The association of comorbidities with sleep quality among Australians with multiple sclerosis: Insights from the Australian Multiple Sclerosis Longitudinal Study.

BACKGROUND: Comorbidities and poor sleep quality are prevalent among individuals with multiple sclerosis (MS). Our understanding of the effects of comorbidities on sleep quality in MS remains limited. OBJECTIVES: The objectives were to investigate whether the number and presence of specific comorbidities have associations with sleep quality and to assess the relative contribution of comorbidity groups to sleep quality. METHODS: We collected data on sleep quality (using Pittsburgh Sleep Quality Index (PSQI)) and presence of comorbidities in people with MS (n = 1597). Associations between comorbidities and sleep quality were examined using linear regression and dominance analysis. RESULTS: Having more comorbidities was associated with poorer sleep quality (p for trend < 0.001). All 13 groups of comorbidities explained 12.9% of the variance in PSQI from which half of the variance was contributed by mental health disorders. In total, 16 of the 28 comorbidities were associated with significantly worse sleep quality, with the strongest associations seen for 'other autoimmune diseases' (ß = 1.98), depression (ß = 1.76), anxiety (ß = 1.72) and rheumatoid arthritis (ß = 1.62). CONCLUSIONS: Many individual comorbidities are associated with poorer sleep quality, with mental health disorders making the largest relative contribution. Optimal management of comorbidities that make the greatest contributions could have the largest benefit for improving sleep in MS.

Keratinocyte carcinomas, area-level socioeconomic status and geographic remoteness in Tasmania: cross-sectional associations and temporal trends.

OBJECTIVE: This article aims to examine cross-sectional associations and assess temporal trends in keratinocyte carcinoma (KC) incidence by area-level socioeconomic status (SES) and geographic remoteness in Tasmania, Australia. METHODS: KCs - basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (SCC) - registered by the Tasmanian Cancer Registry were assigned to area-level SES and remoteness area. Incidence rate ratios (2014-2018) were estimated using Poisson regression. Average annual percentage changes (2001-2018) were estimated using the Joinpoint Regression Program. RESULTS: BCC incidence increased with increasing area-level advantage (p-value for trend <0.001), but no trend was found for SCC. SCC incidence was higher in rural than urban areas (p-value <0.001), and BCC incidence was slightly higher in rural than urban areas for females (p-value = 0.009), but not for males (p-value = 0.373). BCC and SCC incidence increased between 2001 and the mid-2010s, when it peaked across most areas. CONCLUSIONS: Associations were found between BCC and higher area-level SES, and between SCC and geographic remoteness. The findings suggest differences in sun exposure behaviours, skin cancer awareness and access to services, or ascertainment bias. IMPLICATIONS FOR PUBLIC HEALTH: Efforts to control and deliver KC services in Tasmania should consider targeting populations with specific area-level characteristics.

Association between knee magnetic resonance imaging markers and knee symptoms over 6-9 years in young adults.

OBJECTIVES: To describe associations between MRI markers with knee symptoms in young adults. METHODS: Knee symptoms were assessed using the WOMAC scale during the Childhood Determinants of Adult Health Knee Cartilage study (CDAH-knee; 2008-2010) and at the 6- to 9-year follow-up (CDAH-3; 2014-2019). Knee MRI scans obtained at baseline were assessed for morphological markers (cartilage volume, cartilage thickness, subchondral bone area) and structural abnormalities [cartilage defects and bone marrow lesions (BMLs)]. Univariable and multivariable (age, sex, BMI adjusted) zero-inflated Poisson (ZIP) regression models were used for analysis. RESULTS: The participants' mean age in CDAH-knee and CDAH-3 were 34.95 (s.d. 2.72) and 43.27 (s.d. 3.28) years, with 49% and 48% females, respectively. Cross-sectionally, there was a weak but significant negative association between medial femorotibial compartment (MFTC) [ratio of the mean (RoM) 0.99971084 (95% CI 0.9995525, 0.99986921), P < 0.001], lateral femorotibial compartment (LFTC) [RoM 0.99982602 (95% CI 0.99969915, 0.9999529), P = 0.007] and patellar cartilage volume [RoM 0.99981722 (95% CI 0.99965326, 0.9999811), P = 0.029] with knee symptoms. Similarly, there was a negative association between patellar cartilage volume [RoM 0.99975523 (95% CI 0.99961427, 0.99989621), P = 0.014], MFTC cartilage thickness [RoM 0.72090775 (95% CI 0.59481806, 0.87372596), P = 0.001] and knee symptoms assessed after 6-9 years. The total bone area was negatively associated with knee symptoms at baseline [RoM 0.9210485 (95% CI 0.8939677, 0.9489496), P < 0.001] and 6-9 years [RoM 0.9588811 (95% CI 0.9313379, 0.9872388), P = 0.005]. The cartilage defects and BMLs were associated with greater knee symptoms at baseline and 6-9 years. CONCLUSION: BMLs and cartilage defects were positively associated with knee symptoms, whereas cartilage volume and thickness at MFTC and total bone area were weakly and negatively associated with knee symptoms. These results suggest that the quantitative and semiquantitative MRI markers can be explored as a marker of clinical progression of OA in young adults.

Examining the environmental risk factors of progressive-onset and relapsing-onset multiple sclerosis: recruitment challenges, potential bias, and statistical strategies.

It is unknown whether the currently known risk factors of multiple sclerosis reflect the etiology of progressive-onset multiple sclerosis (POMS) as observational studies rarely included analysis by type of onset. We designed a case-control study to examine associations between environmental factors and POMS and compared effect sizes to relapse-onset MS (ROMS), which will offer insights into the etiology of POMS and potentially contribute to prevention and intervention practice. This study utilizes data from the Primary Progressive Multiple Sclerosis (PPMS) Study and the Australian Multi-center Study of Environment and Immune Function (the AusImmune Study). This report outlines the conduct of the PPMS Study, whether the POMS sample is representative, and the planned analysis methods. The study includes 155 POMS, 204 ROMS, and 558 controls. The distributions of the POMS were largely similar to Australian POMS patients in the MSBase Study, with 54.8% female, 85.8% POMS born before 1970, mean age of onset of 41.44 ± 8.38 years old, and 67.1% living between 28.9 and 39.4° S. The POMS were representative of the Australian POMS population. There are some differences between POMS and ROMS/controls (mean age at interview: POMS 55 years vs. controls 40 years; sex: POMS 53% female vs. controls 78% female; location of residence: 14.3% of POMS at a latitude ≤ 28.9°S vs. 32.8% in controls), which will be taken into account in the analysis. We discuss the methodological issues considered in the study design, including prevalence-incidence bias, cohort effects, interview bias and recall bias, and present strategies to account for it. Associations between exposures of interest and POMS/ROMS will be presented in subsequent publications.

Tracking of Cardiorespiratory Fitness from Childhood to Mid-adulthood.

High cardiorespiratory fitness (CRF) in adulthood is important for survival from major chronic diseases and preserving good health. We examined how childhood CRF tracks, or persists, into adulthood. Among a cohort of 748 school children followed over 34 years, we found child CRF correlated with young- (r = 0.30) and mid-adulthood (r = 0.16) CRF.

Trajectory of metabolic syndrome and its association with knee pain in middle-aged adults.

OBJECTIVE: Metabolic syndrome (MetS) is characterised by the clustering of central obesity with metabolic abnormalities. We aimed to describe the association of MetS and trajectories of MetS over 10-13 years with knee symptoms in general population-based middle-aged adults. METHODS: Fasting blood biochemistry, waist circumference and blood pressure measures were collected during Childhood Determinants of Adult Health (CDAH)-1 study (year:2004-6; n = 2447; mean age:31.48 ± 2.60) and after 10-13 year at CDAH-3 (year:2014-2019; n = 1549; mean age:44 ± 2.90). Participants were defined as having MetS as per International Diabetes Federation (IDF) definition. Knee symptoms were assessed using Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scale at CDAH-3 (mid-adulthood). RESULTS: The prevalence of MetS increased from 8 % at young adulthood (female:52.06 %) to 13 % in mid-adulthood (female:53.78 %) over 10-13 years. Presence of MetS at mid-adulthood was associated with knee symptoms at mid-adulthood [ratio of means (RoM): 1.33; 95%CI:1.27,1.39]. Four MetS trajectories were identified-'No MetS' (85.01 %); 'Improved MetS' (2.14 %), 'Incident MetS' (8.81 %), and 'Persistent MetS, (4.04 %). Compared to 'No MetS', 'Persistent MetS' [RoM:1.15; 95%CI:1.06,1.25], 'Incident MetS' [RoM:1.56; 95%CI:1.48,1.65], and 'Improved MetS' [RoM:1.22; 95%CI:1.05,1.41] was associated with higher knee symptoms. Notably, 'Incident MetS' was strongly associated with knee symptoms [RoM: 1.56; 95%CI:1.48,1.65] and pain [RoM:1.52; 95%CI:1.37,1.70] at mid-adulthood. CONCLUSION: In this sample of middle-aged adults, there was a significant positive association between MetS and knee symptoms. Relative to those without MetS at either life stage, the elevation in mean knee pain scores was more pronounced for those who developed MetS after young adulthood than for those who had MetS in young adulthood.

Long-term effects of vitamin D supplementation and maintaining sufficient vitamin D on knee osteoarthritis over 5 years.

OBJECTIVES: This study aimed to investigate the long-term effect of vitamin D supplementation compared to placebo over 5 years in participants with knee osteoarthritis (OA). We also aimed to describe the effect of maintaining sufficient serum vitamin D levels over five years in knee OA. METHODS: Participants (n = 173) from the Hobart centre of the Vitamin D Effects on Osteoarthritis (VIDEO) trial were extensively followed up 3 years after the cessation of 2-year investigational treatment. Participants were classified as maintaining sufficient vitamin D (n = 79) and not maintaining sufficient vitamin D (n = 61) groups. RESULTS: There was no significant difference in change in the knee symptoms, depression, and serum levels of IL6 and hs-CRP between both comparisons after 3 years of cessation of the clinical trial. However, among participants who reported no knee surgery (KS), there was a significant improvement in WOMAC function (ß: - 83.7, 95% CI: - 167.3, 0) and depression scores (ß: - 1.3, 95% CI: - 2.3, - 0.2) in vitamin D group compared to the placebo group. Similarly, those who maintained adequate vitamin D levels over 5 years had significantly less WOMAC knee pain (ß: - 33.9, 95% CI: - 65.7, - 2) and physical dysfunction (ß: - 105.5, 95% CI: - 198.2, - 12.8) than participants with vitamin D deficiency over 5 years. CONCLUSION: Vitamin D supplementation over 2 years or maintaining vitamin D sufficiency for 5 years was not associated with statistically significant differences in change in knee symptom scores over 5 years. However, among participants who did not report KS, 2-year vitamin D supplementation and maintaining sufficient vitamin D was linked to modest improvements in knee symptoms and depression scores in knee OA.

Association of body mass index from childhood to mid-adulthood with health-related quality of life in mid-adulthood.

PURPOSE: Most studies regarding the association of obesity with health-related quality of life (HRQoL) have assessed obesity at only one or two time points. We aimed to examine the associations of life course body mass index (BMI) from childhood with health-related quality of life (HRQoL) in mid-adulthood. METHODS: Data were from a cohort study of Australian children (n = 2254, mean baseline age 12.0 (2.0) years in 1985, 46.8% male). Weight and height were measured at baseline and measured or self-reported on average 20, 25, and 30 years later. Age and sex-standardised BMI-z score was calculated at each time point. Physical and mental HRQoL and health state utilities (HSUs) were measured by SF-12 and SF-6D at the last adult follow-up. Linear regression was used to examine the associations adjusting for age, sex, and childhood health status. RESULTS: Higher BMI-z score in childhood (ßadjusted - 1.39, 95% CI - 1.73 to - 1.05) and increasing BMI-z score from childhood to young adulthood (ßadjusted - 1.82, 95% CI - 2.17 to - 1.46) and from young to mid-adulthood (ßadjusted - 1.77, 95% CI - 2.28 to - 1.26) were associated with lower physical HRQoL in mid-adulthood. Similar results were found for mid-adulthood HSUs (ßadjusted ranged - 0.006 to - 0.014, all P < 0.05). Only increasing BMI-z score from young to mid-adulthood significantly related to poorer mental HRQoL (ßadjusted - 0.74, 95% CI - 1.29 to - 0.19) in mid-adulthood. CONCLUSION: High BMI from childhood to mid-adulthood had only modest associations with HRQoL and HSUs, with effects on physical HRQoL most apparent.

trips4health: a single-blinded randomised controlled trial incentivising adult public transport use for physical activity gain.

BACKGROUND: Public transport users tend to accumulate more physical activity than non-users; however, whether physical activity is increased by financially incentivising public transport use is unknown. The trips4health study aimed to determine the impact of an incentive-based public transport intervention on physical activity. METHODS: A single-blinded randomised control trial of a 16-week incentive-based intervention involved Australian adults who were infrequent bus users (≥ 18 years; used bus ≤ 2 times/week) split equally into intervention and control groups. The intervention group were sent weekly motivational text messages and awarded smartcard bus credit when targets were met. The intervention group and control group received physical activity guidelines. Accelerometer-measured steps/day (primary outcome), self-reported transport-related physical activity (walking and cycling for transport) and total physical activity (min/week and MET-min/week) outcomes were assessed at baseline and follow-up. RESULTS: Due to the COVID pandemic, the trial was abandoned prior to target sample size achievement and completion of all assessments (N = 110). Steps/day declined in both groups, but by less in the intervention group [-557.9 steps (-7.9%) vs.-1018.3 steps/week (-13.8%)]. In the intervention group, transport-related physical activity increased [80.0 min/week (133.3%); 264.0 MET-min/week (133.3%)] while total physical activity levels saw little change [35.0 min/week (5.5%); 25.5 MET-min/week (1.0%)]. Control group transport-related physical activity decreased [-20.0 min/week (-27.6%); -41.3 MET-min/week (-17.3%)], but total physical activity increased [260.0 min/week (54.5%); 734.3 MET-min/week (37.4%)]. CONCLUSION: This study found evidence that financial incentive-based intervention to increase public transport use is effective in increasing transport-related physical activity These results warrant future examination of physical activity incentives programs in a fully powered study with longer-term follow-up. TRIAL REGISTRATION: This trial was registered with the Australian and New Zealand Clinical Trials Registry August 14th, 2019: ACTRN12619001136190; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=377914&isReview=true.

Tracking handgrip strength asymmetry from childhood to mid-life.

AIM: Determine if asymmetric handgrip strength exists in childhood and adulthood and quantify the degree of tracking of handgrip strength asymmetry over time. METHODS: Participants from the Childhood Determinants of Adult Health Study had their right and left handgrip strength measured using handgrip dynamometry in childhood (1985: 9-15 y), young adulthood (2004-06: 26-36 y) and/or mid-adulthood (2014-19: 36-49 y). Handgrip strength asymmetry was calculated as: strongest handgrip strength/strongest handgrip strength on the other hand. Participants were categorised based on the degree of their asymmetry (0.0%-10.0%, 10.1%-20.0%, 20.1%-30.0%, >30.0%). Tracking was quantified using Spearman's correlations and log binomial regression. RESULTS: Handgrip strength asymmetry was present in childhood and adulthood (>30.0% asymmetry: childhood = 6%, young adulthood = 3%, mid-adulthood = 4%). Handgrip strength asymmetry did not track between childhood and young- (r = 0.06, 95% CI = -0.02, 0.12) and mid-adulthood (r = 0.01, 95% CI = -0.09, 0.10). Tracking was more apparent between young- and mid-adulthood (r = 0.16, 95% CI = 0.09, 0.22). Participants with >30.0% asymmetry were at greater risk to maintain this status between childhood and young- (RR = 3.53, 95% CI = 1.15, 10.87) and mid-adulthood (RR = 2.14, 95% CI = 0.45, 10.20). CONCLUSION: Although handgrip strength asymmetry tracked relatively poorly, asymmetric handgrip strength was apparent in children and adults. Handgrip strength asymmetry does not exclusively affect older adults and should be considered in protocols to better understand its role across the life course.

Prevalence and correlates of the use of complementary and alternative medicines among older adults with joint pain.

BACKGROUND: There is increasing use of complementary and alternative medicines (CAMs) alone or as an adjuvant therapy to conventional medicines in osteoarthritis (OA) patients. OBJECTIVES: This study aimed to describe the prevalence and correlates of the use of CAMs among community-dwelling older adults. METHODS: Data from the Tasmania Older Adult Cohort Study (TASOAC, n = 1099) were used to describe the prevalence of CAM use. Correlates of CAM use were assessed by comparing CAM users and non-users. To further assess correlates of CAM use, participants with at least one joint with pain were classified into four categories: CAM-only, analgesics-only, co-therapy, and "neither CAMs nor analgesics" (NCNA). RESULTS: In all, 385 (35.0%) of our participants reported use of CAMs, among which vitamins/minerals were used most (22.6%, n = 232). Compared with CAM non-users, CAM users were more likely to be female, were less likely to be overweight, were better educated, had more joints with OA, had fewer WOMAC scores, and did more steps per day. Among participants with any joint pain, the CAM-only group were less likely to be overweight, consumed more alcohol, had higher quality of life, had more steps per day, and had fewer pain-related symptoms compared with the analgesic-only group. CONCLUSION: Complementary and alternative medicines were commonly used among Tasmanian older adults, with 35% of the population using CAMs either alone or in combination with conventional analgesics. CAM users were more likely to be female, be better educated, have more joints with OA, and had healthier lifestyles, including lower body mass index and higher number of steps per day.

Tracking of Cardiorespiratory Fitness and Physical Activity from Youth to Young Adulthood: Findings from the Prospective Special Turku Coronary Risk Factor Intervention Project (STRIP).

Using data from the Special Turku Coronary Risk Factor Intervention Project, cardiorespiratory fitness (rank-order correlation coefficient = 0.60-0.62) tracked stronger than physical activity (rank-order correlation coefficient = 0.27-0.38) between youth (age = 17 years) and young adulthood (age = 26 years). Cardiorespiratory fitness could help identify individuals at risk of maintaining poor fitness levels or developing adverse health in adulthood.

Keratinocyte carcinomas, area-level socioeconomic status and geographic remoteness in Tasmania: cross-sectional associations and temporal trends.

OBJECTIVE: This article aims to examine cross-sectional associations and assess temporal trends in keratinocyte carcinoma (KC) incidence by area-level socioeconomic status (SES) and geographic remoteness in Tasmania, Australia. METHODS: KCs-basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (SCC)-registered by the Tasmanian Cancer Registry were assigned to area-level SES and remoteness area. Incidence rate ratios (2014-2018) were estimated using Poisson regression. Average annual percentage changes (2001-2018) were estimated using the Joinpoint Regression Program. RESULTS: BCC incidence increased with increasing area-level advantage (p value for trend <0.001), but no trend was found for SCC. SCC incidence was higher in rural than urban areas (p value <0.001), and BCC incidence was slightly lower in rural than urban areas for males (p value = 0.026), but not for females (p value = 0.381). BCC and SCC incidence increased between 2001 and the mid-2010s, when it peaked across most areas. CONCLUSIONS: Associations were found between BCC and higher area-level SES, and between SCC and geographic remoteness. The findings suggest differences in sun exposure behaviours, skin cancer awareness and access to services, or ascertainment bias. IMPLICATIONS FOR PUBLIC HEALTH: Efforts to control and deliver KC services in Tasmania should consider targeting populations with specific area-level characteristics.

A pro-inflammatory diet in people with multiple sclerosis is associated with an increased rate of relapse and increased FLAIR lesion volume on MRI in early multiple sclerosis: A prospective cohort study.

BACKGROUND: A pro-inflammatory diet has been posited to induce chronic inflammation within the central nervous system (CNS), and multiple sclerosis (MS) is an inflammatory disease of the CNS. OBJECTIVE: We examined whether Dietary Inflammatory Index (DII®)) scores are associated with measures of MS progression and inflammatory activity. METHODS: A cohort with a first clinical diagnosis of CNS demyelination was followed annually (10 years, n = 223). At baseline, 5- and 10-year reviews, DII and energy-adjusted DII (E-DIITM) scores were calculated (food frequency questionnaire) and assessed as predictors of relapses, annualised change in disability (Expanded Disability Status Scale) and two magnetic resonance imaging measures; fluid-attenuated inversion recovery (FLAIR) lesion volume and black hole lesion volume. RESULTS: A more pro-inflammatory diet was associated with a higher relapse risk (highest vs. lowest E-DII quartile: hazard ratio = 2.24, 95% confidence interval (CI) = -1.16, 4.33, p = 0.02). When we limited analyses to those assessed on the same manufacturer of scanner and those with a first demyelinating event at study entry (to reduce error and disease heterogeneity), an association between E-DII score and FLAIR lesion volume was evident (ß = 0.38, 95% CI = 0.04, 0.72, p = 0.03). CONCLUSION: There is a longitudinal association between a higher DII and a worsening in relapse rate and periventricular FLAIR lesion volume in people with MS.

A prospective study of the impact of COVID-19-related restrictions on activities and mobility upon physical activity, travel behaviour and attitudes.

Background and aims: Public health measures adopted to contain the spread of COVID-19 included restrictions on activities and mobility as people were asked to stay at home and schools moved to online learning. This may have increased risk of non-communicable disease by limiting recreational and transport-related physical activity. Building on an existing study, we assessed changes in self-reported and device-measured physical activity and travel behaviour before, during and after the peak of local COVID-19 outbreak and restrictions (March-July 2020). We examined beliefs in effectiveness of strategies to increase active and public transport after restrictions were reduced. Methods: A longitudinal study of adult infrequent bus users (average ≤ 2 trips per week; n = 70; 67% women) in Hobart, Australia. One-week assessment periods at four separate timepoints (before, during, 0-3 months after, and 3-6 months after the peak restrictions period) involved wearing an accelerometer, daily transport diaries, online surveys and tracking bus smartcard boardings. Results: Physical activity (especially among older participants), bus use and private motor vehicle use declined significantly during or 0-3 months after the peak restrictions period and returned to pre-restrictions levels by 3-6 months after the peak restrictions period, except bus use which remained significantly lower. Retrospective surveys overstated declines in bus use and active transport and self-reports understated declines in physical activity. Social distancing and improving service efficiency and frequency were seen as effective strategies for increasing bus use after restrictions but belief in effectiveness of distancing decreased over time. Conclusions: When restrictions on mobility are increased, supportive health promotion measures are needed to prevent declines in physical activity, particularly for older adults. Public transport systems need capacity to implement temporary distancing measures to prevent communicable disease transmission. Providing convenient, flexible, and efficient options for public transport may help to replenish public transport use after restrictions are reduced.

Effect of Curcuma longa extract on serum inflammatory markers and MRI-based synovitis in knee osteoarthritis: secondary analyses from the CurKOA randomised trial.

BACKGROUND: Curcuma longa (CL) extract is modestly effective for relieving knee symptoms in knee osteoarthritis (OA) patients; however, its mechanism of action is unclear. PURPOSE: We aimed to determine the effects of CL treatment on serum inflammatory markers over 12 weeks and to explore its potential effects on synovitis assessed by contrast-enhanced magnetic resonance imaging (CE-MRI) of the knee. METHODS: Secondary analyses were conducted on the CL for knee OA (CurKOA) trial, which compared CL (n = 36) and placebo (n = 34) over 12 weeks for the treatment of knee OA. Systemic inflammatory markers (TNFα, IL6, and hsCRP) and a cartilage extracellular matrix degradative enzyme (MMP-3) were measured. A subgroup of participants (CL, n = 7; placebo, n = 5) underwent CE-MRI at baseline and a 12-week follow-up. RESULTS: Over 12 weeks, there were no between-group differences in change in hsCRP, IL-6, and TNFα levels. MMP-3 levels decreased in both CL (-1.31 ng/ml [95%CI: -1.89 to -0.73]) and placebo (-2.34 ng/ml [95%CI: -2.95 to -1.73]) groups, with the placebo group having a slightly greater decrease (1.03 ng/ml [95%CI: 0.19 to 1.88]). Most (10 of 12) sub-study participants had normal synovial thickness scores at baseline. One participant had mild synovitis in each of the placebo and CL groups. Synovitis status was stable for all except two participants, one each in the CL and placebo group, whose synovitis score increased. CONCLUSION: This is the first study that explored the effect of CL treatment on local and systemic inflammation using biochemical markers and CE-MRI outcomes on knee OA patients. Secondary analyses from this pilot study suggest that CL is unlikely to have clinically significant effects on systemic (inflammatory and cartilage) or local synovitis (CE-MRI) biomarkers compared to placebo. The mechanism of action for CL effect on pain remains unclear.

Identification of a novel recurrent EEF2 gene amplification in familial prostate tumors.

Recurrent tumor copy number variations (CNVs) in prostate cancer (PrCa) have predominantly been discovered in sporadic tumor cohorts. Here, we examined familial prostate tumors for novel CNVs as prior studies suggest these harbor distinct CNVs. Array comparative genomic hybridization of 12 tumors from an Australian PrCa family, PcTas9, highlighted multiple recurrent CNVs, including amplification of EEF2 (19p13.3) in 100% of tumors. The EEF2 CNV was examined in a further 26 familial and seven sporadic tumors from the Australian cohort and in 494 tumors unselected for family history from The Cancer Genome Atlas (TCGA). EEF2 overexpression was observed in seven PcTas9 tumors, in addition to seven other predominantly familial tumors (ntotal  = 34%). EEF2 amplification was only observed in 1.4% of TCGA tumors, however 7.5% harbored an EEF2 deletion. Analysis of genes co-expressed with EEF2 revealed significant upregulation of two genes, ZNF74 and ADSL, and downregulation of PLSCR1 in both EEF2 amplified familial tumors and EEF2 deleted TCGA tumors. Furthermore, in TCGA tumors, EEF2 amplification and deletion were significantly associated with a higher Gleason score. In summary, we identified a novel PrCa CNV that was predominantly amplified in familial tumors and deleted in unselected tumors. Our results provide further evidence that familial tumors harbor distinct CNVs, potentially due to an inherited predisposition, but also suggest that regardless of how EEF2 is dysregulated, a similar set of genes involved in key cancer pathways are impacted. Given the current lack of gene-based biomarkers and clinical targets in PrCa, further investigation of EEF2 is warranted.

Risk of subsequent keratinocyte carcinomas after a first diagnosis in Tasmania, Australia.

BACKGROUND/OBJECTIVE: A history of keratinocyte carcinoma (KC) is a risk factor for further KCs, but population-based studies quantifying the risk are lacking in Australia. We aimed to describe the risk of subsequent KCs after first KCs in the Australian state of Tasmania. METHODS: Tasmanian residents identified in the Tasmanian Cancer Registry with a first histologically confirmed basal cell carcinoma (BCC), squamous cell carcinoma (SCC) or synchronous BCC and SCC (within 3 months) between January 1985 and December 2013 were followed up for at least 5 years for the development of a subsequent KC. Cumulative risk, incidence rates and standardised incidence ratios (SIRs) were calculated. RESULTS: Those first diagnosed with BCC-only, SCC-only or synchronous BCC and SCC had (i) 5-year cumulative risks of subsequent KCs of 32%, 29% and 51%, (ii) annualised 5-year incidence rates of 8100/100,000 person-years at risk (PYR), 7747/100,000 PYR and 16,634/100,000 PYR and (iii) SIRs of 10.6 (95% CI: 10.5-10.6), 12.5 (95% CI: 12.4-12.6) and 313.0 (95% CI: 305.2-321.1), respectively. Risk estimates increased substantially when multiple (two or more) lesions of any type were diagnosed synchronously. CONCLUSIONS: In the first Australian population-based study to describe the risk of subsequent KCs according to histological types, around one in three Tasmanians diagnosed with first KCs were diagnosed with subsequent KCs within 5 years. The risk of subsequent KCs was higher among those with a history of multiple synchronous lesions, especially if they included both BCC and SCC lesions.

A Randomised Controlled Trial of YOGa and Strengthening Exercise for Knee OsteoArthritis: Protocol for a Comparative Effectiveness Trial (YOGA Trial).

Osteoarthritis (OA) is a common joint disorder for which there is no cure. Current treatments are suboptimal. Exercise is a core treatment for knee OA, with muscle strengthening exercise commonly recommended. Yoga is a mind-body exercise intervention that can improve flexibility, muscle strength, balance, and fitness and potentially reduce symptoms of OA. However, there is a scarcity of robust, high-quality conclusive evidence on the efficacy of yoga in knee OA. We are currently conducting the first randomised comparative effectiveness and cost-effectiveness trial of a yoga program compared with a strengthening exercise program in patients with symptomatic knee OA. This study protocol describes the design and conduct of this trial. The YOGA study is a phase III, single-centre, parallel, superiority, randomised, active-controlled trial which will be conducted in Hobart, Australia. One hundred and twenty-six participants (63 in each arm) aged over 40 years with symptomatic knee OA will be recruited from the community and randomly allocated to receive either a 24-week yoga program (3×/week) or a strengthening exercise program (3×/week). The primary outcome will be change in knee pain over 12 weeks, assessed using a 100 mm visual analogue scale (VAS). The secondary outcomes include change in knee pain, patient global assessment, physical function, quality of life, gait speed, biomarkers, and others over 12 and 24 weeks. We will also assess whether the presence of neuropathic pain moderates the effects of yoga compared to strengthening exercise. Additional data, such as cost and resource utilization, will be collected for the cost-effectiveness analysis. The primary analysis will be conducted using an intention-to-treat approach. Adverse events will be monitored throughout the study. Once completed, this trial will contribute to the knowledge of whether yoga can be used as a simple, effective, low-cost option for the management of knee OA, thus saving economic costs in the healthcare system.

Childhood Factors Associated with Muscular Strength Trajectories between Childhood and Mid-Adulthood.

PURPOSE: To promote greater muscular strength across the life course and, in turn, help improve long-term health outcomes, strategies aimed at increasing muscular strength are required. To inform these strategies, this study identified childhood factors associated with muscular strength trajectories. METHODS: Prospective longitudinal study of 1280 Childhood Determinants of Adult Health participants who had a range of potentially modifiable factors (e.g., anthropometric measures, physical activity) and health and risk motivation items (e.g., attitudes, beliefs, and intentions on health-related actions) measured in childhood and had their muscular strength assessed up to three times between childhood and midlife. Associations between childhood factors and three predetermined life course muscular strength trajectories (identified previously using group-base trajectory modeling as follows: above average and increasing, average, and below average and decreasing) were examined using log multinomial regression. RESULTS: Greater physical fitness, physical activity, fat-free mass, enjoyment of physical activity, physical education, and school sports, and positive attitudes regarding the importance of exercising, staying fit, and body image were associated with a lower likelihood of being in the below average and decreasing muscular strength trajectory (relative risk range, 0.45-0.98). Greater physical fitness, physical activity, and fat-free mass, and attending an independent school were associated with a higher likelihood of being in the above average and increasing muscular strength trajectory (relative risk range, 1.03-1.93). CONCLUSIONS: In addition to providing health benefits in the short term, physical activity, physical fitness, positive health attitudes, and healthy weight in childhood may lead to better muscular strength in the long term.