Dietary habits in adolescent male and female handball players: the Swedish Handball Cohort.

Objectives: This cross-sectional study aimed to describe dietary habits in Swedish adolescent handball players and differences with respect to sex and school grade. Methods: Participants in the Swedish Handball Cohort answered a web-survey assessing adherence to sports nutrition recommendations for meal frequency and meal timing, and the Nordic Nutrition Recommendations (NNR) for fruits/vegetables and fish/seafood, food exclusions and use of dietary supplements. Differences with respect to sex and school grade were estimated with generalised linear models, generating prevalence ratios (PR) with 95% CIs. Results: A total of 1040 participants (16.6±0.9 years, 51% males) were included. Overall, 70% and 90%, respectively, met recommendations for meal frequency and meal timing, whereas adherence to recommended carbohydrate intake during training/game was met by 17%. Adherence to the NNR for fruits/vegetables and fish/seafood was met by 16% and 37%, respectively. Twenty-eight per cent reported using dietary supplements. Females reported lower frequency of meals, especially morning snacks (-0.6 days/week (95% CI -0.3 to -0.9)) and evening snacks (-0.8 days/week (95% CI -0.5 to -1.1)), higher prevalence of exclusions due to intolerances (PR 1.66 (95% CI 1.31 to 2.01)) and other reasons (PR 1.36 (95% CI 1.08 to 1.64)), higher adherence to the NNR for fruits/vegetables (PR 2.30 (95% CI 1.98 to 2.62)) and use of micronutrient supplements (PR 1.72 (95% CI 1.43 to 2.00)) compared with males. Only small differences were observed between school grades. Conclusions: Swedish adolescent handball players' dietary habits are fairly in accordance with sports nutrition recommendations but not the NNR. Females appear to display more restrictive habits than males.

Perceived knowledge gained from school-based sexuality education - results from a national population-based survey among young people in Sweden.

BACKGROUND: School-based sexuality education is a core component of securing young people's right to attain health equity regarding sexual and reproductive health and rights. This paper aims to explore how perceived knowledge (sufficient or insufficient) of taking care of one's sexual health is associated with knowledge gained from school-based sexuality education and social determinants. METHODS: The data material is drawn from a population-based survey conducted in Sweden in 2015. The survey had 7755 respondents and a response rate of 26%. To explore the aim descriptive statistics and logistic regression models were used. RESULTS: Our results show that perceived insufficient knowledge from school-based sexuality education was associated with higher odds of reporting not being able to take care of one's sexual health. The highest significant excess risk for insufficient knowledge was found among young people from sexual minorities. CONCLUSIONS: Young people in Sweden do not have equal abilities to receive knowledge needed to take care of their sexual health and thus attain sexual health literacy. There is an unequal distribution of perceived knowledge, and LGBTQI+ youth particularly face barriers in using school-based sexuality education as a resource for sexual health literacy.

Strengths of associations between depressive symptoms and loneliness, perfectionistic concerns, risky alcohol use and physical activity across levels of sleep quality in Swedish university students: A cross-sectional study.

Previous research shows that sleep quality may interact with some other predictors of depression, such that poor sleep could strengthen the association between these factors and depression. We aimed to determine the presence of statistical interactions between sleep quality and loneliness, risky alcohol use, perfectionistic concerns and/or physical inactivity in relation to depressive symptoms. Further, we aimed to describe the functional form of the statistical interactions and associations. We used a cross-sectional design and included 4262 Swedish university students. All measures were self-reported, sleep quality was measured with the Pittsburgh Sleep Quality Index, and depressive symptoms with the short-form Depression, Anxiety and Stress Scale. Regression models of increasing complexity (linear and non-linear, with and without interactions) were compared to determine the presence of associations and statistical interactions, and to explore the best functional form for these associations and interactions. Out-of-sample R2 from repeated cross-validation was used to select the final models. We found that sleep quality was associated with depressive symptoms in all final models. Sleep quality showed a linear interaction with perfectionistic concerns in relation to depressive symptoms, such that perfectionistic concerns were more strongly associated with depressive symptoms when sleep quality was poor. Loneliness, risky alcohol use and physical inactivity were non-linearly associated with depressive symptoms but did not interact with sleep quality. We concluded that out of the four examined variables, only perfectionistic concerns interacted with sleep quality in relation to depressive symptoms. This interaction was weak and explained little of the overall variance in depressive symptoms.

Lifestyle characteristics in adolescent female football players: data from the Karolinska football Injury Cohort.

BACKGROUND: Normative values of lifestyle characteristics in adolescent female football players may be used by clinicians and coaches to take actions because the potential important for well-being, performance on the pitch, and risk of injury. The aim was to report descriptive characteristics of lifestyle factors in adolescent female football players and potential changes over 1 year. METHODS: We included 419 adolescent competitive female football players from 12 clubs and 27 teams (age 14 ± 1 years, range 12-17 years) and 286 were followed over 1 year. The players completed an extensive questionnaire regarding demographics, football-related factors, and lifestyle factors including tobacco consumption, alcohol use, medicine intake, eating and sleeping habits, well-being, stress, coping, and passion. Baseline data are presented for the total cohort and separately for 4 age groups (12, 13, 14, and 15-17 years). RESULTS: 12% skipped breakfast, 8% skipped lunch and 11% used protein supplements several days per week. 16% slept less than 8 h/night, 8% had impaired sleep with daytime consequences, and 22% stated that they were tired in daily activities several days per week. 32% experienced stress some or most days/week and 24% were classified as having psychological distress. Medicine intake (23% vs. 34%), skipping breakfast or lunch several days per week (10% vs. 47% and 20 vs. 33%), tiredness (20% vs. 27%), stress (26% vs. 40%), and psychological distress (27% vs. 37%) increased significantly (P = 0.031 to < 0.001) at the 1-year follow-up. CONCLUSION: Many adolescent female football players skip breakfast and lunch, have insufficient sleep, experience stress and are classified as having psychological distress. These factors increased over 1 year.

Normative values and changes in range of motion, strength, and functional performance over 1 year in adolescent female football players: Data from 418 players in the Karolinska football Injury Cohort study.

OBJECTIVE: To study normative values of range of motion (ROM), strength, and functional performance and investigate changes over 1 year in adolescent female football players. DESIGN: Cross-sectional. PARTICIPANTS: 418 adolescent female football players aged 12-17 years. MAIN OUTCOME MEASURES: The physical characteristic assessments included (1) ROM assessment of the trunk, hips, and ankles; (2) strength measures (maximal isometric and eccentric strength for the trunk, hips, and knees, and strength endurance for the neck, back, trunk and calves), and (3) functional performance (the one-leg long box jump test and the square hop test). RESULTS: Older players were stronger, but not when normalized to body weight. Only small differences in ROM regarding age were found. ROM increased over 1 year in most measurements with the largest change in hip external rotation, which increased by 6-7° (Cohen's d = 0.83-0.87). Hip (d = 0.28-1.07) and knee (d = 0.38-0.53) muscle strength and the square hop test (d = 0.71-0.99) improved over 1 year. CONCLUSIONS: Normative values for ROM and strength assessments of neck, back, trunk, hips, knees, calves and ankles are presented for adolescent female football players. Generally, fluctuations in ROM were small with little clinical meaning, whereas strength improved over 1 year.

The Effect of Shoulder and Knee Exercise Programmes on the Risk of Shoulder and Knee Injuries in Adolescent Elite Handball Players: A Three-Armed Cluster Randomised Controlled Trial.

BACKGROUND: The risk of injury in adolescent handball is high, and shoulder and knee injuries are among the most frequent and burdensome. The Swedish Knee Control programme reduced the risk of anterior cruciate ligament injuries in female youth football players and traumatic knee injuries in male and female youth floorball players. However, to date, Knee Control has not been evaluated in an elite youth sport setting. The literature on the prevention of shoulder injuries in sport is scarce, and there are to our knowledge no previous studies evaluating the preventative efficacy of injury prevention exercise programmes (IPEPs) on shoulder injuries in adolescent handball players. OBJECTIVES: To study the preventive efficacy of IPEPs on shoulder and knee injuries in adolescent elite handball players. METHODS: Eighteen Swedish handball-profiled secondary schools (clusters) with players aged 15-19 years, 54% males were randomised into either the Shoulder Group or Knee Group (interventions) or a Control Group. Players in the Shoulder Group were instructed to perform the Shoulder Control programme, and  players in the Knee Group to perform the Knee Control programme, three times per week during May 2018 to May 2019. Control Group players continued their usual training. Outcomes were shoulder and knee injuries defined by the Oslo Sports Trauma Research Center Overuse Injury Questionnaire. Intention-to-treat analyses were performed using Cox regression models with hazard rate ratios (HRRs) with corresponding 95% confidence intervals (CI). RESULTS: Six clusters (199 players) in the Shoulder Group, six clusters (216 players) in the Knee Group and six clusters (212 players) in the Control Group were included. There were 100 shoulder injuries and 156 knee injuries. The Shoulder Group had a 56% lower shoulder injury rate, HRR 0.44 (95% CI 0.29 to 0.68), and the Knee Group had a 31% lower knee injury rate, HRR 0.69 (95% CI 0.49 to 0.97) than the Control Group. The absolute risk reduction was 11% and 8%, and the number needed to treat was 9 and 13, respectively. CONCLUSIONS: Adolescent elite handball players who performed the Shoulder Control and the Knee Control programmes had a lower risk of shoulder and knee injuries, respectively, than players who continued their usual training. Further research on how these two programmes can be combined to reduce knee and shoulder injuries in a time effective way is warranted. Trial registration ISRCTN15946352. Key points The burden of knee and shoulder injuries in handball is high. The Shoulder Control programme reduces the risk and overall burden of shoulder injuries in adolescent elite handball players. The Knee Control programme reduces the risk and overall burden of knee injuries in adolescent elite handball players.

Lifestyle behaviors in Swedish university students before and during the first six months of the COVID-19 pandemic: a cohort study.

BACKGROUND: Changes in Swedish university students' lifestyle behaviors during the COVID-19 pandemic are unknown. This study aimed to assess physical activity, sitting time, meal frequency and risk substance use (alcohol, tobacco, and illicit use of drugs) in Swedish university students before and during the first six months of the COVID-19 pandemic, for all and stratified by age and sex. METHODS: Data were obtained from the Sustainable University Life cohort study in which web-based surveys were sent to university students repeatedly for one year. Baseline assessment (before the pandemic) was between August 2019-March 2020, follow-up 1 (FU1) between March-June 2020, and follow-up 2 (FU2) between June-September 2020. Participants reported weekly minutes of physical activity, daily sitting hours, meal frequency by weekly intake of different meals, and motivation for eating irregularly, if so. Also, harmful use of alcohol, tobacco and illicit drugs was assessed. Population means and differences with 95% confidence intervals (95% CI) in lifestyle behaviors between time points were calculated with Generalized Estimating Equations. RESULTS: 1877 students (73% women, mean age 26.5 years) answered the baseline survey. Weekly exercise decreased by -5.7 min (95% CI: -10.0, -1.5) and -7.7 min (95% CI: -12.6, -2.8) between baseline and FU1 and FU2, respectively. Weekly daily activities increased by 5.6 min (95% CI: 0.3, 11.7) and 14.2 min (95% CI: 7.9, 20.5) between baseline and FU1 and FU2. Daily sitting time decreased by -1.4 h (95% CI: -1.7, -1.2) between baseline and FU2. Breakfast intake increased by 0.2 days per week (95% CI: 0.1, 0.3) between baseline and FU2. Lunch intake decreased by -0.2 days per week (95% CI: -0.2, -0.1) between baseline and FU1 and by -0.2 days per week (95% CI: -0.3, -0.0) between baseline and FU2. Dinner intake decreased by -0.1 days per week (95% CI: -0.2, -0.0) between baseline and both FU1 and FU2. Only minor differences in risk substance use were observed. Similar changes were observed in analyses stratified by age and sex. CONCLUSIONS: Lifestyle behaviors in Swedish university students slightly improved during the first six months of the COVID-19 pandemic compared to before. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04465435 . 10/07/2020.

Waning infant pertussis during COVID-19 pandemic.

Measures to reduce the spread of COVID-19 have been associated with reduction in other respiratory infections. Results of a national Swedish cohort study of infant pertussis during April 2020-September 2021 were compared with those during January 2014-March 2020. The number of pertussis cases decreased significantly during the COVID-19 pandemic, from an average of 21 infant cases per quarter of a year before the pandemic to an average of 1 case per quarter during the pandemic. Swedish strategies to mitigate the spread of COVID-19 seem to have had an impact on pertussis incidence in infants.

Preseason Clinical Shoulder Test Results and Shoulder Injury Rate in Adolescent Elite Handball Players: A Prospective Study.

OBJECTIVE: To investigate whether adolescent elite female and male handball players with shoulder muscle weakness, deficits in shoulder rotation range of motion (ROM) or in joint position sense (JPS), or scapular dyskinesis in the preseason had a higher rate of new shoulder injuries compared to players without these characteristics. DESIGN: Prospective cohort study. METHODS: We studied 344 uninjured players (452 player-seasons, 50% female). We measured their shoulder strength in isometric external rotation (IER), isometric internal rotation (IIR), isometric abduction, and eccentric external rotation, as well as their shoulder ROM, JPS, and scapular dyskinesis, during the preseason. Players were monitored weekly regarding match and training hours and shoulder injuries during 1 or 2 seasons. We used multivariable Cox proportional hazard models to calculate hazard rate ratios related to the first injury and 95% confidence intervals (CIs). RESULTS: During 2 seasons, the participants reported 48 new shoulder injuries. In female players, the hazard rate ratio was 2.37 (95% CI: 1.03, 5.44) for IER weakness and 2.44 (95% CI: 1.06, 5.61) for IIR weakness. The hazard rate ratio was 0.85 (95% CI: 0.39, 1.83) for an IER/IIR ratio of less than 0.75 and 1.53 (95% CI: 0.36, 6.52) for scapular dyskinesis. In male players, the hazard rate ratio was 1.02 (95% CI: 0.44, 2.36) for IER weakness, 0.74 (95% CI: 0.31, 1.75) for IIR weakness, 2.0 (95% CI: 0.68, 5.92) for an IER/IIR ratio of less than 0.75, and 3.43 (95% CI: 1.49, 7.92) for scapular dyskinesis. There were no associations between new shoulder injuries and deficits in ROM or JPS. CONCLUSION: In adolescent elite handball, male players with preseason scapular dyskinesis and female players with preseason IIR or IER shoulder weakness had an increased shoulder injury rate. J Orthop Sports Phys Ther 2020;50(2):67-74. Epub 27 Nov 2019. doi:10.2519/jospt.2020.9044.

Socioeconomic disparities associated with 29 common infectious diseases in Sweden, 2005-14: an individually matched case-control study.

BACKGROUND: Although the association between low socioeconomic status and non-communicable diseases is well established, the effect of socioeconomic factors on many infectious diseases is less clear, particularly in high-income countries. We examined the associations between socioeconomic characteristics and 29 infections in Sweden. METHODS: We did an individually matched case-control study in Sweden. We defined a case as a person aged 18-65 years who was notified with one of 29 infections between 2005 and 2014, in Sweden. Cases were individually matched with respect to sex, age, and county of residence with five randomly selected controls. We extracted the data on the 29 infectious diseases from the electronic national register of notified infections and infectious diseases (SmiNet). We extracted information on country of birth, educational and employment status, and income of cases and controls from Statistics Sweden's population registers. We calculated adjusted matched odds ratios (amOR) using conditional logistic regression to examine the association between infections or groups of infections and place of birth, education, employment, and income. FINDINGS: We included 173 729 cases notified between Jan 1, 2005, and Dec 31, 2014 and 868 645 controls. Patients with invasive bacterial diseases, blood-borne infectious diseases, tuberculosis, and antibiotic-resistant infections were more likely to be unemployed (amOR 1·59, 95% CI 1·49-1·70; amOR 3·62, 3·48-3·76; amOR 1·88, 1·65-2·14; and amOR 1·73, 1·67-1·79, respectively), to have a lower educational attainment (amOR 1·24, 1·15-1·34; amOR 3·63, 3·45-3·81; amOR 2·14, 1·85-2·47; and amOR 1·07, 1·03-1·12, respectively), and to have a lowest income (amOR 1·52, 1·39-1·66; amOR 3·64, 3·41-3·89; amOR 3·17, 2·49-4·04; and amOR 1·2, 1·14-1·25, respectively). By contrast, patients with food-borne and water-borne infections were less likely than controls to be unemployed (amOR 0·74, 95% CI 0·72-0·76), to have lower education (amOR 0·75, 0·73-0·77), and lowest income (amOR 0·59, 0·58-0·61). INTERPRETATION: These findings indicate persistent socioeconomic inequalities in infectious diseases in an egalitarian high-income country with universal health care. We recommend using these findings to identify priority interventions and as a baseline to monitor programmes addressing socioeconomic inequalities in health. FUNDING: The Public Health Agency of Sweden.

Female adolescent elite handball players are more susceptible to shoulder problems than their male counterparts.

PURPOSE: Shoulder problems are frequent among senior elite handball players. The objective of this study was to assess the prevalence of shoulder problems among adolescent elite handball players and to investigate potential differences in gender, school grade, playing position and playing level. METHODS: During the 2014 and 2015 pre-season periods, 471 players (age 15-18 years, 54% female) completed a comprehensive baseline questionnaire regarding history of any shoulder pain and shoulder problems experienced during the past season. The players were monitored weekly for one competition season (September-April) regarding shoulder problems and the amount of match and training. Generalised linear models with a binomial link function were used to calculate a prevalence ratio (PR) with 95% confidence interval (CI) to compare the subgroups of players. RESULTS: In total, 110 players (23%) reported having substantial shoulder problems (defined as moderate/severe reduction in training volume, or moderate/severe reduction in performance, or complete inability to participate) at some point during the follow-up season, of which almost half reported complete inability to participate. Of those players reporting substantial problems, 43% (95% CI 39-48) did so for at least 3 consecutive weeks during the season. The prevalence was significantly higher in female players (PR 1.46, 95% 1.04-2.06) and in backcourt players (PR 1.58, 95% CI 1.08-2.32), but no differences were found for school grade (PR 1.21 95% CI 0.88-1.67) or playing level (PR 1.09 95% CI 0.76-1.56). CONCLUSIONS: The prevalence of substantial shoulder problems in adolescent elite handball players is high, especially among females, and this warrants further studies on risk factors for shoulder injury and the development of prevention strategies in handball players already before the age of 15. These findings also highlight the importance of introducing a clinical monitoring programme on a routine basis and improving the medical support, taking gender-related aspects into consideration, at handball-profiled secondary schools. LEVEL OF EVIDENCE: II.

A prospective cohort study identifying risk factors for shoulder injuries in adolescent elite handball players: the Karolinska Handball Study (KHAST) study protocol.

BACKGROUND: Handball is a physical contact sport that includes frequent overhead throwing, and this combination leads to a high rate of shoulder injuries. Several factors have been associated with shoulder injuries in overhead athletes, but strong scientific evidence is lacking for most suggested risk factors. We therefore designed the Karolinska Handball Study (KHAST) with the aim to identify risk factors for shoulder injuries in adolescent male and female elite handball players studying at handball-profiled secondary schools in Sweden. Secondary objectives are to investigate whether shoulder function changes during the competition season and whether the physical profile of the players changes during their time in secondary school. METHODS: Players aged 15 to 19 years were included during the pre-season period of the 2014-2015 and the 2015-2016 seasons. At inclusion, players signed informed consent and filled in a questionnaire regarding playing position, playing level, previous handball experience, history of shoulder problems and athletic identity. Players also completed a detailed test battery at baseline evaluating the shoulder, neck and trunk. Players were then prospectively monitored weekly during the 2014-2015 and/or 2015-2016 competitive seasons regarding injuries and training/match workload. Results from the annual routine physical tests in the secondary school curriculum including bench press, deep squat, hand grip strength, clean lifts, squat jumps, counter movement jumps, <30 m sprints, chins, dips and Cooper's test will be collected until the end of the competitive season 2017-2018. The primary outcome is the incidence of shoulder injuries and shoulder problems. The secondary outcome is the prevalence of shoulder injuries and shoulder problems. DISCUSSION: Shoulder problems are frequent among handball players and a reduction of these injuries is therefore warranted. However, in order to introduce appropriate preventive measures, a detailed understanding of the underlying risk factors is needed. Our study has a high potential to identify important risk factors for shoulder injuries in adolescent elite handball players owing to a large study sample, a high response rate, data collection during consecutive seasons, and recording of potential confounding factors.

Dense genotyping of immune-related loci identifies HLA variants associated with increased risk of collagenous colitis.

OBJECTIVE: Collagenous colitis (CC) is a major cause of chronic non-bloody diarrhoea, particularly in the elderly female population. The aetiology of CC is unknown, and still poor is the understanding of its pathogenesis. This possibly involves dysregulated inflammation and immune-mediated reactions in genetically predisposed individuals, but the contribution of genetic factors to CC is underinvestigated. We systematically tested immune-related genes known to impact the risk of several autoimmune diseases for their potential CC-predisposing role. DESIGN: Three independent cohorts of histologically confirmed CC cases (N=314) and controls (N=4299) from Sweden and Germany were included in a 2-step association analysis. Immunochip and targeted single nucleotide polymorphism (SNP) genotype data were produced, respectively, for discovery and replication purposes. Classical human leucocyte antigen (HLA) variants at 2-digit and 4-digit resolution were obtained via imputation from single marker genotypes. SNPs and HLA variants passing quality control filters were tested for association with CC with logistic regression adjusting for age, sex and country of origin. RESULTS: Forty-two markers gave rise to genome-wide significant association signals, all contained within the HLA region on chromosome 6 (best p=4.2×10-10 for SNP rs4143332). Among the HLA variants, most pronounced risk effects were observed for 8.1 haplotype alleles including DQ2.5, which was targeted and confirmed in the replication data set (p=2.3×10-11; OR=2.06; 95% CI (1.67 to 2.55) in the combined analysis). CONCLUSIONS: HLA genotype associates with CC, thus implicating HLA-related immune mechanisms in its pathogenesis.

An Immunochip-based interaction study of contrasting interaction effects with smoking in ACPA-positive versus ACPA-negative rheumatoid arthritis.

OBJECTIVE: To investigate the gene-environment interaction between smoking and single nucleotide polymorphisms (SNPs), using Immunochip material, on the risk of developing either of two serologically defined subsets of RA. METHODS: Interaction between smoking and 133,648 genetic markers from the Immunochip was examined for two RA subsets, defined by the presence or absence of ACPA. A total of 1590 ACPA-positive and 891 ACPA-negative cases were compared with 1856 controls in the Swedish Epidemiological Investigation of RA (EIRA) case-control study. Logistic regression models were used to determine the presence of interaction. The proportion attributable to interaction was calculated for each smoking-SNP pair. Replication was carried out in an independent dataset from northern Sweden. To further validate and extend the results, interaction analysis was also performed using genome-wide association studies data on EIRA individuals. RESULTS: In ACPA-positive RA, 102 SNPs interacted significantly with smoking, after Bonferroni correction. All 102 SNPs were located in the HLA region, mainly within the HLA class II region, 51 of which were replicated. No additional loci outside chromosome 6 were identified in the genome-wide association studies validation. After adjusting for HLA-DRB1 shared epitope, 15 smoking-SNP pairs remained significant for ACPA-positive RA, with 8 of these replicated (loci: BTNL2, HLA-DRA, HLA-DRB5, HLA-DQA1, HLA-DOB and TAP2). For ACPA-negative RA, no smoking-SNP pairs passed the threshold for significance. CONCLUSION: Our study presents extended gene variation patterns involved in gene-smoking interaction in ACPA-positive, but not ACPA-negative, RA. Notably, variants in HLA-DRB1 and those in additional genes within the MHC class II region, but not in any other gene regions, showed interaction with smoking.

Parity influences the severity of ACPA-negative early rheumatoid arthritis: a cohort study based on the Swedish EIRA material.

BACKGROUND: In women with rheumatoid arthritis (RA) it has been observed that during pregnancy a majority of patients experience amelioration, but after delivery a relapse of the disease is common. However, there are few studies, with diverging results, addressing the effect of parity on the severity of RA over time. Our aim was to explore the impact of parity, with stratification for anti-citrullinated protein antibody (ACPA) status as well as for onset during reproductive age or not. METHODS: Female RA cases aged 18-70 years were recruited for the Epidemiological Investigation of Rheumatoid Arthritis (EIRA). Information on disease severity (the health assessment questionnaire (HAQ) and the disease activity score 28 (DAS28)) was retrieved from the Swedish Rheumatology Quality Register at inclusion and 3, 6, 12 and 24 months after diagnosis. Mixed models were used to compare mean DAS28 and HAQ scores over time in parous and nulliparous women. Mean differences at individual follow-up visits were compared using analysis of covariance. The odds of having DAS28 or HAQ above the median in parous verus nulliparous women were estimated in logistic regression models. RESULTS: A total of 1237 female cases (mean age 51 years, 65 % ACPA-positive) were included. ACPA-negative parous women, aged 18-44 years, had on average 1.17 units higher DAS28 (p < 0.001) and 0.43 units higher HAQ score (p < 0.001) compared to nulliparous women during the follow-up time, adjusted for age. In this subgroup, the average DAS28 and HAQ scores were significantly higher in parous women at all follow-up time points. Younger parous ACPA-negative women were significantly more likely to have DAS28 and HAQ values above the median compared to nulliparous women at all follow-up visits. No association between parity and severity of ACPA-positive disease was observed. CONCLUSIONS: Parity was a predictor of a more severe RA among ACPA-negative younger women, which might indicate that immunomodulatory changes during and after pregnancy affect RA severity, in particular for the ACPA-negative RA phenotype.

Association between Prediagnostic Allergy-Related Serum Cytokines and Glioma.

Allergy is inversely related to glioma risk. To determine whether prediagnostic allergy-related serum proteins are associated with glioma, we conducted a nested case-control study of seven cytokines (IL4, IL13, IL5, IL6, IL10, IFNG, TGFB2), two soluble cytokine receptors (sIL4RA, sIL13RA2) and three allergy-related transcription factors (FOXP3, STAT3, STAT6) using serum specimens from the Janus Serum Bank Cohort in Oslo, Norway. Blood donors subsequently diagnosed with glioma (n = 487) were matched to controls (n = 487) on age and date of blood draw and sex. We first estimated individual effects of the 12 serum proteins and then interactions between IL4 and IL13 and their receptors using conditional logistic regression. We next tested equality of case-control inter-correlations among the 12 serum proteins. We found that TGFB2 is inversely related to glioblastoma (Odds Ratio (OR) = 0.87, 95% Confidence Interval (CI)) = 0.76, 0.98). In addition, ≤ 5 years before diagnosis, we observed associations between IL4 (OR = 0.82, 95% CI = 0.66, 1.01), sIL4RA (OR = 0.80, 95% CI = 0.65, 1.00), their interaction (OR = 1.06, 95% CI = 1.01, 1.12) and glioblastoma. This interaction was apparent > 20 years before diagnosis (IL4-sIL4RA OR = 1.20, 95% CI = 1.05, 1.37). Findings for glioma were similar. Case correlations were different from control correlations stratified on time before diagnosis. Five years or less before diagnosis, correlations among case serum proteins were weaker than were those among controls. Our findings suggest that IL4 and sIL4RA reduce glioma risk long before diagnosis and early gliomagenesis affects circulating immune function proteins.

Circulating levels of interleukin 6 soluble receptor and its natural antagonist, sgp130, and the risk of myocardial infarction.

OBJECTIVE: To investigate the association between circulating levels of the soluble interleukin 6 receptor (sIL6R) and the soluble gp130 (sgp130) with myocardial infarction (MI) and to explore the potential interaction between sIL6R and sgp130 in this association. METHODS: Study population is the Stockholm Heart Epidemiology Program (SHEEP), a population-based case-control study. SIL6R (ng/mL) and sgp130 (ng/mL) levels were measured in serum samples from 682 and 664 MI cases and 1103 and 1062 controls, respectively. Odds ratios (with 95% CIs) for MI were calculated using unconditional logistic regression. We adjusted for age, sex, hospital catchment area (crude) and for hypertension, diabetes, hypercholesterolemia, body mass index and smoking (adjusted model). Synergy index (S) and attributable proportion (AP) were estimated as measures of biological interaction. RESULTS: Elevated concentrations of sIL6R (>75th percentile value) were associated with an increased occurrence of MI (compared to ≤75th percentile), with an adjusted OR of 1.4 (95% CI, 1.1-1.8). Very high (>90th percentile value) levels of sgp130 were associated with a reduced occurrence of MI [OR 0.7 (95% CI, 0.5-0.9)] (adjusted). There was an indication of a possible interaction between high sIL6R and low sgp130 (adjusted S score 1.7, 95% CI = 0.5-6.1; AP 0.19, 95% CI = -0.2-0.5), suggesting that low sgp130 levels may synergize with high sIL6R levels to increase risk of MI. CONCLUSIONS: sIL6R and sgp130 had opposing associations with MI. Indeed, circulating sgp130 levels may modify the association of elevated sIL6R levels with MI.

To what extent is the familial risk of rheumatoid arthritis explained by established rheumatoid arthritis risk factors?

OBJECTIVE: Family history of rheumatoid arthritis (RA) is one of the strongest risk factors for developing RA, and information on family history is, therefore, routinely collected in clinical practice. However, as more genetic and environmental risk factors shared by relatives are identified, the importance of family history may diminish. The aim of this study was to determine how much of the familial risk of RA can be explained by established genetic and nongenetic risk factors. METHODS: History of RA among first-degree relatives of individuals in the Epidemiological Investigation of Rheumatoid Arthritis case-control study was assessed through linkage to the Swedish Multigeneration Register and the Swedish Patient Register. We used logistic regression models to investigate the decrease in familial risk after successive adjustment for combinations of nongenetic risk factors (smoking, alcohol intake, parity, silica exposure, body mass index, fatty fish consumption, and education), and genetic risk factors (shared epitope [SE] and 76 single-nucleotide polymorphisms [SNPs]). RESULTS: Established nongenetic risk factors did not explain familial risk of either seropositive or seronegative RA to any significant degree. Genetic risk factors accounted for a limited proportion of the familial risk of seropositive RA (unadjusted odds ratio [OR] 4.10, SE-adjusted OR 3.72, SNP-adjusted OR 3.46, and SE and SNP-adjusted OR 3.35). CONCLUSION: Established risk factors only provided an explanation for familial risk of RA in minor part, suggesting that many (familial) risk factors remain to be identified, in particular for seronegative RA. Family history of RA therefore remains an important clinical risk factor for RA, the value of which has not yet been superseded by other information. There is thus a need for further etiologic studies of both seropositive and seronegative RA.

Genetic risk scores and number of autoantibodies in patients with rheumatoid arthritis.

OBJECTIVE: Certain HLA-DRB1 alleles and single-nucleotide polymorphisms (SNPs) are associated with rheumatoid arthritis (RA). Our objective was to examine the combined effect of these associated variants, calculated as a cumulative genetic risk score (GRS) on RA predisposition, as well as the number of autoantibodies (none, one or two present). METHOD: We calculated four GRSs in 4956 patients and 4983 controls from four European countries. All four scores contained data on 22 non-HLA-risk SNPs, and three scores also contained HLA-DRB1 genotypes but had different HLA typing resolution. Most patients had data on both rheumatoid factor (RF) and anti-citrullinated proteins antibodies (ACPA). The GRSs were standardised (std.GRS) to account for population heterogeneity. Discrimination between patients and controls was examined by receiveroperating characteristics curves, and the four std.GRSs were compared across subgroups according to autoantibody status. RESULTS: The std.GRS improved its discriminatory ability between patients and controls when HLA-DRB1 data of higher resolution were added to the combined score. Patients had higher mean std.GRS than controls (p=7.9×10(-156)), and this score was significantly higher in patients with autoantibodies (shown for both RF and ACPA). Mean std.GRS was also higher in those with two versus one autoantibody (p=3.7×10(-23)) but was similar in patients without autoantibodies and controls (p=0.12). CONCLUSIONS: The GRS was associated with the number of autoantibodies and to both RF and ACPA positivity. ACPA play a more important role than RF with regards to the genetic risk profile, but stratification of patients according to both RF and ACPA may optimise future genetic studies.