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Purpose of Review: Adequate and balanced nutrition during pregnancy is essential for both the mother's and fetus's health. The increased dietary intake of ultra-processed foods (UPFs) and their significant share in the diet negatively affects diet quality and gestational weight gain during pregnancy. The aim of this systematic review was to examine the association of UPFs consumption with diet quality and gestational weight change among healthy pregnant women, using data from observational studies (PROSPERO Identifier: CRD42023468269) from the last 10 years., Recent Findings: A search was performed in Pubmed, Wiley, Scopus, and Web of Science, and studies published in english language were selected. Study selection and data extraction were made by determining the exclusion and eligible inclusion criterias according to the PECOS framework. Of the 12 studies included, 5 were longitudinal cohort studies and 7 were cross-sectional studies. On average, half of the energy in the participants' daily diets came from UPFs in 3 studies, but the energy share of UPFs was about 20-30% in the remainder studies. UPFs-enriched maternal diet was associated with less dietary intake of legumes, vegetables, fruits and protein sources (seafood and plant protein, total protein) and greater consumption of refined grains compared to those who consume less UPFs. In parallel, UPFs consumption was negatively associated with Healthy Eating Index. UPF intake during pregnancy has a negative impact on diet quality and gestational weight gain. Increasing awareness of UPFs during this period may reduce potential complications during pregnancy and fetal growth., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To investigate whether micronutrient intake from food as well as the regular uptake of specific vitamins and/or minerals are associated with leucocyte telomere length (LTL)., Methods: This is a cross-sectional study using data from 422,693 UK Biobank participants aged from 40 to 69 years old, during 2006-2010. LTL was measured as the ratio of telomere repeat number to a single-copy gene and was log e -transformed and z-standardized (z-LTL). Information concerning supplement use was collected at baseline through the touchscreen assessment, while micronutrient intake from food were self-reported through multiple web-based 24 h recall diaries. The association between micronutrient intake or supplement use and z-LTL was assessed using multivariable linear regression models adjusting for demographic, lifestyle and clinical characteristics., Results: About 50% (n = 131,810) of the participants, with complete data on all covariates, self-reported regular supplement intake. Whilst overall supplement intake was not associated with z-LTL, trends toward shorter z-LTL with regular vitamin B (-0.019 (95% CI: -0.041; 0.002)) and vitamin B9 (-0.027 (-0.054; 0.000)) supplement intake were observed. z-LTL was associated with food intake of pantothenic acid (-0.020 (-0.033; -0.007)), vitamin B6 (-0.015 (-0.027; -0.003)), biotin (0.010 (0.002; 0.018)) and folate (0.016 (0.003; 0.030)). Associations of z-LTL with these micronutrients were differentiated according to supplement intake., Conclusion: Negative associations equivalent to a year or less of age-related change in LTL between micronutrient intake and LTL were observed. Due to this small effect, the clinical importance of the associations and any relevance to the effects of vitamin and micronutrient intake toward chronic disease prevention remains uncertain., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

The high cost of gluten-free products (GFPs) is being discussed as a potential barrier to adherence to a gluten-free diet, rendering monitoring of their pricing an ongoing demand in a market subject to continuous fluctuations. The current study aimed to assess the current pricing status of GFPs in the Greek retail market, with a focus on differences between staple and non-staple foods. The retail price and packaging weight of all available GFPs and their gluten-containing (GCPs) counterparts of a GFP-shopping basket (formulated based on the results of a preceding online survey) were recorded by visiting one store of the five most popular reported supermarket chains. The food categories were grouped into staple (e.g. breads, pasta and flours) and non-staple (e.g. chips, sweets and sauces) foods. Adjusting for supermarket chain and product type, a quantile mixed regression model was applied to assess the extent to which median product price (per 100 g) differed between GFPs and GCPs. The unique products recorded were 1058 (of which 408 GFPs), with a total of 2165 retail price recordings. While the overall median price/100 g of GFPs was not found to be significantly different from that of GCPs, the median price of staple GFPs was estimated to be higher than staple GCPs (+€1.03 [95% CI: €0.93; €1.13] per 100 g), whilst that of non-staple GFPs was slightly lower (-€0.20 [95% CI: -€0.37; -€0.02] per 100 g). In conclusion, the persisting higher cost of staple GFPs suggests the need for ongoing financial support for people with coeliac disease., (© 2024 The Author(s). Nutrition Bulletin published by John Wiley & Sons Ltd on behalf of British Nutrition Foundation.)

Childhood overweight/obesity (OV/OB) is a major public health problem in Western countries, often accompanied with comorbidities (e.g., hypertension and insulin resistance) (i.e., metabolically unhealthy obesity-MUO). Among diet-related risk factors of OV/OB risk and MUO, meal patterns remain limitedly studied. The aim of this systematic review was to explore associations between meal patterns and the risk of childhood OV/OB and MUO in children/adolescents aged 2-19 years. Longitudinal studies and randomised controlled trials from PUBMED and Scopus published between January 2013 and April 2024 were retrieved. Twenty-eight studies were included, all of which reported on OV/OB risk, with none on MUO risk. Regular consumption of breakfast ( n = 3) and family meals ( n = 4) and avoiding dining while watching TV ( n = 4) may be protective factors against childhood OV/OB, whereas meal skipping (primarily breakfast; n = 4) may be a detrimental factor. Mixed effects of meal frequency on OV/OB risk were observed; no effects of frequency of lunch or of fast-food consumption and of meals served at school were found. There was insufficient evidence to support the role of other patterns (meal timing, eating in other social contexts). Meals were mainly participant-identified, leading to increased heterogeneity. Research focusing on childhood MUO and the use of harmonised definitions regarding the assessment of meal patterns are highly warranted.

Background: Amblyopia is a common neurodevelopmental condition and leading cause of childhood visual impairment. Given the known association between neurodevelopmental impairment and cardiometabolic dysfunction in later life, we investigated whether children with amblyopia have increased risk of cardiometabolic disorders in adult life., Methods: This was a cross-sectional and longitudinal analysis of 126,399 United Kingdom Biobank cohort participants who underwent ocular examination. A subset of 67,321 of these received retinal imaging. Data analysis was conducted between November 1st 2021 and October 15th 2022. Our primary objective was to investigate the association between amblyopia and a number of components of metabolic syndrome and individual cardiometabolic diseases. Childhood amblyopia, dichotomised as resolved or persisting by adulthood, cardiometabolic disease and mortality were defined using ophthalmic assessment, self-reported, hospital admissions and death records. Morphological features of the optic nerve and retinal vasculature and sublayers were extracted from retinal photography and optical coherence tomography. Associations between amblyopia and cardiometabolic disorders as well as retinal markers were investigated in multivariable-adjusted regression models., Findings: Individuals with persisting amblyopia (n = 2647) were more likely to be obese (adjusted odds ratio (95% confidence interval): 1.16 (1.05; 1.28)), hypertensive (1.25 (1.13; 1.38)) and diabetic (1.29 (1.04; 1.59)) than individuals without amblyopia (controls, (n = 18,481)). Amblyopia was also associated with an increased risk of myocardial infarction (adjusted hazard ratio: 1.38 (1.11; 1.72)) and death (1.36 (1.15; 1.60)). On retinal imaging, amblyopic eyes had significantly increased venular caliber (0.29 units (0.21; 0.36)), increased tortuosity (0.11 units (0.03; 0.19)), but lower fractal dimension (-0.23 units (-0.30; -0.16)) and thinner ganglion cell-inner plexiform layer (mGC-IPL, -2.85 microns (-3.47; -2.22)). Unaffected fellow eyes of individuals with amblyopia also had significantly lower retinal fractal dimension (-0.08 units (-0.15; -0.01)) and thinner mGC-IPL (-1.14 microns (-1.74; -0.54)). Amblyopic eyes with a persisting visual deficit had smaller optic nerve disc height (-0.17 units (-0.25; -0.08)) and width (-0.13 units (-0.21; -0.04)) compared to control eyes., Interpretation: Although further research is needed to understand the basis of the observed associations, healthcare professionals should be cognisant of greater cardiometabolic dysfunction in adults who had childhood amblyopia. Differences in retinal features in both the amblyopic eye and the unaffected non-amblyopic suggest generalised versus local processes., Funding: Medical Research Council (MR/T000953/1) and the National Institute for Health and Care Research., Competing Interests: We declare no competing interests., (© 2024 The Authors.)

Background: Childhood vision impairment (VI) can adversely impact health and social outcomes and limit life chances. We investigated whether its adverse impacts into adult life changed during a period in which legislation, policy and services to address inequalities relating to disability were implemented., Methods: Cross-cohort study comprising 14 247 participants from the 1946, 1958 and 1970 British birth cohorts (BC). Participants dichotomized as VI at age 15/16 (distance visual acuity was 6/12 or worse in the better-seeing eye) or normally sighted. Associations of childhood VI with health, well-being, socioeconomic and social participation outcomes in mid-adult life were investigated using regression models adjusted for participants' early life socioeconomic markers and sex. Change in adjusted odds ratios of >10% in the same direction in successive cohorts, or a > 20% difference between 1970BC and one older cohort were considered meaningful., Results: Trends over time in impacts of childhood onset VI into mid-adult life were complex. This included worsening of odds of poorer physical health (odds ratio 1.47; 95% confidence interval 1.02-2.14), living in unsatisfactory (1.54; 1.03-2.29) or overcrowded (2.34; 1.26-4.06) households, being unemployed (2.19; 1.19-3.97) and not gaining additional educational qualifications during mid-adult life (1.61; 1.08-2.47). By contrast the odds of not participating in some social activities (e.g. seeing friends) improved over time. Associations with other outcomes were unchanged., Conclusions: Many adverse impacts of childhood VI do not appear ameliorated over time by legislation, policies and provision that would have been expected to reduce inequalities. Moreover, some were increased. Childhood VI continues to cast a life-long shadow., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Public Health Association.)

The use of the lambda-mu-sigma (LMS) method for estimating centiles and producing reference ranges has received much interest in clinical practice, especially for assessing growth in childhood. However, this method may not be directly applicable where measures are based on a score calculated from question response categories that is bounded within finite intervals, for example, in psychometrics. In such cases, the main assumption of normality of the conditional distribution of the transformed response measurement is violated due to the presence of ceiling (and floor) effects, leading to biased fitted centiles when derived using the common LMS method. This paper describes the methodology for constructing reference intervals when the response variable is bounded and explores different distribution families for the centile estimation, using a score derived from a parent-completed assessment of cognitive and language development in 24 month-old children. Results indicated that the z-scores, and thus the extracted centiles, improved when kurtosis was also modeled and that the ceiling effect was addressed with the use of the inflated binomial distribution. Therefore, the selection of the appropriate distribution when constructing centile curves is crucial.

Introduction: Sarcomatoid urothelial carcinoma (SUC) is a rare and aggressive variant of bladder cancer with limited data guiding prognosis. In this study, we present the first prognostic nomograms in the literature for 3- and 5-year overall survival (OS) and disease-specific survival (DSS), for patients with SUC derived from the surveillance, epidemiology and end results database (SEER)., Materials and Methods: Patients with SUC were identified by using the ICD-10 topography codes C67.0-C67.9 (bladder cancer), and the morphologic code 8122 (SUC). Patients were randomly divided into a training cohort (TC) and a validation cohort (VC) (7:3 ratio). Variables significantly associated with OS and DSS were identified with multivariate Cox regression and were used to build the nomograms. Harrel's C-statistic with bootstrap resampling and calibration curves were used for internal (TC) and external (VC) validation. Clinical utility of the nomograms was assessed with the decision curve analysis (DCA). Goodness of fit between the nomograms and the AJCC 8th edition staging system was compared with the likelihood ratio test., Results: A total of 741 patients with SUC were included (507 TC, 234 VC). No statistically significant differences in baseline characteristics were identified between the 2 cohorts. Sex, SEER stage, radical cystectomy and chemotherapy were common variables for the OS and the DSS nomograms with the addition of age in the former. Optimism-corrected C-statistic for the nomograms was 0.68 and 0.67 for OS and DSS respectively. In comparison, C-statistic for AJCC was 0.59 for OS and 0.60 for DSS (P < 0.001). Calibration curves constructed for the nomograms showed appropriate consistency between predicted and actual survival. The nomograms demonstrated optimal clinical utility in the DCA, outperforming the AJCC staging system, by maintaining a higher clinical net benefits than treat all, treat none and AJCC curves, across threshold probabilities., Conclusion: We present the first prognostic nomograms developed in patients with SUC. Our models demonstrated superior prognostic performance to the AJCC system, by utilizing a set of variables readily available in daily practice and may serve as useful tools for the individualized risk assessment of these patients., Competing Interests: Conflict of Interest Jonathan L. Wright has received royalties from UpToDate. He has done clinical trials for Movember Foundation, Merck, Nucleix, Altor Biosciences and is consultant at Sanofi Genzyme. Petros Grivas: (in the last 3 years; all unrelated to this manuscript) has provided consulting to AstraZeneca, Astellas Pharma, Boston Gene, Bristol Myers Squibb, Dyania Health, EMD Serono, Exelixis, Fresenius Kabi, Genentech/Roche, Gilead Sciences, GlaxoSmithKline, Guardant Health, G1 Therapeutics, Infinity Pharmaceuticals, Janssen, Lucence Health, Merck, Mirati Therapeutics, Pfizer, PureTech, QED Therapeutics, Regeneron Pharmaceuticals, Seattle Genetics, Silverback Therapeutics, 4D Pharma PLC, and UroGen. His institution has received grants from Bavarian Nordic, Bristol Myers Squibb, Clovis Oncology, Debiopharm, EMD Serono, G1 Therapeutics, Gilead Sciences, GlaxoSmithKline, Merck, Mirati Therapeutics, Pfizer, and QED Therapeutics. The remaining authors have stated that they have no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Shorter telomere length (TL) is associated with risk of several age-related diseases and decreased life span, but the extent to which dietary patterns and practices associate with TL is uncertain., Objective: This study aimed to investigate the association of dietary patterns and practices and leucocyte TL (LTL)., Design: This was a cross-sectional study., Participants and Setting: Data collected voluntarily from up to 422,797 UK Biobank participants, during 2006-2010., Main Outcome Measures: LTL was measured as a ratio of the telomere repeat number to a single-copy gene and was log e -transformed and standardized (z-LTL)., Statistical Analyses Performed: Adherence a priori to a Mediterranean-style diet was assessed through the MedDietScore. Principal component analysis was used to a posteriori extract the "Meat" and "Prudent" dietary patterns. Additional dietary practices considered were the self-reported adherence to "Vegetarian" diet, "Eating 5-a-day of fruit and vegetables" and "Abstaining from eggs/dairy/wheat/sugar." Associations between quintiles of dietary patterns or adherence to dietary practices with z-LTL were investigated through multivariable linear regression models (adjusted for demographic, lifestyle, and clinical characteristics)., Results: Adherence to the "Mediterranean" and the "Prudent" patterns, was positively associated with LTL, with an effect magnitude in z-LTL of 0.020 SD and 0.014 SD, respectively, for the highest vs the lowest quintile of adherence to the pattern (both P values < 0.05). Conversely, a reversed association between quintile of the "Meat" pattern and LTL was observed, with z-LTL being on average shorter by 0.025 SD (P = 6.12×10 -05 ) for participants in the highest quintile of the pattern compared with the lowest quintile. For adherents to "5-a-day" z-LTL was on average longer by 0.027 SD (P = 5.36×10 -09 ), and for "abstainers," LTL was shorter by 0.016 SD (P = 2.51×10 -04 ). The association of LTL with a vegetarian diet was nonsignificant after adjustment for demographic, lifestyle, and clinical characteristics., Conclusions: Several dietary patterns and practices associated with beneficial health effects are significantly associated with longer LTL. However, the magnitude of the association was small, and any clinical relevance is uncertain., (Copyright © 2023 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Objective: The aim of the study was to assess the clinical effectiveness of the national cardiovascular disease (CVD) prevention programme-National Health Service Health Check (NHSHC) in reduction of CVD risk., Design: Prospective cohort study., Setting: 147 primary care practices in Leicestershire and Northamptonshire in England, UK., Participants: 27 888 individuals undergoing NHSHC with a minimum of 18 months of follow-up data., Outcome Measures: The primary outcomes were NHSHC attributed detection of CVD risk factors, prescription of medications, changes in values of individual risk factors and frequency of follow-up., Results: At recruitment, 18% of participants had high CVD risk (10%-20% 10-year risk) and 4% very high CVD risk (>20% 10-year risk). New diagnoses or hypertension (HTN) was made in 2.3% participants, hypercholesterolaemia in 0.25% and diabetes mellitus in 0.9%. New prescription of stains and antihypertensive medications was observed in 5.4% and 5.4% of participants, respectively. Total cholesterol was decreased on average by 0.38 mmol/L (95% CI -0.34 to -0.41) and 1.71 mmol/L (-1.48 to -1.94) in patients with initial cholesterol >5 mmol/L and >7.5 mmol/L, respectively. Systolic blood pressure was decreased on average by 2.9 mm Hg (-2.3 to -3.7), 15.7 mm Hg (-14.1 to -17.5) and 33.4 mm Hg (-29.4 to -37.7), in patients with grade 1, 2 and 3 HTN, respectively. About one out of three patients with increased CVD risk had no record of follow-up or treatment., Conclusions: Majority of patients identified with increased CVD risk through the NHSHC were followed up and received effective clinical interventions. However, one-third of high CVD risk patients had no follow-up and therefore did not receive any treatment. Our study highlights areas of focus which could improve the effectiveness of the programme., Trial Registration Number: NCT04417387., Competing Interests: Competing interests: KK was a national advisor for the NHS Health Checks programme., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Objectives: Endurance athletes are at an increased risk of atrial fibrillation (AF) when compared with the general population. However, the risk of stroke in athletes with AF is unknown., Design and Setting: We aimed to assess this risk using an international online survey., Patients: Individuals that had competed in ≥1 competitive events and were ≥40 years old were included., Interventions: Self-reported demographic, medical history, and training history data were collected, and a CHA 2 DS 2 -VASc was calculated., Main Outcome Measures: Binary logistic regression was used to assess variables associated with AF and stroke., Results: There were 1002 responses from participants in 41 countries across Africa, Asia, Australasia, Europe, and North and South America, and 942 were included in the final analysis. The average age was 52.4 ± 8.5 years, and 84% were male. The most common sports were cycling (n = 677, 72%), running (n = 558, 59%), and triathlon (n = 245, 26%). There were 190 (20%) individuals who reported AF and 26 individuals (3%) who reported stroke; of which, 14 (54%) had AF. Lifetime exercise dose [odds ratio (OR), 1.02, 95% confidence interval (95% CI),1.00-1.03, P = 0.02] and swimming (OR, 1.56, 95% CI, 1.02-2.39, P = 0.04) were associated with AF in multivariable analysis, independent of other risk factors. Atrial fibrillation was associated with stroke (OR, 4.18, 95% CI, 1.80-9.72, P < 0.01), even in individuals with a low (0/1) CHA 2 DS 2 -VASc score (OR, 4.20, 95% CI, 1.83-9.66, P < 0.01)., Conclusions: This survey provides early evidence that veteran endurance athletes who develop AF may be at an increased risk of developing stroke, even in those deemed to be at low risk by CHA 2 DS 2 -VASc score., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Aims: Most patients who receive implantable cardioverter defibrillators (ICDs) for primary prevention do not receive therapy during the lifespan of the ICD, whilst up to 50% of sudden cardiac death (SCD) occur in individuals who are considered low risk by conventional criteria. Machine learning offers a novel approach to risk stratification for ICD assignment., Methods and Results: Systematic search was performed in MEDLINE, Embase, Emcare, CINAHL, Cochrane Library, OpenGrey, MedrXiv, arXiv, Scopus, and Web of Science. Studies modelling SCD risk prediction within days to years using machine learning were eligible for inclusion. Transparency and quality of reporting (TRIPOD) and risk of bias (PROBAST) were assessed. A total of 4356 studies were screened with 11 meeting the inclusion criteria with heterogeneous populations, methods, and outcome measures preventing meta-analysis. The study size ranged from 122 to 124 097 participants. Input data sources included demographic, clinical, electrocardiogram, electrophysiological, imaging, and genetic data ranging from 4 to 72 variables per model. The most common outcome metric reported was the area under the receiver operator characteristic (n = 7) ranging between 0.71 and 0.96. In six studies comparing machine learning models and regression, machine learning improved performance in five. No studies adhered to a reporting standard. Five of the papers were at high risk of bias., Conclusion: Machine learning for SCD prediction has been under-applied and incorrectly implemented but is ripe for future investigation. It may have some incremental utility in predicting SCD over traditional models. The development of reporting standards for machine learning is required to improve the quality of evidence reporting in the field., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Competing Interests: Conflict of interest: none declared.

Background and Purpose: Vascular tone is regulated by the relative contractile state of vascular smooth muscle cells (VSMCs). Several integrins directly modulate VSMC contraction by regulating calcium influx through L-type voltage-gated Ca 2+ channels (VGCCs). Genetic variants in ITGA9, which encodes the α9 subunit of integrin α9β1, and SVEP1, a ligand for integrin α9β1, associate with elevated blood pressure; however, neither SVEP1 nor integrin α9β1 has reported roles in vasoregulation. We determined whether SVEP1 and integrin α9β1 can regulate VSMC contraction., Experimental Approach: SVEP1 and integrin binding were confirmed by immunoprecipitation and cell binding assays. Human induced pluripotent stem cell-derived VSMCs were used in in vitro [Ca 2+ ] i studies, and aortas from a Svep1 +/- knockout mouse model were used in wire myography to measure vessel contraction., Key Results: We confirmed the ligation of SVEP1 to integrin α9β1 and additionally found SVEP1 to directly bind to integrin α4β1. Inhibition of SVEP1, integrin α4β1 or α9β1 significantly enhanced [Ca 2+ ] i levels in isolated VSMCs to Gα q/11 -vasoconstrictors. This response was confirmed in whole vessels where a greater contraction to U46619 was seen in vessels from Svep1 +/- mice compared to littermate controls or when integrin α4β1 or α9β1 was inhibited. Inhibition studies suggested that this effect was mediated via VGCCs, PKC and Rho A/Rho kinase dependent mechanisms., Conclusions and Implications: Our studies reveal a novel role for SVEP1 and the integrins α4β1 and α9β1 in reducing VSMC contractility. This could provide an explanation for the genetic associations with blood pressure risk at the SVEP1 and ITGA9 loci., (© 2022 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Aims: The optimal timing of an invasive strategy (IS) in non-ST-elevation acute coronary syndrome (NSTE-ACS) is controversial. Recent randomized controlled trials (RCTs) and long-term follow-up data have yet to be included in a contemporary meta-analysis., Methods and Results: A systematic review of RCTs that compared an early IS vs. delayed IS for NSTE-ACS was conducted by searching MEDLINE, Embase, and Cochrane Central Register of Controlled Trials. A meta-analysis was performed by pooling relative risks (RRs) using a random-effects model. The primary outcome was all-cause mortality. Secondary outcomes included myocardial infarction (MI), recurrent ischaemia, admission for heart failure (HF), repeat re-vascularization, major bleeding, stroke, and length of hospital stay. This study was registered with PROSPERO (CRD42021246131). Seventeen RCTs with outcome data from 10 209 patients were included. No significant differences in risk for all-cause mortality [RR: 0.90, 95% confidence interval (CI): 0.78-1.04], MI (RR: 0.86, 95% CI: 0.63-1.16), admission for HF (RR: 0.66, 95% CI: 0.43-1.03), repeat re-vascularization (RR: 1.04, 95% CI: 0.88-1.23), major bleeding (RR: 0.86, 95% CI: 0.68-1.09), or stroke (RR: 0.95, 95% CI: 0.59-1.54) were observed. Recurrent ischaemia (RR: 0.57, 95% CI: 0.40-0.81) and length of stay (median difference: -22 h, 95% CI: -36.7 to -7.5 h) were reduced with an early IS., Conclusion: In all-comers with NSTE-ACS, an early IS does not reduce all-cause mortality, MI, admission for HF, repeat re-vascularization, or increase major bleeding or stroke when compared with a delayed IS. Risk of recurrent ischaemia and length of stay are significantly reduced with an early IS., Competing Interests: Conflict of interest: S.A.K. reports personal fees from Bayer. C.P.G. reports personal fees from AstraZeneca, personal fees from Amgen, personal fees from Bayer, grants from BMS, personal fees from Boehrinher-Ingelheim, personal fees from Chiesi, personal fees from Daiichi Sankyo, personal fees from Vifor Pharma, grants from Abbott, personal fees from Menarini, personal fees from Wondr Medical, personal fees from Raisio Group, personal fees from Zydus, personal fees from Oxford University Press, grants from Abbott Diabetes, grants from BMS grants from British Heart Foundation, grants from NIHR, grant from Horizon 2020, grants from ESC, outside the submitted work. N.C. reports unrestricted research grants from Boston Scientific, HeartFlow, Beckman Coulter, and speaker/consultancy fees from Boston, Abbott, HeartFlow outside the submitted work. A.P.B. reports speaker fees from Boston Scientific, Medtronic, Abbott, and Miracor. G.P.M. reports research grants from NIHR, BHF, MRC, and AstraZeneca outside the submitted the work. The remaining authors have no conflicts of interest to declare., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Frailty is a multidimensional syndrome of decline that affects multiple systems and predisposes to adverse health outcomes. Although chronological age is the major risk factor, inter-individual variation in risk is not fully understood. Leucocyte telomere length (LTL), a proposed marker of biological age, has been associated with risk of many diseases. We sought to determine whether LTL is associated with risk of frailty., Methods: We utilized cross-sectional data from 441 781 UK Biobank participants (aged 40-69 years), with complete data on frailty indicators and LTL. Frailty was defined as the presence of at least three of five indicators: weaker grip strength, slower walking pace, weight loss in the past year, lower physical activity, and exhaustion in the past 2 weeks. LTL was measured using a validated qPCR method and reported as a ratio of the telomere repeat number (T) to a single-copy gene (S) (T/S ratio). Association of LTL with frailty was evaluated using adjusted (chronological age, sex, deprivation, smoking, alcohol intake, body mass index, and multimorbidity) multinomial and ordinal regression models, and results are presented as relative risk (RRR) or odds ratios (OR), respectively, alongside the 95% confidence interval (CI). Mendelian randomization (MR), using 131 genetic variants associated with LTL, was used to assess if the association of LTL with frailty was causal., Results: Frail participants (4.6%) were older (median age difference (95% CI): 3 (2.5; 3.5) years, P = 2.73 × 10 -33 ), more likely to be female (61%, P = 1.97 × 10 -129 ), and had shorter LTL (-0.13SD vs. 0.03SD, P = 5.43 × 10 -111 ) than non-frail. In adjusted analyses, both age and LTL were associated with frailty (RRR = 1.03 (95% CI: 1.02; 1.04) per year of older chronological age, P = 3.99 × 10 -12 ; 1.10 (1.08; 1.11) per SD shorter LTL, P = 1.46 × 10 -30 ). Within each age group (40-49, 50-59, 60-69 years), the prevalence of frailty was about 33% higher in participants with shorter (-2SD) versus longer telomeres (+2SD). MR analysis showed an association of LTL with frailty that was directionally consistent with the observational association, but not statistically significant (MR-Median: OR (95% CI): 1.08 (0.98; 1.19) per SD shorter LTL, P = 0.13)., Conclusions: Inter-individual variation in LTL is associated with the risk of frailty independently of chronological age and other risk factors. Our findings provide evidence for an additional biological determinant of frailty., (© 2022 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Background: Telomere length is associated with risk of several age-related diseases and cancers. We aimed to investigate the extent to which telomere length might be modifiable through lifestyle and behaviour, and whether such modification has any clinical consequences., Methods: In this population-based study, we included participants from UK Biobank who had leukocyte telomere length (LTL) measurement, ethnicity, and white blood cell count data. We investigated associations of LTL with 117 potentially modifiable traits, as well as two indices of healthy behaviours incorporating between them smoking, physical activity, diet, maintenance of a healthy bodyweight, and alcohol intake, using both available and imputed data. To help interpretation, associations were summarised as the number of equivalent years of age-related change in LTL by dividing the trait β coefficients with the age β coefficient. We used mendelian randomisation to test causality of selected associations. We investigated whether the associations of LTL with 22 diseases were modified by the number of healthy behaviours and the extent to which the associations of more healthy behaviours with greater life expectancy and lower risk of coronary artery disease might be mediated through LTL., Findings: 422 797 participants were available for the analysis (227 620 [53·8%] were women and 400 036 [94·6%] were White). 71 traits showed significant (p<4·27 × 10 -4 ) associations with LTL but most were modest, equivalent to less than 1 year of age-related change in LTL. In multivariable analyses of 17 traits with stronger associations (equivalent to ≥2 years of age-related change in LTL), oily fish intake, educational attainment, and general health status retained a significant association of this magnitude, with walking pace and current smoking being additionally significant at this level of association in the imputed models. Mendelian randomisation analysis suggested that educational attainment and smoking behaviour causally affect LTL. Both indices of healthy behaviour were positively and linearly associated with LTL, with those with the most healthy behaviours having longer LTL equivalent to about 3·5 years of age-related change in LTL than those with the least heathy behaviours (p<0·001). However, healthy behaviours explained less than 0·2% of the total variation in LTL and did not significantly modify the association of LTL with risk of any of the diseases studied. Neither the association of more healthy behaviours on greater life expectancy or lower risk of coronary artery disease were substantially mediated through LTL., Interpretation: Although several potentially modifiable traits and healthy behaviours have a quantifiable association with LTL, at least some of which are likely to be causal, these effects are not of a sufficient magnitude to substantially alter the association between LTL and various diseases or life expectancy. Attempts to change telomere length through lifestyle or behavioural changes might not confer substantial clinical benefit., Funding: UK Medical Research Council, UK Biotechnology and Biological Sciences Research Council, and British Heart Foundation., Competing Interests: We declare no competing interests., (© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.)

Leukocyte telomere length (LTL) is a proposed marker of biological age. Here we report the measurement and initial characterization of LTL in 474,074 participants in UK Biobank. We confirm that older age and male sex associate with shorter LTL, with women on average ~7 years younger in 'biological age' than men. Compared to white Europeans, LTL is markedly longer in African and Chinese ancestries. Older paternal age at birth is associated with longer individual LTL. Higher white cell count is associated with shorter LTL, but proportions of white cell subtypes show weaker associations. Age, ethnicity, sex and white cell count explain ~5.5% of LTL variance. Using paired samples from 1,351 participants taken ~5 years apart, we estimate the within-individual variability in LTL and provide a correction factor for this. This resource provides opportunities to investigate determinants and biomedical consequences of variation in LTL., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

This study investigated temporal trends in the epidemiology of primary myopia and associations with key environmental risk factors in a UK population. Data were collected at recruitment (non-cycloplegic autorefraction, year of birth, sex, ethnicity, highest educational attainment, reason and age of first wearing glasses and history of eye disease) from 107,442 UK Biobank study participants aged 40 to 69 years, born between 1939 and 1970. Myopia was defined as mean spherical equivalent (MSE) ≤-1 dioptre (D). Temporal changes in myopia frequency by birth cohort (5-year bands using date of birth) and associations with environmental factors were analysed, distinguishing both type (childhood-onset, <18 years versus adult-onset) and severity (three categories: low -1.00 to -2.99D, moderate -3.00 to -5.99D or high ≥-6.00D). Overall myopia frequency increased from 20.0% in the oldest cohort (births 1939-1944) to 29.2% in the youngest (1965-1970), reflecting a relatively higher increase in frequency of adult-onset and low myopia. Childhood-onset myopia peaked in participants born in 1950-54, adult-onset myopia peaked in the cohort born a decade later. The distribution of MSE only shifted for childhood-onset myopia (median: -3.8 [IQR -2.4, -5.4] to -4.4 [IQR -3.0, -6.2]). The magnitude of the association between higher educational attainment (proxy for educational intensity) and myopia overall increased over time (adjusted Odds Ratio (OR) 2.7 [2.5, 2.9] in the oldest versus 4.2 [3.3, 5.2] in the youngest cohort), being substantially greater for childhood-onset myopia (OR 3.3 [2.8, 4.0] to 8.0 [4.2, 13]). Without delineating childhood-onset from adult-onset myopia, important temporal trends would have been obscured. The differential impact of educational experience/intensity on both childhood-onset and high myopia, amplified over time, suggests a cohort effect in gene-environment interaction with potential for increasing myopia frequency if increasing childhood educational intensity is unchecked. However, historical plateauing of myopia frequency does suggest some potential for effective intervention., Competing Interests: The authors have declared that no competing interests exist.

Objectives: This study aimed to investigate associations between persisting amblyopia into adulthood and its "real-life" impacts and inform the current debate about the value of childhood vision screening programs., Methods: Associations between persisting amblyopia and diverse socioeconomic, health, and well-being outcomes were investigated in multivariable-adjusted (sex, age, ethnicity, deprivation) regression models, with 126 400 participants (aged 40-70 years) of the UK Biobank with complete ophthalmic data. Analysis by age group (cohort 1, 60-70 years; cohort 2, 50-59 years; cohort 3, 40-49 years) assessed temporal trends., Results: Of 3395 (3%) participants with confirmed amblyopia, overall 77% (2627) had persisting amblyopia, declining from 78% in cohort 1 to 73% in cohort 3. The odds of persisting amblyopia were 5.91 (5.24-6.66) and 2.49 (2.21-2.81) times greater in cohort 1 and cohort 2, respectively, than cohort 3. The odds were also higher for more socioeconomically deprived groups and for white ethnicity. Reduced participation in sport, adverse general and mental health, and well-being were all independently associated with persisting amblyopia, with the strongest associations in the youngest cohorts. Associations with lower educational attainment and economic outcomes were only evident in the oldest cohort., Conclusions: There has been a decline in the overall frequency of persisting amblyopia since the introduction of universal child vision screening in the United Kingdom. Nevertheless, most adults treated for amblyopia in childhood have persisting vision deficits. There was no evidence that persisting amblyopia has vision-mediated effects on educational, employment-related, or economic outcomes. The observed adverse outcomes were largely those not directly mediated by vision. Patients undergoing treatment should be counseled about long-term outcomes., (Copyright © 2021 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Telomeres, the end fragments of chromosomes, play key roles in cellular proliferation and senescence. Here we characterize the genetic architecture of naturally occurring variation in leukocyte telomere length (LTL) and identify causal links between LTL and biomedical phenotypes in 472,174 well-characterized UK Biobank participants. We identified 197 independent sentinel variants associated with LTL at 138 genomic loci (108 new). Genetically determined differences in LTL were associated with multiple biological traits, ranging from height to bone marrow function, as well as several diseases spanning neoplastic, vascular and inflammatory pathologies. Finally, we estimated that, at the age of 40 years, people with an LTL >1 s.d. shorter than the population mean had a 2.5-year-lower life expectancy compared with the group with ≥1 s.d. longer LDL. Overall, we furnish new insights into the genetic regulation of LTL, reveal wide-ranging influences of LTL on physiological traits, diseases and longevity, and provide a powerful resource available to the global research community., (© 2021. The Author(s).)

Objective: To investigate percutaneous coronary intervention (PCI) practice in an international cohort of patients with spontaneous coronary artery dissection (SCAD). To explore factors associated with complications and study angiographic and longer term outcomes., Methods: SCAD patients (n=215, 94% female) who underwent PCI from three national cohort studies were investigated and compared with a matched cohort of conservatively managed SCAD patients (n=221)., Results: SCAD-PCI patients were high risk at presentation with only 8.8% undergoing PCI outside the context of ST-elevation myocardial infarction/cardiac arrest, thrombolysis in myocardial infarction (TIMI) 0/1 flow or proximal dissections. PCI complications occurred in 38.6% (83/215), with 13.0% (28/215) serious complications. PCI-related complications were associated with more extensive dissections (multiple vs single American Heart Association coronary segments, OR 1.9 (95% CI: 1.06-3.39),p=0.030), more proximal dissections (proximal diameter per mm, OR 2.25 (1.38-3.67), p=0.001) and dissections with no contrast penetration of the false lumen (Yip-Saw 2 versus 1, OR 2.89 (1.12-7.43), p=0.028). SCAD-PCI involved long lengths of stent (median 46mm, IQR: 29-61mm). Despite these risks, SCAD-PCI led to angiographic improvements in those with reduced TIMI flow in 84.3% (118/140). Worsening TIMI flow was only seen in 7.0% (15/215) of SCAD-PCI patients. Post-PCI major adverse cardiovascular and cerebrovascular events (MACCE) and left ventricular function outcomes were favourable., Conclusion: While a conservative approach to revascularisation is favoured, SCAD cases with higher risk presentations may require PCI. SCAD-PCI is associated with longer stent lengths and a higher risk of complications but leads to overall improvements in coronary flow and good medium-term outcomes in patients., Competing Interests: Competing interests: DA has received research funding to support a clinical research fellow from Abbott Vascular Inc. He has also received funding from AstraZeneca Inc. for unrelated research and has undertaken consultancy to support research funds for General Electric Inc. TJ has received consultancy/speaker fees from Abbott Vascular, Boston Scientific, Medtronic and Terumo. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Background Older age is the most powerful risk factor for adverse coronavirus disease-19 (COVID-19) outcomes. It is uncertain whether leucocyte telomere length (LTL), previously proposed as a marker of biological age, is also associated with COVID-19 outcomes. Methods We associated LTL values obtained from participants recruited into UK Biobank (UKB) during 2006-2010 with adverse COVID-19 outcomes recorded by 30 November 2020, defined as a composite of any of the following: hospital admission, need for critical care, respiratory support, or mortality. Using information on 130 LTL-associated genetic variants, we conducted exploratory Mendelian randomisation (MR) analyses in UKB to evaluate whether observational associations might reflect cause-and-effect relationships. Findings Of 6775 participants in UKB who tested positive for infection with SARS-CoV-2 in the community, there were 914 (13.5%) with adverse COVID-19 outcomes. The odds ratio (OR) for adverse COVID-19 outcomes was 1·17 (95% CI 1·05-1·30; P = 0·004) per 1-SD shorter usual LTL, after adjustment for age, sex and ethnicity. Similar ORs were observed in analyses that: adjusted for additional risk factors; disaggregated the composite outcome and reduced the scope for selection or collider bias. In MR analyses, the OR for adverse COVID-19 outcomes was directionally concordant but non-significant. Interpretation Shorter LTL is associated with higher risk of adverse COVID-19 outcomes, independent of several major risk factors for COVID-19 including age. Further data are needed to determine whether this association reflects causality. Funding UK Medical Research Council, Biotechnology and Biological Sciences Research Council and British Heart Foundation., Competing Interests: Declaration of Competing Interest These authors declare no competing interests., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Sidestream dark field (SDF) imaging enables direct visualisation of the microvasculature from which quantification of key variables is possible. The new MicroScan USB3 (MS-U) video-microscope is a hand-held SDF device that has undergone significant technical upgrades from its predecessor, the MicroScan Analogue (MS-A). The MS-U claims superior quality of sublingual microcirculatory image acquisition over the MS-A, however, this has yet to be robustly confirmed. In this manuscript, we therefore compare the quality of image acquisition between these two devices. The microcirculation of healthy volunteers was visualised to generate thirty video images for each device. Two independent raters, blinded to the device type, graded the quality of the images according to the six different traits in the Microcirculation Image Quality Score (MIQS) system. Chi-squared tests and Kappa statistics were used to compare not only the distribution of scores between the devices, but also agreement between raters. MS-U showed superior image quality over MS-A in three of out six MIQS traits; MS-U had significantly more optimal images by illumination (MS-U 95% optimal images, MS-A 70% optimal images (p-value 0.003)), by focus (MS-U 70% optimal images, MS-A 35% optimal images (p-value 0.002)) and by pressure (MS-U 72.5% optimal images, MS-A 47.5% optimal images (p-value 0.02)). For each trait, there was at least 85% agreement between the raters, and all the scores for each trait were independent of the rater (all p-values > 0.05). These results show that the new MS-U provides a superior quality of sublingual microcirculatory image acquisition when compared to old MS-A.

Background: Muscle wasting in the critically ill is up to 2% per day and delays patient recovery and rehabilitation. It is linked to inflammation, organ failure and severity of illness. The aims of this study were to understand the relationship between muscle depth loss, and nutritional and inflammatory markers during prolonged critical illness. Secondly, to identify when during critical illness catabolism might decrease, such that targeted nutritional strategies may logically be initiated., Methods: This study was conducted in adult intensive care units in two large teaching hospitals. Patients anticipated to be ventilated for >48 hours were included. Serum C-reactive protein (mg/L), urinary urea (mmol/24h), 3-methylhistidine (μmol/24h) and nitrogen balance (g/24h) were measured on days 1, 3, 7 and 14 of the study. Muscle depth (cm) on ultrasound were measured on the same days over the bicep (bicep and brachialis muscle), forearm (flexor compartment of muscle) and thigh (rectus femoris and vastus intermedius)., Results: Seventy-eight critically ill patients were included with mean age of 59 years (SD: 16) and median Intensive care unit (ICU) length of stay of 10 days (IQR: 6-16). Starting muscle depth, 8.5cm (SD: 3.2) to end muscle depth, 6.8cm (SD: 2.2) were on average significantly different over 14 days, with mean difference -1.67cm (95%CI: -2.3 to -1cm), p<0.0001. Protein breakdown and inflammation continued over 14 days of the study., Conclusion: Our patients demonstrated a continuous muscle depth loss and negative nitrogen balance over the 14 days of the study. Catabolism remained dominant throughout the study period. No obvious 'nutritional tipping point" to identify anabolism or recovery could be identified in our cohort. Our ICU patient cohort is one with a moderately prolonged stay. This group showed little consistency in data, reflecting the individuality of both disease and response. The data are consistent with a conclusion that a time based assumption of a tipping point does not exist., Trial Registration: International Standard Randomised Controlled Trial Number: ISRCTN79066838. Registration 25 July 2012., Competing Interests: The authors have declared that no competing interests exist.

Background: The Parent Report of Children's Abilities-Revised (PARCA-R) can be used to identify preterm born children at risk for developmental delay at age 24 months. However, standardised scores for assessing all children in the general population and quantifying development relative to the norm are unavailable, thus limiting the use of the questionnaire. We aimed to develop scores that are standardised by age and sex for the PARCA-R to assess children's cognitive and language development at age 24-27 months., Methods: Anonymised data from PARCA-R questionnaires that were completed by parents of 2-year-old children in three previous studies were obtained to form a standardisation sample that was representative of the UK general population. Anonymised data were obtained from three further studies to assess the external validity and clinical validity of the standardised scores. We used the lambda-mu-sigma (lambda for skewness, mu for median, sigma for the coefficient of variation) method to develop scores that are standardised by age and sex for three scales (non-verbal cognitive development, language development, and total parent report composite [PRC]) for children in four 1-month age bands, spanning age 23·5-27·5 months., Findings: We included 6402 children (mean age 25 months and 1 day [range 23 months and 16 days to 27 months and 15 days]) in the standardisation sample and 709 (mean age 24 months and 19 days [23 months and 16 days to 27 months and 15 days]) to test the external validity and 1456 (mean age 24 months and 8·5 days [23 months and 16 days to 27 months and 15 days]) to test the clinical validity of the standardised scores. For all PARCA-R scales, mean standardised scores approximated 100 (SD 15) in both sexes and all age groups. These scores were independent of socioeconomic status. Standardised scores were close to 100 (15) in the external validation sample, showing the validity of the scores. Standardised scores for the total PRC scale for children born very preterm (<32 weeks' gestation) were 0·47 SD lower on average than the normative mean, and for children with neonatal sepsis were 0·73 SD lower on average than the normative mean. These scores were equivalent to a standardised score of 93 (95% CI 91-94) for children born very preterm and 89 (88-91) for children with neonatal sepsis, thus showing clinical validity., Interpretation: The PARCA-R provides a norm-referenced, standardised assessment of cognitive and language development at 24-27 months of age. The questionnaire is available non-commercially in English with translations available in 14 other languages, thus providing clinicians and researchers with a cost-effective tool for assessing development and identifying children with delay., Funding: Action Medical Research (Ref: GN2580)., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Critically ill patients lose up to 2% of muscle mass per day. We assessed the feasibility of administering a leucine-enriched essential amino acid (L-EAA) supplement to mechanically ventilated trauma patients with the aim of assessing the effect on skeletal muscle mass and function., Methods: A randomised feasibility study was performed over six months in intensive care (ICU). Patients received 5 g L-EAA five times per day in addition to standard feed (L-EAA group) or standard feed only (control group) for up to 14 days. C-reactive protein, albumin, IL-6, IL-10, urinary 3-MH, nitrogen balance, protein turnover ([1-13C] leucine infusion), muscle depth change (ultrasound), functional change (Katz and Barthel indices) and muscle strength Medical Research Council (MRC) sum score to assess ICU Acquired Weakness were measured sequentially., Results: Eight patients (9.5% of screened patients) were recruited over six months. L-EAA doses were provided on 91/124 (73%) occasions. Inflammatory and urinary marker data were collected; serial muscle depth measurements were lacking due to short length of stay. Protein turnover studies were performed on five occasions. MRC sum score could not be performed as patients were not able to respond to the screening questions. The Katz and Barthel indices did not change. L-EAA delivery was achievable, but meaningful functional and muscle mass outcome measures require careful consideration in the design of a future randomised controlled trial., Conclusion: L-EAA was practical to provide, but we found significant barriers to recruitment and measurement of the chosen outcomes which would need to be addressed in the design of a future, large randomised controlled trial., Trial Registration: ISRCTN Registry, ISRCTN79066838 . Registered on 25 July 2012.

Objectives: Children born preterm are at higher risk for special educational needs and poor academic attainment compared with term-born peers, yet education professionals receive limited training and have poor knowledge of preterm birth. We have developed an interactive e-learning resource and evaluated its efficacy in improving teachers' knowledge of preterm birth and their confidence in supporting the learning of children born preterm., Setting: Eight primary, infant or junior schools in England., Participants: 61 teachers of children aged 4-11 years, of which 55 (90%) were female., Intervention: Interactive e-learning resource designed to improve education professionals' knowledge of long-term outcomes following preterm birth and strategies that can be used to support children's learning (www.pretermbirth.info). In a repeated measures design, participants were given up to 30 days access to the e-learning resource, before and after which they completed the Preterm Birth Knowledge Scale (PB-KS; scores 0-33; higher scores indicate greater knowledge) to assess knowledge of outcomes of prematurity. Four Likert scale items were used to assess confidence in supporting children's learning and 10 items were used to evaluate the utility of the resource. PB-KS scores and responses on confidence item were compared pre-resource and post-resource use., Results: PB-KS scores significantly increased after accessing the e-learning resource (median (95% CI): pre-resource 13 (11 to 14); post-resource 29 (28 to 30)), equating to a 2.6 SD increase in PB-KS scores. Teachers' confidence in supporting children born preterm was also significantly improved after using the resource. The utility of the resource was evaluated positively by participants with 97% reporting that they would recommend its use to others., Conclusions: The e-learning resource substantially improved teachers' knowledge of preterm birth and their confidence in supporting preterm children in the classroom. Use of this resource may represent a key advance in improving educational outcomes for children born preterm., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Refractive error is an increasing global public health concern that requires robust and reliable research to identify modifiable risk factors and provide accurate estimates of population burden. We investigated the impact of reclassification of individuals when using different threshold values of spherical equivalent (SE) to define myopia, on estimates of frequency, distribution and associations with risk factors, to inform current international initiatives to standardise definitions., Methods: A random sample of 1985 individuals from the 1958 British birth cohort, at age 44, had autorefraction and self-reported on educational attainment and social class.Refraction status assigned in three different models using SE: (A) moderate to high myopia -3 diopters (D) or more extreme (≤-3.00D), (B) hypermetropia +1.00D or more extreme (≥+1.00D) and (C) mild myopia using three different thresholds: -1.00D, -0.75D or -0.50D, hence reciprocal changes in definition of emmetropia., Results: Frequency estimates and associations with risk factors altered significantly as the threshold value for myopia moved towards SE 0.0D: prevalence of mild myopia increased from 28% to 47%, the association with highest educational attainment attenuated and with higher social class strengthened, with changes in risk ratios of approximately 20%., Conclusion: Even small changes in the threshold definition of myopia (±0.25D) can significantly affect the conclusions of epidemiological studies, creating both false-positive and false-negative associations for specific risk factors. An international classification for refractive error, empirically evidenced and cognisant of the question(s) being addressed and the population(s) being studied, is needed to serve better translational research, practice and policy., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: To evaluate modifiable, lifestyle risk factors of cardiovascular disease (CVD) among older adults, across ageing, in the Mediterranean area., Methods: During 2005-2017, 3131 individuals from 26 Mediterranean islands of 5 countries, ≥65 years of age, were voluntarily enrolled. Anthropometrical, clinical and socio-demographic characteristics, dietary habits, lifestyle parameters were measured through standard procedures. Analyses were performed by year and across consecutive age groups of the participants., Results: A decrease in the prevalence of current smoking (p < 0.001), engagement in physical activities (p = 0.001) and participation in social events (p = 0.001) for every year increase in age was found. Moderate alcohol drinking increased through ageing (p = 0.008), whereas adherence to Mediterranean diet remained stable, but adequate (p = 0.90). Trend analysis also revealed that a quadratic (U-shape) function better characterized the association between ageing and total cardiometabolic risk factors burden (p for trend <0.001)., Conclusions: The gaps in the understanding of factors affecting longevity and healthy ageing remain; public health authorities and stakeholders should focus on the lifestyle determinants of healthy ageing, that seems to be an effective mean for improving older peoples' health., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Depression has been linked to a large and growing economic and societal burden worldwide. In Europe, depression is one of the most frequent mental disorders across all age groups, but particularly in people aged 65 years and over, and higher depressive symptoms have been reported among individuals with chronic diseases (e.g., diabetes and heart disease)., Aim: To evaluate the role of adherence to the Mediterranean diet (MedDiet) in depression in a sample of older people living in the Mediterranean basin., Methods: Standard procedures were used to determine socio-demographic, lifestyle, and clinical characteristics of the participants, as well as their dietary habits, and depressive symptoms were evaluated using the Geriatric Depression Scale (GDS). Multi-adjusted logistic and linear regression analyses were carried out to evaluate the associations between participants' characteristics and depression., Results: Participants classified as having mild or severe depression were less educated and physically active, and more diabetic, and they reported less adherence to the MedDiet. Adherence to the MedDiet was associated with the absence of depression [(OR, 95% CI): 0.65, 0.50-0.85]. In addition, daily tea drinking was also related to the absence of depression [(OR, 95% CI): 0.51, 0.40-0.65]., Conclusions: Greater adherence to the MedDiet and daily tea drinking seem to have a beneficial effect on depressive symptoms in older adults., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The role of diet and inflammation in successful ageing is not transparent, and as such, is still being investigated. The aim of the present work was to evaluate the inflammatory potential of dietary habits in the successful ageing of a random sample of older adults living in the Mediterranean basin and who participated in the MEDIS (MEDiterranean ISlands) study., Methods: During 2005-2016, 3,128 older adults (aged 65-100 years) from 24 Mediterranean islands and the rural Mani region (Peloponnesus) of Greece were enrolled in the study. A multidimensional successful ageing index consisting of 10 components was employed. A validated and reproducible Food Frequency Questionnaire (FFQ) was used to evaluate the dietary habits of the older adults. A nutrition anti-inflammatory (NAI) score based on the participants' specific dietary habits was assessed., Results: Participants with high NAI scores (proinflammatory nutrition) had a higher prevalence of hypercholesterolemia and lower levels of successful ageing. After adjusting for several confounders, the NAI score was associated with successful ageing (-0.03, 95% CI -0.5 to -0.006). Stratified analysis by gender and advanced age revealed heterogeneity in the NAI score, predicting successful ageing., Conclusions: The inflammatory potential of nutrition was reported as an important factor for successful ageing, suggesting that further research is needed on the role of anti- and proinflammatory dietary habits in healthy and successful ageing., (© 2017 S. Karger AG, Basel.)

Importance: Despite the existing country-specific strategies tackling social inequalities in visual health in adults, little is known about trends in visual function in childhood and its association with social position., Objective: To investigate the distribution of childhood visual function in the United Kingdom and associations with early-life social position between 1961 and 1986, a period of significant social change., Design, Setting, and Participants: Longitudinal cohort study using harmonized data sets from the British 1946, 1958, and 1970 national birth cohorts. In total, 14 283 cohort members with complete data on visual acuity at age 15 or 16 years, measured in 1961, 1974, and 1986, respectively, for each cohort, and social position were assessed., Main Outcomes and Measures: Using habitual distance visual acuity (with correction if prescribed), participants were assigned to a visual function category ranging from bilateral normal to visual impairment/severe visual impairment/blindness (International Statistical Classification of Diseases, Tenth Revision, Clinical Modification). Distribution of visual function over time and associations with social position (risk ratios [RRs] and 95% confidence intervals) were analyzed., Results: Complete data were available for 3152 participants (aged 15 years; 53% boys [n = 1660]) in the 1946 Medical Research Council National Survey of Health and Development, 6683 participants (aged 16 years; 51% boys [n = 3420]) in the 1958 National Child Development Study, and 4448 participants (aged 16 years; 48% boys [n = 2156]) in the 1970 British Birth Cohort Study. The proportion of children with bilateral normal vision decreased by 1.3% (95% CI, -5.1% to 2.7%) in 1974 and 1.7% (95% CI, -5.9% to 2.7%) in 1986. The risk of overall impaired vision increased by 1.20 times (95% CI, 1.01-1.43) and the risk of visual impairment/severe visual impairment/blindness by 1.75 times (95% CI, 1.03-2.98) during this period. Girls were consistently at increased risk of all vision impairment categories. Higher social position at birth and in childhood was associated with reduced risk of visual impairment/severe visual impairment/blindness (RR, 0.58; 95% CI, 0.20-1.68) and unilateral impairment (RR, 0.89; 95% CI, 0.72-1.11), respectively., Conclusions and Relevance: Our study provides evidence of temporal decline in childhood visual function between 1961 and 1986. Despite the limited power of the analysis owing to the small sample size of those with impaired vision, we found an emergence of a contribution of sociodemographic status to the cohort effect that may be the antecedent of the current picture of childhood blindness. Equally, early-life social position may also have contributed to the current social patterning in visual function in older adults in the United Kingdom. These findings highlight the potential value of targeting children in national ophthalmic public policies tackling inequalities.

Objective: The aim of the present study was to examine serum cystatin C levels in association with the Mediterranean diet in a healthy Greek population., Methods: Cystatin C together with basic clinical chemistry tests was measured in a total of 490 adults (46±16 years, 40% of males), who underwent an annual health check. Demographic, anthropometric and lifestyle characteristics were recorded, while adherence to the Mediterranean diet was evaluated through the MedDietScore (0-55)., Results: The mean level of serum cystatin C was 0.84 mg/L, while men had increased serum cystatin C levels compared to women (0.86 mg/L vs. 0.83 mg/L, respectively, 0.017). After adjusting for age, gender, body mass index, smoking status, hypertension, diabetes, hypercholesterolemia, estimated glomerular filtration rate (eGFR), albumin and ferritin levels, each unit increase in MedDietScore led to 0.002 mg/dL drop off in cystatin C serum levels., Conclusions: We have demonstrated an inverse relationship between the MedDietScore and serum cystatin C levels. Our finding that increases in MedDietScore are associated with decreases in serum cystatin C levels could imply that adherence to the Mediterranean diet may reduce the cardiovascular risk, as assessed by cystatin C, a prognostic marker of the cardiometabolic risk. This notion could have a great impact on public health., (Copyright© by the National Institute of Public Health, Prague 2017)

Background: Adherence to a Mediterranean dietary pattern is a well-established protective factor against cardiovascular disease (CVD). However, diet quality is only one aspect of the overall healthy lifestyle adopted by Mediterranean populations. The latter has never been evaluated as a multi-factorial composite lifestyle. Thus, the aim of the present study was to provide a broader picture of the Mediterranean lifestyle and its effects on CVD risk, among elderly individuals., Methods: During 2005-2015, 2,749 older (aged 65-100 years) from 21 Mediterranean islands (MEDIS) and the rural Mani region (Peloponnesus) of Greece were voluntarily enrolled onto the study. Dietary habits, physical activity status, socio-demographic characteristics, lifestyle parameters (sleep, smoking habits, social life and educational status) and clinical profile aspects were derived through standard procedures., Results: The overall prevalence of the traditional CVD risk factors were 62.3% for hypertension, 22.3% for diabetes mellitus (type 2) and 47.7% for hypercholesterolemia. The presence of diabetes mellitus was positively predicted by the geriatric depression scale (GDS) [odds ratio (OR) =1.13, 95% confidence interval (CI): 1.02-1.25] and by an urban residential environment (OR =2.57, 95% CI: 1.10-6.06) after adjusting for several confounders. Presence of hypertension was predicted by increasing age (OR =1.07, 95% CI: 1.02-1.12), increasing body mass index (BMI) (OR =1.12, 95% CI: 1.04-1.21), the habit of midday sleep (OR =2.07, 95% CI: 1.07-4.02) and inversely predicted by the frequency of socializing with friends (OR =0.767, 95% CI: 0.616-0.955). The estimated score in the GDS was the only independent positive predictor for the presence of hypercholesterolemia (OR =1.10, 95% CI: 1.01-1.21)., Conclusions: Lifestyle parameters such as social life, midday sleep (siesta) and residential environment are strongly associated with the presence of CVD risk factors in elderly and should be part of broader CVD prevention strategies to reduce the burden of the disease., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Purpose: The aim of the present work was to evaluate the relation between car use and the level of successful aging of a random sample of older adults living in the Mediterranean basin., Methods: During 2005-2011, 2749 older (aged 65-100 years) from 22 islands and the rural Mani region (Peloponnesus) of Greece were voluntarily enrolled in the Mediterranean islands cross-sectional study. Sociodemographics, medical conditions, and dietary and lifestyle habits were derived throughout standard procedures. Car use was recorded with a standard binary question. A successful aging index ranging from 0-10 was used., Results: Older adults who used a car on regular basis had significantly higher levels of successful aging, as well as less prevalence of obesity and hypertension while were more physically active (P < .001). After adjusting for several confounders car use was still positively related with elderly islander's successful aging level (beta coefficient [95% confidence interval]: 0.65 [0.54-0.77])., Conclusions: In conclusion, the activity of car use seems to be an indicator of quality of life among older adults, as measured through successful aging., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The aim of the present study was to evaluate the role of parental longevity and parental cardiovascular disease (CVD) history in CVD risk and successful aging of a random sample of older adults living in the Mediterranean basin and who participated in the MEDiterranean Islands (MEDIS) study. During 2005 to 2011, 2663 elders were voluntarily enrolled. A multidimensional successful aging index consisting of 10 components was used. Paternal and maternal longevity was defined as those older participants of whom both parents lived above the age of 90. The burden of CVD-related factors (CVD-RFs) was calculated as the total score of 4 major CVD-RFs (range 0-4). After adjustment, parental longevity was inversely associated with the burden of CVD-RFs ( P = .04). Moreover, parental longevity was positively associated with the older adults' successful aging score (β-coefficient [95% confidence interval]: .38 [0.06-0.71]). Parent's long living was revealed as an important factor for successful aging and for reduced CVD risk, suggesting that further research is needed in the genetic predisposition of longevity.

Objectives: By the end of the 2000s, the economic situation in many European countries started to deteriorate, generating financial uncertainty, social insecurity and worse health status. The aim of the present study was to investigate how the recent financial crisis has affected the lifestyle health determinants and behaviours of older adults living in the Mediterranean islands., Methods: From 2005 to 2015, a population-based, multi-stage convenience sampling method was used to voluntarily enrol 2749 older adults (50% men) from 20 Mediterranean islands and the rural area of the Mani peninsula. Lifestyle status was evaluated as the cumulative score of four components (range, 0 to 6), that is, smoking habits, diet quality (MedDietScore), depression status (Geriatric Depression Scale) and physical activity., Results: Older Mediterranean people enrolled in the study from 2009 onwards showed social isolation and increased smoking, were more prone to depressive symptoms, and adopted less healthy dietary habits, as compared to their counterparts participating earlier in the study (p<0.05), irrespective of age, gender, several clinical characteristics, or socioeconomic status of the participants (an almost 50% adjusted increase in the lifestyle score from before 2009 to after 2009, p<0.001)., Conclusions: A shift towards less healthy behaviours was noticeable after the economic crisis had commenced. Public health interventions should focus on older adults, particularly of lower socioeconomic levels, in order to effectively reduce the burden of cardiometabolic disease at the population level.

Objectives: Several lifestyle parameters including diet, physical activity and sleep were associated in isolation with the presence of Metabolic Syndrome (MetS) in adults, to date there is a paucity of studies which evaluated their combined role aging populations and especially with respect to gender. Therefore, the aim of the present study was to provide a global consideration of the lifestyle factors associated with MetS among elderly individuals., Design: Cross-sectional observational study., Setting: 21 Mediterranean islands and the rural Mani region (Peloponnesus) of Greece., Participants: during 2005-2015, 2749 older (aged 65-100 years) from were voluntarily enrolled in the study., Measurements: Dietary habits, energy intake, physical activity status, socio-demographic characteristics, lifestyle parameters (sleeping and smoking habits) and clinical profile aspects were derived through standard procedures. The presence of MetS was defined using the definition provided by NCEP ATP III (revised) and cluster analysis was used to identify overall dietary habit patterns., Results: The overall prevalence of MetS in the study sample was 36.2%, but occurred more frequently in females (40.0% vs. 31.8%, respectively, p=0.03). Individuals with MetS were more likely to sleep during the day (89.4% vs. 76.8% respectively, p=0.039) and frequent 'siesta' was positively linked to the odds of MetS presence in females (Odds Ratio (OR) =3.43, 95% Confidence Intervals (CI): 1.08-10.9), but not for men (p=0.999). The lower carbohydrate (i.e., 45.2% of total daily energy, 120±16gr/day) dietary cluster was inversely associated with the odds for MetS presence, but only for men (OR=0.094, 95%CI: 0.010-0.883)., Conclusions: Lifestyle parameters including sleep and diet quality are strongly associated with the presence of MetS in elderly cohort, but different their level of influence appears to be different, depending on gender. Further research is needed to better consider the role of lifestyle characteristics in the management of MetS in clinical practice., Competing Interests: None to declare

The purpose of this study was to investigate the effects of dietary nitrate supplementation, in the form of beetroot juice, on acute mountain sickness (AMS) symptoms and physiological responses, in a group of young males trekking to Mount Everest Base Camp (EBC). Forty healthy male students (mean age (SD): 16 (1) yrs) trekked to EBC over 11 days. Following an overnight fast, each morning participants completed the Lake Louise AMS questionnaire and underwent a series of physiological tests: resting blood pressure as well as resting and exercising heart rate, respiratory rate, and peripheral oxygen saturation. The exercise test consisted of a standardised 2-min stepping protocol and measurements were taken in the last 10 s. Participants in the intervention arm of the study consumed 140 ml of concentrated beetroot juice daily, containing approximately 10 mmol of nitrate, while those in the control arm consumed 140 ml of concentrated blackcurrant cordial with negligible nitrate content. Drinks were taken for the first seven days at high altitude (days 2-8), in two equal doses; one with breakfast, and one with the evening meal. Mixed modelling revealed no significant between-groups difference in the incidence of AMS (Odds Ratio - nitrate vs., Control: 1.16 (95% CI: 0.59; 2.29)). Physiological changes occurring during ascent to high altitude generally were not significantly different between the two groups (Model Coef (95% CI) - average difference nitrate vs., Control: systolic blood pressure, 0.16 (-4.47; 4.79); peripheral oxygen saturation, 0.28 (-0.85; 1.41); heart rate, -0.48 (-8.47; 7.50) (Model Coef (95% CI) - relative difference nitrate vs., Control: ventilatory rate, 0.95 (0.82; 1.08)). Modelling revealed that diastolic blood pressure was 3.37 mmHg (0.24; 6.49) higher for participants in the beetroot juice, however this difference was no larger than that found at baseline and no interaction effect was observed. Supplementation with dietary nitrate did not significantly change symptoms of AMS or alter key physiological variables, in a group of adolescent males during a high altitude trekking expedition. There was no evidence of harm from dietary nitrate supplementation in this context. Given the wide confidence intervals in all models, a larger sample size would be required to exclude a false negative result. Our data suggest that prolonged oral nitrate supplementation is safe and feasible at altitude but has little physiological or clinical effect., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: The aim of the present study was to evaluate lifestyle and health determinants of cardiovascular disease (CVD) risk among Greek elderly residents living in Eastern Aegean islands, in both Greece and Turkey., Methods: Under the context of the MEDIS study, 724 older adults (aged 65 to 100 years) from 8 Eastern Aegean Sea Greek islands (n=100 living in Samothrace, 142 in Lesvos, 150 in Limnos, 76 in Ikaria, 52 in Kassos, 149 in Rhodes and Karpathos) and from Turkey (n=55older adults of Greek origin living on Gökçeada Island) were voluntarily recruited. Overall cardiometabolic risk was measured as the sum (range 0-4) of four common CVD risk factors (hypertension, diabetes, dyslipidemia and obesity)., Results: Greek islanders had higher CVD scores compared to Greeks of Gökçeada (1.9±1.1 vs 1.4±1.0 risk factors / participant, p<0.001). Further analysis revealed that the diet of Greek islanders was similar to the traditional Mediterranean diet; however, these individuals demonstrated 2-times higher odds (95% CI, 1.04-3.87) for having hypertension, 1.53-times higher odds (95% CI, 0.66-3.54) for having diabetes, 3.29-times higher odds (95% CI, 1.58-6.81) for having hypercholesterolemia; whereas they had 0.78-times lower odds (95% CI, 0.40-1.52) for being obese, compared to elderly Greek adults living on Gökçeada., Conclusions: Overall, CVD risk seems to be low among Eastern Aegean Islanders; certain differences in CVD risk factors exist between Greek islanders and their counterparts living in Gökçeada, and those differences may be attributed to various environmental, cultural and lifestyle factors., (Copyright © 2016 Hellenic Cardiological Society. Published by Elsevier B.V. All rights reserved.)

Background: The determinants that promote successful ageing still remain unknown. The aim of the present work was to evaluate the role of skeletal muscle mass and body fat percentage (BF%), in the level of successful ageing., Methods: during 2005-2011, 2663 older (aged 65-100 years) from 21 Mediterranean islands and the rural Mani region (Peloponnesus) of Greece were voluntarily enrolled in the study. Appendicular skeletal muscle mass (ASM), skeletal muscle mass index (SMI) and BF% were calculated using population formulas. Dietary habits, energy intake, expenditure and energy balance were derived throughout standard procedures. A successful ageing index ranging from 0 to 10 was used., Results: The mean ASM mass was 24±6.0kg, the SMI was 0.84±0.21 and the BF% was 44%. Females had lower SMI and higher BF% in comparison with males, respectively [(SMI: 0.66±0.09 vs. 1.03±0.11; BF%: 51% vs. 34%, (p<0.001)]. High successful agers had better rates in ASM (p=0.01), SMI (p<0.001) and BF% (p<0.001), compared with the medium and low successful ones. Changes in SMI [b-coefficient (95% CI):2.14 (1.57 to 2.71)] were positively associated with successful ageing, while changes in BF% [b-coefficient (95% CI): -0.04 (-0.05 to -0.03)] were inversely associated with successful ageing. Results from sensitivity analysis showed that the effects of variations on body composition were consistent, less pronounced in the positive energy balance group and more pronounced among the oldest old., Conclusions: Body composition changes seem to be associated with lower quality of life in the older adults, as measured through successful ageing., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Knowledge about long-term variability of lung function in healthy children is essential when monitoring and treating those with respiratory disease over time. The aim of this study was to define the natural variability in spirometry in young children after an interval of 12 months.The Size and Lung function In Children study was a prospective study designed to assess spirometry and body size, shape and composition in a multi-ethnic population of London school children. 14 schools with a wide range of socioeconomic circumstances were recruited. Spirometric and anthropometric assessments and parental questionnaires pertaining to respiratory symptoms, previous medical history, pubertal status and socioeconomic circumstances were completed at baseline and ∼1 year later.Technically acceptable spirometry data on two occasions ∼1 year apart (range 9-16 months) were available in 758 children (39% boys, mean±sd age 8.1±1.6 years), 593 of whom were classified as "healthy". Mean±sd within-subject between-test variability was 0.05±0.6 z-scores, with 95% of all the children achieving a between-test variability within ±1.2 z-scores (equating to ∼13% predicted).Natural variations of up to 1.2 z-scores occur in healthy children over ∼1 year. These must be considered when interpreting results from annual reviews in those with lung disease who are otherwise stable, if unnecessary further investigations or changes in treatment are to be avoided., (Copyright ©ERS 2016.)

To evaluate the role of geography i.e., continental vs. insular Mediterranean, on successful aging among older inhabitants. During 2005-2014, 2693 elderly (aged 65 to 100 years) individuals from 21 Mediterranean islands in Greece, Italy and Spain as well as Cyprus, Malta, and the rural region of Mani (southeast continental region of Greece keeping old-time traditions), were voluntarily recruited. Successful aging was evaluated using a validated index composed of 10 health-related socio-lifestyle and clinical characteristics. After accounting for age, sex, body mass index (BMI), physical activity, smoking habits, MedDietScore and access to health care services, the older inhabitants of islands were found to have a higher level of the successful aging index when compared to their counterparts in Mani (Beta=0.174, p<0.001); moreover, islanders exhibited slightly more years of "good" health (68.7 vs 68.4 years for Mani residents (p=0.99)). However, compared to the residents of Mani, islanders had 1.64 times higher odds (95%CI, 1.08-2.48) for having hypertension, 2.4-times higher odds (95%CI, 1.34-4.21) for having diabetes and 1.52 times higher odds (95%CI, 0.97-2.38) for having hypercholesterolemia. Engaging in physical activities and healthy dietary habits were the major determinants of healthy aging, among islanders as compared to their counterparts of continental Mani region. Elder residents of the continental Mani area enjoyed a better health status, whereas elder islanders had a higher level of successful aging; a finding which could be attributed to differences in lifestyle among elders.

Methods: Spirometry datasets from South-Asian children were collated from four centres in India and five within the UK. Records with transcription errors, missing values for height or spirometry, and implausible values were excluded(n = 110)., Results: Following exclusions, cross-sectional data were available from 8,124 children (56.3% male; 5-17 years). When compared with GLI-predicted values from White Europeans, forced expired volume in 1s (FEV1) and forced vital capacity (FVC) in South-Asian children were on average 15% lower, ranging from 4-19% between centres. By contrast, proportional reductions in FEV1 and FVC within all but two datasets meant that the FEV1/FVC ratio remained independent of ethnicity. The 'GLI-Other' equation fitted data from North India reasonably well while 'GLI-Black' equations provided a better approximation for South-Asian data than the 'GLI-White' equation. However, marked discrepancies in the mean lung function z-scores between centres especially when examined according to socio-economic conditions precluded derivation of a single South-Asian GLI-adjustment., Conclusion: Until improved and more robust prediction equations can be derived, we recommend the use of 'GLI-Black' equations for interpreting most South-Asian data, although 'GLI-Other' may be more appropriate for North Indian data. Prospective data collection using standardised protocols to explore potential sources of variation due to socio-economic circumstances, secular changes in growth/predictors of lung function and ethnicities within the South-Asian classification are urgently required.

Unlabelled: The raised volume rapid thoracoabdominal compression (RVRTC) technique is commonly used to obtain full forced expiratory manoeuvres from infants, but reference equations derived from 'in-house' equipment have been shown to be inappropriate for current commercially available devices., Aim: To explore the impact of equipment differences on RVRTC outcomes, derive robust equipment-specific RVRTC reference ranges and investigate their potential clinical impact on data interpretation., Method: RVRTC data from healthy subjects using Jaeger BabyBody or the 'Respiratory Analysis Software Program, RASP' systems were collated from four centres internationally. Data were excluded if gestational age <37 weeks or birth weight <2.5 kg. Reference equations for RVRTC outcomes were constructed using the LMS (lambda-mu-sigma) method, and compared with published equations using data from newborn screened infants with cystic fibrosis (CF)., Results: RVRTC data from 429 healthy infants (50.3% boys; 88% white infants) on 639 occasions aged 4-118 weeks were available. When plotted against length, flows were significantly higher with RASP than Jaeger, requiring construction of separate equipment-specific regression equations. When comparing results derived from the new equations with those from widely used published equations based on different equipments, discrepancies in forced expiratory volumes and flows of up to 2.5 z-scores were observed, the magnitude of which increased with age. According to published equations, 25% of infants with CF fell below the 95% limits of normal for FEV0.5, compared with only 10% when using the new equations., Conclusions: Use of equipment-specific prediction equations for RVRTC outcomes will enhance interpretation of infant lung function results; particularly during longitudinal follow-up., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)