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ID PMID Title PublicationDate abstract
24406619 Significant association of interleukin-4 gene intron 3 VNTR polymorphism with susceptibili 2014 Mar 1 OBJECTIVE: Interleukin-4 (IL-4) is a strong chondroprotective cytokine and polymorphisms within this gene may be a risk factor for osteoarthritis (OA). We aimed to investigate genotype and allele frequencies of IL-4 gene intron 3 variable number of tandem repeats (VNTR) polymorphism in patients with knee OA in a Turkish population. METHODS: The study included 202 patients with knee OA and 180 healthy controls. Genomic DNA was isolated and IL-4 gene 70 bp VNTR polymorphism determined by using polymerase chain reaction (PCR) with specific primers followed by restriction fragment length polymorphism (RFLP) analysis. RESULTS: Our result show that there was statistically significant difference between knee OA patients and control group with respect to IL-4 genotype distribution and allele frequencies (p=0.000, OR: 0.20, 95% CI: 0.10-0.41, OR: 0.22, 95% CI: 0.12-0.42, respectively). CONCLUSIONS: Our findings suggest that there is an association of IL-4 gene intron 3 VNTR polymorphism with susceptibility of a person for development of knee OA. As a result, IL-4 gene intron 3 VNTR polymorphism could be a genetic marker in OA in a Turkish study population. This is the first association study that evaluates the associations between IL-4 gene VNTR polymorphism and knee OA.
23891668 Recipients of electric-powered indoor/outdoor wheelchairs provided by a national health se 2013 Dec OBJECTIVE: To describe the characteristics across all ages of powered wheelchair users and the assistive technology prescribed by a regional specialist wheelchair service. DESIGN: Cross-sectional study. SETTING: Regional wheelchair service. PARTICIPANTS: Electric-powered indoor/outdoor wheelchair (EPIOC) users (N=544) with 262 boys and men (mean age ± SD, 41.7±20.7y; range, 8-82y) and 282 girls and women (mean age ± SD, 47.2±19.7y; range, 7-92y). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Demographic, clinical/diagnostic details of EPIOC recipients, including pain, (kypho)scoliosis, and ventilators. Technical features, including specialized (adaptive) seating, tilt in space, and modified control systems. Factors were related to age groups: 1 (0-15y), 2 (16-24y), 3 (25-54y), 4 (55-74y), and 5 (≥75y). RESULTS: Neurologic/neuromuscular conditions predominated (81%) with cerebral palsy (18.9%) and multiple sclerosis (16.4%). Conditions presenting at birth or during childhood constituted 39%. Of the participants, 99 had problematic pain, 83 had (kypho)scoliosis, and 11 used ventilators. Specialized (adaptive) seating was provided to 169 users (31%); most had cerebral palsy or muscular dystrophy. Tilt in space was used by 258 (53%) participants. Younger people were more likely to receive tilt in space than older ones. Only 92 had specialized (adaptive) seating and tilt in space (mean age ± SD, 29±17.8y; range, 8-72y). Of the participants, 52 used modified control systems. CONCLUSIONS: The diversity of EPIOC users across age and diagnostic groups is shown. Their complex interrelations with these technical features of EPIOC prescriptions are explored. Younger users were more complex because of age-related changes. This study provides outcomes of the EPIOC prescription for this heterogeneous group of very severely disabled people.
25229347 5-Lipoxygenase inhibitors attenuate TNF-α-induced inflammation in human synovial fibrobla 2014 The lipoxygenase isoform of 5-lipoxygenase (5-LOX) is reported to be overexpressed in human rheumatoid arthritis synovial tissue and involved in the progress of inflammatory arthritis. However, the detailed mechanism of how 5-lipoxygenase regulates the inflammatory response in arthritis synovial tissue is still unclear. The aim of this study was to investigate the involvement of lipoxygenase pathways in TNF-α-induced production of cytokines and chemokines. Human synovial fibroblasts from rheumatoid patients were used in this study. 5-LOX inhibitors and shRNA were used to examine the involvement of 5-LOX in TNF-α-induced cytokines and chemokines expression. The signaling pathways were examined by Western Blotting or immunofluorescence staining. The effect of 5-LOX inhibitor on TNF-α-induced chemokine expression and paw edema was also explored in vivo in C57BL/6 mice. Treatment with 5-LOX inhibitors significantly decreased TNF-α-induced pro-inflammatory mediators including interleukin-6 (IL-6) and monocyte chemo-attractant protein-1 (MCP-1) in human synovial fibroblasts. Knockdown of 5-LOX using shRNA exerted similar inhibitory effects. The abrogation of NF-κB activation was involved in the antagonizing effects of these inhibitors. Furthermore, 5-LOX inhibitor decreased TNF-α-induced up-regulation of serum MCP-1 level and paw edema in mouse model. Our results provide the evidence that the administration of 5-LOX inhibitors is able to ameliorate TNF-α-induced cytokine/chemokine release and paw edema, indicating that 5-LOX inhibitors may be developed for therapeutic treatment of inflammatory arthritis.
25051330 Repeated intravenous injections in non-human primates demonstrate preclinical safety of an 2015 May Dendrimers are nanosized hyperbranched polymers synthesized through an iterative step-by-step process; their size and structure are perfectly controlled, and they are widely used for biomedical purposes. Previously, we showed that a phosphorous-based dendrimer capped with anionic AzaBisPhosphonate groups (so-called ABP dendrimer) has immunomodulatory and anti-inflammatory properties toward the human immune system. It dramatically inhibits the onset and development of experimental arthritis in a mouse model relevant for human rheumatoid arthritis, a chronic inflammatory disease of auto-immune origin. In this article, we demonstrate in an unprecedented study that cynomolgus macaques repeatedly injected with the ABP dendrimer displayed no adverse response. Indeed, biochemical, haematological, clotting and immunological parameters remained with a normal physiological range during the study. Moreover, quantification of serum cytokines and histopathological analyses failed to reveal any noticeable lesion or noteworthy non-physiological occurrence. These results strengthen the potential of the ABP dendrimer as an innovative drug-candidate for the treatment of inflammatory diseases and favor the regulatory preclinical development of the molecule.
24830475 Disease or no disease? Disagreement on diagnoses between self-reports and medical records 2015 Mar BACKGROUND: Previous studies reported moderate to good agreement between patients' self-reported diseases and physicians' registered diseases. Disagreement might hamper a good doctor-patient relationship and hamper good quality of care. Disagreement can be associated with demographic and psychosocial patient characteristics. OBJECTIVES: To evaluate the level of agreement on reported chronic diseases between patients and their general practitioners (GPs); to assess whether disagreement relates to patient characteristics. METHODS: This study is embedded in a large GP based prospective cohort. Questionnaires of 2893 patients reporting on 14 chronic diseases are used. The agreement (percentage) between self-reported chronic diseases and the medical records was assessed first by descriptive statistics. To control for agreement by chance alone Cohen's kappa value was calculated. Type of (dis) agreement was further evaluated and associated with patient characteristics. RESULTS: Despite high agreement on diseases between patients and GPs, kappa's varied from 0.17 (inflammatory joint diseases and rheumatoid arthritis) to 0.86 (diabetes mellitus). Most often under-reporting and over-reporting was related to a decreased physical and mental quality of life and higher age. CONCLUSION: kappa values between patients and GPs appeared to be low in this study.
24477731 Sialometry: aspects of clinical interest. 2013 Nov Whole saliva is a multiglandular secretion complex consisting of gingival fluid, desquamated epithelial cells, microorganisms, products of bacterial metabolism, food debris, leukocytes mucus from the nasal cavity and the pharynx. Saliva has many functions, including tissue repair, tamponage, protection, digestion, taste, antimicrobial action, maintaining tooth integrity and antioxidant defense system. A decrease in salivary flow (hyposalivation) is a common disorder and it is estimated that approximately 20% of the general population have this alteration. Hyposalivation may be due to diabetes mellitus, hypothyroidism, dehydration, impaired glandular parenchyma by infectious processes, granulomatous diseases or autoimmune and inflammatory conditions (such as Sjogren's syndrome and rheumatoid arthritis), radiotherapy of head and/or neck region, or it may be associated with mood disorders, adverse effects caused by the use of some medications or even be idiopathic. Conventional therapies for the treatment of reduced saliva flow with the use of chemical and gustatory secretagogues are still limited. However, new alternatives have shown great perspective in the treatment of this disorder. To diagnose a patient as having chronic hyposalivation is a challenge in clinical practice and methods of salivary flow assessment are little known by rheumatologists. The serial evaluation of salivary flow is important for the diagnosis and prognosis of certain oral and systemic conditions. This review addresses some aspects related to the role of saliva, the consequences of hyposalivation and methods of salivary flow rate measurement, useful concepts in the daily practice of rheumatology.
23981219 The use of virtual planning and navigation in the treatment of temporomandibular joint ank 2013 Sep Temporomandibular joint ankylosis is not common in our community but can occur as a result of severe facial trauma or significant connective tissue disorders such as rheumatoid arthritis, osteoarthritis and psoriatic arthritis, and unfortunately as a result of iatrogenic causes. Ankylosis surgery is aimed at gap arthroplasty and mobilization of the joints. However, the removal of the bony ankylosis and the production of a gap between the ramus of the mandible and the base of the skull is often difficult because of the size of the ankylosis and the anatomy on the inner aspect of the mandible. As a result of this, the author has found that surgical navigation has been useful with the removal of the ankylosis, both on the medial side of the mandible and the cranial base. Once the ankylosis has been freed and the mandible mobilized, the gap arthroplasty needs to be maintained or the release of the ankylosis will fail and the joints will re-ankylose. It is important to maintain the space produced by the arthroplasty but this is difficult when autogenous materials such as temporalis muscle, dermis fat and other like materials are used. The gap ultimately closes under the influence of the masseter and medial pterygoid muscles and the ankylosis may return. This case report presents three representative patients in whom ankylosis has been released and the gap reconstructed with a total alloplastic joint replacement. All patients have had their ankylosis removed with the aid of a navigation system and all patients have been reconstructed with bilateral Biomet prosthesis. One patient has had their implant selected using virtual planning and the production of templates to help with placement of the stock implant.
23276893 Efficacy and safety of biologic treatments in Familial Mediterranean Fever. 2013 Aug OBJECTIVE: Colchicine is the mainstay treatment for Familial Mediterranean Fever (FMF). However 5% to 10% of the patients with FMF are unresponsive or intolerant to colchicine. Biologics are efficient in many rheumatic diseases, including rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, cryopyrin-associated periodic syndromes. We performed a systematic review to analyze patients with FMF, including juvenile patients who received treatment with biologics. METHODS: A MEDLINE search, including articles published in English language between 1990 and May 2012, was performed. Patients who had Mediterranean fever variants but could not be classified as FMF according to Tel-Hashomer criteria were excluded. RESULTS: There is no controlled trial on the efficacy and safety of biologics in FMF. Fifty-nine (32 female and 27 male) patients with FMF who had been treated with biologics (infliximab, etanercept, adalimumab, anakinra, and canakinumab) were reported in 24 single reports and 7 case series. There were 16 children and 43 adults (7- to 68-year olds). Five patients were reported to have colchicine intolerance or had adverse events related to colchicine use, and the rest 54 were unresponsive to colchicine treatment. CONCLUSIONS: The current data are limited to case reports, and it is difficult to obtain a quantitative evaluation of response to biologic treatments. However, on the basis of reported cases, biologic agents seem to be an alternative treatment for patients with FMF who are unresponsive or intolerant to colchicine therapy and seem to be safe. Controlled studies are needed to better evaluate the safety and efficacy of biologics in the treatment of patients with FMF.
23809696 Peripheral blood derived gene panels predict response to infliximab in rheumatoid arthriti 2013 BACKGROUND: Biological therapies have been introduced for the treatment of chronic inflammatory diseases including rheumatoid arthritis (RA) and Crohn's disease (CD). The efficacy of biologics differs from patient to patient. Moreover these therapies are rather expensive, therefore treatment of primary non-responders should be avoided. METHOD: We addressed this issue by combining gene expression profiling and biostatistical approaches. We performed peripheral blood global gene expression profiling in order to filter the genome for target genes in cohorts of 20 CD and 19 RA patients. Then RT-quantitative PCR validation was performed, followed by multivariate analyses of genes in independent cohorts of 20 CD and 15 RA patients, in order to identify sets ofinterrelated genes that can separate responders from non-responders to the humanized chimeric anti-TNFalpha antibody infliximab at baseline. RESULTS: Gene panels separating responders from non-responders were identified using leave-one-out cross-validation test, and a pool of genes that should be tested on larger cohorts was created in both conditions. CONCLUSIONS: Our data show that peripheral blood gene expression profiles are suitable for determining gene panels with high discriminatory power to differentiate responders from non-responders in infliximab therapy at baseline in CD and RA, which could be cross-validated successfully. Biostatistical analysis of peripheral blood gene expression data leads to the identification of gene panels that can help predict responsiveness of therapy and support the clinical decision-making process.
24853910 Pericyte dynamics during angiogenesis: new insights from new identities. 2014 Therapies aimed at manipulating the microcirculation require the ability to control angiogenesis, defined as the sprouting of new capillaries from existing vessels. Blocking angiogenesis would be beneficial in many pathologies (e.g. cancer, retinopathies and rheumatoid arthritis). In others (e.g. myocardial infarction, stroke and hypertension), promoting angiogenesis would be desirable. We know that vascular pericytes elongate around endothelial cells (ECs) and are functionally associated with regulating vessel stabilization, vessel diameter and EC proliferation. During angiogenesis, bidirectional pericyte-EC signaling is critical for capillary sprout formation. Observations of pericytes leading capillary sprouts also implicate their role in EC guidance. As such, pericytes have recently emerged as a therapeutic target to promote or inhibit angiogenesis. Advancing our basic understanding of pericytes and developing pericyte-related therapies are challenged, like in many other fields, by questions regarding cell identity. This review article discusses what we know about pericyte phenotypes and the opportunity to advance our understanding by defining the specific pericyte cell populations involved in capillary sprouting.
24575502 On-spot rheumatology consultations in a multilevel geriatric hospital. 2014 Jan BACKGROUND: Musculoskeletal and joint disorders are extremely common in the elderly. They directly affect mobility, gait stability, quality of life, and independence. OBJECTIVES: To assess the nature of joint problems encountered in a geriatric inpatient population and evaluate the contribution of a rheumatologist. METHODS: We reviewed the rheumatology consultation records that were conducted in a geriatric medical center over a 10 year period. RESULTS: A total of 474 consultations were held; most of these patients (86%) were hospitalized in the acute geriatric departments, 10% in the rehabilitation ward and 4% in the long-term care wards. Some patients were seen more than once. A rheumatologic joint problem was the main reason for hospitalization in 53% of these patients. Monoarthritis was the most frequent complaint (50%), followed by pauciarticular arthritis (two to five joints) in 30% of patients. Arthrocentesis, diagnostic and therapeutic, was performed in 225 patients, most of them in knee joints (81%). The most frequent diagnosis was osteoarthritis with acute exacerbation (28%), followed by gout (18%), pseudo-gout (9%) and rheumatoid arthritis (9%). In 86 cases (18%) the diagnosis was a non-specific rheumatologic problem: arthralgia, nonspecific generalized pain, or fibromyalgia. CONCLUSIONS: Prompt and appropriate evaluation, as well as arthrocentesis and treatment initiation, including local injections, were made possible by the presence of an in-house rheumatologist.
24306049 [Ankle arthrodesis with an posterolateral approach using a polyaxial angle stable Talarloc 2013 Dec OBJECTIVE: Safe arthrodesis of the ankle as well as load carrying capacity free of pain. INDICATION: Painful arthritis of the ankle joint occurring idiopathic or posttraumatic, resulting from rheumatoid arthritis or neuromuscular diseases. Extensive bony defects in varus or valgus ankle deformities and after failed prosthesis. Complex hindfoot deformities in neurological disease, paralysis and instabilities. Joint destruction after infection. CONTRAINDICATIONS: Active osteitis, extensive skin ulcers in the approach area, periphery artery occlusive disease. SURGICAL TECHNIQUE: Posterolateral skin incision. Sparing cartilage resection. Penetrating sclerosis zones. Reorientating anatomic positioning of the talus thereby correcting axis deformities. Talarlock(®) plate positioning and tibiotalar arthrodesis. POSTOPERATIVE MANAGEMENT: Full weight bearing in an arthodesis boot for 6 weeks. After bone grafting partial weight bearing (20 kg) in an arthrodesis boot for 8 weeks. Full weight bearing after 10weeks. RESULTS: Ten patients were operated on using this procedure. The follow-up time was 1 year. There were no complications requiring further surgical procedures. Ankle fusion and a good clinical outcome could be achieved in all cases.
23972099 Evaluation of WO2013076170: the use of a dihydroorotate dehydrogenase inhibitor for the tr 2013 Oct Inhibition of dihydroorotate dehydrogenase (DHODH) modulates pyrimidine biosynthesis. Effective inhibitors are immunomodulatory drugs clinically useful in the treatment of diseases such as rheumatoid arthritis, psoriatic arthritis and multiple sclerosis. There is limited evidence of their potential utility in treating psoriasis. This patent application claims topical formulations of the non-hepatotoxic DHODH inhibitor 2-[(3,5-difluoro-3'-methoxy-1,1'-biphenyl-4-yl)amino]nicotinic acid for use in the treatment of psoriasis. This inhibitor had previously been claimed to be useful in treating various autoimmune disease.
23604593 ANA (+) ANCA (+) systemic vasculitis associated with the use of minocycline: case-based re 2013 Jul Minocycline is a synthetic tetracycline-derived antibiotic with significant anti-inflammatory properties that may benefit patients with rheumatoid arthritis. Surprisingly, chronic exposure to minocycline can also cause a breach in immunologic tolerance resulting in a variety of autoimmune syndromes such as drug-induced lupus or autoimmune hepatitis. Vasculitis, most commonly resembling cutaneous polyarteritis nodosa, has also been seen in patients taking this drug. Herein, we present a case of biopsy-proven systemic vasculitis presenting as an ANA (+) ANCA (+) polyarteritis nodosa-like syndrome in a male patient who was taking minocycline for his acne for approximately 2 years. Patient initially presented with constitutional symptoms such as profound weight loss and fatigue, along with myalgias, oligoarticular arthritis, and livedo reticularis. About 2 months later, he developed a severe left testicular pain. Biopsy showed vasculitis complicated with the infarction of the left testis. Angiography revealed microaneurysms in the renal and splenic circulation. Stopping the offending drug, along with the short course of prednisone and hydroxychloroquine, resulted in prompt resolution of his symptoms. We additionally present a comprehensive review of biopsy-proven cases of vasculitis associated with chronic minocycline treatment focusing on its pathogenesis and clinical manifestations.
25012837 Vagal and recurrent laryngeal neuropathy following stereotactic ablative radiation therapy 2014 Jul PURPOSE: To identify clinical and dosimetric factors associated with vagus nerve (VN) and recurrent laryngeal nerve (RecLN) injury following stereotactic ablative radiation therapy (SABR) in the chest. METHODS AND MATERIALS: We examined the clinical courses and SABR plans of 67 patients treated for T1 or T2 non-small cell lung cancer of the upper right or left lung, including 2 who developed vocal cord paresis (VCP) following treatment. After developing a contouring atlas for the VN and RecLN in the thorax, dose to those structures was retrospectively determined for each patient, and we identified 12 patients whose treatment imparted significant dose to either nerve and who were assessable for more than 12 months follow-up. Biologically effective doses using linear-quadratic (LQ) and linear quadratic-linear (LQ-L) modeling were correlated with VN and RecLN toxicity. RESULTS: Of 12 patients, 2 developed VCP. The first underwent repeat SABR and received a cumulative single fraction equivalent dose (alpha/beta = 3; SFED3) of 37.4 or 64.5 Gy to the VN and 13.7 or 15.3 Gy to the RecLN (by LQ or LQ-L modeling, respectively). This was the highest VN dose and fifth highest RecLN dose in the cohort. The second had rheumatoid arthritis and connective tissue disease and received a SFED3 of 16 Gy to the VN and 19.5 Gy to the RecLN (by both LQ and LQ-L modeling). This was in the upper tertile of VN and RecLN doses for the cohort. CONCLUSIONS: Following SABR for non-small cell lung cancer, VCP was associated with high cumulative dose to the VN in 1 patient and a moderately high dose to the VN and RecLN in another patient with rheumatoid arthritis and connective tissue disease. Particularly in the setting of reirradiation or connective tissue disease, potential toxicity to the VN or RecLN should be considered.
24180333 Familial CD3+ T large granular lymphocyte leukemia: evidence that genetic predisposition a 2014 Aug CD3+ T-large granular lymphocyte (T-LGL) proliferations often present with cytopenias and splenomegaly and are linked to autoimmunity, especially rheumatoid arthritis and Felty's syndrome. We report here the intra-family occurrence of T-LGL leukemia in a father and son, both presenting with cytopenias and splenomegaly. Both patients carried the HLA-DRB1*04 allele, strongly associated with rheumatoid arthritis and Felty's syndrome, exhibited distinctive histopathological features suggestive of immune-mediated suppression of hematopoiesis and expressed a remarkably skewed T-cell receptor beta chain gene repertoire with overtime evolution (clonal drift). Immunoinformatics analysis and comparisons with clonotype sequences from various entities revealed (quasi)identities between (i) father and son, and (ii) father or son and patients with autoimmune disorders, T-LGL leukemia or chronic idiopathic neutropenia. Altogether, our results further corroborate antigen selection in the ontogeny of T-LGL leukemia and point to the interplay between genetics and the (micro)environment in shaping the outcome of cytotoxic T cell responses.
23848215 Prosthetic joint-associated infections treated with DAIR (debridement, antibiotics, irriga 2013 Aug BACKGROUND AND PURPOSE: For prosthetic joint-associated infection (PJI), a regimen of debridement, antibiotics, irrigation, and retention of the prosthesis (DAIR) is generally accepted for acute infections. Various risk factors associated with treatment success have been described. The use of local antibiotic carriers (beads and sponges) is relatively unknown. We retrospectively analyzed risk factors in a cohort of patients from 3 hospitals, treated with DAIR for PJI. PATIENTS AND METHODS: 91 patients treated with DAIR for hip or knee PJI in 3 Dutch centers between 2004 and 2009 were retrospectively evaluated. The mean follow-up was 3 years. Treatment success was defined as absence of infection after 2 years, with retention of the prosthesis and without the use of suppressive antibiotics. RESULTS: 60 patients (66%) were free of infection at follow-up. Factors associated with treatment failure were: a history of rheumatoid arthritis, late infection (> 2 years after arthroplasty), ESR at presentation above 60 mm/h, and infection caused by coagulase-negative Staphylococcus. Symptom duration of less than 1 week was associated with treatment success. The use of gentamicin sponges was statistically significantly higher in the success group, and the use of beads was higher in the failure group in the univariate analysis, but these differences did not reach significance in the logistic regression analysis. Less surgical procedures were performed in the group treated with sponges than in the group treated with beads. INTERPRETATION: In the presence of rheumatoid arthritis, duration of symptoms of more than 1 week, ESR above 60 mm/h, late infection (> 2 years after arthroplasty), and coagulase-negative Staphylococcus PJI, the chances of successful DAIR treatment decrease, and other treatment methods should be considered.
25105206 Higher risk of tuberculosis reactivation when anti-TNF is combined with immunosuppressive 2014 Nov OBJECTIVE: Treatment with tumour necrosis factor antagonists (anti-TNF) has been recognized as a risk factor for tuberculosis (TB) reactivation. Our aim was to evaluate risk of TB reactivation in rheumatologic and non-rheumatologic diseases treated with the same anti-TNF agents with and without concomitant therapies. METHODS: We searched for randomized controlled trials (RCTs) evaluating infliximab, adalimumab, and certolizumab in both rheumatologic and non-rheumatologic diseases until 2012. Results were calculated as pooled rates and/or pooled odd ratios (OR). RESULTS: Overall, 40 RCTs with a total of 14,683 patients (anti-TNF: 10,010; placebo: 4673) were included. TB reactivation was 0.26% (26/10,010) in the anti-TNF group and 0% (0/4673) in the control group, corresponding to an OR of 24.8 (95% CI 2.4-133). TB risk was higher when anti-TNF agents were combined with methotrexate or azathioprine as compared with either controls (24/4241 versus 0/4673; OR 54; 95% CI 5.3-88) or anti-TNF monotherapy (24/4241 versus 2/5769; OR 13.3; 95% CI 3.7-100). When anti-TNF was used as monotherapy, TB risk tended to be higher than placebo (2/5769 versus 0/4673; OR 4; 95% CI 0.2-15.7). CONCLUSIONS: TB risk with anti-TNF agents appeared to be increased when these agents were used in combination with methotrexate or azathioprine as compared with monotherapy regimen. TB risk seemed to be higher than placebo, even when monotherapy is prescribed.
24104186 A review of peripheral biomarkers in major depression: the potential of inflammatory and o 2014 Jan 3 Biomarkers are regularly used in medicine to provide objective indicators of normal biological processes, pathogenic processes or pharmacological responses to therapeutic interventions, and have proved invaluable in expanding our understanding and treatment of medical diseases. In the field of psychiatry, assessment and treatment has, however, primarily relied on patient interviews and questionnaires for diagnostic and treatment purposes. Biomarkers in psychiatry present a promising addition to advance the diagnosis, treatment and prevention of psychiatric diseases. This review provides a summary on the potential of peripheral biomarkers in major depression with a specific emphasis on those related to inflammatory/immune and oxidative stress/antioxidant defences. The complexities associated with biomarker assessment are reviewed specifically around their collection, analysis and interpretation. Focus is placed on the potential of peripheral biomarkers to aid diagnosis, predict treatment response, enhance treatment-matching, and prevent the onset or relapse of major depression.
24969316 Treat-to-target in spondyloarthritis: implications for clinical trial designs. 2014 Jul Spondyloarthritis (SpA) is a chronic inflammatory disease involving the spine and peripheral joints, and extra-articular manifestations such as uveitis, psoriasis and bowel inflammation. The treatment goals for SpA are maintenance of physical function, control of disease activity and prevention of radiographic progression. However, unlike the well-established treat-to-target (T2T) guidance in rheumatoid arthritis, the T2T concept for treating SpA is still immature. Clinical evidence of T2T in SpA is still lacking. To develop evidence of T2T in SpA, several research agendas need to be accomplished. Firstly, a well-accepted measureable treatment target needs to be defined through expert consensus. Secondly, a T2T treatment algorithm for monitoring disease activity and adjusting therapies needs to be generated. Finally, well-designed comparative clinical trials to compare this T2T strategy with the current standard of treatment should be conducted to demonstrate long-term benefits and risks. In SpA clinical trials, T2T comparative studies should have a clear disease definition for enrollment of patients with ankylosing spondylitis (AS), psoriatic arthritis, axial SpA or non-radiographic axial SpA. Endpoints should be assessment with AS International Working Group criteria for 20% improvement (ASAS20), ASAS40, and the Ankylosing Spondylitis Disease Activity Score (ASDAS) with inactive and moderate disease activity at month 3. Long-term efficacy endpoints such as the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) of radiographic progression and magnetic resonance imaging (MRI) score at 2 years are encouraged. More sensitive assessment tools to detect structural damage and new bone formation, such as low-radiation computerized tomography (CT), are promising.