Interplay between chronic widespread pain and lifestyle factors on the risk of type 2 diabetes: longitudinal data from the Norwegian HUNT Study

Introduction Chronic widespread pain (CWP) and diabetes commonly co-occur; however, it is unclear whether CWP infers an additional risk for diabetes among those with known risk factors for type 2 diabetes. We aimed to examine if CWP magnifies the effect of adverse lifestyle factors on the risk of diabetes. Research design and methods The study comprised data on 25 528 adults in the Norwegian HUNT Study without diabetes at baseline (2006–2008). We calculated adjusted risk ratios (RRs) with 95% CIs for diabetes at follow-up (2017–2019), associated with CWP and body mass index (BMI), physical activity, and insomnia symptoms. The relative excess risk due to interaction (RERI) was calculated to investigate the synergistic effect between CWP and adverse lifestyle factors. Results Compared with the reference group without chronic pain and no adverse lifestyle factors, those with BMI ≥30 kg/m2 with and without CWP had RRs for diabetes of 10.85 (95% CI 7.83 to 15.05) and 8.87 (95% CI 6.49 to 12.12), respectively; those with physical activity <2 hours/ week with and without CWP had RRs for diabetes of 2.26 (95% CI 1.78 to 2.88) and 1.54 (95% CI 1.24 to 1.93), respectively; and those with insomnia symptoms with and without CWP had RRs for diabetes of 1.31 (95% CI 1.07 to 1.60) and 1.27 (95% CI 1.04 to 1.56), respectively. There was little evidence of synergistic effect between CWP and BMI ≥30 kg/m2 (RERI=1.66, 95%CI −0.44 to 3.76), low physical activity (RERI=0.37, 95%CI −0.29 to 1.03) or insomnia symptoms (RERI=−0.09, 95%CI −0.51 to 0.34) on the risk of diabetes. Conclusions These findings show no clear interaction between CWP and adverse lifestyle factors on the risk of diabetes

DE-PASS Best Evidence Statement (BESt): modifiable determinants of physical activity and sedentary behaviour in children and adolescents aged 5–19 years–a protocol for systematic review and meta-analysis

Introduction Physical activity among children and adolescents remains insufficient, despite the substantial efforts made by researchers and policymakers. Identifying and furthering our understanding of potential modifiable determinants of physical activity behaviour (PAB) and sedentary behaviour (SB) is crucial for the development of interventions that promote a shift from SB to PAB. The current protocol details the process through which a series of systematic literature reviews and meta-analyses (MAs) will be conducted to produce a best-evidence statement (BESt) and inform policymakers. The overall aim is to identify modifiable determinants that are associated with changes in PAB and SB in children and adolescents (aged 5–19 years) and to quantify their effect on, or association with, PAB/SB. Methods and analysis A search will be performed in MEDLINE, SportDiscus, Web of Science, PsychINFO and Cochrane Central Register of Controlled Trials. Randomised controlled trials (RCTs) and controlled trials (CTs) that investigate the effect of interventions on PAB/SB and longitudinal studies that investigate the associations between modifiable determinants and PAB/SB at multiple time points will be sought. Risk of bias assessments will be performed using adapted versions of Cochrane’s RoB V.2.0 and ROBINS-I tools for RCTs and CTs, respectively, and an adapted version of the National Institute of Health’s tool for longitudinal studies. Data will be synthesised narratively and, where possible, MAs will be performed using frequentist and Bayesian statistics. Modifiable determinants will be discussed considering the settings in which they were investigated and the PAB/SB measurement methods used. Ethics and dissemination No ethical approval is needed as no primary data will be collected. The findings will be disseminated in peer-reviewed publications and academic conferences where possible. The BESt will also be shared with policy makers within the DE-PASS consortium in the first instance

DE-PASS Best Evidence Statement (BESt):modifiable determinants of physical activity and sedentary behaviour in children and adolescents aged 5–19 years–a protocol for systematic review and meta-analysis

Introduction: Physical activity among children and adolescents remains insufficient, despite the substantial efforts made by researchers and policymakers. Identifying and furthering our understanding of potential modifiable determinants of physical activity behaviour (PAB) and sedentary behaviour (SB) is crucial for the development of interventions that promote a shift from SB to PAB. The current protocol details the process through which a series of systematic literature reviews (SLRs) and meta-analyses (MAs) will be conducted to produce a best-evidence statement (BESt) and inform policy makers. The overall aim is to identify modifiable determinants that are associated with changes in PAB and SB in children and adolescents (aged 5-19 years) and to quantify their effect on, or association with, PAB/SB. Methods and analysis: A search will be performed in MEDLINE, SportDiscus, Web of Science, PsychINFO and Cochrane Central Register of Controlled Trials. Randomized controlled trials (RCTs) and controlled trials (CTs) that investigate the effect of interventions on PAB/SB and longitudinal studies that investigate the associations between modifiable determinants and PAB/SB at multiple time points will be sought. Risk of bias assessments will be performed using adapted versions of Cochrane’s RoB 2.0 and ROBINS-I tools for RCTs and CTs, respectively, and an adapted version of the National Institute of Health’s tool for longitudinal studies. Data will be synthesised narratively and, where possible, MAs will be performed using frequentist and Bayesian statistics. Modifiable determinants will be discussed considering the settings in which they were investigated and the PAB/SB measurement methods used. Ethics and dissemination: No ethical approval is needed as no primary data will be collected. The findings will be disseminated in peer-reviewed publications and academic conferences where possible. The BESt will also be shared with policy makers within the DE-PASS consortium in the first instance. Systematic review registration: CRD4202128287

DE-PASS Best Evidence Statement (BESt): modifiable determinants of physical activity and sedentary behaviour in children and adolescents aged 5-19 years-a protocol for systematic review and meta-analysis

Introduction Physical activity among children and adolescents remains insufficient, despite the substantial efforts made by researchers and policymakers. Identifying and furthering our understanding of potential modifiable determinants of physical activity behaviour (PAB) and sedentary behaviour (SB) is crucial for the development of interventions that promote a shift from SB to PAB. The current protocol details the process through which a series of systematic literature reviews and meta-analyses (MAs) will be conducted to produce a best-evidence statement (BESt) and inform policymakers. The overall aim is to identify modifiable determinants that are associated with changes in PAB and SB in children and adolescents (aged 5-19 years) and to quantify their effect on, or association with, PAB/SB. Methods and analysis A search will be performed in MEDLINE, SportDiscus, Web of Science, PsychINFO and Cochrane Central Register of Controlled Trials. Randomised controlled trials (RCTs) and controlled trials (CTs) that investigate the effect of interventions on PAB/SB and longitudinal studies that investigate the associations between modifiable determinants and PAB/SB at multiple time points will be sought. Risk of bias assessments will be performed using adapted versions of Cochrane's RoB V.2.0 and ROBINS-I tools for RCTs and CTs, respectively, and an adapted version of the National Institute of Health's tool for longitudinal studies. Data will be synthesised narratively and, where possible, MAs will be performed using frequentist and Bayesian statistics. Modifiable determinants will be discussed considering the settings in which they were investigated and the PAB/SB measurement methods used. Ethics and dissemination No ethical approval is needed as no primary data will be collected. The findings will be disseminated in peer-reviewed publications and academic conferences where possible. The BESt will also be shared with policy makers within the DE-PASS consortium in the first instance. Systematic review registration CRD42021282874

Type I interferon-mediated autoinflammation due to DNase II deficiency

Microbial nucleic acid recognition serves as the major stimulus to an antiviral response, implying a requirement to limit the misrepresentation of self nucleic acids as non-self and the induction of autoinflammation. By systematic screening using a panel of interferon-stimulated genes we identify two siblings and a singleton variably demonstrating severe neonatal anemia, membranoproliferative glomerulonephritis, liver fibrosis, deforming arthropathy and increased anti-DNA antibodies. In both families we identify biallelic mutations in DNASE2, associated with a loss of DNase II endonuclease activity. We record increased interferon alpha protein levels using digital ELISA, enhanced interferon signaling by RNA-Seq analysis and constitutive upregulation of phosphorylated STAT1 and STAT3 in patient lymphocytes and monocytes. A hematological disease transcriptomic signature and increased numbers of erythroblasts are recorded in patient peripheral blood, suggesting that interferon might have a particular effect on hematopoiesis. These data define a type I interferonopathy due to DNase II deficiency in humans

A comprehensive evaluation of somatosensory function in acute low back pain and pain-free individuals using quantitative sensory testing

Thesis by publication.Includes bibliographical references.Chapter 1. Introduction -- Chapter 2. Early changes in somatosensory function in low back pain -- Chapter 3. A comparison of somatosensory function between acute low back pain and pain-free controls -- Chapter 4. Conditioned pain modulation in acute low back pain and pain-free controls : a comparison using two test paradigms -- Chapter 5. The prognostic value of Quantitative Sensory Testing in low back pain -- Chapter 6. The long-term reliability of Quantitative Sensory Testing in healthy individuals -- Chapter 7. The temporal development of somatosensory changes in acute low back pain -- Chapter 8. Discussion -- Appendices.Low back pain is a common complaint and has the highest global disability burden when measured as years lived with a disability. After an episode of low back pain, up to two-thirds of people will experience variable levels of chronic pain after one year and around 10% will be significantly disabled in association with low back pain. Recent research has revealed that people with chronic low back pain are characterised by widespread pain hypersensitivity, suggesting that neuroplastic changes at the central nervous system underlie this condition. While this knowledge has enhanced our understanding of pathophysiological processes in chronic low back pain, it is currently unclear how early these somatosensory changes develop. Therefore, the broad aims of this thesis are: to investigate the time course of somatosensory changes from the acute stage of low back pain without serious pathology; to examine the prognostic utility of this information in low back pain; and to address methodological aspects of such assessment using quantitative sensory testing (QST).In order to meet these aims, several research approaches have been undertaken. Two systematic reviews of the literature were carried out to establish whether somatosensory changes are a feature of acute low back pain compared to healthy controls (Chapter 2) and to investigate the prognostic ability of QST in low back pain (Chapter 5). An inception cohort study, using a comprehensive QST assessment, was carried out to inform whether early somatosensory changes can be detected soon after low back pain onset compared to pain-free individuals (Chapter 3). The assessment included evaluation of endogenous pain modulation (Chapter 4) and tracked changes in somatosensory function over time, until 4 months after onset (Chapter 7). This comprehensive data set has also enabled the evaluation of important methodological issues related to the stability of QST over time in healthy individuals (Chapter 6).Overall, the work presented in this thesis has contributed to the body of evidence regarding the evaluation of somatosensory function in the early stages of low back pain, as well as providing novel methodological insights into QST testing. This scholarly work has specific implications for clinicians and researchers addressing low back pain, the condition of highest disability burden worldwide.Mode of access: World wide web1 online resource (xvi, 169 pages) diagrams, table