Understanding the Mechanisms of Pain in Rheumatoid Arthritis

Pain is a debilitating feature of rheumatoid arthritis (RA) and is often described by patients as their most important symptom. Rheumatoid arthritis pain has traditionally been attributed solely to joint inflammation, however despite the advent of increasingly effective disease modifying agents, patients continue to report pain at long term follow up. The cause for ongoing pain is multifactorial and includes joint damage and pain sensitisation. In this book chapter, we will describe the mechanisms underlying the distinct components of pain which are manifest in rheumatoid arthritis and discuss why a thorough assessment of pain is vital to target treatments appropriately

Clustering and correlates of screen-time and eating behaviours among young children

Background: Screen-time and unhealthy dietary behaviours are highly pervasive in young children and evidence suggests that these behaviours often co-occur and are associated. Identifying clusters of unhealthy behaviours, and their influences early in childhood, can assist in the development of targeted preventive interventions. The purpose of this study was to examine the sociodemographic, behavioural, and home physical environmental correlates of co-occurring screen-time and unhealthy eating behaviours and to assess the clustering of screen-time and unhealthy dietary behaviours in young children. Methods: Parents of 126 children, from the UK, aged 5–6 years (49% boys) completed a questionnaire which assessed their child’s screen-time (ST), fruit and vegetable (FV), and energy-dense (ED) snack consumption. Categories of health behaviours were created based on frequencies of children meeting recommendations for FV and ST and median splits of frequencies for ED snacks. Parents reported on their own behaviours (ST, FV, and ED snack consumption), how often they ate meals and watched TV with their child, and on the availability and accessibility of foods within the home. An observed over expected ratio (O/E) was used to assess behavioural clustering. Multivariable multinomial logistic regression was used to examine correlates of behaviour patterns. Results: Approximately 25% of children had two or three health risk behaviours. Correlates consistently associated with clusters included parental income, eating meals at the TV, parental ST and ED snack food consumption, and home availability of ED snack foods. Observed over expected ratios were close to 1 and ranged from 0.78 to 1.43. The three-risk behaviour combination of insufficient FV consumption, high ED snack consumption, and excessive ST occurred more frequently than expected (1.23 (95% CI 0.89, 1.58)). Conclusions: ST and unhealthy dietary behaviours cluster in children as young as 5 years of age and parents’ own behaviours appear to be important influencing factors. Further research into the development of behavioural clustering in young children to identify and further understand the mechanisms underlying the synergy among health behaviours is needed. Feasibility interventions promoting reductions in both screen-time and unhealthy dietary behaviours reciprocally, while simultaneously focusing on changing parental behaviours, are warranted

CASE HISTORIES USING SYNTHETIC FIBER REINFORCED CONCRETE

Synthetic fiber reinforced concrete has been used in shotcrete for many years. This paper discusses select project case histories from around the world. The discussion focuses on why fibers are used and explains how there are many benefits, advantages, and features regarding the choice of fibers. Also discussed is why and how the fibers affect the overall project performance, schedule, costs, and construct-ability. Further discussion shows that the fiber choice is in the details. The best fiber choice must meet certain project criteria established by all the decision makers involved in the project. Lastly, the versatility in the use of a specific blend of synthetic fibers in shotcrete shows the potential for even more diverse applications of synthetic fiber reinforcement

Clustering and correlates of screen-time and eating behaviours among young adolescents

Background: Screen-time and eating behaviours are associated in adolescents, but few studies have examined the clustering of these health behaviours in this age group. The identification of clustered health behaviours, and influences on adolescents’ clustered health behaviours, at the time when they are most likely to become habitual, is important for intervention design. The purpose of this study was to assess the prevalence and clustering of health behaviours in adolescents, and examine the sociodemographic, individual, behavioural, and home social and physical environmental correlates of clustered health behaviours. Methods: Adolescents aged 11–12 years (n=527, 48% boys) completed a questionnaire during class-time which assessed screen-time (ST), fruit and vegetable (FV), and energy-dense (ED) snack consumption using a Food Frequency Questionnaire. Health behaviours were categorised into high and low frequencies based on recommendations for FV and ST and median splits for ED snacks. Adolescents reported on their habits, self-efficacy, eating at the television (TV), eating and watching TV together with parents, restrictive parenting practices, and the availability and accessibility of foods within the home. Behavioural clustering was assessed using an observed over expected ratio (O/E). Correlates of clustered behaviours were examined using multivariate multinomial logistic regression. Results: Approximately 70% reported having two or three health risk behaviours. Overall, O/E ratios were close to 1, which indicates clustering. The three risk behaviour combination of low FV, high ED, and high ST occurred more frequently than expected (O/E ratio = 1.06 95% CI 1.01, 1.15. Individual, behavioural, and social and physical home environmental correlates were differentially associated with behavioural clusters. Correlates consistently associated with clusters included eating ED snacks while watching TV, eating at the TV with parents, and the availability and accessibility of ED snack foods within the home. Conclusions: There is a high prevalence of screen time and unhealthy eating, and screen time is coupled with unhealthy dietary behaviours. Strategies and policies are required that simultaneously address reductions in screen time and changes to habitual dietary patterns, such as TV snacking and snack availability and accessibility. These may require a combination of individual, social and environmental changes alongside conscious and more automatic (nudging) strategies

Motivation in physical education across the primary-secondary school transition

The purpose of this study was to examine the temporal patterns of approach-avoidance achievement goals, implicit theories of ability and perceived competence in physical education across the transition from primary to secondary school. We also evaluated the predictive utility of implicit theories and perceived competence with regard to achievement goal adoption, and determined the moderating influence of gender on temporal patterns and antecedent–goal relationships. One hundred and forty pupils (mean age at start of study = 11.37 years, SD =.28) completed measures of entity and incremental beliefs, perceived competence and goals on four occasions during a 12-month period. Mastery-approach, performance-approach and perform-ance-avoidance goals, as well as entity and incremental beliefs, exhibited a linear decline over time. Mastery-avoidance goals showed no significant change. Girls exhibited a linear decline in perceived competence, whereas for boys the trajectory was curvilinear. Competence perceptions predicted initial scores, but not rate of change, on mastery-approach and both types of performance goals. Incrementa

O03 A case of hyperinflammatory COVID-19 that responded to tocilizumab therapy

Case report - Introduction Coronavirus disease 19 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2), has reached pandemic level and led to over 46,000 deaths in the UK. COVID-19 is primarily a respiratory illness and 10-20% of infected individuals develop severe disease with interstitial pneumonia or acute respiratory distress syndrome (ARDS). In this subgroup of patients, severe clinical manifestations are postulated to result from a hyperactive immune response. This has led to the proposal that immunomodulatory medications could be used for the treatment of COVID-19. Here, we report a case of COVID-19 that was treated with the IL-6 inhibitor, tocilizumab. Case report - Case description A 54-year-old Middle Eastern woman presented to A&E with a one-week history of fever, cough, headache and ageusia. Her past medical history was significant for asthma, chronic headaches, gastro-oesophageal reflux syndrome and subarachnoid haemorrhage. On presentation, she had a low-grade temperature (37.8 °C) but her observations were otherwise normal, and her oxygen saturations were 99% on room air. Examination revealed right basal chest crackles. Bloods showed a mild lymphopenia (0.9x109/l) and a raised CRP (82mg/l) and a chest radiograph demonstrated bibasal shadowing. The patient was diagnosed with probable COVID-19 and discharged with a course of oral doxycycline and a plan for review in the ambulatory unit the following day. When reviewed the next day, her oxygen saturations had fallen to 90% on room air. At this point, her SARS-CoV-2 assay had been resulted as positive and a decision was made to admit her for oxygen therapy. The patient continued to deteriorate despite optimal supportive therapy and the addition of intravenous benzylpenicillin for possible superadded bacterial infection. On day 7 of admission, her respiratory rate was 32-38 breaths per minute, and she required 13l/min of oxygen. Her bloods revealed CRP 474mg/L, D dimer >6000 ng/ml, ferritin 224 μg/L, neutrophils 9.5x109/l and lymphocytes 0.6 x109/l. There were no signs of superadded bacterial infection despite a thorough infection screen. Given her clinical deterioration, she was reviewed by the critical care team for consideration of transfer to higher-level care. The ward team decided to administer a single dose of the anti-IL-6 agent tocilizumab for the treatment of a cytokine storm secondary to COVID-19 infection.  Within 24 hours of tocilizumab treatment, her oxygen requirements fell to 5l/min and her work of breathing significantly improved. On day 15 of admission, she was discharged with saturations of 92% on room air.  Case report - Discussion The patient described in this case showed significant clinical deterioration with features suggestive of cytokine storm secondary to COVID-19. IL-6 is thought to be a key cytokine responsible for initiating the acute phase response and we postulate that IL-6 levels were raised in this patient. Unfortunately, we did not have the assay available to measure this. The treating clinical team decided to prescribe a single dose of tocilizumab on a compassionate use basis. This resulted in a rapid clinical improvement and the patient was subsequently discharged without the need for intensive care. In this case, we propose that tocilizumab inhibited further cytokine activation and prevented the positive feedback loop of inflammation that can otherwise result in rapid clinical deterioration. There are several interesting points to be noted from this case. In this patient, tocilizumab resulted in a rapid reduction in CRP levels. This is thought to correspond to the inhibition of IL-6 mediated release of acute phase proteins by the liver. Therefore, it should be noted that post-tocilizumab treatment, patients should be closely monitored for superadded bacterial infection as they may not mount a full immune response. Larger trials of tocilizumab for the treatment of COVID-19 are currently underway and are required to confirm the efficacy of IL-6 inhibition for COVID-19. The phase III COVACTA trial of tocilizumab in COVID-19 patients did not meet its primary endpoint of improved clinical status however a trend towards shorter hospital admissions was seen. Further studies are ongoing to investigate the role of tocilizumab in other treatment settings, including in combination with an antiviral medication. Further information is required to determine which patients should receive immunomodulatory medications and at which point in their illness. Data is also needed to understand the most efficacious dosing regimen for tocilizumab and its side-effect profile in COVID-19 patients. Case report - Key learning points The COVID-19 pandemic has affected millions of people worldwide and has led to an unprecedented effort from the scientific community to understand the pathophysiology of the disease and to find effective treatments. Emerging evidence suggests that SARS-CoV-2 can induce a hyperactive immune response in a subgroup of patients who develop highly elevated levels of acute phase proteins. It has been proposed that the overactive immune response is responsible for some of the severe clinical manifestations seen and this has led to the suggestion that immunomodulatory medications could be used for the treatment of COVID-19. Indeed, dexamethasone has been shown to be an effective treatment and other immunomodulatory medications including hydroxychloroquine, the IL-1 inhibitor anakinra and JAK-kinase inhibitors are currently being trialled for the treatment of COVID-19. This case highlights the clinical and biochemical features of a patient who developed features suggestive of a cytokine storm secondary to COVID-19 and who responded to treatment with the IL-6 inhibitor tocilizumab. Further work is required to understand the role of immunomodulatory medications for the management of COVID-19 infection

Energy expenditure during common sitting and standing tasks: examining the 1.5 MET definition of sedentary behaviour

Background: Sedentary behavior is defined as any waking behavior characterized by an energy expenditure of 1.5 METS or less while in a sitting or reclining posture. This study examines this definition by assessing the energy cost (METs) of common sitting, standing and walking tasks. Methods: Fifty one adults spent 10 min during each activity in a variety of sitting tasks (watching TV, Playing on the Wii, Playing on the PlayStation Portable (PSP) and typing) and non-sedentary tasks (standing still, walking at 0.2, 0.4, 0.6, 0.8, 1.0, 1.2, 1.4, and 1.6 mph). Activities were completed on the same day in a random order following an assessment of resting metabolic rate (RMR). A portable gas analyzer was used to measure oxygen uptake, and data were converted to units of energy expenditure (METs). Results: Average of standardized MET values for screen-based sitting tasks were: 1.33 (SD: 0.24) METS (TV), 1.41 (SD: 0.28) (PSP), and 1.45 (SD: 0.32) (Typing). The more active, yet still seated, games on the Wii yielded an average of 2.06 (SD: 0.5) METS. Standing still yielded an average of 1.59 (SD: 0.37) METs. Walking MET values increased incrementally with speed from 2.17 to 2.99 (SD: 0.5 - 0.69) METs. Conclusions: The suggested 1.5 MET threshold for sedentary behaviors seems reasonable however some sitting based activities may be classified as non-sedentary. The effect of this on the definition of sedentary behavior and associations with metabolic health needs further investigation

Associations between sedentary behaviour and physical activity in children and adolescents: a meta-analysis

Physical activity and sedentary behaviour are associated with metabolic and mental health during childhood and adolescence. Understanding the inter-relationships between these behaviours will help to inform intervention design. This systematic review and meta-analysis synthesized evidence from observational studies describing the association between sedentary behaviour and physical activity in young people (<18 years). English-language publications up to August 2013 were located through electronic and manual searches. Included studies presented statistical associations between at least one measure of sedentary behaviour and one measure of physical activity. One hundred sixty-three papers were included in the meta-analysis, from which data on 254 independent samples was extracted. In the summary meta-analytic model (k = 230), a small, but significant, negative association between sedentary behaviour and physical activity was observed (r = -0.108, 95% confidence interval [CI] = -0.128, -0.087). In moderator analyses, studies that recruited smaller samples (n < 100, r = -0.193, 95% CI = -0.276, -0.109) employed objective methods of measurement (objectively measured physical activity; r = -0.233, 95% CI = -0.330, -0.137) or were assessed to be of higher methodological quality (r = -0.176, 95% CI = -0.215, -0.138) reported stronger associations, although effect sizes remained small. The association between sedentary behaviour and physical activity in young people is negative, but small, suggesting that these behaviours do not directly displace one another