Correction:A two-arm parallel double-blind randomised controlled pilot trial of the efficacy of Omega-3 polyunsaturated fatty acids for the treatment of women with endometriosis-associated pain (PurFECT1)

[This corrects the article DOI: 10.1371/journal.pone.0227695.]

Cam morphology but neither acetabular dysplasia nor pincer morphology is associated with osteophytosis throughout the hip: findings from a cross-sectional study in UK Biobank

Objectives: to examine whether acetabular dysplasia (AD), cam and/or pincer morphology are associated with radiographic hip osteoarthritis (rHOA) and hip pain in UK Biobank (UKB) and, if so, what distribution of osteophytes is observed.Design: participants from UKB with a left hip dual-energy X-ray absorptiometry (DXA) scan had alpha angle (AA), lateral centre-edge angle (LCEA) and joint space narrowing (JSN) derived automatically. Cam and pincer morphology, and AD were defined using AA and LCEA. Osteophytes were measured manually and rHOA grades were calculated from JSN and osteophyte measures. Logistic regression was used to examine the relationships between these hip morphologies and rHOA, osteophytes, JSN, and hip pain.Results: 6,807 individuals were selected (mean age: 62.7; 3382/3425 males/females). Cam morphology was more prevalent in males than females (15.4% and 1.8% respectively). In males, cam morphology was associated with rHOA [OR 3.20 (95% CI 2.41–4.25)], JSN [1.53 (1.24–1.88)], and acetabular [1.87 (1.48–2.36)], superior [1.94 (1.45–2.57)] and inferior [4.75 (3.44–6.57)] femoral osteophytes, and hip pain [1.48 (1.05–2.09)]. Broadly similar associations were seen in females, but with weaker statistical evidence. Neither pincer morphology nor AD showed any associations with rHOA or hip pain.Conclusions: cam morphology was predominantly seen in males in whom it was associated with rHOA and hip pain. In males and females, cam morphology was associated with inferior femoral head osteophytes more strongly than those at the superior femoral head and acetabulum. Further studies are justified to characterise the biomechanical disturbances associated with cam morphology, underlying the observed osteophyte distribution

Investigation of the Relationship Between Susceptibility Loci for Hip Osteoarthritis and Dual X-Ray Absorptiometry–Derived Hip Shape in a Population-Based Cohort of Perimenopausal Women

This publication is the work of the authors and does not necessarily reflect the views of any funders. Supported by the UK Medical Research Council (grant G1001357 for collection of hip shape), and the Wellcome Trust (grants WT092830M for collection of hip shape and WT088806 for genotyping). Core support for the Avon Longitudinal Study of Parents and Children is provided by the UK Medical Research Council, the Wellcome Trust (102215/2/13/2), and the University of Bristol. Dr. Baird's work was supported by Arthritis Research UK (grant 20244). Mr. Faber's work was supported by an Elizabeth Blackwell Institute Clinical Research Primer Scheme.Peer reviewedPostprin

Motor development in infancy and spine shape in early old age: findings from a British birth cohort study

Spine shape changes dramatically in early life, influenced by attainment of developmental milestones such as independent walking. Whether these associations persist across life is unknown. Therefore, we investigated associations between developmental milestones and spine shape, as determined using statistical shape models (SSMs) of lumbar spine from DXA scans in 1327 individuals (688 female) at 60‐64y in the MRC National Survey of Health and Development. Lumbar lordosis angle (L4 inferior endplate to T12 superior endplate) was measured using the two‐line Cobb method. In analyses adjusted for sex, height, lean and fat mass, socioeconomic position and birthweight, later walking age was associated with greater lordosis described by SSM1 (regression coefficient 0.023, 95%CI 0.000‐0.047, p=0.05) and direct angle measurement. Modest associations between walking age and less variation in anterior‐posterior vertebral size caudally (SSM6) were also observed (0.021, 95%CI ‐0.002‐0.044, p=0.07). Sex interactions showed that later walking was associated with larger relative vertebral anterior‐posterior dimensions in men (SSM3; ‐0.043, 95%CI ‐0.075‐0.01, p=0.01) but not women (0.018, 95%CI ‐0.0007‐0.043, p=0.17). Similar associations were observed between age at independent standing and SSMs but there was little evidence of association between sitting age and spine shape. Unadjusted associations between walking age and SSMs 1 and 6 remained similar after adjustment for potential confounders and mediators. This suggests that these associations may be explained by altered mechanical loading of the spine during childhood growth, although other factors could contribute. Early life motor development, particularly walking, may have a lasting effect on features of spine morphology with clinical significance

Age at onset of walking in infancy is associated with hip shape in early old age

Bones' shapes and structures adapt to the muscle and reaction forces they experience during everyday movements. Onset of independent walking, at approximately 12 months, represents the first postnatal exposure of the lower limbs to the large forces associated with bipedal movements, and, accordingly, earlier walking is associated with greater bone strength. However, associations between early life loading and joint shape have not been explored. We therefore examined associations between walking age and hip shape at age 60-64y in 1423 individuals (740 women) from the MRC National Survey of Health and Development, a nationally-representative British birth cohort. Walking age in months was obtained from maternal interview at age 2y. Ten modes of variation in hip shape (HM1-HM10), described by statistical shape models, were ascertained from dual-energy X-ray absorptiometry (DXA) images. In sex-adjusted analyses, earlier walking age was associated with higher HM1 and HM7 scores; these associations were maintained after further adjustment for height, body composition and socioeconomic position. Earlier walking was also associated with lower HM2 scores in women only, and lower HM4 scores in men only. Taken together, this suggests that earlier walkers have proportionately larger (HM4) and flatter (HM1,4) femoral heads, wider (HM1,4,7) and flatter (HM1, 7) femoral necks, smaller neck-shaft angle (HM1,4), anteversion (HM2,7) and development of osteophytes (HM1). These results suggest that age at onset of walking in infancy is associated with variations in hip shape in older age. Early walkers have a larger femoral head and neck and smaller neck-shaft angle; these features are associated with reduced hip fracture risk, but also represent an osteoarthritic-like phenotype. Unlike results of previous studies of walking age and bone mass, associations in this study were not affected by adjustment for lean mass suggesting that associations may relate directly to skeletal loading in early life when joint shape changes rapidly. This article is protected by copyright. All rights reserved.</p

Machine-learning derived acetabular dysplasia and cam morphology are features of severe hip osteoarthritis : findings from UK Biobank

Acknowledgements and disclosures The authors would like to thank Dr Martin Williams, Consultant Musculoskeletal Radiologist North Bristol NHS Trust, who provided substantial training and expertise in osteophyte assessment on DXA images. This research has been conducted using the UK Biobank Resource (application number 17295). Financial Support: RE, MF, FS are supported, and this work is funded by a Wellcome Trust collaborative award (reference number 209233). BGF is supported by a Medical Research Council (MRC) clinical research training fellowship (MR/S021280/1). CL was funded by the MRC, UK (MR/S00405X/1) as well as a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (223267/Z/21/Z). NCH acknowledges support from the MRC and NIHR Southampton Biomedical Research Centre, University of Southampton, and University Hospital Southampton. This research was funded in whole, or in part, by the Wellcome Trust [Grant number 223267/Z/21/Z]. NCH has received consultancy, lecture fees and honoraria from Alliance for Better Bone Health, AMGEN, MSD, Eli Lilly, Servier, UCB, Shire, Consilient Healthcare, Kyowa Kirin and Internis Pharma. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.Peer reviewedPublisher PD

Entry of antiepileptic drugs (valproate and lamotrigine) into the developing rat brain [version 1; peer review: 2 approved]

Background: Women with epilepsy face difficult choices whether to continue antiepileptic drug treatment during pregnancy, as uncontrolled seizures carry great risk to mother and fetus but continuing treatment may have adverse effects on baby’s development. This study aimed at evaluating antiepileptic drug entry into developing brain. Methods: Anaesthetised pregnant, non-pregnant adult females, postnatal and fetal rats were injected intraperitoneally with different doses, single or in combinations, of valproate and lamotrigine, all within clinical range. Injectate included 3H-labelled drug. After 30min, CSF, blood and brain samples were obtained; radioactivity was measured using liquid scintillation counting. Some animals were also exposed to valproate in feed throughout pregnancy and into neonatal period. Drug levels were measured by liquid chromatography coupled to mass spectrometry (LC-MS). Results are given as CSF or tissue/plasma% as index of drug entry. Results: Entry of valproate into brain and CSF was higher at E19 and P4 compared to adult but was not dose-dependent;  placental transfer increased significantly at highest dose of 100mg/Kg. Lamotrigine entry into the brain was dose dependent only at E19. Chronic valproate treatment, or combination of valproate and lamotrigine had little effect on either drug entry, except for reduced valproate brain entry in adult brain with chronic treatment. Placental transfer decreased significantly after chronic valproate treatment. LC-MS measurement of valproate in adults confirmed that rat plasma values were within the clinical range and CSF/plasma and brain/plasma ratios for LC-MS and 3H-valproate were similar. Conclusion: Results suggest that entry of valproate may be higher in developing brain, the capacity of barrier mechanism is mostly unaffected by doses within the clinical range, with or without addition of lamotrigine. Chronic valproate exposure may result in upregulation in cellular mechanisms restricting its entry into the brain. Entry of lamotrigine was little different at different ages and was not dose dependent

Associations between life course longitudinal growth and hip shapes at ages 60-64 years: evidence from the MRC National Survey of Health and Development

Objective We sought to examine associations between height gain across childhood and adolescence with hip shape in individuals aged 60-64 years from the Medical Research Council National Survey of Health and Development, a nationally representative British birth cohort. Methods Height was measured at ages 2, 4, 6, 7, 11 and 15 years, and self-reported at age 20 years. 10 modes of variation in hip shape (HM1-10), described by statistical shape models, were previously ascertained from DXA images taken at ages 60-64 years. Associations between (1) height at each age; (2) Super-Imposition by Translation And Rotation (SITAR) growth curve variables of height size, tempo and velocity; and (3) height gain during specific periods of childhood and adolescence, and HM1-10 were tested. Results Faster growth velocity was associated with a wider, flatter femoral head and neck, as described by positive scores for HM6 (regression coefficient 0.014; 95% CI 0.08 to 0.019; p<0.001) and HM7 (regression coefficient 0.07; 95% CI 0.002 to 0.013; p=0.009), and negative scores for HM10 (regression coefficient -0.006; 95% CI -0.011 to 0.00, p=0.04) and HM2 (males only, regression coefficient -0.017; 95% CI -0.026 to -0.09; p<0.001). Similar associations were observed with greater height size and later height tempo. Examination of height gains during specific periods of childhood and adolescence identified those during the adolescence period as being most consistently associated. Conclusion Our analyses suggest that individual growth patterns, particularly in the adolescent period, are associated with modest variations in hip shape at 60-64 years, which are consistent with features seen in osteoarthritis

Durvalumab (MEDI 4736) in combination with extended neoadjuvant regimens in rectal cancer : a study protocol of a randomised phase II trial (PRIME-RT)

Acknowledgements We are grateful to Mr George Davidson and Ms Monica Jeffers for their input with writing the PRIME-RT protocol and patient information sheet. This study is co-sponsored by the University of Glasgow and NHS Greater Glasgow and Clyde. Funding PRIME-RT is funded by Astrazeneca and receives core funding from CRUK Clinical Trials Unit Glasgow for the purposes of trial set-up and data collection. The trial is co-sponsored by the University Of Glasgow and NHS Greater Glasgow and Clyde.Peer reviewedPublisher PD

Accelerated partner therapy contact tracing for people with chlamydia (LUSTRUM): a crossover cluster-randomised controlled trial.

BACKGROUND Accelerated partner therapy has shown promise in improving contact tracing. We aimed to evaluate the effectiveness of accelerated partner therapy in addition to usual contact tracing compared with usual practice alone in heterosexual people with chlamydia, using a biological primary outcome measure. METHODS We did a crossover cluster-randomised controlled trial in 17 sexual health clinics (clusters) across England and Scotland. Participants were heterosexual people aged 16 years or older with a positive Chlamydia trachomatis test result, or a clinical diagnosis of conditions for which presumptive chlamydia treatment and contact tracing are initially provided, and their sexual partners. We allocated phase order for clinics through random permutation within strata. In the control phase, participants received usual care (health-care professional advised the index patient to tell their sexual partner[s] to attend clinic for sexually transmitted infection screening and treatment). In the intervention phase, participants received usual care plus an offer of accelerated partner therapy (health-care professional assessed sexual partner[s] by telephone, then sent or gave the index patient antibiotics and sexually transmitted infection self-sampling kits for their sexual partner[s]). Each phase lasted 6 months, with a 2-week washout at crossover. The primary outcome was the proportion of index patients with a positive C trachomatis test result at 12-24 weeks after contact tracing consultation. Secondary outcomes included proportions and types of sexual partners treated. Analysis was done by intention-to-treat, fitting random effects logistic regression models. This trial is registered with the ISRCTN registry, 15996256. FINDINGS Between Oct 24, 2018, and Nov 17, 2019, 1536 patients were enrolled in the intervention phase and 1724 were enrolled in the control phase. All clinics completed both phases. In total, 4807 sexual partners were reported, of whom 1636 (34%) were steady established partners. Overall, 293 (19%) of 1536 index patients chose accelerated partner therapy for a total of 305 partners, of whom 248 (81%) accepted. 666 (43%) of 1536 index patients in the intervention phase and 800 (46%) of 1724 in the control phase were tested for C trachomatis at 12-24 weeks after contact tracing consultation; 31 (4·7%) in the intervention phase and 53 (6·6%) in the control phase had a positive C trachomatis test result (adjusted odds ratio [OR] 0·66 [95% CI 0·41 to 1·04]; p=0·071; marginal absolute difference -2·2% [95% CI -4·7 to 0·3]). Among index patients with treatment status recorded, 775 (88·0%) of 881 patients in the intervention phase and 760 (84·6%) of 898 in the control phase had at least one treated sexual partner at 2-4 weeks after contact tracing consultation (adjusted OR 1·27 [95% CI 0·96 to 1·68]; p=0·10; marginal absolute difference 2·7% [95% CI -0·5 to 6·0]). No clinically significant harms were reported. INTERPRETATION Although the evidence that the intervention reduces repeat infection was not conclusive, the trial results suggest that accelerated partner therapy can be safely offered as a contact tracing option and is also likely to be cost saving. Future research should find ways to increase uptake of accelerated partner therapy and develop alternative interventions for one-off sexual partners. FUNDING National Institute for Health Research