Anxiety and depression in pregnant women who have experienced a previous perinatal loss: a case-cohort study from Scandinavia.

BACKGROUND: Perinatal loss can have long-lasting adverse effects on a woman's psychosocial health, including during subsequent pregnancies. However, maternal mental health status after perinatal loss during subsequent pregnancy is understudied with very little data available for Scandinavian populations. AIMS: The primary aim of the study was to explore the association between previous perinatal loss and anxiety/depression symptoms of expectant mothers during the subsequent pregnancy. The secondary aim of this study was to explore possible determinants of maternal mental health during the subsequent pregnancy, independent of previous perinatal loss. METHOD: This case-cohort study is based on primary data from Scandinavian Successive Small-for-Gestational Age Births Study (SGA Study) in Norway and Sweden. The total case-cohort sample in the current study includes 1458 women. Cases include 401 women who had reported a previous perinatal loss (spontaneous abortion, stillbirth, or neonatal death) and who responded to two mental health assessment instruments, the State-Trait Anxiety Inventory (STAI), and the Centre for Epidemiological Studies Depression (CES-D) scale. Multiple linear regression models were used to assess the association between previous perinatal loss and maternal mental health in subsequent pregnancy. RESULTS: Scandinavian pregnant women with previous perinatal loss reported higher symptoms for both anxiety and depression during their subsequent pregnancy compared to mothers in the same cohort reported no previous perinatal loss. Multiple linear regression analyses showed a positive association between previous perinatal loss and per unit increase in both total anxiety score (ß: 1.22, 95% CI: 0.49-1.95) and total depression score (ß: 0.90, 95% CI: 0.06-1.74). We identified several factors associated with maternal mental health during pregnancy independent of perinatal loss, including unintended pregnancy despite 97% of our population being married/cohabitating. CONCLUSION: Women who have experienced previous perinatal loss face a significantly higher risk of anxiety and depression symptoms in their subsequent pregnancy.

The blood metabolome of incident kidney cancer: A case-control study nested within the MetKid consortium.

BACKGROUND: Excess bodyweight and related metabolic perturbations have been implicated in kidney cancer aetiology, but the specific molecular mechanisms underlying these relationships are poorly understood. In this study, we sought to identify circulating metabolites that predispose kidney cancer and to evaluate the extent to which they are influenced by body mass index (BMI). METHODS AND FINDINGS: We assessed the association between circulating levels of 1,416 metabolites and incident kidney cancer using pre-diagnostic blood samples from up to 1,305 kidney cancer case-control pairs from 5 prospective cohort studies. Cases were diagnosed on average 8 years after blood collection. We found 25 metabolites robustly associated with kidney cancer risk. In particular, 14 glycerophospholipids (GPLs) were inversely associated with risk, including 8 phosphatidylcholines (PCs) and 2 plasmalogens. The PC with the strongest association was PC ae C34:3 with an odds ratio (OR) for 1 standard deviation (SD) increment of 0.75 (95% confidence interval [CI]: 0.68 to 0.83, p = 2.6 × 10-8). In contrast, 4 amino acids, including glutamate (OR for 1 SD = 1.39, 95% CI: 1.20 to 1.60, p = 1.6 × 10-5), were positively associated with risk. Adjusting for BMI partly attenuated the risk association for some-but not all-metabolites, whereas other known risk factors of kidney cancer, such as smoking and alcohol consumption, had minimal impact on the observed associations. A mendelian randomisation (MR) analysis of the influence of BMI on the blood metabolome highlighted that some metabolites associated with kidney cancer risk are influenced by BMI. Specifically, elevated BMI appeared to decrease levels of several GPLs that were also found inversely associated with kidney cancer risk (e.g., -0.17 SD change [ßBMI] in 1-(1-enyl-palmitoyl)-2-linoleoyl-GPC (P-16:0/18:2) levels per SD change in BMI, p = 3.4 × 10-5). BMI was also associated with increased levels of glutamate (ßBMI: 0.12, p = 1.5 × 10-3). While our results were robust across the participating studies, they were limited to study participants of European descent, and it will, therefore, be important to evaluate if our findings can be generalised to populations with different genetic backgrounds. CONCLUSIONS: This study suggests a potentially important role of the blood metabolome in kidney cancer aetiology by highlighting a wide range of metabolites associated with the risk of developing kidney cancer and the extent to which changes in levels of these metabolites are driven by BMI-the principal modifiable risk factor of kidney cancer.

Circulating markers of cellular immune activation in prediagnostic blood sample and lung cancer risk in the Lung Cancer Cohort Consortium (LC3).

Cell-mediated immune suppression may play an important role in lung carcinogenesis. We investigated the associations for circulating levels of tryptophan, kynurenine, kynurenine:tryptophan ratio (KTR), quinolinic acid (QA) and neopterin as markers of immune regulation and inflammation with lung cancer risk in 5,364 smoking-matched case-control pairs from 20 prospective cohorts included in the international Lung Cancer Cohort Consortium. All biomarkers were quantified by mass spectrometry-based methods in serum/plasma samples collected on average 6 years before lung cancer diagnosis. Odds ratios (ORs) and 95% confidence intervals (CIs) for lung cancer associated with individual biomarkers were calculated using conditional logistic regression with adjustment for circulating cotinine. Compared to the lowest quintile, the highest quintiles of kynurenine, KTR, QA and neopterin were associated with a 20-30% higher risk, and tryptophan with a 15% lower risk of lung cancer (all ptrend < 0.05). The strongest associations were seen for current smokers, where the adjusted ORs (95% CIs) of lung cancer for the highest quintile of KTR, QA and neopterin were 1.42 (1.15-1.75), 1.42 (1.14-1.76) and 1.45 (1.13-1.86), respectively. A stronger association was also seen for KTR and QA with risk of lung squamous cell carcinoma followed by adenocarcinoma, and for lung cancer diagnosed within the first 2 years after blood draw. This study demonstrated that components of the tryptophan-kynurenine pathway with immunomodulatory effects are associated with risk of lung cancer overall, especially for current smokers. Further research is needed to evaluate the role of these biomarkers in lung carcinogenesis and progression.

Is high vitamin B12 status a cause of lung cancer?

Vitamin B supplementation can have side effects for human health, including cancer risk. We aimed to elucidate the role of vitamin B12 in lung cancer etiology via direct measurements of pre-diagnostic circulating vitamin B12 concentrations in a nested case-control study, complemented with a Mendelian randomization (MR) approach in an independent case-control sample. We used pre-diagnostic biomarker data from 5183 case-control pairs nested within 20 prospective cohorts, and genetic data from 29,266 cases and 56,450 controls. Exposures included directly measured circulating vitamin B12 in pre-diagnostic blood samples from the nested case-control study, and 8 single nucleotide polymorphisms associated with vitamin B12 concentrations in the MR study. Our main outcome of interest was increased risk for lung cancer, overall and by histological subtype, per increase in circulating vitamin B12 concentrations. We found circulating vitamin B12 to be positively associated with overall lung cancer risk in a dose response fashion (odds ratio for a doubling in B12 [ORlog2B12 ] = 1.15, 95% confidence interval (95%CI) = 1.06-1.25). The MR analysis based on 8 genetic variants also indicated that genetically determined higher vitamin B12 concentrations were positively associated with overall lung cancer risk (OR per 150 pmol/L standard deviation increase in B12 [ORSD ] = 1.08, 95%CI = 1.00-1.16). Considering the consistency of these two independent and complementary analyses, these findings support the hypothesis that high vitamin B12 status increases the risk of lung cancer.

Short interpregnancy interval and poor fetal growth: Evaluating the role of pregnancy intention.

BACKGROUND: Previous studies have demonstrated that short interpregnancy interval (the interval between delivery and estimated last menstrual period of a subsequent pregnancy) is associated with small for gestational age birth. It is controversial if this association is causal, as few studies have accounted for likely confounding factors such as unintended pregnancy. We examined the association between interpregnancy interval and infant birthweight, adjusting for pregnancy intention and other socio-economic and obstetrical risk factors. METHODS: We used data from the Scandinavian Successive Small-for-Gestational-Age births study (1986-1988). Birthweight was expressed as a gestational age-standardised z-score. RESULTS: Among 1406 women, a trend towards lower birthweight z-score with short interpregnancy interval was not statistically significant (unadjusted difference in birthweight z-score of -0.25, 95% confidence interval (CI) -0.55, 0.05). After adjusting for pregnancy intention, detailed measures of socio-economic status, and other covariates, the estimated magnitude of effect between interpregnancy interval and birthweight z-score was further attenuated (adjusted difference in birthweight z-score of -0.13, 95% CI -0.46, 0.20). CONCLUSIONS: In this cohort study with detailed information on pregnancy intention and socio-economic status, short interpregnancy interval was not associated with lower birthweight. These findings suggest that previously observed associations between short interpregnancy interval and lower birthweight may reflect confounding by socio-economic and/or other unmeasured confounders.

Prenatal exposure to persistent organic pollutants and child overweight/obesity at 5-year follow-up: a prospective cohort study.

BACKGROUND: Prenatal exposure to persistent organic pollutants (POPs), may influence offspring weight gain. More prospective epidemiological studies are needed to compliment the growing body of evidence from animal studies. METHODS: Serum from 412 pregnant Norwegian and Swedish women participating in a Scandinavian prospective cohort study were collected in 1986-88, and analyses of two perfluoroalkyl substances (PFASs) and five organochlorines (OCs) were conducted. We used linear and logistic regression models with 95% confidence intervals (CIs) to evaluate the associations between maternal serum POP concentrations at 17-20 weeks of gestation and child overweight/obesity (body mass index (BMI) ≥ 85th percentile) at 5-year follow-up. Results were further stratified by country after testing for effect modification. We also assessed potential non-monotonic dose-response (NMDR) relationships. RESULTS: In adjusted linear models, we observed increased BMI-for-age-and-sex z-score (ß = 0.18, 95% CI: 0.01-0.35), and increased triceps skinfold z-score (ß = 0.15, 95% CI: 0.02-0.27) in children at 5-year follow-up per ln-unit increase in maternal serum perfluorooctane sulfonate (PFOS) concentrations. We observed increased odds for child overweight/obesity (BMI ≥ 85th percentile) for each ln-unit increase in maternal serum PFOS levels (adjusted OR: 2.04, 95% CI: 1.11-3.74), with stronger odds among Norwegian children (OR: 2.96, 95% CI: 1.42-6.15). We found similar associations between maternal serum perfluorooctanoate (PFOA) concentrations and child overweight/obesity. We found indications of NMDR relationships between PFOS and polychlorinated biphenyl (PCB) 153 and child overweight/obesity among Swedish children. CONCLUSION: We found positive associations between maternal serum PFAS concentrations and child overweight/obesity at 5-year follow-up, particularly among Norwegian participants. We observed some evidence for NMDR relationships among Swedish participants.

Developmental course of anxiety and depression from adolescence to young adulthood in a prospective Norwegian clinical cohort.

Anxiety and depression are often co-occurring disorders, reflecting both homotypic and heterotypic continuity as possible developmental pathways. The present study aimed to examine homotypic and heterotypic continuities of anxiety and depression across 3 years in adolescence and young adulthood. Participants included patients presenting to psychiatric care with diagnoses of anxiety and/or depressive disorders aged 13-18 at T1 (N = 717, 44% initial participation rate) and aged 16-21 at T2 (N = 549, 80% follow-up participation rate). McNemar's mid-p test and ordinal proportional odds logistic regression analyses were used to assess changes in prevalence within and across diagnostic categories, respectively. More adolescents had an anxiety disorder (+ 11%), whereas fewer had a depressive disorder (- 11%), at T2 compared to T1. Of adolescents with anxiety and/or depression at T1, only 25% recovered or were non-symptomatic 3 years after referral to a psychiatric clinic. Homotypic continuity was observed for anxiety disorders in general (OR = 2.33), for phobic anxiety disorders (OR = 7.45), and for depressive disorders (OR = 2.15). For heterotypic continuity, depression predicted later anxiety (OR = 1.92), more specifically social anxiety (OR = 2.14) and phobic anxiety disorders (OR = 1.83). In addition, social anxiety predicted later generalized anxiety disorder (OR = 3.11). Heterotypic continuity was thus more common than homotypic continuity. For adolescents presenting with anxiety or depression, treatment should, therefore, target broad internalizing symptom clusters, rather than individual diagnoses. This may contribute to prevent future mental illness, particularly anxiety, in clinical samples.

Maternal serum levels of perfluoroalkyl substances and organochlorines and indices of fetal growth: a Scandinavian case-cohort study.

BACKGROUND: The associations between prenatal exposure to endocrine disruptive chemicals (EDCs) and fetal growth are inconsistent, and few studies have considered small-for-gestational-age (SGA) birth as an outcome. Our current study of Scandinavian parous women aimed to address these inconsistencies and gaps in the literature. METHODS: This case-cohort study included 424 mother-child pairs who participated in a prospective, multi-center study of parous women in Norway (Trondheim and Bergen) and Sweden (Uppsala). We used linear and logistic regression with 95% confidence intervals (CIs) to analyze the associations between two perfluoroalkyl substances (PFASs) and five organochlorines (OCs) from early second trimester and indices of fetal growth. RESULTS: Among Swedish women, prenatal exposure to perfluorooctanoate (PFOA), polychlorinated biphenyl (PCB) 153 and hexachlorobenzene (HCB) were associated with higher odds for SGA birth. We found stronger associations among Swedish male offspring. In the Norwegian cohort, we found no significant associations between EDC exposure and indices of fetal growth. CONCLUSIONS: Some populations may be more vulnerable to EDCs, possibly due to differences in exposure levels, exposure sources and/or modifiable lifestyle factors. Male offspring may be more vulnerable to endocrine disruption.

Serum 25-hydroxyvitamin D level, smoking and lung function in adults: the HUNT Study.

The association between serum 25-hydroxyvitamin D (25(OH)D) level and lung function changes in the general population remains unclear.We conducted cross-sectional (n=1220) and follow-up (n=869) studies to investigate the interrelationship of serum 25(OH)D, smoking and lung function changes in a random sample of adults from the Nord-Trøndelag Health (HUNT) Study, Norway.Lung function was measured using spirometry and included forced expiratory volume in 1 s (FEV1) % predicted, forced vital capacity (FVC) % pred and FEV1/FVC ratio. Multiple linear and logistic regression models estimated the adjusted difference in lung function measures or lung function decline, adjusted odds ratios for impaired lung function or development of impaired lung function and 95% confidence intervals.40% of adults had serum 25(OH)D levels <50 nmol·L(-1). Overall, those with a serum 25(OH)D level <50 nmol·L(-1) showed worse lung function and increased odds of impaired lung function compared to the ≥50 nmol·L(-1) group. These associations tended to be stronger among ever-smokers, including greater decline in FEV1/FVC ratio and greater odds of the development of impaired lung function (FEV1/FVC <70% OR 2.4, 95% CI 1.2-4.9). Associations among never-smokers were null. Results from cross-sectional and follow-up studies were consistent. There were no associations between serum 25(OH)D levels and lung function or lung function changes in never-smokers, whereas significant associations were observed in ever-smokers.

Serum 25-hydroxyvitamin D levels and lung function in adults with asthma: the HUNT Study.

The association between vitamin D status and lung function in adults with asthma remains unclear. We studied this cross-sectional association and possible modification by sex and allergic rhinitis in 760 adults (aged 19-55 years) with self-reported asthma in the Nord-Trøndelag Health Study. Serum 25-hydroxyvitamin D (25(OH)D) level <50 nmol·L(-1) was considered deficient. Lung function measurements included forced expiratory volume in 1 s (FEV1) % predicted, forced vital capacity (FVC) % predicted and FEV1/FVC ratio. Multiple linear regression models were used to estimate adjusted regression coefficients (ß) and 95% confidence intervals. 44% of asthma adults had serum 25(OH)D levels <50 nmol·L(-1). Its associations with lung function measures seemed to be modified by sex and allergic rhinitis (p<0.03 for three-way interaction term). Overall, a serum 25(OH)D level <50 nmol·L(-1) was not associated with lung function measurements in subjects with allergic rhinitis in this asthma cohort. In men with asthma but without allergic rhinitis, however, a serum 25(OH)D level <50 nmol·L(-1) was significantly associated with lower FEV1/FVC ratio (ß=-8.60%; 95% CI: -16.95%- -0.25%). Low serum 25(OH)D level was not associated with airway obstruction in most asthma adults with the exception of men with asthma but without allergic rhinitis.

A Comprehensive Look Behind Team Composition for Long Duration Spaceflight.

BACKGROUND: How to determine team composition is one of many key topics when developing humanity's next deep space exploration programs. Behavioral health and performance among spaceflight teams are key aspects impacted by team composition and cohesiveness.METHODS: This narrative review highlights areas of consideration for building cohesive teams in long duration spaceflight environments. The authors gathered information from a variety of team-behavior related studies that focused on team composition, cohesion, and dynamics, as well as others topics such as faultlines and subgroups, diversity, personality traits, personal values, and crew compatibility training.RESULTS: The literature suggests that team cohesion occurs more easily when individuals are similar to one another, and deep-level variables such as personality and personal values have a greater impact on crew compatibility than surface level variables such as age, nationality, or gender. Diversity can have both positive and negative impacts on team cohesiveness.CONCLUSION: Team composition, as well as pre-mission conflict resolution training can greatly impact group cohesion. This review aims to map areas of concern and assist with crew planning for long duration spaceflight missions.Gangeme A, Simpson B, De La Torre GG, Larose TL, Diaz-Artiles A. A comprehensive look behind team composition for long duration spaceflight. Aerosp Med Hum Perform. 2023; 94(6):457-465.

Excessive Daytime Sleepiness and Associated Factors in Military Search and Rescue Personnel.

BACKGROUND: Abnormal excessive daytime sleepiness (EDS) has been reported worldwide, but too little is known about EDS and its determinants in Search and Rescue (SAR) populations. We aimed to determine the prevalence of abnormal EDS and contributing factors among Royal Norwegian Air Force (RNoAF) SAR helicopter personnel.METHODS: In this cross-sectional study, a total of N = 175 RNoAF SAR personnel completed an electronic survey including socio-demographic and lifestyle questions. The Epworth Sleepiness Scale (ESS) was used as both a continuous and categorical outcome variable to measure EDS.RESULTS: Abnormal EDS defined by ESS was found in 41% of the participants in this study. We observed no associations between socio-demographic and lifestyle factors and abnormal EDS in this study. DISCUSSION: There is a high prevalence of abnormal EDS in the current RNoAF SAR population. Despite this elevated level of fatigue, we did not find that the socio-demographic and lifestyle factors assessed in this study were associated with abnormal EDS in RNoAF SAR helicopter personnel. Also unusually, the study cohort did not demonstrate higher scores in factors found to change ESS scores in similar study populations (e.g., caffeine use, tobacco use, exercise level). Further research is required to investigate other factors (organizational, operational) that may be associated with abnormal EDS in this and other SAR populations.Akter R, Larose TL, Sandvik J, Fonne V, Meland A, Wagstaff AS. Excessive daytime sleepiness and associated factors in military search and rescue personnel. Aerosp Med Hum Perform. 2021; 92(12):975-979.

AMADEE-18 and the Analog Mission Performance Metrics Analysis: A Benchmarking Tool for Mission Planning and Evaluation.

Analog research of human or combined human and robotic missions is an established tool to explore the workflows, instruments, risks, and challenges of future planetary surface missions in a representative terrestrial environment. Analog missions that emulate selected aspects of such expeditions have risen in number, expanded their range of disciplines covered, and seen a significant increase in their operational and programmatic impact on mission planning. We propose a method to compare analog missions across agencies, disciplines, and complexities/fidelities to improve scientific output and mission safety and maximize effectiveness and efficiency. This algorithm measures mission performance, provides a tool for an objective postmission evaluation, and catalyzes programmatic progress. It does not evaluate individual sites or instruments but focuses at mission level. By applying the algorithm to several missions, we compare the missions' performance for benchmarking purposes. Methodically, a combination of objective data sets and questionnaires is used to evaluate three areas: two sections of closed and quantitative questions and a third section dedicated to the level or representativeness of the test site. By using a weighted metric, the complexity and fidelity of a mission are compared with reference missions, which yield strengths and weaknesses in mission planning.

Maternal serum retinol, 25(OH)D and 1,25(OH)2D concentrations during pregnancy and peak bone mass and trabecular bone score in adult offspring at 26-year follow-up.

BACKGROUND: Vitamin A and D deficiency is prevalent in pregnant women worldwide. Both vitamins are involved in fetal skeletal development. A positive association between maternal vitamin D levels and offspring bone mineral density (BMD) at adulthood has been observed. The impact of maternal vitamin A status in pregnancy on offspring peak bone mass remains unclear. METHOD AND FINDINGS: Forty-one mother-child pairs were recruited from a population-based prospective cohort study in Trondheim, Norway, where pregnant women were followed from gestational week 17. Their term-born infants were followed from birth (1986-88). Regression analyses were performed for vitamin A (retinol), 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] in maternal serum (gestational weeks 17, 33, 37) and cord blood. Offspring BMD and spine trabecular bone score (TBS), a measure of bone quality, were analyzed by dual x-ray absorptiometry at 26 years. Average levels during pregnancy of retinol, 25(OH)D and 1,25(OH)2D were 1.66 (0.32) µmol/L, 59.0 (20.6) nmol/L, and 251.3 (62.4) pmol/L, respectively. 1,25(OH)2D levels were similar in those with 25(OH)D levels <30 and >75 nmol/L. After adjustment for maternal age, BMI, smoking, and education, and offspring birth weight, maternal serum retinol was positively associated with offspring spine BMD [mean change 30.8 (CI 7.6, 54.0) mg/cm2 per 0.2 µmol/L retinol], and with offspring TBS, although non-significant (p = 0.08). No associations were found between maternal 25(OH)D and 1,25(OH)2D levels and offspring bone parameters. Vitamin levels in cord blood were not associated with offspring BMD or TBS. CONCLUSIONS: This is the first study to show an association between maternal vitamin A status and offspring peak bone mass. Our findings may imply increase future risk for osteoporotic fracture in offspring of mothers with suboptimal vitamin A level. No associations were observed between 25(OH)D and 1,25(OH)2D and offspring BMD.

In utero exposure to endocrine disrupting chemicals, micro-RNA profiles, and fetal growth: a pilot study protocol.

Background: The developing fetus is particularly vulnerable to the effects of endocrine disrupting chemicals (EDCs). Molecular fingerprints of EDCs can be identified via microRNA (miRNA) expression profiles and may be etiologically implicated in the developmental origin of disease (DOHaD). Methods/design: This pilot study includes pregnant women at high risk (smoking at conception), and low risk (non-smoking at conception) for SGA birth (birthweight<10th percentile for gestational age). We have randomly selected 12 mothers (3 high-risk SGA birth, 3 low-risk SGA birth, 3 high-risk non-SGA birth, 3 low-risk non-SGA birth), with EDC measurements from gestational week 17. All offspring are female. We aim to test the stability of our samples (maternal serum, cord blood, placenta tissue), observe the differential expression of miRNA profiles over time (gestational weeks 17, 25, 33, 37, birth), and study the consistency between maternal EDC measures and miRNA expression profiles across our repeated measures. Expected impact of the study for Public Health: Results from this pilot study will inform the development of a larger cohort wide analysis, and will impact the current state of knowledge in the fields of public health, epigenetics, and the DOHaD.

Circulating high sensitivity C reactive protein concentrations and risk of lung cancer: nested case-control study within Lung Cancer Cohort Consortium.

OBJECTIVES: To conduct a comprehensive analysis of prospectively measured circulating high sensitivity C reactive protein (hsCRP) concentration and risk of lung cancer overall, by smoking status (never, former, and current smokers), and histological sub-type. DESIGN: Nested case-control study. SETTING: 20 population based cohort studies in Asia, Europe, Australia, and the United States. PARTICIPANTS: 5299 patients with incident lung cancer, with individually incidence density matched controls. EXPOSURE: Circulating hsCRP concentrations in prediagnostic serum or plasma samples. MAIN OUTCOME MEASURE: Incident lung cancer diagnosis. RESULTS: A positive association between circulating hsCRP concentration and the risk of lung cancer for current (odds ratio associated with a doubling in hsCRP concentration 1.09, 95% confidence interval 1.05 to 1.13) and former smokers (1.09, 1.04 to 1.14) was observed, but not for never smokers (P<0.01 for interaction). This association was strong and consistent across all histological subtypes, except for adenocarcinoma, which was not strongly associated with hsCRP concentration regardless of smoking status (odds ratio for adenocarcinoma overall 0.97, 95% confidence interval 0.94 to 1.01). The association between circulating hsCRP concentration and the risk of lung cancer was strongest in the first two years of follow-up for former and current smokers. Including hsCRP concentration in a risk model, in addition to smoking based variables, did not improve risk discrimination overall, but slightly improved discrimination for cancers diagnosed in the first two years of follow-up. CONCLUSIONS: Former and current smokers with higher circulating hsCRP concentrations had a higher risk of lung cancer overall. Circulating hsCRP concentration was not associated with the risk of lung adenocarcinoma. Circulating hsCRP concentration could be a prediagnostic marker of lung cancer rather than a causal risk factor.

Epidemiology and Risk Factors for Kidney Cancer.

The purpose of this narrative review is to summarize evidence of the epidemiology of and risk factors for kidney cancer with a focus on renal cell carcinoma in adults. The etiology of kidney cancer is largely unknown and the main epidemiologic determinants are large geographic and temporal variations in incidence rates. Established risk factors include tobacco smoking, body size, and history of hypertension and chronic kidney disease. Other suspected risk factors require additional investigation, as do the underlying biologic mechanisms that are responsible for disease occurrence. Opportunities to prevent kidney cancer include targeting modifiable risk factors-for example, smoking abstinence/cessation and body weight control-as well as interventions along the diagnostic pathway to improve early diagnosis. Molecular epidemiology, including, but not limited to, metabolomics and tumor genomics, are new areas of research that promise to play important roles in identifying some of the underlying causes of kidney cancer.

Circulating cotinine concentrations and lung cancer risk in the Lung Cancer Cohort Consortium (LC3).

Background: Self-reported smoking is the principal measure used to assess lung cancer risk in epidemiological studies. We evaluated if circulating cotinine-a nicotine metabolite and biomarker of recent tobacco exposure-provides additional information on lung cancer risk. Methods: The study was conducted in the Lung Cancer Cohort Consortium (LC3) involving 20 prospective cohort studies. Pre-diagnostic serum cotinine concentrations were measured in one laboratory on 5364 lung cancer cases and 5364 individually matched controls. We used conditional logistic regression to evaluate the association between circulating cotinine and lung cancer, and assessed if cotinine provided additional risk-discriminative information compared with self-reported smoking (smoking status, smoking intensity, smoking duration), using receiver-operating characteristic (ROC) curve analysis. Results: We observed a strong positive association between cotinine and lung cancer risk for current smokers [odds ratio (OR ) per 500 nmol/L increase in cotinine (OR500): 1.39, 95% confidence interval (CI): 1.32-1.47]. Cotinine concentrations consistent with active smoking (≥115 nmol/L) were common in former smokers (cases: 14.6%; controls: 9.2%) and rare in never smokers (cases: 2.7%; controls: 0.8%). Former and never smokers with cotinine concentrations indicative of active smoking (≥115 nmol/L) also showed increased lung cancer risk. For current smokers, the risk-discriminative performance of cotinine combined with self-reported smoking (AUCintegrated: 0.69, 95% CI: 0.68-0.71) yielded a small improvement over self-reported smoking alone (AUCsmoke: 0.66, 95% CI: 0.64-0.68) (P = 1.5x10-9). Conclusions: Circulating cotinine concentrations are consistently associated with lung cancer risk for current smokers and provide additional risk-discriminative information compared with self-report smoking alone.

Modelling study to estimate the health burden of foodborne diseases: cases, general practice consultations and hospitalisations in the UK, 2009.

OBJECTIVE: To generate estimates of the burden of UK-acquired foodborne disease accounting for uncertainty. DESIGN: A modelling study combining data from national public health surveillance systems for laboratory-confirmed infectious intestinal disease (IID) and outbreaks of foodborne disease and 2 prospective, population-based studies of IID in the community. The underlying data sets covered the time period 1993-2008. We used Monte Carlo simulation and a Bayesian approach, using a systematic review to generate Bayesian priors. We calculated point estimates with 95% credible intervals (CrI). SETTING: UK, 2009. OUTCOME MEASURES: Pathogen-specific estimates of the number of cases, general practice (GP) consultations and hospitalisations for foodborne disease in the UK in 2009. RESULTS: Bayesian approaches gave slightly more conservative estimates of overall health burden (∼511 000 cases vs 566 000 cases). Campylobacter is the most common foodborne pathogen, causing 280 400 (95% CrI 182 503-435 693) food-related cases and 38 860 (95% CrI 27 160-55 610) GP consultations annually. Despite this, there are only around 562 (95% CrI 189-1330) food-related hospital admissions due to Campylobacter, reflecting relatively low disease severity. Salmonella causes the largest number of hospitalisations, an estimated 2490 admissions (95% CrI 607-9631), closely followed by Escherichia coli O157 with 2233 admissions (95% CrI 170-32 159). Other common causes of foodborne disease include Clostridium perfringens, with an estimated 79 570 cases annually (95% CrI 30 700-211 298) and norovirus with 74 100 cases (95% CrI 61 150-89 660). Other viruses and protozoa ranked much lower as causes of foodborne disease. CONCLUSIONS: The 3 models yielded similar estimates of the burden of foodborne illness in the UK and show that continued reductions in Campylobacter, Salmonella, E. coli O157, C. perfringens and norovirus are needed to mitigate the impact of foodborne disease.

Factors Associated with Maternal Serum Levels of Perfluoroalkyl Substances and Organochlorines: A Descriptive Study of Parous Women in Norway and Sweden.

INTRODUCTION: Perfluoroalkyl substances (PFASs) and organochlorines (OCs) are ubiquitous and persistent in the environment and proposed endocrine disrupting chemicals (EDCs). They can be transferred across the placenta during pregnancy, and studies suggest that the prenatal period may be particularly sensitive for influences on fetal growth and development. Several studies have investigated socio-demographic and pregnancy related factors associated with maternal serum PFAS and OC levels, but few studies have been conducted in time periods with increasing emissions of PFASs and recent emissions of OCs. METHODS: Serum from 424 pregnant women participating in the NICHD Scandinavian Successive Small-for-gestational Age (SGA) births study was collected in 1986-1988, and analyses of two PFASs and six OCs were conducted. Associations between EDCs and geographic, time dependent, socio-demographic and pregnancy related variables were evaluated by using multivariable linear regression models. RESULTS: Previous breastfeeding duration, time since last breastfeeding period, sampling date and country of residence were important factors associated with serum levels of PFOS and PFOA. Smoking status and pre-pregnancy BMI were negatively associated with PFOS, and maternal height was borderline negatively associated with PFOS and PFOA. Glomerular filtration rate (GFR) was negatively associated with PFOS in a sub-sample. Maternal serum levels of OCs were positively associated with maternal age, and negatively associated with previous breastfeeding duration and sampling date. Smoking had a consistently negative association with PCB 118 in a dose-dependent manner. Education level, pre-pregnancy BMI and alcohol consumption varied in importance according to the compound under study. CONCLUSIONS: Several maternal factors, including potentially modifiable factors, markers of pregnancy physiology and factors also related to perinatal outcomes were associated with EDC levels. Results from this study are relevant to populations with still high PFAS and OC levels, i.e. developing countries. Moreover, we can use this knowledge about associated factors on emerging EDCs with similar properties.