The Lancet. Child & adolescent health最新文献

Controlled medicines, defined here as any pharmaceutical product whose active principles are listed under the international drug Conventions, are essential for the medical care of children. Global disparities in controlled medicine access contribute to an immense burden of disease and serious health-related suffering for children across multiple health conditions, particularly in many low-income and middle-income settings. In this Review, we clarify the extent and nature of the problem of insufficient access to controlled medicines for children and explore its causal determinants. Children frequently experience additional barriers in accessing controlled medicines for several reasons, including their vulnerability to neglect in general policies and health services, inadequate availability of child-specific formulations, and gaps in knowledge and expertise. The poor visibility of children in global research on controlled medicines, as evidenced by this Review's rapid bibliographic analysis, underscores the need for targeted research and interventions focused specifically on improving children's access to controlled medicines.

Children face multiple challenges in accessing controlled medicines-defined here as any pharmaceutical product whose active principles are listed under the international drug Conventions-particularly in low-income and middle-income countries. Although many barriers to accessing controlled medicines for children are known, there is a need for comprehensive, policy-driven, and system-level responses to address this global inequity. With a paucity of research on effective policy strategies for improving access to paediatric controlled medicines, transferrable policy lessons and expert guidance are crucial for informing such responses. This Health Policy purposively reviews relevant policy guidance and resources and highlights policy lessons from three low-income and middle-income countries (Uganda, India, and Costa Rica). Guided by key literature and the multidisciplinary expertise of the authors, it proposes research and intervention priorities and formulates a functional framework that outlines actionable levers for improving appropriate access to controlled medicines for children.

Background: Homozygous familial hypercholesterolaemia (HoFH) is a rare genetic disease characterised by extremely high plasma LDL cholesterol from birth, causing atherosclerotic cardiovascular disease at a young age. Lipoprotein apheresis in combination with lipid-lowering drugs effectively reduce LDL cholesterol, but long-term health outcomes of such treatment are unknown. We aimed to investigate the long-term cardiovascular outcomes associated with lipoprotein apheresis initiated in childhood or adolescence.

Methods: In this cohort study, data were drawn from the HoFH International Clinical Collaboration (HICC) and the international registry for Children with Homozygous Hypercholesterolemia on Lipoprotein Apheresis (CHAIN). An overall cohort included patients diagnosed with HoFH aged 0-18 years who were alive and in follow-up between Jan 1, 2010, and Nov 8, 2021, and whose high plasma LDL cholesterol concentrations made them eligible for lipoprotein apheresis. To compare cardiovascular outcomes, patients who initiated lipoprotein apheresis in childhood (lipoprotein apheresis group) and patients who only received lipid-lowering drugs (pharmacotherapy-only group) were matched by sex and untreated plasma LDL cholesterol concentrations. The primary outcome was a composite of cardiovascular death, myocardial infarction, ischaemic stroke, percutaneous coronary intervention, coronary artery bypass grafting, aortic valve replacement, peripheral artery disease, carotid endarterectomy, angina pectoris, and supra-aortic or aortic stenosis (collectively referred to as atherosclerotic cardiovascular disease), for which survival analyses were performed in the matched cohort. Cox regression analyses were used to compare disease-free survival between cohorts and to calculate hazard ratio (HR) and 95% CI adjusted for sex, age at diagnosis, untreated plasma LDL cholesterol concentration, and number of lipid-lowering therapies other than lipoprotein apheresis.

Findings: The overall cohort included 404 patients with a median age at diagnosis of 6·0 years (IQR 3·0-9·5) and median untreated plasma LDL cholesterol of 17·8 mmol/L (14·7-20·8). The matched cohorts included 250 patients (125 patients per group), with a median untreated LDL cholesterol of 17·2 mmol/L (14·8-19·7). Mean reduction in plasma LDL cholesterol concentrations between baseline and final follow-up was greater in the lipoprotein apheresis group (-55% [95% CI -60 to -51] vs -31% [-36 to -25]; p<0·0001). Patients in the lipoprotein apheresis group had longer atherosclerotic cardiovascular disease-free survival (adjusted HR 0·52 [95% CI 0·32-0·85]) and longer cardiovascular death-free survival (0·0301 [0·0021-0·4295]). Cardiovascular death was more common in the pharmacotherapy-only group than in the lipoprotein apheresis group (ten [8%] vs one [1%]; p=0·010), whereas median age at coronary artery bypass grafting was lower in the lipopro