A pilot randomised double blind controlled trial of the efficacy of purified fatty acids for the treatment of women with endometriosis-associated pain (PurFECT):study protocol

Abstract Background Endometriosis affects 6–10% of women and is associated with debilitating pelvic pain. It costs the UK > £2.8 billion per year in loss of productivity. Endometriosis can be managed by surgical excision or medically by ovarian suppression. However, ~ 75% symptoms recur after surgery and available medical treatments have undesirable side effects and are contraceptive. Omega-3 purified fatty acids (PUFA) have been shown in animal models to reduce factors that are thought to lead to endometriosis-associated pain, have minimal side effects, and no effects on fertility. This paper presents a protocol for a two-arm, pilot parallel randomised controlled trial (RCT) which aims to inform the planning of a future multicentre trial to evaluate the efficacy of Omega-3 PUFA in the management of endometriosis-associated pain in women. Methods The study will recruit women with endometriosis over a 12-month period in the National Health Service (NHS) Lothian, UK, and randomise them to 8 weeks of treatment with Omega-3 PUFA or comparator (olive oil). The primary objective is to assess recruitment and retention rates. The secondary objectives are to determine the effectiveness/acceptability to participants of the proposed methods of recruitment/randomisation/treatments/questionnaires, to inform the sample size calculation and to refine the research methodology for a future large randomised controlled trial. Response to treatment will be monitored by pain scores and questionnaires assessing physical and emotional function compared at baseline and 8 weeks. Discussion We recognise that there may be potential difficulties in mounting a large randomised controlled trial for endometriosis to assess Omega-3 PUFA because they are a dietary supplement readily available over the counter and already used by women with endometriosis. We have therefore designed this pilot study to assess practical feasibility and following the ‘Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials’ recommendations for the design of chronic pain trials. Trial registration ISRCTN4420234

Macrophage-derived human resistin is induced in multiple helminth infections and promotes inflammatory monocytes and increased parasite burden.

Parasitic helminth infections can be associated with lifelong morbidity such as immune-mediated organ failure. A better understanding of the host immune response to helminths could provide new avenues to promote parasite clearance and/or alleviate infection-associated morbidity. Murine resistin-like molecules (RELM) exhibit pleiotropic functions following helminth infection including modulating the host immune response; however, the relevance of human RELM proteins in helminth infection is unknown. To examine the function of human resistin (hResistin), we utilized transgenic mice expressing the human resistin gene (hRetnTg+). Following infection with the helminth Nippostrongylus brasiliensis (Nb), hResistin expression was significantly upregulated in infected tissue. Compared to control hRetnTg- mice, hRetnTg+ mice suffered from exacerbated Nb-induced inflammation characterized by weight loss and increased infiltration of inflammatory monocytes in the lung, along with elevated Nb egg burdens and delayed parasite expulsion. Genome-wide transcriptional profiling of the infected tissue revealed that hResistin promoted expression of proinflammatory cytokines and genes downstream of toll-like receptor signaling. Moreover, hResistin preferentially bound lung monocytes, and exogenous treatment of mice with recombinant hResistin promoted monocyte recruitment and proinflammatory cytokine expression. In human studies, increased serum resistin was associated with higher parasite load in individuals infected with soil-transmitted helminths or filarial nematode Wuchereria bancrofti, and was positively correlated with proinflammatory cytokines. Together, these studies identify human resistin as a detrimental factor induced by multiple helminth infections, where it promotes proinflammatory cytokines and impedes parasite clearance. Targeting the resistin/proinflammatory cytokine immune axis may provide new diagnostic or treatment strategies for helminth infection and associated immune-mediated pathology

The BSR-PsA:study protocol for the British Society for Rheumatology psoriatic arthritis register

Acknowledgements We acknowledge contribution of BSR-PsA study staff, under the supervision of KFK: Maureen Heddle, Barry Morris, Jonathan Lock and Jane Brady. We also acknowledge the support from the Centre for Healthcare Randomised Trials (CHaRT) at the University of Aberdeen, especially Mark Forrest and Brian Taylor, for database and IT support. We would like to thank Professor Iain McInnes from the University of Glasgow, and our International Advisory Committee (Professors Merete Hetland, Oliver Fitzgerald and Philip Mease), for their comments when developing the protocol and for advice in harmonising data collection with other international studies, and the staff at the British Society for Rheumatology, in particular Alan Roach, Ross Matthews, Chris Hiley and Debbie MacDonald. Finally, we are indebted to the staff at all participating NHS trusts (details of which are available from www.abdn.ac.uk/bsr-psa) and especially the NIHR Clinical Research Network research nurses for their assistance with participant recruitment and data collection. Funding The BSR-PsA is funded by the BSR as part of its rheumatology registers portfolio and, in turn, receives funding for this from pharmaceutical companies. At the time of publication, only Amgen (previously Celgene) have contributed to the funding of the BSR-PsA. Pharmaceutical companies providing funds to BSR do not participant in the conduct or oversight of the study. However, they do receive advance notice of publications on which they are able to comment. Companies contributing to the funding of the register can request anonymised data on clinically confirmed serious adverse events and some events of special interest (e.g. pregnancy) among participants prescribed the specific bDMARD or tsDMARD agents that they manufacture. Other than this information, they do not have access to any raw data. They may, however, request specific analyses to be performed, for which a pre-specific analysis plan is discussed, and additional funds are provided.Peer reviewedPublisher PD

How has child growth around adiposity rebound altered in Scotland since 1990 and what are the risk factors for weight gain using the Growing Up in Scotland birth cohort 1?

This is the final version of the article. Available from BioMed Central via the DOI in this record.Background Adiposity rebound is considered critical to the development of overweight and obesity. The purpose of this study was to investigate how growth has changed in comparison to the UK 1990 BMI growth reference curves between the ages 4–8 years and identify any marked deviations in growth. We also examined potential maternal and child risk/protective factors associated with the altered growth patterns. Methods We used data from birth cohort 1 of the Growing Up in Scotland study. Height and weight data (N = 2 857) were available when the children were aged approximately 4 (sweep 4), 6 (sweep 6) and 8 years (sweep 7). For each child, percentile change per month was calculated to identify deviations from the UK 1990 growth patterns. Marked changes (>10 % annual change) in percentiles or weight category between each sweep for each child were considered as reflecting a decreasing (leptogenic), increasing (obesogenic) or no change pattern. Logistic regression was used to explore which maternal or child risk factors were associated with belonging to the different growth patterns. Results Sixty six percent (66 %) of the cohort did not show marked changes in BMI percentile and growth compared to the UK 1990 reference population. However, the median BMI percentile of this group was around the 70th. The most common deviation in BMI percentile was early decrease (11.5 %). In terms of weight categories, contemporary maternal obesity (odd ratio (OR) =2.89; 95 % confidence interval (CI) 2.09, 3.98) and mother smoking during pregnancy (OR =1.56; 95 % CI 1.13, 2.15) were found to be significantly associated with increased odds of obesogenic growth trajectory relative to no change trajectory. Breastfeeding (OR = 1.18; 95 % CI 0.88, 1.57) was also associated with increased odds of obesogenic growth but this was not significant in the adjusted model. Conclusions This study has shown that there is a substantial shift in the general population distribution of BMI since 1990. We identified maternal weight status as the strongest obesogenic factor and this is an indication that more innovative obesity preventive strategies should also consider intergenerational approaches.This work was funded by the SCPHRP core grant from the Medical Research Council (Grant Number MR/K023209/1) and the Chief Scientist Office of Scotland. AJW is now at the University of Exeter but was previously supported by the Farr Institute @ Scotland, which is supported by a 10-funder consortium: Arthritis Research UK, the British Heart Foundation, Cancer Research UK, the Economic and Social Research Council, the Engineering and Physical Sciences Research Council, the Medical Research Council, the National Institute of Health Research, the National Institute for Social Care and Health Research (Welsh Assembly Government), the Chief Scientist Office (Scottish Government Health Directorates), (MRC Grant No: MR/K007017/1). The funders played no role in the conceptualisation or realisation of the research and no role in the decision to submit it for publication

Light-intensity physical activity and cardiometabolic biomarkers in US adolescents

BackgroundThe minimal physical activity intensity that would confer health benefits among adolescents is unknown. The purpose of this study was to examine the associations of accelerometer-derived light-intensity (split into low and high) physical activity, and moderate- to vigorous-intensity physical activity with cardiometabolic biomarkers in a large population-based sample.MethodsThe study is based on 1,731 adolescents, aged 12&ndash;19 years from the 2003/04 and 2005/06 National Health and Nutrition Examination Survey. Low light-intensity activity (100&ndash;799 counts/min), high light-intensity activity (800 counts/min to &lt;4 METs) and moderate- to vigorous-intensity activity (&ge;4 METs, Freedson age-specific equation) were accelerometer-derived. Cardiometabolic biomarkers, including waist circumference, systolic blood pressure, diastolic blood pressure, HDL-cholesterol, and C-reactive protein were measured. Triglycerides, LDL- cholesterol, insulin, glucose, and homeostatic model assessments of &beta;-cell function (HOMA-%B) and insulin sensitivity (HOMA-%S) were also measured in a fasting sub-sample (n=807).ResultsAdjusted for confounders, each additional hour/day of low light-intensity activity was associated with 0.59 (95% CI: 1.18&ndash;0.01) mmHG lower diastolic blood pressure. Each additional hour/day of high light-intensity activity was associated with 1.67 (2.94&ndash;0.39) mmHG lower diastolic blood pressure and 0.04 (0.001&ndash;0.07) mmol/L higher HDL-cholesterol. Each additional hour/day of moderate- to vigorous-intensity activity was associated with 3.54 (5.73&ndash;1.35) mmHG lower systolic blood pressure, 5.49 (1.11&ndash;9.77)% lower waist circumference, 25.87 (6.08&ndash;49.34)% lower insulin, and 16.18 (4.92&ndash;28.53)% higher HOMA-%S.ConclusionsTime spent in low light-intensity physical activity and high light-intensity physical activity had some favorable associations with biomarkers. Consistent with current physical activity recommendations for adolescents, moderate- to vigorous-intensity activity had favorable associations with many cardiometabolic biomarkers. While increasing MVPA should still be a public health priority, further studies are needed to identify dose-response relationships for light-intensity activity thresholds to inform future recommendations and interventions for adolescents.</div

High-normal blood glucose levels may be associated with decreased spatial perception in young healthy adults.

The negative effects of high normal glucose on cognitive function were previously reported in euglycemic individuals of middle age and the elderly population. This study aimed at examining the effect of baseline blood glucose levels on spatial ability, specifically verticality perception on the computerized rod and frame test (CRFT) in young healthy adults. 63 healthy male medical students (age range from 18-23 years), of whom 30 were non-fasting outside the month of Ramadan and 33 fasting during Ramadan of the year 2016, were recruited in order to create varying degrees of glycemia during which verticality perception was carried out. Baseline blood glucose reading was obtained prior to commencing the CRFT test. Blood glucose levels at the time of testing decreased as the duration between the last meal and testing increased. A blood glucose range of 62-117 mg/dl was achieved among participants for this study. Linear regression analysis showed that blood glucose level at testing correlated positively with all alignment spatial error parameters, indicating a probable reduction of spatial perception ability with higher blood glucose levels. These results are consistent with other cognitive studies in older healthy humans and emphasize the critical impact of early glucose dys-homeostasis on cognitive function. They also indicate that elevated blood glucose may affect cognitive functioning outside of the usual complications of diabetes