3,462 research outputs found
Patient-reported outcomes measures of X-linked hypophosphataemia participants: findings from a prospective cohort study in the UK
Background X-linked hypophosphataemia (XLH) is a rare genetic condition passed on through the X chromosome which causes multiple symptoms including weakened teeth, bones, and muscles. Due to the rarity of the condition, little is known about the health outcomes as reported by people with the disease. The objectives of this study were threefold: to characterise key patient reported outcome measures (PROMs) in adults with XLH, to identify clusters of symptom-severity groups based on PROMs, and to analyse the longitudinal progression of available PROMs.
Methods Data from 48 participants from the Rare and Undiagnosed Diseases cohort Study (RUDY) was used to analyse both cross-sectional and longitudinal patient-reported outcomes. We analysed data for health-related quality of life (HRQL): EuroQol 5 dimensions-5 levels (EQ-5D-5L), Short-form 36 (SF-36) Physical Component Score (PCS), and SF-36 Mental Component Score (MCS), sleep: Pittsburgh sleep quality index (PSQI) and Epworth Sleepiness scale (ESS), fatigue: Fatigue Severity Scale (FSS) and Functional assessment of chronic illness therapy-fatigue (FACIT-F), pain: Short form McGill pain questionnaire version 2 (SF-MPQ-2) and PainDETECT, and mental well-being: Hospital anxiety and depression scale (HADS) anxiety and depression. Summary statistics, tests of mean differences, mixed-effects models, and cluster analysis were used to describe and examine the various health dimensions of individuals with XLH.
Results Overall mean scores were EQ-5D-5L = 0.65, SF-36-PCS = 32.7, and SF-36-MCS = 48.4 for HRQL, ESS = 5.9 and PSQI = 8.9 for sleep, FSS = 32.8 and FACIT-F = 104.4 for fatigue, SF-MPQ-2 = 1.9 for pain, and HADS-depression = 4.7 and HADS-anxiety = 6.2 for mental well-being. 7% reported neuropathic pain (PainDETECT). Whilst many adults with XLH reported good outcomes, extreme or severe problems were reported across all outcomes. Cluster analysis identified that adults with XLH could be divided into two distinct groups, one reporting worse (35.3%) and the other better outcomes (64.7%) (less pain, fatigue, depression, and higher levels of sleep). Longitudinal analysis showed that FACIT-F and HADS-anxiety scores worsened slightly over two years with statistically significant (p
Conclusion Although about two thirds of adult participants of the RUDY cohort with XLH report good health outcomes, for a considerable third much worse outcomes are reported. More research is needed to examine why some experience good and others poor health outcomes and the characteristics which identify them
Predicting incident radiographic knee osteoarthritis in middle-aged women within 4 years:the importance of knee-level prognostic factors.
ObjectiveDevelop and internally validate risk models and a clinical risk score tool to predict incident radiographic knee osteoarthritis (RKOA) in middle‐aged women.MethodsWe analysed 649 women in the Chingford 1000 Women study. The outcome was incident RKOA, defined as Kellgren/Lawrence grade 0‐1 at baseline and ≥2 at year 5. We estimated predictors' effects on the outcome using logistic regression models. Two models were generated. The clinical model considered patient characteristics, medication, biomarkers, and knee symptoms. The radiographic model considered the same factors, plus radiographic factors (e.g., angle between the acetabular roof and ilium's vertical cortex (hip α‐angle)). The models were internally validated. Model performance was assessed using calibration and discrimination (area under the receiver characteristic curve, AUC).ResultsThe clinical model contained age, quadriceps circumference, and a cartilage degradation marker (CTX‐II) as predictors (AUC = 0.692). The radiographic model contained older age, greater quadriceps circumference, knee pain, knee baseline Kellgren/Lawrence grade 1 (versus 0), greater hip α‐angle, greater spinal bone mineral density, and contralateral RKOA at baseline as predictors (AUC = 0.797). Calibration tests showed good agreement between the observed and predicted incident RKOA. A clinical risk score tool was developed from the clinical model.ConclusionTwo models predicting incident RKOA within 4 years were developed; including radiographic variables improved model performance. First‐time predictor hip α‐angle and contralateral RKOA suggest osteoarthritis origins beyond the knee. The clinical tool has the potential to help physicians identify patients at risk of RKOA in routine practice, but should be externally validated
Risk of Injury in Royal Air Force Training: Does Sex Really Matter?
IntroductionMusculoskeletal injuries are common during military and other occupational physical training programs. Employers have a duty of care to reduce employees’ injury risk, where females tend to be at greater risk than males. However, quantification of principle co-factors influencing the sex–injury association, and their relative importance, remain poorly defined. Injury risk co-factors were investigated during Royal Air Force (RAF) recruit training to inform the strategic prioritization of mitigation strategies.Material and MethodsA cohort of 1,193 (males n = 990 (83%); females n = 203 (17%)) recruits, undertaking Phase-1 military training, were prospectively monitored for injury occurrence. The primary independent variable was sex, and potential confounders (fitness, smoking, anthropometric measures, education attainment) were assessed pre-training. Generalized linear models were used to assess associations between sex and injury.ResultsIn total, 31% of recruits (28% males; 49% females) presented at least one injury during training. Females had a two-fold greater unadjusted risk of injury during training than males (RR = 1.77; 95% CI 1.49–2.10). After anthropometric, lifestyle and education measures were included in the model, the excess risk decreased by 34%, but the associations continued to be statistically significant. In contrast, when aerobic fitness was adjusted, an inverse association was identified; the injury risk was 40% lower in females compared with males (RR = 0.59; 95% CI: 0.42–0.83).ConclusionsPhysical fitness was the most important confounder with respect to differences in males’ and females’ injury risk, rather than sex alone. Mitigation to reduce this risk should, therefore, focus upon physical training, complemented by healthy lifestyle interventions
Patient-reported symptoms and diagnostic journey in Multiple Myeloma
IntroductionLate presentation of multiple myeloma (MM) heightens the risk of complication risks, including end-organ damage. This study aimed to: 1) detail the diagnostic journey of MM patients, encompassing symptoms, initial diagnoses, and healthcare professionals met; 2) establish the median duration from symptom onset to MM diagnosis; and 3) examine factors linked to timely MM diagnosis within 12 weeks. MethodsA total of 300 adults self-reporting MM were analysed from the Rare and Undiagnosed Diseases cohort Study (RUDY). The RUDY study is a web-based platform, where participants provide dynamic consent and self-report their MM diagnosis and information about their diagnostic journey. This includes the estimated date of initial potential first symptoms, descriptions of these symptoms, the healthcare professionals they consulted, and other diagnoses received before the MM diagnosis. Descriptive statistics, combinatorial analyses and logistic regression analyses were used to describe and examine the diagnostic journey of individuals with MM.ResultsOverall, 52% of the participants reported other diagnoses before MM diagnosis, with musculoskeletal disorders (47.8%), such as osteoporosis, costochondritis, or muscle strains, being the most common. The most prevalent initial reported symptom was back pain/vertebral fractures (47%), followed by chest/shoulder pain, including rib pain and fractures (20%), and fatigue/tiredness (19.7%). 40% of participants were diagnosed by direct referral from primary care to haematology without seeing other healthcare professionals whilst 60% consulted additional specialists before diagnosis. The median time from symptom onset to MM diagnosis was 4 months (IQR 2-10 months, range 0-172). Seeing an Allied Healthcare Professional such as a physiotherapist, chiropractor or an osteopath (OR = 0.25, 95% CI [0.12, 0.47], p <0.001), experiencing infection symptoms (OR = 0.32, 95% CI [0.13, 0.76], p = 0.013), and having chest or shoulder pain (OR = 0.45, 95% CI [0.23, 0.86], p = 0.020) were associated with a lower likelihood of being diagnosed with MM within 12 weeks. Older age (OR = 1.04, 95% CI [1.02, 1.07], p = 0.001) was associated with a higher likelihood of diagnosis within 12 weeks.DiscussionDeveloping resources for allied health professionals may improve early recognition of MM
Progression of chronic pain and associated health-related quality of life and healthcare resource use over 5 years after total knee replacement: evidence from a cohort study
Objective As part of the STAR Programme, a comprehensive study exploring long-term pain after surgery, we investigated how pain and function, health-related quality of life (HRQL), and healthcare resource use evolved over 5 years after total knee replacement (TKR) for those with and without chronic pain 1 year after their primary surgery.
Methods We used data from the Clinical Outcomes in Arthroplasty Study prospective cohort study, which followed patients undergoing TKR from two English hospitals for 5 years. Chronic pain was defined using the Oxford Knee Score Pain Subscale (OKS-PS) where participants reporting a score of 14 or lower were classified as having chronic pain 1-year postsurgery. Pain and function were measured with the OKS, HRQL using the EuroQoL-5 Dimension, resource use from yearly questionnaires, and costs estimated from a healthcare system perspective. We analysed the changes in OKS-PS, HRQL and resource use over a 5-year follow-up period. Multiple imputation accounted for missing data.
Results Chronic pain was reported in 70/552 operated knees (12.7%) 1 year after surgery. The chronic pain group had worse pain, function and HRQL presurgery and postsurgery than the non-chronic pain group. Those without chronic pain markedly improved right after surgery, then plateaued. Those with chronic pain improved slowly but steadily. Participants with chronic pain reported greater healthcare resource use and costs than those without, especially 1 year after surgery, and mostly from hospital readmissions. 64.7% of those in chronic pain recovered during the following 4 years, while 30.9% fluctuated in and out of chronic pain.
Conclusion Although TKR is often highly beneficial, some patients experienced chronic pain postsurgery. Although many fluctuated in their pain levels and most recovered over time, identifying people most likely to have chronic pain and supporting their recovery would benefit patients and healthcare systems
Risk Factors for Mobility Decline in Community-Dwelling Older Adults: A Systematic Literature Review
Mobility is essential to maintaining independence for older adults. This systematic review aimed to summarize evidence about self-reported risk factors for self-reported mobility decline; and to provide an overview of published prognostic models for self-reported mobility decline among community-dwelling older adults. Databases were searched from inception to June 2, 2020. Studies were screened by two independent reviewers who extracted data and assessed study quality. Sixty-one studies (45,187 participants) were included, providing information on 107 risk factors. High-quality evidence and moderate/large effect sizes for the association with mobility decline were found for older age beyond 75 years, the presence of widespread pain, and mobility modifications. Moderate-high quality evidence and small effect sizes were found for a further 21 factors. Three model development studies demonstrated acceptable model performance, limited by high risk of bias. These findings should be considered in intervention development, and in developing a prediction instrument for practical application
Association of metabolic syndrome with knee and hand osteoarthritis:A community-based study of women
CD69 is a TGF-β/1α,25-dihydroxyvitamin D3 target gene in monocytes
CD69 is a transmembrane lectin that can be expressed on most hematopoietic cells. In monocytes, it has been functionally linked to the 5-lipoxygenase pathway in which the leukotrienes, a class of highly potent inflammatory mediators, are produced. However, regarding CD69 gene expression and its regulatory mechanisms in monocytes, only scarce data are available. Here, we report that CD69 mRNA expression, analogous to that of 5-lipoxygenase, is induced by the physiologic stimuli transforming growth factor-β (TGF-β) and 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) in monocytic cells. Comparison with T- and B-cell lines showed that the effect was specific for monocytes. CD69 expression levels were increased in a concentration-dependent manner, and kinetic analysis revealed a rapid onset of mRNA expression, indicating that CD69 is a primary TGF-β/1α,25(OH)2D3 target gene. PCR analysis of different regions of the CD69 mRNA revealed that de novo transcription was initiated and proximal and distal parts were induced concomitantly. In common with 5-lipoxygenase, no activation of 0.7 kb or ~2.3 kb promoter fragments by TGF-β and 1α,25(OH)2D3 could be observed in transient reporter assays for CD69. Analysis of mRNA stability using a transcription inhibitor and a 3′UTR reporter construct showed that TGF-β and 1α,25(OH)2D3 do not influence CD69 mRNA stability. Functional knockdown of Smad3 clearly demonstrated that upregulation of CD69 mRNA, in contrast to 5-LO, depends on Smad3. Comparative studies with different inhibitors for mitogen activated protein kinases (MAPKs) revealed that MAPK signalling is involved in CD69 gene regulation, whereas 5-lipoxygenase gene expression was only partly affected. Mechanistically, we found evidence that CD69 gene upregulation depends on TAK1-mediated p38 activation. In summary, our data indicate that CD69 gene expression, conforming with 5-lipoxygenase, is regulated monocyte-specifically by the physiologic stimuli TGF-β and 1α,25(OH)2D3 on mRNA level, although different mechanisms account for the upregulation of each gene
Determination of the antimutagenicity of an aqueous extract of Rhizophora mangle L. (Rhizophoraceae), using in vivo and in vitro test systems
An aqueous extract of Rhizophora mangle L. bark is used as raw material in pottery making in the State of Espirito Santo, Brazil. This extract presents large quantities of tannins, compounds possessing antioxidant properties. Tannin antioxidant activity, as a plant chemical defense mechanism in the process of stabilizing free radicals, has been an incentive to studies on anti-mutagenicity. The present work aimed to evaluate possible antimutagenic activity of a R. mangle aqueous extract, using the Allium cepa test-system and micronuclear (MN) assay with blockage of cytokinesis in Chinese hamster ovary cells (CHO-K1). The Allium cepa test-system indicated antimutagenic activity against the damage induced by the mutagenic agent methyl methanesulfonate. A reduction in both MN cell frequency and chromosome breaks occurred in both the pre and post-treatment protocols. The MN testing of CHO-K1 cells revealed anti-mutagenic activity of the R. mangle extract against methyl methanesulfonate and doxorubicin in pre, simultaneous and post-treatment protocols. These results suggest the presence of phyto-constituents in the extract presenting demutagenic and bio-antimutagenic activities. Since the chemical constitution of Rhizophora mangle species presents elevated tannin content, it is highly probable that these compounds are the antimutagenic promoters themselves
Real-World Six- and Twelve-Month Drug Retention, Remission, and Response Rates of Secukinumab in 2,017 Patients With Psoriatic Arthritis in Thirteen European Countries
Objective There is a lack of real-life studies on interleukin-17 (IL-17) inhibition in psoriatic arthritis (PsA). We assessed real-life 6- and 12-month effectiveness (i.e., retention, remission, low disease activity [LDA], and response rates) of the IL-17 inhibitor secukinumab in PsA patients overall and across 1) number of prior biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs), 2) years since diagnosis, and 3) European registries. Methods Thirteen quality registries in rheumatology participating in the European Spondyloarthritis Research Collaboration Network provided longitudinal, observational data collected as part of routine care for secondary use. Data were pooled and analyzed with Kaplan-Meier plots, log rank tests, Cox regression, and multiple linear and logistic regression analyses. Results A total of 2,017 PsA patients started treatment with secukinumab between 2015 and 2018. Overall secukinumab retention rates were 86% and 76% after 6 and 12 months, respectively. Crude (LUNDEX adjusted) 6-month remission/LDA (LDA including remission) rates for the 28-joint Disease Activity Index for Psoriatic Arthritis, the Disease Activity Score in 28 joints using the C-reactive protein level, and the Simplified Disease Activity Index (SDAI) were 13%/46% (11%/39%), 36%/55% (30%/46%), and 13%/56% (11%/47%), and 12-month rates were 11%/46% (7%/31%), 39%/56% (26%/38%), and 16%/62% (10%/41%), respectively. Clinical Disease Activity Index remission/LDA rates were similar to the SDAI rates. Six-month American College of Rheumatology 20%/50%/70% improvement criteria responses were 34%/19%/11% (29%/16%/9%); 12-month rates were 37%/21%/11% (24%/14%/7%). Secukinumab effectiveness was significantly better for b/tsDMARD-naive patients, similar across time since diagnosis (4 years), and varied significantly across the European registries. Conclusion In this large real-world study on secukinumab treatment in PsA, 6- and 12-month effectiveness was comparable to that in previous observational studies of tumor necrosis factor inhibitors. Retention, remission, LDA, and response rates were significantly better for b/tsDMARD-naive patients, were independent of time since diagnosis, and varied significantly across the European countries.Peer reviewe
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