UNASSIGNED: The manuscript summarizes the outcomes of a one-day conference by the South Asian College of American College of Clinical Pharmacology (SAC-ACCP) in July 2023, at Bhopal. The theme of the conference was \"Advancing pediatric drug development in South Asia.\" SAC-ACCP organized this event in Bhopal to foster the discipline of clinical pharmacology and to motivate researchers and physicians in the in the central part of India. The conference featured presentations on regional approaches to pediatric drug development in Asia by pediatric scientific experts from the pharmaceutical industry, regulatory agencies, as well as independent consultancies. The speakers highlighted several important aspects of the evolving regulatory landscape in India and proposed numerous actionable steps in acceleration of pediatric drug development. This commentary provides insights from presentations and the panel discussion at this conference and also makes an attempt to connect to similar discussions that occurred at the SAC-ACCP drug development conference in 2017.

UNASSIGNED: Quantitative and systems pharmacology (QSP) is an innovative and integrative approach combining physiology and pharmacology to accelerate medical research. This review focuses on QSP\'s pivotal role in drug development and its broader applications, introducing clinical pharmacologists/researchers to QSP\'s quantitative approach and the potential to enhance their practice and decision-making. The history of QSP adoption reveals its impact in diverse areas, including glucose regulation, oncology, autoimmune disease, and HIV treatment. By considering receptor-ligand interactions of various cell types, metabolic pathways, signaling networks, and disease biomarkers simultaneously, QSP provides a holistic understanding of interactions between the human body, diseases, and drugs. Integrating knowledge across multiple time and space scales enhances versatility, enabling insights into personalized responses and general trends. QSP consolidates vast data into robust mathematical models, predicting clinical trial outcomes and optimizing dosing based on preclinical data. QSP operates under a \"learn and confirm paradigm,\" integrating experimental findings to generate testable hypotheses and refine them through precise experimental designs. An interdisciplinary collaboration involving expertise in pharmacology, biochemistry, genetics, mathematics, and medicine is vital. QSP\'s utility in drug development is demonstrated through integration in various stages, predicting drug responses, optimizing dosing, and evaluating combination therapies. Challenges exist in model complexity, communication, and peer review. Standardized workflows and evaluation methods ensure reliability and transparency.

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BACKGROUND: Percutaneous coronary intervention (PCI) is frequently used for patients with chronic coronary syndrome (CCS). However, the role of PCI beyond symptom relief in CCS remains controversial. The objective of this study was to determine whether PCI is associated with better outcomes, compared with medical therapy (MT) alone.
METHODS: We conducted a retrospective cohort study. Using the Swedish Coronary Angiography and Angioplasty Registry, we included all patients with CCS undergoing coronary angiography in Sweden between 2010 and 2020. Two groups were formed based on treatment strategy: PCI+MT versus MT alone. One-to-one propensity score (PS) matching was used to address confounding. Outcome was assessed using matched win ratio analysis, a statistical method that ranks the components of the composite by clinical importance. The primary outcome was net adverse clinical event (NACE) within 5 years. In the win ratio analysis, the components of NACE were ranked as follows: (1) all-cause mortality, (2) myocardial infarction (MI), (3) bleeding and (4) urgent revascularisation. Secondary outcomes were the individual components of NACE, major adverse cardiovascular events (MACE) and cardiovascular mortality.
RESULTS: After PS matching, two groups of 7220 patients each were formed. The hierarchical outcome analysis of NACE and MACE showed that PCI was associated with improved outcome (matched win ratio: 1.28 (95% CI 1.20 to 1.36, p<0.001) and matched win ratio: 1.38 (95% CI 1.29 to 1.48, p<0.001), respectively). The use of PCI was associated with higher win ratio of MI (matched win ratio: 1.15, 95% CI 1.04 to 1.28, p=0.008), urgent revascularisation (matched win ratio: 1.85, 95% CI 1.69 to 2.03, p<0.001) and cardiovascular mortality (matched win ratio: 1.15, 95% CI 1.00 to 1.34, p=0.044). No difference in win ratio was observed for all-cause mortality or bleeding.
CONCLUSIONS: In this study, which sought to evaluate the outcomes of patients with CCS using a hierarchical approach, patients selected for revascularisation with PCI experienced better outcome compared with MT alone.

BACKGROUND: Studies comparing the safety of orexin receptor antagonists and other hypnotic types for older patients with heart failure (HF) remain lacking. This study aimed to compare orexin receptor antagonists (suvorexant) with benzodiazepines or Z-drugs for sleep treatment and investigate the risk of acute HF-related rehospitalisation in older patients with HF.
METHODS: This study used a cohort design to analyse data from an administrative claims database from April 2008 to December 2020. The study population was determined based on inclusion and exclusion criteria from a cohort of 1 159 937 patients aged ≥65 years, selected through random sampling. The follow-up period was censored based on multiple criteria, including outcome occurrences and hypnotic classification changes. Kaplan-Meier survival analysis and Cox proportional hazards models were conducted for risk assessment.
RESULTS: The analysis included 1858 patients, aged ≥65 years and experiencing their first HF-related hospitalisation. These patients were categorised based on the initially prescribed hypnotic classification, including suvorexant, benzodiazepines and Z-drugs in 490, 606 and 762 patients, respectively. The average age and SD were similar across all hypnotic classes at 82.7±7.6 years. Kaplan-Meier curves indicated a higher trend of rehospitalisation risk for benzodiazepines and Z-drugs than for suvorexant. The adjusted HRs were 2.77 (95% CI 1.17 to 6.52) for benzodiazepines and 2.98 (95% CI 1.33 to 6.68) for Z-drugs.
CONCLUSIONS: Suvorexant administration for sleep treatment in older patients with HF shows a potentially reduced risk of acute HF-related rehospitalisation compared with benzodiazepines and Z-drugs. The results of this study provide valuable information for selecting hypnotics in older patients with HF having concurrent sleep disorders.

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For patients with heart failure and reduced or mildly reduced left ventricular ejection fraction, iron deficiency is common and associated with more severe symptoms, worse quality of life and an increased risk of hospitalisations and death. Iron deficiency can be swiftly, effectively and safely treated by administering intravenous iron, either as ferric carboxymaltose or ferric derisomaltose, which improves patient well-being and reduces the risk of hospitalisations including those for heart failure. However, the current definition of iron deficiency in heart failure has serious flaws. A serum ferritin <100 µg/L does not identify patients more likely to respond to intravenous iron. In contrast, patients with transferrin saturations <20%, most of whom are also anaemic, are more likely to have a beneficial response to intravenous iron. In this review, we summarise the available evidence for use of intravenous iron in heart failure and provide recommendations for targeted future research and practical considerations for the general cardiologist.

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