Explore the vast range of titles available.

This paper provides guidelines for performing Mendelian randomization investigations. It is aimed at practitioners seeking to undertake analyses and write up their findings, and at journal editors and reviewers seeking to assess Mendelian randomization manuscripts. The guidelines are divided into nine sections: motivation and scope, data sources, choice of genetic variants, variant harmonization, primary analysis, supplementary and sensitivity analyses (one section on robust statistical methods and one on other approaches), data presentation, and interpretation. These guidelines will be updated based on feedback from the community and advances in the field. Updates will be made periodically as needed, and at least every 18 months.

In a Guest Editorial, Cosetta Minelli and Gianluca Baio explain how VOI analysis can prioritize research projects by identifying uncertainty in existing knowledge and then estimating expected benefits from reducing that uncertainty.

Background Several statistical approaches have been proposed to assess and correct for exposure measurement error. We aimed to provide a critical overview of the most common approaches used in nutritional epidemiology. Methods MEDLINE, EMBASE, BIOSIS and CINAHL were searched for reports published in English up to May 2016 in order to ascertain studies that described methods aimed to quantify and/or correct for measurement error for a continuous exposure in nutritional epidemiology using a calibration study. Results We identified 126 studies, 43 of which described statistical methods and 83 that applied any of these methods to a real dataset. The statistical approaches in the eligible studies were grouped into: a) approaches to quantify the relationship between different dietary assessment instruments and “true intake”, which were mostly based on correlation analysis and the method of triads; b) approaches to adjust point and interval estimates of diet-disease associations for measurement error, mostly based on regression calibration analysis and its extensions. Two approaches (multiple imputation and moment reconstruction) were identified that can deal with differential measurement error. Conclusions For regression calibration, the most common approach to correct for measurement error used in nutritional epidemiology, it is crucial to ensure that its assumptions and requirements are fully met. Analyses that investigate the impact of departures from the classical measurement error model on regression calibration estimates can be helpful to researchers in interpreting their findings. With regard to the possible use of alternative methods when regression calibration is not appropriate, the choice of method should depend on the measurement error model assumed, the availability of suitable calibration study data and the potential for bias due to violation of the classical measurement error model assumptions. On the basis of this review, we provide some practical advice for the use of methods to assess and adjust for measurement error in nutritional epidemiology.

BackgroundPrevious studies have reported an association between warm temperature and asthma hospitalisation. They have reported different sex-related and age-related vulnerabilities; nevertheless, little is known about how this effect has changed over time and how it varies in space. This study aims to evaluate the association between asthma hospitalisation and warm temperature and investigate vulnerabilities by age, sex, time and space.MethodsWe retrieved individual-level data on summer asthma hospitalisation at high temporal (daily) and spatial (postcodes) resolutions during 2002–2019 in England from the NHS Digital. Daily mean temperature at 1 km×1 km resolution was retrieved from the UK Met Office. We focused on lag 0–3 days. We employed a case–crossover study design and fitted Bayesian hierarchical Poisson models accounting for possible confounders (rainfall, relative humidity, wind speed and national holidays).ResultsAfter accounting for confounding, we found an increase of 1.11% (95% credible interval: 0.88% to 1.34%) in the asthma hospitalisation risk for every 1°C increase in the ambient summer temperature. The effect was highest for males aged 16–64 (2.10%, 1.59% to 2.61%) and during the early years of our analysis. We also found evidence of a decreasing linear trend of the effect over time. Populations in Yorkshire and the Humber and East and West Midlands were the most vulnerable.ConclusionThis study provides evidence of an association between warm temperature and hospital admission for asthma. The effect has decreased over time with potential explanations including temporal differences in patterns of heat exposure, adaptive mechanisms, asthma management, lifestyle, comorbidities and occupation.

To explore the link between COVID-19 incidence, socio-economic covariates, and NHL incidence. Ecological study design. Sardinia, Italy. We used official reports on the total cases of COVID-19 in 2020, published data on NHL incidence, and socio-economic indicators by administrative unit, covering the whole regional population. We used multivariable regression analysis to explore the association between the natural logarithm (ln) of the 2020 cumulative incidence of COVID-19 and the ln-transformed NHL incidence in 1974-2003, weighing by population size and adjusting by socioeconomic deprivation and other covariates. The cumulative incidence of COVID-19 increased in relation to past incidence of NHL (p < 0.001), socioeconomic deprivation (p = 0.006), and proportion of elderly residents (p < 0.001) and decreased with urban residency (p = 0.001). Several sensitivity analyses confirmed the finding of an association between COVID-19 and NHL. This ecological study found an ecological association between NHL and COVID-19. If further investigation would confirm our findings, shared susceptibility factors should be investigated among the plausible underlying mechanisms.

There is evidence suggesting that birth weight may influence lung function in adulthood, but it is unclear whether it might differentially affect restrictive (FVC) and obstructive (FEV /FVC) patterns. To summarize evidence available on the association of birth weight, weight at 1 year, and weight gain in the first year of life with FVC and FEV /FVC in adulthood. We performed a systematic review of the literature by searching MEDLINE, EMBASE, and Web of Science through January 2015. Data were combined using inverse-variance weighted meta-analysis with random effects models and between-study heterogeneity evaluated. We conducted a priori subgroup or sensitivity analyses by age, country wealth, ethnicity, sex, and smoking. We evaluated risk of bias using the Newcastle Ottawa Scale and reporting bias using funnel plots. Eighteen articles were included in the review and 13 in the meta-analyses. Most studies were from high-income countries, and all had a low risk of bias. We found strong evidence of an association of birth weight with adult FVC, a 59.4 ml higher FVC in adulthood per kilogram increase in birth weight (95% confidence interval, 43.3-75.5), with no evidence of heterogeneity. Evidence of an association of birth weight with FEV /FVC was weaker and showed some inconsistency across studies. Only one study investigated weight at 1 year, and another one reported weight gain in the first year. Our meta-analyses show strong and consistent evidence of an association of birth weight with adult FVC, a measure of restrictive impairment, with much weaker evidence for airflow obstruction.

BackgroundVitamin A, an essential micronutrient obtained through the diet, plays a crucial role in lung development and contributes to lung regeneration. We aimed to investigate its effect on adult lung function using triangulation of evidence from both observational and genetic data.MethodsUsing data on 150 000 individuals from UK Biobank and correcting for measurement error (generalised structural equation modelling), we first investigated the association of dietary vitamin A intake (total vitamin A, carotene and retinol) with lung function (forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1)/FVC)). We then assessed the causality of these associations using Mendelian randomisation (MR), and we investigated the effects on adult lung function of 39 genes related to vitamin A, and their interaction with vitamin A intake.FindingsOur observational analysis suggests a positive association between carotene intake and FVC only (13.3 mL per 100 µg/day; p=2.9×10−9), with stronger associations in smokers, but no association of retinol intake with FVC or FEV1/FVC. The MR similarly shows a beneficial effect of serum beta-carotene on FVC only, with no effect of serum retinol on FVC nor FEV1/FVC. Nine of the vitamin A-related genes were associated with adult lung function, six of which have not been previously identified in genome-wide studies and three (NCOA2, RDH10, RXRB) in any type of genetic study of lung function. Five genes showed possible gene-vitamin A intake interactions.InterpretationOur triangulation study provides convincing evidence for a causal effect of vitamin A, carotene in particular, on adult lung function, suggesting a beneficial effect of a carotene-rich diet on adult lung health.

Although several studies demonstrated that platelet count is higher in women, decreases with age, and is influenced by genetic background, most clinical laboratories still use the reference interval 150-400×10(9) platelets/L for all subjects. The present study was to identify age- and sex-specific reference intervals for platelet count. We analysed electronic records of subjects enrolled in three population-based studies that investigated inhabitants of seven Italian areas including six geographic isolates. After exclusion of patients with malignancies, liver diseases, or inherited thrombocytopenias, which could affect platelet count, reference intervals were estimated from 40,987 subjects with the non parametric method computing the 2.5° and 97.5° percentiles. Platelet count was similar in men and women until the age of 14, but subsequently women had steadily more platelets than men. The number of platelets decreases quickly in childhood, stabilizes in adulthood, and further decreases in oldness. The final result of this phenomenon is that platelet count in old age was reduced by 35% in men and by 25% in women compared with early infancy. Based on these findings, we estimated reference intervals for platelet count ×10(9)/L in children (176-452), adult men (141-362), adult women (156-405), old men (122-350) and, old women (140-379). Moreover, we calculated an \"extended\" reference interval that takes into account the differences in platelet count observed in different geographic areas. The age-, sex-, and origin-related variability of platelet count is very wide, and the patient-adapted reference intervals we propose change the thresholds for diagnosing both thrombocytopenia and thrombocytosis in Italy.

Observational studies on pubertal timing and asthma, mainly performed in females, have provided conflicting results about a possible association of early puberty with higher risk of adult asthma, possibly due to residual confounding. To overcome issues of confounding, we used Mendelian randomisation (MR), i.e., genetic variants were used as instrumental variables to estimate causal effects of early puberty on post-pubertal asthma in both females and males. MR analyses were performed in UK Biobank on 243,316 women using 254 genetic variants for age at menarche, and on 192,067 men using 46 variants for age at voice breaking. Age at menarche, recorded in years, was categorised as early (<12), normal (12-14), or late (>14); age at voice breaking was recorded and analysed as early (younger than average), normal (about average age), or late (older than average). In females, we found evidence for a causal effect of pubertal timing on asthma, with an 8% increase in asthma risk for early menarche (odds ratio [OR] 1.08; 95% CI 1.04 to 1.12; p = 8.7 × 10(-5)) and an 8% decrease for late menarche (OR 0.92; 95% CI 0.89 to 0.97; p = 3.4 × 10(-4)), suggesting a continuous protective effect of increasing age at puberty. In males, we found very similar estimates of causal effects, although with wider confidence intervals (early voice breaking: OR 1.07; 95% CI 1.00 to 1.16; p = 0.06; late voice breaking: OR 0.93; 95% CI 0.87 to 0.99; p = 0.03). We detected only modest pleiotropy, and our findings showed robustness when different methods to account for pleiotropy were applied. BMI may either introduce pleiotropy or lie on the causal pathway; secondary analyses excluding variants associated with BMI yielded similar results to those of the main analyses. Our study relies on self-reported exposures and outcomes, which may have particularly affected the power of the analyses on age at voice breaking. This large MR study provides evidence for a causal detrimental effect of early puberty on asthma, and does not support previous observational findings of a U-shaped relationship between pubertal timing and asthma. Common biological or psychological mechanisms associated with early puberty might explain the similarity of our results in females and males, but further research is needed to investigate this. Taken together with evidence for other detrimental effects of early puberty on health, our study emphasises the need to further investigate and address the causes of the secular shift towards earlier puberty observed worldwide.

Smoking is the main risk factor for most of the leading causes of death. Cessation is the single most important step that smokers can take to improve their health. With the aim of informing policy makers about decisions on future tobacco control strategies, we estimated time and age trends in smoking cessation in Europe between 1980 and 2010. Data on the smoking history of 50,228 lifetime smokers from 17 European countries were obtained from six large population-based studies included in the Ageing Lungs in European Cohorts (ALEC) consortium. Smoking cessation rates were assessed retrospectively, and age trends were estimated for three decades (1980-1989, 1990-1999, 2000-2010). The analyses were stratified by sex and region (North, East, South, West Europe). Overall, 21,735 subjects (43.3%) quit smoking over a total time-at-risk of 803,031 years. Cessation rates increased between 1980 and 2010 in young adults (16-40 years), especially females, from all the regions, and in older adults (41-60 years) from North Europe, while they were stable in older adults from East, South and West Europe. In the 2000s, the cessation rates for men and women combined were highest in North Europe (49.9 per 1,000/year) compared to the other regions (range: 26.5-32.7 per 1,000/year). A sharp peak in rates was observed for women around the age of 30, possibly as a consequence of pregnancy-related smoking cessation. In most regions, subjects who started smoking before the age of 16 were less likely to quit than those who started later. Our findings suggest an increasing awareness on the detrimental effects of smoking across Europe. However, East, South and West European countries are lagging behind North Europe, suggesting the need to intensify tobacco control strategies in these regions. Additional efforts should be made to keep young adolescents away from taking up smoking, as early initiation could make quitting more challenging during later life.