Comparison of Clinical Manifestations in Rheumatoid Arthritis vs. Spondyloarthritis: A Systematic Literature Review.

INTRODUCTION: Misclassification of spondyloarthritis (SpA) as rheumatoid arthritis (RA) may lead to delayed SpA diagnosis and suboptimal therapeutic outcomes. Here, we evaluate the literature on clinical manifestations in patients with SpA and RA, particularly seronegative RA, to understand the potential overlap, distinctions, and most reliable approaches to accurate diagnosis. METHODS: In this systematic literature review, conducted according to PRISMA guidelines, we searched key biomedical databases for English-language publications of original research articles (up to July 23, 2020) and rheumatology conference abstracts (January 1, 2018-July 31, 2020) reporting key SpA clinical presentations in patients with SpA or RA. Publications were assessed for eligibility by two independent reviewers; discrepancies were resolved by a third. Studies were evaluated for publication quality using the Downs and Black checklist. RESULTS: Of 4712 records retrieved, 79 met the inclusion criteria and were included in the analysis. Of these, 54 included study populations with SpA and RA, and 25 with seropositive and/or seronegative RA. Entheseal abnormalities were more frequently reported among patients with SpA than RA and with seronegative vs. seropositive RA. Psoriasis, nail psoriasis, and dactylitis were exclusively seen in SpA vs. RA. In most publications (70 of 79), advanced imaging techniques allowed for more accurate distinction between SpA and RA. Overlapping clinical characteristics occur in SpA and RA, including inflammation and destruction of joints, pain, diminished functional ability, and increased risk for comorbidities. However, of 54 studies comparing SpA and RA populations, only seven concluded that no distinction can be made based on the SpA manifestations and outcomes examined. CONCLUSIONS: Typical SpA-related clinical symptoms and signs were observed in patients with RA, suggesting that misclassification could occur. Availability of advanced imaging modalities may allow for more prompt and comprehensive evaluation of peripheral manifestations in SpA and RA, reducing misclassification and delayed diagnosis.

Spondyloarthritis (SpA) is a group of chronic, inflammatory diseases that includes axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA), in addition to other peripheral forms of SpA. AxSpA primarily affects the spine and can cause chronic back pain. PsA occurs in patients with the skin condition psoriasis and patients often experience symptoms including joint pain, stiffness, and swelling. Quick and accurate diagnosis of SpA is necessary to prevent joint damage and physical limitations. Rheumatoid arthritis (RA) is characterized by pain, swelling, and stiffness in multiple joints, and delayed diagnosis and treatment can have lasting effects. However, many patients with SpA and RA who initially seek medical care often experience delayed diagnoses. This study evaluated the literature on symptoms in patients with SpA and RA, particularly patients with RA without antibodies typically associated with the disease, to understand the potential overlap, differences, and most reliable ways to accurately diagnose patients. Data from 79 records were included in the analysis, 54 of which included study populations with SpA and RA. Skin and nail psoriasis, as well as swelling of the fingers and toes, was only seen in patients with SpA. Most studies showed that enhanced imaging allowed for distinguishing between SpA and RA. This study showed that typical signs and symptoms of SpA, including inflammation and joint pain, could also be seen in patients with RA, which suggests that challenges exist for accurately identifying SpA. This highlights the importance of advanced imaging to diagnose and treat patients with SpA in a timely manner.

Utility value estimates in cardiovascular disease and the effect of changing elicitation methods: a systematic literature review.

OBJECTIVE: Identify the most recent utility value estimates for cardiovascular disease (CVD) via systematic literature review (SLR) and explore trends in utility elicitation methods in the last 6 years. METHODS: This SLR was updated on January 25, 2018, and identified studies reporting utilities for myocardial infarction (MI), stroke, angina, peripheral artery disease (PAD), and any-cause revascularization by searching Embase, PubMed, Health Technology Assessment Database, and grey literature. RESULTS: A total of 375 studies reported CVD utilities (pre-2013 vs post-2013: MI, 38 vs 32; stroke, 86 vs 113; stable angina, 8 vs 9; undefined/unstable angina, 23 vs 8; PAD, 29 vs 13; revascularization, 54 vs 40). Median average utilities for MI, stroke, and revascularization increased over time (pre-2013 vs post-2013: MI, 0.71 vs 0.79; stroke, 0.63 vs 0.64; revascularization, 0.76 vs 0.81); angina and PAD showed a decrease in median values over time (stable angina, 0.83 vs 0.72; undefined/unstable angina, 0.70 vs 0.69; PAD, 0.76 vs 0.71). The proportion of utility estimates from trials increased across health states (pre-2013 vs post-2013: 22.5% vs 37.2%), as did the proportion of trials using the EuroQol Five Dimensions Questionnaire (EQ-5D; pre-2013 vs post-2013: 73.8% vs 91.4%). Use of methods such as the standard gamble, time trade-off, and Health Utilities Index has declined. CONCLUSIONS: Health state utilities for cardiovascular health states have changed in the last 6 years, likely due to changes in the types of studies conducted, the patient populations evaluated, and possibly changing utility elicitation methods. The EQ-5D has been used more frequently.

Anti-depressant like effect of curcumin and its combination with piperine in unpredictable chronic stress-induced behavioral, biochemical and neurochemical changes.

Curcumin, a yellow pigment extracted from rhizomes of the plant Curcuma longa (turmeric), has been widely used as food additive and also as a herbal medicine throughout Asia. The present study was designed to study the pharmacological, biochemical and neurochemical effects of daily administration of curcumin to rats subjected to chronic unpredictable stress. Curcumin treatment (20 and 40 mg/kg, i.p., 21 days) significantly reversed the chronic unpredictable stress-induced behavioral (increase immobility period), biochemical (increase monoamine oxidase activity) and neurochemical (depletion of brain monoamine levels) alterations. The combination of piperine (2.5 mg/kg, i.p., 21 days), a bioavailability enhancer, with curcumin (20 and 40 mg/kg, i.p., 21 days) showed significant potentiation of its anti-immobility, neurotransmitter enhancing (serotonin and dopamine) and monoamine oxidase inhibitory (MAO-A) effects as compared to curcumin effect per se. This study provided a scientific rationale for the use of curcumin and its co-administration with piperine in the treatment of depressive disorders.

Antidepressant activity of curcumin: involvement of serotonin and dopamine system.

RATIONALE: Curcumin is a major active principle of Curcuma longa, one of the widely used preparations in the Indian system of medicine. It is known for its diverse biological actions. OBJECTIVE: The present study was designed to investigate the involvement of monoaminergic system(s) in the antidepressant activity of curcumin and the effect of piperine, a bioavailability enhancer, on the bioavailability and biological effects of curcumin. METHODS AND OBSERVATIONS: Behavioral (forced swim test), biochemical (monoamine oxidase (MAO) enzyme inhibitory activity), and neurochemical (neurotransmitter levels estimation) tests were carried out. Curcumin (10-80 mg/kg, i.p.) dose dependently inhibited the immobility period, increased serotonin (5-hydroxytryptamine, 5-HT) as well as dopamine levels (at higher doses), and inhibited the monoamine oxidase enzymes (both MAO-A and MAO-B, higher doses) in mice. Curcumin (20 mg/kg, i.p.) enhanced the anti-immobility effect of subthreshold doses of various antidepressant drugs like fluoxetine, venlafaxine, or bupropion. However, no significant change in the anti-immobility effect of imipramine and desipramine was observed. Furthermore, combination of subthreshold dose of curcumin and various antidepressant drugs resulted in synergistic increase in serotonin (5-HT) levels as compared to their effect per se. There was no change in the norepinephrine levels. The coadministration of piperine (2.5 mg/kg, i.p.), a bioavailability enhancing agent, with curcumin (20 and 40 mg/kg, i.p.) resulted in potentiation of pharmacological, biochemical, and neurochemical activities. CONCLUSION: The study provides evidences for mechanism-based antidepressant actions of curcumin. The coadministration of curcumin along with piperine may prove to be a useful and potent natural antidepressant approach in the management of depression.