Lived experiences of informal caregivers of people with chronic musculoskeletal pain: a systematic review and meta-ethnography

BACKGROUND: People with chronic pain often seek support from friends and family for everyday tasks. These individuals are termed informal caregivers. There remains uncertainty regarding the lived experiences of these people who care for individuals with chronic musculoskeletal pain. The aim of this paper is to synthase the evidence on the lived experiences of informal caregivers providing care to people with chronic musculoskeletal pain. METHODS: A systematic literature review was undertaken of published and unpublished literature databases including: EMBASE, MEDLINE, CINAHL, PubMed, the WHO International Clinical Trial Registry and ClinicalTrials.gov registry (to September 2019). Qualitative studies exploring the lived experiences of informal caregivers of people with chronic musculoskeletal pain were included. Data were synthesised using a meta-ethnography approach. Evidence was evaluated using the Critical Appraisal Skills Programme (CASP) qualitative appraisal tool. RESULTS: From 534 citations, 10 studies were eligible (360 participants: 171 informal caregivers of 189 care recipients). The evidence was moderate quality. Seven themes arose: the relationship of caregivers to healthcare professionals, role reversal with care recipients; acting the confidant to the care recipient; a constant burden in caregiving; legitimising care recipient’s condition; knowledge and skills to provide caregiving; and the perception of other family members and wider-society to the caregiver/care recipient dyad. CONCLUSIONS: The lived experiences of caregivers of people with chronic musculoskeletal pain is complex and dynamic. There is an inter-connected relationship between caregivers, care recipients and healthcare professionals. Exploring how these experiences can be modified to improve a caregiving dyad’s lived experience is now warranted

Randomized controlled trial of adalimumab in patients with nonpsoriatic peripheral spondyloarthritis

Objective. To evaluate the efficacy and safety of adalimumab in patients with active nonpsoriatic peripheral spondyloarthritis (SpA). Methods. ABILITY-2 is an ongoing phase III, multicenter study of adalimumab treatment. Eligible patients age 18 years fulfilled the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for peripheral SpA, did not have a prior diagnosis of psoriasis, psoriatic arthritis (PsA), or ankylosing spondylitis (AS), and had an inadequate response or intolerance to nonsteroidal antiinflammatory drugs (NSAIDs). Patients were randomized 1:1 to receive adalimumab 40 mg every other week or matching placebo for 12 weeks, followed by a 144-week open-label period. The primary end point was the proportion of patients achieving 40% improvement in disease activity according to the Peripheral SpA Response Criteria (PSpARC40) at week 12. This was defined as 40% improvement from baseline (20-mm absolute improvement on a visual analog scale) in patient's global assessments of disease activity and pain, and 40% improvement in at least one of the following features: swollen joint and tender joint counts, total enthesitis count, or dactylitis count. Adverse events were recorded throughout the study. Results. In total, 165 patients were randomized to a treatment group, of whom 81 were randomized to receive placebo and 84 to receive adalimumab. Baseline demographics and disease characteristics were generally similar between the 2 groups. At week 12, a greater proportion of patients receiving adalimumab achieved a PSpARC40 response compared to patients receiving placebo (39% versus 20%; P = 0.006). Overall, improvement in other outcomes was greater in the adalimumab group compared to the placebo group. The rates of adverse events were similar in both treatment groups. Conclusion. Treatment with adalimumab ameliorated the signs and symptoms of disease and improved physical function in patients with active nonpsoriatic peripheral SpA who exhibited an inadequate response or intolerance to NSAIDs, with a safety profile consistent with that observed in patients with AS, PsA, or other immune-mediated diseases

Rings of real functions in pointfree topology

AbstractThis paper deals with the algebra F(L) of real functions on a frame L and its subclasses LSC(L) and USC(L) of, respectively, lower and upper semicontinuous real functions. It is well known that F(L) is a lattice-ordered ring; this paper presents explicit formulas for its algebraic operations which allow to conclude about their behaviour in LSC(L) and USC(L).As applications, idempotent functions are characterized and previous pointfree results about strict insertion of functions are significantly improved: general pointfree formulations that correspond exactly to the classical strict insertion results of Dowker and Michael regarding, respectively, normal countably paracompact spaces and perfectly normal spaces are derived.The paper ends with a brief discussion concerning the frames in which every arbitrary real function on the α-dissolution of the frame is continuous

Localized Nasopharyngeal Amyloidosis

A mass in the nasopharynx often implies a malignancy in adults, particularly in the endemic areas of Epstein-Barr virus-associated undifferentiated carcinoma. We report an 86-year-old male patient who presented to our rhinologic outpatient department with postnasal drip for several years, with no other associated nasal symptoms. Physical examination with nasal endoscopy found a prominent bulge in the nasopharynx. Pathological examination of the biopsied specimens identified features consistent with amyloidosis. Magnetic resonance imaging demonstrated an enhanced soft-tissue mass localized to the nasopharyngeal region. We excluded the possibility of a partial representation of a potential systemic amyloidosis. Regular follow-up including nasal endoscopy was undertaken. Over 3 years of observation, the disease process remained silent. Here, the clinical presentation, diagnosis and treatment options of this rare entity are discussed

The JAK inhibitor tofacitinib suppresses synovial JAK1-STAT signalling in rheumatoid arthritis.

ObjectiveTofacitinib is an oral Janus kinase (JAK) inhibitor for the treatment of rheumatoid arthritis (RA). The pathways affected by tofacitinib and the effects on gene expression in situ are unknown. Therefore, tofacitinib effects on synovial pathobiology were investigated.MethodsA randomised, double-blind, phase II serial synovial biopsy study (A3921073; NCT00976599) in patients with RA with an inadequate methotrexate response. Patients on background methotrexate received tofacitinib 10 mg twice daily or placebo for 28 days. Synovial biopsies were performed on Days -7 and 28 and analysed by immunoassay or quantitative PCR. Clinical response was determined by disease activity score and European League Against Rheumatism (EULAR) response on Day 28 in A3921073, and at Month 3 in a long-term extension study (A3921024; NCT00413699).ResultsTofacitinib exposure led to EULAR moderate to good responses (11/14 patients), while placebo was ineffective (1/14 patients) on Day 28. Tofacitinib treatment significantly reduced synovial mRNA expression of matrix metalloproteinase (MMP)-1 and MMP-3 (p<0.05) and chemokines CCL2, CXCL10 and CXCL13 (p<0.05). No overall changes were observed in synovial inflammation score or the presence of T cells, B cells or macrophages. Changes in synovial phosphorylation of signal transducer and activator of transcription 1 (STAT1) and STAT3 strongly correlated with 4-month clinical responses (p<0.002). Tofacitinib significantly decreased plasma CXCL10 (p<0.005) at Day 28 compared with placebo.ConclusionsTofacitinib reduces metalloproteinase and interferon-regulated gene expression in rheumatoid synovium, and clinical improvement correlates with reductions in STAT1 and STAT3 phosphorylation. JAK1-mediated interferon and interleukin-6 signalling likely play a key role in the synovial response.Trial registration numberNCT00976599

A survey of cost-sensitive decision tree induction algorithms

The past decade has seen a significant interest on the problem of inducing decision trees that take account of costs of misclassification and costs of acquiring the features used for decision making. This survey identifies over 50 algorithms including approaches that are direct adaptations of accuracy based methods, use genetic algorithms, use anytime methods and utilize boosting and bagging. The survey brings together these different studies and novel approaches to cost-sensitive decision tree learning, provides a useful taxonomy, a historical timeline of how the field has developed and should provide a useful reference point for future research in this field

Sustained improvements in MRI outcomes with abatacept following the withdrawal of all treatments in patients with early, progressive rheumatoid arthritis

Objectives: To assess structural damage progression with subcutaneous abatacept (ABA) in the Assessing Very Early Rheumatoid arthritis Treatment (AVERT) trial following abrupt withdrawal of all rheumatoid arthritis (RA) medication in patients achieving Disease Activity Score (DAS)-defined remission or low disease activity. Methods: Patients with early, active RA were randomised to ABA plus methotrexate (ABA/MTX) 125 mg/week, ABA 125 mg/week or MTX for 12 months. All RA treatments were withdrawn after 12 months in patients with DAS28 (C reactive protein (CRP)) <3.2. Adjusted mean changes from baseline in MRI-based synovitis, osteitis and erosion were calculated for the intention-to-treat population. Results: 351 patients were randomised and treated: ABA/MTX (n=119), ABA (n=116) or MTX (n=116). Synovitis and osteitis improved, and progression of erosion was statistically less with ABA/MTX versus MTX at month 12 (−2.35 vs −0.68, −2.58 vs −0.68, 0.19 vs 1.53, respectively; p<0.01 for each) and month 18 (−1.34 vs −0.49 −2.03 vs 0.34, 0.13 vs 2.0, respectively; p<0.01 for erosion); ABA benefits were numerically intermediate to those for ABA/MTX and MTX. Conclusions: Structural benefits with ABA/MTX or ABA may be maintained 6 months after withdrawal of all treatments in patients who have achieved remission or low disease activity

Ensemble of a subset of kNN classifiers

Combining multiple classifiers, known as ensemble methods, can give substantial improvement in prediction performance of learning algorithms especially in the presence of non-informative features in the data sets. We propose an ensemble of subset of kNN classifiers, ESkNN, for classification task in two steps. Firstly, we choose classifiers based upon their individual performance using the out-of-sample accuracy. The selected classifiers are then combined sequentially starting from the best model and assessed for collective performance on a validation data set. We use bench mark data sets with their original and some added non-informative features for the evaluation of our method. The results are compared with usual kNN, bagged kNN, random kNN, multiple feature subset method, random forest and support vector machines. Our experimental comparisons on benchmark classification problems and simulated data sets reveal that the proposed ensemble gives better classification performance than the usual kNN and its ensembles, and performs comparable to random forest and support vector machines

Evaluating the cost-effectiveness of biologic treatments for psoriatic arthritis: : can we make better use of patient data registries?

The primary aim of this study is to explore the extent to which registry data may fulfill the evidence requirements of cost-effectiveness analysis (CEA) studies evaluating biologic therapies for the treatment of psoriatic arthritis (PsA), where trial data are lacking or insufficient. In addition, the paper aims to identify how future data collection in PsA registries might be better tailored to inform CEA research. A review of the literature was performed to identify existing registries containing PsA patients. Where possible, information was extracted on the design and characteristics of the registries. The registries were then appraised according to a set of criteria that was formulated based on the methods currently used to model PsA in the CEA literature. A review of the literature identified 21 potentially relevant registries from around the world containing patients with PsA. There was substantial variation regarding the extent to which the registries, as a whole, were useful for the purposes of CEA studies. There were also notable disparities found in terms of the accessibility of the registries to researchers. The critical review conducted in this study showed that all of the registries identified are potentially useful, at least in some degree, for the purposes of informing CEA studies in PsA. However, no individual registry on its own was found to meet all of the evidence requirements when considering how the disease has been modeled previously