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Alf Inge Hellevik,1,2 Marianne Bakke Johnsen,3,4 Arnulf Langhammer,1 Valborg Baste,5 Ove Furnes,6,7 Kjersti Storheim,3,4 John Anker Zwart,3,4 Gunnar Birkeland Flugsrud,2 Lars Nordsletten2,4 1The HUNT Research Centre, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, NTNU, Norwegian University of Science and Technology, Levanger, 2Division of Orthopaedic Surgery, Oslo University Hospital, Oslo, 3Research and Communication Unit for Musculoskeletal Health, Division of Clinical Neuroscience, Oslo University Hospital, Oslo, 4Faculty of Medicine, University of Oslo, Oslo, 5Uni Research Health, Bergen, 6The Norwegian Arthroplasty Register, Department of Orthopedic Surgery, Haukeland University Hospital, Bergen, 7Department of Clinical Medicine, Institute of Medicine and Dentistry, University of Bergen, Bergen, Norway Objective: Biochemical changes associated with obesity may accelerate osteoarthritis beyond the effect of mechanical factors. This study investigated whether metabolic syndrome and its components (visceral obesity, hypertension, dyslipidemia and insulin resistance) were risk factors for subsequent total hip replacement (THR) or total knee replacement (TKR) due to primary osteoarthritis.Design: In this prospective cohort study, data from the second survey of the Nord-Trøndelag Health Study 2 (HUNT2) were linked to the Norwegian Arthroplasty Register for identification of the outcome of THR or TKR. The analyses were stratified by age (

Objectives: To evaluate the feasibility of recruitment, appointment adherence, intervention compliance, acceptance and comprehensibility, in addition to retention rate and data completeness. An ancillary aim was to describe within-group changes in the secondary outcome measures (patient-reported and performance-based)., Design: A single-centre, three-armed, randomised controlled feasibility trial with a parallel design, with follow-up after 3 and 6 months., Setting: Participants were recruited from the outpatient clinic at Oslo University Hospital., Participants: Patients with lateral epicondylalgia, commonly known as tennis elbow., Interventions: Participants were randomised in a 1:1:1 ratio to heavy slow resistance training, radial extracorporeal shock wave therapy or information and advice., Main Outcome Measures: Feasibility was assessed according to a priori criteria for success., Results: In total, 89 patients were screened for eligibility, and 69 (78%) patients were eligible for randomisation. 60 (92%) participants were randomised which gave a recruitment rate of 3.4 per month (against an a priori success cut-off of 3.75). The participants rated all the interventions as acceptable and comprehensive. Only 6 of 19 (32%) did comply with heavy slow resistance training. Retention rate and completeness of data were successful at 3 months. At 6 months, the retention rate was below the criteria for success. Patient-reported and performance-based outcomes improved in all groups., Conclusion: The current study shows that the process of recruitment and the retention rate at follow-up can be feasible with minor amendments. Participants had low compliance with heavy slow resistance training mainly due to pain aggravation, which suggests that this intervention was not suitable for patients with tennis elbow. Shock wave therapy and information and advice should be investigated further in a full-scale randomised controlled trial including sham shock wave therapy., Trial Registration Number: NCT04803825., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Objectives: To identify, critically appraise and evaluate the performance measures of the available prediction models for outcomes in people with low back pain (LBP) receiving conservative treatment., Study Design and Setting: In this systematic review, literature searches were conducted in Embase, Medline, and cumulative index of nursing and allied health literature from their inception until February 2024. Studies containing follow-up assessment (eg, prospective cohort studies, registry-based studies) investigating prediction models of outcomes (eg, pain intensity and disability) for people with LBP receiving conservative treatment were included. Two independent reviewers performed the study selection, the data extraction using the Checklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies, and risk of bias assessment using the Prediction model Risk of Bias Assessment. Findings of individual studies were reported narratively taking into account the discrimination and calibration measures of the prediction models., Results: Seventy-five studies developing or investigating the validity of 216 models were included in this review. Most prediction models investigated people receiving physiotherapy treatment and most models included sociodemographic variables, clinical features, and self-reported measures as predictors. The discriminatory capacity of the internal validity of the 27 prediction models for pain intensity varied greatly showing a c-statistic ranging from 0.48 to 0.94. Similarly, the discriminatory capacity for 31 models for disability had the same pattern showing a c-statistic ranging from 0.48 to 0.86. The calibration measures of the internal validity of the prediction models predicting pain intensity and disability showed to be adequate. Only one of 3 studies testing the external validity of models to predict pain intensity and disability and reported both discrimination and calibration measures, which showed to be inadequate. The prediction models predicting the secondary outcomes (eg, self-reported recovery, quality of life, return to work) showed varied performance measures for internal validity, and only 2 studies tested the external validity of models although they did not provide performance the performance measures., Conclusion: Several prediction models have been developed for people with LBP receiving conservative treatment; however, most show inadequate discriminatory validity. A few studies externally validated the prediction models and future studies should focus on testing this before implementing in clinical practice., Competing Interests: Declaration of competing interest There are no competing interests for any author., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Greater Trochanteric Pain Syndrome (GTPS) is a common chronic musculoskeletal condition that may affect physical function, quality of life and sleep. The Victorian Institute of Sport Assessment-Gluteal questionnaire (VISA-G) has been developed as a Patient-Reported Outcome Measurement (PROM) to address pain, everyday activities, physical activities, and difficulty with weight bearing activities. The aim of the study was to test the reliability, validity and floor and ceiling effects of the Norwegian version of the VISA-G (VISA-G-Norwegian) in a population with GTPS in a specialist health care setting., Methods: This psychometric evaluation of the VISA-G-Norwegian questionnaire were conducted with a prospective observational design. The VISA-G was translated into Norwegian following recommended guidelines. A subgroup repeated the VISA-G-Norwegian a week after the initial submission. For the reliability, the Intraclass Correlation Coefficient (ICC 2.1 ), Standard Error of the Measurement (SEM) and the Smallest Detectable Change (SDC 95% ) were calculated. Internal consistency was measured using a Cronbach´s alpha. Floor and ceiling effects were evaluated, and construct validity was assessed with three a priori hypotheses., Results: 78 participants were included in the study of which 47 stable participants undertook the test-retest reliability arm of the study. The ICC 2.1 for the total score was 0.85 (95% CI 0.68, 0.92), SEM was 6.6 points and SDC 95% 18.4 points. Cronbach`s alpha was 0.77 (95% CI 0.69, 0.84). No floor or ceiling effects were found in the total score, but ceiling effect was found in three of the eight items. For construct validity, one of the three hypotheses were confirmed. VISA-G-Norwegian correlated to the modified Harris Hip Score (mHHS), Oswestry Disability Questionnaire (ODI) and Numeric Pain Rating Scale (NPRS), 0.64, -0.75 and - 0.63 respectively., Conclusion: The VISA-G-Norwegian has acceptable reliability and validity, despite ceiling effect of individual items. The large SDC 95% should be considered when measuring change in similar cohorts with GTPS. For a potential future version, it would be recommended to consider response options for questions with ceiling effect and the comprehensibility of question eight., Trial Registration: Registered at ClinicalTrials.gov the 28/02/2020 (NCT04289922)., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objectives: The purpose of this study was to investigate whether self-reported musculoskeletal pain (MSP) was associated with a future anterior cruciate ligament reconstruction (ACLR)., Methods: In this population-based prospective cohort study, we included 8087 participants from the adolescent part of the Trøndelag Health Study (Young-HUNT) in Norway. The exposure was self-reported MSP from the Young-HUNT3 study (2006-2008), which was categorised into two MSP load groups (high MSP and low MSP) based on frequency and number of pain sites. The outcome was ACLRs recorded in the Norwegian Knee Ligament Register between 2006 and 2019. Logistic regression was used to investigate association between MSP load and ACLR, given as ORs with 95% CIs. All tests were two-sided and p values of ≤0.05 were considered statistically significant., Results: 8087 adolescents were included. We identified a total of 99 ACLRs, with 6 ACLRs (0.9%) in adolescents who reported high MSP load and 93 ACLRs (1.3%) among those who reported low MSP load. Adolescents reporting high MSP load had 23% lower odds of an ACLR (OR 0.77, 95% CI 0.31 to 1.91) compared with adolescents with low MSP load. However, the CIs were very wide., Conclusion: Self-reported high MSP load in adolescents was not associated with increased risk of future ACLR. Although the number of participants was high, the relatively few cases of ACLR mean that we cannot be conclusive about the presence or absence of an association., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: At present, there is no cure for osteoarthritis (OA), but severe hip joint degeneration can require total hip arthroplasty (THA). The literature on OA after elite sport is limited. We hypothesise that elite athletic activity increases the risk of receiving a THA later in life., Methods: We linked a cohort of former Norwegian world-class athletes (1402 females and 1902 males, active 1936-2006) to the Norwegian Arthroplasty Register (THA performed 1987-2020). We used standardised incidence ratio (SIR), one-minus Kaplan-Meier and relative Cox regression (relative HR, RHR), with 95% CIs, and funnel plots at age 75, to assess THA risk for different sport disciplines, joint impact categories of sport disciplines and sex. The risk of THA for the corresponding general Norwegian population was used as reference., Results: We found an overall increased risk for THA for the former elite athletes (SIR 2.11, 95% CI 1.82 to 2.40) at age 75 years, compared with the general population. THA risk at age 75 years was 11.6% for female athletes and 8.3% for male athletes. SIR was 1.90 (95% CI 1.49 to 2.31) for female and 2.28 (95% CI 1.87 to 2.70) for male athletes. Among males, high joint impact sport disciplines were associated with increased risk compared with low-impact sport disciplines (RHR 1.81, 95% CI 1.06 to 3.08, p=0.029)., Conclusion: Having been an elite athlete was associated with a doubling of THA risk compared with the general population for both sexes. High joint impact sport disciplines were associated with subsequent THA for male athletes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To examine the possible bidirectional association between insomnia and comorbid chronic low back pain (LBP) and lower limb pain and to explore whether high-sensitivity C-reactive protein (hsCRP) amplifies these associations., Methods: We calculated adjusted risk ratios (RR) with 95% confidence intervals (CI) for the development of insomnia and mild-to-severe chronic LBP and lower limb pain at 11 years follow-up in participants aged ≥32 years and with hsCRP ≤10 mg/L at baseline in 2007-2008: 3,714 without chronic LBP or lower limb pain (sample 1) and 7,892 without insomnia (sample 2)., Results: Compared to participants without chronic pain, participants with comorbid chronic LBP and lower limb pain had a RR of insomnia of 1.37 (95% CI 1.12-1.66). Compared with participants without insomnia, participants with insomnia did not have an increased risk of comorbid chronic LBP and lower limb pain (RR: 1.06, 95% CI 0.76-1.46); however, participants with insomnia had a RR of chronic LBP of 1.20 (95% CI 1.02-1.42). There was no strong amplifying effect of elevated hsCRP (3.00-10.0 mg/L) on these associations., Conclusions: These findings suggest that elevated hsCRP does not amplify the associations between insomnia and mild-to-severe chronic LBP and lower limb pain. Further research using data on the temporal relation between insomnia, chronic pain, and inflammatory responses are required to fully understand the causal pathways., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Migraine affects over a billion individuals worldwide but its genetic underpinning remains largely unknown. Here, we performed a genome-wide association study of 102,084 migraine cases and 771,257 controls and identified 123 loci, of which 86 are previously unknown. These loci provide an opportunity to evaluate shared and distinct genetic components in the two main migraine subtypes: migraine with aura and migraine without aura. Stratification of the risk loci using 29,679 cases with subtype information indicated three risk variants that seem specific for migraine with aura (in HMOX2, CACNA1A and MPPED2), two that seem specific for migraine without aura (near SPINK2 and near FECH) and nine that increase susceptibility for migraine regardless of subtype. The new risk loci include genes encoding recent migraine-specific drug targets, namely calcitonin gene-related peptide (CALCA/CALCB) and serotonin 1F receptor (HTR1F). Overall, genomic annotations among migraine-associated variants were enriched in both vascular and central nervous system tissue/cell types, supporting unequivocally that neurovascular mechanisms underlie migraine pathophysiology., (© 2022. The Author(s).)

Late-onset Alzheimer's disease is a prevalent age-related polygenic disease that accounts for 50-70% of dementia cases. Currently, only a fraction of the genetic variants underlying Alzheimer's disease have been identified. Here we show that increased sample sizes allowed identification of seven previously unidentified genetic loci contributing to Alzheimer's disease. This study highlights microglia, immune cells and protein catabolism as relevant to late-onset Alzheimer's disease, while identifying and prioritizing previously unidentified genes of potential interest. We anticipate that these results can be included in larger meta-analyses of Alzheimer's disease to identify further genetic variants that contribute to Alzheimer's pathology., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Objectives: To investigate the impact of educational level and employment status on change in pain intensity after treatment among patients with knee and hip osteoarthritis (OA)., Design: A prospective cohort study., Setting and Participants: We analysed 22 588 patients participating in the Good Life with osteoArthritis in Denmark (GLA:D). GLA:D consists of two patient education sessions and 12 supervised exercise sessions., Primary Outcome: Baseline educational level and employment status were used as exposures. We investigated the impact of both exposures separately on mean change in pain intensity (visual analogue scale 0-100 mm) from baseline to immediately after treatment (approximately 3 months) and at 12 months, using linear mixed models., Results: On average, all patients improved in pain intensity. The average improvement in pain did not differ by educational level, except for one group. Patients with long-term education had less improvement after treatment (2.0 mm, 95% CI 0.8 to 3.1) and at 12 months (2.0 mm, 95% CI 0.6 to 3.4) compared with primary school only (reference). According to employment status, patients on sick leave had the greatest improvement in pain after treatment (-3.4, 95% CI -4.9 to -1.9) and at 12 months (-4.5, 95% CI -6.4 to -2.6) compared with retired patients (reference)., Conclusions: On average, all patients reported improvement in pain at short-term and long-term follow-up. Change in pain intensity did not substantially differ by educational level or employment status, as the absolute differences were small and most likely not clinically important., Competing Interests: Competing interests: ER is deputy editor of Osteoarthritis and Cartilage, the developer of the Knee injury and Osteoarthritis Outcome Score (KOOS) and several other freely available patient-reported outcome measures and cofounder of Good Life with Osteoarthritis in Denmark (GLA:D), a not-for-profit initiative hosted at University of Southern Denmark aimed at implementing clinical guidelines for osteoarthritis in clinical practice. STS is associate editor of the Journal of Orthopaedic & Sports Physical Therapy, has received grants from The Lundbeck Foundation, personal fees from Munksgaard, all of which are outside the submitted work. He is cofounder of GLA:D., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Rupture of an intracranial aneurysm leads to subarachnoid hemorrhage, a severe type of stroke. To discover new risk loci and the genetic architecture of intracranial aneurysms, we performed a cross-ancestry, genome-wide association study in 10,754 cases and 306,882 controls of European and East Asian ancestry. We discovered 17 risk loci, 11 of which are new. We reveal a polygenic architecture and explain over half of the disease heritability. We show a high genetic correlation between ruptured and unruptured intracranial aneurysms. We also find a suggestive role for endothelial cells by using gene mapping and heritability enrichment. Drug-target enrichment shows pleiotropy between intracranial aneurysms and antiepileptic and sex hormone drugs, providing insights into intracranial aneurysm pathophysiology. Finally, genetic risks for smoking and high blood pressure, the two main clinical risk factors, play important roles in intracranial aneurysm risk, and drive most of the genetic correlation between intracranial aneurysms and other cerebrovascular traits.

Objective: To develop and externally validate prediction models for incident hand osteoarthritis (OA) in a large population-based cohort of middle aged and older men and women., Design: We included 17,153 men and 18,682 women from a population-based cohort, aged 35-70 years at baseline (1995-1997). Incident hand OA were obtained from diagnostic codes in the Norwegian National Patient Register (1995-2018). We studied whether a range of self-reported and clinically measured predictors could predict hand OA, using the Area Under the receiver-operating Curve (AUC) from logistic regression. External validation of an existing prediction model for male hand OA was tested on discrimination in a sample of men. Bootstrapping was used to avoid overfitting., Results: The model for men showed modest discriminatory ability (AUC = 0.67, 95% CI 0.62-0.71). Adding a genetic risk score did not improve prediction. Similar discrimination was observed in the model for women (AUC = 0.62, 95% CI 0.59-0.64). Prediction was not improved by adding a genetic risk score or hormonal and reproductive factors. Applying external validation, similar results were observed among men in HUNT (The Nord-Trøndelag Health Study) as in the developmental sample (AUC = 0.62, 95% CI 0.57-0.65)., Conclusion: We developed prediction models for incident hand OA in men and women. For women, the model included body mass index (BMI), heavy physical work, high physical activity and perceived poor health. The model showed moderate discrimination. For men, we have shown that a prediction model including BMI, education and information on sleep can predict incident hand OA in several populations with moderate discriminative ability., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The global obesity epidemic raises long-term health concerns which underline the importance of preventive efforts. We aimed to investigate individual and combined effects of common health problems in adolescence on the probability of obesity in young adulthood. This prospective population-based study included data from participants in the Nord-Trøndelag Health Study in Norway (Young-HUNT1 (1995-1997), age 13-19, baseline) who participated in HUNT3 as young adults 11 years later (age 23-31). Exposure variables at baseline included self-reported physical activity, musculoskeletal pain, and psychological distress. We examined associations between exposure variables and the main outcome of obesity in young adulthood (BMI ≥ 30 kg/m 2 ) using univariate and multiple logistic regression, stratified by sex. Probabilities of obesity for given combinations of the exposure variables were visualized in risk matrixes. The study sample consisted of 1859 participants (43.6% boys). Higher probabilities of obesity in young adulthood were found across combinations of lower physical activity levels and presence of musculoskeletal pain in adolescence. Additional adverse effects of psychological distress were low. Proactive intervention strategies to promote physical activity and facilitate sports participation for all adolescents, whilst addressing musculoskeletal pain and its potential individual causes, could prove helpful to prevent development of obesity in young adulthood.

Objective: It is currently unknown whether osteoarthritis (OA) is inherited mainly from the mother, father, or both. This study was undertaken to explore the effect of maternal and paternal factors on hip, knee, and hand OA in offspring., Methods: Participants from the Musculoskeletal Pain in Ullensaker Study (MUST) (69% female; mean ± SD age 64 ± 9 years) and a Norwegian OA twin study (Nor-Twin) (56% female; 49 ± 11 years) reported whether their mother and/or father had OA. Using a recurrence risk estimation approach, we calculated whether maternal and paternal OA increased the risk of 1) surgically defined hip and knee OA (i.e., total joint replacement) and 2) clinically defined hip, knee, and hand OA (i.e., the American College of Rheumatology criteria) using logistic regression. Relative risks (RRs) with 95% confidence intervals (95% CIs) were calculated., Results: Maternal OA consistently increased the risk of offspring OA across different OA locations and severities. Having a mother with OA increased the risk of any OA in daughters (RR 1.13 [95% CI 1.02-1.25] in the MUST cohort; RR 1.44 [95% CI 1.05-1.97] in the Nor-Twin cohort) but not (or with less certainty) in sons (RR 1.16 [95% CI 0.95-1.43] in the MUST cohort; RR 1.31 [95% CI 0.71-2.41] in the Nor-Twin cohort). Having a father with OA was less likely to increase the risk of any OA in daughters (RR 1.00 [95% CI 0.85-1.16] in the MUST cohort; RR 1.52 [95% CI 0.94-2.46] in the Nor-Twin cohort) and sons (RR 1.08 [95% CI 0.83-1.41] in the MUST cohort; RR 0.93 [95% CI 0.35-2.48] in the Nor-Twin cohort)., Conclusion: OA in the mother increased the risk of surgically and clinically defined hip, knee, and hand OA in offspring, particularly in daughters. Our findings imply that heredity of OA may be linked to maternal genes and/or maternal-specific factors such as the fetal environment., (© 2019 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.)

Objectives: Knowledge of how physical activity (PA) and sport participation are related to mental health throughout adolescence is scarce. Our objective was to describe PA levels and sport participation in a population-based sample of adolescents, and to explore how they relate to mental health in different age groups., Design: A population-based cross-sectional study., Setting and Participants: The adolescent part of the Nord-Trøndelag Health Study, a Norwegian population-based health survey, conducted from 2006 to 2008. Of 10 464 invited participants (age 13-19 years), 7619 (73%) participated, of whom 3785 (50%) were boys., Outcome Measures: Mental health outcomes included psychological distress assessed using a short version of the Hopkins Symptom Check List Five items, self-esteem assessed using a short version of the Rosenberg Self-Esteem Scale and life satisfaction assessed with a single-item satisfaction with life measure., Method: Logistic regression models were used to estimate the likelihood of psychological distress, low self-esteem and low life satisfaction, according to self-reported PA level and type of sport participation, stratified by gender and school level (junior vs senior high school)., Results: Fewer senior high school students participated in team sports compared with junior high school students (p<0.001). Physically active adolescents and participants in team sports had higher self-esteem and life satisfaction. A high PA level, compared with a low PA level, was associated with reduced odds of psychological distress among senior high school students (OR 0.63, 95% CI 0.46 to 0.86 for girls and OR 0.46, 95% CI 0.27 to 0.79 for boys). Team sport participation was associated with reduced odds of psychological distress in senior high school girls., Conclusion: A high PA level was favourably associated with various dimensions of mental health, especially for adolescents in senior high school. Team sport participation may have a positive impact on mental health and should, therefore, be encouraged., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: It has been suggested that smoking is associated with reduced risk of knee osteoarthritis (OA). However, supplementary studies are needed to further investigate any such potential association. Thus, our aim was to examine the relationship between smoking and early or more established knee OA in a cohort of relatively young patients with meniscal tears., Methods: This cross-sectional study included 620 participants from the Knee Arthroscopy Cohort Southern Denmark (KACS) undergoing knee arthroscopy for a meniscal tear (mean age 49.2 (18.0-76.8) years). Recruitment of patients was performed between February 1, 2013, and January 31, 2015, at four different hospitals in Denmark. We defined early or more established knee OA as the combination of patient-reported frequent knee pain, degenerative meniscal tissue and presence of cartilage defects assessed by the operating surgeons. The relationship between smoking status and knee OA was examined by risk ratio (RR) with a 95% confidence interval (CI), estimated from logistic regression adjusted for age, sex, BMI, education, work status and level of physical activity., Results: The prevalence of early or more established knee OA was 37.7% in current smokers and 45.0% in non-smokers. We found no statistically significant association between current smoking and knee OA (adjusted RR 1.09, 95% CI 0.91-1.30)., Conclusions: This study found no relationship between current smoking and early or more established knee OA in a cohort of patients undergoing arthroscopic meniscal surgery. Thus, the inverse association between smoking and knee OA that has been suggested by previous studies was not confirmed.

Background and Purpose: Headache has been associated with various lifestyle and psychosocial factors, one of which is smoking. The aim of the present study was to investigate whether the association between smoking intensity and headache is likely to be causal., Method: A total of 58 316 participants from the Nord-Trøndelag Health (HUNT) study with information on headache status were genotyped for the rs1051730 C>T single-nucleotide polymorphism (SNP). The SNP was used as an instrument for smoking intensity in a Mendelian randomization analysis. The association between rs1051730 T alleles and headache was estimated by odds ratios with 95% confidence intervals. Additionally, the association between the SNP and migraine or non-migrainous headache versus no headache was investigated. All analyses were adjusted for age and sex., Results: There was no strong evidence that the rs1051730 T allele was associated with headache in ever smokers (odds ratio 0.99, 95% confidence interval 0.95-1.02). Similarly, there was no association between the rs1051730 T allele and migraine or non-migrainous headache versus no headache., Conclusion: The findings from this study do not support that there is a strong causal relationship between smoking intensity and any type of headache. Larger Mendelian randomization studies are required to examine whether higher smoking quantity can lead to a moderate increase in the risk of headache subtypes., (© 2018 EAN.)

To investigate the total effect of smoking on total hip or knee replacement (THR/TKR) due to primary osteoarthritis (OA) and to quantify the indirect effect of smoking through body mass index (BMI). Participants from the Nord-Trøndelag Health Study (the HUNT Study) were linked to the Norwegian Arthroplasty Register to detect the first THR or TKR due to primary OA. A mediation analysis was used to decompose the total effect of smoking into a direct and indirect effect. BMI was considered a mediator in the analysis. All effects were estimated as hazard ratios (HRs) with 95% confidence intervals (CIs). The indirect effect of smoking mediated through BMI was expressed as a percentage (proportion*100). In total 55 188 participants were followed up during 17.2 years (median). We identified 1322 THRs and 754 TKRs. For men, the total effect of current vs. never smoking revealed a decreased risk of THR (HR 0.59, 95% CI 0.46-0.76) and TKR (HR 0.47, 95% CI 0.32-0.66). For women, current smoking increased the risk of THR (HR 1.34, 95% CI 1.11-1.60). For men, 6% and 7% of the risk reduction for THR and TKR, respectively, was mediated by BMI. We found a negative association between smoking and THR or TKR for men. On the contrary, smoking was associated with increased risk of THR for women. Most of the effect of smoking on joint replacement risk remained unexplained by BMI.

Objective: To investigate whether parity, age at menarche, menopausal status, age at menopause, use of oral contraceptives (OC) or use of hormone replacement therapy (HRT) were associated with total knee replacement (TKR) or total hip replacement (THR) due to primary osteoarthritis., Method: In a prospective cohort study of 30,289 women from the second and third surveys of the Nord-Trøndelag Health Study, data were linked to the Norwegian Arthroplasty Register (NAR) in order to identify TKR or THR due to primary osteoarthritis. Cox proportional hazards models were used to estimate the hazard ratios (HRs)., Results: We observed 430 TKRs and 675 THRs during a mean follow-up time of 8.3 years. Increasing age at menarche was inversely associated with the risk of TKR (P-trend < 0.001). Past users and users of systemic HRT were at higher risk of TKR compared to never users (HR 1.42 (95% confidence interval (CI) 1.06-1.90) and HR 1.40 (95% CI 1.03-1.90), respectively). No association was found between parity, age at menarche, menopausal status, age at menopause, oral contraceptive use or HRT use and THR., Conclusion: We found that increasing age at menarche reduced the risk of TKR. Past users and users of systemic HRT were at higher risk of TKR compared to never users. Parity did not increase the risk of THR or TKR., (Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: Smoking has been associated with a reduced risk of hip and knee osteoarthritis (OA) and subsequent joint replacement. The aim of the present study was to assess whether the observed association is likely to be causal., Method: 55,745 participants of a population-based cohort were genotyped for the rs1051730 C > T single-nucleotide polymorphism (SNP), a proxy for smoking quantity among smokers. A Mendelian randomization analysis was performed using rs1051730 as an instrument to evaluate the causal role of smoking on the risk of hip or knee replacement (combined as total joint replacement (TJR)). Association between rs1051730 T alleles and TJR was estimated by hazard ratios (HRs) and 95% confidence intervals (CIs). All analyses were adjusted for age and sex., Results: Smoking quantity (no. of cigarettes) was inversely associated with TJR (HR 0.97, 95% CI 0.97-0.98). In the Mendelian randomization analysis, rs1051730 T alleles were associated with reduced risk of TJR among current smokers (HR 0.84, 95% CI 0.76-0.98, per T allele), however we found no evidence of association among former (HR 0.97, 95% CI 0.88-1.07) and never smokers (HR 0.97, 95% CI 0.89-1.06). Neither adjusting for body mass index (BMI), cardiovascular disease (CVD) nor accounting for the competing risk of mortality substantially changed the results., Conclusion: This study suggests that smoking may be causally associated with the reduced risk of TJR. Our findings add support to the inverse association found in previous observational studies. More research is needed to further elucidate the underlying mechanisms of this causal association., (Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Background: To study whether thyroid function was associated with risk of hip or knee replacement due to primary osteoarthritis., Methods: In a prospective cohort study, data from the second and third survey of the Nord-Trøndelag Health Study were linked to the Norwegian Arthroplasty Register in order to identify total hip or knee replacement as a result of primary osteoarthritis., Results: Among 37 891 participants without previously known thyroid disease we recorded 978 total hip replacements (THRs) and 538 total knee replacements (TKRs) during a median follow-up time of 15.7 years. The analyses were adjusted for sex, age, BMI (body mass index), smoking, physical activity and diabetes. We did not find any association between TSH (thyroid stimulating hormone) and THR or TKR due to osteoarthritis. Neither were changes in TSH over time, or overt hypo- or hyperthyroidism, associated with incidence of THR or TKR., Conclusion: No association was found between thyroid function and hip or knee joint replacement due to osteoarthritis.

Background: Prevalence of musculoskeletal pain among adolescents is high, and pain in adolescence increases the risk of chronic pain in adulthood. Studies have shown conflicting evidence regarding associations between physical activity and musculoskeletal pain, and few have evaluated the potential impact of sport participation on musculoskeletal pain in adolescent population samples., Purpose: To examine the associations between physical activity level, sport participation, and musculoskeletal pain in the neck and shoulders, low back, and lower extremities in a population-based sample of adolescents., Study Design: Cross-sectional study; Level of evidence 4., Methods: Data from the Nord-Trøndelag Health Study (Young-HUNT3) were used. All 10,464 adolescents in the Nord-Trøndelag county of Norway were invited, of whom 74% participated. Participants were asked how often they had experienced pain, unrelated to any known disease or acute injury, in the neck and shoulders, low back, and lower extremities in the past 3 months. The associations between (1) physical activity level (low [reference], medium or high) or (2) sport participation (weekly compared with no/infrequent participation) and pain were evaluated using logistic regression analyses, stratified by sex, and adjusted for age, socioeconomic status, and psychological distress., Results: The analyses included 7596 adolescents (mean age, 15.8 years; SD, 1.7). Neck and shoulder pain was most prevalent (17%). A moderate level of physical activity was associated with reduced odds of neck and shoulder pain (OR = 0.79 [95% CI, 0.66-0.94]) and low back pain (OR = 0.75 [95% CI, 0.62-0.91]), whereas a high level of activity increased the odds of lower extremity pain (OR = 1.60 [95% CI, 1.29-1.99]). Participation in endurance sports was associated with lower odds of neck and shoulder pain (OR = 0.79 [95% CI, 0.68-0.92]) and low back pain (OR = 0.77 [95% CI, 0.65-0.92]), especially among girls. Participation in technical sports was associated with increased odds of low back pain, whereas team sports were associated with increased odds of lower extremity pain. Strength and extreme sports were related to pain in all regions., Conclusion: We found that a moderate physical activity level was associated with less neck and shoulder pain and low back pain, and that participation in endurance sports may be particularly beneficial. Our findings highlight the need for health care professionals to consider the types of sports adolescents participate in when evaluating their musculoskeletal pain., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: This work was funded by The Norwegian Fund for Post-Graduate Training in Physiotherapy.

Background: An anterior cruciate ligament (ACL) injury is a severe injury that may require ACL reconstruction (ACLR) to enable the return to sport. Risk factors for ACLR have not firmly been established in the general adolescent population., Purpose: To investigate the incidence and risk factors for ACLR in a population-based cohort of adolescents., Study Design: Cohort study; Level of evidence, 3., Methods: We prospectively followed 7644 adolescents from the adolescent part of the Nord-Trøndelag Health Study, included from 2006 to 2008. The main risk factors of interest were the level of sport participation (level I, II, or III) and sport competitions. The endpoint was primary ACLR recorded in the Norwegian National Knee Ligament Registry between January 2006 and December 2013., Results: A total of 3808 boys and 3836 girls were included in the analyses. We identified 69 (0.9%) ACLRs with a median of 7.3 years of follow-up, providing an overall ACLR incidence of 38.9 (95% CI, 30.7-49.3) per 100,000 person-years. The hazard ratio (HR) for ACLR associated with level I sport participation was 3.93 (95% CI, 0.92-16.80) for boys and 3.31 (95% CI, 1.30-8.43) for girls. There was a stronger association related to participating in sport competitions. Girls had over 5 times a higher risk (HR, 5.42; 95% CI, 2.51-11.70) and boys over 4 times the risk (HR, 4.22; 95% CI, 1.58-11.30) of ACLR compared with those who did not compete., Conclusion: Participating in level I sports and sport competitions significantly increased the risk of undergoing primary ACLR. Preventive strategies should be implemented to reduce the incidence and future burden of ACLR., (© 2016 The Author(s).)

Background: The relationship between leisure time physical activity (LPA) and hip and knee OA and subsequent joint replacement has not yet been clearly defined. Some studies have found the risk of knee replacement (TKR) to increase with high levels of LPA, while others have found no overall relationship to either TKR or hip replacement (THR). The aim was to investigate the association between LPA and the risk of severe end-stage OA, defined as THR or TKR due to primary OA, in a large population-based cohort., Methods: Participants in the Nord-Trøndelag Health Study (HUNT) were followed prospectively to identify THR and TKR using the Norwegian Arthroplasty Register. Self-reported LPA was classified as inactive, low, moderate or high. The Cox proportional hazards model was used to calculate hazard ratios (HRs) according to levels of LPA with adjustments for confounding variables. Analyses were performed by age (<45, 45-59 and ≥60 years) and sex., Results: A total of 66 964 participants (mean age 46.8 years (SD 16.3) were included in the analyses. We identified 1636 THRs and 1016 TKRs due to primary OA during 17.0 years (median) of follow-up. High LPA was significantly associated with THR for women <45 years (HR 1.78, 95 % CI 1.08-2.94) and men between 45-59 years (HR 1.53, 95 % CI 1.10-2.13) at baseline. A significant trend was found only among women < 45 years at baseline (p = 0.02). We found that LPA was significantly associated with TKR for women only (HR 1.45, 95 % CI 1.03-2.04). No measures of LPA were associated with TKR for men., Conclusion: In this population-based study, high level of LPA was associated with increased risk of THR where a significant trend of LPA was seen among women <45 years at baseline. For TKR, high LPA was associated with increased risk only in women. In contrast to previous studies, this study shows a possible association between high LPA and the risk of THR.

Purpose: Single-legged hop tests and isokinetic muscle torque are common outcome measures in the evaluation of knee function. The reliability of the single-legged hop tests in children has not been documented. The aim was to examine inter- and intrarater reliability of four single-legged hop tests and isokinetic muscle torque measurements in children., Methods: Twenty-eight sports-active children (12.4 ± 0.3 years old) were tested three times in two test sessions separated by 1 week. They performed four single-legged hop tests and concentric isokinetic torque measurements during knee extension and flexion. Inter- and intrarater reliability were calculated using the intraclass correlation coefficient (ICC 2,1). Relative terms of the standard error of measurement (SEM %) and smallest real difference(SRD %) were emphasized to allow comparison between the different variables., Results: Twenty-six children were included for statistical analysis. ICCs for inter- and intrarater reliability were moderate to high for the hop tests (0.62-.91) and isokinetic measurements (0.76-0.87). SEMs % were low for the hop tests (3.9-7.4 %) and the isokinetic measurements (5.2-8.9 %). SRDs % were 20.5 % or less for the hop tests, 15.7 % or less for knee extension, and 24.6 % or less for knee flexion., Conclusion: The single-legged hop tests and isokinetic muscle torque measurements demonstrated moderate-to high reliability with low measurement error in sports-active children. A change above 20.5 % for the single-legged hop tests, 15.7 % for knee extension, and 24.6 % for knee flexion is necessary to represent a real change in knee function. Level of evidence III.