+C+OMCT, respectively (p=0.652). In the post-NACT surgical evaluation, the tumors of 16 (64%) patients in TPF and 11 (52.38%) patients in the P+C+OMCT arm were found to be resectable (p=0.425).
Discussion: Compared to the TPF regimen, P+C+OMCT demonstrated comparable, if not superior efficacy in terms of response rates and resectability in locally advanced HNCs. Hence, P+C+OMCT might provide a promising alternative to the TPF regimen in patients for whom administration of TPF is not an option.

Introduction: The antibody-drug conjugate (ADC) acts as a "magic bullet" in cancer treatment, combining monoclonal antibodies' targeting ability with a cytotoxic payload. Trastuzumab deruxtecan, comprising trastuzumab and deruxtecan, is approved for advanced HER2-positive or HER2-low breast cancer, HER2-positive gastric cancer, lung cancer, and solid tumors, and became available in Taiwan in 2022.

Aims: To provide clarity on its utilization, we conducted an evaluation of the application of trastuzumab deruxtecan in a regional hospital.

Methods: We retrospectively collected data on patients who received treatment with trastuzumab deruxtecan at the regional hospital from 2022 to April 2024. We then analyzed various parameters, including cancer type, stage, treatment course, dosage, side effects, and subsequent treatment plans.

Results: In the study, twelve patients participated, with one having HER2-positive lung cancer and the remaining having HER2-positive breast cancer. Their mean age was 58.3±8.3 years, and all had an Eastern Cooperative Oncology Group (ECOG) score of 0-1. On average, patients received 6.8±5.7 treatment courses, with an average dosage strength of 62.3±19.2% compared to the recommended 5.4mg/kg dose. Most side effects were grade 1, including liver enzyme elevation, anemia, alopecia, fatigue, diarrhea, increased serum creatinine, and hypokalemia. However, some experienced grade 2 side effects such as neutropenia (8%), anemia (25%), and diarrhea (8%), necessitating treatment delay or dose reduction. There were no reported cases of interstitial lung disease. All patients continued treatment until disease progression or expiration, except for one who declined further treatment due to financial constraints.

Discussion: Our review indicates that physicians frequently favored lower-dose treatment, potentially due to financial constraints or concerns regarding toxicity. Nonetheless, our findings demonstrate that the treatment's efficacy was satisfactory, with no discontinuations attributable to toxicity. Although most side effects were mild, grade 2 neutropenia, anemia, and diarrhea warrant careful consideration.