Gender difference in symptomatic radiographic knee osteoarthritis in the Knee Clinical Assessment – CAS(K): A prospective study in the general population

<p>Abstract</p> <p>Background</p> <p>A recent study of adults aged ≥50 years reporting knee pain found an excess of radiographic knee osteoarthritis (knee ROA) in symptomatic males compared to females. This was independent of age, BMI and other clinical signs and symptoms. Since this finding contradicts many previous studies, our objective was to explore four possible explanations for this gender difference: X-ray views, selection, occupation and non-articular conditions.</p> <p>Methods</p> <p>A community-based prospective study. 819 adults aged ≥50 years reporting knee pain in the previous 12 months were recruited by postal questionnaires to a research clinic involving plain radiography (weight-bearing posteroanterior semiflexed, supine skyline and lateral views), clinical interview and physical examination. Any knee ROA, ROA severity, tibiofemoral joint osteoarthritis (TJOA) and patellofemoral joint osteoarthritis (PJOA) were defined using all three radiographic views. Occupational class was derived from current or last job title. Proportions of each gender with symptomatic knee ROA were expressed as percentages, stratified by age; differences between genders were expressed as percentage differences with 95% confidence intervals.</p> <p>Results</p> <p>745 symptomatic participants were eligible and had complete X-ray data. Males had a higher occurrence (77%) of any knee ROA than females (61%). In 50–64 year olds, the excess in men was mild knee OA (particularly PJOA); in ≥65 year olds, the excess was both mild and moderate/severe knee OA (particularly combined TJOA/PJOA). This male excess persisted when using the posteroanterior view only (64% vs. 52%). The lowest level of participation in the clinic was symptomatic females aged 65+. Within each occupational class there were more males with symptomatic knee ROA than females. In those aged 50–64 years, non-articular conditions were equally common in both genders although, in those aged 65+, they occurred more frequently in symptomatic females (41%) than males (31%).</p> <p>Conclusion</p> <p>The excess of knee ROA among symptomatic males in this study seems unlikely to be attributable to the use of comprehensive X-ray views. Although prior occupational exposures and the presence of non-articular conditions cannot be fully excluded, selective non-participation bias seems the most likely explanation. This has implications for future study design.</p

Reverse engineering: transaminase biocatalystdevelopment using ancestral sequencereconstruction

The development of new biocatalysts using ancestral sequence reconstruction is reported. When applied to an ω-transaminase, the ancestral proteins demonstrated novel and superior activities with eighty percent of the forty compounds tested compared to the modern day protein, and improvements in activity of up to twenty fold. These included a range of compounds pertinent as feedstocks in polyamide manufacture.MW and SK were supported by CSIRO Research Office Postdoctoral Fellowships

Acute Flares of Knee Osteoarthritis (the ACT-FLARE Study): Protocol for a Web-Based Case-Crossover Study in Community-Dwelling Adults.

BACKGROUND The cardinal feature of osteoarthritis (OA) is pain. Although heterogeneity in pain and function have been demonstrated in the long-term course of OA, the more proximate determinants of acute flare-ups remain less clear. How short-term intermittent or transient exposures trigger acute flare-ups has important implications for effective and sustainable self-management strategies. OBJECTIVE The primary objective of this study is to identify potential triggers of acute flares in knee OA. Secondary objectives are to determine their course and consequences and describe high-risk participant profiles. METHODS We carried out a Web-based case-crossover study. This study aims to recruit 620 community-dwelling adults aged ≥40 years, resident in England, and who have knee pain, with or without a recorded diagnosis of knee OA, and no preexisting diagnosis of inflammatory arthropathy. Participants will be recruited via 3 routes: (1) general practice registers, (2) offline community advertisement, and (3) online social media advertisement. By using questionnaires comparing periods before participants' self-reported flare-up episodes (hazard periods) with periods during the study when their knee OA symptoms are stable (control periods), triggers preceding flare-ups will be identified and examined using conditional logistic regression. Time-to-resolution of flare-up will be examined by monitoring people's daily pain, bothersomeness, and medication usage until the participant reports when their flare-up episode ends. Rates of flare-ups will be examined across different participant and flare characteristics using regression models to identify high-risk participant profiles. A study-specific Patient Advisory Group (PAG) is providing suggestion, input, and ongoing support for all stages of the research process. RESULTS Participant recruitment opened in July 2018 and is anticipated to continue for 6 months. The study results will be disseminated through a number of channels, including relevant national or international conferences and peer-reviewed publication in a medical journal, via advocacy or charity organizations, such as Versus Arthritis and across social media. Findings will be fed back to members of our PAG, study participants, and clinicians from participating primary care general practices. The PAG will also take an active role in the overall dissemination strategy. CONCLUSIONS This study will provide empirical evidence to help patients identify common knee OA flare triggers and provide health care professionals with questions to identify patients at most risk of frequent flare-ups. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/13428

The Knee Clinical Assessment Study – CAS(K). A prospective study of knee pain and knee osteoarthritis in the general population: baseline recruitment and retention at 18 months

BACKGROUND: Selective non-participation at baseline (due to non-response and non-consent) and loss to follow-up are important concerns for longitudinal observational research. We investigated these matters in the context of baseline recruitment and retention at 18 months of participants for a prospective observational cohort study of knee pain and knee osteoarthritis in the general population. METHODS: Participants were recruited to the Knee Clinical Assessment Study – CAS(K) – by a multi-stage process involving response to two postal questionnaires, consent to further contact and medical record review (optional), and attendance at a research clinic. Follow-up at 18-months was by postal questionnaire. The characteristics of responders/consenters were described for each stage in the recruitment process to identify patterns of selective non-participation and loss to follow-up. The external validity of findings from the clinic attenders was tested by comparing the distribution of WOMAC scores and the association between physical function and obesity with the same parameters measured directly in the target population as whole. RESULTS: 3106 adults aged 50 years and over reporting knee pain in the previous 12 months were identified from the first baseline questionnaire. Of these, 819 consented to further contact, responded to the second questionnaire, and attended the research clinics. 776 were successfully followed up at 18 months. There was evidence of selective non-participation during recruitment (aged 80 years and over, lower socioeconomic group, currently in employment, experiencing anxiety or depression, brief episode of knee pain within the previous year). This did not cause significant bias in either the distribution of WOMAC scores or the association between physical function and obesity. CONCLUSION: Despite recruiting a minority of the target population to the research clinics and some evidence of selective non-participation, this appears not to have resulted in significant bias of cross-sectional estimates. The main effect of non-participation in the current cohort is likely to be a loss of precision in stratum-specific estimates e.g. in those aged 80 years and over. The subgroup of individuals who attended the research clinics and who make up the CAS(K) cohort can be used to accurately estimate parameters in the reference population as a whole. The potential for selection bias, however, remains an important consideration in each subsequent analysis

The DINGO dataset: a comprehensive set of data for the SAMPL challenge

Part of the latest SAMPL challenge was to predict how a small fragment library of 500 commercially available compounds would bind to a protein target. In order to assess the modellers’ work, a reasonably comprehensive set of data was collected using a number of techniques. These included surface plasmon resonance, isothermal titration calorimetry, protein crystallization and protein crystallography. Using these techniques we could determine the kinetics of fragment binding, the energy of binding, how this affects the ability of the target to crystallize, and when the fragment did bind, the pose or orientation of binding. Both the final data set and all of the raw images have been made available to the community for scrutiny and further work. This overview sets out to give the parameters of the experiments done and what might be done differently for future studies

Predictors of pain interference and potential gain from intervention in community dwelling adults with joint pain: A prospective cohort study.

INTRODUCTION: There is little research on identifying modifiable risk factors that predict future interference of pain with daily activity in people with joint pain, and the estimation of the corresponding population attributable risk (PAR). The present study therefore investigated modifiable predictors of pain interference and estimated maximum potential gain from intervention in adults with joint pain. METHODS: A population-based cohort aged ≥50 years was recruited from eight general practices in North Staffordshire, UK. Participants (n = 1878) had joint pain at baseline lasting ≥3 months and indicated no pain interference. Adjusted associations of self-reported, potentially modifiable prognostic factors (body mass index, anxiety/depressive symptoms, widespread pain, inadequate joint pain control, physical inactivity, sleep problems, smoking and alcohol intake) with onset of pain interference 3 years later were estimated via Poisson regression, and corresponding PAR estimates were obtained. RESULTS: Inadequate joint-specific pain control, insomnia and infrequent walking were found to be independently significantly associated with the onset of pain interference after 3 years, with associated PARs of 6.3% (95% confidence interval -0.3, 12.4), 7.6% (-0.4, 15.0) and 8.0% (0.1, 15.2), respectively, with only the PAR for infrequent walking deemed statistically significant. The PAR associated with insomnia, infrequent walking and inadequate control of joint pain simultaneously was 20.3% (8.6, 30.4). CONCLUSIONS: There is potential to reduce moderately the onset of pain interference from joint pain in the over-50s if clinical and public health interventions targeted pain management and insomnia, and promoted an active lifestyle. However, most of the onset of significant pain interference in the over-50s, would not be prevented, even assuming that these factors could be eliminated

The Knee Clinical Assessment Study – CAS(K). A prospective study of knee pain and knee osteoarthritis in the general population

BACKGROUND: Knee pain affects an estimated 25% of the adult population aged 50 years and over. Osteoarthritis is the most common diagnosis made in older adults consulting with knee pain in primary care. However, the relationship between this diagnosis and both the current disease-based definition of osteoarthritis and the regional pain syndrome of knee pain and disability is unclear. Expert consensus, based on current evidence, views the disease and the syndrome as distinct entities but the clinical usefulness of these two approaches to classifying knee pain in older adults has not been established. We plan to conduct a prospective, population-based, observational cohort study to investigate the relative merits of disease-based and regional pain syndrome-based approaches to classification and prognosis of knee pain in older adults. METHODS: All patients aged 50 years and over registered with three general practices in North Staffordshire will be invited to take part in a two-stage postal survey. Respondents to this survey phase who indicate that they have experienced knee pain within the previous 12 months will be invited to attend a research clinic for a detailed assessment. This will consist of clinical interview, physical examination, digital photography, plain x-rays, anthropometric measurement and a brief self-complete questionnaire. All consenting clinic attenders will be followed up by (i) general practice medical record review, (ii) repeat postal questionnaire at 18-months

On the need for an international effort to capture, share and use crystallization screening data

Development of an ontology for the description of crystallization experiments and results is proposed

"I feel so stupid because I can't give a proper answer ..." How older adults describe chronic pain: a qualitative study

Background - Over 50% of older adults experience chronic pain. Poorly managed pain threatens independent functioning, limits social activities and detrimentally affects emotional wellbeing. Yet, chronic pain is not fully understood from older adults’ perspectives; subsequently, pain management in later life is not necessarily based on their priorities or needs. This paper reports a qualitative exploration of older adults’ accounts of living with chronic pain, focusing on how they describe pain, with a view to informing approaches to its assessment. Methods - Cognitively intact men and women aged over sixty-five who lived in the community opted into the study through responding to advertisements in the media and via contacts with groups and organisations in North-East Scotland. Interviews were transcribed and thematically analysed using a framework approach. Results - Qualitative individual interviews and one group interview were undertaken with 23 older adults. Following analysis, the following main themes emerged: diversity in conceptualising pain using a simple numerical score; personalising the meaning of pain by way of stories, similes and metaphors; and, contextualising pain in relation to its impact on activities. Conclusions - The importance of attending to individuals’ stories as a meaningful way of describing pain for older adults is highlighted, suggesting that a narrative approach, as recommended and researched in other areas of medicine, may usefully be applied in pain assessment for older adults. Along with the judicious use of numerical tools, this requires innovative methods to elicit verbal accounts, such as using similes and metaphors to help older adults describe and discuss their experience, and contextualising the effects of pain on activities that are important to them