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ID PMID Title PublicationDate abstract
29165795 Therapeutic potency of mTOR signaling pharmacological inhibitors in the treatment of proin 2018 Jun Mammalian target of rapamycin (mTOR) signaling pathway controls cell energy metabolism. There is an interplay between mTOR and proinflammatory signaling pathways, supporting the role of the pathway in the pathogenesis of inflammatory diseases. Inhibition of mTOR signaling using specific pharmacological inhibitors could offer therapeutic promise in several inflammatory-associated diseases. In this review, we summarize recent findings on the regulatory effects of mTOR signaling on inflammation and the therapeutic potency of mTOR pharmacological inhibitors in the treatment of inflammatory diseases including cancer, neurodegenerative diseases, atherosclerosis, sepsis, and rheumatoid arthritis for a better understanding and hence a better management of these diseases.
28339992 Rheumatoid arthritis-specific cardiovascular risk scores are not superior to general risk 2017 Jul 1 OBJECTIVES: Cardiovascular disease (CVD) risk calculators developed for the general population do not accurately predict CVD events in patients with RA. We sought to externally validate risk calculators recommended for use in patients with RA including the EULAR 1.5 multiplier, the Expanded Cardiovascular Risk Prediction Score for RA (ERS-RA) and QRISK2. METHODS: Seven RA cohorts from UK, Norway, Netherlands, USA, South Africa, Canada and Mexico were combined. Data on baseline CVD risk factors, RA characteristics and CVD outcomes (including myocardial infarction, ischaemic stroke and cardiovascular death) were collected using standardized definitions. Performance of QRISK2, EULAR multiplier and ERS-RA was compared with other risk calculators [American College of Cardiology/American Heart Association (ACC/AHA), Framingham Adult Treatment Panel III Framingham risk score-Adult Treatment Panel (FRS-ATP) and Reynolds Risk Score] using c-statistics and net reclassification index. RESULTS: Among 1796 RA patients without prior CVD [mean ( s . d .) age: 54.0 (14.0) years, 74% female], 100 developed CVD events during a mean follow-up of 6.9 years (12430 person-years). Estimated CVD risk by ERS-RA [mean ( s . d .) 8.8% (9.8%)] was comparable to FRS-ATP [mean ( s . d .) 9.1% (8.3%)] and Reynolds [mean ( s . d .) 9.2% (12.2%)], but lower than ACC/AHA [mean ( s . d .) 9.8% (12.1%)]. QRISK2 substantially overestimated risk [mean ( s . d .) 15.5% (13.9%)]. Discrimination was not improved for ERS-RA (c-statistic = 0.69), QRISK2 or EULAR multiplier applied to ACC/AHA compared with ACC/AHA (c-statistic = 0.72 for all) or for FRS-ATP (c-statistic = 0.75). The net reclassification index for ERS-RA was low (-0.8% vs ACC/AHA and 2.3% vs FRS-ATP). CONCLUSION: The QRISK2, EULAR multiplier and ERS-RA algorithms did not predict CVD risk more accurately in patients with RA than CVD risk calculators developed for the general population.
28188994 Anxiety disorder among rheumatoid arthritis patients: Insights from real-life data. 2017 Apr 15 BACKGROUND: Psychiatric disorders occur in a considerable proportion of patients with rheumatoid arthritis (RA), often reflecting the difficulties of these patients in coping with a chronic debilitating disorder. AIM OF THE STUDY: To evaluate the proportion of anxiety disorder in RA patients using a large database analysis. METHODS: The study was designed as a case-control population-based study using data from the Clalit Health Services (CHS) database. Patients were defined as having RA or anxiety disorder when there was at least one documented diagnosis identified by the International Classification of Diseases-9 (ICD-9) from the medical records. The proportion of anxiety disorder was compared between RA patients and controls. A logistic regression model was used to estimate the association between RA and anxiety disorder in a multivariate analysis adjusted for age, gender and socioeconomic status (SES). RESULTS: The study included 11,782 patients with RA and 57,973 age- and sex-frequency matched controls. The proportion of anxiety in RA patients was higher than in controls (7.1% vs 6.3%, p=0.001). In multivariate analysis, RA was found to be independently associated with anxiety (OR 1.11 [95%CI 1.03-1.20], p=0.01). Our study has some shortcomings, as its cross-sectional nature does not allow to make inferences about a causal relationship between RA and anxiety. CONCLUSION: Our study confirms the higher proportion of anxiety in RA patients, especially young women with low SES. Physicians should be aware of such findings and, therefore, apply proper screening strategies.
29238018 [Regulation of bone by IL-17-producing T cells]. 2017   Bone is a component of the skeletal-locomotor system but also functions as an immunological organ that harbors hematopoietic stem and progenitor cells. Since the immune and skeletal systems are closely related through a number of shared regulatory molecules including cytokines and receptors, bone can be affected in various immune disorders. Rheumatoid arthritis is a typical disease in which the immune system affects the bone metabolism. The enhanced activity of osteoclasts by the activation of Th17 cells causes the joint destruction in rheumatoid arthritis. Studies on bone destruction associated rheumatoid arthritis have highlighted the importance of the interplay between the immune and bone systems, and promoted the new interdisciplinary field of "osteoimmunology". Furthermore, recent studies have suggested that regulation of bone tissues by IL-17 is more complicated than we had expected. IL-17-prodcuing cells contribute to new bone formation at the enthesis in ankylosing spondylitis, and IL-17-producing γδ T cells promote bone regeneration by acting on the mesenchymal stem cells in bone fracture healing. It would be necessary to comprehensively understand the interplay between the immune and bone systems for elucidation of the molecular mechanisms underlying the pathogenesis of various diseases that involves the two systems.
27995383 Ultrasound resistive index, power Doppler, and clinical parameters in established rheumato 2017 Apr Ultrasonography (US) is a useful tool for the evaluation of sinovial vascularization and proliferation in rheumatoid arthritis (RA). Accordingly, resistive index (RI) on spectral Doppler (sD) US provides a quantitative analysis of vascular inflammation, but its utility in the evaluation of RA activity has not been established. Our objective was to determine the association of RI with other US parameters of synovitis and with clinical disease activity in established RA. Patients with positive power Doppler (pD) were included in a prospective cross-sectional study. Disease activity and disability were evaluated using the Disease Activity Score in 28-joints (DAS28) and Health Assessment Questionnaire (HAQ), respectively. Gray scale (GS) synovitis, pD, and sD analyses were performed by one of two examiners in wrists and the second and third metacarpophalangeal and proximal interphalangeal joints. The 10-joint GS and 10-joint pD scores and mean RI were then calculated. Weighted kappa (WK) values were employed to assess interobserver reability, and correlations were tested using the Spearman coefficient. Ninety-five RA patients (median duration of disease of 7 years and mean DAS28 of 4.32 ± 1.66) were included. WK values in real-time US were 0.77 for synovitis, 0.87 for pD, and 0.68 for RI. There were no significant correlations of RI with 10-joint GS, 10-joint pD, DAS28, joint counts, or HAQ (P > 0.10 for all tests). Patients in remission had a mean RI similar to those with high disease activity (0.62 ± 0.10, n = 15 versus 0.63 ± 0.13, n = 34, respectively). The addition of the RI score did not seem to improve US performance in patients with established RA.
28831575 A simplified and validated ultrasound scoring system to evaluate synovitis of bilateral wr 2018 Jan The objective of this study was to develop and validate an optimal simplified combination of joints for ultrasonographic assessment of synovitis in wrists and hands in patients with rheumatoid arthritis (RA). Twenty-two joints, including bilateral wrists, all proximal interphalangeal (PIP), and metacarpophalangeal (MCP) joints, were evaluated by grey-scale (GS) and power Doppler (PD) ultrasound using semi-quantitative scoring systems in 705 RA patients. Candidate joint sets were then selected by multiple linear regression analysis and the optimal candidate set was eventually validated in 235 RA patients. Through multiple linear regression analysis, the standard coefficient (β) of MCP2, MCP3, and MCP5 joints in terms of GS was higher than other joints. The adjusted R (2) of the model composed of wrist, MCP2, MCP3, and MCP5 joints was greater than 0.9. Among the sum GS and PD scores of various selected joint combinations, total score-8, including bilateral wrist, MCP2, MCP3, and MCP5 joints, not only showed highest sensitivity and negative predictive value (93.86 and 92.90% for GS; 97.20 and 97.21% for PD, respectively) but also the best correlation with the total score-22 (r = 0.955 and 0.972 for GS and PD). The score-8 was further validated in 235 RA patients. The sensitivity for detecting synovitis by GS and PD was 94.35 and 94.12%, and the negative predictive values were 94.07 and 95.68%, respectively. Total score-8 system, including bilateral wrist, MCP2, MCP3, and MCP5 joints, is simple and efficient to pick up active synovitis of wrists and hands in patients with RA in daily practice.
28705494 Inflammation initiated by stressed organelles. 2018 Jul Key cellular functions including those related to energy metabolism, organization of the genetic information or production of membrane-bound and secreted proteins are compartmentalized within organelles. Various stresses such as differentiation programs, viral and bacterial infections, perturbations in protein production, mechanical constraints, changes in the environment and nutriment accessibility can impact cellular homeostasis and organelle integrity. Perturbations of these cellular compartments trigger repair and adaptation programs aimed at restoring homeostasis. These events are often associated with low-grade inflammation also termed parainflammation. While the nature and mechanisms of danger signals released by irremediably damaged cells are well understood, how transiently stressed cells trigger inflammation is still poorly understood. Emerging studies highlighted new mechanisms by which stress pathways promote inflammation. Cytosolic innate immune pathways are engaged by signals stemming from perturbed organelles such as the mitochondria, the endoplasmic reticulum (ER) or the nuclear envelope (NE). These observations indicate that these pathways function as guardians of cellular homeostasis and may contribute to disease in pathologies characterized by perturbations of cellular homoeostasis. Mitochondria-stress, ER-stress or NE-stress are emerging as proinflammatory signals that contribute to human conditions and diseases.
28720503 Discovery of 3-morpholino-imidazole[1,5-a]pyrazine BTK inhibitors for rheumatoid arthritis 2017 Aug 15 8-Amino-imidazo[1,5-a]pyrazine-based Bruton's tyrosine kinase (BTK) inhibitors, such as 6, exhibited potent inhibition of BTK but required improvements in both kinase and hERG selectivity (Liu et al., 2016; Gao et al., 2017). In an effort to maintain the inhibitory activity of these analogs and improve their selectivity profiles, we carried out SAR exploration of groups at the 3-position of pyrazine compound 6. This effort led to the discovery of the morpholine group as an optimized pharmacophore. Compounds 13, 23 and 38 displayed excellent BTK potencies, kinase and hERG selectivities, and pharmacokinetic profiles.
28600026 MetabolitePredict: A de novo human metabolomics prediction system and its applications in 2017 Jul Human metabolomics has great potential in disease mechanism understanding, early diagnosis, and therapy. Existing metabolomics studies are often based on profiling patient biofluids and tissue samples and are difficult owing to the challenges of sample collection and data processing. Here, we report an alternative approach and developed a computation-based prediction system, MetabolitePredict, for disease metabolomics biomarker prediction. We applied MetabolitePredict to identify metabolite biomarkers and metabolite targeting therapies for rheumatoid arthritis (RA), a last-lasting complex disease with multiple genetic and environmental factors involved. MetabolitePredict is a de novo prediction system. It first constructs a disease-specific genetic profile using genes and pathways data associated with an input disease. It then constructs genetic profiles for a total of 259,170 chemicals/metabolites using known chemical genetics and human metabolomic data. MetabolitePredict prioritizes metabolites for a given disease based on the genetic profile similarities between disease and metabolites. We evaluated MetabolitePredict using 63 known RA-associated metabolites. MetabolitePredict found 24 of the 63 metabolites (recall: 0.38) and ranked them highly (mean ranking: top 4.13%, median ranking: top 1.10%, P-value: 5.08E-19). MetabolitePredict performed better than an existing metabolite prediction system, PROFANCY, in predicting RA-associated metabolites (PROFANCY: recall: 0.31, mean ranking: 20.91%, median ranking: 16.47%, P-value: 3.78E-7). Short-chain fatty acids (SCFAs), the abundant metabolites of gut microbiota in the fermentation of fiber, ranked highly (butyrate, 0.03%; acetate, 0.05%; propionate, 0.38%). Finally, we established MetabolitePredict's potential in novel metabolite targeting for disease treatment: MetabolitePredict ranked highly three known metabolite inhibitors for RA treatments (methotrexate:0.25%; leflunomide: 0.56%; sulfasalazine: 0.92%). MetabolitePredict is a generalizable disease metabolite prediction system. The only required input to the system is a disease name or a set of disease-associated genes. The web-based MetabolitePredict is available at:http://xulab. CASE: edu/MetabolitePredict.
28375194 Primary Breast Lymphoma with cutaneous involvement in a patient with Rheumatoid Arthritis 2017 Apr It is well established that rheumatoid arthritis is associated with an increased risk of lymphoma. The use of tumor-necrosis factor-α inhibitors as a therapy in rheumatoid arthritis has been related to higher incidence of lymphoma arising at atypical and/or unusual locations; however, recent data shows their safety. We report the case of a 79 year-old woman with rheumatoid arthritis treated with infliximab, who presented a primary breast lymphoma with cutaneous involvement.
28583280 Clinical Value of FDG-PET/CT for the Evaluation of Rheumatic Diseases: Rheumatoid Arthriti 2017 Jul FDG is a tracer for visualizing glucose metabolism. PET/CT using FDG is widely used for the diagnosis of cancer, because glycolysis is elevated in cancer cells. Similarly, active inflammatory tissue also exhibits elevated glucose metabolism because of glycolysis in activated macrophages and proliferating fibroblasts. Elevated FDG uptake by active inflammatory tissues, such as those affected by arthritis, vasculitis, lymphadenitis, and chondritis, has enabled the diagnosis of inflammatory diseases using FDG-PET/CT. Rheumatoid arthritis (RA) is a systemic, chronic inflammation of the joints resulting in synovitis. Several clinical studies of RA have demonstrated that FDG uptake in affected joints reflects the disease activity of RA, with strong correlations between FDG uptake and various clinical parameters having been noted. Furthermore, the use of FDG-PET for the sensitive detection and early monitoring of the response to RA therapy has been reported. RA is sometimes associated with subclinical vasculitis, which is related to systemic inflammation. FDG-PET/CT can be used to evaluate subclinical vasculitis in the aorta or carotid artery. Polymyalgia rheumatica (PMR) is an autoimmune musculoskeletal disease of unknown etiology characterized by pain and stiffness in the shoulder, neck, and pelvic girdle, but not in the small finger joints in the hands, together with fever, fatigue, and weight loss. There is no specific test for PMR, and its diagnosis is based on clinical diagnostic criteria and the exclusion of other diseases with similar symptoms. However, FDG-PET/CT reveals a characteristic FDG uptake by the bursitis in ischial tuberosity, greater trochanter, lumbar or cervical spinous process, and scapulohumeral joint. A combination of FDG-PET/CT findings showed a high diagnostic value for PMR in a differential diagnosis from RA. FDG-PET/CT is also very useful for evaluating large vessel vasculitis, which is often associated with PMR. Relapsing polychondritis is a rare multisystem disease of unknown etiology involving cartilaginous and proteoglycan-rich structures. Its rarity and diversity of symptoms often result in a delayed diagnosis. FDG-PET/CT reveals unique FDG uptake findings for chondritis in the auricular, nasal, trachea, bronchial tree, and costal cartilage and in the cartilage of joints. Thus, the spread of knowledge regarding these very specific FDG-PET/CT findings could promote the early diagnosis and improved disease control of relapsing polychondritis.
28189039 Low dose prednisolone and insulin sensitivity differentially affect arterial stiffness and 2017 Mar BACKGROUND AND AIMS: Glucocorticoids could impair vascular function directly, or indirectly by reducing insulin sensitivity. The aim of this study was to determine the direct and indirect effects of acute and chronic low dose prednisolone on arterial stiffness and endothelial function. METHODS: Twelve subjects with inflammatory arthritis, who had not taken oral glucocorticoids for ≥6 months, and 12 subjects with inflammatory arthritis, taking chronic (>6 months) low dose (6.3 ± 2.2 mg/day) prednisolone, were studied. Patients not on glucocorticoids underwent measurement of arterial stiffness (pulse wave velocity (PWV)) and endothelial function (reactive hyperaemia index (RHI)) before and after 7-10 days of prednisolone (6 mg/day), to assess the acute effects of prednisolone. Baseline data from patients not on glucocorticoids were compared with patients on long-term prednisolone to assess the chronic effects of prednisolone. Hepatic insulin sensitivity was estimated from percentage suppression of endogenous glucose production and peripheral insulin sensitivity as glucose infusion rate (M/I) during a hyperinsulinaemic-euglycaemic clamp. RESULTS: There were no significant changes in PWV with acute (9.2 ± 0.8 vs. 8.9 ± 0.8 m/sec, p = 0.33) or chronic (8.9 ± 0.8 vs. 9.0 ± 0.7 m/sec, p = 0.69) prednisolone. In multiple regression analysis, PWV was negatively associated with M/I during hyperinsulinemic-euglycemic clamp (p = 0.02), but not with suppression of endogenous glucose production (p = 0.15) or glucocorticoid use (p = 0.70). Chronic (2.4 ± 0.2 vs. 1.9 ± 0.1, p = 0.02), but not acute (1.8 ± 0.2 vs. 1.9 ± 0.1, p = 0.24), prednisolone resulted in a higher RHI. CONCLUSIONS: Arterial stiffness is not affected by low dose prednisolone per se, but is negatively associated with peripheral insulin sensitivity. Patients with rheumatoid arthritis taking long-term prednisolone had better endothelial function.
28053336 Leptin in the interplay of inflammation, metabolism and immune system disorders. 2017 Feb Leptin is one of the most relevant factors secreted by adipose tissue and the forerunner of a class of molecules collectively called adipokines. Initially discovered in 1994, its crucial role as a central regulator in energy homeostasis has been largely described during the past 20 years. Once secreted into the circulation, leptin reaches the central and peripheral nervous systems and acts by binding and activating the long form of leptin receptor (LEPR), regulating appetite and food intake, bone mass, basal metabolism, reproductive function and insulin secretion, among other processes. Research on the regulation of different adipose tissues has provided important insights into the intricate network that links nutrition, metabolism and immune homeostasis. The neuroendocrine and immune systems communicate bi-directionally through common ligands and receptors during stress responses and inflammation, and control cellular immune responses in several pathological situations including immune-inflammatory rheumatic diseases. This Review discusses the latest findings regarding the role of leptin in the immune system and metabolism, with particular emphasis on its effect on autoimmune and/or inflammatory rheumatic diseases, such as rheumatoid arthritis and osteoarthritis.
29213124 The RA-MAP Consortium: a working model for academia-industry collaboration. 2018 Jan Collaboration can be challenging; nevertheless, the emerging successes of large, multi-partner, multi-national cooperatives and research networks in the biomedical sector have sustained the appetite of academics and industry partners for developing and fostering new research consortia. This model has percolated down to national funding agencies across the globe, leading to funding for projects that aim to realise the true potential of genomic medicine in the 21st century and to reap the rewards of 'big data'. In this Perspectives article, the experiences of the RA-MAP consortium, a group of more than 140 individuals affiliated with 21 academic and industry organizations that are focused on making genomic medicine in rheumatoid arthritis a reality are described. The challenges of multi-partner collaboration in the UK are highlighted and wide-ranging solutions are offered that might benefit large research consortia around the world.
27428854 Reciprocal Relationship Between Sleep Macrostructure and Evening and Morning Cellular Infl 2017 Jan OBJECTIVE: This study examined the reciprocal associations between sleep macrostructure and levels of cellular inflammation in rheumatoid arthritis (RA) patients and controls. METHODS: RA patients (n = 24) and matched controls (n = 48) underwent all-night polysomnography, along with assessment of spontaneous- and Toll-like receptor-4-stimulated monocytic production of tumor necrosis factor α (TNF) and interleukin (IL)-6 at 11:00 PM and 8:00 AM. RESULTS: As compared with controls, RA patients showed lower levels of sleep efficiency (mean [standard deviation], 88.1 [6.1] versus 83.8 [7.0]), a higher percentage stage 3 sleep (9.3 [6.4] versus 13.1 [6.9]), and higher levels of percentage of monocytes either spontaneously expressing TNF at 11:00 PM (log transformed, 1.07 [0.28] versus 1.22 [0.17]), and higher Toll-like receptor-4-stimulated production of IL6 at 8:00 AM (log transformed, 3.45 [0.80] versus 3.83 [0.39]). Higher levels of stimulated production of TNF at 11:00 PM were associated with higher sleep efficiency (0.74). In turn, sleep efficiency had a countervailing relationship on TNF production at 8:00 AM (-0.64). Higher levels of spontaneous and stimulated production of IL6 at 11:00 PM were associated with more stage 3 (0.39), stage 4 (0.43), and slow-wave sleep (0.49), with evidence that stage 4 had a countervailing relationship on IL6 production at 8:00 AM (-0.60). CONCLUSIONS: RA patients show evidence of sleep fragmentation, greater sleep depth, and higher levels of cellular inflammation. Sleep maintenance and sleep depth show countervailing relationships with evening and morning levels of monocytic production of TNF and IL-6, respectively, which support the hypothesis of a feedback loop between sleep maintenance, slow-wave sleep, and cellular inflammation that is cytokine specific.
28404610 Hand exercises for patients with rheumatoid arthritis: an extended follow-up of the SARAH 2017 Apr 12 OBJECTIVES: The Stretching And strengthening for Rheumatoid Arthritis of the Hand (SARAH) randomised controlled trial evaluated the effectiveness of a hand exercise programme and demonstrated it was clinically effective and cost-effective at 12 months. The aim of this extended follow-up was to evaluate the effects of the SARAH programme beyond 12 months. METHODS: Using postal questionnaires, we collected the Michigan Hand Questionnaire hand function (primary outcome), activities of daily living and work subscales, pain troublesomeness, self-efficacy and health-related quality of life. All participants were asked how often they performed hand exercises for their rheumatoid arthritis. Mean difference in hand function scores were analysed by a linear model, adjusted for baseline score. RESULTS: Two-thirds (n=328/490, 67%) of the original cohort provided data for the extended follow-up. The mean follow-up time was 26 months (range 19-40 months).There was no difference in change in hand function scores between the two groups at extended follow-up (mean difference (95% CI) 1.52 (-1.71 to 4.76)). However, exercise group participants were still significantly improved compared with baseline (p=0.0014) unlike the best practice usual care group (p=0.1122). Self-reported performance of hand exercises had reduced substantially. CONCLUSIONS: Participants undertaking the SARAH exercise programme had improved hand function compared with baseline >2 years after randomisation. This was not the case for the control group. However, scores were no longer statistically different between the groups indicating the effect of the programme had diminished over time. This reduction in hand function compared with earlier follow-up points coincided with a reduction in self-reported performance of hand exercises. Further intervention to promote long-term adherence may be warranted. TRIAL REGISTRATION NUMBER: ISRCTN89936343; Results.
25775146 Cervical myelopathy due to atraumatic odontoid fracture in patients with rheumatoid arthri 2017 Sep To highlight the risk of cervical myelopathy due to occult, atraumatic odontoid fracture in patients with rheumatoid arthritis, we retrospectively reviewed radiographic findings and clinical observations for 7 patients with this disorder. This fracture tends to occur in patients with long-lasting rheumatoid arthritis and to be misdiagnosed as simple atlantoaxial dislocation. Since this fracture causes multidirectional instability between C1 and C2 and is expected to have poor healing potential due to bone erosion and inadequate blood supply, posterior spinal arthrodesis surgery is indicated upon identification of the fracture to prevent myelopathy.
28930656 More Is Less: IL-9 in the Resolution of Inflammation. 2017 Sep 19 In a recent study in Nature Medicine, Rauber et al. (2017) identify interleukin-9 (IL-9) derived from group 2 innate lymphoid cells as crucial regulators inducing resolution of chronic inflammation in rheumatoid arthritis. Their findings provide insight into the varied functions of IL-9 and open the door to novel therapeutic interventions.
29648739 Reducing out-of-pocket cost barriers to specialty drug use under Medicare Part D: addressi 2017 Mar OBJECTIVES: Medicare Part D specialty drug users not qualifying for low-income subsidies (non-LIS beneficiaries) face high and variable cost sharing during the calendar year. We examined their out-of-pocket (OOP) cost patterns under the existing Part D cost-sharing policies and proposed changes to these policies. METHODS: Using 100% Medicare claims data from 2012, we examined mean annual and monthly OOP drug costs for Medicare Part D patients who were full-year users of Part D specialty drugs for rheumatoid arthritis (RA) (n = 1063), multiple sclerosis (MS) (n = 2256), or chronic myeloid leukemia (CML) (n = 1135) under existing policy. Using the same data, we simulated costs under both proposed Medicare Payment Advisory Commission (MedPAC) policy recommendations and our own recommendations. RESULTS: In 2012, our sample faced mean annual cumulative OOP drug costs (for all medications) of $3949 (RA), $5238 (MS), and $6322 (CML). Mean OOP costs were $977 (RA), $1613 (MS), and $2456 (CML) in January alone. A substantial proportion of total annual OOP prescription spending also occurred during the catastrophic coverage phase (RA: $1229 [31%]; MS: $2456 [47%]; CML: $3546 [56%]). Under proposed MedPAC changes, patients would have faced maximum annual OOP spending of $4700, but mean OOP costs in January and February would have been higher compared with the existing policy. Under our proposed strategy, OOP costs would have been spread evenly over 12 months (≤$392 per month). The potential incremental costs of our proposed strategy would have been $23.55 per non-LIS Part D beneficiary per year. CONCLUSIONS: The existing Part D cost-sharing structure creates a substantial financial burden for specialty drug users, especially early in the year. Implementing both annual and monthly OOP maximum spending limits would result in lower, more consistent OOP costs, potentially increasing patients' ability to access treatments for life-threatening, chronic, and rare diseases.
27095187 Evaluation of learned helplessness, self-efficacy and disease activity, functional capacit 2017 Jan OBJECTIVES: To evaluate the association between learned helplessness (LH) and self-efficacy (SE) with disease activity, functional capacity, and level of pain in patients with rheumatoid arthritis (RA) and to compare LH and SE between patients in remission and patients with active disease. METHOD: This multicentre, cross-sectional study included consecutive patients (aged ≥ 18 years) with RA according to 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria. LH was measured by the Rheumatology Attitude Index (RAI), Spanish version; SE with the Arthritis Self-efficacy Scale (ASES), Spanish version; functional capacity with the Health Assessment Questionnaire, Argentinian version (HAQ-A); and perceived pain by the visual analogue scale (VAS). Disease activity was measured by the Clinical Disease Activity Index (CDAI). RESULTS: A total of 115 patients (82% females) with a mean (± sd) age of 58 ± 13 years were included. We found a significantly positive correlation between LH and perceived pain (p < 0.001), HAQ-A score (p < 0.001), and CDAI (p < 0.001) and a significantly negative correlation between SE and perceived pain (p < 0.001), HAQ-A score (p < 0.001), and CDAI (p < 0.001). We found greater levels of SE and lower grades of LH in patients in remission compared to those with active disease (median 76 vs. 58; p < 0.001 and 6 vs. 11; p < 0.001, respectively). CONCLUSIONS: LH and SE correlated significantly with disease activity, functional capacity, and perceived pain. Levels of SE were higher in patients in remission compared to those with active disease as opposed to levels of LH, which were lower in patients in remission compared to those with active disease. These results show that cognitive factors are related to disease activity and their modifications may have importance in the management of RA.