Introduction: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are novel injectable lipid-lowering medications, but poor medication adherence in real-world settings may compromise their effectiveness. This study synthesizes evidence on medication adherence to PCSK9 inhibitors across initiation, implementation, persistence, and reinitiation phases to identify challenges and inform clinical practice.

Aims: To determine the prevalence of medication adherence to PCSK9 inhibitors in observational studies.

Methods: We searched MEDLINE, EMBASE, PsychInfo, CINAHL Plus, and medRxiv from inception to 2 August 2024 for observational studies that reported on at least one phase of medication adherence for alirocumab, evolocumab, or inclisiran. Measures were categorized into initiation, implementation, persistence, and reinitiation phases. Data were pooled using random-effects meta-analysis with multi-level models to account for measurements at multiple time points.

Results: 94 studies (101 cohorts) were included, with 56 studies (74,589 patients) contributing to the quantitative synthesis. The pooled initiation rate was 91.7% (95%CI: 83.6-96.0; I² = 94.2%). For implementation measures, the mean medication possession ratio (MPR) at 24 months was 86.5% (95%CI: 80.2-92.9; I² = 99.7%) and the proportion of days covered (PDC) at 12 months was 69.7% (95%CI: 55.9-83.5; I² = 99.8%). For persistence measures, proportion of persistent patients at 12 months was 81.8% (95%CI: 68.2-90.4; I² = 99.1%) and 12-month discontinuation rate was 12.1% (95%CI: 7.4-19.0; I² = 98.9%), with adverse effects being the most commonly reported reason. The proportion resuming PCSK9 inhibitor treatment after a temporary interruption was 50.4% (95%CI: 38.5-62.2; I² = 87.0%). Multi-level meta-analyses demonstrated a decline in MPR and persistence beyond 12 months of follow-up.

Conclusion: While PCSK9 inhibitor initiation is high, implementation and persistence decline substantially over time. Comparative real-world data for inclisiran versus monoclonal antibodies remain limited, and longitudinal studies (>24 months) are needed to clarify long-term adherence patterns.

Keywords: PCSK9 inhibitors, medication adherence, real-world evidence

Introduction: The benefits of lipid-lowering therapy (LLT) are being investigated in the VESALIUS-CV trial (NCT03872401) among high-risk patients without prior myocardial infarction or stroke. In parallel, the global VESALIUS-REAL study examines the burden of high-risk populations across 11 countries. Here, we provide findings from Hong Kong (HK).
Aims: To describe lipid management patterns in patients at high-risk for a first myocardial infarction (MI) or stroke in HK.
Methods: A retrospective cohort study was conducted using the HK Hospital Authority database (2010–2020). It contains electronic health records, including prescriptions, diagnoses, procedures, and laboratory test results. Patients aged ≥50 years with elevated lipids; coronary artery disease (CAD), peripheral artery disease (PAD), cerebrovascular disease (CeVD), or high-risk diabetes (DM), and other predefined high CV risk factors were selected. The earliest date when patients met all eligibility criteria was defined as the index date. Intensification was defined as a dose increase, switching to more intensive LLT, or adding drug classes.
Results: Of 118,463 patients (median age: 69 years; 47.2% were women; median low-density lipoprotein cholesterol [LDL-C]: 2.64 mmol/L), 43.6% had CAD, 8.7% had CeVD, 5.6% had PAD, and 44.9% had high-risk DM. Less than half of patients (N=54,425) were on LLT at index (94.8% on statin monotherapy and 1.2% on combination therapy). Of the 47,564 patients on LLT at index with available LDL-C measurements (mean LDL-C: 2.65 mmol/L) during the one-year follow-up period, 68.4% exceeded the LDL-C level of 1.8 mmol/L, a target commonly used by local clinicians, and only 7.9% had intensified treatment.
Conclusion: Over half of the high-risk population for first MI or stroke in HK was not on LLT, and most patients did not achieve the guideline-recommended LDL-C target during follow-up. Our results highlight a treatment gap in improving lipid management in these patients and preventing major ischemic events.

Background:
The FDA’s Accelerated Approval (AA) pathway has enabled earlier access to oncology drugs. However, uncertainty remains over whether post-marketing confirmatory trial results are acted upon promptly, posing an ongoing regulatory challenge. The Food and Drug Omnibus Reform Act (FDORA), enacted in 2022, sought to strengthen the FDA’s authority to enforce timely confirmatory trials and withdraw unsubstantiated approvals.
Aims:
This study assesses whether FDORA mechanisms were applied in recent AA withdrawals and whether regulatory actions aligned with confirmatory trial outcomes.
Methods:
We conducted a retrospective review of regulatory documents for five oncology drugs (Pepaxto, Exkivity, Truseltiq, Trodelvy, and Aloqopa) withdrawn from the AA pathway in 2024. Truseltiq was excluded from in-depth analysis due to its withdrawal for business reasons. For the remaining four, we compared regulatory history, withdrawal rationale, and confirmatory trial outcomes. Safety risk ratios (RR) were calculated based on adverse event data from confirmatory trials that led to approval withdrawal.
Results:
Despite FDORA’s provisions, four of the five accelerated approval withdrawals in 2024 were initiated voluntarily by sponsors, without formal FDA enforcement. Pepaxto was the only case withdrawn following a formal FDA-initiated process under FDORA, based on hematologic toxicity and lack of efficacy. Across the four analyzed drugs, confirmatory trials failed to show survival benefit, and their risk–benefit profiles raised concerns. Safety analyses revealed elevated risks of serious treatment-related adverse events, with RR for grade ≥4 or serious TRAEs ranging from 1.39 to 1.87.
Conclusion:
Among the oncology drugs withdrawn in 2024 following accelerated approval, Pepaxto remains the only FDA-initiated withdrawal under FDORA. This highlights the critical importance of timely, rigorous confirmatory trials and benefit–risk reassessment in post-approval surveillance of accelerated oncology therapeutics. To ensure consistent regulatory enforcement, clearer criteria and operational triggers for FDORA-driven withdrawals should be articulated and standardized.
Keywords:
Accelerated approval, regulatory withdrawal, confirmatory trials

Introduction: Attention-deficit/hyperactivity disorder (ADHD) frequently co-occurs with various psychiatric comorbidities, complicating pharmacological treatment planning and clinical decision-making. National clinical guidelines differ significantly in their recommendations, particularly regarding comorbidity-specific pharmacotherapy strategies.

Aims: This study aimed to compare and evaluate pharmacological treatment recommendations for psychiatric comorbidities by systematically analyzing national ADHD guidelines from seven countries.

Methods: A structured literature search was conducted to identify national ADHD guidelines published between 2015 and 2024 in OECD countries. Guidelines were considered eligible if they included pharmacological recommendations addressing psychiatric comorbidities. Two reviewers independently extracted relevant data using a standardized extraction form covering 18 predefined comorbidities. Key components extracted included treatment prioritization (ADHD vs. comorbidity), recommended first- and second-line medications, contraindications, and safety considerations. Guideline quality was evaluated using the AGREE II instrument, which assesses six domains including rigor of development and applicability.

Results: Among 942 records identified, 548 remained after deduplication. Following title and full-text screening, seven national ADHD guidelines from Korea, Germany, the United States, the United Kingdom, Ireland, Canada, and Australia were included. The number of psychiatric comorbidities with pharmacological treatment recommendations varied considerably, ranging from 2 (UK) to 16 (Canada). Canada, the United States, and Australia addressed over 80% of the 18 comorbidities, while the others covered fewer. Substance use disorder was the only comorbidity addressed by all guidelines. Canada and the United States provided condition-specific recommendations, while Australia and the UK offered more general principles. Germany required additional clinical interpretation. Korean and Irish guidelines included only limited recommendations. AGREE II results showed high clarity but low scores for development rigor and applicability, revealing significant variability in guideline quality.

Conclusions: Substantial variation exists in pharmacological recommendations for psychiatric comorbidities in ADHD across countries. These findings highlight the need for clearer, harmonized guidelines to promote consistent, evidence-based care.

Keywords: ADHD; Comorbidities; Pharmacological Treatment

Introduction: The validity of International Classification of Diseases 10th Revision (ICD-10) codes related to chronic kidney disease (CKD) in Japan has not been evaluated.
Aims: To assess the validity of ICD-10 codes related to CKD.
Methods: We used the JMDC hospital-based database, which includes claims and laboratory data from over 1,000 medical institutions in Japan. Patients who underwent two serum creatinine measurements between April 2014 and August 2022 were identified; the second measurement was obtained between 90 and 365 days after the first. The estimated glomerular filtration rate (eGFR) was calculated. As the gold standard, CKD was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria—specifically, an eGFR < 60 mL/min/1.73 m² on both measurements. We identified patients assigned ICD-10 codes related to CKD (N183, N184, N185, N189, N19, E102, E112, E142, and I120) within 365 days of the initial serum creatinine measurement. Subsequently, we calculated the positive predictive value (PPV), sensitivity, specificity, and negative predictive value (NPV). 　
Results: A total of 618,208 patients were included. Among these patients, 59,139 were assigned ICD-10 codes related to CKD, and 172,657 met the KDIGO criteria for CKD. Overall, the PPV, sensitivity, specificity, and NPV were 57.9%, 19.8%, 94.4%, and 75.2%, respectively. Notably, the PPVs for ICD-10 codes such as N183, N184, N185, and N189 were high, all exceeding 80% (80.9%–99.1%), whereas the sensitivities were low (0.7%–12.7%).
Conclusions: In the Japanese setting, the PPV of ICD-10 codes for CKD was 57.9%, which is slightly lower than previously reported values in the U.S. (86.1%) and Canada (60.1%). In contrast, the PPV of N183, N184, N185, and N189 was more than 80%, suggesting that these codes may be useful for accurately identifying patients with CKD, despite their limited sensitivity.
Keywords: Chronic Kidney Disease, hospital‐based database, positive predictive value

Introduction: Ensuring patient safety in outpatient settings poses unique challenges for both providers and patients. The overwhelming workload faced by healthcare providers directly hinders the effective assessment of medication use safety, particularly in ambulatory care settings. Clinical pharmacists have huge potential to address this contextual concern.

Aim: To evaluate the medication use safety assessment program in ambulatory patients with chronic disease.

Methods: An interventional study was carried out in an ambulatory setting of a tertiary care hospital for a period of 12-months. Patients above 18 years of age with chronic conditions and visiting the study site were included. The medication safety assessment program was initiated by an ambulatory pharmacist in collaboration with the general medicine outpatient department. Under this program, patients’s prescriptions and clinical findings were recorded using a structured data collection tool. Obtained data screened with multiple medication safety assessment tools & drug database. Descriptive & inferential statistics were used to analyze the data.

Results: A total of 402 patients of age 52.78±12.04 years were enrolled; among them, 30% were on polypharmacy (n=121). The majority were diagnosed with hypertension (n=192, 47.76%), diabetes (n=124, 30.84%), and rheumatoid arthritis (n=77, 13.8%). During the medication safety assessment, a total of 88 adverse reactions and 533 (73.9%) clinically important potential drug-drug interactions (pDDIs) were identified. Out of which 93.3% (n=112) of clinically important pDDIs & 18.3% (n=22) of adverse reactions (ADRs) were seen in patients with polypharmacy. Gender, age, comorbidity burden, medication burden, adherence status, and betel nut-user show statistically significant correlations with clinically significant pDDIs; however, only age and comorbidity burden show statistically significant correlations with ADRs.

Conclusion: An ambulatory pharmacist-led medication use safety program can significantly enhance the quality of outpatient care. Implementation of such a program will significantly improve patient safety.

Keywords: ambulatory care, adverse events, drug interactions, medication safety.

Introduction: Poisoning remains a major medical emergency and public health concern, especially in low- and middle-income countries with limited healthcare access. Early severity assessment is vital to reduce mortality. Developing accurate, practical scoring system for poisoning cases is crucial for timely treatment, guiding clinical decisions, improving outcomes, and optimizing healthcare resource use.

Aims: To develop a novel poison severity and mortality scale for assessment of poisoning cases.

Methods: An ambispective study was conducted over 7 months at a tertiary care hospital in India, analyzing 151 retrospective poisoning cases to identify key clinical parameters from patient medical records. Novel scale was developed through standardized process, which included domain determination, item development, and scale formulation. Suggestions of expert panels, statistical methods like descriptive statistics, Content Validity Ratio (CVR), Content Validity Index (CVI), Scale-CVI (S-CVI), modified Kappa coefficient, and Intraclass Correlation Coefficient (ICC) were used to evaluate the validity and reliability of the improved scale.

Results: A total of 151 retrospective poisoning cases were analyzed (mean age: 29.46 years), mostly from urban areas, pesticide poisoning being most common (36%). An initial 71-item scale (26 mortality domain, 45 severity domain) was reviewed by 25 experts from emergency, intensive care unit, and general medicine departments. Items with CVR < 0.37 and CVI < 0.78 were removed, retaining 37 items. The average S-CVI was 0.90, and the modified kappa for all items was found to be more than 0.80, depicting excellent reliability. Face validity showed unanimous expert agreement, and ICC was 0.894, indicating excellent consistency and reliability.

Conclusions: Poisoning remains a significant public health challenge. While the scale demonstrates strong reliability for acute cases, its single-center design limits generalizability. Future studies should be multicenter, include pediatric and geriatric groups, and address all exposure types for broader clinical relevance.

Keywords: Poisoning, Severity and Mortality Scale, Content Validation