Introduction:
Patients with end-stage chronic kidney disease (CKD) require frequent dialysis treatments to sustain their lives, imposing a substantial healthcare burden on them and their families.

Aims:
To investigate the healthcare burden of dialysis-dependent (DD) and non-dialysis dependent (NDD) CKD patients with anemia in China.

Methods:
We utilized national cohort data from Tianjin Inspur Healthcare Big Data. Patients with renal anemia aged over 18 who visited any hospital in Tianjin from January 2018 to June 2023 were included. The total population was divided into two subgroups based on dialysis status: 1) non-dialysis dependent (NDD) group; and 2) dialysis-dependent (DD) group. Average patient costs for inpatient, outpatient, and emergency care, as well as per person per month (PPPM) costs, were assessed.

Results:
A total of 130,863 incident CKD patients were identified, with 123,463 in the NDD group and 20,544 in the DD group. NDD patients with renal anemia had 334,902 hospitalizations, incurring costs in 332,840 cases. The mean hospitalization cost was approximately RMB 20,097.8, with an adjusted mean of RMB 20,598.2. The total follow-up duration was 682,783 months, resulting in a PPPM hospitalization cost of approximately RMB 13,860.5, and an adjusted PPPM of RMB 14,205.7. In contrast, DD patients with renal anemia experienced 31,764 hospitalizations, incurring costs in 31,682 cases. The mean hospitalization cost was RMB 19,959.6, with an adjusted mean of RMB 20,276.5. The total follow-up duration was 445,669.4 months, with a PPPM hospitalization cost of approximately RMB 13,369.9, and an adjusted PPPM of RMB 13,582.2.

Discussion:
The study results indicate that the economic burden of renal anemia is higher in dialysis-dependent patients compared to non-dialysis dependent patients.

Introduction. This study aims to evaluate the risk of PDA-ligation from combining furosemide with NSAIDs, focusing on NSAIDs' renal side effects in PDA infants, often requiring diuretics to manage decreased urine output.
Methods. Data were sourced from the National Health Insurance Research Database provided by the Health and Welfare Data Science Center of the Ministry of Health and Welfare of Taiwan. The study population included infants under one year old diagnosed with PDA between January 1, 2008, and December 31, 2017, identified based on hospitalization diagnoses within one month after birth.
The population was divided into exposed and control groups based on furosemide use: the exposed group received at least one oral or intravenous furosemide within one month of birth and combination treatment with Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). The control group consisted of infants treated solely with NSAIDs for PDA. The date of birth served as the index date, used to track PDA diagnosis and surgery. Infants were monitored from one month post-birth to one year to determine if they underwent PDA-ligation.
Propensity score matching was employed in a 1:1 ratio to address potential confounding factors such as weight, gestational age, degree of prematurity, and other diuretic agents. Multivariable logistic regression analysis was performed to evaluate the association between combined furosemide use and the risk of PDA-ligation.
Results. We identified 1,153 infants with PDA, 718 (62.3%) in the exposure group. Among these, 292 underwent PDA-ligation, including 269 from the exposure group. Combined furosemide and NSAIDs treatment significantly increased the risk of PDA-ligation (aOR = 3.45, 95% CI = 1.93-6.15). Survival analysis was not applied because the hospitalization records did not consistently specify the exact dates of surgery.
Discussion. This study found that combining furosemide and NSAIDs for PDA treatment in Taiwanese infants increased the likelihood of requiring PDA-ligation. Therefore, it is recommended to avoid combining furosemide with NSAIDs during PDA treatment unless necessary to minimize the risk of PDA treatment failure.

Introduction
Infertility, a growing global health concern, causes enormous stresses and substantially affects the quality of life (QoL) for women and their partners. However, evidence regarding the association between psychological stresses and QoL in women undergoing fertility treatments is scare.

Aim
This study assessed the optimal QoL threshold for classifying infertile women experiencing anxiety/depression.

Methods
Study data were collected from 11 hospitals with different accreditation levels in Taiwan during February-July, 2023. Patients’ QoL and anxiety/depression were assessed using FertiQoL and PHQ-4, respectively, and repeatedly over fertility treatments. Machine learning (i.e., decision tree [DT] model) and biostatistical (i.e., generalized linear model [GLM]) models were employed to assess the association between the QoL and anxiety/depression of women. Model performance was evaluated using the Youden index (ranging 0 to 1, with higher values indicating better performance).

Results
There were 320 individuals with a total of 444 repeated measurements obtained for analysis. The DT model which considered all FertiQoL sub-items, medical institution types, gender and infertility treatment stages indicated an optimal FertiQoL score threshold of 63.60, with the Youden index of 0.48. The average PHQ-4 scores for individuals with FertiQoL scores< and ≥63.60 were 4.04 (± 2.08) and 1.75 (± 1.59), respectively. Also, the GLM which adjusted individual clinical characteristics selected via stepwise regression analyses determined the optimal FertiQoL threshold score of 69.85, with the Youden index of 0.45. The average PHQ-4 scores for individuals with FertiQoL scores< and ≥69.85 were 3.62 (± 2.10) and 1.55 (± 1.56), respectively.

Conclusion
Both the DT and GLM models yield comparable performance in identifying an optimal QoL score threshold, as supported by similar Youden index scores. Given its operational simplicity and autonomous data adaptation, the ML-based DT model is preferred for determining the best QoL threshold to facilitate timely psychological support and thereby enhance infertility treatment outcomes.

Introduction: Chronic Kidney Disease (CKD) is a growing global disease burden leading to a range of systemic complications. Considering the altered pharmacokinetics in CKD patients, the standard antibiotic dosing regimen is often inadequate or unsafe in treating infections.

Aim: To assess appropriateness of antibiotic dosing in chronic kidney disease patients.

Methods: A prospective observational study was carried out after the approval of institutional ethics committee. CKD patients with age ≥18 years prescribed with antimicrobials were included in the study. Creatinine clearance or eGFR was calculated using Modification of Diet in Renal Disease (MDRD) equation. The main outcome measured was antimicrobial dosing appropriateness based on Stanford Antimicrobial Dosing guidelines.

Results: The study was carried out in 101 patients admitted to nephrology department. There was a male preponderance with 64.4 %. Hypertension was the predominant co-morbidity observed. 83% patients belonged to stage 5 CKD. The most commonly prescribed intravenous antibiotic was Cefoperazone/Sulbactam (83.2%) 1.5g BD. The gram-negative pathogens were prevalent in study site with epidemiological data supporting the antibiotic. This was followed by Meropenam (10.5%) 500mg OD and Ceftriaxone (4.2%) 750mg BD. Antimicrobial dose of 88.6% prescriptions were appropriate. Eighty-two percent of the patients converted to oral antibiotics, primarily Cefixime (61.4%) 200 mg BD.

Discussion: The hurdle of calculating creatinine clearance based on a single equation is a reality. The assessment of dose appropriateness using MDRD equation and Stanford antimicrobial dosing guidelines have shown that majority prescriptions are appropriate. Knowledge gap exists in the need of an equation with ease of calculation and reliability to address wide population variabilities.

Keywords: CKD, MDRD, Antibiotics, Appropriateness

Introduction: Whether dynamic hemoglobin changes over time affect various clinical outcomes of patients with chronic kidney disease (CKD) is uncertain, despite substantial evidence showing undesirable consequences following greater hemoglobin variability.

Aims: To assess distinct hemoglobin trajectories and associated clinical outcomes for non-dialysis-dependent CKD Stage 5 and dialysis-dependent patients.

Methods: Patients having at least two records of eGFR≤15 ml/min/1.73m2 with an interval between two consecutive records within three to six months during 2013-2014 were identified from the linked Chang-Gung Research Database and National Health Insurance Research Database. Group-based trajectory modelling was utilized to determine distinct hemoglobin trajectories over three years, with a 6-month and 1-month interval of hemoglobin measurements analyzed for non-dialysis-dependent CKD Stage 5 and dialysis-dependent patients, respectively. Clinical outcomes included kidney events (i.e., dialysis and kidney transplantation) and death.

Results: Several hemoglobin trajectory groups were identified, namely "persistently moderate anemia” (Group 1), “mild-to-moderate anemia” (Group 2), “mild anemia with slight decline” (Group 3), “persistent non-anemia” (Group 4) among CKD Stage 5 patients, and "persistently moderate anemia” (Group 1), “persistently mild anemia” (Group 2), “mild-to-normal anemia” (Group 3), “persistent non-anemia” (Group 4) among dialysis-dependent CKD patients. In CKD Stage 5 patients, compared to Group 4 cases, the adjusted subdistribution hazard ratios (aSDHRs) (95%CIs) of Groups 1, 2, and 3 on kidney events/death were 2.3 (1.2-4.4)/12.7 (1.2-136.5), 2.3 (1.3-3.9)/6.8 (0.7-68.4), and 2.5 (1.4-4.4)/8.6 (0.8-91.4), respectively; for dialysis-dependent patients, compared to Group 4 cases, the aSDHRs (95% CIs) of Groups 1, 2 and 3 on death were 1.5 (1.0-2.1), 1.2 (0.8-1.6), and 1.0 (0.7-1.3), respectively. Sensitivity analyses with time-varying adjustment of eGFR had consistent findings with main analyses.

Discussion: Late-stage CKD patients maintaining moderate anemia might be at risk of increased mortality, irrespective of dialysis status, and CKD stage 5 patients with slightly declining hemoglobin were potentially progression to kidney dialysis/transplantation.

Introduction: Oral anti-hypertensives are acceptable first-line agents for treating Hypertensive disorders of pregnancy (HDP) in outpatient settings. However, the maternal and neonatal safety of these drugs remains unclear.
Aim: To identify the safety signals of oral anti-hypertensive medications used in pregnancy related to neonatal and maternal adverse events
Methods: We carried out a retrospective case/non-case study using spontaneous reports in the FDA Adverse Event Reporting System (FAERS) from the date of approval by the FDA to 30th December 2023. The study employed a disproportionality analysis, calculating the Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR), and Information Component (IC) to identify safety signals related to neonatal and maternal safety adverse events (if PRR ≥ 2, Lower Bound (LB) ROR > 1, and IC025 > 0) for anti-hypertensive drugs during the pregnancy. We also performed a signal refinement analysis by eliminating the confounding co-prescribed medications to identify the robustness of the findings.
Results: Using disproportionality analysis, 46 neonatal safety (Labetalol=27, Nifedipine=18, Amlodipine=1, Methyldopa=8, and hydralazine=2) signals of considerable strength such as neonatal respiratory distress syndrome and neonatal respiratory failure signals were observed for labetalol [PRR=27.4 (χ2=849.7), (LB)ROR=19.6, IC025=3.8; PRR=15.5 (χ2=40.3), LB ROR=5.0, IC025=0.3], and nifedipine [PRR=14.9 (χ2=802.8), LB ROR=11.6, IC025 =3.3; PRR=10.4 (χ2=58.2), (LB)ROR=4.9, IC025=1.4]. Neonatal Intraventricular hemorrhage identified for methyldopa and amlodipine [PRR=10.4 (χ2=34.0), (LB)ROR=3.9, IC025=0.6; PRR=3.8 (χ2=160.9), (LB)ROR=3.0, IC025=1.5]. Signals of considerable strength in maternal adverse events such as postpartum hemorrhage, pre-eclampsia signals were observed for labetalol [PRR=22.3 (χ2=160.3), (LB)ROR=11.1, IC025=2.1; PRR=91.4 (χ2=10179.8), (LB)ROR=77.2, IC025 =5.7], and nifedipine [PRR=4.7 (χ2=17.5), (LB)ROR=2.1, IC025=0.5; PRR=21.0 (χ2=1791.2); (LB)ROR=17.2, IC025 = 3.9].
Conclusion: Our analysis uncovers notable safety signals for both neonatal and maternal outcomes associated with oral anti-hypertensive medications during pregnancy, which emphasize the imperative for cautious prescription and close monitoring for adverse outcomes in hypertensive pregnant women.

Introduction
Cancer drugs, including antineoplastic and supportive agents, play an important role in the treatment and supportive care of cancer, especially childhood cancer. However, the population-based cancer drug use pattern of childhood cancer patients in China was unknown.
Aims
To characterize the utilization of cancer drugs among Chinese childhood cancer patients.
Methods
This cross-sectional analysis uses claim data from Chinese Basic Medical Insurance from 2015 to 2017. We identified childhood patients aged 0-19 years with malignant neoplasms. The primary outcome was the prevalence of cancer drug use, which were classified as antineoplastic agents, cancer supportive agents, and traditional Chinese medicines for cancer. The secondary outcomes were average annual direct medical and out-of-pocket costs.
Results
Among 262,287 cancer beneficiaries contained in the database, 766 childhood cancer inpatients were identified. The prevalence of cancer drug use of all sample patients was 70.6%, and 71.9% for children with hematological malignancy. Patients in economically developed areas with the lowest share of out-of-pocket expenditure (48.5%) had the highest cancer drug use (82.3%). In comparison, only 49.2% of children in the deprived area had ever used cancer drugs. Older children had a significantly higher prevalence of traditional Chinese medicines prescription than patients in the 0-4 years group (all p<0.01).
Discussion
Our study showed that the use of cancer drugs differed among economic groups and cancer types in mainland China. More progress in reimbursement, research and development, and approval of effective medication should be made to remove economic inequity and improve the accessibility of effective pediatric cancer treatment.

Introduction: The high incidence of drug-resistant tuberculosis (TB) in Indonesia presents a significant public health challenge, exacerbating the difficulty in controlling and eradicating the disease. Multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) cases are rising, necessitating more complex and prolonged treatment regimens, which often come with severe side effects. Consequently, rigorous monitoring of adverse drug reactions in TB patients is crucial to ensure treatment efficacy and patient safety.

Aim: This study was conducted to assess adverse drug reactions and their management in drug-resistant TB patients.

Methods: This was a retrospective descriptive study, using data of drug-resistant TB patients who completed therapy from January 1st, 2021 to December 31st, 2023 at the Tuberculosis Outpatient unit at the PKU Gombong Hospital, Central Java, Indonesia. Data were collected from patients’ medical records.

Results: There were 84 patients included in this study, 96% of them were identified having adverse drug reactions. The five most prevalent adverse effects found in this study were gastrointestinal disorders ( 39.02%) followed by musculoskeletal disorders (22.83%), neurotoxicity (11.27%), ototoxicity (6.07%), and blood disorder (5.78%). The strategies employed to manage adverse drug reactions involved incorporating symptomatic medications and/or modifying the treatment regimen

Conclusions: Due to the limited sample size, we cannot draw a definitive conclusion. However, the findings of this study are crucial as they provide valuable insights into the adverse effects experienced by drug-resistant TB patients in Indonesia.

Keywords: Adverse drug reactions; management; pharmacovigilance; resistant tuberculosis.

Introduction: Bone Marrow Transplant (BMT) and hemat-oncology units are specialized medical facilities treating patients with complex conditions, often requiring intensive pharmacological interventions. Understanding and comparing adverse drug reactions (ADRs) in these settings is crucial for optimizing patient care and safety.
Aims: To compare the adverse drug reactions experienced by patients treated in BMT and hemat-oncology setting.
Methods: A prospective comparative analysis of ADRs reported in BMT and hematology unit over a nine-month period was estimated. Data were collected from electronic health records, focusing on ADR incidence, severity, implicated medications, and patient demographics. The causality of the reported ADR’s was classified based on Naranjo’s algorithm.
Results: A total of 234 ADRs were identified, with 167 (71%) occurring in the BMT unit and 67 (29%) in the hemat-oncology unit. The most frequently reported ADRs in both units were Vomiting (21%) and Febrile neutropenia (16%), although the distribution varied slightly between units. Severe ADRs requiring medical intervention were more prevalent in the BMT unit, whereas moderate ADRs were more common in the hemat-oncology unit. Analysis of implicated medications revealed high dose chemotherapy agents such as Fludarabine, ATG showed higher number of severe adverse drug reactions (72%), whereas corticosteroids (15%) and anti-fungals (13%) also exhibited moderately severe adverse reactions. Probable ADRs (56%) were more prevalent in the BMT setting, likely due to the intensive therapeutic regimens and compromised immune status of patients. Conversely, possible ADRs (58%) appeared to be more common in the hemat-oncology unit.
Discussion: This comparative analysis provides insights into the differences in ADR profiles between BMT and hemat-oncology units. Understanding these variations can aid in developing targeted strategies for ADR prevention, management, and pharmacovigilance in each setting, ultimately improving patient safety. Further research is warranted to explore underlying factors contributing to these differences and mitigate ADR incidences in both units.

Introduction:

Lymphoma chemotherapy patients frequently experience neutropenia, leading to high mortality rates and increased healthcare costs. The CSCO guidelines recommend PEG-rhG-CSF for preventing febrile neutropenia (FN) due to its efficacy, safety, and improved compliance compared to rhG-CSF, which is used for primary prevention of FN and covered by medical insurance. PEG-rhG-CSF, on the other hand, is used only for secondary prevention.
Aims:

To assess the effectiveness and safety of PEG-rhG-CSF versus rhG-CSF in preventing neutropenia in lymphoma patients undergoing chemotherapy. Additionally, this study aims to examine differences in patient adherence and healthcare costs between the two treatments.
Methods:

Data were retrospectively collected from the Hospital Health Information System (HIS) and the Jiangsu Province Population Health Big Data Platform. The cohort included lymphoma patients who received chemotherapy between January 1, 2019, and December 31, 2023, and who were first-time users of either PEG-rhG-CSF or rhG-CSF for preventive purposes. Basic patient information such as age and tumor stage was recorded.
Results:

This study is in the data screening stage, with established inclusion and exclusion criteria. Preliminary screening identified 74,925 cases of lymphoma patients based on hospitalization and outpatient records.
Discussion:

This research utilizes extensive datasets to compare the impacts of long-acting (PEG-rhG-CSF) versus short-acting (rhG-CSF) medications on the management and mitigation of FN. It evaluates the potential of PEG-rhG-CSF as a primary preventative strategy, providing data-driven insights to inform health policy and clinical practice. Additionally, the study aims to enhance therapeutic options for lymphoma patients, thereby reducing their financial burden.

Aims: To explore the disease characteristics, treatment choices, and clinical outcomes in Chinese Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) patients following discontinuation of BTK inhibitor therapy.

Methods: This is a multicenter, retrospective, observational database study. We extracted CLL/SLL data from the electronic medical records of three Grade-A Tertiary hospitals located in Northern China between July 1, 2017, and December 31, 2021.

Results: Among the 37 eligible patients who discontinued BTKi, the mean age at the time of BTKi discontinuation was 62.67 ± 10.11 years, with the majority being male (25/37, 67.57%). The median duration from BTKi discontinuation to the last visit was 6.44 months (interquartile range [IQR] 2.04–15.67). Most patients (23/37, 62.16%) were relapsed/refractory (R/R) CLL/SLL patients, with the remaining being treatment-naïve (14/37, 37.84%). Treatment- naïve patients were significantly younger than R/R patients (56.93 ± 10.94 years versus 66.16 ± 8.16 years, p=0.005). The reasons for discontinuation included resistance (18/37, 48.65%), intolerance (12/37, 32.43%), and other factors (7/37, 18.92%). The most frequently used regimen among the first therapy after BTKi discontinuation was rituximab (R)-based (9/17, 52.90%). The disease control rate upon discontinuation of BTKi was 78.13% for all patients. The median progression-free survival (PFS) for BTKi therapy was 19.09 months (IQR 8.97–not reached [NR]), 19.09 months (IQR 15.58–NR) for treatment-naïve patients, and 14.39 months (IQR 5.88–NR) for R/R patients. The minimum median PFS (7.86 months, IQR 5.88–31.28) was observed in patients with resistance. Following discontinuation of BTKi, patients exhibited shorter PFS durations, with median PFS for the first and second treatments post-BTKi cessation at 8.87 (IQR 6.15–NR) and 5.32 (IQR 4.21–NR) months, respectively. No significant difference was observed in overall survival.

Conclusion: Our study shows inferior clinical outcomes for R/R patients who underwent BTKi discontinuation, especially in cases of resistance to BTKi.

Keywords: CLL/SLL; BTKi; Discontinuation; Multicenter Study

Introduction. The Japanese clinical guideline for appropriate use of granulocyte colony-stimulating factor (G-CSF) does not state strongly that the use G-CSF for primary prevention of febrile neutropenia (FN) in patients with diffuse large B-cell lymphoma (DLBCL) receiving R-CHOP therapy due to little evidence. The actual use of G-CSF in clinical practice has not been revealed in detail.
Aims. To clarify the actual use of G-CSF and to compare the characteristics of patients with/without G-CSF, by using real-world data.
Methods. We used the Japanese Medical Data Vision (MDV) database (data period: April 2008 to June 2021). The study population was hospitalized patients receiving R-CHOP therapy for newly diagnosed DLBCL. We observed annual trends in the proportion of the study population receiving G-CSF. We also conducted a nested case-control study in the study population, with G-CSF users as case and non-users as control, to compare the characteristics of them.
Results. A total of 9,941 were extracted for the study population, with 7,335 case and 2,606 control. During the data period, the proportion of G-CSF users tended to increase (38.5% in 2008 to 72.7% in 2021). Compared with control, case showed characteristics such as an older age, lower initial dose intensity of R-CHOP therapy, frailty, lower BMI (Body Mass Index), more advanced stage cancer, concurrent comorbidities, a history of various medical treatments, and a history of FN.
Discussion. The use of G-CSF has recently increased to be established as a concomitant drug for R-CHOP therapy. Based on the comparison results, overall, G-CSF users were more likely to be frail. This suggests that the criteria for G-CSF administration in clinical practice consider such as patient’s age, severity of illness, and medical history, and is to some extent in compliance with the guideline, which weakly recommends administration to elderly patients or patients with comorbidities.

Introduction: Immune checkpoint inhibitors (ICI) have advanced the treatment of non-small cell lung cancer (NSCLC). However, concerns about ICI-related cardiac adverse events have arisen. Previous studies have focused on Caucasian populations, leaving a gap in understanding the cardiotoxicity associated with ICIs, particularly in Asian populations.
Aims: This study aims to epidemiologically describe the cardiac adverse events in NSCLC patients receiving ICIs in an Asian cohort, hypothesizing variations in cardiac injuries across different ICI types and treatment regimens.
Methods: The study cohort included adult patients with NSCLC at participating hospitals between 2015 and 2023. Stratification occurred into four cohorts: patients receiving chemotherapy, ICI (involving Pembrolizumab, Nivolumab, Camrelizumab, Sintilimab, Tislelizumab, Toripalimab, Serplulimab) with chemotherapy, ICI without chemotherapy, and a control group receiving no NSCLC-directed therapy. The primary endpoint was myocarditis, ascertained through patients' medical records. The secondary endpoints were abnormality in any cardiac biomarkers, including creatine kinase, creatine kinase isoenzyme, troponin I, or troponin T, or the conjoint elevation of creatine kinase, lactate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase.
Results: Among 28,626 NSCLC patients, 102 underwent chemotherapy, 6,707 received ICI (3,334 with chemotherapy, 3,373 without), and 21,817 were unmanaged. The incidence of myocarditis was 8 (0.03%), with 0.07 per 100 person-years. Abnormality in any cardiac biomarker occurred in 622 (2.2%) patients, exhibiting respective incidence rates of 10.70, 9.61, 5.25, 14.10, and 4.21 per 100 person-years across subgroups. Conjoint elevation occurred in 188 (0.7%) patients, exhibiting respective incidence rates of 5.36, 3.21, 2.59, 3.86, and 1.18 per 100 person-years across subgroups. In ICI group, patients receiving Pembrolizumab or Camrelizumab had a higher risk of cardiac injury compared to patients receiving other ICIs.
Discussion: NSCLC patients who received chemotherapy or ICI without chemotherapy had a higher risk of cardiac injury. There was significant heterogeneity in cardiac injury among NSCLC patients in different treatment groups.

Introduction:
Osteonecrosis of the jaw (ONJ), atypical femur fractures (AFF), and hypocalcemia are adverse events (AEs) of interest for all bone antiresorptive therapies. Most trial and post-marketing safety data are from non-Asian populations. Denosumab (120 mg) is indicated in Taiwan for the prevention of skeletal-related events (SRE) in patients with bone metastases from solid tumors, multiple myeloma, hypercalcemia of malignancy, and giant cell tumor of the bone.

Aims:
Using the Taiwan National Health Insurance database, we sought to describe the incidence rate of AEs among patients receiving denosumab for SRE prevention within an ethnic Chinese population.

Methods:
The study included patients with breast, prostate, or lung cancer, who initiated denosumab inclusive of 2013 through 2019. As the data source did not require bone metastasis to be uniformly recorded, patients were excluded having a diagnosis suggestive of other indicated uses for denosumab. Follow-up started at patient’s initial denosumab administration and continued through the earliest date of 91 days after the last administration, switching, or end of study. AEs were defined by algorithms adapted from the literature and local clinical opinion (e.g. hospitalized hypocalcemia events defined as a primary diagnosis of hypocalcemia at hospitalization or emergency room visit). The cumulative incidence (first event) and 95%CI were calculated.

Results:
Patients (n = 18029, 58% women, mean age 64y) initiating denosumab were followed for a mean of 9.7 months. The two-year cumulative incidence of ONJ and number of patients with an event were 2.03% (1.72% - 2.40%), 140; AFF, 0.03% (0.01% - 0.10%), 5; and hospitalized hypocalcemia, 0.31% (0.21% - 0.46%), 25.

Conclusion:
Among patients initiating denosumab for the prevention of SRE, the observed incidence of AEs in ethnic Chinese was consistent with the incidence of AEs in clinical practice reported for global populations.

Introduction
Chimeric Antigen Receptor (CAR) T- cell immunotherapies are approved for treatment of refractory or relapsing large B-cell lymphoma, Multiple Myeloma and patients with B-cell Acute Lymphoblastic Leukemia.

Objectives
To evaluate the potential risk of secondary malignancies related to T-cells including T-cell lymphoma and leukemia, with CAR T-cell medicines: Ciltacabtagene Autoleucel (CARVYKTI®), Tisagenlecleucel (KYMRIAH®) and Axicabtagene Ciloleucel (YESCARTA®).

Methods
A systematic literature search was conducted from inception until January 2024, using PubMed, Google scholar, Cochrane library and Adis Insight database. In addition, searching the local adverse drug reactions database and World Health Organization (WHO) database was performed via signal detection tool (Vigilyze) using the terms “CARVYKTI®” OR “KYMRIAH® ” OR “YESCARTA®” (substance (WHO Drug) [AND] " T-cell lymphoma" OR “T-cell leukemia” (preferred term (PT) (MedDRA). Then, the causality assessment was performed using the WHO-Uppsala Monitoring Center causality system.

Result
We found one case report of patient developed CAR T-Cell Lymphoma post CARVYKTI® therapy for relapsed refractory multiple myeloma. In addition, a phase I clinical trial was reported 2 cases of T-cell malignancies associated with use of CD19 CAR therapy. The search of WHO global database resulted in 12 cases as follows: T- cell lymphoma [(KYMRIAH® (n=5), YESCARTA® (n= 4), CARVYKTI® (n=2)], one case reported T- cell leukemia with YESCARTA®. Of them, 7 (58.3%) cases were females, 4(33.3%) males. All cases were serious, most of them (60%) reported death outcome. Based on the WHO causality assessment, 2(16.6%) cases were probably associated with medications use. However, the majority of cases (n=10, 83.3%) considered un-assessable due to lack of information such as time of onset, de challenge/ re-challenge data.

Conclusion
The Available evidence suggests a potential association between secondary malignancies of T cell origin with the use of CAR T cell immunotherapies. Further epidemiological studies are needed to assess this potential association.

Introduction: Traveling or going on vacation might cause dialysis patients to miss their dialysis schedules, adversely affecting their health. Hence, facilities must help dialysis patients access information regarding dialysis centers in other locations.
Aim: To understand the challenges faced by dialysis patients regarding travel and accessibility to dialysis centers, and to identify their needs for travel, including vacations, family functions, and business meetings.
Methods: We conducted a cross-sectional questionnaire survey in which all patients on dialysis who met our inclusion criteria were enrolled. The required data was collected using a self-developed questionnaire. Frequency was used for categorical variables, and mean ± standard deviation or median and interquartile range (IQR) were used to calculate continuous variables. The chi-square test was used to assess patients' willingness to utilize holiday hemodialysis facilities based on their age and duration of dialysis treatment.
Results: Most patients (80.95%) had abstained entirely from traveling since the initiation of hemodialysis for multiple reasons. Among the remaining patients who went on vacation, the maximum duration and frequency were three days and 2-3 times a year. This was due to a lack of proper facilities to undergo dialysis at the travel destination. None of the patients in our center knew about holiday hemodialysis facilities; however, when informed, many were willing to utilize them. Their willingness was dependent on their age group as well as the duration of their dialysis treatment.
Discussion/Conclusion: Holiday hemodialysis facilities should be developed and promoted in India to provide affordable and safe travel experiences for people undergoing hemodialysis.

INTRODUCTION: In October 2018, sevelamer, a non-calcium-based phosphate binder, was included on the subsidy list for patients with chronic kidney disease who are intolerant of calcium-based phosphate binders, or have persistent hyperphosphataemia despite optimising treatment with calcium-based phosphate binders.

AIMS: This study compared real-world outcomes between calcium-based and non-calcium-based phosphate binders and assessed the impact of the subsidy decision on the healthcare system in Singapore.

METHODS: Using linked national health record databases, this retrospective cohort study included patients with end-stage renal failure initiated on calcium-based or non-calcium-based phosphate binders from October 2016 to September 2020. Patient demographics, comorbidities, baseline laboratory values and concomitant drugs were balanced using propensity score matching. Cox regression estimated the hazard ratios (HR) with 95% confidence interval (CIs) for cardiovascular (CV) events and other secondary outcomes. Additionally, a Markov model was constructed to extrapolate the number of events avoided and potential cost savings from the use of non-calcium-based phosphate binders.

RESULTS: After propensity score matching, 804 comparable patients remained in each cohort. Over 80% of patients were initiated on the phosphate binder as treatment add-on or switch. Patients on non-calcium-based phosphate binders were less likely to develop a CV event (HR: 0.82; 95% CI 0.67–0.99) over a median follow-up period of 1.5 years. Subsidy listing of sevelamer led to increased utilisation, reduced drug costs from value-based pricing and potentially resulted in 383 fewer CV hospitalisations, translating to about $26 million saved over 10 years.

DISCUSSION/CONCLUSION: While most real-world studies include only new patients without prior use of other phosphate binders, most patients in our matched cohorts received the phosphate binder as second-line therapy, which aligned with the subsidy criteria and local clinical practice for non-calcium-based phosphate binders. In summary, subsidy listing of sevelamer had a significant positive impact on patient outcomes and the healthcare system.

Introduction: Nocturnal polyuria (NP) is one of the three main types of nocturia. NP is a kidney-driven urine production disease, which characterized by overproduction of urine at night. The standard treatment for NP is a neuropeptide similar to endogenous vasopressin, desmopressin. Yet, the prevalence of NP and its current treatment pattern in Taiwan is understudied.
Aims: 1) to update the prevalence of NP in Taiwan 2) to identify desmopressin prescription patterns in NP patients
Methods: We use the 2016-2020 claims data from Taiwan’s National Health Insurance Research Database for this study. For Aim 1, we had three definitions of NP: 1) diagnosed NP (ICD-10 codes: R35.81), 2) diagnosed nocturia but not coded urinary retention or overactive bladder, or 3) diagnosed nocturia and prescribed desmopressin or alpha-1 blockers at bedtime. In addition, we performed a subgroup analysis for the prevalence of NP in patients with LUTS. For Aim2, we identified the desmopressin usage pattern in NP patients based on the first and second definitions in Aim1. We documented the interval between the diagnosis of NP and desmopressin prescription, prescription continuity, and other combination therapies (anticholinergics, TCA, and alpha blockers) for NP.
Results. In Aim 1, we did not identify any patients having a diagnosis code of NP. With the second and third definitions of NP, the overall prevalence increased from 0.42% in 2016 to 0.58% in 2020. The prevalence in patients with LUTS increased from 11.30% to 13.57%. Regarding treatment patterns, the median interval between the NP diagnosis date and desmopressin prescription is 0 days, with an IQR that spanned from 0 to 14 days. Notably, 68.44% of NP patients received a prescription for desmopressin on the same day as their NP diagnosis. Additionally, 5.78% of NP patients continuously used desmopressin over three months. Eighty-three percent of NP patients who used desmopressin combined it with at least one other therapy for NP.
Discussion. Our results showed a low prevalence of NP in Taiwan. The low prevalence may be caused by the under-coded of NP and under-diagnose of NP. Most of the NP patients were treated with desmopressin right after diagnosed, and mostly in combination with other therapies.

Introduction:
Diabetic Kidney Disease (DKD) is kidney damage that occurs as a result of long-term diabetes. It is one of the complications of diabetes mellitus and a major cause of renal failure in diabetic patients. Despite its diverse clinical course, there are limited examples using real-world data in Japan to describe the patient journey of DKD treatment.

Aims:
This study aimed to illustrate the treatment course of DKD. As a secondary objective, we examine if revisions in clinical guidelines are observable through Patient Journey using real-world data.

Methods:
In the RWD database, 356,478 Type 2 diabetes patients were identified. Based on glomerular filtration rate (GFR) categories, 7,621 with stage G3b (G3b group) and 6,510 with stage G4 (G4 group) were captured. Changes in prescriptions of hypoglycemic agent, antihypertensive agent, and nephroprotective medications before and after recording stage G3b or stage G4 were observed for both groups.

Results:
Focusing on the top 10 drugs administered in cases, hypoglycemic agent, antihypertensive agent, and nephroprotective medications, and cardiovascular disease medications were identified.
An increasing trend in hypertension medication was noted in both groups (G3b and G4) post-stage progression (G3b: 48% to 65%, G4: 57% to 76%), with a notable increase in furosemide, a loop diuretic.
Similarly, prescription for diabetes medications showed an upward trend (G3b: 38% to 51% G4: 42% to 57%), with a slight decrease in metformin usage in G4, where it's contraindicated.
Additionally, there was an increase in nephroprotective medication treatment in both stages.

Discussion:
These findings indicate that the patient journey in DKD treatment reflects changes in medication prescriptions consistent with clinical guidelines.
Future research will dive into prescription trends surrounding guideline revisions and their clinical implications, exploring the application of machine learning to better understand DKD treatment realities.

Aim/Objective: Compare the sensitivity and specificity of serum procalcitonin (PCT) and C-reactive protein (CRP) levels, for the diagnosis of acute kidney injury in sepsis patients.
Methods: A retrospective case-control study was conducted in Kasturba Medical College, Manipal, Karnataka at the Department of Nephrology. The study population included critically ill patients suffering from septicaemia. The cases patients were diagnosed with sepsis and AKI as per KDIGO guidelines. Whereas the control encompassed septicaemic patients who did not develop AKI. An equal number of cases and control were selected. Important clinical and laboratory variables, medical history, were collected along with PCT, CRP and serum creatinine (Sr.Cr) levels from both cases and control. A comparison of the sensitivity and specificity of PCT, CRP and Sr.Cr was done using MedCalc statistical software.
Results: Most of the patients in the case group were between the age group of 61-70 years with a percentage of 24% (n=56) compared to 23.3% (n=52) of the patients in the control group who were between 51-60 years of age. There were noticeably more males than females, with males accounting for 78.5% (n=183) in the case group and 63.5% (n=148) in the control group. Sensitivity, specificity and AUC of ROC (with 95% confidence interval) of PCT, CRP and Sr.Cr were 59.66%, 54.08%, 0.59, 46.78%, 62.23%, 0.59, 80.26%, 66.09% and 0.83 respectively.
Conclusion: Among the biomarkers compared serum creatine found to be more sensitive and specific for the diagnosis of acute kidney injury among septicaemic patients.

Introduction: Influenza has emerged as the leading cause of death worldwide; however, there have been few studies on influenza mortality rates that take into account the COVID-19 epidemic pandemic.

Aims: To examine long-term international influenza mortality trends from 2001 to 2022.

Methods: Fourteen countries were included in the study. We analyzed the influenza mortality rates in 2001–2022 using the vital death registration data from the WHO Mortality Database. Long-term trends were assessed for the 14 countries by 2022: Armenia, Australia, Canada, Estonia, Georgia, Hungary, Iceland, Lithuania, Luxembourg, Mauritius, the Netherlands, Serbia, Singapore, and Sweden. Deaths due to influenza were considered if the International Classification of Diseases 9 and 10 codes for influenza (ICD-9: 487, ICD-10: J10, and J11) were listed as the underlying cause of death.

Results: In 2018, Estonia, the Netherlands, Canada, and Sweden had peak age-adjusted mortality rates (AR) for influenza, whereas Australia, Georgia, Serbia, and Lithuania had peak AR in 2019. The highest AR in 2018 and 2019 were 1.56 and 1.85 in Sweden and Australia, respectively.
In all 14 countries, the AR for influenza significantly declined through 2021, but the AR for influenza increased in all countries in 2022. Moreover, a similar trend was observed in the older individuals aged ≥65 years.

Discussion: Influenza mortality rates decreased from 2019–2021 in all 14 countries and showed an increasing from 2021–2022. The decrease in global influenza mortality rates by 2021 may be caused by that many countries have adopted measures to prevent COVID-19 infection.

Introduction: Glucocorticoid-induced leucine zipper (GILZ) represents a novel anti-inflammatory molecule with potential implications for the development of novel therapeutic strategies targeting inflammatory conditions, including sepsis. However, the effect of epidemiologic factors, notably comorbidity, on GILZ remains unclear.

Aims: This study aimed to describe the GILZ protein concentration in sepsis patients with different comorbidities.

Methods: We conducted enzyme-linked immunosorbent assay (ELISA) techniques to measure the GILZ protein concentration of sepsis patients in the intensive care unit (ICU). Furthermore, we cross-sectionally compared the GILZ protein concentration between sepsis patients with single or multiple comorbidities and those without comorbidities.

Results: We conducted a study involving 36 sepsis patients, comprising an equal number of 18 females and 18 males, with an average age of 59.61 ± 14.85 years (see Table 1). The study included 11 (30.55%) patients without comorbidities, 10 (27.78%) patients with multiple comorbidities, 6 (16.67%) patients with chronic kidney disease, 5 (13.89%) patients with acute kidney injury, 2 (5.56%) patients with type 2 diabetes mellitus, and 2 (5.56%) patients with hypertension. The ELISA findings (refer to Figure 1) indicated that there were no significant differences in the GILZ protein concentration among sepsis patients without comorbidities (0.112 ± 0.035 ng/ml) compared to those with multiple comorbidities (0.109 ± 0.029 ng/ml, p=0.944), chronic kidney disease (0.119 ± 0.036 ng/ml, p=0.920), acute kidney injury (0.095 ± 0.014 ng/ml, p=0.193), type 2 diabetes mellitus (0.087 ± 0.008 ng/ml, p=0.114), and hypertension (0.097 ± 0.017 ng/ml, p=0.430).

Conclusion: Our study findings indicate no significant differences in the GILZ protein concentration between sepsis patients without comorbidities and those with different comorbidities. Nonetheless, further research involving larger populations and more advanced techniques is necessary to gain a deeper understanding of this potential novel anti-inflammatory molecule.

Keywords: anti-inflammatory agents, comorbidity, epidemiologic factors, multimorbidity, sepsis syndrome, systemic inflammatory response syndrome

Introduction: Antimicrobial Resistance (AMR) is a global health threat caused by the widespread use of antimicrobials, which leads to microbes developing defense mechanisms against them. AMR emphasizes the need to implement a One Health approach to tackle AMR nationally and international. Action plans from drug regulatory agencies to tackle AMR have been implemented to minimize its spread, maintain the effectiveness of available antimicrobials, and support the development of new antimicrobials.

Aim: This study aims to review and improve the currently implemented national legislations to tackle AMR based on national data of antimicrobial use among food-producing animals and in alignment with international drug regulatory agencies in order to minimize global AMR spread.

Method: This is a literature review study of international drug regulatory agencies action plan to tackle AMR, taking into consideration, the national data of antimicrobial use among food-producing animals.

Result: The results showed that some antimicrobials classified as highly important with limited or no alternatives to treat serious infections in human are still being used in food- producing animals locally.

Discussion: To address the control use of antimicrobials, the study proposes a new classification system for veterinary antimicrobials as prohibited, restricted, and accessible. These classifications were based on the national data on antimicrobial use in food-producing animals and international categorization of antimicrobial importance for human and animal health.

Conclusion: Establishing a one health approach is needed to limit the spread of antimicrobials resistance among humans and animals. National and international actions need to be taken into consideration to maintain the effectiveness of currently available antimicrobials and develop new antimicrobials to tackle the antimicrobial resistance problem.

Aim/Objective: Rotavirus (RV) is the most common cause of severe diarrhea in infants and children globally. ROTATEQ® demonstrated high overall and serotype-specific efficacy against RV gastroenteritis (RVGE) in clinical trials worldwide and has been approved in China in 2018. The study objective was to assess the effectiveness of ROTATEQ® in children treated in hospitals for RVGE due to at least one of the RV serotypes G2/G3/G4 and G1/G2/G3/G4/G9 respectively in China.
Methods and results: Test-negative case-control design. A primary data collection study was conducted to prospectively identify serotype-specific RVGE Cases and RV negative acute gastroenteritis (AGE) Controls. Case Group 1 included RV G2/G3/G4 cases while Case Group 2 included RV G1/G2/G3/G4/G9 cases.
Children, age-eligible to be fully vaccinated with 3 doses of ROTATEQ® and receiving treatment for AGE were enrolled from 35 hospitals across China. Data from AGE cases admitted to the inpatient ward or from AGE cases who received continuous intravenous rehydration treatment for ≥2 days in an outpatient setting were collected from October 2020 to April 2023.
Stool samples were tested by enzyme-linked immunosorbent assay(ELISA) for group A RV antigen and ELISA-positive samples were genotyped(VP7) by multiplex RT-PCR.
Multivariate logistic regression models were fitted to obtain odds ratio for comparing the likelihood of ROTATEQ® vaccination among case and control groups.
The results will be presented during the conference.
Conclusion: This is the first post-marketing commitment effectiveness study of ROTATEQ® in mainland China. The analysis confirmed the high protection of ROTATEQ® against RVGE due to G2/G3/G4 and G1/G2/G3/G4/G9 among Chinese children in a real-world setting.

Introduction:
Community pharmacy staff play a significant role in dispensing antibiotics and can significantly influence public practices and attitudes towards antibiotic use. Understanding the knowledge and practices of pharmacy staff regarding antibiotic use and AMR is essential to identify gaps, improve training, and develop targeted interventions.
Objective: To explore the knowledge and practice of community pharmacy staff towards antibiotic dispensing and AMR.
Methods: A convenience sampling method was used to recruit 22 participants (pharmacists and non-pharmacists) at community pharmacies after obtaining written consent. A validated semi-structured questionnaire was developed to gather respondents' demographics, antibiotic dispensing practices, and knowledge of AMR. The data was coded and classified for thematic analysis.
Results: A total of 22 participants were included, predominantly male (91%) with a mean age of 37 ± 0.7 years. Out of 22 participants, 10 (45.5%) were pharmacists and 12 (54.5%) were non pharmacist dispensing staff. The four major themes that emerged were knowledge of AMR, dispensing patterns, patient behavior, and the training needs on AMR. The study findings reveal lack of AMR awareness among non-pharmacists and dispensing of antibiotics without a prescription was common among both pharmacist’s and non-pharmacist. All 22 participants acknowledged that they dispense more of Watch category antibiotics as classified by World Health Organization (WHO) AWaRe classification. Dispensing of fixed-dose combinations of antibiotics that are widely available were also highlighted by the study participants. Additionally, the participants identified challenges in patient- related factors, non-adherence, inability to buy a full course of antibiotics due to cost, and lack of trust towards pharmacists’ advice.
Conclusion: As the primary antibiotic gatekeepers, community pharmacy staff are key stakeholders in the reduction of AMR in India. The study findings reinforce the importance of developing and instituting an antibiotic training programme for community pharmacy staff and need for antimicrobial stewardship activities in India.

Introduction: Antibiotic deprescribing can improve patient outcomes, reduce side effects, and maximize cost-effectiveness; it is especially important in areas where antibiotic misuse is common.
Aims: To assess the perceptions of antibiotic deprescribing among physicians and to determine the various factors that influence the deprescribing of antibiotics.
Methods: A cross-sectional survey study was conducted among 71 physicians in a tertiary care hospital after obtaining institutional ethical approval. A questionnaire containing 20 items was developed and validated. The final Scale-level Content Validity Index universal agreement (S-CVI UA) average score was 1, indicating a satisfactory level of content validity. Fisher’s exact test is used to determine the association between the background characteristics of physicians and perceptions of antibiotic deprescribing and related factors.
Results: Only 69% of participating physicians know antibiotic deprescribing, despite the majority (98.6%) recognizing antibiotic overuse. Time restraints (25.4%), ignorance (74.6%), side effect worries (42.3%), and patient/family reluctance (19.7%) are among the challenges. Deprescribing can be aided by facilitators such as departmental attention (54.9%), pharmacist involvement (268.8%), and recommendations (83.1%). 71.8 percent of doctors are willing to participate in deprescribing programs, indicating that they are receptive to maximizing the use of antibiotics.
Conclusion: The study assessed the physicians' perception of deprescribing of antibiotics. There are still gaps in confidence and expertise in antibiotic deprescribing. Focused teaching and assistance programs could improve deprescribing procedures, guaranteeing the prudent use of antibiotics in medical care.
Keywords: Deprescribing, antibiotics, perception

Background
Antibiotic resistance has evolved into a formidable challenge, with microorganisms now demonstrating resistance to multiple drugs, presenting significant challenges to the medical profession. It is crucial to understand the prevalence and patterns of these resistant bacteria for prompt decision-making in clinical settings.
Aim: The aim of the study is to determine the prevalence of antibiotic resistance patterns by analyzing clinical specimens collected from a tertiary care hospital in a South Indian community.
Methodology: A cross-sectional study was conducted retrospectively using the microbiology laboratory registration book to understand the patterns and prevalence of antimicrobial and multi-drug resistance in a tertiary care hospital. Data on isolated organisms and sensitivity reports from the years 2020 to 2023 were compiled and compared to assess trends over time.
Results: The study analyzed 693 bacterial isolates, with 62.8% gram-negative and 37.2% gram-positive. Most isolates were from children under 5 (48.2%) and males (1.13:1 ratio). Urine samples had the most isolates (36.2%), followed by pus (27.4%) and blood (18.9%). Staphylococcus aureus was most prevalent among GPB (22.5%), while Klebsiella spp. dominated GNB (22.2%). GPB showed resistance to cotrimoxazole, penicillin G, norfloxacin, and ceftazidime. Enterobacteriaceae resisted ampicillin (92.5%), cotrimoxazole (85%), and tetracycline (85%). Non-Enterobacteriaceae resisted tetracycline (100%), cotrimoxazole (93.1%), and ampicillin (92.9%). Multi-drug resistance (MDR) was high (75.5%), with Klebsiella spp. showing the highest MDR (87.7%), followed by Enterococcus spp. (83.9%), Acinetobacter spp. (83.3%), and Enterobacter spp. (83.3%). S. aureus had the lowest MDR (57.7%), along with S. pneumoniae, Proteus spp., Salmonella spp., Shigella spp., and N. gonorrhoea (57.1%-66.7%).
Conclusion: This study underscores the high prevalence of antibiotic resistance among bacterial isolates in the South Indian community. Effective management requires antibiotic selection based on susceptibility reports.

Objectives: To determine the effect of artemether-lumefantrine on plasma levels of four liver enzymes, namely; alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [ALP], and gamma-glutamyl transpeptidase [GGT] in children with uncomplicated Plasmodium falciparum infection.
Methods: We reviewed the records of all children who participated in a clinical trial of antimalarial drugs in Ibadan, Nigeria. A sample of 102 children with microscopically-proven Plasmodium falciparum infection; who met eligibility criteria were treated with 6-dose artemether-lumefantrine at recommended age-specific doses for 3 days. Study participants were followed up on days 0 to 3, 7, 14, 21, and 28 according to the World Health Organization recommendation for treatment of malaria therapeutic efficacy studies. Inclusion criteria included symptoms compatible with acute uncomplicated malaria, including parasite density of at least 1000/µL and absence of chronic illness or danger signs of severe malaria. The results of ALT (U/L),AST (U/L),ALP (U/L)and GGT (U/L) at baseline (day 0),on day 3, and on day 28 post-treatments were extracted and compared using Friedman tests.
Results: The median age of participants was 25 months (range = 3 to 119), and 49% were male. The mean values of ALT and AST did not change significantly throughout the 28-day follow-up from baseline (25.8 – 19.1U/L p= 0.0984 and 50.4 – 52.2U/L p= 0.1943 respectively). GGT decreased substantially between baseline 17.0 U/L (11.0 - 22.5) andday 28 15.0U/L (10.5-21.5) p= 0.0010 while ALP increased over time (baseline: 305.0U/L (216.0 – 403.5); day 28: 345.0 U/L (241.0 – 492.5) p=0.0303. Elevated ALT, AST, ALP, and GGT were observed in 8.5%, 20.0%, 20.9%, and 14.8% of participants,respectively.
Conclusions: Considerable rise in plasma levels occurred in ALP which could be indicative of liver injury occurring during antimalarial treatment among Nigerian children. Further research is needed to identify the underlying mechanism responsible for this possible drug-induced liver toxicity.

Background: Tuberculosis (TB) is a bacterial infection. It mostly affects the lungs (pulmonary TB), but it can also affect other organs. This cross-sectional study evaluated knowledge, attitudes, and practices (KAP) related to TB among King Khalid University (KKU) students between October and November 2023.

Objective: The objective of this study was to investigate current TB knowledge, attitudes, and practices of students at King Khalid University in Abha, Saudi Arabia.

Methods: A self-administered, cross-sectional, descriptive, web-based questionnaire was conducted from October to December 2023 among the students of King Khalid University. We used a 29-item questionnaire with five sections. Section 1 contained five questions about sociodemographic factors, there were 13 knowledge questions in Section 2, Section 3 contained 7 attitude questions, Section 4 contained 3 practice questions, and Section 5 contained 1 source of information question. A chi-squared test was used to assess differences in participants’ knowledge, attitude, and practices in relation to their demographic variables (p < 0.05).

Results: A total of 518 students completed the questionnaire. 53.66% were healthcare students and 46.33% non-healthcare students. The mean scores for healthcare and non-healthcare students, respectively, were as follows: knowledge 11.80 ± 4.81, 7.35 ± 4.96; attitude 6.94 ± 1.33, 5.05 ± 2.09; and practice 2.26 ± 0.85, 1.14 ± 0.87. The results of this study showed good knowledge (24.82 and 5.83% for healthcare and non-healthcare students, respectively) good attitude (67.62 and 46.25%) and good practice (45.32 and 9.58%). A total of 24.32% healthcare students and 28.18% non-healthcare students reported that most effective sources for obtaining information about TB were social networks, the internet and the radio.

Conclusion: The current study concludes that the knowledge, attitude, and practice about TB among healthcare faculty students is better than their non-healthcare counterparts.

Introduction
Hepatitis C virus (HCV) replication and infection depend on host lipid metabolism. Since the HCV lifecycle requires lipoprotein particles, direct-acting antivirals (DAA) raise total cholesterol (TC) after sustained viral response (SVR).
Aims
This systematic review and network meta-analysis of cohort studies examines how DAA medicines affect TC metabolism results as TC evaluations lack length and DAA treatment follow-up.
Methods
Using Boolean operators and search phrases, we conducted a thorough literature search from PubMed, Cochrane Library, EMBASE, and MEDLINE-OVID electronic databases from inception to October 31, 2023. The search was not restricted to years of publication or language-specific literature and publications that were found using cohort study filtering. Using the Newcastle-Ottawa Scale (NOS) and random-effects models analysis using the MetaInsight v5.2.1 website, the quality of the included research has been evaluated.
Results
Out of the 4896 patients who were a part of the nine studies that comprised this assessment, four treatments were appropriate to include in our analysis: multiple DAAs (M), sofosbuvir-base (SOF), paritaprevir/ritonavir/ombitasvir (PTVr/OBV), and daclatasvir/asunaprevir (DCV/ASV).
Compared to baseline individuals, those on DCV/ASV regimens had a TC mean (MD) increase of 22.42 (95% confidence interval, CI: 9.47 to 34.25) at the post-end of treatment 4 (P4) week and a TC MD increase of 25.33 (12.74 to 37.25) at the P12 weeks.
TC increases at M-end of treatment and M-P24 weeks were 15.02 (8.91 to 22.6) and 20.57 (13.78 to 27.74) compared to baseline MD. Additionally, the SOF shows no statistically significant modifications, and PTVr/OBV P24 weeks has an MD of 27.35 (10.43 to 43.99).
Discussion/Conclusion
Post-therapy TC levels rise and peak 24 weeks later. TC levels are unaltered by medication discontinuation, especially for PTVr/OBV and various regimens, which last 48 weeks. In contrast, sofosbuvir-base is unaffected. This finding provides reference data for chronic illnesses and HCV therapy.

Introduction: Influenza causes significant morbidity and mortality, and represents a major global health challenge. The World Health Organization (WHO) estimates that seasonal influenza causes 290,000–650,000 respiratory deaths annually. Despite its impact, few comprehensive studies have analyzed temporal trends in influenza mortality over the last decade.

Aims: This study aimed to examinerecent trends in influenza mortality rates from 2010–2022.

Methods: Influenza mortality data were extracted from the WHO mortality database. Long-term trends were evaluated for each WHO region (the Americas, Europe, Western Pacific, and others), with data available for at least seven years between 2010 and 2022. Joinpoint regression analysis was used to analyze the trends and estimate the annual average percentage change.

Results: Nineteen countries were included. The combined influenza mortality for both sexes increased in most countries, excluding Japan (-10.3%), South Africa (-10.0%), the Philippines (-2.0%), and Morocco (-1.2%). The highest increase was observed in Germany (43.5%), followed by the United Kingdom (34.6%), New Zealand (22.2%), and Thailand (20.1%), with increases of > 20%. Additionally, some countries, such as Germany, Mexico, and the Republic of Korea, showed a single joinpoint near 2016, which was the peak mortality.

Discussion: Our analysis of influenza mortality trends from 2010–2022 across 19 countries revealed diverse patterns. While most countries have experienced increasing influenza mortality rates, countries, such as Japan and South Africa, have declined. Joinpoint regression analysis highlighted trend changes, particularly in 2016. Countries, such as Germany and the United Kingdom, have seen significant increases, raising concerns about the current prevention strategies. Understanding these trends is crucial to tailor interventions and allocate resources. Continuous surveillance is essential for the implementation of effective public health policies to combat influenza.

Introduction:
Accredited Social Health Activists (ASHAs) are community health workers in India who serve as the first point of contact for healthcare in rural areas. However, they are under-trained to resolve community health challenges like antimicrobial resistance (AMR).
Aims: To assess the impact of role-plays on improving the understanding of antimicrobial resistance and promotion of responsible antibiotic usage in communities by the ASHAs.
Methods: A mixed-methods approach was adopted, involving 58 ASHAs from six primary health centers (PHCs). The cross-sectional quantitative component assessed the knowledge and practices towards antibiotic use using a validated questionnaire and fifty-eight in depth interviews explored the likelihood of discussing AMR, effectiveness of role plays and ASHA worker actions based on role-plays in community. A descriptive analysis was performed for the quantitative data, and a thematic analysis was performed for qualitative data.
Results:
A total of 58 participants from six primary health centres (PHCs) took part in this study. The mean age of participants was 39 ± 4 years and nearly one-half of the participants (44.8%) had 11 to 15 years of experience. About 56 (96.5%) participants strongly agreed that the role-play scenario emphasized the information on the importance of completing antibiotic courses as prescribed. A total of 52(89.6%) participants strongly agreed that they feel more informed about the risks and consequences of improper antibiotic usage after witnessing the role-play sessions. About 50 (86.2%) participants acknowledged that after the role-play, they are more equipped to discuss the topic of AMR and proper antibiotic usage with the community.
Conclusion:
ASHAs have the potential to become change agents for increasing rational antibiotic use in the community. The findings reinforce the need for ongoing education and advocacy efforts within primary healthcare systems to combat AMR effectively and promote better health outcomes through ASHAs for communities at large.

Macrolides are widely used in Thailand and they have been known for side effects such as gastrointestinal disturbances, abdominal pain and hepatotoxicity. They may also cause allergic reactions, including rash and anaphylaxis. Among existing epidemiological evidence from scientific database until year 2022 showed that the most three serious side effects from macrolides had caused more cardiac disorders or changes in liver enzymes compared to placebo. Recently, the stringent countries have introduced legal measures to reduce risk from serious effects of macrolides including strictly used in patients with underlying cardiac diseases due to its much used. The study is aimed to quantify the serious adverse events and its risk management. Methods: Retrospective study was used in surveillance database of the Thai Vigibase
The passive surveillance in Thailand between year 2021-2023 had revealed the general anti-infectives for systemic use were 18,087 events (45.32%) from total 36,259 adverse events reported from hospitals under the Ministry of Public Health. Among these were 12.5% with serious effects from widely antibiotic use. The proportion of female: male was 1.2:1. Serious adverse effects included arrythmias and hepatotoxicity were found in erythromycin and roxithromycin use. In 2024, Thai FDA has implemented the legal warnings to macrolides specified to reduce the most serious risks in cardiovascular, hepatotoxicity and skin disorders. In summary, the surveillance system has disclosed the serious risk of macrolides. The legal warnings have endorsed the safe use of macrolides in Thai patients.

Introduction: Worldwide, People Living with Human Immunodeficiency Virus (PLW-HIV) adhere to Antiretroviral Therapy (ART). ART has increased risk for Drug Interactions (DIs) due to comorbidities (COs), Poly Pharmacy.
Aims: To study the pattern of DIs in HIV patients with-comorbidities (WC) versus (vs) without comorbidities (WOC).
Methods: In India, five years of retrospective data from Hospital Medical Record Department were screened for DIs in HIV patient’s WC vs WOC. DIs were assessed using databases of University of Liverpool (ULP), Micromedex (MM), Epocrates (EP), for Severity and Clinical significance of DIs.
Results: Total of 1643 HIV patients were Hospitalised; 713 HIV seropositive cases were selected based on study criteria. Out of 713 HIV patients, 546 (77.1%) of HIV patients WC and 167(22.9%) WOC. Out of 713 patients, one sample t-test showed (p-value < 0.001) in 549 HIV Patients with DIs 427(78%) WC vs 122 (78%) WOC in comparison with no DDIs in 164 HIV Patients 119 (21.7%) WC vs 45 (26%) WOC. COs associated with DIs were higher in cardiovascular disease (23%) followed by Renal (12.5%). Severity of DIs as per ULP were “Red” Drugs that should not be co-administered 14(4.4%) in WC vs 2(2.7%) in WOC, “Amber” Potential clinically significant interaction 196(62%) in WC vs 32(43.8%) in WOC, “Yellow” Potential weak interaction 106(33.5%) in WC vs 39(53.4%) in WOC. MM-DIs were “Contraindicated” 12(3%) WC vs 1(1.2%) in WOC, “Major” 240(60.3%) in WC vs 57(71.2%) in WOC, “Moderate” 129(32.4%) WC vs 19(23.7%) in WOC, “Minor” DIs 17(4.3%) in WC vs 3(3.7%) in WOC. EP DIs were ‘Avoid” 158(24.8%) WC vs 33 (21.4) WOC, “Monitor” 304 (47.7%) WC vs 82 (53.2%), “Caution” 169(26.5%) WC vs 39 (25.3%) WOC. Higher DIs were in TDF+3TC+EFV 308(78.8%) followed by TDF+FTC+EFV 241(70.8%).
Conclusion: Clinicians must Check for DIs while prescribing ART with Other drugs for Comorbidities.

Introduction. Current treatment guidelines recommend fidaxomicin and oral vancomycin as first-line treatments for Clostridioides difficile infection (CDI). Disparities in the prevalence of CDI and the availability of novel treatments require understanding of contemporary trends in fidaxomicin and oral vancomycin consumption at the global level.
Aims. To assess international trends in the consumption and expenditures of fidaxomicin and oral vancomycin.
Methods. We used the IQVIA-MIDAS global sales database to analyse data from 2012 to 2023 for fidaxomicin and oral vancomycin in 43 countries. We used defined daily doses per 100,000 inhabitants per year (DDD/100K) and manufacture level price (standardised in 2023 US dollars) to evaluate consumption and expenditure. Changes in consumption and expenditure were estimated using compound annual growth rates (CAGR).
Results. Average consumption of fidaxomicin across 43 countries increased rapidly from 21.68 DDD/100K in 2012 to 126.68 DDD/100K in 2023 (CAGR = 17.42%) and similar increases in expenditure (2012 = 0.07 USD/capita, 2023 = 0.34 USD/capita; CAGR = 14.96%). During the same period, oral vancomycin consumption increased from 71.61 to 120.82 DDD/100K (CAGR = 4.87%), but a decreasing trend in expenditure (2012 = 0.20 USD/capita, 2023 =0.03 USD/capita; CAGR = -15.16%). The earliest adoption of fidaxomicin in middle-income economies occurred five years later than in high-income economies. Despite higher CAGRs, consumption of fidaxomicin and oral vancomycin in middle-income economies was only 1.9% and 2.3%, respectively, of that in high-income economies in 2023. Regionally, although Northern America experienced a high increase in consumption of oral vancomycin (CAGR = 6.55%), it showed the largest decrease in expenditure (CAGR = -17.44).
Discussion. Consumption of fidaxomicin and oral vancomycin continues to increase globally. However, the global utilization of fidaxomicin and oral vancomycin exhibits significant economic and geographical disparities, showing inequitable accessibility. Efforts to improve the availability of affordable medication in non-high-income economies are essential.

Introduction: The prevalence of dermatophytosis is increasing in India, with patients presenting with multiple-site lesions, extensive skin lesions, and unusually large lesions. Frequent recurrence and the chronic nature of this disease complicate its treatment. Given the evolving nature of dermatophytosis, current standard treatment options may be insufficient.
Aim: To compare the effectiveness and safety of conventional itraconazole and super-bioavailable itraconazole, along with adjuvant therapy, in patients with disseminated dermatophytosis.
Methods: This study was designed as a prospective, observational cohort study over a period of one year. Patients with disseminated dermatophytosis were recruited after obtaining informed consent. They were divided into two cohorts: one receiving oral itraconazole 200 mg once daily, and the other receiving super-bioavailable itraconazole once daily. Clinical and economic outcomes were assessed using the Physician's Global Assessment (PGA) scale and cost-effectiveness analysis, respectively. Direct medical costs were used to calculate the incremental cost-effectiveness ratio (ICER).
Results: The cure rates at 6 weeks were 73.7% (45 out of 61 patients) for cohort 1 and 68.2% (15 out of 22 patients) for cohort 2 (p=0.61), indicating that both treatments are equally effective. Patients who achieved clinical cure were subsequently monitored for clinical relapse over an additional four weeks. During this follow-up period, clinical relapses were observed in 20% (9 out of 45 patients) of cohort 1 and 6.6% (1 out of 15 patients) of cohort 2 (p=0.29). The cost-effectiveness analysis determined the ICER between conventional itraconazole and super-bioavailable itraconazole to be 265.86 INR.
Discussion: Patients with disseminated dermatophytosis treated with either conventional itraconazole or super-bioavailable itraconazole exhibit similar clinical responses and clinical relapse profiles. Both treatment groups showed significant reductions in PGA scores, indicating no superiority of super-bioavailable itraconazole over conventional itraconazole. Cost-effectiveness analysis suggests a marginal advantage for the super-bioavailable itraconazole regimen.

Aim/Objective: The aim of this study was carried out to compare the change in hematocrit following four antimalarial treatments.
Methods: Data were extracted from 313 case record forms of children that met the eligibility criteria aged 3-119 months enrolled in antimalarial clinical trials in Southwest Nigeria between 1998 and 2014. Change in haematocrit levels from baseline through 28 days follow-up period were compared among children treated with artemether-lumefantrine (82), atovaquone-proguanil (41), artesunate-amodiaquine (156) and chloroquine (34).
Repeated measures analysis was done by fitting a general linear model (GLM).
Results: The median age of the study population was 25 months and 54% were males. The mean differences (95% CI) in haematocrit from baseline were 4.7% (95% CI = 3.6, 5.8), 4.4% (95% CI = 2.7, 6.0), 3.8% (95% CI = 3.0, 4.7) and 2.4% (95% CI = 0.5, 4.4), for artemether-lumefantrine, atovaquone-proguanil and artesunate-amodiaquine and chloroquine, respectively. Using the general linear model, repeated measure analysis showed significant differences in the mean haematocrit level over the 28-day follow-up among the four treatment groups (p<0.05).
Conclusions: All children experienced increased haematocrit after treatment, with artemether-lumefantrine appearing to result in a greater increase in haematocrit than other antimalarial drugs. Children who are more susceptible to haemolyze during and after malarial infection such as Sickle Cell Disease and G6PD deficiency patients might benefit more from using the artemether-lumefantrine combination than the other antimalarial drugs in the Nigerian market.
Keywords: Anaemia, Haematocrit, Antimalarial Drugs

Introduction: According to a research in 2022, global influenza mortality rates increased from 2001–2018. However, trends in influenza mortality among regions following the COVID-19 pandemic have not been determined.

Aim: We aimed to assess the changes in regional influenza mortality trends due to the COVID-19 pandemic.

Methods: Using the vital death registration data from the WHO Mortality Database from 2001–2022, influenza mortality was analyzed by classifying WHO member countries into seven regional groups. Deaths due to influenza were defined using the International Classification of Diseases 9 and 10 codes (ICD-9:487, ICD-10: J10, and J11).
To show global trends in crude and age-standardized mortality rates, we used locally weighted scatterplot smooth curves.

Results: Seventy-six countries were analyzed. All regions, excluding Latin America and the Caribbean, showed a declining trend; Western Europe peaked at 0.68 in 2020, Eastern Europe at 0.30 in 2018, North America at 1.01 in 2017, Oceania at 0.84 in 2017, and Asia peaked at 0.30 in 2016 and has been declining thereafter. Africa has exhibited a constant downward trend since 2010. Many regions showed a similar trend, although the CR values were higher for older individuals aged ≥65 years in each region. Additionally, mortality rates of several countries may increase by 2022.

Discussion: Overall, influenza mortality has decreased since 2018, although there are regional differences. However, in some countries, the mortality rates have returned to the same level as the pre-COVID-19 pandemic period; therefore, continued observation is needed.

- Introduction: Colorectal cancer (CRC) is linked to Type 2 Diabetes Mellitus (T2DM), which increases CRC risk. Despite guidelines emphasizing the importance of CRC screening for early detection, variability in screening adherence among adults with diabetes remains underexplored.

- Aims: This study aimed to 1) investigate the prevalence of CRC among US adults by diabetes status, and 2) examine preventive CRC screening patterns in adults aged 40-75 without CRC in 2021.

- Methods: Adult respondents aged between 40-75 years were the study population. Self-reported diabetes-and CRC-related questionnaires in 2021 NHIS data were used to identify diabetes and CRC status, which relied on affirmative responses to questions “Ever had diabetes”, “Colon cancer mentioned”, “Rectal cancer mentioned”, and “Colorectal cancer mentioned.” Preventive CRC screening was defined as respondents with diabetes but without CRC who answered yes to questions “Colonoscopy or sigmoidoscopy”, “Ever had colonography/virtual colonoscopy”, “Ever had home blood stool test”, and “Ever had Cologuard”. Prevalence of diabetes, CRC, and CRC screening were weighted and adjusted by the NHIS clustering and stratification sample design. Analyses included chi-square tests and multivariable logistic regression which were used to compare screening patterns and evaluate associations between diabetes and screening uptake.

- Results: There were 3,134 patients with diabetes enrolled in this study. Among adults aged 40-75, patients with diabetes had a higher CRC prevalence than patients without diabetes (0.86% versus 0.46%; P<0.05), consistent with the result in overall adult patients (1.06% versus 0.44%; P<0.01). In CRC-free patients, those with diabetes were more likely to have any CRC screening than those without diabetes (86.3% vs. 79.9%; p<0.05).

- Discussion/Conclusion: In the U.S., adults with diabetes had an increased risk of developing CRC. Higher preventive screening rates were observed among patients aged 40-75 years with diabetes, underscoring the necessity for continued emphasis on screening within this demographic.

Introduction:
The molecular interplay and pathogenesis of this poor prognosis disease called anaplastic thyroid cancer, is poorly understood, posing an unmet clinical need in the diagnosis and therapy of the neoplasia. Chromosomal aberrations play an important role in the pathogenesis of a disease. However, all mutations may not be transcribed, and all altered mRNAs may not be expressed due to transcriptional regulations.
It is important to screen along the central dogma to evaluate the underlying molecular pathway of pathogenesis. Theoretically, drugs approved against a disease can be repurposed for another

Aims:
1. Build an affordable actionable actionable minimum molecular diagnostic panel for ATC
2. Identify drugs that may be repurposed in ATC

Methods:
Two methods were used; (1) HuGE Navigator Database curation of literature (2) cBio Portal mutation analysis.
The Open Target Database scored the genes generated by the HuGE Navigator Database. Top ten genes were selected. Patient samples were analyzed on the cBio portal, yielding 183 mutations. EnrichR was used to demonstrate the interlinking processes of the genes found. An association connectome and information on the protein anomalies in this disease were constructed on the Cytoscape database. To acquire drug repurposing data, all the genes obtained were loaded into DrugBank. Medications that target a single gene were selected for additional examination.

Results: Out of the 622 genes from HuGE Navigator, 10 genes; PAX8, CCDC6, NCOA4, AKT1, TP53, BRAF, among others, had a high association score. 15 genetic mutations, 6 of which were in common with Huge Navigator analysis, were found in more than 5% of the patients.
Pathway analysis of the genes highlighted p53, VEGF, RAS signaling, PI3K/AKT and mTOR pathways among others. Approved drugs specific to only one identified target were found on DrugBank.

Conclusion: The identified theoretically repurposable drugs can be analyzed further using molecular docking.

Introduction
The incidence of early-onset cancer is rising, with observed uncertainty in geographic variability.

Aim
This study aimed to describe patients with metastatic colorectal cancer and advanced gastric cancer in Japan and the US.

Methods
The data sources were de-identified, electronic health record-derived, Flatiron Health databases from Japan and the US. We selected patients diagnosed with colorectal or gastric cancer between 1 January 2015 and 31 December 2023, excluding those under 18 at diagnosis. The study defined ‘early-onset’ disease as a metastatic diagnosis of colorectal or gastric cancer before the age of 50. Descriptive statistics were analyzed in a trusted research environment compliant with local legal and ethical requirements.

Results
The population in Japan consisted of 811 patients (390 with colorectal cancer, 421 with gastric cancer). The median (IQR) age of patients with colorectal cancer was 61 (49-69), 58% were male, and 3.7% had an ECOG score of 2 or above at the time of their first treatment. The median (IQR) age of patients with gastric cancer at diagnosis was 66 (58, 72), 67% were male, and 4.4% had an ECOG score of 2 or above at the time of their first treatment. There was a higher prevalence of early-onset disease in Japan compared to the US: 27% compared to 15% (n=31,642), respectively, for colorectal cancer, and 14% compared to 10% (n=3,235), respectively, for gastric cancer.

Discussion/Conclusion
Compared to the US, the Japan cohort included a higher proportion of patients with early-onset disease. A strength of this study was the availability of disease stage, metastatic diagnosis date, and other clinical characteristics that were abstracted from patient charts. Further research will explore the generalizability of these findings and the survival outcomes for early-onset patients in Japan and the US, to generate robust evidence to inform targeted treatment strategies.

Introduction: Tuberculosis (TB) has been a major public health concern. Achieving an optimal therapeutic outcome is hindered by many factors including, drug related, patient related, and system related. Drug-related problems (DRPs) in anti-TB treatment include adverse drug reactions, drug interactions, and non-adherence to medication. To optimize patient outcomes Pharmacists play a crucial role in addressing these issues through counselling, monitoring treatment, and managing drug regimens.
Aims: To assess Drug Related Problems associated with anti-tubercular medications.
Methodology: This prospective interventional study, conducted over 9 months at Urban Primary Health Centres and tertiary hospital in Mysore. Patients were selected based on specific criteria. Baseline details including demographic, medication history was collected, and patients were monitored on each visit. Various tools were used to assess DRPs: Hepler and Strand classification, WHO-UMC Causality Assessment, Naranjo Adverse Drug Reaction Probability Scale, Hartwig and Siegel severity assessment, Shumock and Thornton Preventability scale, and the 10-item Medication Adherence Rating Scale (MARS).
Results: Out of 230 patients, [61.30%] were males, and [30.86%] were aged 31-45 years. [97.13%] were new TB cases, and [75.65%] had no family history of TB. Detection was primarily through microbiological confirmation [62.17%], and [73.91%] resided in urban slums. Isoniazid, rifampicin, and pyrazinamide were prescribed to [above 98%] of patients. Among 445 DRPs, adverse drug reactions accounted for [46.06%], drug interactions [23.59%], and drug use without indication [5.61%]. Gastrointestinal disorders [46.82%] and hepatobiliary disorders [17.56%] were the most common adverse reactions. Barriers to adherence included fear of infecting family [87.06%], stigma and discrimination [75.43%], and income loss [72.4%]. Adherence improved over 180 days. Chi-Square test using MARS showed a highly significant relationship between adherence and non-adherence [p < 0.0001].
Conclusion: Clinical Pharmacists play a vital role in reducing DRPs and improving patient outcomes in TB treatment.
Keywords: Anti-Tubercular Therapy, Drug-related problem, Medication adherence, Barriers