Association of a dietary inflammatory index with cardiometabolic, endocrine, liver, renal and bones biomarkers: cross-sectional analysis of the UK Biobank study.

BACKGROUND AND AIMS: Research into the relationship between an Energy-adjusted Diet-Inflammatory Index (E-DII) and a wider health-related biomarkers profile is limited. Much of the existing evidence centers on traditional metabolic biomarkers in populations with chronic diseases, with scarce data on healthy individuals. Thus, this study aims to investigate the association between an E-DII score and 30 biomarkers spanning metabolic health, endocrine, bone health, liver function, cardiovascular, and renal functions, in healthy individuals. METHODS AND RESULTS: 66,978 healthy UK Biobank participants, the overall mean age was 55.3 (7.9) years were included in this cross-sectional study. E-DII scores, based on 18 food parameters, were categorised as anti-inflammatory (E-DII < -1), neutral (-1 to 1), and pro-inflammatory (>1). Regression analyses, adjusted for confounding factors, were conducted to investigate the association of 30 biomarkers with E-DII. Compared to those with an anti-inflammatory diet, individuals with a pro-inflammatory diet had increased levels of 16 biomarkers, including six cardiometabolic, five liver, and four renal markers. The concentration difference ranged from 0.27 SD for creatinine to 0.03 SD for total cholesterol. Conversely, those on a pro-inflammatory diet had decreased concentrations in six biomarkers, including two for endocrine and cardiometabolic. The association range varied from -0.04 for IGF-1 to -0.23 for SHBG. CONCLUSION: This study highlighted that a pro-inflammatory diet was associated with an adverse profile of biomarkers linked to cardiometabolic health, endocrine, liver function, and renal health.

Schizophrenia and Types of Stroke: A Mendelian Randomization Study.

BACKGROUND: Previous studies suggest an association between schizophrenia and stroke, but no studies have investigated stroke subtypes. We examined potential causal associations between schizophrenia and a range of atherosclerotic, embolic, and hemorrhagic stroke outcomes. METHODS AND RESULTS: Two-sample Mendelian randomization analyses were conducted. The summary-level data (restricted to European ancestry) were obtained for schizophrenia and stroke: ischemic stroke, large-artery stroke, small-vessel stroke, cardioembolic stroke, and intracerebral hemorrhage. The associations between schizophrenia and each outcome were analyzed by an inverse variance weighting method primarily and Mendelian randomization Egger, weighted median, and weighted mode subsequently. The presence of pleiotropy was also tested by Cochran Q statistic, I2 index, and Mendelian randomization Egger intercept with scatter and funnel plots. We found associations between schizophrenia and cardioembolic stroke (odds ratio [OR], 1.070 [95% CI, 1.023-1.119]) and intracerebral hemorrhage (OR, 1.089 [95% CI, 1.005-1.180]) using inverse variance weighting. Little evidence of associations with the other stroke subtypes was found. Different Mendelian randomization methods corroborated the association with cardioembolic stroke but not intracerebral hemorrhage. CONCLUSIONS: We have provided evidence of a potentially causal association between schizophrenia and cardioembolic stroke. Our findings suggest that cardiac evaluation should be considered for those with schizophrenia.

Prospective study design and data analysis in UK Biobank.

Population-based prospective studies, such as UK Biobank, are valuable for generating and testing hypotheses about the potential causes of human disease. We describe how UK Biobank's study design, data access policies, and approaches to statistical analysis can help to minimize error and improve the interpretability of research findings, with implications for other population-based prospective studies being established worldwide.

Association of five diet scores with severe NAFLD incidence: A prospective study from UK Biobank.

AIM: This study aimed to contrast the associations of five common diet scores with severe non-alcoholic fatty liver disease (NAFLD) incidence. MATERIALS AND METHODS: In total, 162 999 UK Biobank participants were included in this prospective population-based study. Five international diet scores were included: the 14-Item Mediterranean Diet Adherence Screener (MEDAS-14), the Recommended Food Score (RFS), the Healthy Diet Indicator (HDI), the Mediterranean Diet Score and the Mediterranean-DASH Intervention for Neurodegenerative Delay score. As each score has different measurements and scales, all scores were standardized and categorized into quartiles. Cox proportional hazard models adjusted for confounder factors investigated associations between the standardized quartiles and severe NAFLD incidence. RESULTS: Over a median follow-up of 10.2 years, 1370 participants were diagnosed with severe NAFLD. When the analyses were fully adjusted, participants in quartile 4 using the MEDAS-14 and RFS scores, as well as those in quartiles 2 and 3 using the HDI score, had a significantly lower risk of severe incident NAFLD compared with those in quartile 1. The lowest risk was observed in quartile 4 for the MEDAS-14 score [hazard ratio (HR): 0.76 (95% confidence interval (CI): 0.62-0.94)] and the RFS score [HR: 0.82 (95% CI: 0.69-0.96)] and as well as in quartile 2 in the HDI score [HR: 0.80 (95% CI: 0.70-0.91)]. CONCLUSION: MEDAS-14, RFS and HDI scores were the strongest diet score predictors of severe NAFLD. A healthy diet might protect against NAFLD development irrespective of the specific approach used to assess diet. However, following these score recommendations could represent optimal dietary approaches to mitigate NAFLD risk.

Different Sources of Fiber Intake and Risk of 17 Specific Cancers and All Cancers Combined: Prospective Study of 364,856 Participants in the UK Biobank.

Inverse associations between dietary fiber (DF) and colorectal cancer risk are well-established. However, evidence is limited in relation to other cancer sites. This study, of 364,856 participants from the UK Biobank, aimed to evaluate the associations between total and source-specific partial DF and risk of 17 specific cancers and all cancers combined. Partial DF was derived from baseline touchscreen questionnaire data on cereal, bread, fruit, and vegetable intake. The outcomes were incident cancer at 17 sites and all cancers combined. Cox proportional hazards models were applied. Over a median 8.8-year follow-up period, 30,725 people were diagnosed with cancer. After adjusting for sociodemographic and lifestyle factors, those in the highest quintile of partial DF compared with the lowest quintile (<9.6 vs ≥19.1 g/day) had 10% lower risk of cancer overall, with the greatest risk reductions observed for cervical (hazard ratio (HR) = 0.33, 95% confidence interval (CI): 0.14; 0.82), esophageal (HR = 0.66, 95% CI: 0.52; 0.84), lung (HR = 0.67, 95% CI: 0.59; 0.76), bladder (HR = 0.72, 95% CI: 0.56; 0.91), and kidney (HR = 0.75, 95% CI: 0.61; 0.92) cancers. Associations between DF and lung cancer were observed only in current and former smokers. Higher DF intake, in particular cereal fiber and fruit and vegetable fiber, was associated with a lower risk of overall and multiple site-specific cancers.

In people with type 2 diabetes, sarcopenia is associated with the incidence of cardiovascular disease: A prospective cohort study from the UK Biobank.

AIM: To investigate the association of sarcopenia with cardiovascular disease (CVD) incidence in people with type 2 diabetes. MATERIALS AND METHODS: A prospective cohort study with 11 974 White European UK Biobank participants with type 2 diabetes, aged 40-70 years, included. Sarcopenia was defined based on the European Working Group on Sarcopenia in Older People as either non-sarcopenic or sarcopenic. Outcomes included CVD, stroke, heart failure (HF) and myocardial infarction (MI). The association between sarcopenia and the incidence of outcomes was investigated using Cox proportional hazard models adjusted for sociodemographic and lifestyle factors. The rate advancement period was used to estimate the time period by which CVD is advanced because of sarcopenia. RESULTS: Over a median follow-up of 10.7 years, 1957 participants developed CVDs: 373 had a stroke, 307 had an MI and 742 developed HF. Compared with non-sarcopenia, those with sarcopenia had higher risks of CVD (HR 1.89 [95% CI 1.61; 2.21]), HF (HR 2.59 [95% CI 2.12; 3.18]), stroke (HR 1.90 [95% CI 1.38; 2.63]), and MI (HR 1.56 [95% CI 1.04; 2.33]) after adjustment for all covariates. Those with sarcopenia had CVD incidence rates equivalent to those without sarcopenia who were 14.5 years older. Similar results were found for stroke, HF and MI. CONCLUSIONS: In people with type 2 diabetes, sarcopenia increased the risk of developing CVD, which might occur earlier than in those without sarcopenia. Therefore, sarcopenia screening and prevention in patients with type 2 diabetes may be useful to prevent the complications of CVD.

Association of Stair Use With Risk of Major Chronic Diseases.

INTRODUCTION: Physical inactivity is associated with a higher risk of chronic diseases. Regular stair use can contribute to increasing physical activity in the population. This study aimed to investigate the association between flights of stairs used daily at home and all-cause mortality and cause-specific incidence and mortality. METHODS: Of the 502,628 UK Biobank participants recruited between 2007 and 2010, 442,027 (mean age, 56±8 years) had available data and were included in the analyses conducted in 2023. Participants were categorized on the basis of flights of stairs climbed daily (1-5, 6-10, 11-15, >15). The disease-specific outcomes were cardiovascular disease, respiratory disease, cancer, type 2 diabetes, and all-cause dementia. Cox proportional hazard models, adjusted for sociodemographic, lifestyle, and health-related confounding factors, were used to analyze the associations between stair use frequency and health outcomes. RESULTS: Participants were followed up for a median of 10.9 years. Climbing stairs >15 times per day was associated with a lower risk of 8 of the 9 outcomes analyzed than not using stairs. The magnitude of association ranged from 3% (95% CI=0.94, 0.99) lower risk for all-cause cancer to 51% (95% CI=0.39, 0.60) lower risk of chronic obstructive pulmonary disease. Findings were similar for mortality outcomes, with the hazard ratios ranging from 0.82 (95% CI=0.77, 0.87) for all-cause cancer to 0.46 (95% CI=0.23, 0.92) for chronic obstructive pulmonary disease mortality. CONCLUSIONS: Stair use was associated with a lower risk of all-cause mortality and cause-specific incidence and mortality independent of confounding factors, including adiposity and multimorbidity.

The impact of COVID-19 and associated lockdowns on traumatic spinal cord injury incidence: a population based study.

STUDY DESIGN: Natural experiment OBJECTIVES: To determine whether COVID-19 restrictions were associated with changes in the incidence of traumatic spinal cord injury (TSCI) in Scotland. SETTING: The Queen Elizabeth National Spinal Injuries Unit (QENSIU), the sole provider of treatment for TSCI in Scotland. METHODS: Time series analysis of all admissions for TSCI between 1st January 2015 and 31st August 2022. RESULTS: Over the 8-year study period, 745 patients were admitted to the QENSIU with a TSCI. Interrupted time series analysis showed that level 3 and 4 COVID-19 lockdown restrictions (the most severe levels) were associated with lower incidence of TSCI (RR 0.63, CI% CI 0.47, 0.82, p < 0.001). The associations were stronger in people aged over 45 (additive interaction p = 0.001), males (additive interaction p = 0.01) and non-tetraplegia (additive interaction p = 0.002). The incidence of TSCI due to deliberate self-harm was higher (0.41 versus 0.23 per month) during restrictions. CONCLUSIONS: Overall, TSCI incidence reduced in Scotland when lockdowns were implemented, presumably due to lower engagement in risky activities. The increase in TSCI due to deliberate self-harm may reflect increased mental health problems and social isolation and should be anticipated and targeted in future pandemics. The change in incidence during the COVID-19 pandemic may have an economic impact and see a temporary reduction in the burden on health and social care. The results of this study will be useful for resource planning in future pandemics.

Association between menstrual cycle phase and metabolites in healthy, regularly menstruating women in UK Biobank, and effect modification by inflammatory markers and risk factors for metabolic disease.

BACKGROUND: Preliminary evidence demonstrates some parameters of metabolic control, including glycaemic control, lipid control and insulin resistance, vary across the menstrual cycle. However, the literature is inconsistent, and the underlying mechanisms remain uncertain. This study aimed to investigate the association between the menstrual cycle phase and metabolites and to explore potential mediators and moderators of these associations. METHODS: We undertook a cross-sectional cohort study using UK Biobank. The outcome variables were glucose; triglyceride; triglyceride to glucose index (TyG index); total, HDL and LDL cholesterol; and total to HDL cholesterol ratio. Generalised additive models (GAM) were used to investigate non-linear associations between the menstrual cycle phase and outcome variables. Anthropometric, lifestyle, fitness and inflammatory markers were explored as potential mediators and moderators of the associations between the menstrual cycle phase and outcome variables. RESULTS: Data from 8694 regularly menstruating women in UK Biobank were analysed. Non-linear associations were observed between the menstrual cycle phase and total (p < 0.001), HDL (p < 0.001), LDL (p = 0.012) and total to HDL cholesterol (p < 0.001), but not glucose (p = 0.072), triglyceride (p = 0.066) or TyG index (p = 0.100). Neither anthropometric, physical fitness, physical activity, nor inflammatory markers mediated the associations between the menstrual cycle phase and metabolites. Moderator analysis demonstrated a greater magnitude of variation for all metabolites across the menstrual cycle in the highest and lowest two quartiles of fat mass and physical activity, respectively. CONCLUSIONS: Cholesterol profiles exhibit a non-linear relationship with the menstrual cycle phase. Physical activity, anthropometric and fitness variables moderate the associations between the menstrual cycle phase and metabolite concentration. These findings indicate the potential importance of physical activity and fat mass as modifiable risk factors of the intra-individual variation in metabolic control across the menstrual cycle in pre-menopausal women.

Cross-Regional Data Initiative for the Assessment and Development of Treatment for Neurological and Mental Disorders.

Purpose: To describe and categorize detailed components of databases in the Neurological and Mental Health Global Epidemiology Network (NeuroGEN). Methods: An online 132-item questionnaire was sent to key researchers and data custodians of NeuroGEN in North America, Europe, Asia and Oceania. From the responses, we assessed data characteristics including population coverage, data follow-up, clinical information, validity of diagnoses, medication use and data latency. We also evaluated the possibility of conversion into a common data model (CDM) to implement a federated network approach. Moreover, we used radar charts to visualize the data capacity assessments, based on different perspectives. Results: The results indicated that the 15 databases covered approximately 320 million individuals, included in 7 nationwide claims databases from Australia, Finland, South Korea, Taiwan and the US, 6 population-based electronic health record databases from Hong Kong, Scotland, Taiwan, the Netherlands and the UK, and 2 biomedical databases from Taiwan and the UK. Conclusion: The 15 databases showed good potential for a federated network approach using a common data model. Our study provided publicly accessible information on these databases for those seeking to employ real-world data to facilitate current assessment and future development of treatments for neurological and mental disorders.

Association between 5-min Apgar score and attention deficit hyperactivity disorder: a Scotland-wide record linkage study of 758,423 school children.

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) affects around 1 in 20 children and is associated with life-long sequelae. Previous studies of the association between Apgar score and ADHD have reported inconsistent findings. METHODS: Record linkage of maternity, prescribing and school pupil census databases was used to conduct a population e-cohort study of singleton children born in Scotland and attending school in Scotland at any point between 2009 and 2013. Binary logistic regression analysis was used to investigate the association between 5-min Apgar score and treated ADHD adjusting for sociodemographic and maternity confounders. RESULTS: Of the 758,423 children, 7,292 (0.96%) received ADHD medication. The results suggested a potential dose-response relationship between Apgar score and treated ADHD independent of confounders. Referent to an Apgar score of 10, risk of treated ADHD was higher for scores of 0-3 (adjusted OR 1.76, 95% CI 1.32-2.34), 4-6 (adjusted OR 1.50, 95% CI 1.21-1.86) and even 7-9 (adjusted OR 1.26, 95% CI 1.18-1.36) which are traditionally considered within the normal range. CONCLUSIONS: In addition to reinforcing the need to maximise Apgar score through good obstetric practice, the findings suggest that Apgar score may be useful in predicting future risk of ADHD and therefore facilitating early diagnosis and treatment.

True prevalence of long-COVID in a nationwide, population cohort study.

Long-COVID prevalence estimates vary widely and should take account of symptoms that would have occurred anyway. Here we determine the prevalence of symptoms attributable to SARS-CoV-2 infection, taking account of background rates and confounding, in a nationwide population cohort study of 198,096 Scottish adults. 98,666 (49.8%) had symptomatic laboratory-confirmed SARS-CoV-2 infections and 99,430 (50.2%) were age-, sex-, and socioeconomically-matched and never-infected. While 41,775 (64.5%) reported at least one symptom 6 months following SARS-CoV-2 infection, this was also true of 34,600 (50.8%) of those never-infected. The crude prevalence of one or more symptom attributable to SARS-CoV-2 infection was 13.8% (13.2%,14.3%), 12.8% (11.9%,13.6%), and 16.3% (14.4%,18.2%) at 6, 12, and 18 months respectively. Following adjustment for potential confounders, these figures were 6.6% (6.3%, 6.9%), 6.5% (6.0%, 6.9%) and 10.4% (9.1%, 11.6%) respectively. Long-COVID is characterised by a wide range of symptoms that, apart from altered taste and smell, are non-specific. Care should be taken in attributing symptoms to previous SARS-CoV-2 infection.

Life expectancy can increase by up to 10 years following sustained shifts towards healthier diets in the United Kingdom.

Adherence to healthy dietary patterns can prevent the development of non-communicable diseases and affect life expectancy. Here, using a prospective population-based cohort data from the UK Biobank, we show that sustained dietary change from unhealthy dietary patterns to the Eatwell Guide dietary recommendations is associated with 8.9 and 8.6 years gain in life expectancy for 40-year-old males and females, respectively. In the same population, sustained dietary change from unhealthy to longevity-associated dietary patterns is associated with 10.8 and 10.4 years gain in life expectancy in males and females, respectively. The largest gains are obtained from consuming more whole grains, nuts and fruits and less sugar-sweetened beverages and processed meats. Understanding the contribution of sustained dietary changes to life expectancy can provide guidance for the development of health policies.

Understanding covid-19 outcomes among people with intellectual disabilities in England.

BACKGROUND: Evidence from the UK from the early stages of the covid-19 pandemic showed that people with Intellectual Disabilities (ID) had higher rates of covid-19 mortality than people without ID. However, estimates of the magnitude of risk vary widely; different studies used different time periods; and only early stages of the pandemic have been analysed. Existing analyses of risk factors have also been limited. The objective of this study was to investigate covid-19 mortality rates, hospitalisation rates, and risk factors in people with ID in England up to the end of 2021. METHODS: Retrospective cohort study of all people with a laboratory-confirmed SARS-CoV-2 infection or death involving covid-19. Datasets covering primary care, secondary care, covid-19 tests and vaccinations, prescriptions, and deaths were linked at individual level. RESULTS: Covid-19 carries a disproportionately higher risk of death for people with ID, above their already higher risk of dying from other causes, in comparison to those without ID. Around 2,000 people with ID had a death involving covid-19 in England up to the end of 2021; approximately 1 in 180. The covid-19 standardized mortality ratio was 5.6 [95% CI 5.4, 5.9]. People with ID were also more likely to be hospitalised for covid-19 than people without ID. The main determinants of severe covid-19 outcomes (deaths and/or hospitalisations) in both populations were age, multimorbidity and vaccination status. The key factor responsible for the higher risk of severe covid-19 in the ID population was a much higher prevalence of multimorbidity in this population. AstraZeneca vaccine was slightly less effective in preventing severe covid-19 outcomes among people with ID than among people without ID. CONCLUSIONS: People with ID should be considered a priority group in future pandemics, such as shielding and vaccinations.

Validating the SMART2 Score in a Racially Diverse High-Risk Nationwide Cohort of Patients Receiving Coronary Artery Bypass Grafting.

Background We tested the potential of the Secondary Manifestations of Arterial Disease (SMART2) risk score for use in patients undergoing coronary artery bypass grafting. Methods and Results We conducted an external validation of the SMART2 score in a racially diverse high-risk national cohort (2010-2019) that underwent isolated coronary artery bypass grafting. We calculated the preoperative SMART2 score and modeled the 5-year major adverse cardiovascular event (cardiovascular mortality+myocardial infarction+stroke) incidence. We evaluated SMART2 score discrimination at 5 years using c-statistic and calibration with observed/expected ratio and calibration plots. We analyzed the potential clinical benefit using decision curves. We repeated these analyses in clinical subgroups, diabetes, chronic kidney disease, and polyvascular disease, and separately in White and Black patients. In 27 443 (mean age, 65 years; 10% Black individuals) US veterans undergoing coronary artery bypass grafting (2010-2019) nationwide, the 5-year major adverse cardiovascular event rate was 25%; 27% patients were in high predicted risk (>30% 5-year major adverse cardiovascular events). SMART2 score discrimination (c-statistic: 64) was comparable to the original study (c-statistic: 67) and was best in patients with chronic kidney disease (c-statistic: 66). However, it underpredicted major adverse cardiovascular event rates in the whole cohort (observed/expected ratio, 1.45) as well as in all studied subgroups. The SMART2 score performed better in White than Black patients. On decision curve analysis, the SMART2 score provides a net benefit over a wide range of risk thresholds. Conclusions The SMART2 model performs well in a racially diverse coronary artery bypass grafting cohort, with better predictive capabilities at the upper range of baseline risk, and can therefore be used to guide secondary preventive pharmacotherapy.

Corrigendum: A comparison of physical activity, muscle strength, and sleep between people with type 2 diabetes in Kuwait and he UK: a cross sectional study.

[This corrects the article DOI: 10.3389/fendo.2022.1067227.].

Consistent effects of the genetics of happiness across the lifespan and ancestries in multiple cohorts.

Happiness is a fundamental human affective trait, but its biological basis is not well understood. Using a novel approach, we construct LDpred-inf polygenic scores of a general happiness measure in 2 cohorts: the Adolescent Brain Cognitive Development (ABCD) cohort (N = 15,924, age range 9.23-11.8 years), the Add Health cohort (N = 9129, age range 24.5-34.7) to determine associations with several well-being and happiness measures. Additionally, we investigated associations between genetic scores for happiness and brain structure in ABCD (N = 9626, age range (8.9-11) and UK Biobank (N = 16,957, age range 45-83). We detected significant (p.FDR < 0.05) associations between higher genetic scores vs. several well-being measures (best r2 = 0.019) in children of multiple ancestries in ABCD and small yet significant correlations with a happiness measure in European participants in Add Health (r2 = 0.004). Additionally, we show significant associations between lower genetic scores for happiness with smaller structural brain phenotypes in a white British subsample of UK Biobank and a white sub-sample group of ABCD. We demonstrate that the genetic basis for general happiness level appears to have a consistent effect on happiness and wellbeing measures throughout the lifespan, across multiple ancestral backgrounds, and multiple brain structures.

Associations and predictive performance of 11 anthropometric measures with incident type 2 diabetes: A prospective cohort study from the UK Biobank.

OBJECTIVE: The study aim was to investigate associations of 11 anthropometric measures with incident type 2 diabetes and compare their predictive performance. METHODS: This prospective cohort study included 161,127 White European UK Biobank participants who were free of diabetes at baseline. Anthropometric measures included height, weight, BMI, A Body Shape Index, waist circumference, waist to hip ratio, waist to height ratio (WHtR), hip circumference, visceral adiposity index, hip index, and anthropometric risk index. The associations were examined using Cox proportional hazard models. The differences in C-index were used to compare predictive performance between BMI and other anthropometric measures. RESULTS: The median follow-up was 10.0 (interquartile range: 9.3-10.8) years, during which 6315 participants developed type 2 diabetes. All markers except height and hip index were positively associated with incident type 2 diabetes. The strongest associations were found for WHtR (hazard ratio per 1-SD increment: 2.27 [95% CI 2.19-2.35] in women; 1.96 [95% CI 1.90-2.01] in men). Compared with BMI, WHtR and anthropometric risk index had significantly better type 2 diabetes risk discrimination. CONCLUSIONS: Although most adiposity markers were associated with type 2 diabetes, the magnitude of the associations differed. WHtR had the strongest associations and predictive ability for type 2 diabetes and thus could be a more suitable marker for clinical use.

Pre-hospital and retrieval medicine in Scotland: a retrospective cohort study of the workload and outcomes of the emergency medical retrieval service in the first decade of national coverage.

BACKGROUND: The Emergency Medical Retrieval Service (EMRS) has provided national pre-hospital critical care and aeromedical retrieval in Scotland since 2010. This study investigates trends in the service and patients attended over the last decade; and factors associated with clinical deterioration and pre-hospital death. METHODS: A retrospective cohort study was conducted of all service taskings over ten years (2011-2020 inclusive). The EMRS electronic database provided data on location, sociodemographic factors, diagnoses, physiological measurements, clinical management, and pre-hospital deaths. Binary logistic regression models were used to determine change in physiology in pre-hospital care, and factors associated with pre-hospital death. Geospatial modelling, using road and air travel time models, was used to explore transfer times. RESULTS: EMRS received 8,069 taskings over the study period, of which 2,748 retrieval and 3,633 pre-hospital critical care missions resulted in patient contact. EMRS was more commonly dispatched to socioeconomically deprived areas for pre-hospital critical care incidents (Spearman's rank correlation, r(8)=-0.75, p = 0.01). In multivariate analysis, systolic blood pressure < 90mmHg, respiratory rate < 6/min or > 30/min, and Glasgow Coma Score ≤ 14 were associated with pre-hospital mortality independent of demographic factors. Geospatial modelling suggested that aeromedical retrieval reduced the mean time to a critical care unit by 1 h 46 min compared with road/ferry transportation. CONCLUSION: EMRS continues to develop, delivering Pre-Hospital and Retrieval Medicine across Scotland and may have a role in addressing health inequalities, including socioeconomic deprivation and geographic isolation. Age, specific distances from care, and abnormal physiology are associated with death in pre-hospital critical care.