Introduction: A transcatheter aortic valve replacement (TAVR) device is used to treat severe aortic stenosis in high-risk patients through a minimally invasive approach; however, despite its benefits, it may also lead to complications. Materiovigilance helps monitor and evaluate such adverse events (AEs) to improve safety. The FDA’s Manufacturer and User Facility Device Experience (MAUDE) database is a key resource for analyzing these post- market device issues.

Aim: This study aimed to evaluate the frequency, type, and reporting characteristics of AEs related to TAVR reported in the MAUDE database over a 10.5-year period
Methods: This study examined adverse events linked TAVR devices reported in the MAUDE database between January 1,2015 and June 30,2025. Data were collected using specific FDA product code (NPT) relevant to TAVR. The analysis focused on identifying device-related complications and event patterns.

Results: Over a 10.5-year period, the MAUDE database documented a total of 62,667 unique adverse event reports involving TAVR devices. The most common device-related issues were, adverse event without perivalvular leak (27.6%), fluid/blood leak (7.23%), degraded(4.51) and dyspnea (4.25%), material deformation (4.05%). Among the reported event types, malfunction accounted for 14.08%, injuries for 75.49%, and deaths for 10.11%. the highest number of adverse events was reported in 2024(10.74%), followed by 2023(9.86%), 2022(7.68%) of the total reports. Most reports originated form United States (42.7%), followed by Japan (17.60%), and Italy (11.05%). Reports were primarily submitted by other physicians, with additional contributions from other healthcare professional and manufacturers.

Conclusion: The findings emphasize the importance of strengthening materiovigilance to minimize TAVR device-related complications. Understanding reported issues can aid in refining device design and informing clinical practice for better patient safety

Keywords: TAVR, MAUDE database, Materiovigilance

Introduction: Critically ill patients are particularly vulnerable to drug-related problems (DRPs) due to complex pharmacotherapy, polypharmacy, and altered drug metabolism. These DRPs including adverse drug reactions, drug interactions, and inappropriate dosing can lead to treatment failures, prolonged hospitalization, and increased mortality. The current study focused on assessing the prevalence, types, and clinical impact of DRPs in critical care to enhance medication safety and optimize therapeutic outcomes.
Aim: To identify and resolve DRPs among critical care patients.
Methods: A six-month prospective observational study was conducted in a tertiary care teaching hospital’s critical care units. Patients (≥18 years) receiving ≥1 antimicrobial agents were included (n=280); patients who were non-cooperative, referred, or terminally ill were excluded. Data were collected from case sheets, treatment charts, and interviews with patients/caregivers. DRPs were classified using Hepler & Strand’s framework; adverse drug reactions (ADRs) were assessed via WHO-UMC causality and Naranjo’s algorithm.
Results : A total of 433 DRPs were identified among 280 patients [155 males (55.3%) and 125 females (44.6%)], out of which 132 (30.48%) were DDIs and 103 (23.7%) were ADRs. Out of the 132 DDIs, severity analysis showed moderate drug-drug interactions (DDIs) predominated [n = 74 (56.06%)]. In the 103 ADRs, 46.6% were male and 53.39% were female. The most reported severity level was ‘moderate’ (Level 3) at 59.2%. It was observed that 41.75% of the ADRs were predictable and 88.35% were not preventable. Using the WHO probability scale, 53.39% were ‘probable’; using Naranjo’s algorithm, 76.69% were ‘probable’. The outcomes of the DRPs revealed that [n = 176 (40.6%)] cases were successfully resolved.
Conclusion: DRPs, particularly moderate DDIs and ADRs, are prevalent in critical care, with low resolution rates (40.6%). Improved antimicrobial stewardship and proactive monitoring are needed to enhance patient safety and rational drug use.
Keywords: Medication safety, Drug-related problems, Critical Care Units.

Abstract
INTRODUCTION: Cochlear implants have significantly improved lives of individuals with severe to profound hearing loss by restoring hearing and enhancing communication. As Class III high-risk medical devices, they warrant careful monitoring due to the potential for serious adverse events. With increasing global usage, post-market surveillance is essential. The FDA’s MAUDE database provides valuable real-world data on adverse events, helping identify complications, device issues, and emerging safety concerns.
AIMS: To analyze MAUDE reports on Cochlear implants, identifying complications, device-related issues, and assessing patient safety profiles.
METHODS: This review analyses adverse events related to Cochlear implants reported in the MAUDE database from May 2023 to May 2025. Using specific search terms and filters, all relevant AE reports were retrieved and categorized based on significant variables and frequencies. The underlying causes and occurrence of AEs were examined to identify patterns and high-risk areas. This comprehensive evaluation provided valuable insights into the safety, performance, and potential areas of improvement for cochlear implants
RESULTS: An analysis of 500 adverse event reports related to Cochlear implants for 2 years revealed that 63.6% cases were classified as injuries (318 cases), while 37% involved malfunctions (185 cases). The most frequent device issue was Mechanical Problem, comprising 123 cases, followed by impedance problem 83 cases and expulsion 48 cases. Patient-related problems which are highly prevalent were headache 187 cases followed by failure of implant 73 cases. Reports were predominantly from the U.S. The COCHLEAR LTD was identified as the manufacturer in 253 reports.
CONCLUSIONS: Cochlear implants play vital role in restoring hearing and improving quality of life for individuals with severe hearing loss. MAUDE data shows cochlear implants are generally safe, but risks persist. Continued monitoring, adherence to best practices, and patient education are essential until further studies clarify long-term outcomes and help improve implant safety and performance.

Introduction: Spinal fusion implants are widely used to manage various spinal disorders, but adverse events (AEs) can compromise patient safety and outcomes. This study utilizes the FDA’s Manufacturing and User Facility Device Experience (MAUDE) database to evaluate reported complications and assess device safety. Recognizing the significance of device-related complications is essential for informed clinical decisions.
Aims: The aim of the study was to evaluate the type, frequency and trends of AEs associated with spinal fusion implants using real-world data.
Methods: AE reports were retrospectively extracted from the Manufacturer and user facility device experience (MAUDE) database using product code KWQ from January 1, 2015 to July 10, 2025. Data included event types, patient and device problems, reporter type and country of origin. Descriptive statistical analysis was conducted to determine the most frequent complications and annual reporting trends.
Results: A total of 4,454 AE reports were documented, with reports peaking in 2021 (13%), 2015 (12%), and 2016 (11%). The United States accounted for highest reports (34.7%), followed by Japan (10.19%) and Switzerland (8.14%). Geriatric patients (77.6%) were most frequently affected, followed by adults (22.4%). Manufacturers (94.6%) were the predominant reporters, followed by physicians (5.4%). In event type, injury was most common (54.4%), followed by malfunctions (45.3%), and death (0.22%). Top device-related problems included unknown adverse event (31.5%), breakage (24.5%), migration or expulsion (16.9%), fractures (11.6%), and dislodgement or dislocation (3.1%). The most common patient-related problems involved implant failure (13.6%), pain (10.6%), injury (9.5%), and hematoma (7.8%).
Conclusions: Spinal fusion implants present ongoing safety challenges, especially among elderly patients. Improved materiovigilance and standardized clinical protocols could improve patient safety and device efficacy. These findings can guide clinicians in risk-based decision-making and support regulatory bodies and manufacturers in enhancing device design and post-market surveillance.
Keywords: spinal fusion, MAUDE database, implant safety

Introduction: Antidepressant use has recently increased across all age groups. Older adults are more vulnerable to adverse reactions due to metabolic decline. Duloxetine is prescribed for depression and pain, but evidence on age-specific adverse event (AE) profiles remain limited.

Aims: To analyze duloxetine-related signals using the Korea Adverse Event Reporting System (KAERS) and compare signals focusing on older adults.

Methods: We conducted retrospective analysis of antidepressant-related spontaneous reports (2013-2022) from the KAERS database. Reports with duplicates, follow-ups, missing sex/age, or age under 20 were excluded. Age groups were categorized as young (20–39), middle-aged (40–64), and older adults (≥65). Frequency analysis of major System Organ Classes (SOCs) was conducted and data mining indices—including proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC) were calculated. AEs were standardized to preferred-terms per MedDRA version 28.0. We identified age-specific signals and unknown signals; AEs not listed in antidepressant labels in either the United States or Korea. Signals were compared across groups by RORs.

Results: Of 20,963 total reports, duloxetine-related reports were 388(14.8%) of 2,624 cases in young, 2,331(24.5%) of 9,511 in middle-aged, and 2,067(23.4%) of 8,828 in older adults. Gastrointestinal disorders were the most reported SOC in older adults, while psychiatric and nervous system disorders were most in young adults. Signal detection identified 13, 20, and 13 signals in young, middle-aged, and older adults, respectively, including 1, 8, and 2 unknown signals and 8, 14, and 7 age-specific signals. Hematuria and neutropenia were more common in middle-aged groups: relative ROR of 0.16 (95% CI: 0.02–0.98) and 0.41 (0.21–0.76), respectively. Both AE were unknown signals.

Conclusions: Age-specific variations in duloxetine signals, including unknown ones, were identified. These findings support the need for age-tailored monitoring to improve Korea’s age-stratified drug safety surveillance.

Keywords: Duloxetine, Adverse events, Age-specific signal detection, Older adults, Korea

Introduction:
A medical device is any instrument, apparatus, appliance, software, implant, or other article intended to be used, alone or in combination, for a medical treatment purpose. Regulations for High-risk medical devices vary across countries, and necessary to understand the differences to meet healthcare priorities and administrative requirements.
Aims:
To study the Approval Process of High-Risk Medical Devices in India, USA, Europe and Australia.
Methods:
Approval process of high-risk devices (Class C & D devices) was evaluated using the Central Drugs Standard Control Organization (CDSCO) in India, the Food and Drug Administration (FDA) guidelines for Class III devices, in the European Union through the Medical Device Regulation (EU MDR 2017/745), and Australian Register of Therapeutic Goods (ARTG) for Class III and Active Implantable Medical Devices.
Results:
Approval Process of High-risk medical devices vary from country to country. The minimum waiting period for approval of the medical devices varies from 9 months (India), Australia (12 months) the EU (18 months), to 24 months (the USA). The approval pathway includes import & manufacturing licence process in India, premarket approval in the USA, conformity assessment by CE in EU and ARTG in Australia.
Conclusions:
The approval processes for high-risk medical devices vary significantly across India, the USA, Europe, and Australia in terms of regulatory frameworks, timelines, and evidence requirements. While the USA and Europe have well-established, stringent pathways focusing on clinical data and risk-benefit analysis, India and Australia are evolving toward more harmonized and streamlined systems. Overall, global alignment and increased transparency could enhance patient safety and foster innovation in the high-risk medical device sector.
Keywords: High Risk Medical Devices, CDSCO, FDA, EMA, TGA.

Introduction: Antibiotic utilization has been streamlined in various countries because of the national stewardship programs. Besides the efficacy component of antibiotics, the safety profile is a predominant area that requires special consideration in real-world settings. Many adverse events from antibiotics are unnoticed, detrimentally affecting the patients’ treatment outcomes.

Aim: To identify aseptic meningitis induced by antibiotics (AMA) through disproportionality analysis.

Methods: A retrospective case/non-case disproportionality analysis was performed in the FAERS database using OpenVigil 2.1, a web-based pharmacovigilance tool, to identify AMA. The data from 2004 to the end of 2024 were extracted by using the preferred term, i.e, aseptic meningitis, of MedDRA terminology and the drug terms under the category of antibiotics. Frequentist techniques assessed the degree of association between aseptic meningitis and antibiotics. A signal is identified when the Proportional Reporting Ratio (PRR) > 2, the Reporting Odds Ratio (ROR) lower bound > 1, and the Chi-Square > 4.

Results: The study had 56% reports of AMA in the female population. The patients on sulfamethoxazole (n=74) and trimethoprim (n=73) had the highest report of aseptic meningitis, which was from the US. Aseptic meningitis was also reported in patients on amoxicillin, ampicillin, azithromycin, cefazolin, cefepime, cefotaxime, ceftriaxone, ciprofloxacin, clarithromycin, colistin, meropenem, metronidazole, minocycline, and vancomycin. A potential signal for AMA was reported in patients on cefcapene (PRR: 360.35), followed by garenoxacin (PRR: 45.39), ceftibuten (PRR: 32.03), colistin (PRR: 27.94), cefotaxime (PRR: 26.685), and amoxicillin (PRR: 22). Hospitalization (n=511) was the most prominent outcome reported in AMA patients.

Conclusions: Several occurrences of aseptic meningitis were reported with antibiotics. However, a well-designed study is required to confirm the association of aseptic meningitis with different antibiotics.

Introduction: Critically ill patients are highly susceptible to infections caused by Gram-negative (GN) or Gram-positive (GP) bacteria, necessitating rapid and accurate differential diagnosis to guide targeted antibiotic therapy and mitigate antimicrobial overuse. Point-of-Care testing (POCT) facilitates prompt diagnosis; however, its precision in distinguishing GN from GP infections warrants rigorous evaluation.
Objective: This study aims to assess the diagnostic accuracy of POCT methods, including biomarkers, molecular detection techniques based on pathogens, omics, and clinical symptoms, for differentiating GN and GP infections in critically ill patients.
Methods: A systematic search was conducted across PubMed, Embase, Web of Science, and Cochrane Library for studies published from May 2005 to May 2025 evaluating the diagnostic accuracy of POCT for GN/GP infections. The quality of studies was assessed using the QUADAS-2 framework. Pooled sensitivity, specificity, and area under the curve (AUC) were calculated employing a bivariate random-effects model.
Results: Of 87 studies included, 68 underwent quantitative analysis. Procalcitonin (PCT, 3.0–5.0 ng/mL) exhibited a pooled sensitivity of 0.84 (95% CI 0.62–0.95), specificity of 0.83 (95% CI 0.70–0.91), and hierarchical summary receiver operating characteristic (HSROC) AUC of 0.90 (95% CI 0.87–0.92). Other biomarkers (n=26) demonstrated that the pooled sensitivity ranges from 0.72 to 0.76, and the pooled specificity ranges from 0.61 to 0.80. Molecular diagnostics, including matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and polymerase chain reaction (PCR), achieved sensitivities and specificities of 91–98%. Clinical symptom-based assessments yielded low accuracy (AUC 0.62–0.68), whereas omics-based approaches showed moderate performance (AUC 0.75–0.84).
Conclusion: Among biomarkers, PCT (3.0–5.0 ng/mL) demonstrates robust diagnostic accuracy in differentiating between GN/GP infections, while molecular diagnostic methods provide superior precision through direct pathogen detection. Future investigations should focus on integrated host-pathogen diagnostic models to enhance the rational use of antibiotics.
Keywords: Gram-Negative/Gram-Positive bacteria; Point-of-Care testing; Diagnostic accuracy

Introduction: Human Immunodeficiency Virus (HIV) is an infectious disease that decreases CD4 count, weakens persons immune system and further causes opportunistic infections, if left untreated. Most of the patients are still non-adherent because of pill burden, forgetfulness, stigma and lack of knowledge. Therefore, adherence is a key component in optimizing patient’s therapy. Educational intervention can be an effective method in improving patient’s adherence.

Aim: The objective of the study was to evaluate the impact of educational intervention on medication adherence among HIV positive patients.

Methodology: This study was conducted at two ART centers of which we included HIV positive patients above 18 years of age. Patients were randomized into two groups i.e., Control and Intervention (leaflet) group. A standard questionnaire-Medication adherence rating (MARS) scale and Drug Attitude Inventory (DAI) scale was used to assess the adherence and attitude towards the medications at baseline, 1st month, 2nd month, and 3rd month. Statistical analysis was done using SPSS software version 22.

Results: A total of 397 patients were included in the study. Results showed that at baseline there was no significant difference in the MARS and DAI scores between the two groups however, statistically significant difference was observed between the control and interventional groups at third month follow up (P-value < 0.05). The common barriers for non-adherence in control group was forgetfulness and lack of knowledge whereas in intervention group it was forgetfulness and stigma.

Conclusion: There was a significant difference in the scores of MARS and DAI between the patients of control and interventional group which showed that Patient Information Leaflet (PIL) could be an effective method in improving the adherence and attitude towards the medication in HIV patients.

Key words: HIV/AIDS, Medication Adherence, Drug Attitude, Patient Information Leaflet

Background: Drug-related problems (DRPs) are prevalent safety concerns for patients with neurological disorders due to complex medication regimens.
Objective: To assess DRP rates and patterns in patients with neurological disorders through clinical pharmacist integration and describe recommendation acceptance rates.
Methods: Six-month prospective interventional study in Neurology Department of a tertiary care hospital. Patients aged ≥18 years, >24-hour hospitalization were monitored for DRPs and ADRs using a patient-centric clinical pharmacist intervention model involving daily medication review and therapeutic recommendations.
Results: Among 200 patients reviewed (112 males, 88 females; mean age 52.3±16.7 years), 310 prescriptions were analyzed, identifying 306 DRPs. A total of 174 patients (87%) experienced at least one DRP, averaging 1.75 DRPs per patient: 89 patients (51.1%) had one DRP, 52 patients (29.9%) had two DRPs, and 33 patients (19.0%) had three or more DRPs.
Drug-drug interactions comprised 254 cases (83%), ADRs 12 cases (4%), drug duplications 9 cases (3%), inappropriate drug selection 15 cases (4.9%), dosing problems 10 cases (3.3%), and therapeutic duplication 6 cases (1.8%). Among 254 DDIs, 144 (56.69%) were pharmacokinetic and 110 (43.3%) pharmacodynamic. Pharmacokinetic interactions included 113 metabolic changes (78.47%), 18 absorption changes (12.5%), and 13 distribution/elimination changes (9.03%). Pharmacodynamic interactions showed 50 synergistic (45.45%), 35 antagonistic (31.82%), and 25 additive effects (22.73%).
Common conditions included stroke (78 patients, 39%), epilepsy (45 patients, 22.5%), Parkinson's disease (32 patients, 16%). ADRs included hyponatremia (4 cases, 33.3%), nausea/vomiting (3 cases, 25%), dizziness (2 cases, 16.7%). Causality assessment: 7 possible (58.3%), 3 probable (25%), 2 definite (16.7%). Severity: 5 mild (41.7%), 4 moderate (33.3%), 3 severe (25%).
Clinical pharmacists achieved 89.97% (275/306) recommendation acceptance, leading to therapeutic modifications in 245 patients (89.1%).
Conclusion: Substantial DRP burden, particularly DDI, demonstrates the value of collaborative clinical pharmacist interventions in optimizing neurological patient safety.
Keywords: DRP, DDI, Clinical Pharmacist intervention, ADR

Introduction: Drug-related problems (DRPs) refer to issues in drug therapy that may disrupt health outcomes, negatively impact patients, increase healthcare costs, and lower quality of life.
Aims: This study identifies and categorizes DRPs such as incorrect dosages, inappropriate indications, duplicate prescriptions, and drug-drug interactions. It also examines associations between DRPs and factors like gender, age, and physician specialization.
Methods: A six-month prospective cross-sectional study was conducted in two community pharmacies after Institutional Ethics Committee approval (Ref No. IEC2-540/2024). Random prescription samples were assessed using case record forms (CRFs). DRPs were categorized as per the Pharmaceutical Care Network Europe (PCNE) classification system, and drug interactions were identified using Micromedex®. DRP frequencies and associations were analyzed using the Chi-square test. Data entry and statistical analysis were performed using IBM SPSS v20.0.
Results: Among 620 prescriptions reviewed, 120 (19.3%) contained at least one DRP. The mean patient age was 46.58 years, with DRPs being more prevalent in males (73 cases; 60.8%) and those aged >55 years. General medicine prescriptions had the highest DRP proportion (62 cases; 51.7%). The most common DRP was drug-drug interactions (118 cases; 98.3%), followed by inappropriate indications (1 case; 0.8%) and dosing times (1 case; 0.8%). A statistically significant association (p<0.042) was observed between male gender and DRP occurrence.
Conclusions: Drug-drug interactions were the most prevalent DRP, especially among elderly males. Strengthening prescription review processes may reduce these risks and improve patient safety.

Introduction: Type 2 Diabetes Mellitus (T2DM) presents a significant health burden in India, necessitating strong self-management practices for optimal glycemic control. These practices encompass lifestyle modifications and psychosocial adjustments, as emotional distress and poor adherence can impair self-care and worsen outcomes. International studies on self-management often miss psychological factors affecting adherence and lack follow-up or interventions for poor self-care. This study addresses these gaps by assessing self-management in T2DM patients with validated tools, identifying related factors, and offering counseling and follow-up as needed. Understanding how sociodemographic, therapeutic, and emotional elements influence self-management is vital to improving diabetes care.
Aims: To assess factors influencing self-management among T2DM patients using Diabetes Self-Management Questionnaire (DSMQ) and Problem Areas in Diabetes (PAID-5) scales. To provide counselling for those with low DSMQ scores and evaluate outcomes.
Methods: This prospective study enrolled 140 T2DM patients from a tertiary care hospital in Bangalore, India. Baseline data on demographics, therapy, and emotional distress were collected. The DSMQ and PAID-5 scale were used for assessment. Participants with low DSMQ scores received structured counselling. A three-month follow-up assessed changes in self-care behaviors.
Results: Among 140 patients, better self-management practices were associated with age 40–59 years (p=0.0046), urban residence (p=0.00027), private-sector employment (p=0.029), middle socioeconomic status (p=0.00077), regular exercise (p=0.031), and absence of comorbidities (p=0.0027). No significant associations were found with gender, BMI, education, diet, smoking, alcohol use, or type of medication. Follow-up showed improved DSMQ scores post counselling, indicating positive behavioral changes.
Conclusions: The study found that self-management in type 2 diabetes is significantly influenced by age, urban residence, employment, socioeconomic status, exercise, comorbidities and emotional distress; while factors like gender and medication type showed no impact. Targeted counselling and interventions targeting at-risk populations improved self-management, demonstrating its effectiveness in diabetes care.
Keywords: Type 2 diabetes mellitus, DSMQ, PAID-5

Introduction: In the current scenario, patient perceptions of diseases are frequently poor due to inadequate communication and a lack of patient-centered treatment, which leads to decreased trust in clinicians and, ultimately, poorer health outcomes such as treatment failure and lower medication adherence. This study examines how people perceive their illnesses and how effectively they follow their prescribed medications.

Aim: To assess differences in patient perceptions and medication adherence across various chronic diseases.

Methods: A prospective observational study was conducted at a tertiary care hospital in Southern India for 6 months among patients with hypertension (HTN), diabetes mellitus (DM), and rheumatoid arthritis (RA). Patient perception scores were assessed using the Brief Illness Perception Questionnaire, consisting of eight questions graded on a scale of 1 to 10. The Morisky Medication Adherence Scale (MMAS-8) was used to assess adherence, consisting of eight questions, each with a yes or no answer. MMAS-8 values of 8 indicate high adherence, 6-7 moderate adherence, and <6 low adherence.

Results: A total of 200 patients were included in the study: 104 (52%) males and 96 (48%) females. Patients' perception scores were lowest for treatment control in HTN and DM. For the other questions, patients had moderate levels of perception. Among MMAS-8 scores, 54 (27%) were low adherers, 99 (49.5%) were moderate adherers, and 47 (23.5%) were high adherers.

Conclusion: Patients demonstrated moderate levels of perception, except in the treatment control domain of HTN and DM, indicating a balanced understanding of their condition. The majority of individuals were moderate adherers, suggesting inconsistent medication use. Hence, pharmacists can play a key role in enhancing these outcomes by providing patients with education and guidance about their disease, which could empower them to take an active role in their care.

Keywords: Chronic Diseases, Perception, Adherence

Introduction: Alopecia is a common dermatological condition, and the safety profiles of its primary pharmacological treatments—finasteride, dutasteride, and minoxidil—have raised ongoing concerns. Reports began to emerge of suicidal ideation and completed suicides among men using finasteride, promoting attention from regulatory bodies. Despite increased investigation, the psychiatric safety of these medications remains incompletely understood.
Aims: To address this gap, we conducted a pharmacovigilance study using real-world data to evaluate the association of suicidality and depression with finasteride, dutasteride and minoxidil.
Methods: We analyzed adverse event (AE) reports from two major pharmacovigilance databases: the U.S. Food and Drug Administration Adverse Event Reporting System (FAEAS, Q1 2004 to Q1 2025) and the Japanese Adverse Drug Event Report (JADER, Q1 2004 to Q2 2025). Disproportionality analyses were conducted using the reporting odds ratio (ROR) to detect safety signals. Subgroup analysis were also performed.
Results: After deduplication, a total of 4,007 AE reports were included (FAERS: 3,984; JADER: 23). Significant disproportionality signals were observed for suicidality (FAERS: ROR = 6.51 [95% CI: 6.15–6.90]; JADER: ROR = 5.42 [2.99–9.82]) and depression (FAERS: ROR = 9.71 [9.33–10.10]; JADER: ROR = 7.98 [4.40–14.47]) among finasteride users. In FAERS, dutasteride was also associated with a significant signal for depression (ROR = 2.14 [1.68–2.74]), but no signal was identified for minoxidil. Subgroup analysis in FAERS revealed elevated RORs for suicidality among younger patients (<45 years) (ROR = 1.37 [1.17–1.60], P < 0.05) and those using finasteride for alopecia (ROR = 1.27 [1.06–1.53], P < 0.05).
Conclusions: Finasteride use was significantly associated with increased reports of suicidality and depression, particularly in patients under 45 years treated for alopecia. These findings highlight the importance of ongoing pharmacovigilance, the need for further confirmatory studies, and consideration of safety label updates for finasteride.
Keywords: finasteride, suicidality, pharmacovigilance

Introduction
Preclinical studies have demonstrated that leukotriene receptor antagonists (LTRAs), commonly used to treat asthma, can reduce dementia-related pathology and improve cognitive function in animal models. However, clinical evidence in humans remains limited and inconclusive.

Aims
To examine whether LTRA use is associated with a reduced risk of dementia among patients with asthma.

Methods
We emulated 420 sequential target trials at monthly intervals, defining trial entry based on age, from 50 years to 84 years old. Data were sourced from the UK Clinical Practice Research Datalink, linked to Hospital Episode Statistics and Office for National Statistics. Individuals initiating LTRAs were compared to non-initiators. The primary outcome was incident dementia. Propensity score matching was employed to address baseline confounding. We used pooled logistic regression models, with follow-up time divided into 3-month intervals, to estimate hazard ratios (HRs) and risk differences, emulating both intention-to-treat and per-protocol effects. Nonparametric bootstrapping was used to compute the 95% confidence intervals (CIs).

Results
The analysis included 106,844 matched pairs. During a median follow-up of 5.08 years (LTRA group) and 4.99 years (non-LTRA group), 3,097 and 3,233 dementia cases were observed, respectively. A modest reduction in dementia risk was found in the LTRA group in the intention-to-treat analysis (HR=0.94, 95% CI: 0.89–0.99; 10-year risk difference = -0.36%, 95% CI: -0.66% to -0.08%) and in the per protocol analysis (HR=0.89, 95% CI: 0.80–0.97; 10-year risk difference = -0.70%, 95% CI: -1.39% to -0.17%). The effect was more pronounced in older age groups and among females.

Conclusions
This study found a modest association between LTRA use and reduced dementia risk in patients with asthma. These findings support further investigation into LTRAs as potential therapeutic agents for dementia, particularly in exploring age- and sex-specific effects, optimal dosing, and timing across stages of neurodegeneration.

Background
Gout is a chronic inflammatory arthritis caused by monosodium urate crystal deposition, leading to severe pain and joint damage. Recent studies suggest that proton pump inhibitors (PPIs) may increase gout risk. PPIs inhibit gastric H⁺/K⁺ ATPase activity, leading to adenosine triphosphate accumulation, which is metabolized to uric acid and may trigger gouty arthritis.
Aim
This study evaluated the association between PPI use and gout risk among South Korean adults. We hypothesized that PPI exposure would increase gout incidence.
Methods
We analyzed data from the Korean National Health Insurance Service database (2002–2019). The control cohort was generated using inverse probability of treatment weighting (IPTW) based on age, sex, Charlson Comorbidity Index score, and index year. Baseline balance before and after IPTW was assessed using standardized mean differences (SMDs), with SMD <0.1 indicating adequate balance. Cox proportional hazards models estimated adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for gout.
Results
After IPTW, baseline covariates were well balanced between exposure and control groups. PPI use was significantly associated with an increased risk of gout compared with controls (aHR = 1.806; 95% CI, 1.763–1.850). Additional factors linked to higher risk included anti-tubercular drugs (aHR = 1.961), and angiotensin-converting enzyme inhibitors (aHR = 1.799). Conversely, female sex (aHR = 0.690), congestive heart failure (aHR = 0.757), and cerebrovascular disease (aHR = 0.823) were associated with a lower risk of gout. The proportional hazards assumption was satisfied, supporting the robustness of the Cox model estimates.
Conclusion
PPI use was independently associated with an increased risk of gout in this large nationwide cohort. These findings suggest that PPI therapy may contribute to the development of gout and underscore the need for careful prescription and further prospective studies to confirm causality.

Introduction: Penicillin allergy is common and has been linked to worse outcomes in acute COVID-19. However, its association with post-COVID-19 condition (PCC) and subsequent clinical outcomes (≥90 days post-COVID Diagnosis) including nonfatal stroke, myocardial infarction, and all-cause mortality remain unknown.
Aim: To evaluate whether penicillin allergy labelling is associated with an increased risk of PCC and subsequent clinical outcomes, and to assess whether PCC mediates this relationship.
Methods: We conducted a population-based retrospective cohort study using UK primary care data from the CPRD Aurum database (March 2020–July 2023). Adults (≥18 years) with confirmed SARS-CoV-2 infection between March 2020 and March 2023 were included, excluding those with less than one year of prior GP records. The primary outcome was PCC, defined by a PCC diagnostic code or at least one WHO-listed symptom occurring 90–365 days post-infection, without the same symptom recorded in the previous 180 days. The secondary outcome was a composite of subsequent clinical events. Adjusted hazard ratios (aHRs) and risk differences (RD) were estimated using multivariable models controlling for baseline factors. Mediation analysis assessed whether PCC mediated the link between penicillin allergy labeling and subsequent clinical outcomes.
Results:Among 1,587,288 individuals, 36,350 had a penicillin allergy label. The allergy-labelled group had a 10.8% higher 1-year risk of PCC (aHR = 1.09, 95% CI: 1.07–1.12), with consistent results across subgroups. Penicillin allergy was also associated with an increased risk of subsequent clinical outcomes (aHR = 1.10, 95% CI: 1.01,1.21), although PCC did not mediate this association.
Conclusion: Penicillin allergy labelling was associated with increased risks of PCC and adverse outcomes, though PCC did not mediate this relationship. These findings underscore the importance of accurate allergy assessment and de-labelling.

Background: Cardiovascular disease (CVD) remains a global health burden. Despite the benefits of pharmacological therapy, medication adherence remains poor. Understanding the barriers and enablers across diverse settings is essential for developing effective, context-specific interventions.

Objective: To explore barriers and enablers to cardiovascular medication adherence across diverse populations using qualitative evidence synthesis.

Methods: A systematic review was conducted in accordance with PRISMA guidelines (PROSPERO registration ID: CRD42024588402). Studies were sourced from Medline, Embase, PsycINFO, and CINAHL. Purposive maximum variation sampling was used to examine key population groups: low-income countries, underserved communities, rural populations, and primary vs. secondary CVD prevention settings. Framework analysis, based on the World Health Organization’s adherence model, guided the synthesis approach. Sub-framework analysis identified cross-group similarities and differences.

Results: Of 145 eligible studies, 27 were sampled. Common barriers included fear of medication side effects, limited symptom awareness, negative beliefs about medication, and poor communication with providers. Enablers included strong provider relationships, a clear understanding of treatment purpose, simplified drug regimens, and social support. Key differences emerged: individuals in primary prevention settings often reported non-adherence due to the absence of symptoms, which led to a low perceived urgency or necessity for medication. In contrast, those in secondary prevention, having experienced a cardiovascular event, expressed a stronger perceived need for medication. Structurally disadvantaged groups; including low-income populations, rural residents, and Indigenous communities, faced additional barriers such as mistrust in the healthcare system, financial hardship, travel-related burdens, and limited access to providers.

Conclusion: Improving cardiovascular medication adherence requires context-specific strategies that address systemic barriers. These findings inform the design of future interventions by emphasising the need for co-designed, patient-centred approaches that reflect diverse lived experiences. They also provide actionable insights for research, clinical practice, and health policy, supporting the development of sustainable and equitable solutions across diverse populations.

Keywords: Medication-adherence, multimorbidity

Introduction: The GSK (Arexvy), Pfizer (Abrysvo), and mResvia (Moderna) respiratory syncytial virus (RSV) vaccines are both indicated for adults aged ≥60 years, but only Abrysvo is approved for use in pregnancy.
Aims: This descriptive study examined characteristics and outcomes of adverse event (AE) reports of marketed RSV vaccines to the United States FDA Vaccine Adverse Event Reporting System (VAERS).
Methods: This retrospective analysis examined VAERS reports between May 1, 2023 and February 28, 2025 and focused on AE reports related to RSV vaccines. Patient characteristics (age and sex) and AE outcomes (death, life-threatening illness, emergency room visits, hospitalization, disability, and birth defect) were summarized. The top 15 most frequently reported AEs for Arexvy and Abrysvo were described.
Results: Significant numbers of RSV vaccines were administered to individuals <18 years old [Arexvy (n=13, 0.3%), Abrysvo (n=58, 2.8%), mResvia (n=1, 3.0%), and unknown brand (n=2, 2.9%)] and those aged 18-59 (Arexvy (n=288, 5.9%), Abrysvo (n=294, 14.0%), and mResvia (n=5, 15.2%)]. Higher proportion of RSV vaccines were administered to females [Arexvy (66.0%), Abrysvo (63.0%), mResvia (75.8%)]. A total of 7088 AE reports related to RSV vaccines were identified: Arexvy (n=4882, 68.9%), Abrysvo (n=2105, 29.7%), mResvia (Moderna, n=33, 0.5%), and unknown brand (n=68, 1.0%). Hospitalization [Arexvy (4.0%), Abrysvo (8.8%)], life-threatening illness [Arexvy (1.0%), Abrysvo (8.8%)], disability [Arexvy (1.2%), Abrysvo (1.9%)], and death [Arexvy (0.6%), Abrysvo (0.8%)] were reported. The top 15 most frequently reported AEs for Arexvy and Abrysvo were similar including pain and fatigue. However, significant proportions of AEs for Arexvy were Exposure During Pregnancy (6.7%) and Wrong Product Administered (5.3%). About 5.0% of AEs for both Arexvy and Abrysvo were Product Administered to Patients of Inappropriate Age.
Conclusions: Preventable administration errors related to RSV vaccines are observed in clinical practice, which calls for proper education and training among healthcare professionals.

Introduction: Previous studies from various countries and regions have demonstrated that bloodstream infections (BSIs) pose a substantial disease burden. However, most studies are limited by incomplete clinical characterization, lack of distinction between infection-related and unrelated mortality, and a narrow focus on specific BSI types without considering host-pathogen interactions.
Aims: To comprehensively assess the burden of disease attributable to BSIs across entire clinical trajectories, stratified by different criteria.
Methods: To better characterize the clinical trajectories of BSIs, electronic medical records of patients discharged from all public hospitals in Hong Kong between 2012 and 2021 were utilized to identify bacterial BSI events. Each BSI event was temporally defined by identifying the entire duration of infection over time and subsequently categorized according to the causative pathogens and targeting antimicrobial resistance (AMR) patterns. Combined with patient demographics and clinical characteristics, the disease burden of BSI was estimated by evaluating the incidence, BSI-associated mortality, case fatality risks (CFRs), and the clinical course of infection.
Results: During our study period, a total of 143,776 BSI events finally identified. The overall incidence and BSI-associated mortality rates were 101 events per 100,000 person-years and 28 deaths per 100,000 person-years after age standardization, with a CFR of 14.6% (95% CI, 14.4-14.7%). The median course of infection per BSI event was 11 (IQR, 6-18) days. Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Acinetobacter species are major contributors to the disease burden of BSIs, with our targeting AMR strains associated with a consistently higher burden compared to their susceptible counterparts.
Conclusion: Our study characterizes the variations in the disease burden of BSIs among hospitalized patients, highlighting the influence of both patient characteristics and pathogen-related factors. These findings underscore the importance of individualized risk assessment and the implementation of targeted prevention and treatment strategies to reduce the overall impact of BSIs.

Introduction
People with reduced kidney function experience worse outcomes following non-ST elevation myocardial infarction and are largely excluded from relevant clinical trials. Thus, there is clinical uncertainty about the benefits versus risks of early invasive versus conservative NSTEMI management in this population, and to what extent management strategies changed during the COVID-19 pandemic.

Aims
To evaluate variation in NSTEMI management during the COVID-19 pandemic, and use this variation to study the clinical and cost-effectiveness of early invasive versus conservative NSTEMI management among people with reduced kidney function.

Methods
We used data from the British Heart Foundation Secure Data Environment (English primary and secondary care) to describe variation in NSTEMI management during the COVID-19 pandemic. This variation was used to compare the clinical and cost-effectiveness of NSTEMI management in an instrumental variable analysis to reduce the risk of unmeasured confounding. Our primary clinical outcome was all-cause death at 1-year. We triangulated our results with other analytical methods (including clone-censor-weighting) to consider other biases (namely, immortal time bias).

Results
We included 16,655 adults who presented with NSTEMI between Nov-2019 and Dec-2024 and who had an estimated glomerular filtration rate <60ml/min/1.73m2. Using the hospital’s tendency to manage early invasively vs conservatively as an instrumental variable, amongst those who survived the first 7 days of the admission, there was no evidence of a benefit of early invasive management on 1-year all-cause mortality (Hazard Ratio (HR) 0.84, 95% Confidence Interval (CI) 0.46 to 1.44), and uncertain cost-benefit (-£243, 95% CI -£4,386 to £3,900). The clone-censor-weighted analysis (addressing immortal time bias) was biased by unmeasured confounding (HR 0.65, 95% CI 0.63 to 0.67 ).

Conclusions
In patients with NSTEMI and reduced kidney function, there is no evidence that a strategy of early invasive management improves survival or lowers costs compared to using a conservative management strategy.

Introduction: Dental devices play a critical role in delivering quality oral healthcare, but are not without risk. Adverse events associated with dental devices (DDAEs) can compromise both patient safety and clinical outcomes. Traditional pharmacovigilance strategies, such as spontaneous reporting, often underrepresent device-related events, especially in dentistry, due to underreporting, lack of awareness, and limited follow-up mechanisms. By contrast, a prospective approach may provide more comprehensive and systematic data on device safety.
Aim: To determine the prevalence, severity, causality, and characteristics of DDAEs through a structured prospective materiovigilance system and develop safety guidelines for commonly used dental devices.
Methods: This prospective observational study was conducted over 6 months at a tertiary care dental hospital. Data on DDAEs were collected, analyzed, and classified using standardized tools and criteria for severity and causality. Comparisons were made considering the limitations of spontaneous reporting systems.
Results: In a cohort of 6,000 dental outpatients, 526 instances of DDAEs were recorded, indicating a prevalence of 8.77%. Events were more frequent among females (56%), pediatric (29.46%), and geriatric (13.7%) groups. Most DDAEs were linked to low/moderate-risk devices (57.6%), and 6.27% involved high-risk devices. Serious adverse events occurred in 18% of the patients. Invasive and sterile devices contributed to 50.7% and 15% of the DDAEs, respectively, and 55.5% involved single-use devices. The causality assessment revealed 59.5% related and 31.9% probable associations. SOPs were developed for the top 100 dental devices, from procurement to disposal.
Conclusion: Prospective materiovigilance identified a higher prevalence of DDAEs than that typically captured by spontaneous reporting, demonstrating the value of proactive surveillance. The implementation of SOPs and materiovigilance training can strengthen reporting systems, promote early detection, and enhance patient safety in dental practice.


Keywords: Medical Devices, Adverse events, Materiovigilance

Introduction: Autism Spectrum Disorder (ASD) prevalence is rising globally. Prenatal medication exposure has been linked to ASD risk, but most research has focused on a narrow range of drug classes.

Aims: To perform a hypothesis-free screen of maternal Level-3 ATC drug classes and assess their associations with ASD in offspring.

Methods: Using Japan’s JMDC claims database, we identified mother–child pairs with ≥1 year of maternal history before delivery and ≥2 years of child follow-up. Oral medications were classified at ATC Level 3; exposure was defined as ≥2 prescription claims during the 3-month pregnancy period. ASD at ≥2 years (ICD-10 F84) was the outcome. Multivariable logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs): Model 1 adjusted for maternal age and child sex; Model 2 additionally for maternal psychiatric and neurological disorders; Model 3 further for indication-specific comorbidities (e.g., diabetes, hypertension, thyroid disease). Sensitivity analyses used 36- and 32-week gestational windows.

Results: Among 227 247 children, 11 872 (5.2 %) were diagnosed with ASD. In Model 1, 27 drug classes, including antipsychotics, thyroid-related, and gastrointestinal agents, showed elevated ORs. Most estimates were reduced by 10–30 % in Model 2. In fully adjusted Model 3, persistent associations remained for antiepileptics (N03A; aOR 1.30, 1.00–1.68), antithyroid agents (H03B; aOR 1.30, 1.00–1.68), laxatives (A06A; aOR 1.10, 1.01–1.20), and systemic adrenergic respiratory drugs (R03C; aOR 1.60, 1.06–2.40). Associations with psychotropic drugs attenuated to null after adjusting for maternal psychiatric history.

Conclusions: We re-confirmed the elevated ASD risk associated with antiepileptic drugs and identified novel associations with antithyroid agents, gastrointestinal motility drugs, and bronchodilators. The absolute risk attributable to these medications was very low, indicating no need for altered clinical practice. This is the first systematic evaluation of these associations and will guide future studies using causal-inference methods.

Keywords: Autism, Pregnancy drugs, Hypothesis-free screening.

Introduction: Statins are the cornerstone treatment for the primary prevention of cardiovascular disease (CVD), but intolerance and side effects can hinder adherence. Berberine, with promising lipid-lowering effects and good tolerance, presents a potential alternative for statin-intolerant patients.
Aims: To estimate and compare the cost-effectiveness of statins, berberine, and their combined use for primary CVD prevention.
Methods: The Scottish CVD Policy Model was used to predict long-term health and cost outcomes in Scottish adults aged 40 years or older without pre-existing CVD. Intervention and cost inputs were sourced from published literature and health service cost data. The primary outcome measure was the lifetime incremental cost-effectiveness ratio (ICER), evaluated as cost per quality-adjusted life year (QALY) gained. The intervention strategies of no intervention, atorvastatin 20 mg per day (“statins”), berberine 1000 mg per day (“berberine”), simvastatin 20 mg plus berberine 1500 mg per day (“combined intervention 1”) and simvastatin 20 mg plus berberine 900 mg per day (“combined intervention 2”) were analyzed for individuals with ASSIGN risk scores ≥20% and ≥10%.
Results: All intervention strategies were cost-effective (statins: ICER £1,260.7/QALY, 95%CI: £-2,528.6/QALY ~ £2,305.5/QALY; berberine: ICER £6,192.4/QALY, 95%CI: £4,655.7/QALY ~ £11,387.0/QALY; combined intervention 1: ICER £5,506.5/QALY, 95%CI: £4,506.8/QALY ~ £10,732.0/QALY; combined intervention 2: ICER £3,846.4/QALY, 95%CI: £3,107.0/QALY ~ £5,270.1/QALY), compared to no intervention, at the threshold of ICER of £20,000 per QALY. Compared to statins, berberine was less cost-effective, but the combination remained cost-effective (£10,198.6/QALY [95%CI: £6,740.4/QALY ~ £58,473.3/QALY]; £6,362.8/QALY [95%CI: £5,187.7/QALY ~ £12,499.2/QALY]) at the threshold of £20,000/QALY. Notably, when using drug costs from China, berberine and combined interventions were preferable to statins alone.
Conclusions: Statins, berberine, and combined interventions are all cost-effective options for primary CVD prevention. Berberine could be considered a valuable complementary therapy, particularly if its price decreases below that of statins.
Key words: statins; berberine; combination; cost-effective

Introduction: Self-controlled case series (SCCS) are frequently used in vaccine safety studies, but is ill-suited for outcomes that affect future exposure or censor observation period, such as mortality. We aimed to compare estimates from three design options: the modified SCCS developed for this situation, the standard SCCS, and the unidirectional SCCS.

Methods: Using Malaysia’s nationwide data from 2021-2022, we analysed deaths (all-cause deaths, non-COVID-19 deaths, cardiovascular deaths) among individuals aged ≥5 years. Exposure was vaccination with BNT162b2, CoronaVac, or ChAdOx1. Modified SCCS model was used for primary analysis, and compared with two other models: standard SCCS and SCCS unidirectional (follow-up starts at vaccination). Incidence rate ratio (IRR) and 95% confidence interval (CI) were computed using conditional Poisson regression for risk of deaths 21-day after vaccination versus referent window.

Results: The modified SCCS model showed that the risk of all-cause deaths in the 21-day focal window was not significantly increased following vaccination (all doses: IRR 0.60; 95%CI 0.59-0.61). The IRRs were below 1 across vaccine doses (doses 1, 2, and 3) and vaccine types. Estimates from the standard SCCS model were slightly increased (all doses: IRR 1.04; 95% CI 1.02-1.05) with dose-specific IRRs ranging from 0.97 to 1.17. The unidirectional model yielded lower estimates than the standard SCCS (all doses: IRR 0.74; 95%CI 0.73-0.76) and IRR ranged from 0.66 to 0.84. Similar results were observed for non-COVID-19 deaths and cardiovascular deaths.

Conclusion: As expected, the standard SCCS may overestimate the effect of vaccination on an outcome like mortality that violates key design assumptions. Both the modified SCCS and the unidirectional SCCS appear viable alternatives that address this issue. However, estimates from the modified model were lower than those of the unidirectional model. These findings support the favourable safety profile of these COVID-19 vaccines, with no evidence of increased mortality following vaccination.

Introduction:
Medication errors, particularly in self-administration, are a significant risk to patient safety, leading to adverse drug events (ADEs). Studies indicate that medication errors occur in 5% to 10% of hospital inpatients, with self-administration errors contributing substantially. Existing assessment tools focus mainly on provider-administered medications, overlooking patient-administered errors. The Self-Administration Medication Error (SAME) tool was developed to address these challenges.
Objectives:
To develop and validate the SAME tool in patients of a tertiary care hospital
Methods:
This cross-sectional, quantitative study was conducted at Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, from May 2023 to April 2024. The tool was developed through a literature review and patient interviews, resulting in ten items evaluating various aspects of self-administration. Content validity was assessed by four experts using a 4-point Likert scale, and the Content Validity Index (CVI) was calculated. The tool was then tested on 100 adult patients with chronic diseases (e.g., diabetes, hypertension, cardiovascular diseases, epilepsy) attending the JIPMER pharmacy. Internal consistency was measured with Cronbach's alpha, and Pearson product-moment correlation analysis was used to assess validity.
Results:
The SAME tool demonstrated strong content validity, with all items achieving a CVI of ≥0.88 and an overall Scale-Level CVI (S-CVI) of 1.0. Cronbach's alpha was 0.815, indicating good internal consistency. Pearson correlation coefficients for individual items ranged from 0.492 to 0.740, all statistically significant (p < 0.05), confirming the tool's validity. The estimated prevalence of self-administration errors among participants was 17%, emphasising the need for effective assessment tools.
Conclusion:
The SAME tool is a reliable and valid for identifying self-administration errors, highlighting its potential to enhance patient safety and improve medication management. Future research should explore its application across diverse healthcare settings.
Keywords: Self-Administration, Medication Errors, Tool Development, Patient Safety.

Introduction
The Korea Institute of Drug Safety and Risk Management (KIDS) conducts monthly pharmacovigilance activities to manage serious adverse events (SAEs) and generate drug safety information.

Aims
To identify and evaluate safety signals from reported SAEs and inform regulatory decision-making on the basis of the findings.

Methods
SAEs were extracted from individual case safety reports submitted to the Korea Adverse Event Reporting System in July 2023. Three complementary methods are used for the monthly evaluations. All cases involving death or congenital anomalies are reviewed individually to determine whether a causal relationship can be excluded. To minimize the risk of rare but serious adverse events being overlooked, a qualitative assessment is applied to designated medical events (DMEs). Quantitative analysis is also conducted using data mining techniques to detect statistically significant safety signals. Drug–DME combinations with potential safety concerns are managed as accumulations. When a causal relationship cannot be ruled out through both qualitative and quantitative analyses, further investigation and long-term monitoring are conducted. On the basis of these results, KIDS may propose safety labeling changes to the Ministry of Food and Drug Safety (MFDS).

Results
During the monthly evaluation of drug–DME combinations from reported cases, KIDS reviewed reports of SAEs of anaphylactic reactions in patients receiving lidocaine as a local anesthetic. A causal relationship between lidocaine injection and the anaphylactic reactions could not be excluded. Therefore, on the basis of the findings of this review and international regulatory information, including product information from the USA, Japan, and other countries, KIDS submitted a proposal for new safety information to the MFDS.

Conclusions
In May 2025, the product information for lidocaine was updated to include the risk of anaphylactic reactions.

Keywords: lidocaine, anaphylactic reactions, Korea Adverse Event Reporting System

INTRODUCTION: Methotrexate(MTX) is an antimetabolite drug used to treat various conditions by inhibiting the Dihydrofolate reductase(DHFR) enzyme. The adverse events(AEs) associated with MTX therapy should be considered to reduce their severity with subsequent doses. Here, disproportionality analysis using the FDA adverse event reporting system(FAERS) databases helps to identify potential signals related to MTX therapy in pediatrics.

AIM: This study aims to find the AEs associated with MTX in children and identify and characterize associated signals.

METHOD: The Open Vigil 2.1 platform was used for extraction, cleaning, and standardization of data from FAERS to retrieve AEs of MTX reported from Q4 2004 to Q4 2024 in children aged 1 to 17 years. The inclusion criteria were set to reports with a frequency greater than three and were deduplicated. The study assesses the Disproportionality through Reporting odds ratio (ROR), Proportional reporting ratio (PRR), and Chi-square test. A signal was detected if ROR >1, PRR≥2, and chi-square >4 were observed in the Frequentist data. Data analysis and visual interpretation were carried out using R-Software v 4.4.1.

RESULTS: A total of 30111 AEs were reported with MTX, with a higher occurrence in males, 15619(51.9%), than in females, 13470(44.7%). More cases were reported in the age group of 1-10(52.22%). Canada(22.3%) is ranked first among the reported countries, followed by the United States(19%). A total of 981 Preferred terms were included, and 508 signals were identified. Pseudostroke(PRR=334.164) and Pneumonia(PRR=290.577) were the strongest signals. Febrile neutropenia-FN(n=741) and Neurotoxicity(n=323) were the most frequently reported cases.

CONCLUSION: Our comprehensive study identified the significant safety signals associated with MTX and revealed that Pseudostroke and pneumonia were the strongest signals with MTX therapy, FN and Neurotoxicity were the Most reported AEs. This study warrants careful clinical consideration.

KEYWORDS: Disproportionality analysis, Methotrexate, Adverse events

Introduction:
Placenta previa (PP) is a major risk factor for maternal morbidity and mortality including peripartum hemorrhage. However, strategies to prevent PP remain largely absent. Placental inflammation due to intrauterine infections is known to increase PP risk. However, specific maternal infections and their treatment effectiveness in reducing PP have not been well-investigated. Emerging literature has shown that pregnant women with genital herpes simplex virus (GHSV) infection are at higher risk of placental inflammation.

Aims:
To determine whether treating women with GHSV infection during pregnancy reduces PP.

Methods:
A prospective cohort study was conducted among 88,205 pregnant Kaiser Permanente Northern California members. Four cohorts were established based on GHSV infection and treatment status, treatment timing and presence/absence of symptoms during pregnancy. Cox proportional hazards regression was used to estimate the risk of PP associated with GHSV infection and its treatment, while accounting for different gestational ages at outcome (PP), timing of initial treatment, and potential confounders.

Results:
Pregnant women with GHSV infection had 2.6 times higher PP risk compared to women without GHSV infection (adjusted hazard ratio [aHR]=2.62, 95% CI=2.31-2.98). Treating GHSV infection during pregnancy was associated with a 65% reduced PP risk compared to untreated GHSV infection (aHR=0.35, 95% CI=0.26-0.47). Starting treatment early in pregnancy (< 20 weeks of gestation) was more effective (aHR=0.32, 95% CI=0.23-0.44) than starting treatment after 20 weeks (aHR=0.75, 95%CI=0.36-1.58). Women with symptomatic (active) GHSV infection during pregnancy were at particularly higher risk of PP (aHR=4.99, 95% CI=4.15-6.00) than women with asymptomatic GHSV infection (aHR=1.89, 95% CI=1.59-2.23). Consequently, treating symptomatic GHSV infection was more effective, an 83% reduction in PP risk (aHR=0.17, 95%CI=0.12-0.25) than treating asymptomatic GHSV infection (aHR=0.58, 95% CI=0.35-0.97).

Conclusions:
GHSV infection increases PP risk and treating GHSV infection, especially early in pregnancy and for symptomatic GHSV, is highly effective in reducing PP risk.

Introduction Overuse of antibiotics can lead to resistance and increased healthcare costs by affecting therapy outcomes, disease incidence, length of hospital stay, and overall hospital expenses. While antimicrobial stewardship programs (AMS) address these issues, the economic impact of antibiotic consumption and resistance is rarely investigated.

Aim This study aimed to compare monthly economic outcomes of restricted antibiotic consumption and resistance between two hospital wards, focusing on: excess costs from unauthorized dispensing of restricted antibiotics, hospital stay costs, and culture sensitivity test costs.

Methods A retrospective cross-sectional study reviewed 1,928 dispensing records from two adult wards in a government hospital (March 2019–February 2020). Monthly per-patient costs were analyzed for: over-dispensed restricted antibiotics, hospital stays, and culture sensitivity tests. Restricted antibiotics included 4th generation cephalosporins, aztreonam, carbapenems, colistin, vancomycin, and linezolid. Cost outcomes were compared between Ward 1 (with a pharmacist) and Ward 3 (without a pharmacist) using statistical analysis.

Results One-year costs of over-dispensed restricted antibiotics were significantly lower by 60% in Ward 1 vs. Ward 3 (p = 0.0356). Average monthly costs for hospital stay and laboratory tests were also lower in Ward 1, but not statistically significant (p = 0.5822 and p = 0.3989, respectively). Both wards showed declining use of piperacillin-tazobactam. Levofloxacin was most prescribed in Ward 3 (350.2 DDD/1000 PD), while ciprofloxacin was more used in Ward 1 (23.3 DDD/1000 PD). Acinetobacter baumannii resistance to these antibiotics was significantly lower in Ward 1 by about 20% (p = 0.0328, p = 0.0165, p = 0.0173, respectively).

Conclusion The presence of pharmacist in Ward 1 played a crucial role in monitoring restricted antibiotics, leading to improved patient outcomes and cost savings. Reduced consumption of restricted antibiotics in both wards highlights the AMS program’s importance in minimizing unnecessary antibiotic use.

Keywords: Antibiotic consumption, antibiotic resistance, restricted antibiotics

Introduction
Malnutrition and worm infestation remain significant contributors to poor health among tribal children in India. The Koraga tribal community in South India faces unique socio-cultural and economic challenges, further worsening the risk of undernutrition. Limited parental knowledge and suboptimal practices further exacerbate the condition.
Aim: To improve parental knowledge, attitude, and practice (KAP) through a structured educational program and evaluate its impact on the nutritional status of children aged 5-10 years of Koraga tribal community.
Methods:
A quasi-experimental pre-post study was conducted among caregivers of the Koraga tribal community in rural villages of Udupi district, Karnataka. Baseline KAP was assessed among 122 families, and those scored below average (n=26) were recruited for the pilot WINS educational program. The intervention included an audio-visual module, pictographic food charts and bi-monthly home visits over six-months. Pre- and post-intervention assessments measured parental KAP, children’s anthropometry, haemoglobin (Hb) levels, stool analysis, and health-related quality of life (HRQoL) using PedsQL 4.0. Data was analysed using paired t-tests to evaluate intervention effects.
Results:
Parental KAP scores improved significantly (p<0.001) after six months. Children’s mean Hb increased from 9.39±0.75g/dL to 10.38±0.75g/dL (p<0.001), eliminating severe anaemia and reducing moderate anaemia from 92.3% to 23.1%. Nutritional indicators like BAZ-scores improved from -1.14±1.09 to -0.88±0.95 (p=0.004), WAZ scores from -2.64±1.21 to -2.51±1.11(p=0.007), while HAZ scores slightly declined from -2.75±1.05 to -2.83±0.98 (p=0.002) due to the short follow up period. HRQoL improved significantly, with child self-reported scores increasing from 43.56±6.73 to 52.34±8.36 (p<0.001) and parent proxy-report scores rising from 39.96±8.25 to 50.29±8.24 (p<0.001). Importantly, no child tested positive for worm infestation.
Conclusions:
The WINS educational intervention significantly improved parental KAP and children’s nutritional and health outcomes in Koraga tribal community. Future studies with longer follow-ups are recommended to sustain these improvements.
Keywords:
Health education intervention, Koraga tribe, Malnutrition

Introduction: Inappropriate antibiotic use and disposal contribute to antimicrobial resistance (AMR), particularly in low- and middle-income countries (LMICs). In Sri Lanka, mothers are primary caregivers and significantly influence household antibiotic practices, although misconceptions and improper disposal persist.
Aims: To assess the impact of home-based educational visits on mothers’ KAP regarding antibiotic use and disposal in the Boralesgamuwa Medical Officer of Health area.
Methods: This study explores the effectiveness of home-based educational visits in improving mothers’ knowledge, attitudes, and practices (KAP) regarding antibiotic use. A quasi-experimental study was conducted among 110 eligible mothers (aged 18–50, Sinhala/Tamil/English-speaking), divided into intervention (n=55) and control (n=55) groups. Full randomization was not feasible due to household availability and willingness. The control group received no intervention. Mothers with mental illness or sensory impairments were excluded. A pre-tested, adapted KAP questionnaire (15 knowledge: 10 use, 5 disposal, 7 attitude, 5 practice questions) was used. The intervention involved home visits, leaflets, and weekly calls. KAP changes were assessed using paired and independent t-tests via SPSS v25.
Results: The intervention group showed a statistically significant improvement in knowledge (mean score from 6.5 to 8.9; p = 0.001), attitudes (from 4.1 to 6.3; p = 0.003), and practices (from 2.7 to 4.5; p = 0.004). In contrast, the control group showed no significant improvement: knowledge (6.4 to 6.6, p = 0.108), attitudes (4.2 to 4.4, p = 0.097), and practices (2.8 to 2.9, p = 0.152). Correct disposal methods, such as pharmacy returns and burning, increased from 9.1% to 38.2%. In contrast, the control group showed minimal improvement and persistent misconceptions.
Conclusion: Home-based educational visits effectively improved mothers’ antibiotic-related KAP, particularly in proper disposal practices. This low-resource, culturally acceptable approach can be integrated into national public health initiatives to mitigate AMR in Sri Lanka.
Keywords: Antibiotic, home-based educational visits, mothers

Background:
Access to comprehensive, evidence-based education on the risks and benefits of sex hormone therapy (SHT) is fundamental for empowering gender minority individuals to make informed decisions about their healthcare. Equally, it equips healthcare providers with the knowledge required to offer safer, more effective, and person-centered care. In the Indian context, particularly in regional and semi-urban settings, such as Mysuru, there is a significant lack of structured guidance and educational support around gender-affirming hormone therapy. Many transgender individuals initiate SHT without formal medical supervision, which can result in inconsistent follow-up, underreported side effects, and a poor understanding of long-term health implications.
Aim: This study sought to explore the demographic and clinical characteristics of transgender individuals undergoing SHT in Mysuru and to assess their awareness, understanding, and perception of the therapy's associated risks and benefits. The goal was to identify key gaps in knowledge and clinical literacy that could hinder safe and effective hormone use.
Methods:
A mixed-methods approach was employed. Twenty-three participants (20 transwomen and 3 transmen) were selected using purposive sampling. Data were collected through structured, self-administered questionnaires, capturing demographics, details of hormone use, onset year, and the type and frequency of perceived adverse effects.
Results:
Most transwomen began SHT between 1991 and 2000 using oral estradiol formulations. Transmen typically used injectable or transdermal testosterone preparations. Psychiatric symptoms—especially forgetfulness—were frequently reported among transwomen, while transmen highlighted masculinizing physical changes such as hair growth. Notably, comorbidities like hypertension and diabetes were either underreported or poorly managed, indicating gaps in patient education and monitoring.
Conclusion:
The findings underscore the urgent need for targeted health literacy programs and communication strategies. Culturally appropriate educational interventions are essential to ensure that gender minority individuals can safely navigate the complexities of long-term hormone therapy.
Keywords: Patient education, Gender minorities, Hormonal risk awareness, Transgender medicine

Introduction: Potential immune-mediated disorders (pIMDs) and adverse pregnancy outcomes (APOs) bring significant public health burdens. However, efficiently and accurately identifying these complex cases within regional healthcare databases requires specifically developed and validated algorithms.
Aims: To enable accurate identification of pIMDs and APOs from real-world clinical data by refining a fuzzy retrieval-based diagnostic algorithm.
Methods: We conducted a validation study using data from the Xiamen Health and Medical Big Data Center (Sep 1, 2016–Dec 31, 2022). A fuzzy retrieval algorithm using Chinese diagnostic terms or ICD-10 codes was applied to identify suspected cases. A 10% random sample underwent manual chart review by two clinicians, with adjudication by a third if needed. Cases were classified as confirmed, not confirmed, or insufficient information. Positive predictive values (PPVs) were calculated as the proportion of confirmed cases among those reviewed. and refinement strategies were evaluated based on visit type, hospital level, visit frequency, and precise case retrieval strategy specificity.
Results: The PPV-optimized algorithm for identifying pIMDs cases was the presence of three hospitalizations or physician claims for pIMDs during the study period. Compared with the pre-optimization period, the number of pIMDs with PPVs >70% increased from 2 to 6. The remaining 4 pIMDs conditions demonstrated lower validity. The optimal algorithm for identifying APOs cases was Clear Chinese diagnostic name and Fuzzy Chinese diagnostic name AND ICD-10 code. Compared with the pre-optimization optimization period, the number of APOs with PPVs >70% increased from 10 to 25, while the remaining 3 APOs conditions demonstrated lower validity.
Conclusions:The initial fuzzy algorithm showed limited validity for several conditions. Refinement based on clinical encounter frequency and diagnostic specificity improved case ascertainment. These findings support the feasibility of using structured real-world data for safety signal detection in large-scale database studies.
Keywords: Potential immune-mediated disorders; adverse pregnancy outcomes; Positive predictive values

Introduction: Tracheal tubes are critical medical devices used to secure airway patency during surgery, intensive care, and emergencies. Evaluating adverse events (AEs) through materiovigilance approach, is vital to enhance safety, performance. Retrospective data was collected from the FDA’s Manufacturer and User Facility Device Experience (MAUDE) database, a comprehensive repository of real-world reports that compiles details of device-related events.

Aim: This study aimed to evaluate the frequency, event type, and reporting characteristics of AEs related to tracheal tubes reported in the MAUDE database over a 10 year period.

Methods: This retrospective descriptive study investigated AEs related to tracheal tubes reported in the MAUDE database from January 1, 2015, to June 30, 2025. Relevant data were extracted using appropriate FDA product code (BTR) and downloaded within the selected period. Detailed analysis was conducted to identify patterns in device-related problems, event types, providing insights into the safety, performance of tracheal tubes.

Results: Over a 10-year period, the MAUDE database documented 12,602 unique AEs reports related to tracheal tubes. The most frequently reported device issues include use-related problems (13%), inflation problems (9.99%), leak/splashes (5.13%) and material split/cut/torn (2.74%). Among reported event types, (78.30%) were malfunctions, (18.43%) involved injuries, and (1.12%) reported deaths. The highest number of events was reported in 2024 (22.99%), followed by 2019 (12.34%), and 2021, 2023 (9.32%). Majority of reports originated from the United States (51.72%), followed by Japan (14.36%), Switzerland (7.98%) and France (5.94%). Health care professionals (86.92%) were the primary reporters, with contributions from respiratory therapists (34.21%), physicians (28.37%), and nurses (24.34%).

Conclusion: These findings highlight the need for enhanced materiovigilance to reduce tracheal tubes related AEs. Recognizing failure modes support safer device safety. This study offers guidance for clinicians, and regulatory authorities in improving patient outcomes.

Keywords: Tracheal tube safety, Materiovigilance, MAUDE adverse event reporting

Introduction: Severe paediatric respiratory tract infections (RTIs) lead to a major global health burden causing approximately 740,000 deaths in children under five. Accurate assessment of RTI severity is critical to guide timely clinical interventions. This study addresses a critical gap by jointly evaluating RTI severity and drug utilization in low resource hospital settings.
Aims: To determine the severity of RTIs through PRESS scoring system and examine prescription patterns using WHO drug-utilization indicators in hospitalized children.
Methods: A six month prospective, cross sectional study was conducted in the paediatric ward of a tertiary care hospital. Children aged 0–12 years admitted with any RTI were enrolled. A structured Case Report Form was developed to record demographics, lab values, diagnosis, medications prescribed, and the five PRESS score parameters, which guided clinical severity assessment. All prescribed medications including route, antibiotic use, and brand versus generic status were evaluated using WHO prescribing indicators. Data were analysed using descriptive statistics and chi-square tests and interpreted graphically.
Results: A total of 123 children (mean age 4.2 ± 3.1 years; 54% male) with various respiratory tract infections were enrolled. Lower RTIs were predominant (83.7%), with 69.9% of admissions in children under five. According to PRESS scoring; most of the cases (42.3%) were mild. Analysis of prescribing patterns revealed that 58.3% of all drugs were administered parenterally; antibiotics accounted for 34.7% of drug encounters. A significant discrepancy was observed between prescribed daily doses and recommended standards (p < 0.05).
Conclusion: The study highlights a high burden of lower RTIs in young children with frequent use of parenteral and branded antibiotics, and notable dosing inconsistencies. These findings from a comprehensive DUE, underscore the need for enhanced antibiotic stewardship and adherence to dosing guidelines.
Keywords: RTI, PRESS, DUE

Introduction: Denosumab was placed under EMA additional monitoring (AM) in April 2013 and received an FDA black box warning (BBW) in January 2024 for severe hypocalcemia in patients with chronic kidney disease. The impact of these regulatory actions on adverse event (AE) reporting patterns and signal detection remains unclear.
Aims: To evaluate changes in hypocalcemia reporting patterns for denosumab and detect signals before and after regulatory interventions by the FDA and EMA, using VigiBase.
Methods: A disproportionality analysis was conducted using VigiBase from May 26, 2010 to June 1, 2025. Bisphosphonates—alendronate, risedronate, ibandronate, and zoledronate—were used as comparators. AEs of interest were hypocalcemia and calcium metabolism disorders. Reports with only denosumab or bisphosphonates as suspected drug were analyzed using Poisson regression across phases;before AM (Phase 1), between two regulatory actions (Phase 2), and after BBW (Phase 3). Signal detection was performed per phase using Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR), and Information Component (IC), with thresholds PRR≥2, ROR≥2, IC05>0, and χ2≥4, requiring ≥3 reports.
Results: In total, 2,374 hypocalcemia reports for denosumab and 773 for bisphosphonates were identified. Among denosumab reports, 8.1% were reported in Phase 1, 78.5% in Phase 2, and 13.4% in Phase 3. Compared to Phase 1, hypocalcemia reporting declined in Phase 2 (RR=0.64; 95% CI: 0.57–0.72) and rose in Phase 3 (RR=8.24; 95% CI: 7.13–9.53). Disproportionality analysis showed consistent signals, strongest in Phase 1 (PRR=25.15; ROR=25.82; IC=3.23), and still above thresholds in Phases 2 and 3.
Conclusions: Regulatory actions may influence AE reporting patterns. Signal strength peaked after initial approval. Reporting declined in Phase 2, possibly due to limited awareness as AM did not specify hypocalcemia and rose in Phase 3 after a targeted warning. These findings highlight the need to consider regulatory context when interpreting signals.
Keywords: Signal detection; Real-World Data; Denosumab;

Background: Adverse drug reactions (ADRs) significantly impact global health, contributing to a substantial proportion of hospital admissions (0.2% to 59.6%) and a 1.8% fatality rate, particularly affecting low- and middle-income countries (LMIC). The Medication Regimen Complexity Index (MRCI) is a measure of medication regimen complexity, which takes into account factors such as dosage forms, frequencies, and administration routes. It reflects the challenges faced in managing medication regimens, particularly in populations with chronic conditions like HIV.
Objectives: To determine the correlation of MRCI in PLHIV with the hospitalisation rate.
Methodology: enrolled 285 adults (PLHIV) between August 2019 and November 2021, with a 78-week follow-up. Demographic profiles, ADRs, clinical and MRCI data were collected and analysed using EpiData and SPSS Version 11. The MRCI tool consists of three parts: A assesses pharmaceutical formulation, B evaluates drug administration frequency, and C examines medication administration directions. Each section is scored independently, and the total MRCI score is calculated by summing scores.
A median ART duration of 6 years (IQR, 4–9). Clinical data were collected, validated using EpiData, and analysed with SPSS version 11.

Results of objects completed till date: In this study of 285 participants, 48% were female. A median ART duration of 6 years (IQR, 4–9).Nine (3%) participants were lost to follow-up.
Statistical analysis using the Chi-Square test (χ² = 6.233, df = 1, p = 0.013) and Spearman's rank correlation coefficient (ρ = 0.148, p = 0.012) revealed a significant association between Medication Regimen Complexity Index (MRCI) and Hospitalisation due to Adverse Drug Reactions (ADR).
Specifically, as the MRCI increases, there is a corresponding increase in the likelihood of hospitalization due to ADR.

Conclusion: This finding suggests that a more complex medication regimen, as measured by MRCI, may be associated with a higher risk of experiencing adverse drug reactions leading to hospitalisation.

Introduction: Antimicrobial resistance is a growing threat to public health systems across the world, making harder to treat infectious diseases. To address this the WHO introduced the AWaRe framework, serving as a surveillance and policy tool in 2017, categorizing antibiotics into Access, Watch and Reserve groups to promote rational antibiotic use and guide antibiotic stewardship efforts.

Aim: To evaluate the antibiotics prescription in community pharmacy as per the AWaRe classification and to identify the prescribing factors associated with the AWaRe class of antibiotics.

Methodology: A prospective cross-sectional study was conducted at Radha Medicals, a community pharmacy in Udupi, Karnataka, India over ten months period. Random prescription samples were collected, allowing us to estimate the prevalence of AWaRe class of antibiotics in community pharmacy prescriptions. Antibiotics were classified based on WHO AWaRe Classification (2023). The frequency and association between patient demographic characteristics, specialization of the physician with AWaRe classification were analysed.

Results: Out of a total of 634 prescriptions reviewed, majority (58.8%) contained antibiotics from the WHO Watch category, followed by the Access (39.1%) and Reserve (2.1%) categories. The mean age of the patients were young adults aged 18 to 35 years, making up about 60.7% of the group, followed by middle-aged adults. In terms of gender, there were slightly more males (52.8%) than females. Majority of prescriptions originated from doctors with MBBS and MD qualification, who are prescribing antibiotics across all three AWaRe categories, indicating their significant role in antibiotic selection.

Conclusion: A high proportion of prescriptions from the Watch category is a concern, as overuse can make them less effective due to increased resistance. To address this issue, the study calls for strong antibiotic stewardship programs to guide prescribers and pharmacists on proper antibiotic selection, dosage, and duration.

Keywords: AWaRe Classification, Antimicrobial resistance, Antimicrobial Stewardship Program, Community pharmacy, Prescription

Introduction: Nebivolol, a selective beta-1 adrenergic receptor blocker, is commonly prescribed for the management of hypertension and heart failure. While its safety profile is well established, rare and serious adverse drug reactions (ADRs) may remain undetected until post-marketing surveillance. Signal detection and disproportionality analysis are essential tools to uncover such potential ADRs.

Aim: This study aimed to identify and evaluate the signal of melaena associated with nebivolol use, as reported in the USFDA Adverse Event Reporting System (FAERS) database.

Methodology: An in-depth case/non-case retrospective disproportionality analysis was conducted in the publicly available FAERS database for Nebivolol. Nebivolol was approved by FDA on 17 December 2007. All the reports of Nebivolol were analyzed. The investigation delved into the USFDA adverse event reporting system database, employing the top 2 data mining algorithms in widespread use for signal detection such as Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR) from the OpenVigil database. A value of PRR≥2 and ROR-1.96SE>2 was considered as positive signal.

Results: Among the total 30,668,520 FAERS reports, 4,685 were related to Nebivolol. The Nebivolol reports (4,487) were classified as serious, and many fatal reactions were reported. The total number of adverse events reported for Melaena is 97 on OpenVigil. On analysis, data mining algorithms showed the results as ROR of 6.22(5.092; 7.602) and PRR of 6.19 (5.07; 7.558). The ROR and PRR confirmed the occurrence of the adverse reaction cachexia for Nebivolol.

Conclusion: This analysis suggests that melaena may be a potential adverse reaction in patients receiving nebivolol. Healthcare professionals should be vigilant for signs of gastrointestinal bleeding in patients treated with nebivolol. Further epidemiological studies are warranted to validate this signal and clarify its clinical significance.

Keywords: Nebivolol, Signal detection, Melaena, FAERS, Disproportionality analysis

Background: Tirzepatide is an FDA-approved drug that works through dual incretin-based mechanisms to manage blood sugar levels and promote weight loss in individuals with Type-2 Diabetes Mellitus. Signal detection is used to identify previously unrecognized adverse drug reactions associated with a medication.
Objective: The study aimed to identify the newly reported signal associated with Tirzepatide in the USFDA Adverse Event Reporting System (FAERS) database.
Methodology: In this study, data from the FDA Adverse Event Reporting System (FAERS) was analyzed to identify a potential novel adverse event associated with Tirzepatide. The Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR) were obtained from the OpenVigil database. A signal is considered positive if the number of adverse events (AE) exceeded 3, PRR was ≥2, the lower limit of the 95% confidence interval for ROR (ROR − 1.96SE) >2, and the chi-square value was greater than 4.
Results: The database contains a total of 30,668,520 reported adverse events. Among these, 55,341 were associated with Tirzepatide following its approval by the USFDA in 2022. According to OpenVigil data, there were 29 cases of intermenstrual hemorrhage and 38 cases of postmenopausal hemorrhage linked to the drug. The analysis revealed a PRR of 2.792 (95% CI: 1.936–4.026) and an ROR of 2.793 (95% CI: 1.937–4.028) for intermenstrual haemorrhage. For postmenopausal haemorrhage, the PRR was 6.7 (95% CI: 4.854–9.248) and the ROR was 6.704 (95% CI: 4.856–9.255). These findings indicate the presence of a statistically significant positive signal. Though the incidence of intermenstrual and postmenopausal hemorrhage reports is currently low ie.,15 and 27 respectively, the observed disproportionality suggests a potentially emerging pharmacovigilance concern
Conclusion: The results revealed that Tirzepatide may cause Abnormal uterine haemorrhage. The genes and proteins showed association between Tirzepatide and Abnormal uterine haemorrhage.
Keywords: Tirzepatide, Intermenstrual hemorrhage, Postmenopausal hemorrhage, Signal Detection, Adverse Drug Reactions

Introduction: The increasing incidence of serious adverse events (SAEs) and fatalities linked to Ferric Carboxymaltose (FCM) necessitates a rigorous re-evaluation of its safety profile, highlighting an urgent public health concern.

Aim: This study aimed to comprehensively assess the safety of FCM by identifying and characterizing its associated SAE signals using extensive pharmacovigilance data and a systematic review of case reports.

Methods: A retrospective case/non-case study was conducted utilizing FDA Adverse Event Reporting System (FAERS) and VigiBase data from Q4 2003 to Q4 2024. Signal detection employed Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR), and Information Component (IC). Concomitant medication influence was refined using OpenVigil 2.1. A systematic search of PubMed, Scopus, and Google Scholar (inception to April 12, 2025) identified FCM-induced adverse event case reports.

Results: While 46 deaths were reported in FAERS, no significant death signal was detected (PRR=0.3, lower bound (LB) ROR=0.2, IC025=-2.3). However, significant safety signals emerged for SAEs including anaphylactic shock (PRR=3.9, LB ROR=2.3, IC025=1.0), circulatory collapse (PRR=14.6, LB ROR=10.5, IC025=3.1), respiratory distress (PRR=9.6, LB ROR=7.1, IC025=2.6), hypophosphatemia (PRR=520.7, LB ROR=530.1, IC025=8.0), and arrhythmia (PRR=3.3, LB ROR=2.2, IC025=1.0). These signals remained robust after adjusting for concomitant medications. VigiBase data similarly revealed 42 fatal cases and potential signals for hypersensitivity (PRR=4.5, LB ROR=4.4, IC025=2.1), anaphylactic shock (PRR=2.3, LB ROR=1.9, IC025=0.9), circulatory collapse (PRR=7.2, LB ROR=6.0, IC025=2.5), respiratory distress (PRR=6.9, LB ROR=5.7, IC025=2.5), and hypophosphatemia (PRR=245.1, LB ROR=234.8, IC025=7.5) with Ferinject. Eleven systematic review case reports further corroborated these SAE associations.

Conclusions: This study definitively reveals that FCM is associated with SAEs. Healthcare providers must exercise heightened vigilance, meticulously weighing the therapeutic benefits against patient-specific risks when prescribing FCM.

Keywords: Disproportionality Analysis; Ferric Carboxymaltose; Serious Adverse Events; Systematic Review.

Introduction: Vulvovaginal candidiasis is highly prevalent among pregnant women, and its treatment is crucial. However, there is a lack of evidence regarding the risks to fetal outcomes associated with the use of antifungal medications during the first trimester of pregnancy.
Aim: This study examined the association between antifungal use during the first trimester of pregnancy and the risk of major congenital malformations (MCMs) in infants.
Methods: We conducted a cohort study using a pregnancy cohort nested in JMDC Claims Database from Japan, including women who gave birth between 2010 and 2019. Among the antifungal medications frequently dispensed or prescribed during the first trimester of pregnancy in this cohort, miconazole, oxiconazole, and isoconazole were assessed for the risk of MCMs, using clotrimazole, an antifungal medication with established safety during pregnancy, as a reference. Propensity score overlap weighting was applied to adjust for covariates, including maternal age, delivery year, maternal comorbidities, number of diagnoses and prescribed medications, and exposure to suspected teratogenic medications.
Results: Among 4,072 women who were diagnosed with vulvovaginal candidiasis and exposed to clotrimazole, oxiconazole, isoconazole, or miconazole, the overall prevalence of MCMs was 5.8% (n = 237). After applying propensity score overlap weighting, no increased risks of MCMs in infants were observed in pregnancies exposed to oxiconazole, isoconazole, and miconazole compared to clotrimazole (odds ratio [95% confidence interval]: 0.875 [0.599-1.277], 1.001 [0.611-1.640], and 0.887 [0.497-1.581], respectively).
Conclusion: There was no significant association between exposure to oxiconazole, isoconazole, and miconazole during the first trimester of pregnancy and the risk of MCMs in infants.
Keywords: vulvovaginal candidiasis, antifungal medications, malformation

Introduction: Implantable pacemaker pulse generators are critical for managing cardiac arrhythmias, but device-related adverse events (AEs) can lead to serious harm. Identifying patterns of these complications is key to improving device safety. The FDA’s Manufacturer and User Facility Device Experience (MAUDE) database provides essential post-marketing surveillance to detect safety signals and emerging trends.

Aim: This study aimed to evaluate the frequency, type, and reporting characteristics of AEs related to Implantable pacemaker pulse generators reported in the MAUDE database over a 10.5-year period.

Methods: This retrospective study analyzed AEs associated with an implantable pacemaker pulse generator reported in the MAUDE database between January 21, 2015, to June 30, 2025. Data were extracted using a specific product code (DXY), downloaded, and analyzed to identify event type, trends, and insights into the safety of these medical devices.

Results: During the study period total of 10,600 AEs associated with implantable pacemaker pulse generators were reported. Adverse events such as injury accounted for 52.187%, followed by malfunction 39.793%, and death 5.784%. Device problems such as oversensing 3.811%, Failure to capture, interrogate, or backup charge with 3.745%, signal artifact 3.63%, and premature discharge of battery 2.93%. The highest number of AEs was reported in the year 2018 (29.7%), 2017 (21.17%), and 2015 (16.50%). The majority of reports originated from the United States(50%), followed by Germany(18%) and Japan(12%). Reporter occupations were primarily physicians(42%), followed by healthcare professionals(27%), and manufacturers(21%).

Conclusion: The analysis highlights recurring device issues and underscores critical areas for safety improvement. Continuous monitoring through materiovigilance systems like MAUDE is essential to mitigate risks and enhance the reliability of implantable cardiac devices. These insights can guide manufacturer improvements, and strengthen regulatory oversight to ensure long-term patient safety.

Keywords: Implantable Pacemaker Pulse generator, MAUDE database, Materiovigilance

Background
Gastric acid suppressants, including proton pump inhibitors (PPIs) and histamine H₂-receptor antagonists (H₂RAs), are widely prescribed. However, evidence regarding their association with peritonitis risk in peritoneal dialysis (PD) patients remains inconsistent.
Objectives
To evaluate the association between incident PPI or H₂RA use and peritonitis risk among PD patients, compared to non-users, employing a target trial emulation framework with sequential analyses.
Methods
We conducted a cohort study with target trials frame with sequential emulating monthly initiation cohorts from January 2006 to December 2019 using a PD cohort identified in Hong Kong. Exposure was defined by PPI or H₂RA prescription in the index month. A multinomial logistic regression model estimated propensity scores for exposure group (PPI, H₂RA, non-user), incorporating age, sex, comorbidities, and anticoagulant/antiplatelet use. Inverse probability weighting was used to balancing baseline characteristics. Peritonitis risk and mortality risk at 5 years, both risk ratio and risk difference were estimated using pooled logistic regression. 500 bootstrapping was used for 95% confidence interval (95% CI). Subgroup analyses by sex and age (<65 vs. ≥65 years) were performed.
Results
240,431 person-trials were analysed, with 0.8% (n=2,113) for PPIs and 1.5% (n=3,654) for H₂RAs. IPW balanced most covariates (SMD<0.1), except diabetes and pre-baseline drug use. Both PPIs and H₂RAs users were associated with significantly increased peritonitis risk compared to non-users: H₂RA (RR: 1.36, 95% CI: 1.23–1.51) and PPI (RR: 1.87, 95% CI: 1.60–2.18). All-cause mortality risk was similarly elevated: H₂RA (HR: 1.42, 95% CI: 1.34–1.51) and PPI (HR: 2.32, 95% CI: 2.16–2.50).
Conclusions
PPIs or H₂RAs was associated with higher peritonitis and all-cause mortality risk in PD patients compared to non-use, with PPIs demonstrating greater risk. These findings highlight the critical need for judicious prescription and risk-benefit assessment of gastric acid suppressants in this vulnerable population.

Introduction: Stem cell therapy holds immense potential in the field of regenerative medicine, and its clinical development has garnered significant attention.
Aims: This study aimed to summary a comprehensive evaluation of stem cell clinical trials registered on the ClinicalTrials.gov, analyzing the landscape and time trends of stem cell clinical development.
Methods: We analyzed data from Aggregate Analysis of ClinicalTrials.gov (AACT) database, focusing on stem cell trials (interventional studies) started between 1 January 2000 through 31 December 2024. Joinpoint regression analysis was employed to assess the geographical and temporal trends in stem cell clinical development.
Results: As of December 2024, a total of 1712 stem cell clinical trials were included. Trend analysis revealed a rapid increase in the number of stem cell clinical trials between 2008 and 2012, followed by a slowdown around 2018. Notably, in 2018, the number of trials using allogeneic stem cells surpassed those using autologous stem cells, marking a key inflection point in the shift between the two types of trials. The United States (476/1712, 27.80%) and China (385/1712, 22.49%) emerged as the leading countries in conducting these trials. The primary tissue sources were bone marrow (604/1712, 35.28%), umbilical cord (302/1712, 17.64%), and adipose tissue (277/1712, 16.18%). Injection was the most common route of administration (1059/1712, 61.86%). Most trials (927/1712, 54.15%) did not specify the dosage. The common ranges were 1-10*10^6 cells/kg (286/1712, 16.71%) and 10-100*10^6 cells/kg (191/1712, 11.16%).
Conclusion: This study outlines the development of stem cell clinical trials over the past two decades, showing early growth followed by a slowdown after 2018. A shift from autologous to allogeneic cell sources was observed, with most trials conducted in high-income regions and at early phases.

Introduction: Heart Failure (HF) contributes to morbidity and hospitalization in India. Despite the availability of Guideline-Directed Medical Therapy (GDMT), real-world adherence to these recommendations is suboptimal. This study evaluated GDMT adherence in an Indian tertiary care setting, quantified deviations from evidence-based therapeutic protocols, and identified barriers for non-adherence. The analysis is particularly relevant owing to the evolving HF pharmacotherapy landscape, including the recent integration of Sodium-Glucose Co-transporter-2 Inhibitors (SGLT2) into standard management protocols.

Aim: To assess adherence to GDMT in HF and identify barriers contributing to deviations in an Indian tertiary care setting.

Method: This prospective observational study was conducted at a tertiary care hospital which included 85 patients diagnosed with HF. Data were collected from hospital records, including discharge summaries and medication charts. The prescribed drug classes in HF patients were analyzed for their adherence with American Heart Association (AHA) GDMT. Further, barriers to adherence were identified by interviewing providers, stakeholders, and patients.

Results: Adherence to AHA-GDMT was identified in only 28% of patients, indicating significant deviation. Diuretics were the most frequently prescribed agents (80%), followed by beta-blockers (64.6%), SGLT2 inhibitors (38.5%), mineralocorticoid receptor antagonists (30.8%), and angiotensin receptor-neprilysin inhibitors (24.6%). Prescription rates for ACE inhibitors, ARBs, ivabradine, and inotropes were below 8%. Key barriers contributing to GDMT deviation included financial constraints, polypharmacy, and limited prescriber familiarity with newer therapies. Additionally, GDMT was deferred unless NT-proBNP levels were significantly elevated, displaying reliance on biomarker thresholds.

Conclusion: The study highlights suboptimal adherence to GDMT in HF management. Limited prescription of key drug categories, particularly SGLT2 inhibitors and angiotensin receptor-neprilysin inhibitors, signifies gaps in clinical practice. Financial barriers, prescriber unfamiliarity, and reliance on NT-proBNP levels hinder optimal treatment. These findings emphasize the need for focused strategies to improve GDMT adherence.

Keywords: Heart Failure, Guideline-Directed Medical Therapy, SGLT2 Inhibitors.

Introduction
It is unclear whether changes in diagnostic recording due to COVID-19 pandemic restrictions could lead to measurement errors, that affect estimates of causal effects of treatments on outcomes.

Aims
To assess potential measurement errors due to changes in diagnostic recording during pandemic restrictions

Methods
We replicated a published cohort study using data from UK Clinical Practice Research Datalink Aurum linked with Hospital Episode Statistics between 1/1/2006-31/3/2023. We estimated absolute rate differences (RD) and hazard ratios (HR) for tendon rupture comparing fluoroquinolones vs. cephalosporins, using propensity scores (PS) for confounder adjustment. We estimated treatment effects using pre-pandemic data only and compared that with combining all data, and with using post-pandemic data only. Study start year was varied to examine the impact of including different proportions of study time covered by the pandemic.

Results
Using pre-pandemic data (1/1/2006-15/3/2020), PS-weighted HR for tendon rupture was 1.78 (95%:1.34-2.38) and RD of 0.72/1000 person-year, comparing fluoroquinolones with cephalosporin, consistent with the published study. Using all data (1/1/2006-31/3/2023), results were similar with a RD of 0.72/1000 person-year and HR of 1.77 (95%:1.35-2.32). The HR of the interaction term between treatment and a binary indicator of pre-pandemic vs. during/post-pandemic was 0.86 (95%CI:0.38-1.97). Using post-pandemic data (17/4/2022-31/3/2023), the HR was 3.80 (95%:0.74-19.46) and RD was 0.90/1000 person-year.
Varying the study start year from 2007 to 2012, HRs slightly reduced ranging from 1.65 (95%CI:1.24-2.20) to 1.62 (95%:1.08-2.41), with small variations of RDs from 0.69/1000 to 0.8/1000 person-year. Results were imprecise when the study start year was from 2013-2023.

Conclusion
Combining pre-, during, and post-pandemic data did not meaningfully affect effect estimates investigating effects of fluoroquinolones on tendon rupture. Future research with a longer study period is recommended to assess whether the HR based on pre-pandemic data remains consistent with that based on post-pandemic data.

Keywords:
electronic health records;COVID-19;bias

Introduction: Effective management of hypertension requires consistent and long-term therapy. In Indonesia, the effect of exposure to medication information on medication adherence has not been investigated. Understanding the effects of medication information exposure is essential, as informed patients are more likely to follow prescribed treatments, leading to better health outcomes. Aims: This study investigates the relationship between exposure to antihypertensive medication information and adherence among hypertensive patients in Indonesia. Methods: This study used secondary data from the Indonesian Health Survey 2023. Medication non-adherence, exposure to antihypertensive medication, and potential confounders such as gender, age, education level, marital status, occupation, and island of residence were assessed through self-reported single-item measures. The association between the lack of information and medication non-adherence was evaluated using multinomial logistic regression after adjusting for confounders. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were reported. Results: The 2023 Indonesian Health Survey included 877,531 individuals aged 15 years and above. However, 823,863 of these individuals did not have hypertension and were therefore excluded, resulting in a final sample of 53,668 patients with hypertension for this study. Among 53,668 patients, most were female (66.3%), married (77.4%), aged over 35 years old (95.3%), and unemployed (40.9%). The majority (68.1%) had received information emphasizing the need for regular antihypertensive medication. After adjusting for age, education, marital status, occupation, islands of residence, and duration of hypertension, not receiving information about the continuous use of antihypertensive medication was significantly associated with medication non-adherence (AOR=5.05; 95% CI=4.84–5.26; p-value = 0.000). Conclusion: This study demonstrates a strong association between a lack of exposure to information regarding long-term antihypertensive medication and non-adherence among hypertensive patients in Indonesia. Therefore, there is a need for improved communication strategies between patients and healthcare providers to improve long-term medication adherence.

Keywords: Antihypertensive, Medication adherence, Indonesian Health Survey

Introduction: Globally, pesticide poisoning accounts for over 385 million unintentional cases annually, with a significant burden in low- and middle-income countries. In India, occupational hazards from pesticides remains a common challenge, leading to chronic health issues. However, limited studies have examined how farmers’ knowledge, attitudes, and practices (KAP) relate to Health-Related Quality of Life (HRQoL) and laboratory parameters.
Aim: This study aimed to assess the association of pesticides on KAP and HRQoL domains, by correlating laboratory parameters and perceived health status among pesticide-exposed farmers.
Methods: An analytical, cross-sectional design was implemented to assess baseline KAP, HRQoL and laboratory parameters among 175 farmers in Karnataka, India. A validated KAP questionnaire covering various aspects of pesticides were administered, followed by the SF-36 tool to evaluate HRQoL. Statistical analysis included Spearman’s correlation and regression to assess associations among age, KAP, HRQoL, and lab parameters.
Results: Of the 175 farmers, majority were male (89.1%) with a mean age of 47.66 ± 13.33 years and an average farming experience of 25.62 ± 13.73 years. Baseline KAP scores revealed that 6.9% of farmers reported high knowledge and 2.3% demonstrating good pesticide safety practices. Increasing age showed significant negative correlations with reduced HRQoL (p < 0.01). Knowledge positively correlated with physical functioning (ρ = 0.219) and energy (ρ = 0.215), while practice positively correlated with energy (ρ = 0.356), emotional well-being and general health (p < 0.01). Total protein, serum globulin, and AST showed significant negative correlations with HRQoL domains. Regression analysis revealed that knowledge and practice were significant predictors influencing HRQoL domains (p < 0.05).
Conclusion: This study highlights that higher KAP towards safe pesticide use are significantly associated with better HRQoL among farmers. Targeted educational interventions may support long-term well-being of farmers.
Keywords: Pesticide exposure, Health-related quality of life, KAP assessment

Introduction: Extreme temperature events (ETEs)—such as heat waves and cold spells—are becoming increasingly frequent due to climate change and are known to affect human health. However, their association with intraoperative hypotension (IOH), a modifiable risk factor for postoperative complications, remains poorly characterized. Understanding this relationship is critical for informing climate-adaptive perioperative strategies.

Aims: To assess the association between ETE exposure and both the occurrence and duration of IOH in patients undergoing major surgery.

Methods: We conducted a retrospective cohort study of 276,515 adult patients who underwent major surgery between 2015 and 2023 at three academic medical centers in China. ETEs were defined using percentile-based thresholds of daily ambient temperature over consecutive days. The primary outcome was IOH, defined as a mean arterial pressure (MAP) <65 mmHg sustained for ≥10 minutes. Multivariable logistic regression and generalized linear models were used to estimate associations.

Results: Of the total cohort, 48,023 patients were exposed to heat waves and 42,615 to cold spells. Exposure to heat waves was associated with significantly reduced odds of IOH lasting [10,15) minutes (3.56% incidence; adjusted odds ratio [aOR]: 0.89, 95% confidence interval [CI]: 0.85–0.94; P < 0.001), [15,20) minutes (2.34%; aOR: 0.89, 95% CI: 0.84–0.95; P < 0.001), and ≥20 minutes (11.88%; aOR: 0.88, 95% CI: 0.85–0.91; P < 0.001). Conversely, cold spell exposure was associated with an increased risk of IOH lasting ≥20 minutes (14.42%; aOR: 1.06, 95% CI: 1.03–1.10; P < 0.001). Stratified analysis indicated that younger female patients undergoing non-cardiac surgery were particularly vulnerable to prolonged IOH during cold spells.

Conclusions: ETE exposure is significantly associated with IOH, particularly when sustained for longer durations. These findings highlight the importance of integrating environmental risk factors into perioperative planning to improve patient safety under changing climate conditions.

Keywords: Intraoperative hypotension, extreme temperature events, perioperative risk

Introduction: The introduction of trastuzumab biosimilars—the first anticancer biosimilars in South Korea—marked the onset of biosimilar competition in oncology, underscoring its policy significance. While biosimilars are intended to improve affordability and access, their real-world impact on trastuzumab utilization and healthcare expenditures remains unclear.
Aims: To assess the impact of trastuzumab biosimilar introduction on utilization and healthcare expenditures among HER2-positive breast cancer patients in South Korea.
Methods: We conducted a retrospective cohort study using the K-CURE national claims database, a 10% sample of breast cancer patients with linked data on staging. We identified two cohorts of patients newly diagnosed with HER2-positive breast cancer: pre-biosimilar cohort (diagnosed in 2013–2014), and post-biosimilar cohort (diagnosed in 2018–2019). After 1:1 propensity score matching based on clinically relevant variables—including age, stage, and comorbidities—526 patients were included in each cohort. Outcomes included trastuzumab usage, time to initiation, and per-patient healthcare expenditure. Subgroup analyses were conducted by insurance premium decile. Group comparisons used independent t-tests when the F-test supported equal variances, and Mann–Whitney U tests otherwise (p<0.05).
Results: Following biosimilar introduction, per-patient trastuzumab use increased by 7.8% (P<0.0001). Median time from diagnosis to first dose and to peak utilization both decreased in the post-biosimilar cohort (−56.8 days; P<0.0001). Trastuzumab use increased among lower-income groups (+18.21%) but declined among higher-income patients (-5.03%). Average per-patient healthcare costs rose from $50,472 to $60,828 (P<0.0001); breast cancer-related costs rose from $46,652 to $55,829 (P=0.0071). Costs within one year of diagnosis also increased (P<0.0001).
Conclusion: Biosimilar introduction improved timely access to trastuzumab, especially among lower-income patients, but did not reduce overall healthcare costs. These findings suggest that South Korea’s current price-linking policy may be insufficient to curb rising expenditures, underscoring the need for complementary measures to fully achieve the economic benefits of biosimilar competition.
Keywords: Biosimilar, Trastuzumab, Healthcare cost

Introduction: Traditional over-the-counter (OTC) drug instructions are often difficult to understand due to their complex text structure, which can lead to medication errors. Enhancing the efficiency and comprehensibility of drug information is crucial for public health. This study aims to solve this problem through information visualization to improve user comprehension.
Aims: This study aimed to design, develop, and evaluate an innovative visual drug instruction leaflet. The primary objective was to validate whether the design could significantly improve the speed of information retrieval and the overall user experience while maintaining information accuracy.
Methods: This study first systematically analyzed an official over-the-counter drug database to establish a taxonomy for drug instructions. We then collaborated with pharmacy experts to develop a visual prototype through an iterative design process based on this taxonomy. Finally, a controlled user study compared the effectiveness of the visual version to the traditional text version.
Results: The visual version significantly reduced information retrieval time compared to the text version while maintaining comparable comprehension accuracy. The visual design achieved a significantly higher System Usability Scale (SUS) score, indicating better usability. Subjective feedback from participants was also more positive, as they perceived the visual design as more intuitive and easier to understand. The proposed taxonomy and design solutions were also endorsed by the consulting experts.
Conclusions: This study confirms that well-designed visualization is an effective tool for enhancing the communication efficiency and user experience of over-the-counter drug information. The proposed taxonomy and design principles can be generalized to a broader range of drugs, providing a practical reference for future drug information design.

Introduction: Carbapenem-resistant Enterobacteriaceae (CRE) are resistant to most antibiotic drug classes and are also resistant to carbapenem, one of the “last resort” antibiotic classes.

Aims:
1. To examine the trend of CRE colonisation pre-, during and after the COVID-19 pandemic in Hong Kong.
2. To describe the duration of CRE colonisation.

Methods: We collected data from the Hong Kong Hospital Authority (HA) electronic health record, for patients aged >18 at onset, during a period from 2017/01/01--2023/06/30, for CRE laboratory tests using either genotypic or phenotypic methods.
We examined the changes in CRE monthly incidence before, during, and after the COVID-19 pandemic (i.e. 01/02/2020 – 28/02/2023) in an interrupted time series using quasi-poisson regression model. CRE colonisation duration was categorized into short-term (0-3 months), prolonged (4-6 months), and persistent (6-12 months).

Results: We identified N=65,879 episodes from 63,488 adult patients (aged ≥18) had ≥1 CRE test during the study period. Among which, N=16,122 episodes (24%) had ≥1 CRE positive result. Patients aged ≥85 contributed to the largest share of episodes by N=19,321 (29%).
About half of the episodes (N=34,690, 53%) occurred during the COVID-19 period. The CRE test positive incidence trend showed an increasing pattern with seasonality each year before the start of the COVID-19 pandemic in February 2020. The CRE incidence started to increase rapidly during the COVID-19 (p=0.008) pandemic period in 2021-22, while it exhibited a steeper growth after the pandemic in March 2023.
Among all CRE positive episodes, short-term colonisation made up 26% (N=4,123), while prolonged was 5.2% (N=837), and persistent was 7.6% (N=1,225), while the rest were indeterminate duration (N=9,937, 62%).

Conclusions: The observed growing trend in CRE incidence may be attributed to increased surveillance efforts in public hospitals, and the percentage of CRE positives warrants further investigation to account for testing trends.

Background:
Inclisiran is a small interfering RNA therapeutic approved for lowering LDL cholesterol in patients with hyperlipidemia. Diverticulitis is a condition where small bulging pouches (called diverticula) that can form in the walls of the colon become inflamed or infected. Pharmacovigilance using spontaneous reporting systems such as the FAERS database is critical for identifying previously unrecognized adverse drug reactions (ADRs).
Objective:
This study aimed to identify potential safety signals associated with Inclisiran using disproportionality analysis of data from the FAERS database.
Methodology:
FAERS data were analyzed for Inclisiran-related adverse events using standard signal detection algorithms. The Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR) values are obtained from OpenVigil database. Signals were considered positive if AE >3, PRR ≥2, Chi-square >4, and ROR lower bound >1. Key metrics including PRR, ROR, and confidence intervals were extracted and assessed.
Results:
As of early 2025, the FDA Adverse Event Reporting System (FAERS) has accumulated over 35 million Individual Case Safety Reports (ICSRs), documenting adverse drug reactions from both domestic and international sources. Among these, Inclisiran-related reports were identified and analyzed for disproportionality. Diverticulitis was identified among Inclisiran-related entries. It showed a PRR of 2.73 (1.55, 4.80), ROR of 2.76 (1.645; 5.111), and a Chi-square value of 10.46, surpassing the thresholds for signal detection. Although the absolute number of reports was modest, the strength of the disproportionality metrics suggests a potential link between Inclisiran and the onset of Diverticulitis.

Conclusion:
The results revealed that Inclisiran may cause Diverticulitis. These findings have to be confirmed, and further pharmacoepidemiologic research is required to increase the accuracy of the prevalence and/or risk factors of these events.
Keywords: Inclisiran, Diverticulitis, Signal Detection, Adverse Drug Reactions, FAERS, Pharmacovigilance

Introduction: The World Health Organization (WHO) has reported a global increase in antibiotic use during the COVID-19 pandemic, raising concerns about inappropriate prescribing and contributing to the rise of antimicrobial resistance. In Indonesia, there is limited data on inpatient antibiotic utilization trends during this period.
Aims: This study aimed to evaluate inpatient antibiotic utilization patterns before and during the pandemic using data from a state-owned enterprise hospital.
Methods: We conducted a cross sectional study using inpatient pharmacy claims data from 2019 to 2020. Systemic antibiotics were identified using WHO Anatomical Therapeutic Chemical (ATC) codes J01 and classified according to ATC classes and AWaRe (Access, Watch, Reserve) categories. Utilization was quantified using Defined Daily Doses (DDDs) per 100 patient days. Patient days were calculated based on hospital admission and discharge dates.
Results: A total of 8,354 antibiotic prescriptions were analyzed from 1,214 inpatients. A total of 650 patients (53.54%) were female. The mean age was 54.15 ± 19.09 years, with majority (69.19%) in the 18-65 years age group. Total antibiotic use for two years was 25.66 DDD/100 patient days. Yearly breakdown showed higher utilization in 2019 (28.76 DDD/100 patient days) and a decrease in 2020 (22.13 DDD/100 patient days). Parenteral formulations accounted for the majority of antibiotic use (76.81%). Third-generation cephalosporins, particularly ceftriaxone, were the most frequently prescribed agents (40.02%). Antibiotics categorized under WHO Watch group predominated across both years, representing 83.56% of all prescriptions. Four specific antibiotics demonstrated increased use during the pandemic period (2020): azithromycin, clindamycin, gentamicin, and levofloxacin.
Conclusion: Overall inpatient antibiotic utilization declined in 2020 compared to 2019. Ceftriaxone had the highest level of utilization on both years. High use of watch group antibiotics in both years and increased use of specific agents from the watch categories (azithromycin and levofloxacin) highlights the concerns for antimicrobial resistance risk.

Introduction
Real-world studies (RWS) face unique challenges in ensuring data quality and regulatory compliance, particularly in regions with evolving regulatory environment like China. The dedicated inspection standards remain underdeveloped compared to trials, highlighting the need for targeted quality management.
Objective
To synthesize insights from Chinese literatures on clinical trial inspections and provide actionable recommendations for improving quality management in RWS.
Methods
A systematic search of two Chinese databases (CNKI and Wanfang) from 2015 to 2025 using subject terms “inspection” and “clinical trials” identified 2,214 articles. After removing 466 duplicates and screening for titles and abstracts, 82 articles underwent independent full-text review. Ultimately, 39 articles were included for data extraction using a pre-designed table, including inspection finding types, frequencies and solutions, for content analysis.
Results
Quality issues can be categorized into three main types: participant protection (n=37,94.8%), protocol adherence (n=32,82.1%) and data quality (n=31,79.5%), with data quality as the critical quality concerns in 59.0% studies. First, participant protection issues included non-standard informed consent (n=31), incomplete adverse event reporting (n=30), insufficient ethical review (n=17), and inadequate privacy protection (n=10). Second, protocol deviations were most frequently related to non-compliance of inclusion/exclusion criteria (n=28), follow-up visits exceeded time windows (n=28), and medication adherence (n=25). Finally, data quality concerns centered on data accuracy (n=31) and completeness (n=27). To address these issues, efforts were focus on the life-cycle quality management in improving data traceability, standardizing protocol execution, establishing a regular monitor mechanism, and introducing independent quality check.
Conclusions
The findings highlight common quality issues in Chinese clinical trials, offering valuable lessons for the developing standardized quality management in RWS. Learning from the FDA and EMA well-established inspection system and policies, standardized quality management procedures, including improved data traceability, protocol adherence, and participant protection, are essential for building a high quality RWS in China and beyond.

Introduction: Insulin detemir is widely used for gestational diabetes mellitus (GDM) due to its favorable safety profile. Insulin glargine, however, has been used cautiously because of concerns about elevated insulin-like growth factor-1 and potential fetal overgrowth. Despite recent studies suggesting comparable safety, evidence on their differential effects on birth weight remains limited.

Aims: This study aimed to compare birth weight outcomes, including macrosomia (birth weight > 4,000g) and low birth weight (LBW; birth weight < 2,500g) in offsprings of mothers with GDM treated with insulin detemir or glargine.

Methods: This retrospective cohort study utilized the South Korean National Health Insurance Service (NHIS) mother-child linked database. Children born to mothers with a diagnosis of GDM were included, and outcomes were compared between those whose mothers received glargine and those who received detemir during 2010-2022. We used multivariable logistic regression to estimate propensity scores and applied overlap weighting to address potential confounding. We estimated risk ratios using Poisson regression and assessed mean differences in birth weight using linear regression.

Results: The study included 1,192 children (1,142 mothers) in the glargine group and 10,431 children (9,767 mothers) in the detemir group. Glargine was associated with a higher risk of macrosomia (10.4% vs. 7.5%) and a lower risk of LBW (7.7% vs. 10.3%), compared to detemir. After adjustment, glargine remained associated with an increased risk of macrosomia (RR=1.23, 95% CI: 1.01–1.49), but not with LBW (RR=0.89, 95% CI: 0.69–1.14). The weighted mean birth weight was higher with glargine (3,302 g vs. 3,248 g) (p<0.001).

Conclusion: Insulin glargine use during GDM was associated with a higher risk of macrosomia and increased birth weight compared with insulin detemir. The findings support maintaining detemir as the preferred basal insulin in GDM management.

Keywords: Gestational diabetes mellitus; Insulin treatment; Birth weight

Introduction:
Neuro-medical devices are used to diagnose and treat complex neuro disorders, such as Neurostimulation implants and Deep Brain Stimulators. However, the regulatory vary across the global markets, challenges in ensuring post-market safety and digital risk mitigation. The framework varies across different region which hinder effective surveillance and benefit-risk assessment.
Aims:
This study evaluates the integration of epidemiologic approaches to identify regulatory gaps, to enhance harmonization strategies for neuro-medical device safety and post-market safety risks in neuro-medical devices across global markets.
Methods:
Epidemiologic methods were applied to analyse regulatory data and post-market surveillance reports from the US, EU, and India, focusing on approval processes, adverse event reports, and studies from 2017–2025. Comparative and statistical analyses identified common risks and gaps. Tools such as signal detection and safety trend analysis assessed data quality, surveillance gaps, and harmonization efforts.
Results:
Regulatory approval timelines for neuro-medical devices varied from 6 to 30 months across the US, EU, and India. Signal detection highlighted software malfunctions (35%) and cybersecurity breaches (22%) as dominant safety risks, with underreporting rates between 30–45%. Real-world data integration was lowest in India, compared to 44% (US) and 28% (EU), exposing longitudinal surveillance gaps. Analysis of 250+ adverse event records in USA revealed challenges in tracking device performance. Adoption of ISO and IMDRF frameworks improved harmonization by 25%, underscoring the importance of unified standards and structured oversight for enhanced safety and global regulatory convergence.
Conclusions:
Integrating epidemiologic methods into neuro-medical device regulation enhances risk detection, surveillance, and global safety alignment. The Regulatory gaps and underreporting highlight the need for harmonized evidence standards and collaborative oversight. Strengthening real-world data integration and international regulatory convergence is essential to improve patient outcomes and accelerate safety-driven innovation.
Keywords: Neuro-medical devices, regulatory harmonization, post-market surveillance.

Introduction:
In India, where healthcare is dominated by out-of-pocket spending, health insurance can have a huge impact on whether individuals can pay for the medicines they require. However, much research simplifies insurance coverage to a binary yes-or-no variable, without considering the more profound inequalities embedded in the system. This research looks more closely at how income, gender, and social demographics affect who is insured, and what implications this has for equitable access to necessary medicines.
Aim:
To examine disparities in health insurance coverage across socio-demographic groups using multinomial logistic regression and evaluate their implications for medicine access.
Method:
Secondary analysis was conducted using NFHS-5 data (N = 842,425). Predictors included wealth quintile, religion (Hindu, Muslim, Christian and others), region, residence, and education, adjusted for age and gender. Survey weights accounted for complex sampling. Multicollinearity was not detected. Sensitivity analyses using stratified and unweighted models confirmed robustness.
Results:
Among participants, 34% had no formal education, and 48% lived in rural areas. Insurance coverage varied widely: the richest quintile had higher odds of private insurance uptake than the poorest (North: aOR = 5.13, 95% CI: 4.95–5.32; South: aOR = 3.36, 95% CI: 3.22–3.51). Muslims and Christians had much lower chances of any coverage than Hindus (Muslims: aOR = 0.71, 95% CI: 0.69–0.73; Christians: aOR = 0.79, 95% CI: 0.76–0.82). Education did not remain a significant predictor after adjustment.
Conclusion:
Indian health insurance coverage mirrors entrenched structural inequalities. These disparities most probably lead to postponed or forgone treatment and medication underuse. Strategies need to tackle religious, regional, and economic barriers to make pharmaceuticals accessible in an equitable manner.
Keywords: Health equity, pharmacoepidemiology, health insurance utilization.

Introduction:
Lithium is a first-line medication for the treatment of bipolar disorder. Previous studies indicated that long-term use of lithium would lead to an increased risk of chronic kidney disease (CKD). There is a notable absence of population-based studies examining the impact of lithium discontinuation on CKD. Investigating the discontinuation effect of lithium on the risk of CKD would inform clinical decisions.

Aims:
This study aimed to investigate the association between lithium discontinuation and the risk of developing CKD.

Methods:
A nested case-control study was conducted using data from IQVIA Medical Research Data (IMRD) database, which covers a representative number of general practices and individuals in the United Kingdom. Individuals aged 18 or above with lithium prescriptions of over 90 days were identified, and two groups were compared: individuals who had developed CKD as cases; and individuals who had not developed CKD as controls. The discontinuation duration was included as a continuous exposure variable, adjusting for prior lithium use duration.

Results:
There were 969 case participants and a total of 9,574 control participants matched for analysis, with similar mean ages between cases and controls (57.03 years vs. 56.69 years). The analysis showed that lithium discontinuation was significantly associated with lower risk of CKD, with an adjusted odds ratio (aOR) of 0.79 (95% CI: 0.77-0.80). Notably, comparing age groups, the most significant impact of lithium discontinuation on CKD risk was observed in individuals aged over 70, with a risk reduction by one-fourth for each additional year since the date of discontinuing lithium (aOR: 0.72, 95% CI: 0.67-0.77).

Conclusions:
The findings suggest that discontinuation of lithium significantly lowers the risk of CKD. Close monitoring of renal functions during the use of lithium use is warranted.

Keywords:
Affective mood disorder; Pharmacoepidemiology; Psychiatric epidemiology

Introduction: While the acute neurologic complications of COVID-19 are relatively well characterized, its long-term neurological risks for a progressive condition, including dementia, remain unclear.

Aims: To investigate the long-term risk of new-onset dementia following COVID-19 infection.

Methods: In this retrospective cohort study using a nationwide linked database of COVID-19 registry and health insurance claims data, we identified adults (≥18 years) who had a COVID-19 diagnosis between January 2020 and December 2022. Two control cohorts were established; a contemporary group with acute upper respiratory infection (AURI) diagnosis during the same period and a historical group with AURI before the pandemic. Individuals with a prior diagnosis of dementia or with a COVID-19 or AURI diagnosis inconsistent with their assigned cohort were excluded. COVID-19 patients were 1:1 matched to controls using propensity scores considering age, sex, insurance type, income, SARS-CoV-2 variant period, and dementia-related comorbidities. Hazard ratios (HRs) and 95% confidence intervals (CIs) for dementia defined by diagnosis were estimated using Cox proportional hazards models. The maximum follow-up period was until December 2024.

Results: A total of 1,592,234 COVID-19 patients (mean age 47.3 years [SD 16.6]; 39.3% female) were identified. Compared to the contemporary control group, there was no significant increase in dementia risk (HR 1.45; 95% CI 0.98–2.15), but risk was elevated in those aged ≥65 years (HR 1.60; 95% CI 1.06–2.41). Individuals who remained unvaccinated prior to COVID-19 exhibited a higher risk of dementia (HR 5.00; 95% CI 1.10–22.81), whereas no significant association was observed in vaccinated individuals (HR 1.28; 95% CI 0.84–1.93). Findings were consistent with the historical control analysis.

Conclusion: Our findings indicate that COVID-19 infection was not associated with an increased long-term risk of dementia, however, an elevated risk was observed among unvaccinated individuals, suggesting potential differences in long-term risk by vaccination status.

Introduction: Materiovigilance is vital for ensuring medical device safety and performance. The
study evaluated healthcare professionals’ knowledge, attitudes, and practices (KAP) regarding
monitoring of implantable and other devices in Perinthalmanna, Kerala. The study investigated device-associated
adverse events, analyzed device failure causes, and reported findings to the IPC-NCC..
Materials and Methods: A multicentre observational, cross-sectional study was conducted
from November 2023 to October 2024 at tertiary care Hospital and affiliated healthcare centres in Kerala to identify medical device-associated adverse events (MDAEs) and evaluate healthcare professionals’ knowledge and attitudes towards materiovigilance. A sample size of 109 was determined using standard proportion-based calculations. Data were collected using a validated form and Materiovigilance Programme of India (MvPI) reporting tools. The study involved phased implementation: device selection, inpatient and outpatient monitoring, causality assessment, committee reviews, ophthalmology module development, and dissemination of findings. All MDAEs were reported to MvPI,
contributing to the national safety database.Results: A total of 109 medical device adverse events (MDAEs) were identified, with 60.6% occurring in females and predominantly affecting adults aged 19–65 years. The ophthalmology department accounted for the majority of events (59.6%), followed by dentistry (27.5%) and cardiology (12.8%). Posterior capsular opacification and contact dermatitis were the most
frequently reported adverse events. Devices classified as moderate-high risk (Category C) and
invasive devices were commonly implicated.
. A significant association between profession and knowledge was observed (p = 0.034). The study facilitated enhanced awareness and reporting compliance, underscoring the necessity for mandatory MDAE reporting to improve patient safety and medical device oversight.
Conclusion: The study highlights the critical need for enhanced awareness and reporting of medical device-associated adverse events (MDAEs) across healthcare settings. Tailored interventions and strengthened
surveillance systems are necessary to ensure patient safety, promote a culture of accountability,
and advance the quality of healthcare delivery

Introduction: Medical devices are extensively used in Intensive Care Units (ICUs), particularly among geriatric patients who often present with multiple comorbidities and physiological decline. This group is more susceptible to complications from device use. Adverse events related to medical devices can increase morbidity, prolong hospitalization, and compromise patient safety. The need for targeted Materiovigilance in this population is paramount.
Aims: To assess the pattern of adverse events related to medical devices in geriatric ICU patients and determine the causal relationship between device use and reported events.
Methods: This cross-sectional observational study was conducted over seven months (November 2024–May 2025) at a tertiary care hospital in Bangalore, India. A total of 100 ICU patients aged 65 and above, using one or more medical devices, were included. Adverse events were identified through clinical records, nursing notes, and interviews. In the absence of a validated Indian tool, causality was assessed using the EU MDCG framework, which, though not locally validated, offers a structured and systematic approach. Data were analyzed using descriptive statistics and chi-square tests to explore patterns and significant associations.
Results: A total of 122 medical device-associated adverse events (MDAEs) were documented. Intravenous cannulas, particularly 20G, were most frequently involved (37.7%). Common MDAEs included swelling (30.3%), hematoma (11.5%), leakage (7.4%), and bluish discoloration (6.6%). Most events involved invasive (88.5%), sterile (91.8%), and single-use (91.8%) devices. Causality assessment classified 53.3% of events as probable and 42.6% as related. Significant associations were found with patient age (p=0.03), number of devices used (p=0.01), comorbidities (p=0.04), and education level (p=0.02).
Conclusions: Geriatric ICU patients are at high risk of MDAEs, primarily from commonly used invasive devices. This underscores the need for geriatric-focused Materiovigilance protocols, regular monitoring, and staff training to minimize device-related harm.
Keywords: Materiovigilance, geriatric intensive care, medical device safety

Background:Medical device-related adverse events (MDAEs) pose significant risks in specialized healthcare settings like Pulmonology and Intensive Care Units (ICUs), where devices are integral to patient management. Despite their critical role, limited research has explored the factors influencing causality assessments of MDAEs in these settings. This study addresses this gap by examining demographic, clinical, and device-related factors associated with causality judgments, aiming to improve patient safety and materiovigilance practices.
Objective:To describe the demographic and clinical characteristics of participants experiencing MDAEs, profile the medical devices and adverse events involved, and assess associations between various factors (age, gender, device category, event seriousness, device use, device type) and causality assessments.
Methods:A cross-sectional study was conducted among 64 participants (mean age 63.8±17.1 years; 68.8% aged ≥60; 71.9% male; 96.9% with comorbidities) in Pulmonology and ICU departments. Inclusion criteria included patients who experienced a device-related adverse event; patients with incomplete documentation were excluded. Data were collected on device characteristics (risk category A–D, use: single/reusable; type: diagnostic/therapeutic), event seriousness, and management. Causality was classified as ‘possible’ or ‘probable’. Descriptive statistics and Chi-square (χ²) tests were used for initial analysis. Logistic regression was employed to evaluate the independent contributions of variables while adjusting for confounders.
Results:Catheters were the most frequently implicated devices (35.9%). Category C (moderate-to-high risk) devices accounted for 51.6% of cases. Most MDAEs involved single-use (79.7%) and therapeutic (78.1%) devices, with 87.5% being non-serious. Causality assessments were 57.8% ‘possible’ and 42.2% ‘probable’. Significant associations were observed with device category (χ²=24.4, p=0.001), event seriousness (p=0.045), and device use (p=0.004). No significant association was found with age (p=0.955) or gender (p=0.37).
Conclusion:Device characteristics and event severity significantly influence MDAE causality assessments, highlighting the need for targeted safety protocols and robust reporting systems in critical care settings.
Keywords: medical device vigilance, pulmonology, ICU, adverse events, causality assessment

Introduction: Among patients hospitalized for acute exacerbations of chronic obstructive pulmonary disease (AECOPD), cardiovascular disease (CVD) prevalence reached 55%, but cardiovascular risk control remains suboptimal in clinical practices.
Aims: To evaluate medication patterns, guideline adherence, and compare drug utilization with versus without CVD.
Methods: This study enrolled 2,398 subjects from January 2021 to December 2024. Demographic, clinical and prescriptions data were collected in a tertiary hospital of Shanghai, China. Patients were grouped by ICD-11 into CVD (n=1,888) and non-CVD (n=510). Covariates including age, sex and hospital stay were adjusted in logistic regression models to estimate ORs and their 95%CI. Chi-square and Cochran-Armitage trend tests assessed combination therapies, annual trends, and prescribing differences by CVD status.
Results: Most (86.2%) of subjects were male, with an average hospitalization of 12.36±8.73 days and age of 77.66±8.97 years. The CVD group was older (78.62±8.79 vs 74.12±8.74, P<0.001), had higher female proportion (14.94% vs 9.41%, P=0.001), and longer hospital stays (12.68±8.91 vs 11.20±7.93, P<0.001) versus non-CVD group. The top three medications were mucolytics (78.9%), inhaled corticosteroids (ICS, 70.1%), and methylxanthines (65.4%), while more ICS (OR=1.35, 95% CI: 1.09-1.68) and methylxanthines (OR=1.26, 95% CI: 1.03-1.56) used in CVD group. Also, Methylxanthines + ICS (51.1% vs 43.5%, P=0.009) and Long-Acting Beta2-Adrenoceptor Agonist (LABA) + Long-Acting Muscarinic Antagonist (LAMA) + ICS (38.0% vs 32.6%, P=0.011) were more prevalent in CVD group. Annual trends revealed statistically increases in LABA (P<0.001), LAMA (P<0.001), ICS (P<0.001) and mucolytics (P<0.001) but a decrease in methylxanthines (P<0.05) in CVD group. However, high methylxanthine use in CVD group was against first-line bronchodilator recommendations by the guideline.
Conclusions: COPD guideline adherence is improved overall in Shanghai, while methylxanthines utilization maintains high, especially in CVD inpatients. Multidisciplinary collaboration and targeted clinician education are needed to bridge such safety gap.
Keywords: medication patterns, COPD, CVD

Introduction-Patient-reported outcomes (PROs) focus on the patient’s experience and perspectives, rather than solely relying on clinical assessments. PROs provide a valuable tool for understanding the patient’s voice and are increasingly considered in drug approval and reimbursement decisions, especially in lack of robust clinical and real-world evidence.1 Hereditary angioedema (HAE) is a rare genetic disorder characterized by unpredictable and heterogeneous attacks that require individualized management. While prior real-world studies have described HAE attack patterns globally and in Asia, there are limited insights on the individual attack profiles.2-4 Additionally, earlier studies typically relied on the documentation of HAE attack episodes and characteristics during physician consultations, which may introduce recall bias, resulting in an underestimation of attack frequency.4

Aims-To empower patients with HAE to describe their attack profiles and treatment patterns and provide physicians with insights on the patients’ real-world setting.

Methods-A mobile application, “MyHAE Story” was developed and patients enrolled in an existing HAE patient support program were invited to access the application. The application enabled patients to record their individual attack-related and treatment details.

Results-The mobile diary enabled the capture of attack profile details, including attack location, severity, prodromal symptoms, and treatment. The diary serves as a platform for patients to record and view their past attack profiles, enabling physicians to review the records and tailor individualized treatment plans. While reminders to use the application were sent to registered users, patients were not required to use the diary. Over 200 attacks were recorded over a 12-month period.

Conclusion-While similar web-based and mobile diaries have been piloted for HAE patients, this is the first known study using mobile application-based de-identified patient-reported data to provide real-world insights into HAE attack profile and treatment patterns in Asia. With proper implementation, there is potential to be adapted for other patient groups to support patient-centered care.

Introduction:
Macrolide antibiotics are commonly prescribed for respiratory and other infections, with usage often influenced by seasonal and environmental factors. However, evidence on how temperature and precipitation affect antibiotic consumption in tropical settings remains limited.

Aim:
This study aimed to investigate the relationships between seasonality, temperature, humidity, rainfall, and macrolide antibiotic use over three years among patients at a University hospital in Southern Thailand.

Methods:
We analyzed 2,517 macrolide prescriptions from 2021 to 2023 at a university hospital in southern Thailand. Total Defined Daily Doses (DDDs) were modeled using a Generalized Additive Model (GAM) with a Gamma distribution and log link to handle non-normality and overdispersion. Predictors included cyclic month effects, year, total rainfall, biweekly average temperature, humidity, and lagged biweekly temperature. Climate data were sourced from Google Cloud and NASA Prediction of Worldwide Energy Resources, then linked to patient insurance registration areas. A Distributed Lagged Non-Linear Model was applied for sensitivity analysis to capture lagged temperature effects over 0–4 biweekly periods.

Results:
Higher rainfall quintiles (Q3–Q5) significantly reduced macrolide use: Q3 IRR=0.45, Q4 IRR=0.41, Q5 IRR=0.38. Extreme weather events were associated with higher usage (IRR=59.1, p<0.001). Compared to 2021, usage was significantly lower in 2022 (IRR=0.23) and 2023 (IRR=0.13). Smooth terms for month and climate interactions were significant, suggesting seasonal and bioclimate modulation of use. Lagged temperature effects (0–4 weeks) on total DDDs of macrolides were not statistically significant--there was none of delayed temperature impact. Short-term temperature changes, therefore, did not influence macrolide consumption in this model.

Conclusions:
Seasonal and bioclimatic factors, particularly the interactions between humidity and temperature, significantly influenced macrolide consumption over time. Therefore, these findings highlight the complex climatic impacts on antibiotic consumption in the context of environmental pharmacoepidemiological studies.

Keywords:
Macrolide, Seasonality, Environmental Pharmacoepidemiology

Introduction: Photostability is a critical factor influencing the quality, safety, and efficacy of pharmaceutical products. Active pharmaceutical ingredients (APIs) may undergo photodegradation upon exposure to ultraviolet (UV), visible, or near-infrared (NIR) radiation, potentially reducing therapeutic effect or increasing toxicity. Packaging serves as the primary barrier against radiation-induced degradation, yet its photoprotective potential is often insufficiently assessed. This study highlights the need for non-destructive, reproducible methods for evaluating the photoprotective properties of pharmaceutical packaging for light-sensitive drugs.

Aims: The aim of the study was to evaluate the shielding capacity of multilayer packaging systems used for solid pharmaceutical dosage forms containing digoxin and doxycycline. The focus was placed on identifying packaging layers that offer the most effective protection within critical optical and thermal ranges.

Methods: Commercial drug products were analyzed using hemispherical directional reflectance spectroscopy (335–2500 nm) and passive infrared thermography (7.5–13 µm). Reflectance was measured for tablets or capsules, blister components (PVC, PVDC), and outer cartons using the SOC 410 Solar reflectometer. Thermal buffering capacity was assessed using a FLIR T420s thermal camera after 180 seconds of standardized radiant exposure.

Results: Outer cartons showed the highest reflectance in the 335–540 nm range (up to 80%), while the tablet and capsule surfaces exhibited <20% reflectance. Blisters had intermediate values depending on their composition. Thermal analysis confirmed that unprotected capsules reached ~45 °C, while blister-plus-carton systems limited temperature increase to <35 °C. A strong correlation was observed between high reflectance and reduced thermal absorption.

Conclusions: The combination of hemispherical reflectance and infrared thermography provides a reliable, non-invasive framework for assessing packaging photoprotection. Multilayer systems significantly enhance shielding properties and may serve as a reference in developing improved packaging standards for photosensitive pharmaceuticals.

Keywords: hemispherical directional reflectance, infrared thermography, pharmaceutical packaging, photostability, doxycycline, digoxin

Introduction:
The existing evidence on post-COVID-19 sequelae were predominantly based on findings from single database, with under-representative study populations.

Aims:
This study aims to generate comprehensive evidence on the risk of clinical sequelae over the short-, medium-, and long-term, spanning up to two years following COVID-19 infection through leveraging population-based electronic medical records and claims data from five countries.

Methods
This multinational retrospective cohort study utilized electronic medical records from the US, UK, France, Germany and Italy standardised to the Observational Medical Outcomes Partnership Common Data Model. 303,251 individuals with a COVID-19 infection between December 01, 2019 and December 01, 2020 and propensity score matched non-COVID-19 comparators from 22,108,925 eligible candidates. The incidence of 73 clinical sequelae involving multiple organ systems including the respiratory, cardiovascular, dermatological and endocrine systems over the short (0-6 months), medium (6-12 months) and long-term (1-2 years) following COVID-19 infection. The hazard ratio (HR) and 95% confidence interval (95% CI) of individual disease outcomes were estimated using Cox proportional hazard regression.
Results
Individuals with COVID-19 incurred a greater risk of clinical sequelae involving multiple organ systems including respiratory [France HR 2.23, 95%CI (2.10,2.37) to Italy 13.13 (11.80,14.63)], cardiovascular [Germany 1.39 (1.30,1.50) to US 1.79 (1.74,1.85)] and dermatological [UK 1.13 (1.01,1.25) to Italy 1.77 (1.42,2.21)] disorder over the short-term. Whilst the risk of clinical sequelae has largely subsided during the medium-term, the risk of cardiovascular [US 1.16 (1.11,1.21), France 1.10 (1.01,1.19)] and endocrine [US 1.18 (1.12,1.24), Germany 1.15 (1.03,1.29)] related complications may continue to persist for up to two years.
Conclusion
Through a network of multinational healthcare databases, this study generated comprehensive and robust evidence supporting the extensive multi-organ involvement of post-COVID-19 condition over the short-term period and the subside in risk for most complications over the medium and long-term.
Keywords
COVID-19; Post-COVID-19 conditions; Long COVID

Introduction:Chronic kidney disease (CKD) and its progression to end-stage kidney disease (ESKD) represent major global public health concerns. Home peritoneal dialysis (HPD) and home hemodialysis(HHD), although cost-effective and beneficial for patients quality of life (QOL), remains underutilized in Japan, with only about 3.1% for HPD and 0.2% for HHD of entire dialysis patients. In response, the 2022 revision of the medical fee introduced ICT‑based measures to enhance the quality of HPD(1,150 JPY). In 2023, CKD management guidelines were updated, and the importance of home dialysis were emphasized for patient QOL.

Aim:This study analyzes the effectiveness of new policies in 2022 and 2023 in expanding the nationwide use of HPD in Japan.Differential trends across predefined age cohorts were then analyzed.

Methods:A serial cross‑sectional study design was adopted using open data from the National Database (NDB). Data from fiscal year (FY) 2021 (April 1, 2021 – March 31, 2022) through FY2023 (April 1, 2023 – March 31, 2024) were extracted. The number of the HPD management fee (40,000 JPY) and the number for HHD management fee (100,000 JPY) were defined as outcomes. Subgroup analyses by age group (20–44 years,45-64years,65-74years and ≥75 years) were performed, and year‑over‑year percentage changes were calculated.

Results:HPD claim counts increased from 114,553 in FY2021 to 122,424 in FY2023 (6.9 ％ up), and HHD claim counts rose from 9,276 to 9,655 over the same period (4.1 ％ up). In stratification analysis, the ≥75 years group of HPD claims increased from 27,227 to 31,377 claims (15.24 ％ up), representing the highest growth among age groups.

Conclusion:Substantial expansions were observed for home dialysis after the new incentives for HPD in 2022 and home‑dialysis promotion by CKD guidelines in 2023.

Keywords:Home peritoneal dialysis(HPD),Home hemodialysis(HHD),National Database (NDB)

Introduction
Misuse and overuse of antimicrobial drugs can cause an acquisition of antimicrobial resistance (AMR), and proper antibiotics use is needed to minimize the risk of AMR. In April 2020, the national medical fees were revised in Japan, and instructions to monitor antibiotics usage were added. Additionally, COVID-19 pandemic enhanced preventive actions such as wearing masks for both bacteria and viruses.

Aims
This study analyzed the trend of antimicrobial drug usage after policy implementation during COVID-19 pandemic.

Method
A nationwide serial cross-sectional study was conducted using the open data from the national database (NDB). This study extracted the antibiotic prescription data of all oral medicine and injection for both inpatient and outpatient based on the therapeutic category. The antimicrobial usage was calculated as DDD (Defined Daily Dose) per 1,000 inhabitants per day (DID). Research periods were fiscal year FY2019 (April 2019-March 2020) and FY2020 (April 2020-March 2021). The means (95% Cl) for DID were analyzed with data of 47 prefectures, and paired t-tests were performed. P-values (two-sided) < 0.05 was considered statistically significant.

Result
The nationwide total DID was 13.60 in FY 2019, and 10.48 in FY2020 with approximately 23% reduction. Additionally, the reduction rate of DID was 33% in the 0-19 age group, 24% in the 20-74 age group, and 13% in those aged 75 years and over during FY2019-2020. The means (95% CI) of DID based on prefectures (n=47) are 13.51 (13.13-13.89) for FY2019 and 10.56 (10.26-10.87) for FY2020, and the statistically significant difference was observed (p<0.001).

Conclusion
A substantial reduction of nationwide antimicrobial drug usage was observed after policy implementation during COVID-19.

Keywords
antimicrobial stewardship, COVID-19 pandemic, serial cross-sectional study

Introduction: While the risk of hemorrhagic stroke following COVID-19 mRNA vaccination remains inconclusive, hemorrhagic stroke occurring shortly after vaccination raises important questions about its prognosis. Inspired by milder prognosis observed in vaccine-related myocarditis, we hypothesized that transient vaccine-related mechanisms (e.g., thrombocytopenia) might lead to a more favorable prognosis than naturally acquired cases.
Aims: This study aimed to compare the prognosis of postvaccination hemorrhagic stroke and historical conventional cases.
Methods: A retrospective cohort study was conducted using a territory-wide electronic public healthcare database in Hong Kong, linked with population-based vaccination records. Since the roll-out of mRNA Vaccines (BNT162b2), patients aged 18 years or older hospitalized with hemorrhagic stroke within 28 days after mRNA vaccination were compared with conventional hemorrhagic stroke recorded between 2016 and 2017. The two-year follow-up period began from the diagnosis of hemorrhagic stroke. All-cause mortality and multimorbidity were examined using Cox proportional hazards models, with 95% confidence intervals (95%CIs) derived from bootstrap resampling (1,000 iterations).
Results: A total of 2,578 patients were included for analysis: 110 in the postvaccination group and 2,468 in the conventional group. Over the two-year follow-up period, all-cause death occurred in 27.27% (30/110) of the postvaccination group versus 29.78% (735/2,468) in the conventional group. Multimorbidity was observed in 63.64% (70/110) of postvaccination cases and 73.14% (1,805/2,468) of conventional cases, respectively. Adjusted analyses showed no significant differences in all-cause mortality (adjusted Hazard Ratio [aHR]=0.93, 95%CI:0.64–1.28) or multimorbidity risk (aHR=0.85, 95%CI:0.66–1.05) between the two groups.
Conclusion: This study demonstrated that hemorrhagic stroke following mRNA vaccination had a long-term prognosis similar to conventional cases. These findings suggested that postvaccination hemorrhagic stroke does not have a worse prognosis and may follow a clinical course similar to conventional cases, reinforcing mRNA vaccine safety assessments.
Keywords: mRNA vaccine, hemorrhagic stroke, multimorbidity

Introduction: Patient-reported outcome measures (PROMs) capture patient-centric insights are increasingly used in regulatory decision-making. However, the integration of PROs in post-marketing surveillance (PMS) is gaining traction and varies by Asia-Pacific (APAC) markets.
Aims: This study reviewed the extent of PROMs utilization in PMS across Australia, China, Japan, Korea, Singapore, and Taiwan.
Methods: A targeted PubMed literature search (2020–2025) was conducted to identify PMS studies including PROMs in these markets. Data on PROM collection methods, therapeutic indications, and outcome measures were extracted from eligible publications and analyzed using narrative synthesis.
Results: We identified 43 studies (4% of 1,029 screened publications) that included PROMs in PMS. Most were conducted in Japan (67%), followed by Korea (16%), China (9%), Australia (5%), and multi-country studies (2%). PROMs were used in a range of therapeutic areas, most commonly immunology (19%), rheumatology (7%), and urology (7%). Nearly one-quarter (23%) of the studies used a PROM as a primary endpoint; PROMs were primarily applied to assess treatment effectiveness (74% of studies), followed by quality of life (30%) and safety (12%). In prospective studies (42 out of 43), the most common PROM collection method was a validated scale embedded in an electronic case report form (79%), then custom questionnaires (19%), interviews (2%). Only one study was cross-sectional, utilizing a one-time patient survey.
Conclusions: PROMs are being incorporated into PMS studies across APAC, yet the extent of their use in regulatory decision-making remains unclear. The variation in how PROMs are utilized highlights the need for region-specific guidance to help stakeholders align these patient-centered endpoints with regulatory requirements. Moreover, some PMS studies with PROM components may remain unpublished as agencies may not make the associated PMS reports publicly accessible; thus, current literature could underestimate the true extent of PROM use in this context.
Keywords: Post-marketing surveillance; patient-reported outcome measures; Asia-Pacific

Introduction: Noncommunicable diseases (NCDs) are becoming the leading contributors to Thailand’s health burden, driving more complex treatment needs as multimorbidity becomes increasingly common. Thus, understanding who develops which conditions when, and how diseases co-occur, is essential for healthcare planning.
Aim: To quantify the burden of disease across the life course and describe patterns of multimorbidity and comorbidity in Northern Thailand.
Methods: We conducted a observational cohort study using routinely collected, pseudo-anonymized electronic health records from all public inpatient and outpatient healthcare interactions in Lampang province, covering nearly the entirety of the provincial population. Using data from 2018–2022, we estimated overall, age-, sex-, and year-specific period prevalence for ~300 high-burden conditions, including NCDs and severe infections, based on ICD-10 phenotypes among individuals aged ≥15 years. We also identified the most frequent multimorbidity triads and quantified comorbidities relative to index conditions.
Results: We identified 731,529 individuals. Among those under 40, the most prevalent condition across the life course was dermatitis, affecting 8.79% (95% CI: 8.48–9.09) of those aged 15–19; 5.26% (5.11–5.40) of 20–29-year-olds, and 4.66% (4.54–4.80) of 30–39-year-olds. From age 40 onwards, hypertension became the most common condition, with prevalence increasing steadily from 11.82% (11.62–12.03) in 40–49-year-olds to 90.47% (90.09–90.83) in those aged 80 and above.
Overall, the most common multimorbidity triad was chronic kidney disease (CKD), hypertension and diabetes. With hypertension as the index condition, the most frequent comorbidities were diabetes (33%), chronic CKD disease (17%) and osteoarthritis (15%).
Results varied by age, sex and calendar year.
Conclusions: This study captures real-world clinical experience of individuals in a Southeast Asian setting, highlighting opportunities for drug development and discovery by identifying unmet healthcare needs and frequently co-occurring diseases that may share underlying biological mechanisms
Keywords: Thailand, disease burden, multimorbidity, electronic healthcare records.

Introduction:
While some individuals diagnosed with long COVID require sustained healthcare support, there is limited evidence identifying who experiences persistently high healthcare needs. Understanding these patterns is essential for planning and allocating future services.
Aims:
To characterize patterns of healthcare use and identify factors associated with persistently high utilization at least two years after a long COVID diagnosis.
Methods
We used data from the British Columbia COVID-19 Cohort, including individuals diagnosed with COVID-19 before December 31, 2022, and identified as having long COVID using a validated algorithm. Participants were followed for two years. We assessed daily healthcare encounters including medical visits, emergency department visits, hospitalizations, and classified individuals into four utilization categories: (1)Never high- not in the top 10% in either year; (2)Temporarily high- top 10% in year one only; (3)Incidentally high- top 10% in year two only; (4)Persistently high- top 10% in both years. We used Bayesian multinomial logistic regression to identify factors associated with each category, with the “never-high” group as the reference.
Results:
Among 54,846 individuals with long COVID (62% female; 46.5% aged ≤49), those in high utilization groups were more likely to be older adults, and have more severe acute illness and comorbidities. Women had lower odds of high utilization across all categories of healthcare use (OR ~0.85–0.9). Hospitalization during acute illness was associated with higher odds of persistent (OR 1.37, 95% CI: 1.25–1.50) and temporary high use (OR 1.80, 95% CI: 1.64–1.97). Comorbidities such as problematic alcohol use, cancer, kidney and liver disease, heart disease, diabetes, immunosuppression, stroke, hypertension, and substance use were also associated with higher utilization.
Conclusion:
Older age, severe acute illness, and specific comorbidities are associated with sustained high healthcare use among people with long COVID. Identifying these high-need groups is essential for planning and delivering long-term care services.

Introduction: Dengue is prevalent and endemic in Singapore, with the number of cases ranging from 5261 to 35266 between 2019 and 2021. Dengue vaccines are under development but given the safety concerns of the first dengue vaccine DENGVAXIA, the World Health Organization and dengue experts have recommended that subsequent dengue vaccine development programs should include post-licensure evaluation of vaccine safety.
Aims: The aim of this study was to evaluate data sources within a public healthcare cluster in Singapore as being “fit-for-purpose” for pharmacoepidemiologic studies related to dengue, specifically developing and validating electronic algorithms for detection of dengue and severe dengue (SD).
Methods: This was a retrospective database cohort study of patients diagnosed with dengue at a tertiary adult hospital, a pediatric hospital and a group of polyclinics from 1 Jan 2018 to 30 Jun 2022. Dengue was defined as having a positive test for the dengue virus, virus antigen or virus specific IgM, and/or a dengue diagnostic code. Three SD algorithms were developed among those within the dengue algorithm based on different combinations of disposition (death, ICU admission) and diagnostic codes. The performance of each algorithm was evaluated in each institution using positive predictive values (PPV) based on a sample of 25 dengue cases and 10 from each SD algorithm (total n=30), validated against manual review of relevant clinical documents and laboratory test results by clinicians.
Results: A total of 8603 dengue episodes were detected over the study period. The PPV of the dengue algorithm ranged from 76 – 100%, and that of the SD algorithms ranged from 10 – 90% in the 2 hospitals.
Conclusions: Dengue can be detected with reasonable PPV using the electronic databases. However, the detection of SD is more variable by institution and algorithm.

Introduction. Vaccination plays a vital role in reducing childhood mortality from infectious diseases. However, suboptimal vaccination rates persist due to parental hesitancy, misinformation, and access barriers. Parents’ knowledge, attitudes, and practices (KAP) critically influence vaccination uptake. Understanding these factors is essential for improving vaccine acceptance and coverage.
Aims. To assess parental knowledge, attitudes, and practices toward pediatric vaccination and to explore the potential of a digital reminder system to reduce missed vaccinations.
Methods. A hospital-based cross-sectional survey was conducted among 93 parents at KIMS Al Shifa Hospital and Government District Hospital, Perinthalmanna. Data were collected via an 18-item KAP questionnaire across immunization departments offering daycare and outpatient services.
Results. Most children were aged 0–6 months (38.7%). Knowledge was highest for polio (25.8%) and BCG (18.3%), with limited awareness of other vaccines. Most parents (88.2%) considered vaccines safe, 91.4% supported routine and booster vaccinations, and 93.5% were open to vaccination with more information. While 83.9% knew their child’s vaccination schedule, 51.6% had missed doses—mainly due to lack of awareness. Most believed reminders were effective (91.4%), and 63.4% used digital tools. Only 44.1% contacted providers after missing a dose.
Conclusion. Though attitudes toward vaccination were positive, knowledge gaps and inconsistent practices persist, largely due to insufficient provider communication and lack of structured follow-up. The findings highlight the need for improved health education and digital reminder systems to enhance vaccination coverage.
Keywords: Immunization, KAP survey, Pediatric.

Background: Medication adherence is critical in preventing recurrent events following acute coronary syndrome (ACS), yet up to 50% of patients discontinue at least one cardioprotective medication within 12 months post their cardiovascular event. Non-adherence contributes to hospital readmissions, which occur in 20% of patients within 30 days post-discharge. Pharmacist-led medication education interventions may improve adherence and reduce adverse cardiovascular outcomes.

Aims: To evaluate whether pharmacist-led medication education improves medication adherence and cardiovascular outcomes in patients following ACS.

Methods: We conducted a systematic review and meta-analysis of studies assessing pharmacist-led education interventions in adults with ACS. We searched four databases - Embase, Scopus, MEDLINE, and PsychINFO - from January 2018 (date of last review) to October 2024. Eligible studies included randomised controlled trials (RCTs), cohort studies, and quasi-experimental designs. Outcomes included medication adherence, hospital readmissions, major adverse cardiovascular events (MACE), mortality, and patient-reported outcome measures. Risk of bias and certainty of evidence were assessed.

Results: Nine studies (n = 3,946) were included in the review. Meta-analysis of three observational studies demonstrated improved long-term medication adherence (pooled OR: 1.62; 95% CI: 1.14–2.31; I² = 0%). Three RCTs also suggested adherence benefits, though the duration of effect varied across studies. Meta-analyses showed significant reductions in short-term (OR: 0.48) and long-term (OR: 0.47) hospital readmissions (p < 0.01 for both; I² = 0%). MACE outcomes were mixed, with one study reporting reduced cardiac-related mortality.

Conclusion: Pharmacist-led education improves medication adherence and reduces hospital readmissions in ACS patients. While mortality benefits remain inconclusive, these interventions offer a promising model for secondary prevention. A feasibility or cluster-based study is warranted to assess implementation, scalability, and cost-effectiveness to inform future policy and system integration.

Keywords: Pharmacist-led education, acute coronary syndrome, medication adherence

Introduction: Multimorbidity, significantly impacts patient outcomes, often leading to adherence challenges. This study aimed to evaluate medication non-adherence and non-persistence in patients with multimorbidity and to identify associated factors.
Methods: A retrospective observational cohort study was conducted using pharmacy claims data in Lisbon from 15,944 patients with multimorbidity, collected between 2011 and 2017. Medication adherence was assessed using the Medication Possession Ratio, while persistence was evaluated using refill-sequence analysis with a 90-day grace period, both calculated based on "any-medication". Logistic regression and Kaplan-Meier analyses were employed to identify factors associated with adherence and persistence, respectively.
Results: Overall medication adherence was 68.8%. Females patients (OR1.28 95% CI 1.178– 1.39), patients with initial diagnoses of respiratory disease (OR1.94 95% CI 1.51–2.48), cardiovascular disease (OR1.79 95% CI 1.49–2.14), hypertension (OR1.64 95% CI 1.40–1.91), those with >5 total diseases (OR2.26 95% CI 1.47–3.45), 3 diseases (OR2.00 95% CI 1.82–2.20), 4 diseases (OR1.56 95% CI 1.33–1.83), and those taking >10 medications (OR 116.50 95% CI 67.47 – 201.17), 7-9 medications (OR18.12 95% CI 14.72 – 22.29), and 4-6 medications (OR5.04 95% CI 4.54 – 5.59). were associated with non-adherence medication. All p-values were< 0.001. Moreover, almost half of multimorbidity patients (41.2%) have a non-persistence. Patients with first diagnosed cardiovascular disease (1.39 95%CI 1.23−1.56; p-value <0.001) and hypertension (1.25 95%CI 1.12–1.39; p-value <0.001) had a higher likelihood of medication non persistence compared to those with diabetes mellitus, while first diagnosed bone disease patients had a lower likelihood (0.39 95%CI 0.25–0.54; p-value <0.001).
Conclusion: This study demonstrates that medication adherence and persistence are significantly compromised in patients with multimorbidity. Factors associated with medication adherence were distinct from those influencing persistence. This suggests that interventions and strategies to improve medication-taking behavior must be tailored specifically to the phase of adherence being addressed.

Background: Chronic kidney disease of unknown etiology (CKDu) is emerging as a critical public health concern in several regions, with a concerning rise in incidence by 15-20%.
Objectives: This study aimed to determine the prevalence and risk factors of CKDu in Udupi district of Karnataka, with a particular focus on occupationally vulnerable populations ie., fishermen, labourers, drivers, and farmers. It also aimed to assess disease progression over a one-year follow-up period.
Methodology: A community-based, prospective-cross-sectional study was conducted using a two-stage cluster sampling technique across five outreach centres. Individuals with a history of diabetes (RBS>200mg/dl) or hypertension requiring medications were excluded. After obtaining informed consent, participants were interviewed in their preferred language (English or Kannada) using a pre-validated questionnaire. Anthropometric data were collected and biological samples were obtained for analysis of urinary albumin, glucose, and serum creatinine. Participants with an estimated eGFR<60ml/min/1.73m2 were re-evaluated after 3 and 12 months to monitor disease progression. Multivariate logistic regression was used to identify independent risk factors, with all analyses performed using SPSS vs 20.
Results: The overall prevalence of CKDu was 4.7% among the 1359 screened individuals. The majority of participants were labourers (32%,n=435), followed by fishermen (28%,n=381) and drivers (25%,n=340). Significant associations were observed between CKDu and several exposures, including high pesticide use [OR:1.52(1.23-1.89)], reliance on home remedies for common illnesses [OR:1.24(1.17-1.68)], lack of sub-protective measures during outdoor work [OR:1.87(1.37-2.65)], use of well water as the primary drinking source [OR:2.1(1.58-2.90)]and frequent use of aluminium cooking vessels [OR:1.32(1.04-1.78)]. These risk factors remained consistent among follow-up participants. Loss to follow-up was minimal (0.3%).
Conclusion: The study reported a 4.7% prevalence of CKDu in the Udupi district in the high-risk occupational group. Modifiable environmental and occupational exposures were significantly associated with CKDu. The findings suggest an urgent need for public health interventions and community awareness.

Introduction: HIV has become a manageable chronic disease with universal access to antiretroviral therapy(ART), targeting immune reconstitution and viral suppression. However, some patients experience low-level viraemia(LLV), i.e, low but detectable HIV RNA levels, associated with increased risk of virologic failure, opportunistic infections, and non-communicable diseases (NCDs). Limited data exist on how ART regimens like TLE(Tenofovir+Lamivudine+Efavirenz) or TLD(Tenofovir+Lamivudine+Doutegravir) affect LLV occurrence and outcomes.

Aims: To assess the prevalence, clinical profile, and outcomes of LLV among HIV–1 infected adults on TLE and TLD regimen.

Methods: This retrospective study at an HIV-care centre included adults with LLV between 1/1/2021 and 31/12/2022. Participants were on TLE/TLD for ≥6 months, ≥95% adherence, and had at least two viral-load reports. Follow-up continued until viral suppression, virologic failure, death, or the latest clinic visit. Chi-square test and descriptive analysis were used.

Results: Among 773 records screened, 62 patients (Prevalance-8%) had LLV. High-LLV was significantly associated with cryptococcosis (p = 0.026). TB occurred in 3.2%, all on TLE. Diabetes was the most common NCD(9.6%), more frequent among TLE patients. Immune discordance occurred in 8%, mostly on TLE(80%). Virological failure(1.6%) occurred in one patient who developed LLV after switching from TLE to TLD. Viral suppression was achieved in 93.5%, and persistent LLV occurred in 1.6%, both mostly among those on TLE. Two deaths(3.2%) occurred, one each in TLE and TLD groups.

Conclusion: High-LLV in our study was associated with cryptococcosis, suggesting ART initiation during advanced HIV with larger viral reservoirs. LLV was more common in TLE patients, with improved suppression after switching to TLD. This may suggest resistance from prolonged TLE exposure, though lack of resistance testing limits interpretation. Higher NCD rates in TLE patients likely reflect longer ART duration. Larger studies with resistance testing are needed to clarify LLV’s impact on TLE/TLD.

Keywords: Low-level viremia, ART, TLE/TLD regimen

Introduction: The 2022 economic crisis in Sri Lanka raised uncertainty regarding prices and affordability of essential medicines (EMs).

Aims: This study aimed to assess the impact of the economic crisis on the prices and out-of-pocket affordability of selected EMs in private pharmacies in Sri Lanka.

Methodology: The World Health Organization/Health Action International methodology was adopted to assess the prices and affordability of EMs in private pharmacies across six provinces in Sri Lanka. Price data for Originator Brands (OBs) and Lowest Priced Generics (LPGs) of 67 selected EMs were collected in January 2025. The Median Price Ratio (MPR) was calculated by dividing the median local price by the last updated International Reference Price (IRP) following inflation adjustment. The results were compared with prices from price control gazettes and 2015 historical data. Out-of-pocket affordability was estimated using the median price and the lowest paid government worker’s daily wage in Sri Lanka.

Results: The MPRs of LPGs ranged from 0.1427 to 9.6875, while originators ranged from 0.4956 to 37.1131. A total of 26/67 LPGs and 3/23 originators recorded MPRs <1, and 19.40% of LPGs and 43.48% of originators exceeded two. Comparative MPR analysis with 2015 showed rising trends (LPGs: 45.45%, OB: 50%). Several EMs showed improved pricing, dropping closer to IRPs. Forty-four medicines included in price-control gazettes revealed conformity (97.42%) to the price ceiling. Notably, majority median prices were below the ceiling price, with percentage differences ranging from -0.02% to -1122.46%. Most LPGs (54/67) were affordable except amoxicillin oral suspension, warfarin sodium, sodium valproate and acyclovir tablets.

Conclusion: Our study indicates that although some medicine prices declined, many medicines had increased prices post-economic crisis, but were still affordable. This is likely influenced by government-introduced price control measures for EMs in 2019.

Keywords: Essential Medicines, Medicine Price, Affordability

Introduction: Probiotics supplementation has gained importance in various medical conditions due to their capacity to improve gut health, modulate immune responses, and mitigate antibiotic-associated side effects.
Aims: This study aimed to assess the effect of probiotic supplementation on multiple dimensions of tuberculosis (TB) care, including clinical, humanistic, and safety outcomes.
Methods: This study is a prospective observational study. Data were collected for TB treatment outcome, haematological inflammatory indices, anti-tuberculosis treatment (ATT) induced adverse drug reactions (ADRs), and health-related quality of life (HRQoL) using the EuroQol 5-Dimension 5-level questionnaire to evaluate the effect of probiotics supplementation.
Results: 177 drug-sensitive pulmonary TB (PTB) patients were enrolled. TB treatment success rates between the study group (SG) and the reference group (RG) were 85.1% and 84.6%, respectively (p= 1.000). Among haematological inflammatory indices, only the systemic inflammation response index (SIRI) showed a statistically significant reduction after probiotic supplementation (p= 0.048). No significant changes were observed in HRQoL scores at various time points. ATT-induced ADRs were significantly lower in SG than RG (14.8% vs. 61.3%; p < 0.001).
Conclusion: Probiotic supplementation did not significantly influence TB treatment success or HRQoL outcomes but demonstrated a favorable impact on systemic inflammation and a significant reduction in the incidence of ATT-induced ADRs, especially gastrointestinal side effects. These findings suggest a potential role for probiotics as a supportive adjunct to ameliorate ATT-induced ADRs. Future studies should focus on assessing long-term supplementation effects to investigate humanistic outcomes.
Keywords: Pulmonary tuberculosis, probiotics, drug safety

Introduction
Concerns have been raised regarding the potential psychiatric and neuropsychiatric complications following COVID-19 infection.

Aims
We aimed to investigate short-, medium-, and long-term risks of psychiatric and neuropsychiatric disorders following COVID-19 infection in five countries.

Methods
This population-based multinational cohort study used electronic medical records from France, Italy, Germany, and the UK and claims data from the USA. Individuals with COVID-19 between 01/12/2019 and 01/12/2020 were included as targets. Ten comparators without COVID-19 for each target were selected using the propensity score matching approach. All individuals were followed from the index date until the last record. Cox models were fitted to estimate risks of incident diagnosis of depression, anxiety disorders, alcohol misuse or dependence, substance misuse or dependence, bipolar disorders, psychoses, personality disorders, self-harm and suicide, sleep disorders, dementia, and neurodevelopmental disorders within the first 6 months (short-term), 6 months to 1 year (medium-term), and 1 to 2 years (long-term) post-infection.

Results
A total of 303,251 individuals with COVID-19 and 22,108,925 without COVID-19 from five countries were included. Within the first 6 months, individuals with COVID-19 had a significantly higher risk of any studied disorders in all databases, with HR ranging from 1.14 (95% CI, 1.07–1.22) in Germany to 1.89 (1.64–2.17) in Italy. Increased risks were consistently observed for depression, anxiety disorders, and sleep disorders across almost all countries. During the medium- and long-term periods, higher risks were observed only for depression (medium-term: 1.29, 1.18–1.41; long-term: 1.36, 1.25–1.47), anxiety disorders (1.29, 1.20–1.38; 1.37, 1.29–1.47), and sleep disorders (1.10, 1.01–1.21; 1.14, 1.05–1.24) in France, and dementia (medium-term: 1.65, 1.28–2.10) in the UK.

Conclusions
Our study suggests that increased risks of psychiatric and neuropsychiatric outcomes were observed only within, and not after, the 6-month period across all databases, except for certain conditions in specific countries.

Keywords: Long-COVID; Psychiatric disorders; Neuropsychiatric disorders

Public Health and Pharmaceutical Equity: Availability of Essential Medicines in Public Hospitals
INTRODUCTION
Ensuring access to free essential medicines is a vital aspect of universal health coverage. National Essential Medicines List (NEML) enhances the accessibility and utilisation of essential medicines within healthcare systems.
AIMS
A study was conducted to evaluate the availability of essential medicines, inventory management, and the quality of storage facilities in public sector healthcare establishments.
METHODS
The current research was carried out in 40 public health facilities across the Suryapet district in Telangana state using the ELM approach. The study included six Community Health Centres (CHCs), 26 Primary Health Centres (PHCs), four Urban Primary Health Centres (UPHCs), and three BDKs. The district's drug procurement processes were assessed through document analysis and in-depth interviews with key stakeholders. Stock registers were examined to gather data on the availability of a selection of essential medicines at the PHC level (92), CHC level (132), and tertiary care level (District Hospital/Medical College) (160).
RESULTS
The overall percentage of medicine availability is 45.2%. Anti-hypertensive medicines are available (60%), and anti-diabetic medicines (44%). Every category of medicines, including analgesics/antipyretics, anthelminthics, antispasmodics, antiemetics, antihypertensives, and uterotonics, had at least one drug that was almost always available in public sector facilities. In contrast, medicines such as thrombolytics, anti-cancer agents, and endocrine treatments were found in fewer than 30% of public sector facilities. Among the medicines not stocked during the survey, approximately 60% had been out of stock for 3 to 6 months, while 8% had been unavailable for more than 6 months.
CONCLUSION
Ensuring access to free essential medicines reduces out-of-pocket expenses, providing a sustainable approach to achieving universal health coverage in India.
KEYWORDS
Essential medicines, Public sector, Generic, Anti-hypertensive, Procurement, Universal health care

Introduction: Breast cancer health education is an effort in our study to raise awareness and mitigate the effects of breast cancer via education on risk factors, symptoms, barriers to seeking medical help, and regular practice of BSE, with the hope that vast understanding will guide to sooner detection of the disease and to achieve high survival rates.
Aims : To evaluate the Health Education Intervention among these women after imparting education on the above aspects of breast cancer.
Methods: The study was a descriptive, cross-sectional study conducted during the year of 2017-2023 in Bengaluru. A validated questionnaire was used Pre and post intervention phase. Women within the age group of 15-65 years were included and a total of 3100 were considered for this study . The same group of individuals were analyzed before and after the health educational intervention.
Results: Almost 45.30% of participants had poor knowledge, at baseline regarding BC. This improved up to 71.90% of the subjects having good knowledge after the health education. The data also acknowledged that participants with poor knowledge of signs & symptoms of BC dropped from 45.10% to 1.5% which proves tremendous & positive impact of health education. Post-intervention the participants with good knowledge of BSE screening and practice had increased from 22.7 % to 80.3% which was almost a 4-fold rise after the education program compared to baseline.
Conclusions: This study had given the evidence that supports the improvements in women’s knowledge and compliance with BSE, after health educational intervention. Hence, Health education intervention was effective in improving women's behavior and commitment to breast self- examination as a preventive measure for the breast cancer.
Key words – Health Education, Intervention, Breast Self-Examination

Introduction: Drug-Induced Cerebral Hemorrhage (DICH) or Drug-Induced Hemorrhagic Stroke (DIHS), is a sudden bleeding in the brain tissues or ventricles with drug use. Studies have identified antithrombotic medications as common agents causing DICH. Despite drugs from various other classes being linked to DICH, a comprehensive study on them has not been established.

Aims: This study aims to systematically assess the adverse event signals of therapies inducing DICH using the U.S. FDA Adverse Event Reporting System (FAERS) database, employing disproportionality analysis (DPA) methods.

Methods: Data from FAERS (1988 to Q1 2025) was extracted and analyzed using frequentist statistics. After data standardization, two disproportionality methods were used: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR). Reports coded with the preferred term 'Cerebral Hemorrhage' were extracted and drug-event pairs with ≥10 reported cases were included. A drug-event pair was considered a positive signal if it met all the following thresholds: PRR ≥ 2; χ² ≥ 4 and ROR > 1 with 95% confidence interval.

Results: From 1998 to 2025, 33,888 adverse event reports were recorded, identifying 650 drugs associated with cerebral hemorrhage. Of these, 378 drugs reported ≥10 cases and met the predefined criteria for positive disproportionality signals. Antithrombotic agents accounted for the most frequent and strongest signals, including clopidogrel bisulfate (PRR 15.8), rivaroxaban (PRR 13.56), clopidogrel (PRR 10.32), warfarin (PRR 8.79), aspirin (PRR 6.45) and apixaban (PRR 6.35). Among the top 15 DICH-linked drugs, commonly used non-antithrombotic agents were bisoprolol (PRR 5.2), furosemide (PRR 2.59), metoprolol (PRR 2.26) and amlodipine (PRR 2.01). Identified drugs exhibited χ² values from 346 to 24,347, confirming statistically significant disproportionality.

Conclusions: The findings reveal signals from both expected antithrombotics and non-antithrombotics like bisoprolol, furosemide, metoprolol and amlodipine. Thus, emphasizing the need for adequate/routine drug safety monitoring of these medications.

Keywords: Cerebral Hemorrhage; Disproportionality Analysis; Pharmacovigilance

Introduction: A recently developed Korean claims-based pregnancy algorithm, based on pregnancies with systemic lupus erythematosus, may enhance the identification of pregnancy episodes for observational research. However, its applicability has not yet been validated in the general pregnant population.
Aims: To evaluate and refine the performance of the existing Korean claims-based pregnancy algorithm.
Methods: The nationwide claims database from the Korean National Health Insurance Service between February 27, 2021, and December 31, 2022, was used to identify pregnancy outcomes. Gestational age (GA) was estimated based on the dates of prenatal healthcare utilization, including codes of four types of ultrasound. The Original algorithm prioritized the date from the second-or third-trimester targeted scan (TS), whereas the Modified algorithm prioritized the date of the first-trimester TS. Algorithm performance was evaluated based on the following three criteria: first, the agreement between the estimated GA and the GA included in a PB code among delivery episodes; second, comparison of estimated PB (ePB) rates with national statistics reported by the Korean Statistical Information Service (KOSIS); third, changes in ePB rate according to ultrasound code priority.
Results: Of 456,157 delivery episodes, those with a GA of less than 37 weeks were classified as ePB, with rates of 39.7% in the Original algorithm and 11.9% in the Modified algorithm. In delivery episodes with PB codes that included specified GA ranges, the Modified algorithm demonstrated higher agreement with the specified GA compared to the Original algorithm (96.4% vs. 75.2%). The ePB rate estimated by the Modified algorithm was also more consistent with the 9.4% reported by KOSIS (12.0% vs 39.8%). Algorithms that prioritized first-trimester ultrasound code estimated the lowest ePB rate.
Conclusion: The Modified algorithm, which prioritized first-trimester TS codes, improved GA estimation accuracy and reduced the GA underestimation observed in the Original algorithm.
KEY WORDS: Algorithms, Pregnancy, Gestational age

Introduction:
Drug-drug interactions (DDIs) pose significant risks in chronic disease management, where patients often complex polypharmacy occurs. DDIs can lead to adverse events, reduced therapeutic efficacy, and increased healthcare costs. Although digital DDI checking tools are widely recommended, concerns persist regarding their reliability and clinical validity, as supported by unharmonious DDI tool classifications.
Aim:
To evaluate the reliability and harmonisation of DDI checking tools used in chronic disease and polypharmacy management.
Methods:
Following PRISMA-ScR guidelines, we searched MEDLINE, Embase, Scopus, Web of Science, Google Scholar, ACM, and IEEE Xplore databases for studies published between January 2015 and April 2025 that compared ≥2 DDI checkers in chronic disease settings. Methodological quality and validity used tailored versions of QUADAS-2 and QUADAS-C. Reliability was evaluated via inter-rater reliability metrics and descriptive statistics. Data were reported descriptively.
Results:
Thirty-nine studies met the inclusion criteria. The most frequently assessed tools were Micromedex, Drugs.com, LexiDrug, Medscape, Epocrates, and UpToDate, (median: 3 tools per study). Inter-rater reliability was generally low indicating limited agreement between tools (Fleiss’ Kappa: –0.055 to 0.695; Cohen’s Kappa: –0.065 to 0.644; Gwet’s AC1 was similarly low). A few studies used Kendall’s W and Kruskal-Wallis tests, reporting significant differences in identified DDIs (p < 0.05). Eleven studies relied solely on descriptive statistics. Many studies focused on consensus of tools, with limited studies using a reference standard such as specialised clinicians, FDA labels, or clinical outcomes. High risks of bias were identified in medication selection, reference standard quality and index comparability.
Conclusion:
DDI checking tools show limited reliability and validity, with minimal consensus, raising concerns about the clinical interpretation and classification of DDIs and the validity of supporting evidence. Standardised evaluation frameworks, greater algorithm transparency, and benchmarking against clinical outcomes are needed to improve tool accuracy and harmonisation.

Keywords: drug-drug interactions, drug-drug checkers, medication safety

Introduction: Gastroesophageal reflux disease (GERD) frequently co-occurs in patients with chronic obstructive pulmonary disease (COPD), contributing to worsened respiratory symptoms. Despite their widespread use, proton pump inhibitors (PPIs) have been linked to uncertain respiratory risks. Potassium-competitive acid blockers (P-CABs), introduced in Korea in 2018 as a newer class of acid suppressants, offer an alternative, but their safety in COPD remains unclear.
Aims: To compare the risks of pneumonia and moderate-to-severe COPD exacerbations between P-CAB and PPI use in COPD patients.
Methods: We applied a target trial emulation to compare the risks of pneumonia and COPD exacerbation between P-CAB and PPI users. We identified patients aged 40 years or older with COPD and comorbid GERD who newly initiated P-CAB or PPI therapy between 2019 and 2022. Follow-up continued from treatment initiation until outcome occurrence, treatment discontinuation, drug switching, death, or study end. Study outcomes included pneumonia and moderate-to-severe COPD exacerbation. Propensity score matching (1:3) was used to balance baseline characteristics, and hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazards models.
Results: After matching, 4,671 P-CAB users and 14,013 PPI users were included. The P-CAB group showed a trend toward lower risks of pneumonia (aHR, 0.76; 95% CI, 0.54–1.07) and severe exacerbation (aHR, 0.60; 95% CI, 0.32–1.14), although neither was significant. These trends remained largely consistent across subgroups. Among patients with a Charlson Comorbidity Index ≤ 1, P-CAB use was significantly associated with a reduced risk of severe exacerbation (aHR, 0.31; 95% CI, 0.11–0.88).
Conclusions: P-CABs demonstrated a favorable pattern of reduced risks for pneumonia and severe exacerbation compared to PPIs. These findings may indicate potential respiratory benefits for COPD patients with GERD, particularly those with fewer comorbidities.

Keywords: Potassium-competitive acid blockers (P-CABs), Chronic obstructive pulmonary disease (COPD), Target Trial Emulation (TTE)

Introduction:
Hypervirulent Klebsiella pneumoniae (HvKp) is linked to invasive syndromes, including liver-abscess and meningitis. Its hypermucoviscosity-phenotype, driven by capsular regulators like rmpA and magA, makes standard antibiotics less effective. Rifampicin, a transcriptional-inhibitor, shows potential antivirulence activity but remains under-investigated in HvKp-infections.
Aims:
To assess the impact and outcomes of rifampicin regimens for HvKp-infections.
Methods:
We conducted a systematic search across PubMed, Embase, Scopus, and Cochrane from inception-to-June 2025. Due to the limited volume of high-level evidence, we included in-vitro, in-vivo studies, and case-reports evaluating rifampicin against confirmed HvKp-infections. Extracted data included dose, timing, co-administered agents, and clinical outcomes. Study quality was assessed using the SYRCLE risk-of-bias tool for animal studies and the JBI checklist for case-reports.
Results:
Seven studies met inclusion: one in-vivo murine study, two mechanistic in-vitro studies, and four case-reports. In-vivo, rifampicin combined with zidovudine led to complete bacterial clearance and 100% survival. Mechanistic in-vitro studies demonstrated that rifampicin suppressed mucoviscosity via downregulation of rmpA/magA. Among the four clinical-cases the HvKp strains were was defined by hypermucoviscous phenotype (string-test +ve), three patients recovered following early rifampicin use (within 3–5 days), administered at 450–600 mg/day. These were used in combination with meropenem/cefoperazone+sulbactam, with symptomatic improvement within 3–7 days. One case involving emphysematous pyelonephritis responded to rifampicin with meropenem and levofloxacin. A fourth case, involving a severely immunocompromised patient with delayed rifampicin initiation (>21 days), resulted in deterioration and scummed to death. None of the cases reported rifampicin-associated toxicity.
Conclusions:
Rifampicin may exert antivirulence effects in in-vitro and murine models and appears to offer adjunctive therapeutic benefit when initiated early in HvKp-infections. The apparent synergy with agents like meropenem or zidovudine warrants further investigation. Given the reliance on low-powered, non-randomized designs, these findings should be interpreted cautiously. Controlled trials are essential to validate efficacy, define optimal use, and evaluate safety.

Introduction
Public interest in mRNA vaccines has grown since their rapid COVID 19 rollout in late 2020, but concerns have arisen about potential autoimmune effects, including a possible link to type 1 diabetes. However, assessing a potential causal link between mRNA based COVID 19 vaccines and type 1 diabetes in young adults is challenging and may be affected by unmeasured confounding.

Aims
To evaluate the risk of type 1 diabetes who received mRNA-based COVID‑19 vaccines in young adults.

Methods
We emulated a target trial using multi institutional electronic health records (2021–2023), including young adults (≤40 years) receiving their first dose of either an mRNA based or adenoviral vector–based COVID-19 vaccine. We assigned individuals according to the vaccine type they received for their first dose, and the date of that dose was defined as their index date. Propensity score matching balanced baseline characteristics, and Cox proportional hazards models with negative control outcome calibration estimated adjusted hazard ratios (HRs). We further conducted animal models to explore biological plausibility by assessing pancreatic β cell stress after mRNA based vaccination.

Results
Among 27,849 vaccine recipients (36% male; mean age 29 years), mRNA-based COVID‑19 vaccination was associated with a two‑fold higher risk of incident type 1 diabetes compared with adenoviral vector vaccines (HR 2.00; 95% CI 1.06–3.77). These results remained consistent after controlling for unmeasured confounders (HR: 1.98; 95% CI: 1.05-3.75). Evidence from animal studies indicated that mRNA based vaccination intensified hyperglycemia and impaired glucose tolerance in β cell dysfunction models.

Conclusions
Even after we controlled all confounders, mRNA‑based COVID‑19 vaccines were associated with an elevated type 1 diabetes risk in young adults, with support from animal models indicating β‑cell impairment.

Keywords mRNA vaccination, type 1 diabetes, negative control outcome calibration, animal models

Introduction:
The prevalence of type 2 diabetes among women of reproductive age is increasing, resulting in greater exposure to antidiabetic medications during pregnancy. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT-2is) are commonly used non-insulin agents, but their safety during pregnancy remains uncertain. Though not recommended during conception and pregnancy due to potential risks, unintentional early exposure does occur.

Objectives:
To evaluate maternal and neonatal outcomes after early pregnancy exposure to GLP-1RAs or SGLT-2is, compared to insulin or metformin, among women with type 2 diabetes.

Methods:
We conducted a retrospective cohort study using data from 2019 to 2024, including pregnant women aged 12–55 years with type 2 diabetes and exposure to antidiabetic medications within 90 days before the last menstrual period and during the first 97 days of pregnancy. Descriptive statistics were used. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for selected outcomes.

Results:
Among 777 participants, miscarriage rates were 26.0% for GLP-1RAs and 29.0% for SGLT-2is, higher than in the insulin/metformin group (9.7%). SGLT-2i exposure was associated with a significantly increased risk (HR = 1.83, 95% CI: 1.19–2.79). Preterm birth was less common in the GLP-1RA (9.8%) and SGLT-2i (8.9%) groups versus controls (15.6%), with a significant reduction for SGLT-2i (HR = 0.54, 95% CI: 0.32–0.92). No increase in major birth defects was observed. Glycemic control and neonatal birth weight were similar across groups.

Conclusions:
Early exposure to GLP-1RAs or SGLT-2is may increase miscarriage risk, particularly with SGLT-2is, but does not appear to raise risks of preterm birth or birth defects. These findings suggest that unintended early pregnancy exposure may pose lower risks than previously assumed.

Keywords: Type 2 diabetes, early pregnancy, GLP-1 receptor agonists, SGLT-2 inhibitors

Introduction: Pregnant women frequently experience health issues; in severe cases, medications are often used, though their risks for infant health remain unclear.
Aims: To evaluate the potential effects of analgesics, antibiotics, antiemetics, and progesterone, commonly prescribed during pregnancy, on infant birth anomalies.
Methods: Systematic reviews and meta-analyses were identified through a comprehensive search. Reviews assessing associations between these medications and specific congenital anomalies or birth outcomes (e.g., low birth weight, congenital heart defects, cerebral palsy) were included. Methodological quality was assessed using AMSTAR2, and reporting quality was evaluated by the PRISMA checklist. Pooled estimates of association were extracted from each meta-analysis and evaluated by medication and outcome using the GRADE criteria.
Results: Twenty-five meta-analyses were included. Nonsteroidal anti-inflammatory drugs (NSAIDs) were associated with eight congenital anomalies. Aspirin was linked to congenital heart defects and gastroschisis. Indomethacin was associated with an increased risk of bronchopulmonary dysplasia. Acetaminophen was associated with a reduced risk of low birth weight. Antiemetics were linked to ten distinct birth anomalies. Antibiotics were associated with gastrointestinal and cardiac malformations, congenital hydrocephaly, cerebral palsy, and epilepsy. Whereas progesterone showed no significant associations with outcomes. Although most reviews met the majority of PRISMA criteria, protocol registration, handling of missing data, and assessment of the certainty of evidence were frequently unreported. Using the AMSTAR2 criteria, there were 12 high-quality reviews, 4 medium, 7 low, and 2 critically low. All significant associations between drug type and outcomes were moderate (n = 18) and high (n=1) across the GRADE criteria.
Conclusions: This umbrella review identified associations between medications and birth outcomes. While those were identified, inconsistencies between specific drugs and outcomes, selection bias, and missing protocol registration limited certainty. Potential risks to infant health should be considered when making decisions on medication use during pregnancy.
Keywords: Pregnancy, medication safety, umbrella review

Introduction: In developing countries, limited resources, understaffing, and underdeveloped reporting systems increase the risk and impact of medication errors (MEs). Clinical pharmacists play a critical role in addressing these challenges through active involvement in medication safety and error prevention.
Objectives: This study aimed to establish a medication error reporting and monitoring program in a tertiary care teaching hospital in South India.
Methods: A prospective cohort study was conducted over three years among hospitalized patients aged ≥18 years. Daily interviews with patients, caregivers, and healthcare professionals (HCPs), along with medical record reviews, were used to identify MEs and assess outcomes using the NCC MERP classification and prevention standards. Root cause analysis was performed for each error and findings were shared with relevant HCPs to reduce recurrence.
Results: Among 20,256 hospitalized patients, 1,310 MEs were reported, yielding an incidence rate of 6.4%. The most frequent types were administration errors (38.2%), followed by prescribing/transcribing (28%), and dispensing/procurement errors (17% each). Clinical pharmacists reported the majority of errors (51%), followed by nurses (31%) and doctors (17%). Most errors were classified as Category A (33%) and Category B (32%). Key root causes included distractions (472 cases), workload (422), and communication gaps (341). The most commonly implicated drug classes were analgesics (19.4%) and antibiotics (15.7%). Significant risk factors for MEs included prolonged hospital stay (OR 2.31), polypharmacy (OR 2.30), comorbidities (OR 1.79), and work shifts (OR 2.36), all at 95% confidence interval.
Conclusions: The implementation of a structured medication error reporting system led by clinical pharmacists enhances patient safety in resource-limited settings. Encouraging a non-punitive, collaborative approach among all healthcare stakeholders is essential. Clinical pharmacists are vital in sustaining this system by providing continuous surveillance, education, and system-level interventions in partnership with the healthcare team.
Keywords: Medication Errors, Clinical Pharmacist, Stewardship, Patient Safety

Background
Oral anticoagulants (OACs) are commonly used for stroke prevention in atrial fibrillation (AF), but their effectiveness and safety in individuals with peritoneal dialysis (PD) remain uncertain due to limited and conflicting evidence.
Objectives
To assess the association between OAC use and stroke risk in PD patients using a target trial emulation framework.
Methods
Using territory-wide electronic health records from Hong Kong (2005–2019), the adults with chronic kidney disease on PD with an incident diagnosis of AF were included. A sequential trial emulation approach compared OAC initiators to non-initiators, with monthly eligibility assessment from January 2006 to December 2019. Primary outcomes were a composite stroke (ischemic/haemorrhagic/all-cause mortality) and major bleeding (haemorrhagic stroke, gastrointestinal bleeding and other bleeding events). A logistic regression including baseline covariates (age, sex, CHA₂DS₂-VASc score, comorbidities, antiplatelet use, etc) was used for propensity score (PS). PS matching (1:10) were used to emulated randomization in the target trial. Pooled logistic regression with 500 bootstraps estimated 3-year risk differences (RDs) and 95% confidence intervals. Subgroup analyses by sex and age were prespecified.
Results
Among 8,230 eligible PD patients with AF, only 81 (0.98%) initiated OACs. After matching, 81 initiators and 806 non-initiators were analysed (median follow-up: 357 days). No significant difference was observed in the 3-year cumulative incidence of: composite stroke (RD: −0.03%, 95% CI: −0.18% to 0.11%), major bleeding (RD: −0.01%, 95% CI: −0.15% to 0.12%). Subgroup analyses (age, sex) and sensitivity analyses yielded consistent null associations.
Conclusions
In this population-based study of peritoneal dialysis patients with AF or AFL, OAC initiation did not reduce stroke, mortality, or bleeding risk in PD patients with AF. These findings suggest that the benefits of OACs in this high-risk population remain uncertain.

Introduction:
Asia, with its rapidly developing pharmaceutical markets and heterogeneous healthcare systems, faces significant challenges in adverse drug event (ADE) surveillance. These challenges include under-reporting, late detection, and inefficient cross-border information sharing. Conventional, centralised pharmacovigilance systems often fail to provide real-time, population-relevant safety information.

Aim:
The objective of this research is to conceptualise and propose a blockchain- and federated AI-powered decentralised pharmacovigilance network. This network aims to facilitate real-time detection of ADEs, secure data exchange, and risk stratification at the individual level among Asian healthcare systems.

Methods:
A trilateral pilot scheme involving India, Singapore, and South Korea will be developed. This scheme will incorporate the following components:
- Blockchain (Ethereum-based smart contracts): These will ensure immutability, security, and transparency in event reporting.
- Federated learning: This technology will enable AI-based signal detection on privacy-protected, decentralised datasets.
- Genomic information and mobile health data inputs: These will provide patient-specific ADE prediction capabilities.
- Regulator, hospital, pharmacy, and patient community stakeholder nodes: These will facilitate communication and collaboration within the network.

System Performance Simulation and Assessment:
System performance metrics, including signal lag, false positive rate, and latency, will be simulated and assessed to evaluate the network’s effectiveness.

Expected Results:
The network is anticipated to reduce reporting latency by 60%, enhance the identification of rare ADEs, and enhance public trust in drug safety systems. Genomic profile-guided personalised alerts will facilitate proactive pharmacovigilance.

Conclusion:
This research redefines pharmacovigilance as a smart, decentralised system that enables real-time, ethically controlled drug safety monitoring in Asia. The proposed model sets the foundation for a future where ADE prediction is not an option but a policy-driven norm.

Keywords: Pharmacovigilance, Decentralised Artificial Intelligence (AI), Real-Time Adverse Event Detection (ADE),

Introduction: Ustekinumab (UST) is an established treatment for the long-term management of plaque psoriasis (PsO), providing a reliable balance between effectiveness and safety. In real-world clinical practice, persistence of UST is an important indicator of therapeutic success influenced by efficacy, safety and patient satisfaction.

Aims: This study aims to describe persistence of UST in patients with PsO in Japan and China.

Methods. This retrospective cohort study utilized Japanese Medical Data Vision database (MDV) and Japan Medical Data Center (JMDC) claims data, and electronic medical records from Ruijin Hospital (Ruijin) in China. The study population included adults treated with UST for PsO (ICD-10=L40.0) from 01 January 2012, in Japan and 01 January 2021, in China, through 31 May 2024. Persistence was measured from UST initiation to discontinuation as indicated by a 24-week gap after the last UST prescription. Persistence was assessed using Kaplan-Meier methods, treating discontinuations as events, and loss to follow-up or study end as censoring. Median persistence was reported when 50% of patients remained persistent. Persistence probabilities with 95%CI were estimated at 3-months, 1- and 2-years post UST initiation.

Results: Among 904 MDV, 208 JMDC, and 119 Ruijin patients, 95% were persistent with UST at 3-months. For the MDV and JMDC cohorts, median persistence was 30.0 (27.7-34.0) and 26.2 (20.5-32.5) months, respectively; 1-year persistence probabilities were 73.5% (70.4%-76.3%) and 71.0% (64.1%-76.8%), and 2-year probabilities were 57.7% (54.2%-60.9%) and 51.9% (44.5%-58.8%). Median persistence was unavailable for the Ruijin cohort, as 60% of patients remained persistent until the end of follow-up after 24 months. The 1-year and 2-year persistence probabilities were 71.9% (61.2%-80.1%) and 64.2% (51.0%-74.7%), respectively.

Conclusions: UST showed comparable outcomes of persistence across various types of databases in Japan and China, demonstrating both short-term and long-term benefits for PsO patients in real-world clinical practice.

Keywords: Plaque psoriasis; Ustekinumab; Persistence.

Introduction: FDA expedited programs were introduced to accelerate access to innovative therapies. However, there is a lack of consensus on what constitutes “innovation” in pharmaceuticals.
Aims: This study examines how innovation-related features—first-in-class status, clinical innovation, and orphan designation—influence the likelihood of receiving FDA expedited program designations.
Methods: We conducted a retrospective analysis of 129 new drugs approved by the FDA from 2020 to 2024. Innovation-related features included first-in-class status, orphan designation (from FDA sources), and clinical innovation, based on HTA value ratings from France (HAS) and Germany (IQWiG/G-BA). Outcomes were four FDA expedited programs: Fast Track (FT), Breakthrough Therapy Designation (BTD), Accelerated Approval (AA), and Priority Review (PR). We used univariate and multivariate logistic regression models for each program, and Poisson models to evaluate associations with the number of designations.
Results: Among the 129 drugs, 82 (63.6%) received PR, 47 (36.4%) FT, 46 (35.7%) BTD, and 27 (20.9%) AA. In univariate logistic regression, all three innovation-related features were significantly associated with at least one expedited program. Clinical innovation was associated with all programs except for AA, while orphan designation showed strong associations with BTD and AA. In multivariate models, clinical innovation remained significant for FT (OR=3.33, p=0.009) and BTD (OR=3.93, p=0.007), and orphan designation for BTD (OR=5.81, p<0.001) and AA (OR=4.47, p=0.006). First-in-class status was only associated with PR (OR=2.32, p=0.036). Poisson models showed that orphan designation significantly increased the number of expedited designations (OR=1.69, p<0.001), while other features had weaker or borderline effects. Results were consistent in ordinal logistic models.
Conclusions: Orphan designation showed the strongest association with expedited program use, while clinical innovation had mixed effects and first-in-class status the weakest. These findings highlight differing priorities across programs and the need for clearer alignment between regulatory incentives and meaningful innovation.
Keywords: Innovation, Expedited programs, Regulatory science

Introduction: Methylphenidate is widely prescribed for attention-deficit/hyperactivity disorder, yet its adverse drug reaction (ADR) profile may differ by age, sex, or region due to biological factors and differences in drug use. Evidence for these subgroup risks is limited. Disproportionality analysis can identify subgroup-specific risk for the same medication.

Aims: To detect subgroup-specific safety signals of methylphenidate using disproportionality analysis.

Methods: Disproportionality analyses were conducted on individual case safety reports from the WHO-UMC global database (VigiBase) and the Korean Adverse Event Reporting System (KAERS) for 2015–2019. Reports listing any drug as suspected or interacting were included, while vaccine-related reports were excluded. ADRs were coded using MedDRA preferred terms. Subgroups were defined by sex; seven age groups; and geographic region across six WHO regions (VigiBase only). For signal detection, the Bayesian disproportionality metric Information Component (IC) was calculated for each drug–event pair, with its 99% lower bound (IC₉₉LB) applied to the methylphenidate subgroup and its 95% lower bound (IC₉₅LB) to the full dataset. Differential IC (ΔIC) quantifies disproportionate ADR reporting in subgroups. Signals were defined as: IC₉₉LB > 0 within subgroup; IC₉₅LB ≤ 0 overall; ΔIC > 1; and subgroup reports ≥10. Of these, signals from subgroups contributing ≥80% of methylphenidate or ADR reports were excluded, and identification as known or previously unrecognized ADRs was based on Micromedex.

Results: In VigiBase, 62 subgroup-level signals for methylphenidate were identified: 16 age-specific, 18 sex-specific, and 28 region-specific. Most of these were previously known ADRs. The strongest signal was “feeling abnormal” in children aged 2–11 years (n=82; IC₉₉LB=1.08; ΔIC=2.61). In contrast, no qualifying subgroup-level signals were detected in KAERS.

Conclusions: Subgroup disproportionality analysis in VigiBase identified distinctive signals for methylphenidate that were absent from national data. These findings highlight the importance of large databases like VigiBase for subgroup-specific pharmacovigilance.

Keywords: Methylphenidate, Subgroup Analysis, Pharmacovigilance

BACKGROUND: Due to the complexity of infection types, high resistance risks, and severe clinical consequences, there is an urgent need to optimize antimicrobial prescribing in hospital environment. However, key determinants on physician prescribing behavior remain divergent, evidence on the effectiveness of interventions is controversial.
OBJECTIVE: This study aims to clarify the determinants on physician antimicrobial prescribing in the inpatient environment and assess intervention effectiveness to optimize prescribing.
METHODS: We searched PubMed, Embase, Cochrane Library, and Web of Science up to July 5, 2025, to identify evidence on determinants of and interventions for antibiotic prescribing practices. We categorized determinants into prescriber, patient, and environment factors, then, through a single-arm meta-analysis to quantify the influence of determinants on the prescription behavior. We used a random-effects model to analyze the effect of interventions on prescription outcome. Interventions were categorized by Behavior Change Techniques (BCTs), with Effectiveness Rates (ERs) calculated.
RESULTS: Fifty-nine studies (20 qualitative and 39 quantitative) were included. Study indicated that 81%, 80%, and 65% of participants acknowledged the influence of environmental, prescriber, and patient factors, respectively. The intervention improved rational antimicrobial prescribing by 21%, reduced antimicrobial prescribing by 50%, and reduced antimicrobial consumption by 25%.BCT analysis showed that “behavior feedback” was most effective (ER=3.5).
CONCLUSION: This study confirms that physician antimicrobial prescribing in the inpatient environment is influenced by multiple factors and the interventions effectively improved prescribing practices. However, the effectiveness of the intervention was not sufficiently evaluated in resource-limited settings, and further research should optimize antimicrobial prescribing practices in low- and middle-income countries .
KEYWORDS: Antimicrobial prescribing;Determinants;Interventions

Introduction: Diabetes mellitus is a major public health concern in the United States, with increasing prevalence and treatment costs. Over the last 15 years, new non-insulin glucose-lowering drugs (GLDs) have entered the market, offering improved outcomes but at higher prices. The rising use and cost of these medications present important implications for public health spending.

Aims: This study aimed to examine national trends in the utilization, expenditure, and average cost of non-insulin GLDs from 2008 to 2023.

Methods: We conducted a retrospective trend analysis using 2008–2023 data from the National Medicaid State Drug Utilization database. All non-insulin GLDs were categorized and analyzed for prescription volume, reimbursement amount, and average cost per prescription. Total annual figures were calculated, and drug prices were computed by dividing reimbursement by prescription counts. Data analysis was performed using Excel and SAS 9.4.

Results: Non-insulin GLD prescriptions increased by 305% from 12.9 million in 2008 to 52.3 million in 2023. Metformin dominated utilization (53%) and remained low-cost ($11/prescription in 2023). Medicaid spent $2.8 billion on metformin and $1.2 billion on sulfonylureas. In contrast, GLP-1 receptor agonists and SGLT2 inhibitors showed significant utilization growth, with combined Medicaid expenditures reaching over $50 billion. The average prices of GLP-1 receptor agonists rose to over $1,100/prescription by 2023. SGLT2 inhibitors also increased sharply in cost, reaching over $770/prescription. Total Medicaid expenditure on non-insulin GLDs surged from $746 million in 2008 to $20.4 billion in 2023.

Conclusions: While metformin and sulfonylureas remain the most prescribed and affordable non-insulin GLDs, there has been a clear shift toward newer, costlier drug classes. These trends may have substantial implications for future diabetes care spending in the United States.

Introduction: Influenza vaccination remains the most effective public health measure to reduce influenza-related morbidity and mortality. However, the coronavirus disease 2019 (COVID-19) pandemic disrupted routine healthcare services and may have influenced preventive care behaviours, including influenza vaccine uptake. While several studies have explored this issue, findings on the impact of the COVID-19 pandemic on influenza vaccination coverage in the United States have been inconsistent. Understanding these patterns is critical for informing strategies to maintain or improve vaccine coverage during future public health emergencies.
Aims: To investigate trends of influenza vaccine uptake before and during the COVID-19 pandemic in the United States and explore the associated factors.
Methods: Using self-reported data from the National Health Interview Survey during 2014-2021 (response rates ranging from 50.7-70.1%), we estimated influenza vaccine uptake. Log-binomial regression models were used to test uptake changes with adjustment for and stratification by demographic and health factors.
Results: We included 58,249 children (mean age: 8.7 years; male: 51.1%) and 205,034 adults (mean age: 47.6 years; male: 48.2%). The prevalence ratio (PR) of uptake change comparing the intra- (2020-2021) to the pre-COVID-19 period (2014-2019) was 0.72 among children with a 10.7% reduction. Uptake changes were found across subgroups with higher reduction among those aged 0-2 years, non-Hispanic Black and Hispanic ethnicity, from South and West regions, and with lower household income. For adults, uptake increased before and during COVID-19 (PR=1.15, 95% CI: 1.12-1.18) but a 2.3% reduction was found among healthcare personnel (PR=0.95, 95% CI: 0.90-0.997).
Conclusions: Influenza vaccination decreased during the COVID-19 pandemic among children and healthcare personnel. Structure inequality to influenza vaccination warrants measures to improve vaccine uptake among vulnerable groups.

Introduction: Treatment-resistance is broadly defined as the failure of a disease to respond to adequate treatment. Research into treatment-resistant disease is increasingly conducted using administrative healthcare data; phenotypes are often constructed using available data elements to identify treatment-resistant populations or outcomes.

Aims: To conduct a scoping review and identify the disease areas, definitions, data elements and validation status of treatment-resistance phenotypes used in administrative healthcare data.

Methods: We searched MEDLINE, Embase, and Web of Science from inception to July 5th, 2024 for original articles using the concepts ‘treatment-resistance’, ‘administrative healthcare data’ and ‘identification’. We extracted data on the disease area; data elements and measures used to define treatment-resistance; and the source, validation status, and validation method for identified phenotypes.

Results: We identified 122 articles that identified treatment-resistance in administrative healthcare data, primarily in depression, asthma, epilepsy, cancer, schizophrenia, and hypertension. Most articles (n=121, 99%) utilised pharmacy claims as part of their definition, while almost half (n=58, 47%) used additional elements such as hospital admissions and procedural codes. Operationalisation of treatment-resistance varied substantially, particularly in the consideration of dose, duration, severity, and hospitalisations. Phenotype reuse was uncommon, with over half of articles (n=77, 65%) developing phenotypes on a ‘per-study’ basis, while the remainder reused (n=22, 18%) or adapted (n=21, 17%) existing phenotypes. A minority of identified articles (n=14, 12%) either used or developed a validated phenotype. Of the six unique validated phenotypes, four were validated using manual chart reviews, one using a proxy for treatment-resistance, and one through laboratory measurements.

Conclusions: Treatment-resistance phenotypes in administrative data have been identified across various diseases, mostly utilising pharmacy claims. Most phenotypes were unvalidated and developed on a ‘per-study’ basis. Future research should quantify the impact of phenotype variability in treatment-resistance, and address barriers to phenotype reuse and validation.

Keywords: Treatment-resistance, Computable Phenotypes, Validation

Introduction: The Pharmacy Services Questionnaire (PSQ) was developed to measure patient satisfaction with pharmaceutical care. However, it has not been translated into Cantonese-Chinese and validated in the Hong Kong population.
Aims: To develop and validate a Cantonese-Chinese-translated PSQ among native Chinese patients who have used pharmacy services at community pharmacies in Hong Kong.
Methods: The PSQ was developed and translated into Cantonese-Chinese using iterative forward-backwards translation. Subjects were recruited by convenience sampling at three community pharmacies. Internal consistency, construct validity, discriminant validity, known-group comparison and Confirmatory Factor Analysis (CFA) were performed to confirm that the Cantonese-Chinese-translated PSQ is a valid measure of its intended constructs. Qualitative think-aloud interviews were carried out to test for comprehension and content validity. The subjects' views and interpretation of each questionnaire item were also explored to determine the relevance, comprehensiveness, and adequacy of the response options.
Results: A total of 236 adult subjects were recruited to complete the Cantonese-Chinese PSQ and the Chinese 5-Level EuroQol 5-Dimension (EQ-5D-5L HK) questionnaire. Additionally, think-aloud interviews were carried out with 15 subjects. Most subjects were able to understand and interpret the Cantonese-Chinese PSQ with relative ease. The internal consistency of Cantonese-Chinese PSQ was excellent (Cronbach’s α > 0.96) for the full-scale, Friendly explanation (FE) subscale and Managing therapy (MT) subscale. CFA confirmed the hypothesised two-factor structure of the Cantonese-Chinese PSQ. Individuals with higher education levels showed statistically significantly higher satisfaction levels in the overall PSQ score and MT scale score compared to those with lower levels of education. Additionally, there was no statistically significant correlation between the Cantonese-Chinese PSQ and EQ-5D-5L HK scores, demonstrating discriminant validity.
Conclusion: The Cantonese-Chinese translation of the PSQ is a validated, reliable, and semantically equivalent instrument used to assess satisfaction towards services provided by community pharmacies.
Keywords: Satisfaction, Community pharmacy, Validation

Introduction: Hypertension remains a significant public health issue. In Indonesia, hypertension is increasing among older adults, with challenges like mobility issues and limited healthcare access hindering consistent care. Telemedicine, as the use of technology to deliver remote healthcare services, including consultations, diagnosis, monitoring, and treatment, has emerged as a potential solution to enhance access to healthcare, allowing patients to manage their conditions remotely. Aims: This study aims to investigate the impact of telemedicine usage on adherence to antihypertensive among elderly subjects with hypertension in Indonesia. Methods: This cross-sectional study utilized data from the Indonesia Health Survey 2023, which represents the Indonesian population, focusing on subjects aged 60 years and older with hypertension. Data on medication adherence, telemedicine usage (telemedicine is the use of electronic information and communication technologies to provide and support clinical care when distance separates the participants), and potential confounders (gender, education, residence, and blood pressure monitoring) were collected via self-reported measures. The association between telemedicine usage status and medication non-adherence was evaluated using multivariate logistic regression after adjusting for confounders. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were reported. Results: Total of 21,351 elderly subjects with hypertension. The majority were female (60.87%) and lived in urban areas (61.04%). Additionally, 70.68% received information about antihypertensive use, 39.88% graduated from elementary school, and 49.61% regularly checked their blood pressure. However, 98.43% had never used telemedicine. Multivariate analysis showed a significant association between non-use of telemedicine and lower medication adherence (aOR: 1.984654; 95% CI 1.486283-2.650135; p-value 0.000). Conclusion: Most elderly subjects with hypertension in Indonesia have never used telemedicine, which is linked to lower medication adherence. Improving medication adherence is crucial, and telemedicine offers a promising solution. Enhancing digital literacy and accessibility for the elderly, along with training programs supported by family members, can help increase telemedicine use.

Background
Chronic kidney disease (CKD) is a progressive, non-communicable disease that often advances to end-stage renal disease (ESRD), requiring renal replacement therapy. Patients on maintenance hemodialysis experience considerable morbidity, making health-related quality of life (HRQoL) a vital outcome measure. Evaluating QoL can help identify treatment-related complications and guide improvements in care.

Objectives
-To assess the quality of life in hemodialysis patients at a tertiary healthcare hospital.
-To determine dialysis fluid-related complications
-To conduct causality assessments of those complications.
-To evaluate the relationship between electrolyte imbalance and dialysis-related complications through chemical analysis of dialysate.

Methods
A cross-sectional study was conducted from December 2024 to May 2025 at KIMS Al Shifa Hospital, Kerala. A total of 98 adult patients undergoing maintenance hemodialysis were enrolled based on predefined criteria. Quality of life was evaluated using the KDQOL-36 tool. Dialysis-related complications were documented, and dialysate samples were chemically evaluated for sodium, potassium, calcium, and magnesium deviations. Causality assessments were conducted using WHO-UMC criteria. Data analysis was performed using Jamovi software version 2.6.26, employing descriptive statistics, independent t-tests, and ANOVA (p < 0.05).

Results
Among the 98 patients, 91.8% experienced at least one complication. The most common were muscle cramps (40.8%), fatigue (38.8%), hypertension (30.6%), numbness (22.4%), and hypotension (21.4%). Mean QoL scores were PCS: 39.8 ± 8, MCS: 42 ± 8.8, and Burden of Kidney Disease: 38.8 ± 19.8. Causality assessments found 83.7% of complications as “possible” and 9.2% as “probable.” Dialysate analysis showed mild deviations in electrolyte concentrations, aligning with complication reports.

Conclusion
Dialysis-related complications significantly impaired QoL. Findings suggest that dialysate electrolyte balance is a modifiable factor influencing patient outcomes. Optimizing fluid quality may enhance safety and well-being in hemodialysis patients.

Introduction:.Antimicrobial resistance (AMR) remains a growing concern, particularly in critical care settings where high antibiotic usage is prevalent. Utilization studies play a crucial role in informing antimicrobial stewardship (AMS) programs by identifying prescribing trends, promoting rational use, and guiding interventions to minimize resistance.
Aim: To ensure effective treatment, prevent resistance, support stewardship efforts.
Methods:.A prospective observational study was conducted over six months in the Critical Care Units of JSS Hospital, Mysuru. Antimicrobial prescriptions for prophylactic, empirical, and definitive purposes were reviewed. Data were collected from treatment charts and medical orders. WHO core indicators—Defined Daily Dose (DDD) and Antimicrobial Utilization Density (AUD)—were used to quantify usage. Patient demographics (age, gender, diagnosis, duration of stay) and prescription characteristics (drug name, dose, route, frequency, generic use) were analyzed
Results: Among 280 critically ill patients, piperacillin-tazobactam had the highest DDD (2,490,444.44), followed by colistin (1,764,000) and cefoperazone (340,616.66). In AUD, piperacillin (9685.0) was most frequently used, followed by cefuroxime (8523.5), colistin (7840), clindamycin (3273.1), and ceftriaxone (2528.5). Meropenem (775.6) and linezolid (241.5) showed relatively lower usage. These patterns reflect a high reliance on broad-spectrum antibiotics, emphasizing the need for enhanced stewardship strategies.
Conclusion: The study provides a comprehensive overview of antimicrobial utilization in a critical care setting, identifying agents with high usage and highlighting opportunities for targeted stewardship interventions. These findings can inform policy and guide AMS efforts to optimize therapy and prevent antimicrobial resistance.
Keywords: Utilization pattern, Stewardship efforts, critical care units.

Objective:Systematically reviewing the published literature on clinical studies comparing generic drugs with original drugs, to analyze the research status, reported outcomes, and study designs.Methods:Using evidence-based systematic review methods, formulating search keywords and strategies. Literature on clinical comparative studies of generic and original drugs from the establishment of databases up to November 2024 was retrieved from CNKI, Wanfang, PubMed, and Cochrane databases. Articles were selected based on inclusion and exclusion criteria. Information from four aspects: general details of the literature, drug information, study characteristics, and study outcomes (34 items) were extracted. The quality of RCT was assessed using the Cochrane-recommended RoB 2.0 tool, quasi-experimental study using JBI tool, cohort and case-control study using the NOS scale, and case series report using JBI criteria.Results:A total of 451 articles (242 Chinese, 209 English) met the inclusion criteria, including 469 studies. Chinese studies included 140 RCTs, 6 non-randomized controlled trials, and 106 observational studies, with sample size ranging from 24 to 223,307. English studies included 60 RCTs, 19 non-randomized controlled trials, and 137 observational studies, with sample size from 7 to 577,314. The proportion of studies with statistically significant differences in effectiveness and safety indicators was higher in English studies. 10 Chinese studies show differences in effectiveness. , while 15 show differences in safety. 35 English studies show differences in effectiveness, while 23 show differences in safety. Quality assessment revealed moderate-to-high bias risks in RCTs, particularly in randomization and allocation concealment. Non-randomized and observational studies were rated as low-to-moderate risk. Conclusion: Most of the studies showed no significant difference in efficacy and safety between generic drugs and original drugs. The current clinical comparison studies of generic drugs and original drugs are generally in low quality and small sample size. High-quality studies are still needed to further validate the efficacy and safety of generic drugs.