International Trends in Opioid Prescribing by Age and Sex from 2001 to 2019: An Observational Study Using Population-Based Databases from 18 Countries and One Special Administrative Region.

Objective: To characterize multinational trends and patterns of opioid analgesic prescribing by sex and age.

Design, Setting, And Participants: We studied opioid analgesic prescribing from 2001 to 2019 with common protocol using population-based databases from eighteen countries and one special administrative region.

Main Outcome Measures: We measured opioid prescribing by geographical region, sex and age, estimating annual prevalent, incident, and nonincident opioid prescribing per 100 population with a 95% confidence interval (CI) and meta-analyzed the multinational and regional opioid prescribing with a random-effects model.

Real-world evidence on the survival benefit of immune checkpoint inhibitors in combination with cytotoxic chemotherapy for patients with extensive-disease small-cell lung cancer: the Tokushukai Real World Data Project (TREAD) 06.

Background: Small-cell lung cancer (SCLC) is an aggressive malignancy with a poor prognosis. Despite the initial chemosensitivity, survival for extensive-disease (ED) SCLC remains limited. Immune checkpoint inhibitors (ICIs) in combination with chemotherapy have recently been redefined as the standard of care.

Optimizing long term disease prevention with reinforcement learning: a framework for precision lipid control.

The prevention of chronic disease is a long-term combat with continual fine-tuning to adapt to the course of disease. Without comprehensive insights, prescriptions may prioritize short-term gains but deviate from trajectories toward long-term survival. Here we introduce Duramax, an evidence-based framework empowered by reinforcement learning to optimize long-term preventive strategies.

Barriers and solutions for global access to osteoporosis management: a Position Paper from the International Osteoporosis Foundation.

Our ability to optimally manage bone health across the lifecourse, and so minimise the risk of fractures, has advanced substantially in recent decades. Whilst fractures and osteoporosis in older age were historically viewed simply as inherent in normal ageing, they are now recognised as manifestations of age-related disease. Key to advancing the field was the development of conceptual (relating to impaired bone mass and microarchitecture with increased propensity to fracture), and subsequent World Health Organization densitometric definitions of osteoporosis, cementing the role of dual-energy X-ray absorptiometry in bone health management.

Expert recommendations for biomarker evaluation of advanced non-small cell lung cancer in Thailand.

Background: Growing understanding of the heterogenous molecular profiles of non-small cell lung cancer (NSCLC) has led to changes in the treatment landscape of advanced NSCLC towards precision medicine to target actionable gene alterations. Practical barriers, such as lack of awareness/understanding of biomarkers, suboptimal quality or sample management, inappropriate use of biomarker testing results, limited patient access to biomarker tests and targeted treatments, and reimbursement/payment challenges, hinder the wider adoption of guideline-recommended biomarker testing. Limited reimbursement of targeted therapies is a key consideration for Thai oncologists when making a treatment choice for their patients with advanced NSCLC in Thailand.

Efficacy and Safety of Tezepelumab in Adults With Severe, Uncontrolled Asthma in Asia: Results From the Phase 3 DIRECTION Study.

Background: Tezepelumab, a human monoclonal antibody that blocks thymic stromal lymphopoietin, reduced annualized asthma exacerbation rate (AAER) and improved lung function, asthma control, and health-related quality of life (HRQoL) in patients with severe, uncontrolled asthma (SUA) in the global, phase 3 NAVIGATOR study (NCT03347279).

Objective: DIRECTION was a phase 3, multicenter, double-blind study that assessed the efficacy and safety of tezepelumab in adults with SUA in China, the Philippines, and Republic of Korea.

Methods: Patients (18-80 years) with SUA (no baseline biomarker restrictions) were randomized 1:1 to receive tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks.

Final Analysis Results and Patient-Reported Outcomes From DESTINY-Lung02-A Dose-Blinded, Randomized, Phase 2 Study of Trastuzumab Deruxtecan in Patients With HER2-Mutant Metastatic NSCLC.

Introduction: Trastuzumab deruxtecan (T-DXd) demonstrated strong and durable responses in patients with previously treated HER2 (ERBB2) mutant (HER2m) metastatic NSCLC (mNSCLC) in the DESTINY-Lung02 primary analysis (December 23, 2022, data cutoff). This final analysis evaluated T-DXd efficacy and safety after 8 additional months of follow-up, including clinically relevant subgroups and patient-reported outcomes.

Methods: DESTINY-Lung02 was a randomized, dose-blinded, multicenter, phase 2 trial.

ESGO-ESTRO-ESP guidelines for the management of patients with endometrial carcinoma: update 2025.

In 2023, based on advances in the understanding of the pathological and molecular features of endometrial carcinoma, an updated International Federation of Gynaecology and Obstetrics (FIGO) staging system was published, aiming to better define prognostic groups and identify relevant treatment subgroups by including factors reflecting tumour biology (histological subtypes, lymphovascular space invasion, and molecular classification) alongside refinements of anatomical factors (peritoneal carcinomatosis and lymph node metastasis). As part of its mission to improve the quality of care for people with gynaecological cancers, the European Society of Gynaecological Oncology (ESGO), European Society for Radiotherapy and Oncology (ESTRO), and the European Society of Pathology (ESP) updated the ESGO-ESTRO-ESP evidence-based guidelines published in 2021 by incorporating this revised FIGO staging and the large body of new evidence addressing the management of endometrial carcinoma. The development process of these guidelines was based on a systematic literature review and critical appraisal process involving an international multidisciplinary development group consisting of 30 experts from relevant disciplines (gynaecological oncology, radiation oncology, medical oncology, and pathology).

Characterisation of a clinical trial-like population of high cardiovascular risk patients prior to myocardial infarction or stroke in the real world: design and protocol for a multidatabase retrospective cohort study.

Introduction: Cardiovascular (CV) disease is the leading cause of morbidity and mortality globally. Low-density lipoprotein cholesterol (LDL-C) is an important modifiable risk factor of major adverse cardiovascular events. Patients without prior myocardial infarction (MI) or stroke but with established risk factors and elevated LDL-C may benefit from intensive lipid-lowering therapy (LLT); however, the size and potential healthcare burden of this population globally are not known.

Pembrolizumab monotherapy for previously treated metastatic HER2-negative breast cancer with germline deletion: results of the phase II AUROR study.

Background: A common germline deletion polymorphism in the gene increases the rate of somatic hypermutation in breast cancer, which in turn is associated with greater neoantigen burden and immune activation. This phase II study evaluated the impact of the deletion polymorphism on the response to pembrolizumab monotherapy in metastatic HER2-negative breast cancer patients.

Methods: Eligible patients had a confirmed diagnosis of metastatic HER2-negative breast cancer, 1-3 prior lines of therapy, and documented homozygous or heterozygous germline deletion of .

Utility of CK8/18 in identifying circulating tumor cells derived from lesions in patients with non-small cell lung cancer.

Background: Circulating tumor cells (CTCs) are identified by the absence of pan-leukocyte markers and positive staining for cytokeratin (CK). Anti-panCK antibody (AE1/AE3) is a widely used marker for CK. However, epithelial-mesenchymal transition reduces the expression of panCK markers, leading to low detection rates of CTCs, especially in non-small cell lung cancer (NSCLC).

Evaluation of the effect of multimorbidity on difficult-to-treat asthma using a novel score (MiDAS): a multinational study of asthma cohorts.

Background: Multimorbidity (ie, co-existence of two or more health conditions) is highly prevalent in patients with difficult-to-treat asthma. However, it remains unclear how multimorbidity correlates with disease severity and adverse health outcomes in these patients and which comorbidities are most important. We aimed to address this knowledge gap by developing a patient-centred, clinically descriptive multimorbidity score for difficult-to-treat asthma.

Advancing equitable access to innovation in breast cancer.

This manuscript critically examines the challenges associated with the design and conduct of academic global breast cancer trials outside the influence of pharmaceutical companies, leveraging insights from the Breast International Group (BIG). In the past 4 decades significant declines in breast cancer mortality have occurred, partly related to industry-academic clinical and translational partnerships with long term study follow up. However, in the past decade these partnerships have largely uncoupled.

The short-, medium- and long-term risk and the multi-organ involvement of clinical sequelae after COVID-19 infection: a multinational network cohort study.

ObjectivesTo generate comprehensive evidence on the risk of clinical sequelae involving different organ systems over time after coronavirus disease 2019 (COVID-19) infection.DesignMultinational retrospective cohort study.SettingElectronic medical records from the US, UK, France, Germany and Italy standardised to the Observational Medical Outcomes Partnership Common Data Model.

The mutagenic forces shaping the genomes of lung cancer in never smokers.

Lung cancer in never smokers (LCINS) accounts for around 25% of all lung cancers and has been associated with exposure to second-hand tobacco smoke and air pollution in observational studies. Here we use data from the Sherlock-Lung study to evaluate mutagenic exposures in LCINS by examining the cancer genomes of 871 treatment-naive individuals with lung cancer who had never smoked, from 28 geographical locations. KRAS mutations were 3.

Global, regional, and national trends in routine childhood vaccination coverage from 1980 to 2023 with forecasts to 2030: a systematic analysis for the Global Burden of Disease Study 2023.

Background: Since its inception in 1974, the Essential Programme on Immunization (EPI) has achieved remarkable success, averting the deaths of an estimated 154 million children worldwide through routine childhood vaccination. However, more recent decades have seen persistent coverage inequities and stagnating progress, which have been further amplified by the COVID-19 pandemic. In 2019, WHO set ambitious goals for improving vaccine coverage globally through the Immunization Agenda 2030 (IA2030).

Patient-Reported Outcomes From LIBRETTO-431: First-Line Selpercatinib Versus Chemotherapy With Pembrolizumab in Fusion-Positive NSCLC.

Introduction: The benefit of first-line selpercatinib versus platinum-based chemotherapy with or without pembrolizumab in patients with advanced fusion-positive NSCLC has been previously reported. The patient-reported outcomes (PROs) from the LIBRETTO-431 trial presented here further support the benefit of first-line selpercatinib in this patient population.

Methods: In the intention-to-treat pembrolizumab population, 129 patients received selpercatinib and 83 patients received platinum chemotherapy with pembrolizumab (control).

NEXUS: a phase I dose escalation study of selinexor plus nivolumab and ipilimumab in Asian patients with advanced/metastatic solid malignancies.

Background: Selinexor (SEL) is an oral inhibitor of nuclear export protein Exportin 1 (XPO1) previously shown to upregulate programmed cell death protein 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) expression.

Objective: To investigate the safety and antitumor activity of SEL, nivolumab (NIVO), and ipilimumab (IPI) in Asian patients with treatment-refractory solid organ cancers.

Design: Phase I study of escalating doses of SEL in combination with NIVO + IPI.

Final Survival Outcomes With Ramucirumab Plus Erlotinib Versus Placebo Plus Erlotinib in Patients With Untreated -Mutated Metastatic NSCLC: RELAY Japanese Subset.

Introduction: Significant improvement in progression-free survival (PFS; primary end point) was reported in the phase 3 RELAY study with ramucirumab (RAM) plus erlotinib (ERL) versus placebo (PL) in untreated -mutated NSCLC (hazard ratio [HR] = 0.59, 95% confidence interval [CI]: 0.46-0.

Efficacy and safety of epcoritamab in Japanese patients with relapsed or refractory diffuse large B-cell lymphoma: 3-year follow-up from the EPCORE NHL-3 trial.

Background: Primary results from the EPCORE NHL-3 trial (NCT04542824) showed deep, durable responses in Japanese patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) treated with single-agent epcoritamab, a subcutaneous CD3xCD20 bispecific antibody. Here, we report 3-year follow-up of safety and efficacy.

Methods: Japanese patients with R/R CD20 DLBCL and  ≥ 2 prior systemic therapies received epcoritamab (0.

Preventive Effects of Prasugrel on Cerebrovascular Events Following Percutaneous Coronary Intervention.

Background: Dual antiplatelet drug administration is recommended after percutaneous coronary intervention (PCI) stent placement. Although prasugrel, a newer P2Y12 inhibitor, reportedly suppresses cardiovascular events more effectively than the traditional agent clopidogrel, its preventive effects on cerebrovascular disorders remain a topic of ongoing debate. This study aimed to examine the cerebrovascular efficacy and safety of post-PCI prasugrel and clopidogrel using extensive real-world data in Japan.

Real-World Effectiveness and Safety of Vedolizumab in Patients ≥ 70 Versus < 70 Years With Ulcerative Colitis: Multicenter Retrospective Study.

Background And Aim: Vedolizumab (VDZ) is often used in older patients with ulcerative colitis (UC) in clinical practice; however, real-world evidence is still limited, including in those with late-onset UC.

Methods: This post hoc analysis of a multicenter, retrospective, observational chart review, enrolling 370 patients with UC receiving VDZ between December 2018 and February 2020, compared effectiveness and safety of VDZ among patients ≥ 70 (n = 40) versus < 70 years (n = 330), and among patients ≥ 70 years with and without late-onset UC (age at disease onset: ≥ 70 [n = 13] versus < 70 years [n = 26]).

Results: There were no differences between patients ≥ 70 and < 70 years in clinical remission rates (week 6: 57.

Efficacy of Axicabtagene Ciloleucel Compared to Historical Treatments for Relapsed/Refractory Diffuse Large B-Cell Lymphoma of Asian Descent: A Matching Adjusted Indirect Comparison of ZUMA-1 vs REAL-TREND.

To better understand the comparative effectiveness of axicabtagene ciloleucel (axi-cel) to historical standard of care (SoC) for the treatment of refractory diffused large B-cell lymphoma (DLBCL) among patients of Asian descent, we conducted a matching-adjusted indirect treatment comparison (MAIC) of the pivotal ZUMA-1 trial (NCT02348216) and the Asia-based REAL-TREND cohort. The individual patient data (IPD) from ZUMA-1 (n = 101 infused patients) used the 60-month data-cut, while the REAL-TREND cohort data consisted of aggregate data and pseudo-IPD derived from digitized curves. The outcomes were overall survival (OS), complete response (CR) and overall response rate (ORR), as reported in REAL-TREND.