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Experience sampling methodology and daily diary (ESM/DD) research elicits repeated reports of immediate or very recent experiences from the same sample of people for several days or weeks. Experience sampling and diary methods were almost unheard of in organizational research 15 years ago, but the past decade has seen a rapid rise in their use. These methods are helpful in studying dynamic within-person processes involving affect, behavior, interpersonal interactions, work events, and other transient workplace phenomena over time. Assessing cross-level effects of traits or other stable features on within-person processes and reactivity is also possible with ESM/DD data. We provide an introduction to issues in designing and carrying out an ESM/DD study, including data collection choices and schedules, measures, technology, training and motivation of participants, and analysis of multilevel data. We offer best practice recommendations and refer readers to further resources for additional detail on conducting and analyzing ESM/DD research.

Most people presenting with incident osteoporotic fractures are neither assessed nor treated for osteoporosis to reduce their risk of further fractures, despite the availability of effective treatments. We evaluated the effectiveness of published models of care for the secondary prevention of osteoporotic fractures. We searched eight medical literature databases to identify reports published between 1996 and 2011, describing models of care for secondary fracture prevention. Information extracted from each publication included study design, patient characteristics, identification strategies, assessment and treatment initiation strategies, as well as outcome measures (rates of bone mineral density (BMD) testing, osteoporosis treatment initiation, adherence, re-fractures and cost-effectiveness). Meta-analyses of studies with valid control groups were conducted for two outcome measures: BMD testing and osteoporosis treatment initiation. Out of 574 references, 42 articles were identified as analysable. These studies were grouped into four general models of care—type A: identification, assessment and treatment of patients as part of the service; type B: similar to A, without treatment initiation; type C: alerting patients plus primary care physicians; and type D: patient education only. Meta-regressions revealed a trend towards increased BMD testing ( p  = 0.06) and treatment initiation ( p  = 0.03) with increasing intensity of intervention. One type A service with a valid control group showed a significant decrease in re-fractures. Types A and B services were cost-effective, although definition of cost-effectiveness varied between studies. Fully coordinated, intensive models of care for secondary fracture prevention are more effective in improving patient outcomes than approaches involving alerts and/or education only.

Diabetic retinopathy (DR) is the leading cause of blindness in working-age adults. Early stage DR involves inflammation, vascular leakage, apoptosis of vascular cells and neurodegeneration. In this study, we hypothesized that cells derived from the stromal fraction of adipose tissue (ASC) could therapeutically rescue early stage DR features. Streptozotocin (STZ) induced diabetic athymic nude rats received single intravitreal injection of human ASC into one eye and saline into the other eye. Two months post onset of diabetes, administration of ASC significantly improved \"b\" wave amplitude (as measured by electroretinogram) within 1-3 weeks of injection compared to saline treated diabetic eyes. Subsequently, retinal histopathological evaluation revealed a significant decrease in vascular leakage and apoptotic cells around the retinal vessels in the diabetic eyes that received ASC compared to the eyes that received saline injection. In addition, molecular analyses have shown down-regulation in inflammatory gene expression in diabetic retina that received ASC compared to eyes that received saline. Interestingly, ASC were found to be localized near retinal vessels at higher densities than seen in age matched non-diabetic retina that received ASC. In vitro, ASC displayed sustained proliferation and decreased apoptosis under hyperglycemic stress. In addition, ASC in co-culture with retinal endothelial cells enhance endothelial survival and collaborate to form vascular networks. Taken together, our findings suggest that ASC are able to rescue the neural retina from hyperglycemia-induced degeneration, resulting in importantly improved visual function. Our pre-clinical studies support the translational development of adipose stem cell-based therapy for DR to address both retinal capillary and neurodegeneration.

Background Knee osteoarthritis (OA) is a common and important cause of pain and disability, but interventions aimed at modifying structures visible on imaging have been disappointing. While OA affects the whole joint, synovitis and effusion have been recognised as having a role in the pathogenesis of OA. Krill oil reduces knee pain and systemic inflammation and could be used for targeting inflammatory mechanisms of OA. Methods/design We will recruit 260 patients with clinical knee OA, significant knee pain and effusion-synovitis present on MRI in five Australian cities (Hobart, Melbourne, Sydney, Adelaide and Perth). These patients will be randomly allocated to the two arms of the study, receiving 2 g/day krill oil or inert placebo daily for 6 months. MRI of the study knee will be performed at screening and after 6 months. Knee symptoms, function and MRI structural abnormalities will be assessed using validated methods. Safety data will be recorded. Primary outcomes are absolute change in knee pain (assessed by visual analog score) and change in size of knee effusion-synovitis over 24 weeks. Secondary outcomes include improvement in knee pain over 4, 8, 12, 16 and 20 weeks. The primary analyses will be intention-to-treat analyses of primary and secondary outcomes. Per protocol analyses adjusting for missing data and for treatment compliance will be performed as the secondary analyses. Discussion This study will provide high-quality evidence to assess whether krill oil 2 g/day reduces pain and effusion-synovitis size in older adults with clinical knee OA and knee effusion-synovitis. If krill oil is effective and confirmed to be safe, we will provide compelling evidence that krill oil improves pain and function, changes disease trajectory and slows disease progression in OA. Given the lack of approved therapies for slowing disease progression in OA, and moderate cost of krill oil, these findings will be readily translated into clinical practice. Trial registration Australian New Zealand Clinical Trials Registry, ACTRN12616000726459 . Registered on 02 June 2016. Universal Trial Number (UTN) U1111–1181-7087.

Obesity is associated with a range of disabling musculoskeletal conditions in adults. As the prevalence of obesity increases, the societal burden of these chronic musculosketelal conditions, in terms of disability, health-related quality of life, and health-care costs, also increases. Research exploring the nature and strength of the associations between obesity and musculoskeletal conditions is accumulating, providing a better understanding of underlying mechanisms. Weight reduction is important in ameliorating some of the manifestations of musculoskeletal disease and improving function.

Introduction The Global Burden of Disease Study 2010 estimated the worldwide health burden of 291 diseases and injuries and 67 risk factors by calculating disability-adjusted life years (DALYs). Osteoporosis was not considered as a disease, and bone mineral density (BMD) was analysed as a risk factor for fractures, which formed part of the health burden due to falls. Objectives To calculate (1) the global distribution of BMD, (2) its population attributable fraction (PAF) for fractures and subsequently for falls, and (3) the number of DALYs due to BMD. Methods A systematic review was performed seeking population-based studies in which BMD was measured by dual-energy X-ray absorptiometry at the femoral neck in people aged 50 years and over. Age- and sex-specific mean ± SD BMD values (g/cm2) were extracted from eligible studies. Comparative risk assessment methodology was used to calculate PAFs of BMD for fractures. The theoretical minimum risk exposure distribution was estimated as the age- and sex-specific 90th centile from the Third National Health and Nutrition Examination Survey (NHANES III). Relative risks of fractures were obtained from a previous meta-analysis. Hospital data were used to calculate the fraction of the health burden of falls that was due to fractures. Results Global deaths and DALYs attributable to low BMD increased from 103 000 and 3 125 000 in 1990 to 188 000 and 5 216 000 in 2010, respectively. The percentage of low BMD in the total global burden almost doubled from 1990 (0.12%) to 2010 (0.21%). Around one-third of falls-related deaths were attributable to low BMD. Conclusions Low BMD is responsible for a growing global health burden, only partially representative of the real burden of osteoporosis.

Severe inflammatory stress often leads to vessel rarefaction and fibrosis, resulting in limited tissue recovery. However, signaling pathways mediating these processes are not completely understood. Patients with ischemic and inflammatory conditions have increased systemic Activin A level, which frequently correlates with the severity of pathology. Yet, Activin A’s contribution to disease progression, specifically to vascular homeostasis and remodeling, is not well defined. This study investigated vasculogenesis in an inflammatory environment with an emphasis on Activin A’s role. Exposure of endothelial cells (EC) and perivascular cells (adipose stromal cells, ASC) to inflammatory stimuli (represented by blood mononuclear cells from healthy donors activated with lipopolysaccharide, aPBMC) dramatically decreased EC tubulogenesis or caused vessel rarefaction compared to control co-cultures, concurrent with increased Activin A secretion. Both EC and ASC upregulated Inhibin Ba mRNA and Activin A secretion in response to aPBMC or their secretome. We identified TNFα (in EC) and IL-1β (in EC and ASC) as the exclusive inflammatory factors, present in aPBMC secretome, responsible for induction of Activin A. Similar to ASC, brain and placental pericytes upregulated Activin A in response to aPBMC and IL-1β, but not TNFα. Both these cytokines individually diminished EC tubulogenesis. Blocking Activin A with neutralizing IgG mitigated detrimental effects of aPBMC or TNFα/IL-1β on tubulogenesis in vitro and vessel formation in vivo. This study delineates the signaling pathway through which inflammatory cells have a detrimental effect on vessel formation and homeostasis, and highlights the central role of Activin A in this process. Transitory interference with Activin A during early phases of inflammatory or ischemic insult, with neutralizing antibodies or scavengers, may benefit vasculature preservation and overall tissue recovery.

Summary We investigated change in health-related quality of life due to fracture in Australian adults aged over 50 years. Fractures reduce quality of life with the loss sustained at least over 12 months. At a population level, the loss was equivalent to 65 days in full health per fracture. Purpose We aimed to quantify the change in health-related quality of life (HRQoL) that occurred as a consequence of a fracture using the EQ-5D-3 L questionnaire. Methods Adults aged ≥50 years with a low to moderate energy fracture were recruited from eight study centres across Australia. This prospective study included an 18-month follow-up of participants recruited within 2 weeks of a fracture (hip, wrist, humerus, vertebral and ankle). Information collected at baseline and 4, 12 and 18 months included characteristics of participants such as income level, education and prior fracture status. At 12 months post-fracture, the cumulative loss of quality of life was estimated using multivariate regression analysis to identify the predictors of HRQoL loss. Results Mean HRQoL for all participants before fracture was 0.86, with wrist fracture having the highest pre-fracture HRQoL (0.90), while vertebral fracture had the lowest (0.80). HRQoL declined to 0.42 in the immediate post-fracture period. Only participants with a wrist, humerus or ankle fracture returned to their pre-fracture HRQoL after 18 months. An increased loss of HRQoL over 12 months was associated with HRQoL prior to the fracture, hospitalisation, education and fracture site. The multiple regression explained 30 % of the variation in the cumulative HRQoL loss at 12 months post-fracture for all fractures. Conclusion Low to moderate energy fractures reduce HRQoL, and this loss is sustained for at least 12 months or, in the case of hip and spine fractures, at least 18 months. At a population level, this represents an average loss of 65 days in full health per fragility fracture. This significant burden reinforces the need for cost-effective fracture prevention strategies.

BackgroundHaving a score to assess the occurrence and severity of flares of knee or hip osteoarthritis (OA) to guide interventions is essential.ObjectivesTo compare different methods of constructing a composite score for the Flare-OA-16 self-reported questionnaire for measuring knee and hip OA flare, defined as a cluster of symptoms of sufficient duration and intensity to require initiation, change or increase in therapy [1].MethodsParticipants with a physician diagnosis of knee and hip OA completed a validated 16-item questionnaire [2,3] assessing five dimensions of flare in OA: pain, swelling, stiffness, psychological aspects, and consequences of symptoms, endorsed by OMERACT. Three estimation methods were compared: the score obtained i) by second-order confirmatory factor analysis (CFA) weighting the factor loadings in a linear combination of the five dimensions; ii) by logistic regression, modeling the probability of having a flare according to the participant’s self-report (yes/no); and iii) by Rasch method, using the average of the weighted scores from a Rasch model in each dimension. For the scores obtained by the three methods, the disordered items were modified, and then the scores were standardized on a scale from 0 to 10. The distribution (floor effect without flare (FF) and ceiling effect with flare (CF)) of the scores in each model was compared. The similarity between the scores was analyzed by intraclass correlation coefficient (ICC) and their performance were compared by areas under the ROC curves (AUC) and 95% confidence interval. The intra-score test-retest reliability at 15 days was assessed by ICC.ResultsIn a sample of 381 participants with complete questionnaires, 247 reported having a flare. With CFA, good fit indices (CFI=0.94; RMSEA=.08) justified the estimation of an overall score mean=3.90 (SD=2.79), with FF effect 27.6% and CF 2.0%. For the logistic regression estimation, the overall score was mean=6.48 (SD=3.13), with FF 0% and CF 34.0% effect. With the Rasch model, the composite score was mean=4.15 (SD=2.45), with FF 18.7% and CF 0% effect. Similarity analysis indicated a greater concordance between the CFA and Rasch scores (ICC=.99) than between the logistic regression score and the two others (ICC=.87 for each). The ROC curve indicated similar performance of the overall scores estimated by logistic model (AUC=.88 [.85-.92]), by CFA (AUC=.86 [.82-.90]) and by Rasch model (AUC=.86 [.82-.90]). The performance in terms of reproducibility was ICC=.84[.95-.90] for Rasch and CFA scores and ICC=.78[.66-86] for logistic model.ConclusionThis comparison of methods for constructing a global score for knee and hip OA flare explored three satisfactory alternatives. The second-order CFA confirmed the uniqueness of the flare construct measure, the logistic model had a slight superiority explained by the anchor variable used (patient-reported flare), and the Rasch model ensured that an interval scale was obtained for each dimension. The distribution of scores with the lowest combination of floor and ceiling effects was in favor of the Rasch model. The next step will be to document their respective performance in terms of sensitivity to change. A score obtained from the patient’s point of view can help increase the adherence to the prescribed treatment and help physicians to optimize the scheduling and delivery of medical consultation.References[1]Guillemin F., et al. Developing a Preliminary Definition and Domains of Flare in Knee and Hip Osteoarthritis (OA): Consensus Building of the Flare-in-OA OMERACT Group. J Rheumatol. 2019 Sep;46(9):1188–91.[2]Traore Y., et al. Development and validation of the Flare-OA questionnaire for measuring flare in knee and hip osteoarthritis. Osteoarthritis Cartilage. 2022 May;30(5):689–96.[3]Queiroga F., et al. Validation et réduction d’une échelle de mesure des poussées dans l’arthrose de la hanche et du genou par un modèle de Rasch. Rev Épidémiol Santé Publique. 2022 May;70:S70.AcknowledgementsWe acknowledge the participants of the study samples that were used in the study, without whom this research could not been possible.Financial supportThis work was supported partly by the French PIA project “Lorraine Université d’Excellence”, reference ANR-15-IDEX-04-LUE.Disclosure of InterestsNone Declared.