Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
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| 28572722 | Shared decision-making for biologic treatment of autoimmune disease: influence on adherenc | 2017 | BACKGROUND: Shared decision-making (SDM), a process whereby physicians and patients collaborate to select interventions, is not well understood for biologic treatment of autoimmune conditions. METHODS: This was a cross-sectional survey of adults initiating treatment for Crohn's disease or ulcerative colitis (inflammatory bowel disease, IBD) or psoriatic arthritis or rheumatoid arthritis (RA/PA). Survey data were linked to administrative claims for 6 months before (baseline) and after (follow-up) therapy initiation. Measures included the Shared Decision Making Questionnaire, Patient Activation Measure (PAM), Morisky Medication Adherence Scale (MMAS), general health, and treatment satisfaction. Claims-based Quan-Charlson comorbidity scores, persistence, medication possession ratio (MPR), and health care costs were examined. Patients were compared by participation (SDM) and nonparticipation (non-SDM) in SDM. RESULTS: Among 453 respondents, 357 were eligible, and 306 patients (204 RA/PA and 102 IBD) were included in all analyses. Overall (n=357), SDM participants (n=120) were more often females (75.0% vs 62.5%, P=0.018), had lower health status (48.0 vs 55.4, P=0.005), and higher Quan-Charlson scores (1.0 vs 0.7, P=0.035) than non-SDM (n=237) participants. Lower MMAS scores (SDM 0.17 vs non-SDM 0.41; P<0.05) indicated greater likelihood of adherence; SDM participants also reported higher satisfaction with medication and had greater activation (PAM: SDM vs non-SDM: 66.9 vs 61.6; P<0.001). Mean MPR did not differ, but persistence was longer among SDM participants (111.2 days vs 102.2 days for non-SDM; P=0.029). Costs did not differ by SDM status overall, or among patients with RA/PA. The patients with IBD, however, experienced lower (P=0.003) total costs ($9,404 for SDM vs $25,071 for non-SDM) during follow-up. CONCLUSION: This study showed greater likelihood of adherence and satisfaction for patients who engaged in SDM and reduced health care costs among patients with IBD who engaged in SDM. This study provides a basis for defining SDM participation and detecting differences by SDM participation for biologic treatment selection for autoimmune conditions. | |
| 27913990 | Sirukumab: A Potential Treatment for Mood Disorders? | 2017 Jan | Convergent evidence indicates that abnormalities in the innate immune system may be pertinent to the pathogenesis, phenomenology, and possible treatment of several mental disorders. In keeping with this view, the targeting of interleukin-6 with the human monoclonal antibody sirukumab may represent a possible treatment and disease modification approach, for adults with brain-based disorders (e.g., major depressive disorder). A PubMed/Medline database search was performed using the following search terms: sirukumab; anti-IL-6; IL-6; major depressive disorder; inflammation. A systematic review was conducted of both preclinical and clinical trials reporting on the pharmacology of sirukumab or investigating the efficacy of targeting IL-6 signaling. Overall, sirukumab has been reported to be a safe and well-tolerated agent, capable of modulating the immune response in healthy populations as well as in subjects with inflammatory disorders (e.g., rheumatoid arthritis). Sirukumab's effects on cytokine networks as part of the innate immune system provide a coherent rationale for possible application in neuropsychiatric disorders with possible benefits across several domains of the biobehavioral Research Domain Criteria matrix (e.g., general cognitive processes, positive valence systems). Amongst individuals with complex brain-based disorders (e.g., mood disorders), the dimensions/domains most likely to benefit with sirukumab are negative valence disturbances (e.g., anxiety, depression, rumination), positive valence disturbances (e.g., anhedonia) as well as general cognitive processes. We suggest that sirukumab represents a prototype and possibly a proof-of-concept that agents that engage IL-6 targets have salutary effects in psychiatry. | |
| 28975718 | Effects of Febuxostat in Early Gout: A Randomized, Double-Blind, Placebo-Controlled Study. | 2017 Dec | OBJECTIVE: To assess the effect of treatment with febuxostat versus placebo on joint damage in hyperuricemic subjects with early gout (1 or 2 gout flares). METHODS: In this double-blind, placebo-controlled study, 314 subjects with hyperuricemia (serum uric acid [UA] level of ≥7.0 mg/dl) and early gout were randomized 1:1 to receive once-daily febuxostat 40 mg (increased to 80 mg if the serum UA level was ≥6.0 mg/dl on day 14) or placebo. The primary efficacy end point was the mean change from baseline to month 24 in the modified Sharp/van der Heijde erosion score for the single affected joint. Additional efficacy end points included change from baseline to month 24 in the Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS) scores for synovitis, erosion, and edema in the single affected joint, the incidence of gout flares, and serum UA levels. Safety was assessed throughout the study. RESULTS: Treatment with febuxostat did not lead to any notable changes in joint erosion over 2 years. In both treatment groups, the mean change from baseline to month 24 in the modified Sharp/van der Heijde erosion score for the single affected joint was minimal, with no between-group differences. However, treatment with febuxostat significantly improved the RAMRIS synovitis score at month 24 compared with placebo treatment (change from baseline -0.43 versus -0.07; P <0.001), decreased the overall incidence of gout flares (29.3% versus 41.4%; P < 0.05), and improved serum UA control (62.8% versus 5.7%; P < 0.001). No major safety concerns were reported. CONCLUSION: Urate-lowering therapy with febuxostat improved magnetic resonance imaging-determined synovitis and reduced the incidence of gout flares in subjects with early gout. | |
| 32095470 | Screening study for genetic polymorphisms affecting pharmacokinetics of talniflumate. | 2017 Dec | Talniflumate is a phthalidyl ester of niflumic acid, which has potent analgesic and anti-inflammatory effects and is widely used to treat inflammatory disorders, such as rheumatoid arthritis. To screen the possible genetic factors affecting the pharmacokinetics (PK) of talniflumate, 23 male Korean volunteers were enrolled from two separate bioequivalence studies. All subjects received 740 mg (two tablets) talniflumate in a standard 2×2 cross-over model in a randomized order. For the genetic study, PK parameters of the reference drug were used. We used Illumina Human610Quad v1.0 DNA Analysis BeadChip for whole genome single nucleotide polymorphism (SNP) analysis and whole genome genotyping data were processed by linear regression analysis for PK parameters. Whole genome analysis revealed 1498 significant SNPs (P < 0.0001) for C(max), 65 significant SNPs (P < 0.0001) for T (max), and 1491 significant SNPs (P < 0.0001) for AUC (inf.) For clinical pharmacological purposes, we selected SNPs from drug metabolizing enzymes and transporters, and analyzed the PK parameters of various genotypes. Two SNPs (rs11165069 from ABCA4 (p=0.00002); rs17847036 from CYP2C9 (p=0.000001)) showed significant associations with talniflumate C (max). In the T (max) group, two SNPs (rs3787555 from CYP24A1 (p=0.00035); rs2275034 from ABCA4 (p=0.000587)) showed significant associations with talniflumate T (max). In the AUC (inf) group, two SNPs (rs11165069 from ABCA4 (p=0.00002); rs12461006 from SLC1A6 (p=0.00008)) exhibited significant associations with talniflumate absorption. These results show that genetic factors could affect the PK parameters, and provide information that may be used in the development of personalized talniflumate therapy. | |
| 29155234 | Survivin and autoimmunity; the ins and outs. | 2018 Jan | Autoimmunity is a status that immune mechanisms react against self-structure. The immune mechanisms, including cellular and molecular elements have been developed to immune body against foreign invades. Multiple factors such as genetic and epigenetic background, hormonal status, microbiome, and other factors can cause launching the autoreactive responses, in which the immune tolerance breaks and immune mechanisms are against self-antigens. Apoptosis is one of the important mechanisms in maintaining the tolerance and eliminating the autoreactive lymphocyte clones. Due to survivin roles in apoptosis and proliferation, numerous researches have been paying attention to survivin expression and function in autoreactive lymphocytes and tissue cells, playing important roles in the pathogenesis of autoimmune diseases. New line of evidence has been supporting the role of survivin dysfunction or aberrant expression in deriving autoreactive lymphocytes or some important immune tissues, which may underpin the autoimmune conditions such as Lichen planus (LP), Rheumatoid arthritis (RA), Systemic lupus erythematosus (SLE), Myasthenia gravis (MG), Multiple sclerosis (MS), Systemic sclerosis (SSc), Psoriasis, and Inflammatory bowel disease (IBD). Hence, the purpose of the current paper was to review the survivin role in the etiology and pathogenesis of abovementioned autoimmune diseases. | |
| 29074035 | The IL-12 cytokine family in cardiovascular diseases. | 2019 Oct | Cytokines of the Interleukin (IL)-12 family, consisting of IL-12, IL-23, IL-27 and IL-35, are important regulators in (chronic) inflammatory disorders such as rheumatoid arthritis and multiple sclerosis, but also in cardiovascular diseases. Cytokines of the IL-12 family consist of two subunits and are known for their regulatory functions in the immunologic response, more specifically in the regulation and differentiation of T-helper (Th) cells such as Th1 and Th17 cells. Binding of these cytokines to its specific heterodimeric receptor results in the activation of the JAK-STAT signaling. Despite similarities in structure, the members of the IL-12 family have diverse, both pro- and anti-inflammatory, effects and functions. Because of the pro-inflammatory effects of IL-12 cytokine family members on immune responses, the IL-12 cytokines have been implicated in the development and progression of cardiovascular diseases such as atherosclerosis, but also in acute cardiovascular syndromes such as myocardial infarction and stroke. For example, patients suffering from cardiovascular disease display increased blood levels of IL-12, IL-23 and IL-27, while decreased IL-35 levels have been linked to a lower cardiovascular risk. In this review, we aim to highlight the current understandings of the IL-12 cytokine family and its specific family members to cardiovascular diseases, including both clinical and experimental studies. We will also discuss the potential of these cytokines as a biomarker in acute cardiovascular syndromes. | |
| 28800262 | Risk factors predisposing to the development of hypogammaglobulinemia and infections post- | 2017 Nov 2 | Rituximab (RTX) is a monoclonal antibody against CD20, commonly used in the treatment of hematological malignancies and autoimmune diseases. The use of RTX is related to the development of hypogammaglobulinemia and infections. Aim of this review is to summarize the evidence supporting the association of specific risk factors with the development of hypogammaglobulinemia and infections post-RTX. Immunological complications are more common in patients with malignant diseases as compared to non-malignant diseases. Moreover, the use of more than one dose of RTX, maintenance regimens, low pre-treatment basal immunoglobulin levels and the association with Mycophenolate and purine analogues represent risk factors for the development of hypogammaglobulinemia. The number of RTX courses, the evidence of low IgG levels for more than 6 months, the use of G-CSF, the occurrence of chronic lung disease, cardiac insufficiency, extra-articular involvement in patients with rheumatoid arthritis, low levels of IgG and older age have been correlated with a higher risk of infections. Even though the heterogeneity of the studies in terms of study population age and underlying disease, RTX schedules as well as differences in pre-treatment or concomitant therapy doesn't allow drawing definitive conclusions, the study of the literature highlight the association of specific risk factors with the occurrence of hypogammaglobulinemia and/or infections. A long term randomized controlled clinical trial could be useful to define a personalized evidence-based risk management plan for patients treated with RTX. | |
| 28662932 | Dynamic in vivo 3D atlantoaxial spine kinematics during upright rotation. | 2017 Jul 26 | Diagnosing dysfunctional atlantoaxial motion is challenging given limitations of current diagnostic imaging techniques. Three-dimensional imaging during upright functional motion may be useful in identifying dynamic instability not apparent on static imaging. Abnormal atlantoaxial motion has been linked to numerous pathologies including whiplash, cervicogenic headaches, C2 fractures, and rheumatoid arthritis. However, normal C1/C2 rotational kinematics under dynamic physiologic loading have not been previously reported owing to imaging difficulties. The objective of this study was to determine dynamic three-dimensional in vivo C1/C2 kinematics during upright axial rotation. Twenty young healthy adults performed full head rotation while seated within a biplane X-ray system while radiographs were collected at 30 images per second. Six degree-of-freedom kinematics were determined for C1 and C2 via a validated volumetric model-based tracking process. The maximum global head rotation (to one side) was 73.6±8.3°, whereas maximum C1 rotation relative to C2 was 36.8±6.7°. The relationship between C1/C2 rotation and head rotation was linear through midrange motion (±20° head rotation from neutral) in a nearly 1:1 ratio. Coupled rotation between C1 and C2 included 4.5±3.1° of flexion and 6.4±8.2° of extension, and 9.8±3.8° of contralateral bending. Translational motion of C1 relative to C2 was 7.8±1.5mm ipsilaterally, 2.2±1.2mm inferiorly, and 3.3±1.0mm posteriorly. We believe this is the first study describing 3D dynamic atlantoaxial kinematics under true physiologic conditions in healthy subjects. C1/C2 rotation accounts for approximately half of total head axial rotation. Additionally, C1 undergoes coupled flexion/extension and contralateral bending, in addition to inferior, lateral and posterior translation. | |
| 28567422 | Risk Factors for the Mortality of Pneumocystis jirovecii Pneumonia in Non-HIV Patients Who | 2017 | BACKGROUND: The risk factors for the mortality rate of Pneumocystis jirovecii pneumonia (PCP) who required mechanical ventilation (MV) remained unknown. METHODS: A retrospective chart review was performed of all PCP patients admitted to our intensive care unit and treated for acute hypoxemic respiratory failure to assess the risk factors for the high mortality. RESULTS: Twenty patients without human immunodeficiency virus infection required mechanical ventilation; 19 received noninvasive ventilation; and 11 were intubated. PEEP was incrementally increased and titrated to maintain FIO(2) as low as possible. No mandatory ventilation was used. Sixteen patients (80%) survived. Pneumothorax developed in one patient with rheumatoid arthritis (RA). Median PEEP level in the first 5 days was 10.0 cmH(2)O and not associated with death. Multivariate analysis showed the association of incidence of interstitial lung disease and increase in serum KL-6 with 90-day mortality. CONCLUSIONS: We found MV strategies to prevent pneumothorax including liberal use of noninvasive ventilation, and PEEP titration and disuse of mandatory ventilation may improve mortality in this setting. Underlying disease of interstitial lung disease was a risk factor and KL-6 may be a useful predictor associated with mortality in patients with RA. These findings will need to be validated in larger studies. | |
| 28528521 | Myeloid Populations in Systemic Autoimmune Diseases. | 2017 Oct | Systemic autoimmune diseases (SADs) encompass a wide spectrum of clinical signs as a reflection of their complex physiopathology. A variety of mechanisms related with the innate immune system are in the origin of the loss of self-tolerance in these diseases, and for most of them, the myeloid leukocytes are key actors. Monocytes, macrophages, dendritic cells, and neutrophils are first-line immune effectors located in the interface between innate and adaptive immunity. They are crucial in the organization of the local and systemic responses to damage-associated molecular patterns (DAMPs) and determine the intensity, orientation, and duration of the local immune response through the expression of chemokines, costimulatory or protolerogenic factors. In this review, we summarize the current knowledge about the role of the main myeloid populations in the induction and maintenance of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), primary antiphospholipid antibody syndrome (PAPS), systemic sclerosis (SSc), and Sjögren's syndrome (SjS), based on the data from both mouse preclinical models and patients. According to these data, our challenge in the next few years is to better dissect the fine mechanisms underlying the pathological role of myeloid cells in these diseases in order to define specific cell subsets or proteins that can be potential targets for drug development. | |
| 28478671 | Autonomous Cell Migration to CSF1 Sources via a Synthetic Protein-Based System. | 2017 Aug 18 | Inflammatory lesions, often seen in diseases such as rheumatoid arthritis, atherosclerosis and cancer, feature an acidic (i.e., low pH) microenvironment rampant with cytokines, such as CSF1. For potential therapeutic intervention targeted at these CSF1 sources, we have assembled a system of four proteins inside a cell (i.e., HEK293) that initially had no natural CSF1-seeking ability. This system included a newly engineered CSF1 chimera receptor (named CSF1Rchi), the previously engineered Ca(2+) activated RhoA (i.e., CaRQ), vesicular stomatitis virus glycoprotein G (VSVG) and thymidine kinase (TK). The binding of CSF1 to the CSF1Rchi generated a Ca(2+) signal that activated CaRQ-mediated cellular blebbing, allowing autonomous cell migration toward the CSF1 source. Next, the VSVG protein allowed these engineered cells to fuse with the CSF1 source cells, upon low pH induction. Finally, these cells underwent death postganciclovir treatment, via the TK suicide mechanism. Hence, this protein system could potentially serve as the basis of engineering a cell to target inflammatory lesions in diseases featuring a microenvironment with high levels of CSF1 and low pH. | |
| 27958688 | Results of surgical interventions for critical limb ischemia due to vasculitis or collagen | 2017 Aug | BACKGROUND: In this study, we aimed to clarify both systemic and local prognosis after surgical interventions for critical limb ischemia (CLI) due to vasculitis or connective tissue related disease, and to search for any risk factors that can worsen the prognosis. METHODS: One hundred and ninety three patients that underwent surgical interventions for CLI between 2005 and 2014 were followed up for a median of 2.7 years. The patients were grouped into a group with vasculitis or connective tissue related disease (V) or with atherosclerosis (control: C). Two groups were retrospectively reviewed and compared. RESULTS: Thirty-one patients were grouped into the V group. At three years after intervention, V group showed significantly higher survival rate compared to C group (89% vs. 73%). On the other hand, limb survival rate after bypass surgery was significantly lower (74% vs. 94%), due to lower patency of the bypassed graft. Within V group, preoperative skin perfusion pressure of lower than 20 mmHg showed significantly worse prognosis of the limb. (HR 1.8; P=0.01) Regarding specific diseases, systemic scleroderma, rheumatoid arthritis and systemic lupus erythematosus tended to show worse prognosis. CONCLUSIONS: Patients with CLI due to vasculitis or connective tissue related disease have a longer life expectancy with lower limb salvage rate that can lead to low quality of the remaining life. | |
| 28976997 | Transcription analysis of the responses of porcine heart to Erysipelothrix rhusiopathiae. | 2017 | Erysipelothrix rhusiopathiae (E. rhusiopathiae) is the causative agent of swine erysipelas. This microbe has caused great economic losses in China and in other countries. In this study, high-throughput cDNA microarray assays were employed to evaluate the host responses of porcine heart to E. rhusiopathiae and to gain additional insights into its pathogenesis. A total of 394 DE transcripts were detected in the active virulent E. rhusiopathiae infection group compared with the PBS group at 4 days post-infection. Moreover, 262 transcripts were upregulated and 132 transcripts were downregulated. Differentially expressed genes were involved in many vital functional classes, including inflammatory and immune responses, signal transduction, apoptosis, transport, protein phosphorylation and dephosphorylation, metabolic processes, chemotaxis, cell adhesion, and innate immune responses. Pathway analysis demonstrated that the most significant pathways were Chemokine signaling pathway, NF-kappa B signaling pathway, TLR pathway, CAMs, systemic lupus erythematosus, chemokine signaling pathway, Cytokine-cytokine receptor interaction, PI3K-Akt signaling pathway, Phagosome, HTLV-I infection, Measles, Rheumatoid arthritis and natural-killer-cell-mediated cytotoxicity. The reliability of our microarray data was verified by performing quantitative real-time PCR. This study is the first to document the response of piglet heart to E. rhusiopathiae infection. The observed gene expression profile could help screen potential host agents that can reduce the prevalence of E. rhusiopathiae. The profile might also provide insights into the underlying pathological changes that occur in pigs infected with E. rhusiopathiae. | |
| 28912865 | Elevated levels of soluble fractalkine and increased expression of CX3CR1 in neuropsychiat | 2017 Oct | The aim of the present study was to determine the levels of soluble fractalkine (sFKN) and expression of CX3CR1 in neuropsychiatric systemic lupus erythematosus (NPSLE). Disease activity of SLE was assessed using the SLE Disease Activity Index (SLEDAI). The mRNA expression levels of CX3CR1 and FKN were quantified using reverse transcription-quantitative polymerase chain reaction. Levels of sFKN in the serum and cerebrospinal fluid (CSF) were measured using enzyme-linked immunosorbent assays. The mRNA expression levels of CX3CR1 in peripheral blood mononuclear cells from patients with NPSLE, non-NPSLE and Behcet's disease were significantly higher than that of rheumatoid arthritis and healthy persons. Levels of sFKN in the serum and CSF of cells with diffuse NPSLE (DNPSLE) were significantly higher than those of focal NPSLE (FNPSLE) cells. Serum levels of sFKN were higher in patients with NPSLE or non-NPSLE than heathy persons. sFKN in CSF were significantly higher in DNPSLE than non-NPSLE cells, but there were no significant difference between FNPSLE and control. Treatment reduced sFKN in serum and CSF in patients with NPSLE. There was significant correlation between sFKN in the serum of patients with SLE and the SLEDAI. sFKN levels were correlated with IgG in CSF from patients with NPSLE. The mRNA expression levels of CX3CR1 in the brain tissue of lupus mice were significantly higher than normal mice; however, the mRNA expression of FKN was lower than normal mice. These results suggest that sFKN and CX3CR1 may be involved in vasculitis and SLE, particularly in DNPSLE, which may occur by damaging the blood-brain barrier or recruiting expression microglial cells of CX3CR1. Additionally, sFKN appears to be a serological marker in patients with SLE, and may be useful for the diagnosis and treatment of NPSLE. | |
| 28778705 | Targeting interleukin-6 in autoimmune uveitis. | 2017 Oct | Interleukin-6 (IL-6) is a key cytokine that is strongly up-regulated during infection and inflammation. Featuring pleiotropic activity, IL-6 is responsible for the induction of hepatic acute-phase proteins, trafficking of acute and chronic inflammatory cells, differentiation of adaptive T cell responses, homeostatic regulation, and tissue regeneration. Dysregulated IL-6 production has been associated with the development of a wide variety of systemic immune-mediated, chronic diseases, and even certain types of cancer. From the ocular perspective, significant elevation of IL-6 has been found in ocular fluids derived from diabetic macular edema, retinal vein occlusion, and refractory/chronic uveitis patients. During the last decade, tocilizumab, a neutralizing monoclonal antibody (mAb) that targets the IL-6 receptor (IL-6R), has been approved for the treatment of rheumatoid arthritis in >100 countries worldwide. Furthermore, it has been reported to be effective for the treatment of a number of autoimmune diseases including uveitis and its associated macular edema. Currently numerous candidate molecular strategies targeting the IL-6 signaling pathways are in progress through clinical trials in various disorders. Herein we discuss the basic biology of IL-6 and its pathological role in the development of immune-mediated conditions, particularly focusing on inflammatory eye diseases. It also provides an overview of the on-going clinical trials with the new anti-IL-6 mAbs and their potential use in the clinical practice. | |
| 28744501 | Proximal junctional kyphosis in adult spinal deformity with long spinal fusion from T9/T10 | 2017 Jun | BACKGROUND: Proximal junctional kyphosis (PJK) is a common complication after corrective long spinal fusion for adult spinal deformity. Although some reports evaluated PJK after corrective long spinal fusion, there is no report about analysis of PJK cases in the same fusion area. The purpose of this study to investigated the incidence of and risk factors for PJK in adults undergoing long spinal fusion from the distal thoracic vertebrae (T9/T10) to the ilium. METHODS: We enrolled 56 adult patients (>40 years of age) who underwent posterior corrective surgery with same fusion area from T9 or T10 to the ilium for spinal deformity. Pre- and postoperative radiographic measurements included the sagittal vertical axis (SVA), lumbar lordosis (LL), thoracic kyphosis (TK), pelvic tilt (PT), and pelvic incidence minus LL (PI-LL). The Oswestry disability index (ODI) was used to evaluate patient outcomes preoperatively and one year after surgery. We analyzed the incidence for PJK and compared PJK and non-PJK cases. RESULTS: PJK at the final follow-up occurred in 19 of 56 (33.9%) patients. The mean age and ODI were not significantly different between the PJK and non-PJK groups. Both two groups had good spinopelvic sagittal alignment after surgery in terms of SVA and PI-LL. Only three cases required revision surgery for symptomatic PJK. Three cases had history of rheumatoid arthritis and/or total hip arthroplasty surgery. CONCLUSIONS: The incidence of PJK was 33.9%, and ODI was not significantly different between the PJK and non-PJK groups. Symptomatic PJK was only three cases and all of them had lower extremity joint disorders. We should pay attention also lower extremity joint to prevent symptomatic PJK at the lower thoracic level. | |
| 28709119 | A compensating income variation approach to valuing 34 health conditions in Iceland. | 2017 Nov | Using data from an Icelandic health-and-lifestyle survey carried out in 2007, 2009, and 2012, we employ a compensating income variation (CIV) approach to estimate the monetary value sufficient to compensate individuals for the presence of various sub-optimal health conditions. This method is inexpensive and easy on subjects and has been applied to several desiderata that do not have revealed market prices. The CIV literature is, however, still limited in its application to health and thus information about its suitability is limited. With the aim of shedding light on the methodÌs appropriateness we thus provide a broad-view analysis including a spectrum of diseases and conditions that can be held up against more traditionally used methods. CIV for physical conditions vary greatly, but paralysis, fibromyalgia, chronic back pain, rheumatoid arthritis, urinary incontinence, severe headache and thyroid disease were among those consistently associated with substantial well-being reductions. Mental-health results using this method should be read with caution. The societal value of health interventions is multidimensional, including for example increased productivity in the population. However, one of the main positive aspects of increased health is undoubtedly the increased well-being of the treated subjects. Such quality-of-life effects should thus preferably be taken into account. For this reason, information on the value individuals place on recovery from various sub-optimal health conditions is useful when it comes to prioritizing scarce capital in the health sector. It is therefore vital to estimate the importance individuals place on various health states and hold them up against each other. Furthermore, this paper has scientific value as it sheds light on attributes of a potentially useful method in health evaluations. | |
| 28626499 | The Effects of Blast Exposure on Protein Deimination in the Brain. | 2017 | Oxidative stress and calcium excitotoxicity are hallmarks of traumatic brain injury (TBI). While these early disruptions may be corrected over a relatively short period of time, long-lasting consequences of TBI including impaired cognition and mood imbalances can persist for years, even in the absence of any evidence of overt injury based on neuroimaging. This investigation examined the possibility that disordered protein deimination occurs as a result of TBI and may thus contribute to the long-term pathologies of TBI. Protein deimination is a calcium-activated, posttranslational modification implicated in the autoimmune diseases rheumatoid arthritis and multiple sclerosis, where aberrant deimination creates antigenic epitopes that elicit an autoimmune attack. The present study utilized proteomic analyses to show that blast TBI alters the deimination status of proteins in the porcine cerebral cortex. The affected proteins represent a small subset of the entire brain proteome and include glial fibrillary acidic protein and vimentin, proteins reported to be involved in autoimmune-based pathologies. The data also indicate that blast injury is associated with an increase in immunoglobulins in the brain, possibly representing autoantibodies directed against novel protein epitopes. These findings indicate that aberrant protein deimination is a biomarker for blast TBI and may therefore underlie chronic neuropathologies of head injury. | |
| 28566782 | Early results of an intraosseous device for arthrodesis of the hallux metatarsophalangeal | 2017 May | BACKGROUND: Arthrodesis of the hallux metatarsophalangeal (MTP) joint is commonly done as a primary procedure either to correct severe hallux valgus deformities or for rheumatoid arthritis, hallux rigidus, in patients with neuromuscular disorders and as a salvage procedure for failed bunion surgery or infection. Prominent metalwork frequently can cause soft tissue impingement and thus require removal. In contrast, osteosynthesis with a completely intraosseous implant has the advantage of less damage to the periosteal circulation. We describe a surgical technique and the early results of arthrodesis of the hallux metatarsophalangeal (MTP) joint using an intraosseous fixation device. MATERIALS AND METHODS: Twelve consecutive patients operated with this method were retrospectively reviewed. The average age was 57 years (range 44-88 years). A retrospective review of radiographs and electronic medical notes was conducted. The patients were also asked to fill a satisfaction questionnaire. RESULTS: Overall fusion rate was 91% with a mean hallux valgus angle of 15° (range 4-20°) and a mean dorsiflexion angle of 20° (range 7-30°). Complications included a case of failed fusion, a delayed union, and a case of persisting transfer metatarsalgia. At a mean followup of 14 months (range 5-28 months), the mean visual analog scale improved significantly from a mean of 8.4 (range 7-10) preoperatively, to a mean of 3.1 (range 0-7) postoperatively (P < 0.0001). The mean American Orthopaedic Foot and Ankle Society hallux score also significantly improved from 29.4 (range 10-54) to a mean of 73.3 (range 59-90) (P < 0.0001). The final result was satisfactory for 83% of the patients. CONCLUSIONS: The early results show intraosseous fixation to be a safe and efficient method for the fusion of the hallux MTP joint providing relief from pain and patient satisfaction. | |
| 28318613 | Latent tuberculosis infection screening prior to biological treatment in Tunisian patients | 2017 Oct | OBJECTIVES: The screening of latent tuberculosis infection (LTBI) is necessary to prevent infection in patients with chronic inflammatory disease (CID) undergoing biological treatment. We aimed to assess the efficacy of LTBI screening prior to biological treatment in Tunisia, considered as a high-incidence area of active TB disease. METHODS: We conducted a retrospective study over a period of 8 years [2007-2014] including patients with chronic inflammatory rheumatism receiving biologic agents since at least 6 months. The screening of LTBI was performed according to national Tunisian guidelines. RESULTS: There were 35 men and 78 women. The mean age was 47.67±13.50 years. Rheumatoid arthritis (70.8%) was the most common cause of CID. The diagnosis of LTBI was established in 23 cases. Among these 23 patients, 12 patients had negative tuberculin skin test (TST) associated with positive QuantiFERON-TB Gold (QFT-G), 10 had TST more than 10mm, one patient had a TST between 5 and 10mm associated with positive QFT-G and one patient had a history of tuberculosis inadequately treated. Preventive anti-tuberculous therapy was prescribed before biological therapy initiation in cases of LTBI. During the follow-up period (3.91 years), no case of tuberculosis reactivation has been reported among patients diagnosed with LTBI. However, 2 cases of active pulmonary tuberculosis were reported in patients with initially negative TST and QFT-G. CONCLUSION: Our study showed that the Tunisian recommendations allowed detecting a LTBI in 20% of biologic therapy candidates. Preventive measures including screening of LTBI and eventually a prophylactic treatment improve the safety of biological treatments. |