A genome catalogue of mercury-methylating bacteria and archaea from sediments of a boreal river facing human disturbances.

Methyl mercury, a toxic compound, is produced by anaerobic microbes and magnifies in aquatic food webs, affecting the health of animals and humans. The exploration of mercury methylators based on genomes is still limited, especially in the context of river ecosystems. To address this knowledge gap, we developed a genome catalogue of potential mercury-methylating microorganisms. This was based on the presence of hgcAB from the sediments of a river affected by two run-of-river hydroelectric dams, logging activities and a wildfire. Through the use of genome-resolved metagenomics, we discovered a unique and diverse group of mercury methylators. These were dominated by members of the metabolically versatile Bacteroidota and were particularly rich in microbes that ferment butyrate. By comparing the diversity and abundance of mercury methylators between sites subjected to different disturbances, we found that ongoing disturbances, such as the input of organic matter related to logging activities, were particularly conducive to the establishment of a mercury-methylating niche. Finally, to gain a deeper understanding of the environmental factors that shape the diversity of mercury methylators, we compared the mercury-methylating genome catalogue with the broader microbial community. The results suggest that mercury methylators respond to environmental conditions in a manner similar to the overall microbial community. Therefore, it is crucial to interpret the diversity and abundance of mercury methylators within their specific ecological context.

Mobilizing Endogenous Progenitor Cells Using pSDF1α-Activated Scaffolds Accelerates Angiogenesis and Bone Repair in Critical-Sized Bone Defects.

Mobilizing endogenous progenitor cells to repair damaged tissue in situ has the potential to revolutionize the field of regenerative medicine, while the early establishment of a vascular network will ensure survival of newly generated tissue. In this study, a gene-activated scaffold containing a stromal derived factor 1α plasmid (pSDF1α), a pro-angiogenic gene that is also thought to be involved in the recruitment of mesenchymal stromal cells (MSCs) to sites of injury is described. It is shown that over-expression of SDF1α protein enhanced MSC recruitment and induced vessel-like structure formation by endothelial cells in vitro. When implanted subcutaneously, transcriptomic analysis reveals that endogenous MSCs are recruited and significant angiogenesis is stimulated. Just 1-week after implantation into a calvarial critical-sized bone defect, pSDF1α-activated scaffolds are recruited MSCs and rapidly activate angiogenic and osteogenic programs, upregulating Runx2, Dlx5, and Sp7. At the same time-point, pVEGF-activated scaffolds are recruited a variety of cell types, activating endochondral ossification. The early response induced by both scaffolds leads to complete bridging of the critical-sized bone defects within 4-weeks. The versatile cell-free gene-activated scaffold described in this study is capable of harnessing and enhancing the body's own regenerative capacity and has immense potential in a myriad of applications.

Validation of a questionnaire for Central nervous system Aspects of joint Pain: the CAP questionnaire.

BACKGROUND AND AIMS: Neuropathic-like pain, fatigue, cognitive difficulty, catastrophising, anxiety, sleep disturbance, depression, and widespread pain associate with a single factor in people with knee pain. We report the Central Aspects of Pain questionnaire (CAP) to characterise this across painful musculoskeletal conditions. METHODS: CAP was derived from the 8 item CAP-Knee questionnaire, and completed by participants with joint pain in the Investigating Musculoskeletal Health and Wellbeing survey. Subgroups had osteoarthritis, back pain or fibromyalgia. Acceptability was evaluated by feedback and data missingness. Correlation coefficients informed widespread pain scoring threshold in relation to the other items, and evaluated associations with pain. Factor analysis assessed CAP structure. Intraclass Correlation Coefficient (ICC) between paper and electronic administration assessed reliability. Friedman test assessed score stability over 4 years in people reporting knee osteoarthritis. RESULTS: Data were from 3579 participants (58% female, median age; 71 years), including subgroups with osteoarthritis (n = 1158), back pain (n = 1292) or fibromyalgia (n = 177). Across the 3 subgroups, ≥10/26 painful sites on the manikin scored widespread pain. Reliability was high (ICC= 0.89 (95% CI: 0.84-0.92)) and CAP scores fit to 1 and 2 factor model, with a total CAP score that was associated with pain severity and quality (r = 0.50-0.72). In people with knee pain, CAP scores were stable over 4 years at the group level, but displayed significant temporal heterogeneity within individual participants. CONCLUSIONS: Central Aspects of Pain is reliably measured by the CAP questionnaire across a range of painful musculoskeletal conditions, and is a changeable state.

How Social Connectedness Helps Patients Stay Home After Hospital at Home Enrollment: A Mixed Methods Study.

BACKGROUND: While enrolled in Hospital at Home (HaH) programs, patients rely on their social network to provide supportive behaviors that are routinely provided by hospital staff in the inpatient setting. OBJECTIVE: This study investigated how social connectedness is associated with patient outcomes in a HaH program. DESIGN: The explanatory iterative sequential mixed methods design included an electronic health record review to collect quantitative measures to describe the severity of patient illness and healthcare utilization and then qualitative interviews to explain quantitative findings. PARTICIPANTS: The quantitative phase included 100 patients (18 years or older) admitted to the hospital who were subsequently enrolled in the HaH program. In the qualitative phase, 33 of the 100 patients participated in semi-structured interviews. ANALYSIS: Qualitative data was analyzed using the Sort & Sift, Think & Shift method. Integrated analysis included merged data displays of healthcare utilization data and patient descriptions of their care and genogram-type illustrations to enable variable-oriented analysis of structural support. We then examined patient narratives by two variables: life course and care elevation, to understand differences in the trajectories of six subsets of patients as identified by the quantitative data. KEY RESULTS: Three factors prompted patients to enroll in HaH: low attention from hospital staff during hospital stay; loneliness and isolation during hospital stay; and family encouragement to enroll. After discharge, social support within the home structure facilitated recovery during HaH. Conversely, HaH patients with limited support within the home were more likely to be readmitted. CONCLUSIONS: Structural social connectedness facilitates patient recovery in HaH. Before enrolling patients in HaH, clinicians should take an in-depth social history, including questions about social/familial roles, household responsibilities, and technology acceptance. Clinicians should engage formal and informal caregivers in these conversations early and communicate a clear picture of what caregivers should do to support the patient through recovery.

Is Austerity Responsible for the Stalled Mortality Trends Across Many High-Income Countries? A Systematic Review.

This article systematically reviews evidence evaluating whether macroeconomic austerity policies impact mortality, reviewing high-income country data compiled through systematic searches of nine databases and gray literature using pre-specified methods (PROSPERO registration: CRD42020226609). Eligible studies were quantitatively assessed to determine austerity's impact on mortality. Two reviewers independently assessed eligibility and risk of bias using ROBINS-I. Synthesis without meta-analysis was conducted due to heterogeneity. Certainty of evidence was assessed using the GRADE framework. Of 5,720 studies screened, seven were included, with harmful effects of austerity policies demonstrated in six, and no effect in one. Consistent harmful impacts of austerity were demonstrated for all-cause mortality, life expectancy, and cause-specific mortality across studies and different austerity measures. Excess mortality was higher in countries with greater exposure to austerity. Certainty of evidence was low. Risk of bias was moderate to critical. A typical austerity dose was associated with 74,090 [-40,632, 188,792] and 115,385 [26,324, 204,446] additional deaths per year. Austerity policies are consistently associated with adverse mortality outcomes, but the magnitude of this effect remains uncertain and may depend on how austerity is implemented (e.g., balance between public spending reductions or tax rises, and distributional consequences). Policymakers should be aware of potential harmful health effects of austerity policies.

Serum levels of hydroxylated metabolites of arachidonic acid cross-sectionally and longitudinally predict knee pain progression: an observational cohort study.

OBJECTIVE: To examine associations between serum oxylipins, which regulate tissue repair and pain signalling, and knee pain/radiographic osteoarthritis (OA) at baseline and knee pain at 3 year follow-up. METHOD: Baseline, and 3 year follow-up, knee pain phenotypes were assessed from 154 participants in the Knee Pain in the Community (KPIC) cohort study. Serum and radiographic Kellgren and Lawrence (KL) and Nottingham line drawing atlas OA scores were collected at baseline. Oxylipin levels were quantified using liquid chromatography coupled with mass spectrometry. Associations were measured by linear regression and receiver operating characteristics (ROC). RESULTS: Serum levels of 8,9-epoxyeicosatrienoic acid (EET) (ß(95% confidence intervals (CI)) = 1.809 (-0.71 to 2.91)), 14,15-dihydroxyeicosatrienoic acid (DHET) (ß(95%CI) = 0.827 (0.34-1.31)), and 12-hydroxyeicosatetraenoic acid (HETE) (ß(95%CI) = 4.090 (1.92-6.26)) and anandamide (ß(95%CI) = 3.060 (1.35-4.77)) were cross-sectionally associated with current self-reported knee pain scores (numerical rating scale (NRS) item 3, average pain). Serum levels of 9- (ß(95%CI) = 0.467 (0.18-0.75)) and 15-HETE (ß(95%CI) = 0.759 (0.29-1.22)), 14-hydroxydocosahexaenoic acid (ß(95%CI) = 0.483(0.24-0.73)), and the ratio of 8,9-EET:DHET (ß(95%CI) = 0.510(0.19-0.82)) were cross-sectionally associated with KL scores. Baseline serum concentrations of 8,9-EET (ß(95%CI) = 2.166 (0.89-3.44)), 5,6-DHET (ß(95%CI) = 152.179 (69.39-234.97)), and 5-HETE (ß(95%CI) = 1.724 (0.677-2.77) showed positive longitudinal associations with follow-up knee pain scores (NRS item 3, average pain). Combined serum 8,9-EET and 5-HETE concentration showed the strongest longitudinal association (ß(95%CI) = 1.156 (0.54-1.77) with pain scores at 3 years, and ROC curves distinguished between participants with no pain and high pain scores at follow-up (area under curve (95%CI) = 0.71 (0.61-0.82)). CONCLUSIONS: Serum levels of a combination of hydroxylated metabolites of arachidonic acid may have prognostic utility for knee pain, providing a potential novel approach to identify people who are more likely to have debilitating pain in the future.

Factors Associated with Increased Knowledge about Breast Density in South Australian Women Undergoing Breast Cancer Screening.

Background: There is growing awareness of breast density in women attending breast cancer screening; however, it is unclear whether this awareness is associated with increased knowledge. This study aims to evaluate breast density knowledge among Australian women attending breast cancer screening. Method: This cross-sectional study was conducted on women undergoing breast cancer screening at The Queen Elizabeth Hospital Breast/Endocrine outpatient department. Participants were provided with a questionnaire to assess knowledge, awareness, and desire to know their own breast density. Result: Of the 350 women who participated, 61% were familiar with 'breast density' and 57% had 'some knowledge'. Prior breast density notification (OR = 4.99, 95% CI = 2.76, 9.03; p = 0.004), awareness (OR = 4.05, 95% CI = 2.57, 6.39; p = 0.004), younger age (OR = 0.97, 95% CI = 0.96, 0.99; p = 0.02), and English as the language spoken at home (OR = 3.29, 95% CI = 1.23, 8.77; p = 0.02) were independent predictors of 'some knowledge' of breast density. A significant proportion of participants (82%) expressed desire to ascertain their individual breast density. Conclusions: While knowledge of breast density in this Australian cohort is generally quite low, we have identified factors associated with increased knowledge. Further research is required to determine optimal interventions to increase breast density knowledge.

The Difficulties of Managing Pain in People Living with Frailty: The Potential for Digital Phenotyping.

Pain and frailty are closely linked. Chronic pain is a risk factor for frailty, and frailty is a risk factor for pain. People living with frailty also commonly have cognitive impairment, which can make assessment of pain and monitoring of pain management even more difficult. Pain may be sub-optimally treated in people living with frailty, people living with cognitive impairment and those with both these factors. Reasons for sub-optimal treatment in these groups are pharmacological (increased drug side effects, drug-drug interactions, polypharmacy), non-pharmacological (erroneous beliefs about pain, ageism, bidirectional communication challenges), logistical (difficulty in accessing primary care practitioners and unaffordable cost of drugs), and, particularly in cognitive impairment, related to communication difficulties. Thorough assessment and characterisation of pain, related sensations, and their functional, emotional, and behavioural consequences ("phenotyping") may help to enhance the assessment of pain, particularly in people with frailty and cognitive impairment, as this may help to identify who is most likely to respond to certain types of treatment. This paper discusses the potential role of "digital phenotyping" in the assessment and management of pain in people with frailty. Digital phenotyping is concerned with observable characteristics in digital form, such as those obtained from sensing-capable devices, and may provide novel and more informative data than existing clinical approaches regarding how pain manifests and how treatment strategies affect it. The processing of extensive digital and usual data may require powerful algorithms, but processing these data could lead to a better understanding of who is most likely to benefit from specific and targeted treatments.

A multiyear time series (2004-2012) of bacterial and archaeal community dynamics in a changing Arctic Ocean.

Climate change is profoundly impacting the Arctic, leading to a loss of multiyear sea ice and a warmer, fresher upper Arctic Ocean. The response of microbial communities to these climate-mediated changes is largely unknown. Here, we document the interannual variation in bacterial and archaeal communities across a 9-year time series of the Canada Basin that includes two historic sea ice minima (2007 and 2012). We report an overall loss of bacterial and archaeal community richness and significant shifts in community composition. The magnitude and period of most rapid change differed between the stratified water layers. The most pronounced changes in the upper water layers (surface mixed layer and upper Arctic water) occurred earlier in the time series, while changes in the lower layer (Pacific-origin water) occurred later. Shifts in taxonomic composition across time were subtle, but a decrease in Bacteroidota taxa and increase in Thaumarchaeota and Euryarchaeota taxa were the clearest signatures of change. This time series provides a rare glimpse into the potential influence of climate change on Arctic microbial communities; extension to the present day should contribute to deeper insights into the trajectory of Arctic marine ecosystems in response to warming and freshening.

Effects of Analgesics on Self-Reported Physical Function and Walking Ability in People With Hip or Knee Osteoarthritis: A Systematic Review and Meta-Analysis.

OBJECTIVE: Hip and knee osteoarthritis are among the leading causes of global disability, and one of the main aims of the management is to improve physical function. The objective of this review was to investigate the effect of analgesics on physical function (self-reported physical function and walking ability). METHODS: A systematic review and meta-analysis of the findings were performed. Randomized controlled trials investigating the effect of analgesics on self-reported physical function and walking ability were included. Analgesics were orally administered acetaminophen, nonsteroidal antiinflammatory drugs (NSAIDs), or opioids. Data were pooled in a random-effects model, and the standardized mean difference (SMD) with 95% CI was calculated (SMDs: 0.2-0.4 = small, 0.5-0.7 = medium, and ≥0.8 = large effect sizes). The quality of the evidence was evaluated according to the Grading of Recommendations Assessment, Development, and Evaluation approach. RESULTS: A total of 1454 studies were identified, of which 33 were included. On self-reported physical function, the results showed low- to moderate-quality evidence for a small beneficial effect of acetaminophen (SMD = -0.13 [95% CI = -0.26 to 0.00]), NSAIDs (SMD = -0.32 [95% CI = -0.37 to -0.27]), or opioids (SMD = -0.20 [95% CI = -0.32 to -0.09]). There was moderate-quality evidence for a small effect of NSAIDs on pain during walking (SMD = -0.34 [95% CI = -0.45 to -0.23]). CONCLUSION: In people with hip or knee osteoarthritis, there was low- to moderate-quality evidence for small beneficial effects of analgesics on physical function and walking ability. IMPACT: Analgesics may improve physical function by reducing pain during exercise and walking.

Influence of central aspects of pain on self-management in people with chronic low back pain.

OBJECTIVE: This observational study investigated whether central aspects of pain are associated with self-management domains in individuals with chronic low back pain (CLBP) undertaking a pain management program. METHODS: Individuals with CLBP provided pain sensitivity and self-management data at baseline (n = 97) and 3-months (n = 87). Pressure pain detection threshold (PPT) at the forearm, temporal summation (TS) and conditioned pain modulation (CPM), Widespread Pain Index (WPI), and a Central Aspects of Pain factor (CAPf) were considered as central aspects of pain. Self-management was measured using the 8 domains of the Health Education Impact Questionnaire, as well as Pain Self Efficacy and Health Care Utilisation questionnaires. RESULTS: PPT, CPM, WPI and CAPf predicted worse performance in several self-management domains at 3-months (r = 0.21 to 0.54, p < 0.05 overall). In multivariable regression models (adjusted for baseline scores of self-management, depression, catastrophization, pain and fatigue) low PPT, high TS, and high CAPf at baseline predicted poorer self-management at 3 months (R2 =0.14 to 0.52, ß = -0.37 to 0.35, p < 0.05). CONCLUSIONS: Central aspects of pain are associated with impaired self-management, over and above effects of pain intensity, fatigue, depression and catastrophizing. PRACTICE IMPLICATIONS: Treatments that target central aspects of pain might help improve self-management in people with CLBP.

The STAR care pathway for patients with chronic pain after total knee replacement: four-year follow-up of a randomised controlled trial.

BACKGROUND: The Support and Treatment After Replacement (STAR) care pathway is a clinically important and cost-effective intervention found to improve pain outcomes over one year for people with chronic pain three months after total knee replacement (TKR). We followed up STAR trial participants to evaluate the longer-term clinical- and cost-effectiveness of this care pathway. METHODS: Participants who remained enrolled on the trial at one year were contacted by post at a median of four years after randomisation and invited to complete a questionnaire comprising the same outcomes collected during the trial. We captured pain (co-primary outcome using the Brief Pain Inventory (BPI) pain severity and interference scales; scored 0-10, best to worst), function, neuropathic characteristics, emotional aspects of pain, health-related quality of life, and satisfaction. Electronic hospital informatics data on hospital resource use for the period of one to four years post-randomisation were collected from participating hospital sites. The economic evaluation took an National Health Service (NHS) secondary care perspective, with a four-year time horizon. RESULTS: Overall, 226/337 (67%) of participants returned completed follow-up questionnaires, yielding adjusted between-group differences in BPI means of -0.42 (95% confidence interval, CI (-1.07, 0.23); p = 0.20) for pain severity and - 0.64 (95% CI -1.41, 0.12); p = 0.10) for pain interference. Analysis using a multiple imputed data set (n = 337) showed an incremental net monetary benefit in favour of the STAR care pathway of £3,525 (95% CI -£990 to £8,039) at a £20,000/QALY willingness-to-pay threshold, leading to a probability that the intervention was cost-effective of 0.94. CONCLUSIONS: The magnitude of the longer-term benefits of the STAR care pathway are uncertain due to attrition of trial participants; however, there is a suggestion of some degree of sustained clinical benefit at four years. The care pathway remained cost-effective at four years. TRIAL REGISTRATION: ISRCTN: 92,545,361.

Social security cuts and life expectancy: a longitudinal analysis of local authorities in England, Scotland and Wales.

BACKGROUND: The UK Government's 'welfare reform' programme included reductions to social security payments, phased in over the financial years 2011/2012-2015/2016. Previous studies of social security cuts and health outcomes have been restricted to analysing single UK countries or single payment types (eg, housing benefit). We examined the association between all social security cuts fully implemented by 2016 and life expectancy, for local authorities in England, Scotland and Wales. METHODS: Our unit of analysis was 201 upper tier local authorities (unitary authorities and county councils: 147 in England, 32 in Scotland, 22 in Wales). Our exposure was estimated social security loss per head of the working age population per year for each local authority, calculated against the baseline in 2010/2011. The primary outcome was annual life expectancy at birth between the calendar years 2012 and 2016 (year lagged following exposure). We used a panel regression approach with fixed effects. RESULTS: Social security cuts implemented by 2016 were estimated to be £475 per head of the working age population in England, £390 in Scotland and £490 in Wales since 2010/2011. During the study period, there was either no improvement or only marginal increases in national life expectancy. Social security loss and life expectancy were significantly associated: an estimated £100 decrease in social security per head of working age population was associated with a 1-month reduction in life expectancy. CONCLUSIONS: Social security cuts, at the UK local authority level, were associated with lower life expectancy. Further research should examine causality.

Estimating the cost and epidemiology of mild to severe chronic pain associated with osteoarthritis in England: a retrospective analysis of linked primary and secondary care data.

OBJECTIVE: Osteoarthritis (OA) affects 10% of adults in the UK. Despite over one-third of people with OA experiencing chronic pain, few studies have examined the population-level impact of chronic pain associated with OA. We compared resource-use and epidemiological outcomes in patients with mild, moderate and severe chronic OA-associated pain and matched controls without known OA. DESIGN: Retrospective, longitudinal, observational cohort study (July 2008 to June 2019). SETTING: Electronic records extracted from Clinical Practice Research Datalink GOLD primary care linked to Hospital Episode Statistics (HES). PARTICIPANTS: Patients (cases; n=23 016) aged ≥18 years with chronic OA-associated pain. Controls (n=23 016) without OA or chronic pain matched on age, sex, comorbidity burden, general practitioner practice and available HES data. INTERVENTIONS: None. PRIMARY AND SECONDARY OUTCOME MEASURES: Total healthcare resource use (HCRU), direct healthcare costs in 0-12, 12-24 and 24-36 months postindex. Secondary outcomes included incidence and prevalence of chronic OA-associated pain and pharmacological management. RESULTS: HCRU was consistently greater in cases versus controls for all resource categories during preindex and postindex periods. Across follow-up periods, resource use was greatest in patients with severe pain. In the first 12 months postindexing, mean total costs incurred by cases were four times higher versus matched controls (£256 vs £62); costs were approximately twice as high in cases vs controls for months 12-24 (£166 vs £86) and 24-36 (£150 vs £81; all p<0.0001). The incidence of new cases of chronic pain associated with OA was 2.64 per 1000 person-years; the prevalence was 1.4%. CONCLUSIONS: This study highlights the real-world cost of chronic pain associated with OA in cases versus matched controls. We included patients with mild, moderate and severe pain associated with OA, and showed HCRU in discrete 1-year time frames. The true economic burden of pain associated with OA is likely to be considerably higher when indirect costs are considered.

Chronic Low Back Pain with and without Concomitant Osteoarthritis: A Retrospective, Longitudinal Cohort Study of Patients in England.

Objective: Despite the high prevalence of chronic low back pain (CLBP) and osteoarthritis (OA), few estimates of the economic cost of these conditions in England have been published. The aim of the present analysis was to characterise the economic burden of moderate-to-severe pain associated with CLBP + OA and CLBP alone compared with general population-matched controls without CLBP or OA. The primary objective was to describe the total healthcare resource use (HCRU) and direct healthcare costs associated with the target patient populations. Secondary objectives were to describe treatment patterns and surgical procedures. Methods: This was a retrospective, observational cohort study of patients receiving healthcare indicative of moderate-to-severe chronic pain associated with CLBP, with or without OA. We used linked longitudinal data from the Clinical Practice Research Datalink GOLD and Hospital Episode Statistics (HES). Patients (cases) were matched 1 : 1 with controls on age, sex, comorbidity burden, GP practice, and HES data availability. Results: The CLBP-alone cohort comprised 13 554 cases with CLBP and 13 554 matched controls; the CLBP + OA cohort comprised 7803 cases with both OA and CLBP and 7803 matched controls. Across all follow-up periods, patients with CLBP alone and those with CLBP + OA had significantly more GP consultations, outpatient attendances, emergency department visits, and inpatient stays than controls (all p < 0.0001). By 36 months after indexing, the mean (SD) per-patient total direct healthcare cost in the CLBP-alone cohort was £5081 (£5905) for cases and £1809 (£4451) for controls (p < 0.0001); in the CLBP + OA cohort, the mean (SD) per-patient total direct healthcare cost was £8819 (£7143) for cases and £2428 (£4280) for controls (p < 0.0001). Conclusion: Moderate-to-severe chronic pain associated with CLBP-with or without OA-has a substantial impact on patients and healthcare providers, leading to higher HCRU and costs versus controls among people with CLBP alone or together with OA.

Reproducible microbiome composition signatures of anxiety and depressive symptoms.

The gut microbiome is a significant contributor to mental health, with growing evidence linking its composition to anxiety and depressive disorders. Gut microbiome composition is associated with signs of anxiety and depression both in clinically diagnosed mood disorders and subclinically in the general population and may be influenced by dietary fibre intake and the presence of chronic pain. We provide an update of current evidence on the role of gut microbiome composition in depressive and anxiety disorders or symptoms by reviewing available studies. Analysing data from three independent cohorts (osteoarthritis 1 (OA1); n = 46, osteoarthritis 2 (OA2); n = 58, and healthy controls (CON); n = 67), we identified microbial composition signatures of anxiety and depressive symptoms at genus level and cross-validated our findings performing meta-analyses of our results with results from previously published studies. The genera Bifidobacterium (fixed-effect beta (95% CI) = -0.22 (-0.34, -0.10), p = 3.90e-04) and Lachnospiraceae NK4A136 group (fixed-effect beta (95% CI) = -0.09 (-0.13, -0.05), p = 2.53e-06) were found to be the best predictors of anxiety and depressive symptoms, respectively, across our three cohorts and published literature taking into account demographic and lifestyle covariates, such as fibre intake. The association with anxiety was robust in accounting for heterogeneity between cohorts and supports previous observations of the potential prophylactic effect of Bifidobacterium against anxiety symptoms.

Associations of Muscle Strength with Central Aspects of Pain: Data from the Knee Pain and Related Health in the Community (KPIC) Cohort.

Knee pain is associated with lower muscle strength, and both contribute to disability. Peripheral and central neurological mechanisms contribute to OA pain. Understanding the relative contributions of pain mechanisms to muscle strength might help future treatments. The Knee Pain and related health In the Community (KPIC) cohort provided baseline and year 1 data from people with early knee pain (n = 219) for longitudinal analyses. A cross-sectional analysis was performed with baseline data from people with established knee pain (n = 103) and comparative data from people without knee pain (n = 98). Quadriceps and handgrip strength indicated local and general muscle weakness, respectively. The indices of peripheral nociceptive drive were knee radiographic and ultrasound scores. The indices associated with central pain mechanisms were Pressure Pain detection Threshold (PPT) distal to the knee, and a validated self-report Central Aspects of Pain Factor (CAPF). The associations were explored using correlation and multivariable regression. Weaker quadriceps strength was associated with both high CAPF and low PPT at baseline. Year 1 quadriceps weakness was predicted by higher baseline CAPF (ß = -0.28 (95% CI: -0.55, -0.01), p = 0.040). Weaker baseline and year 1 handgrip strength was also associated with higher baseline CAPF. Weaker baseline quadriceps strength was associated with radiographic scores in bivariate but not adjusted analyses. Quadriceps strength was not significantly associated with total ultrasound scores. Central pain mechanisms might contribute to muscle weakness, both locally and remote from the knee.

What is missing from how we measure and understand the experience of poverty and deprivation in population health analyses?

BACKGROUND: Explaining why some populations are healthier than others is a core task of epidemiology. Socioeconomic position (SEP), encompassing a broad range of exposures relating to economic circumstances, social class and deprivation, is an important explanation, but lacks a comprehensive framework for understanding the range of relevant exposures it encompasses. METHODS: We reviewed existing literature on experiential accounts of poverty through database searching and the identification of relevant material by experts. We mapped relevant concepts into a complex systems diagram. We developed this diagram through a process of consultation with academic experts and experts with direct experience of poverty. Finally, we categorized concepts on the basis of whether they have previously been measured, their importance to the causal flow of the diagram, and their importance to those consulted, creating a list of priorities for future measurement. RESULTS: There are a great many aspects of SEP which are not frequently measured or used in epidemiological research and, for some of these, work is needed to better conceptualize and develop measures. Potentially important missing aspects include stigma, social class processes, access to education, sense of lost potential, neighbourhoods, fairness and justice, emotional labour, masking poverty, being (in)visible, costs, and experiences of power. CONCLUSIONS: Analyses seeking to understand the extent to which SEP exposures explain differences in the health of populations are likely to benefit from a comprehensive understanding of the range and inter-relationships between different aspects of SEP. More research to better conceptualize and measure these aspects is now needed.

The interrater and test-retest reliability of 3 modalities of quantitative sensory testing in healthy adults and people with chronic low back pain or rheumatoid arthritis.

Introduction: Quantitative Sensory Testing (QST) modalities used to assess central pain mechanisms require different protocols in people with different musculoskeletal conditions. Objectives: We aimed to explore the possible effects of musculoskeletal diagnosis and test site on QST interrater and test-retest reliability. Methods: The study included participants with rheumatoid arthritis (RA, n = 18; QST conducted on lower leg) and low back pain (LBP, n = 25; QST conducted on forearm), plus 45 healthy control participants (n = 20 QST on lower leg and n = 25 QST on forearm). Test-retest reliability was assessed from QST conducted 1 to 3 weeks apart. Quantitative sensory testing modalities used were pressure pain detection threshold (PPT) at a site distant to tissue pathology, temporal summation (TS), and conditioned pain modulation (CPM). Temporal summation was calculated as difference or ratio of single and repeated punctate stimuli and unconditioned thresholds for CPM used single or mean of multiple PPTs. Intraclass correlation coefficients (ICCs) were compared between different subgroups. Results: High to very high reliability was found for all assessments of PPT and TS across anatomical sites (lower leg and forearm) and participants (healthy, RA, and LBP) (ICC ≥ 0.77 for PPT and ICC ≥ 0.76 for TS). Reliability was higher when TS was calculated as a difference rather than a ratio. Conditioned pain modulation showed no to moderate reliability (ICC = 0.01-0.64) that was similar between leg or forearm, and between healthy people and those with RA or LBP. Conclusion: PPT and TS are transferable tools to quantify pain sensitivity at different testing sites in different musculoskeletal diagnoses. Low apparent reliability of CPM protocols might indicate minute-to-minute dynamic pain modulation.