Creating a learning health system to include environmental determinants of health: The GroundsWell experience.

Introduction: Policies aiming to prevent ill health and reduce health inequalities need to consider the full complexity of health systems, including environmental determinants. A learning health system that incorporates environmental factors needs healthcare, social care and non-health data linkage at individual and small-area levels. Our objective was to establish privacy-preserving household record linkage for England to ensure person-level data remain secure and private when linked with data from households or the wider environment.

Causal evidence of the association between green and blue spaces (GBS) and maternal and neonatal health: a systematic review and meta-analysis protocol.

Introduction: Previous systematic reviews investigating the effects of green and blue space (GBS) on maternal and neonatal health have mainly focused on cross-sectional evidence, limiting potential causal inferences. The last review on the topic was published in January 2024. This review focused on residential greenness effects and neonatal health only but did not include other green/blue space measures, or maternal health outcomes.

The use of Enhanced Vegetation Index for assessing access to different types of green space in epidemiological studies.

Background: Exposure to green space can protect against poor health through a variety of mechanisms. However, there is heterogeneity in methodological approaches to exposure assessments which makes creating effective policy recommendations challenging.

Objective: Critically evaluate the use of a satellite-derived exposure metric, the Enhanced Vegetation Index (EVI), for assessing access to different types of green space in epidemiological studies.

Safety and Tolerability of GalNAc-Conjugated Antisense Drugs Compared to the Same-Sequence 2'--Methoxyethyl-Modified Antisense Drugs: Results from an Integrated Assessment of Phase 1 Clinical Trial Data.

The triantennary -acetylgalactosamine (GalNAc) cluster has demonstrated the utility of receptor-mediated uptake of ligand-conjugated antisense drugs targeting RNA expressed by hepatocytes. GalNAc-conjugated 2'--methoxyethyl (2'MOE) modified antisense oligonucleotides (ASOs) have demonstrated a higher potency than the unconjugated form to support lower doses for an equivalent pharmacological effect. We utilized the Ionis integrated safety database to compare four GalNAc-conjugated and four same-sequence unconjugated 2'MOE ASOs.

Predicting the pharmacokinetics and pharmacodynamics of antisense oligonucleotides: an overview of various approaches and opportunities for PBPK/PD modelling.

Introduction: Advances in research and development (R&D) have enabled many approvals of antisense oligonucleotides (ASOs). Its administration expanded from systemic to local for treating various diseases, where predicting target tissue exposures and pharmacokinetics (PK) and pharmacodynamics (PD) in human can be critical.

Areas Covered: A literature search for PBPK/PD models of ASOs was conducted using PubMed and Embase (to 1 April 2023).

Green-blue space exposure changes and impact on individual-level well-being and mental health: a population-wide dynamic longitudinal panel study with linked survey data.

Background: Cross-sectional evidence suggests that living near green and blue spaces benefits mental health; longitudinal evidence is limited.

Objectives: To quantify the impact of changes in green and blue spaces on common mental health disorders, well-being and health service use.

Design: A retrospective, dynamic longitudinal panel study.

Ambient greenness, access to local green spaces, and subsequent mental health: a 10-year longitudinal dynamic panel study of 2·3 million adults in Wales.

Background: Living in greener areas, or close to green and blue spaces (GBS; eg, parks, lakes, or beaches), is associated with better mental health, but longitudinal evidence when GBS exposures precede outcomes is less available. We aimed to analyse the effect of living in or moving to areas with more green space or better access to GBS on subsequent adult mental health over time, while explicitly considering health inequalities.

Methods: A cohort of the people in Wales, UK (≥16 years; n=2 341 591) was constructed from electronic health record data sources from Jan 1, 2008 to Oct 31, 2019, comprising 19 141 896 person-years of follow-up.

COMmunity-Based Nutrition RISK Screening in Older Adults Living Independently (COMRISK): Feasibility, Acceptability, and Appropriateness of Community Partnership Models in Alberta, Canada.

This feasibility study of routine nutrition risk screening in community-dwelling older adults using a partnership between health care and community-based organizations (CBO) aimed to (1) evaluate the ability of community-based partnerships to provide screening for nutrition risk, and appropriately refer at-risk individuals for follow-up care and (2) determine the barriers to and facilitators of screening. Adults 65 years of age and older were screened by staff in two primary care and one CBO setting using the Seniors in the Community: Risk Evaluation for Eating and Nutrition (SCREEN)-8 nutrition risk screening tool. Screeners, organization administrators, and registered dietitians responded to surveys regarding SCREEN-8 administration, referral processes, and partnership interactions.

Visiting nature is associated with lower socioeconomic inequalities in well-being in Wales.

Natural environments can promote well-being through multiple mechanisms. Many studies have investigated relationships between residential green/blue space (GBS) and well-being, fewer explore relationships with actual use of GBS. We used a nationally representative survey, the National Survey for Wales, anonymously linked with spatial GBS data to investigate associations of well-being with both residential GBS and time in nature (N = 7631).

Sexual and reproductive health in Britain during the first year of the COVID-19 pandemic: cross-sectional population survey (Natsal-COVID-Wave 2) and national surveillance data.

Objectives: To assess sexual behaviour, and sexual and reproductive health (SRH) outcomes, after 1 year of the COVID-19 pandemic in Britain.

Methods: 6658 participants aged 18-59 and resident in Britain completed a cross-sectional web-panel survey (Natsal-COVID-Wave 2, March-April 2021), 1 year after the first lockdown. Natsal-COVID-2 follows the Natsal-COVID-Wave 1 survey (July-August 2020) which captured impacts in the initial months.

Contraceptive use and pregnancy planning in Britain during the first year of the COVID-19 pandemic: findings from a large, quasi-representative survey (Natsal-COVID).

Background: Contraceptive services were significantly disrupted during the COVID-19 pandemic in Britain. We investigated contraception-related health inequalities in the first year of the pandemic.

Methods: Natsal-COVID Wave 2 surveyed 6658 adults aged 18-59 years between March and April 2021, using quotas and weighting to achieve quasi-representativeness.

GroundsWell: Community-engaged and data-informed systems transformation of Urban Green and Blue Space for population health - a new initiative.

Natural environments, such as parks, woodlands and lakes, have positive impacts on health and wellbeing. Urban Green and Blue Spaces (UGBS), and the activities that take place in them, can significantly influence the health outcomes of all communities, and reduce health inequalities. Improving access and quality of UGBS needs understanding of the range of systems (e.

Boney abnormalities cause arterial, venous, and/or neurogenic thoracic outlet syndrome.

Background: Thoracic outlet syndrome (TOS) is a rare condition caused by compression of the neurovascular structures within the thoracic outlet. Different classifications of TOS exist depending on the neurovascular structure being compressed: neurogenic, venous, or arterial. Any of these forms can present independently or coexist with one other.

Integrated Assessment of Phase 2 Data on GalNAc-Conjugated 2'--Methoxyethyl-Modified Antisense Oligonucleotides.

Receptor-mediated delivery of an antisense oligonucleotide (ASO) using the ligand-conjugated antisense technology is establishing a new benchmark for antisense therapeutics. The triantennary -acetylgalactosamine (GalNAc) cluster is the first conjugated ligand to yield a marked increase in ASO potency for RNA targets expressed by hepatocytes, compared to the unconjugated form. In this study, we present an integrated safety assessment of data available from randomized, placebo-controlled, phase 2 studies for six GalNAc-conjugated 2'--methoxyethyl (2'MOE)-modified ASOs.

Assessment of efficacy and safety of volanesorsen for treatment of metabolic complications in patients with familial partial lipodystrophy: Results of the BROADEN study: Volanesorsen in FPLD; The BROADEN Study.

Background: Volanesorsen, an antisense oligonucleotide, is designed to inhibit hepatic apolipoprotein C-III synthesis and reduce plasma apolipoprotein C-III and triglyceride concentrations.

Objective: The present study assessed efficacy and safety of volanesorsen in patients with familial partial lipodystrophy (FPLD) and concomitant hypertriglyceridemia and diabetes.

Methods: BROADEN was a randomized, placebo-controlled, phase 2/3, 52-week study with open-label extension and post-treatment follow-up periods.

Excellent results seen with both transaxillary and infraclavicular approaches to first rib resection in patients with subclavian vein thrombosis.

Background: Venous thoracic outlet syndrome (VTOS) is a debilitating condition with several well-documented treatment paradigms. We reviewed the outcomes from a large academic institution of patients who had undergone transaxillary first rib resection with delayed venography (TA) or infraclavicular first rib and subclavius muscle resection with concomitant venography (ICV) for VTOS with subclavian vein thrombosis.

Methods: We performed a retrospective review of the medical records of all patients who had undergone first rib resection and scalenectomy for VTOS with subclavian vein thrombosis at a single academic institution.

Disconjugacy of Eye Movements during Attempted Fixation: A Sufficient Marker for Amblyopia?

Background: To investigate whether detection of disconjugacy of eye movements during attempted fixation, or interocular position instability, may serve as a single sensitive test for amblyopia.

Patients/methods And Material: Binocular eye movements were recorded at 500 Hz using the EyeLink 1000 eye tracker (SR Research Ltd., Kanata, Ontario, Canada) and analyzed using EyeLink software and Matlab (MathWorks, Natick, MA, USA).

Assessment of the Effect of Organ Impairment on the Pharmacokinetics of 2'-MOE and Phosphorothioate Modified Antisense Oligonucleotides.

The pharmacokinetics (PK) of 2'-O-methoxyethyl and phosphorothioate antisense oligonucleotides (ASOs), with or without N-acetyl galactosamine conjugation, have been well characterized following subcutaneous or intravenous drug administration. However, the effect of organ impairment on ASO PK, primarily hepatic or renal impairment, has not yet been reported. ASOs distribute extensively to the liver and kidneys, where they are metabolized slowly by endo- and exonucleases, with minimal renal excretion as parent drug (<1%-3%).

Phase 2 Study of the Factor XI Antisense Inhibitor IONIS-FXI in Patients With ESRD.

Introduction: Patients with end-stage renal disease (ESRD) requiring hemodialysis (HD) have an increased risk of thrombotic events and bleeding. Antisense reduction of factor XI (FXI) with IONIS-FXI is a novel strategy that may safely reduce the risk of thrombotic events.

Methods: This multicenter study enrolled 49 patients receiving HD in 2 parts.

Apolipoprotein C-III reduction in subjects with moderate hypertriglyceridaemia and at high cardiovascular risk.

Aims: Hypertriglyceridaemia is associated with increased risk of cardiovascular events. This clinical trial evaluated olezarsen, an N-acetyl-galactosamine-conjugated antisense oligonucleotide targeted to hepatic APOC3 mRNA to inhibit apolipoprotein C-III (apoC-III) production, in lowering triglyceride levels in patients at high risk for or with established cardiovascular disease.

Methods And Results: A randomized, double-blind, placebo-controlled, dose-ranging study was conducted in 114 patients with fasting serum triglycerides 200-500 mg/dL (2.