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ID PMID Title PublicationDate abstract
30231732 Comparison of Drug Use Between Clinical Practice and Regulatory Approval: Results in Older 2016 Nov BACKGROUND: In this study, differences in older patients between drug use as reported in clinical practice and in clinical trials for regulatory approval were examined. METHODS: Electronic medical record (EMR) data such as patient background (age, sex), concomitant drugs, data on laboratory tests, and prescribed doses of drugs from outpatients with rheumatoid arthritis, diabetes, high blood pressure, or depression at Chiba University Hospital were obtained for the period from January 2003 to December 2012. These data were compared with data from relevant clinical trials for regulatory approval in order to examine differences in drug use. RESULTS: There were 5134 eligible patients. The prescribed doses of drugs were lower than the standard approved doses for depression and rheumatoid arthritis but were generally within the approved dose range for type 2 diabetes mellitus and hypertension. When comparing the characteristics of older patients taking tacrolimus, 5.6% to 17.0% of those would not be able to participate in clinical trials because of liver or renal abnormality, and the incidence rates of some adverse drug events (ADEs) differed significantly between clinical practice and clinical trials. CONCLUSIONS: Appropriate doses of drugs for older patients may differ from approved doses in certain diseases. Complex situations such as a lot of polypharmacy, comorbidity, and functional impairment in older patients in clinical practice make it difficult to evaluate safety based on data from clinical trials. In the future, utilization of a database created from the EMR of older patients should be considered for assessment of drug safety in older patients in clinical practice.
27146293 Pleiotropic effects of statins: new therapeutic targets in drug design. 2016 Jul The HMG Co-enzyme inhibitors and new lipid-modifying agents expand their new therapeutic target options in the field of medical profession. Statins have been described as the most effective class of drugs to reduce serum cholesterol levels. Since the discovery of the first statin nearly 30 years ago, these drugs have become the main therapeutic approach to lower cholesterol levels. The present scientific research demonstrates numerous non-lipid modifiable effects of statins termed as pleiotropic effects of statins, which could be beneficial for the treatment of various devastating disorders. The most important positive effects of statins are anti-inflammatory, anti-proliferative, antioxidant, immunomodulatory, neuroprotective, anti-diabetes, and antithrombotic, improving endothelial dysfunction and attenuating vascular remodeling besides many others which are discussed under the scope of this review. In particular, inhibition of Rho and its downstream target, Rho-associated coiled-coil-containing protein kinase (ROCK), and their agonistic action on peroxisome proliferator-activated receptors (PPARs) can be viewed as the principle mechanisms underlying the pleiotropic effects of statins. With gradually increasing knowledge of new therapeutic targets of statins, their use has also been advocated in chronic inflammatory disorders for example rheumatoid arthritis (RA) and in systemic lupus erythematosus (SLE). In the scope of review, we highlight statins and their pleiotropic effects with reference to their harmful and beneficial effects as a novel approach for their use in the treatment of devastating disorders. Graphical abstract Pleiotropic effect of statins.
26677998 Low pre-treatment B-cell counts are not a risk factor of infection in patients treated wit 2016 Mar OBJECTIVES: Rituximab (RTX) is increasingly used in patients with refractory rheumatoid arthritis (RA) and other severe autoimmune diseases (AID). In practice, many clinicians are reluctant to prescribe RTX in patients with low B-cell counts because of the presumed risk of infection. The aim of this study was therefore to investigate whether B-cell counts before treatment or retreatment with RTX predict the occurrence of infections. METHODS: Observational, single-centre study of 161 patients treated with RTX for RA and other AID at a tertiary hospital. CD19+ B-cell counts were assessed by flow cytometry and multivariate statistical analysis adjusted for various potential predictors was performed. RESULTS: The rate of severe infection was 5.9/100 patient-years in RA patients and 24.9 in non-RA AID (P<0.001). Low B-cell counts at the time of RTX infusion were not associated with subsequent severe (HR=0.55, P=0.60) or overall infection (HR=0.85, P=0.58). Significant pre-treatment predictors of severe infection were a diagnosis other than RA (HR=4.68, P<0.001), immunoglobulin (Ig) G levels <7g/L (HR=2.36, P=0.01), age (HR=1.03, P=0.01), and diabetes (HR=3.61, P=0.01). CONCLUSIONS: Low B-cell counts before RTX infusion did not predict subsequent infections in this population treated with RTX for RA and other AID, therefore not supporting the practice of pre-treatment assessment of B-cells. Nevertheless, a higher risk of severe infection was confirmed for low pre-treatment IgG levels, older age, diabetes, and AID other than RA.
26539560 Collagen-Induced Arthritis: A model for Murine Autoimmune Arthritis. 2015 Oct 20 Collagen-induced arthritis (CIA) is a common autoimmune animal model used to study rheumatoid arthritis (RA). The development of CIA involves infiltration of macrophages and neutrophils into the joint, as well as T and B cell responses to type II collagen. In murine CIA, genetically susceptible mice (DBA/1J) are immunized with a type II bovine collagen emulsion in complete Freund's adjuvant (CFA), and receive a boost of type II bovine collagen in incomplete Freund's adjuvant (IFA) 21 days after the first injection. These mice typically develop disease 26 to 35 days after the initial injection. C57BL/6J mice are resistant to arthritis induced by type II bovine collagen, but can develop arthritis when immunized with type II chicken collagen in CFA, and receive a boost of type II chicken collagen in IFA 21 days after the first injection. The concentration of heat-killed Mycobacterium tuberculosis H37RA (MT) in CFA also differs for each strain. DBA/1J mice develop arthritis with 1 mg/ml MT, while C57BL/6J mice require and 3-4 mg/ml MT in order to develop arthritis. CIA develops slowly in C57BL/6J mice and cases of arthritis are mild when compared to DBA/1J mice. This protocol describes immunization of DBA/1J mice with type II bovine collagen and the immunization of C57BL/6J mice with type II chicken collagen.
27153975 Endothelial progenitor cells: Are they displaying a function in autoimmune disorders? 2016 Oct Endothelial Progenitor Cells (EPCs) are bone marrow derived cells able to differentiate in mature endothelial cells (EC) contributing to the generation of new vessels, connecting to fibronectin, and forming colonies and/or colony forming units. Since circulating EPCs can be actively considered part of endothelial damage in several cardiovascular diseases and autoimmune disorders the possibility to have a measure for endothelium damage should be considered of interest to predict the patient out-come. At the same time the EPCs proliferative and regenerative role could be considered for therapeutic applications. Studies have been performed to elucidate the role of EPCs in Systemic Sclerosis and many review and articles published on this topic. In the present paper we aimed to review the role of EPCs in other autoimmune disorders.
26962513 Evaluation of differences in HLA-DR4 gene and its subtypes prevalence among healthy people 2016 BACKGROUND: There are a lot of evidences showing that genetic play an important role in RA disease. Inheritance of some subgroups of HLA-DR4 gene increases the propensity to RA disease. In this paper, the impact of HLA-DR4 gene and its subtypes or subgroups, be consistence on RA patient who lived in Isfahan province, has been evaluated. MATERIALS AND METHODS: In this survey, two groups of people (100 patients in case group and 100 normal persons in control group) have been selected. These two groups were similar in age and gender. Statistical population has been considered among people who visited Al Zahra rheumatology clinic. The participants were from Isfahan province and accepted to participate to the study voluntarily. The prevalence of HLA-DR4 and its 0401-0404 subtypes were evaluated between two groups; DNA was extracted from blood samples and studied using PCR SSCP method. RESULTS: It was found that 35% of RA patients had HLA-DR4 gene, of which 14 persons had 0401, 10 persons had 0404, and 11 persons had other subtypes, whereas 30 people in control group had HLA-DR4 gene, of which 10 people had 0401, 20 people had 0404, and nobody had other subtypes. CONCLUSION: The observed differences between prevalence of HLA-DR4 gene between the case and control group were not statistically significant (P = 0.45; OR = 1.256; 95% CI = 0.69-2.27), but a relation was between HLA-DR4 0404 subtypes and RA (P = 0.02; OR = 0.44; 95% CI = 0.196-0.992).
26819215 Musculoskeletal imaging in preventive medicine. 2016 Feb The aim is to review the modalities in musculoskeletal imaging with view on the prognostic impact for the patient's and for social outcome and with view on three major fields of preventive medicine: nutrition and metabolism, sports, and patient education. The added value provided by preventive imaging is (1) to monitor bone health and body composition with a broad spectrum of biomarkers, (2) to detect and quantify variants or abnormalities of nerves, muscles, tendons, bones, and joints with a risk of overuse, rupture, or fracture, and (3) to develop radiology reports from the widely used narrative format to structured text and multimedia datasets. The awareness problem is a term for describing the underreporting and the underdiagnosis of fragility fractures in osteoporosis.
25999750 Application of a validated algorithm to estimate the effectiveness and cost of biologics f 2015 BACKGROUND: Several biologic medicines are available to treat rheumatoid arthritis (RA), and they differ in administration method (subcutaneous or intravenous [IV]). We analyzed a pharmacy benefit manager database to estimate claims-based, algorithm-determined effectiveness and cost per effectively treated patient for biologics used to treat RA. METHODS: We analyzed the Medco Health Solutions pharmacy benefit manager database to identify patients with one or more claims for a biologic used to treat RA from 2007 to 2012. The first observed claim defined the index date, the previous 180 days were the pre-index period, and follow-up was 365 days after the index date. Effectiveness of a biologic was determined by a validated, published algorithm designed for use in claims database analyses. Cost per effectively treated patient as determined by the algorithm was calculated as the total annual cost of the biologic therapy divided by the number of effectively treated patients. Analyses were conducted for subcutaneous, IV, and individual biologics. RESULTS: The analysis population was 1,090 patients (subcutaneous: 785, IV: 305; etanercept: 440, adalimumab: 345, infliximab: 201, abatacept: 104). The mean age was 49.7±9.4 years, and 78% of the patients were female. Effectiveness according to the algorithm was higher in subcutaneous (36%) versus IV biologics (23%; P<0.001), and in etanercept (36%) versus infliximab (22%; P<0.001) and versus abatacept (24%; P=0.02). Etanercept and adalimumab were similar (35%; P=0.77). The cost per effectively treated patient according to the algorithm was $64,738 for subcutaneous biologics, $80,408 for IV biologics, $62,841 for etanercept, $67,226 for adalimumab, $90,696 for infliximab, and $62,303 for abatacept. CONCLUSION: Effectiveness according to a validated, claims-based algorithm was higher in subcutaneous versus IV biologics. Cost per effectively treated patient according to the algorithm was approximately $16,000 less in subcutaneous versus IV biologics.
25653545 Economic evaluation of anti-TNF agents for patients with rheumatoid arthritis in Greece. 2015 OBJECTIVES: We aimed to estimate the total mean annual treatment cost of different therapy options for patients with moderate-to-severe rheumatoid arthritis (RA) in Greece. METHODS: A cost-minimization approach was adopted. An economic model was developed to estimate the direct costs of the three widely used treatments within a 1-year time horizon, from a health care payer perspective, either for new or for existing patients. Data on resource use, dose escalation, and frequency of therapy were based on a nationwide field survey of rheumatologists. Other analyses were also undertaken based on evidence from the literature. Total cost comprised the cost of drugs, administration, and hospital day care visits. Unit cost data were obtained from the price bulletin and the government gazettes issued by the Ministry of Health. Due to the short time horizon of the study, the cost was not discounted. RESULTS: The mean annual total cost per new (or per existing) responder patient on etanercept was estimated at €9,845 (€9,840), and the total cost on etanercept/methotrexate (MTX) was estimated at €9,857 (€9,852). Therapy with etanercept had lower annual cost relative to adalimumab and infliximab. On an annual basis, it was estimated that the difference between etanercept monotherapy and adalimumab monotherapy was €544 (€1,323). Similarly, the difference between etanercept/MTX and infliximab/MTX was €1,871 (€1,490) and €543 (€1,323), respectively, relative to adalimumab/MTX. Results remained constant under other scenario analyses undertaken. CONCLUSION: In the real-life practice setting in Greece, where dose intensity and frequency differences occur, etanercept alone or in combination with MTX, if prescribed as per label, represents the option with lower annual cost per patient when compared with adalimumab or infliximab in patients with RA. These results hold true as long as the assumptions and data used in the analysis remain stable and may alter if any of the underlying parameters, such as drug price, change.
31557985 Anticytokine Autoantibodies: Association with Infection and Immune Dysregulation. 2016 Jan 15 The association of autoantibodies to cytokines with immune deficiency, autoimmunity and/or immune dysregulation is increasingly being recognized. For example, autoantibodies to interferon gamma have been found to be associated with chronic, treatment refractory infections with intracellular organisms such as mycobacteria, autoantibodies to interleukin 17 with chronic mucocutaneous candidiasis, and anti-interferon alpha autoantibodies with systemic lupus erythematosus. While low titer autoantibodies to these and other cytokines may be detected in normal individuals, patients with infectious or autoimmune manifestations tend to have high titer autoantibodies that may block or potentiate the function of the respective cytokine. Recognition of these autoantibodies is important because it may direct treatment toward a combination of adjunctive immunotherapy to modulate the autoantibody level while continuing with appropriate anti-microbial therapy. This review focuses on the anti-cytokine autoantibodies documented to date, their autoimmune, immune dysregulation and infectious disease associations, methods for detection of these antibodies and potential treatment options.
26483598 Inhibition on JAK-STAT3 Signaling Transduction Cascade Is Taken by Bioactive Peptide Alpha 2015 Aug BACKGROUND: RA is a systemic inflammatory disease that causes developing comorbidity conditions. This condition can cause by overproduction of pro-inflammatory cytokine. In a previous study, we have found bioactive peptide CSN1S2 from Ethawah goat milk for anti-inflammatory for repair the ileum destruction. However, the signaling transduction cascade of bioactive peptides inhibits inflammation still not clear yet. Therefore, we analyzed the signaling transduction cascade via JAK-STAT3 pathway by in vivo and in silico. METHODS: The ileum was isolated DNA and amplification with specific primer. The sequence was analyzed using the Sanger sequencing method. Modeling 3D-structure was predicted by SWISS-MODEL and virtual interaction was analyzed by docking system using Pymol and Discovery Studio 4.0 software. RESULTS: This study showed that STAT3 has target gene 480bp. The normal group and normal treating- CSN1S2 of goat milk have similarity from gene bank. Whereas, RA group had transversion mutation that the purine change into pyrimidine even cause frameshift mutation. Interestingly, after treating with the CSN1S2 protein of goat milk shows reverse to the normal acid sequence group. Based on in silico study, from eight peptides, only three peptides of CSN1S2 protein, which carried by PePT1 to enter the small intestine. The fragments are PepT1-41-NMAIHPR-47; PepT1-182-KISQYYQK-189 and PepT1-214-TNAIPYVR-221. We have found just one bioactive peptide of f182-KISQYYQK-189 is able bind to STAT3. The energy binding of f182-KISQYYQK-189 and RA-STAT3 amino acid, it was Σ = -402.43 kJ/mol and the energy binding of f182-KISQYYQK-189 and RAS-STAT3 amino acid is decreasing into Σ = -407.09 kJ/mol. CONCLUSION: This study suggested that the fragment 182-KISQYYQK-189 peptides from Ethawah goat milk may act as an anti-inflammatory agent via JAK-STAT3 signal transduction cascade at the cellular level.
27896015 Development of a multi-wavelength diffuse optical tomography system for early diagnosis of 2016 Nov 1 A multi-wavelength diffuse optical tomography (DOT) system has been developed to directly extract physiological information, such as total haemoglobin concentration, from tissue in human hand joints. Novel methods for 3D surface imaging and spectrally constrained image reconstruction are introduced and their potential application to imaging of rheumatoid arthritis is discussed. Results are presented from simulation studies as well as experiments using phantoms and data from imaging of three healthy volunteers. The image features are recovered partially for phantom data using transmission measurements only. Images that reveal joint regions and surrounding features within the hand are shown to co-register with co-acquired ultrasound images which are shown to be related to total haemoglobin concentration.
27790046 Different T cells' distribution and activation degree of Th17 CD4+ cells in peripheral blo 2015 OBJECTIVE: To determine distribution of T cells and activation degree of Th CD4+ cells in peripheral blood of patients with osteoarthritis (OA), rheumatoid arthritis (RA), and healthy donors. METHODS: Patients with established diagnosis of RA according to American College of Rheumatology/European League Against Rheumatism 2010 criteria, knee or hip OA according to American College of Rheumatology criteria, and healthy blood donor volunteers were eligible. Multi-channel flow cytometry and monoclonal antibodies against CD3, CD4, CD8, CCR6, CD38, CXCR3, and HLA DR were used to distinguish and evaluate T cells' subpopulation. RESULTS: We analyzed blood samples of 15 patients with well-defined RA, 56 with hip or knee OA, and 20 healthy age matched controls. Blood samples from RA patients showed significantly higher counts of CD4+ CD38+ DR+ (activated CD4 T cells) and Th17 (CCR6+ CXCR3-) cells as compared to OA patients and control group (P<0.01). Furthermore the samples from the OA patients showed a higher percentage of activated CD4 T cells and Th17 cells as compared to control group (P<0.05). Interestingly there was no difference between Th1 (CD4+ CXCR3+ CCR6-) and Th2 (CD4+ CXCR3- CCR6-) between the three groups (P>0.1). CONCLUSION: According to the latest view of OA disease pathogenesis, our preliminary results support the hypothesis that OA may also be a disease with an immunological/inflammatory involvement like RA. It seems that there is a quantitative but non-qualitative difference in Th17 cells' profile, including the expression of activation markers, between RA and OA.
27480610 A novel approach to cricoarytenoid joint injections: An anatomic study. 2017 Jan OBJECTIVES: To demonstrate a novel approach to cricoarytenoid joint (CAJ) injections. STUDY DESIGN: Anatomic feasibility study. METHODS: Five human cadaveric larynges providing 10 CAJ s were used to obtain trajectory measurements of a 27-gauge 1½-inch needle placed between the CAJ capsule and the contralateral cricothyroid membrane. Ten additional larynges providing 20 CAJ s were then used to assess the efficacy of applying the previously obtained measurements to guide 0.2-cc methylene blue injections of the CAJ using a 27-gauge 1½-inch needle. Successful injection was confirmed by direct visualization of methylene blue within the CAJ capsule. RESULTS: The tip of the needle made a 70 ± 1.87 degree (confidence interval [CI] 95%) angle relative to the plane parallel to the anterior lamella of the cricoid cartilage; the needle was within the cricothyroid membrane 5 ± 0.77 mm (CI 95%) lateral to the midsagittal plane; the needle was 4 ± 0.80 mm (CI 95%) anteroinferior from the vocal process of the arytenoid cartilage as measured within the airway; and the distance from the point of airway entry and the CAJ capsule was 17 ± 2.42 mm (CI 95%). Twenty CAJ injections were attempted using the guidelines established here with an 85% success rate. CONCLUSION: The current approach to CAJ injection utilizes microlaryngoscopy in an operative setting. This study is the first to describe the accessibility of the CAJ through percutaneous injection using reliable landmarks, potentially allowing access to the joint in an office-based setting. LEVEL OF EVIDENCE: NA Laryngoscope, 127:199-203, 2017.
26824819 [Use of biological therapy in patients with rheumatoid arthritis in the Republic of Kazakh 2015 AIM: To evaluate the clinical efficacy and safety of infliximab (IFM) in patients with rheumatoid arthritis (RA). SUBJECTS AND METHODS: Twelve inpatients (10 women and 2 men) aged 23 to 65 years with a valid diagnosis of RA, the duration of which was 3 years or more, were retrospectively analyzed. DAS28 for RA corresponded to grades II and III in 4 (33.3%) and 8 (66.7%) patients, respectively. Long before the investigation, all the patients used methotrexate in a weekly dose of 15 mg and nonsteroidal anti-inflammatory drugs; 6 patients received methipred in a daily dose of 4-8 mg. IFM was administered intravenously dropwise on the basis of 3 mg/kg weight in 250 ml of isotonic sodium hydrochloride solution during 2 hours at 0, 2, and 6 weeks after therapy initiation and then every 8 weeks. RESULTS: During combination therapy after the first IFM infusion, all the 12 patients were noted to have a positive clinical effect as a significant reduction in the number of tender joints and swollen joints, morning stiffness, erythrocyte sedimentation rate, C-reactive protein, regression of the clinical manifestations of the disease, and its laboratory activity. The therapy was tolerated well by all the patients. According to the EULAR criteria, a good therapeutic effect was observed in 10 (83%) patients and clinical remission was achieved in 2 (17%) patients. According to the ACR criteria, 50 and 70% improvement was seen in 1 (8%) and 9 (75%) patients, respectively. Two (17%) patients achieved remission. CONCLUSION: Combination therapy with IFM and MT for RA is highly effective, suppresses disease inflammatory activity and joint destruction; furthermore, there may be remission induction.
26113482 Decreased serum cell-free DNA levels in rheumatoid arthritis. 2015 Aug PURPOSE: Recent studies have demonstrated that serum/plasma DNA and RNA molecules in addition to proteins can serve as biomarkers. Elevated levels of these nucleic acids have been found not only in acute, but also in chronic conditions, including autoimmune diseases. The aim of this study was to assess cell-free DNA (cfDNA) levels in sera of rheumatoid arthritis (RA) patients compared to controls. METHODS: cfDNA was extracted from sera of patients with early and established RA, relapsing-remitting multiple sclerosis patients (RRMS) and healthy subjects, and its concentration was determined by quantitative PCR using two amplicons, Alu115 and β-actin205, corresponding to Alu repetitive elements and the β-actin single-copy gene, respectively. Serum DNase activity was measured by a single radial enzyme diffusion method. RESULTS: Reduced levels of cfDNA were observed in patients with established RA in comparison with healthy controls, early RA patients and RRMS patients. There were no significant differences in cfDNA concentration between healthy controls, early RA and RRMS patients. Total DNase activity appeared to be similar in the sera of all tested groups. CONCLUSIONS: Our results demonstrate that cfDNA levels are strongly reduced in the sera of established RA patients, which is not caused by changes in DNase activity. Measurement of cfDNA can distinguish established RA patients from early RA patients. Thus, cfDNA may serve as a biomarker in RA.
25981388 Prevention of stroke in rheumatoid arthritis. 2015 Jul Recognizing that systemic inflammation is a major contributor to the increased risk of cardiovascular disease (CVD), including stroke, in rheumatoid arthritis (RA) serves as the basis for prevention strategies for cerebrovascular disease in RA. In addition to traditional cardiovascular risk factors, recognize that RA may be an independent risk factor for cerebrovascular accident (CVA). The risk of CVD should be assessed in each patient with RA, utilizing modified risk score calculators. Careful monitoring and control of systemic inflammation should be undertaken in conjunction with assessing each patient's CVD risk, acknowledging the benefits and risks of specific RA-directed therapies. Emphasis should be given to early and aggressive control of inflammation in RA patients, particularly those with seropositivity, increased inflammatory markers, long disease duration (>10 years), and/or extra-articular manifestations. In RA patients requiring glucocorticoid therapy, attempts should be made to use or wean to the minimal effective dose (preferably less than 7.5 mg/day). It should be recognized that both disease-modifying antirheumatic drugs (DMARDs), particularly methotrexate, and tumor necrosis factor (TNF)-alpha inhibitors partially mitigate the risk of CVD. In patients with inadequate control of inflammation with DMARDs, consideration should be given to switch to anti-TNF agents earlier in the disease process. Modifiable risk factors should be addressed as per guidelines for the general population. Active RA may be considered as a risk equivalent to diabetes mellitus when applying these guidelines. With regard to lipid management and use of statin therapy, further studies are required given the apparent "lipid paradox" in RA. Use of aspirin for primary prevention in RA has not been well studied; however, when aspirin is used for secondary prevention, one should recognize that concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs) may decrease the antiplatelet effect. Given the cardiovascular risk associated with NSAIDs, the lowest possible dose for the shortest time should be used.
25158802 Impact of rheumatic diseases on oral health and quality of life. 2015 Apr OBJECTIVE: We investigated the effects of rheumatic diseases on oral symptoms, health habits, and quality of life in subjects with and without rheumatic diseases. The hypothesis was that patients with rheumatic diseases have more oral symptoms impairing their quality of life than healthy controls. METHODS: A questionnaire was mailed to a random sample of 1500 members of the Finnish Rheumatism Association, including those with and without rheumatic diseases. We focused on symptoms of the mouth and temporomandibular area, and health habits. Oral Health Impact Profile (OHIP14) was used to evaluate the oral health-related quality of life. We analyzed differences between subjects with and without rheumatic diseases, controlled for age, gender, smoking, and non-rheumatic chronic diseases. RESULTS: Completed questionnaires were received from 995 participants (response rate 66%). Of them, 564 reported rheumatic disease, 431 were used as controls. The patients reported significantly more all orofacial symptoms than controls. Severe dry mouth was reported by 19.6% of patients and 2.9% of controls (P < 0.001), and temporomandibular joint symptoms by 59.2% and 27.2% (P < 0.001), respectively. In the OHIP-14 questionnaire, the mean total score was significantly higher in patients (8.80 ± 11.15) than in controls (3.93 ± 6.60; P < 0.001). CONCLUSION: The study hypothesis was confirmed by showing that the patients with rheumatic diseases reported oral discomfort and reduced quality of life more often when compared with controls.
27980801 Genetic polymorphisms of enzyme proteins and transporters related to methotrexate response 2016 BACKGROUND: Methotrexate (MTX) is currently the anchor drug widely used worldwide in the treatment of rheumatoid arthritis (RA). However, the therapeutic response to MTX has been shown to vary widely among individuals, genders and ethnic groups. The reason for this has been not clarified but it is considered to be partially due to several mechanisms in the cellular pathway of MTX including single-nucleotide polymorphisms (SNPs). The purpose of this study was to investigate the allelic frequencies in different ethnic and/or population groups in the 10 polymorphisms of enzyme proteins and transporters related to the MTX response and pharmacokinetics including MTHFR, TYMS, RFC1, FPGS, GGH, ABCB1, ABCC2 and ABCG2 in unrelated healthy Japanese adults and patients with RA. METHODS: Ten polymorphisms, methylenetetrahydrofolate reductase (MTHFR) 1298, thymidylate synthase (TYMS) 3'-UTR, reduced folate carrier 1 (RFC1) 80 and-43, folypolyglutamyl synthase (FPGS) 1994, γ-glutamyl hydrolase (GGH) 452 and-401, the ABC transporters (ABCB1 3435, ABCC2 IVS23 + 56, ABCG2 914) of enzyme proteins and transporters related to MTX response and pharmacokinetics in 299 unrelated healthy Japanese adults and 159 Japanese patients with RA were investigated to clarify their contributions to individual variations in response and safety to MTX and establish personalized MTX therapy. SNPs were evaluated using real-time polymerase chain reaction (PCR). RESULTS: Comparison of allelic frequencies in our study with other ethnic/population groups of healthy adults and RA patients showed significant differences in 10 polymorphisms among healthy adults and 7 among RA patients. Allelic frequencies of MTHFR 1298 C, FPGS 1994A and ABCB1 3435 T were lower in Japanese than in Caucasian populations and those of ABCC2 IVS23 + 56 C and ABCG2 914A were higher in Japanese than in Caucasian/European populations in both healthy adults and RA patients. Allelic frequencies of MTHFR 1298 C, GGH-401 T, ABCB1 3435 T, and ABCG2 914A were higher in healthy Japanese adults than in an African population, and those of RFC1 80A, RFC1-43C and ABCC2 IVS23 + 56 C in healthy Japanese adults were lower than in Africans. However, no significant differences were seen in the distribution of allelic frequencies between healthy Japanese adults and RA patients. CONCLUSION: The variations in allelic frequencies in different ethnic and/or population groups in healthy adults and RA patients may contribute to individual variations in MTX response and toxicity.
26951286 Vitamin D: A Narrative Review Examining the Evidence for Ten Beliefs. 2016 Jul Over the past decade, a large body of observational evidence has suggested an association between lower vitamin D status (25-hydroxyvitamin D) and multiple acute and chronic disorders, including cancer, multiple sclerosis, depression and respiratory tract infections. This evidence has fostered the hypothesis that increasing vitamin D intake may treat and prevent such disorders. Our objective was to perform a critical analysis of the highest-level evidence for ten common beliefs regarding vitamin D for the prevention of falls, fractures and respiratory tract infections, the reduction of cancer incidence/mortality and overall mortality, and the prevention or treatment of depression/mental well-being, rheumatoid arthritis and multiple sclerosis, as well as maximum dosing and regular testing. We searched the Cochrane Database of Systematic Reviews and PubMed (up to August 2014) for randomized controlled trials and systematic reviews/meta-analyses based on those studies. All searches were performed, all evidence reviewed and each section written by at least two authors. The evidence shows that vitamin D supplementation provides some benefit in fracture prevention (likely ∼10-15 % relative reduction), particularly at a dose ≥800 IU and with calcium; a likely benefit in the rate of falls, though it is less clear whether the number of fallers changes; and a possible small (∼5 %) relative reduction in mortality. Evidence does not support the use of vitamin D supplementation for the prevention of cancer, respiratory infections or rheumatoid arthritis. Similarly, evidence does not support vitamin D supplementation for the treatment of multiple sclerosis and rheumatoid arthritis or for improving depression/mental well-being. Regular testing of 25-hydroxyvitamin D is generally not required, and mega-doses (≥300,000 IU) appear to increase harms. Much of the evidence is at high risk of bias, with multiple flaws, including analyses of secondary endpoints, small and underpowered studies, inconsistent results and numerous other issues. Therefore, enthusiasm for a vitamin D panacea should be tempered.