Timing of invasive strategy in non-ST-elevation acute coronary syndrome: risk and reward?

This commentary refers to ‘Timing of invasive strategy in elevation acute coronary syndrome: a meta-analysis of randomized controlled trials’, by T.A. Kite et al., https://doi.org/10.1093/eurheartj/ehac213 and the discussion piece ‘Timing of early invasive strategy in patients with non-ST-elevation acute coronary syndrome’, by A.I. Aladin et al., https://doi.org/10.1093/eurheartj/ehac466

Trends in the long-term impact of childhood visual impairment on health and social outcomes in the UK: a cross-cohort study across three decades of disability-related legislation and policy implementation

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

Socio-economic and demographic determinants of childhood obesity prevalence in Greece: the GRECO (Greek Childhood Obesity) study

Objective: Given the rapid increase in the prevalence of childhood obesity, identifying the sociodemographic influences on obesity status is important for planning and implementing effective prevention initiatives. However, this type of data is limited for Greek children. Therefore the aim of the present study was to identify possible sociodemographic factors associated with childhood obesity at the national level. Design: Cross-sectional, population-based survey, carried out from October to May 2009. Setting: Under the context of the GRECO (Greek Childhood Obesity) study, a nationwide sample of 2315 primary-school children. Subjects: Children aged 10–12 years and their parents were voluntarily enrolled. Direct anthropometric measurements of the children were obtained and information on sociodemographic characteristics of the parents, as well as their self-reported values of body weight and height, were collected. Results: Overweight and obesity prevalence was 29?5 % and 13?1 %, respectively, among boys; 29?5 % and 9?0 %, respectively, among girls. Multiple logistic regression analysis revealed that the most important sociodemographic predictors of childhood obesity were mother’s age, parental BMI classification and father’s type of occupation. More specifically, increased mother’s age and normal BMI status of the parents seemed to have a protective effect on the likelihood of having an overweight/obese child. Additionally, the odds of a female child of being overweight/obese were reduced when the father’s type of occupation tended to be less manual. Conclusions: Anti-obesity health policy interventions have to address to the parents and promote their active involvement, to effectively confront the alarming magnitude of the paediatric obesity problem in Greece

Temporal trends in frequency, type and severity of myopia and associations with key environmental risk factors in the UK: Findings from the UK Biobank Study

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

Prigodom 60-godišnjice zadružne mlekarne u Škofjoj Loki

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

Timing of invasive strategy in non-ST-elevation acute coronary syndrome: a meta-analysis of randomized controlled trials

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

Association of shorter leucocyte telomere length with risk of frailty.

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.This research has been conducted using the UK Biobank Resource under Application Number 6077. Generation of the LTL measurements was funded by the UK Medical Research Council (MRC), Biotechnology and Biological Sciences Research Council and British Heart Foundation (BHF) through MRC grant MR/M012816/1

Evaluating the clinical effectiveness of the NHS Health Check programme: a prospective analysis in the Genetics and Vascular Health Check (GENVASC) study

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

Shorter leukocyte telomere length is associated with adverse COVID-19 outcomes: A cohort study in UK Biobank.

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.UK Medical Research Council, Biotechnology and Biological Sciences Research Council and British Heart Foundation