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ID PMID Title PublicationDate abstract
22801953 Risk factors associated with the occurrence of hip fracture in Japanese patients with rheu 2013 Apr Risk factors associated with the occurrence of hip fracture in Japanese patients with rheumatoid arthritis (RA) were evaluated in a prospective, observational cohort study. Physical disability, advanced age, history of total knee replacement (TKR), and low body mass index (BMI) appear to be associated with the occurrence of hip fracture. INTRODUCTION: This study seeks to evaluate the association between potential risk factors and the occurrence of hip fractures in Japanese RA patients. METHODS: A total of 9,720 patients (82.1% female; mean age, 55.7 years) with RA were enrolled in a prospective observational study from 2000 to 2010. Self-reported hip fractures were verified using patient medical records. Cox proportional hazards models were used to analyze independent contributions of various risk factors to hip fracture occurrence. RESULTS: During a mean follow-up of 5.2 years, 152 patients reported 152 hip fractures. Among these patients, 97 hip fractures in 97 patients (15 males, 82 females) were verified with medical records. Japanese version of the Health Assessment Questionnaire (J-HAQ) disability score [per 1 score, hazard ratio (HR), 2.64; 95% confidence interval (CI), 1.94-3.58], age (per 10 years; HR, 1.53; 95% CI, 1.25-1.87), history of TKR (HR, 3.75; 95% CI, 1.57-8.96), and BMI (per 1 kg/m2, HR, 0.92; 95% CI, 0.86-0.99) were significantly associated with hip fractures. Among the scores on the eight domains of the J-HAQ, J-HAQ (arising) (HR, 1.74; 95% CI, 1.28-2.36) and J-HAQ (hygiene) (HR, 1.58; 95% CI, 1.11-2.24) were significantly correlated with the occurrence of hip fracture. CONCLUSIONS: High J-HAQ disability score, advanced age, history of TKR, and low BMI appear to be associated with the occurrence of hip fractures in Japanese RA patients. Among the eight domains of the J-HAQ, arising and hygiene disabilities appear to be correlated with the occurrence of hip fractures in this patient population.
22179732 Analysis of SF and plasma cytokines provides insights into the mechanisms of inflammatory 2012 Mar OBJECTIVES: Biologic drugs have revolutionized the care of RA, but are expensive and not universally effective. To further understand the inflammatory mechanisms underlying RA and identify potential biomarkers predicting response to therapy, we measured multiple cytokine concentrations in SF of patients with inflammatory arthritides (IAs) and, in a subset of patients with RA, correlated this with response to TNF-α inhibition. METHODS: SF from 42 RA patients and 19 non-RA IA patients were analysed for 12 cytokines using a multiplex cytokine assay. Cytokines were also measured in the plasma of 16 RA patients before and following treatment with anti-TNF-α. Data were analysed using Mann-Whitney U-test, Spearman's rank correlation and cluster analysis with the Kruskal-Wallis test with Dunn's post-test analysis. RESULTS: RA SF contained significantly elevated levels of IL-1β, IL-1ra, IL-2, IL-4, IL-8, IL-10, IL-17, IFN-γ, G-CSF, GM-CSF and TNF-α compared with other IA SF. RA patients who did not respond to anti-TNF therapy had elevated IL-6 in their SF pre-therapy (P < 0.05), whereas responders had elevated IL-2 and G-CSF (P < 0.05). Plasma cytokine concentrations were not significantly modulated by TNF inhibitors, with the exception of IL-6, which decreased after 12 weeks (P < 0.05). CONCLUSIONS: Cytokine profiles in RA SF vary with treatment and response to therapy. Cytokine concentrations are significantly lower in plasma than in SF and relatively unchanged by TNF inhibitor therapy. Concentrations of IL-6, IL-2 and G-CSF in SF may predict response to TNF inhibitors.
21076131 Homeopathy has clinical benefits in rheumatoid arthritis patients that are attributable to 2011 Jun OBJECTIVES: To assess whether any benefits from adjunctive homeopathic intervention in patients with RA are due to the homeopathic consultation, homeopathic remedies or both. METHODS: Exploratory double-blind, randomized placebo-controlled trial conducted from January 2008 to July 2008, in patients with active stable RA receiving conventional therapy. Eighty-three participants from three secondary care UK outpatient clinics were randomized to 24 weeks of treatment with either homeopathic consultation (further randomized to individualized homeopathy, complex homeopathy or placebo) or non-homeopathic consultation (further randomized to complex homeopathy or placebo). Co-primary outcomes: ACR 20% improvement (ACR20) criteria and patient monthly global assessment (GA). SECONDARY OUTCOMES: 28-joint DAS (DAS-28), tender and swollen joint count, disease severity, pain, weekly patient and physician GA and pain, and inflammatory markers. RESULTS: Fifty-six completed treatment phase. No significant differences were observed for either primary outcome. There was no clear effect due to remedy type. Receiving a homeopathic consultation significantly improved DAS-28 [mean difference 0.623; 95% CI 0.1860, 1.060; P = 0.005; effect size (ES) 0.70], swollen joint count (mean difference 3.04; 95% CI 1.055, 5.030; P = 0.003; ES 0.83), current pain (mean difference 9.12; 95% CI 0.521, 17.718; P = 0.038; ES 0.48), weekly pain (mean difference 6.017; 95% CI 0.140, 11.894; P = 0.045; ES 0.30), weekly patient GA (mean difference 6.260; 95% CI 0.411, 12.169; P = 0.036; ES 0.31) and negative mood (mean difference - 4.497; 95% CI -8.071, -0.923; P = 0.015; ES 0.90). CONCLUSION: Homeopathic consultations but not homeopathic remedies are associated with clinically relevant benefits for patients with active but relatively stable RA. TRIAL REGISTRATION: Current controlled trials, http://www.controlled-trials.com/, ISRCTN09712705.
21922340 Combined influence of genetic and environmental factors in age of rheumatoid arthritis ons 2012 Oct To study the combined effect of both genetic and environmental factors in the age of rheumatoid arthritis onset. Patients (n = 507). Shared epitope characterization was performed using Lifecodes HLA-SSO. Genotyping of protein tyrosine phosphatase non-receptor 22 (PTPN22) rs2476601 and signal transducers and activators of transcription 4 (STAT4) rs7574865 polymorphism was performed using fast real-time PCR System. Shared epitope, antibodies directed against cyclic citrulinated peptide (anti-CCP) antibodies and a higher level of education were associated with a younger age at disease onset (P = 0.033, P = 0.004 and P < 0.0001, respectively). Neither carriers of the minor allele of PTPN22 rs2476601 nor STAT4 rs7574 polymorphisms showed a significant association with a younger age at disease onset (P = 0.355, P = 0.065, respectively). We found an additive effect of the three genetic markers in the age at onset: subjects with three markers were associated with a disease onset 9.56, 8.61, and 6.41 years before than those with none, one, or two genetic markers (P = 0.004, P = 0.006 and P = 0.043, respectively). We also described the additive effect of shared epitope, anti-CCP antibodies, educational level, PTPN22, and STAT4 polymorphisms in age at onset. Patients with two, three, four, or five variables were associated with a significant younger age of disease onset (4.72 [0.05-9.38] years (P = 0.048), 9.56 [4.72-14.40] years (P < 0.0001), 12.74 [6.84-18.64] years (P < 0.0001), and 20.87 [10.40-37.17] years (P < 0.0001)). Risk factors for the development of rheumatoid arthritis are also associated, with an additive effect, with a younger age at disease onset.
22674244 Relationship between finger flexion and extension force in healthy women and women with rh 2012 Jun OBJECTIVE: Balance between flexor and extensor muscle activity is essential for optimal function. The purpose of this pilot study was to compare the relationship between maximum finger flexion force and maximum finger extension force in women with rheumatoid arthritis and healthy women. METHODS: Twenty healthy women (median age 61 years) and 20 women with rheumatoid arthritis (median age 59.5 years, median disease duration 16.5 years) were included in the study. Finger extension force was measured with an electronic device, EX-it, and finger flexion force using Grippit. The Grip Ability Test and the score from the patient-reported outcome Disability Arm Shoulder and Hand were used to evaluate activity limitations. RESULTS: Patients with rheumatoid arthritis showed significantly decreased hand function compared with healthy controls. A correlation was found between extension force and flexion force in the healthy group (r = 0.65, p = 0.002),but not in the rheumatoid arthritis group (r = 0.25, p = 0.289). CONCLUSION: Impaired hand function appears to influence the relationship between maximum finger flexion and extension force. This study showed a difference in the relationship between maximum finger flexion and extension force in healthy controls and those with rheumatoid arthritis.
22893886 Rapidly progressing polyarticular septic arthritis in a patient with rheumatoid arthritis. 2012 Jul Septic arthritis is an orthopedic emergency that can lead to significant morbidity and mortality. Polyarticular involvement is a relatively rare phenomenon occurring primarily in high-risk patients. In this article, we report the rare case of a patient with rheumatoid arthritis presenting with an acute episode of septic arthritis involving most of the joints of the body. Surprisingly, his bilateral total hip arthroplasties were completely unaffected. Unusual polyarticular presentations of septic arthritis, though rare, must still be considered within the differential diagnosis by all healthcare providers when treating certain high-risk groups.
22867927 Lifestyle- and behaviour-change interventions in musculoskeletal conditions. 2012 Jun This review discusses several health behaviours associated with the progression and impact of osteoarthritis (OA) and rheumatoid arthritis (RA), including weight management, physical activity, medication adherence and smoking. An overview of current theories of behaviour-change is provided in terms of principles that can guide medical practice. Finally, evaluation studies of interventions targeting weight loss, physical activity and medication adherence in patients with OA or RA are presented and discussed. Of existing behaviour-change interventions in this population, few have taken a comprehensive theory-based approach to behaviour-change. Practitioners who provide lifestyle or behavioural advice to patients would do well to adopt a less prescriptive and more patient-centred approach in which they, or other health professionals to whom they refer the patient, assist the patient in formulating personal change goals, in translating good intentions into specific action plans and in closely monitoring their progress towards self-chosen goals.
22993229 The structural basis of MRI bone erosions: an assessment by microCT. 2013 Aug OBJECTIVE: To determine whether erosions appearing in MRI in patients with rheumatoid arthritis (RA) represent true erosions. METHODS: 50 RA patients received 1.5 T MRI and microCT (μCT) of the dominant hand. Erosion counts were assessed in coronal T1 weighted MRI sections and in coronal as well as axial μCT sections of the metacarpophalangeal (MCP) joints II-IV. Extent of erosions was assessed by RA MRI Score (RAMRIS) erosion score (MRI) and by three-dimensional assessment of erosion volume (μCT). RESULTS: 111 of the 600 evaluated joint regions showed erosions in the MRI and 137 in the μCT. In only 28 regions false negative lesions (μCT positive, MRI negative) were found, all of which were very small lesions with a volume of less than 10 mm(3). Only two results were false-positive (μCT negative, MRI positive). RAMRIS erosion scores were strongly correlated to erosion volumes in the μCT (Pearson's r=0.514, p<0.001). Mean RAMRIS erosion scores were below 1 with erosion volumes up to 1.5 mm(3), below 2 with erosion volumes up to 20 mm(3) and over 2 with volumes of more than 20 mm(3). DISCUSSION: MRI erosions are generally based on true cortical breaks as shown by μCT. MRI is sensitive to detect bone erosions and only very small lesions escape detection. Moreover, RAMRIS erosion scores are closely linked to the absolute size of bone erosions in the μCT.
22814531 Myeloperoxidase and oxidative stress in rheumatoid arthritis. 2012 Oct OBJECTIVE: To determine whether MPO contributes to oxidative stress and disease activity in RA and whether it produces hypochlorous acid in SF. METHODS: Plasma and where possible SF were collected from 77 RA patients while 120 healthy controls supplied plasma only. MPO and protein carbonyls were measured by ELISAs. 3-Chlorotyrosine in proteins and allantoin in plasma were measured by mass spectrometry. RESULTS: Plasma MPO concentrations were significantly higher in patients with RA compared with healthy controls [10.8 ng/ml, inter-quartile range (IQR): 7.2-14.2; P<0.05], but there was no significant difference in plasma MPO protein concentrations between RA patients with high disease activity (HDA; DAS-28 >3.2) and those with low disease activity (LDA; DAS-28 ≤ 3.2) (HDA 27.9 ng/ml, 20.2-34.1 vs LDA 22.1 ng/ml, 16.9-34.9; P>0.05). There was a significant relationship between plasma MPO and DAS-28 (r=0.35; P=0.005). Plasma protein carbonyls and allantoin were significantly higher in patients with RA compared with the healthy controls. MPO protein was significantly higher in SF compared with plasma (median 624.0 ng/ml, IQR 258.4-2433.0 vs 30.2 ng/ml, IQR 25.1-50.9; P<0.0001). The MPO present in SF was mostly active. 3-Chlorotyrosine, a specific biomarker of hypochlorous acid, was present in proteins from SF and related to the concentration of MPO (r=0.69; P=0.001). Protein carbonyls in SF were associated with MPO protein concentration (r=0.40; P=0.019) and 3-chlorotyrosine (r=0.66; P=0.003). CONCLUSION: MPO is elevated in patients with RA and promotes oxidative stress through the production of hypochlorous acid.
20882667 V-region gene analysis of locally defined synovial B and plasma cells reveals selected B c 2011 Jan OBJECTIVE: To elucidate the development of synovial tissue-specific B cell immune responses, the clonality of individual naive B cells, memory B cells, and plasma cells and their organization and histologic localization in the inflamed tissue were investigated in patients with rheumatoid arthritis (RA). METHODS: B and plasma cells were isolated by laser capture microdissection (LCM) from the synovial tissue of patients with RA. In addition, single naive B cells, memory B cells, and plasma cells were sorted from synovial tissue cell suspensions. RNA was extracted from the cells, and Ig VH genes were amplified, cloned, and sequenced. RESULTS: Both LCM and single cell sorting analyses showed that naive and memory B cells infiltrated the RA synovial tissue. Comparison of the V-gene repertoire of B and plasma cells suggested that synovial plasma cells were generated, by and large, from locally activated B cells, indicating that a selected population of memory B cells differentiates into large plasma cell clones that then accumulate in the inflamed tissue. Clonally related plasma cells were isolated from separate and distinct localized areas of the tissue, suggesting that the newly generated plasma cells have a high migratory capacity. CONCLUSION: These results support the idea of a continuous activation of selected B cell clones, and hence a massive accumulation of plasma cells, in RA synovial tissue. As B cells and their secreted antibodies are an important factor in controlling inflammatory processes, patients with RA displaying intensive synovial tissue lymphocytic infiltrations might benefit from B cell depletion therapy. Early treatment will prevent accumulation of pathogenic plasma cells.
22565655 Strengthening exercises to improve hand strength and functionality in rheumatoid arthritis 2013 Mar Rheumatoid arthritis (RA) is a systemic inflammatory and chronic disease of joints, which may result in irreversible deformities. To evaluate the effects of an exercise programme aimed at improving the hand strength in individuals with hand deformities resulting from RA and to analyse the impact these exercises have on functionality. Twenty women with RA hand deformities participated in the study. They were randomly divided into two groups as follows: Group 1 (n = 13) had women participating in the exercise programme aimed at improving handgrip (HS) and pinch strengths (PS) as well as the motor coordination of the hand; Group 2 (n = 7) had women with RA who received no treatment for their hands (control). The treatment programme for hands consisted of 20 sessions, twice a week and at-home exercises. Both groups were submitted to Health Assessment Questionnaire (HAQ) and evaluation of HS and PS by means of dynamometry. Re-evaluations were performed after 10 and 20 sessions in Group 1 and after 2 months in Group 2. After 20 sessions of physiotherapy, Group 1 had a significant gain in HS and PS (p < 0.05) in addition to the improvement of functionality as assessed by HAQ (p = 0.016). For Group 2, no difference was found between the variables analysed (p > 0.05). The strengthening exercises for individuals with RA hand deformity are beneficial to improve handgrip and pinch strengths as well as functionality.
21546829 The spectrum of large granular lymphocyte leukemia and Felty's syndrome. 2011 Jul PURPOSE OF REVIEW: Patients with chronic large granular lymphocyte (LGL) leukemia often have rheumatoid arthritis (RA), neutropenia and splenomegaly, thereby resembling the manifestations observed in patients with Felty's syndrome, which is a rare complication of RA characterized by neutropenia and splenomegaly. Both entities have similar clinical and laboratory presentation, as well as a common genetic determinant, HLA-DR4, indicating they may be part of the same disease spectrum. This review paper seeks to discuss the underlying pathogenesis and therapeutic algorithm of RA, neutropenia and splenomegaly in the spectrum of LGL leukemia and Felty's syndrome. RECENT FINDINGS: We hypothesize that there may be a common pathogenic mechanism between LGL leukemia and typical Felty's syndrome. Phenotypic and functional data have strongly suggested that CD3 LGL leukemia is antigen-activated. Aberrations in the T-cell repertoire with the emergence of oligoclonal/clonal lymphoid populations have been found to play a pivotal role in pathogenesis of RA. The biologic properties of the pivotal T cell involved in RA pathogenesis are remarkably similar to those in leukemic LGL. SUMMARY: RA-associated T-cell LGL leukemia and articular manifestations of typical Felty's syndrome are not distinguishable. A common pathogenetic link between LGL leukemia and RA is proposed.
21604062 Association of rheumatoid arthritis risk with EGFR genetic polymorphisms in Taiwan's Han C 2012 Aug The involvement of the epidermal growth factor receptor (EGFR) in the pathogenesis of cancer is well documented. In contrast, its role in rheumatoid arthritis (RA) development is not that well defined although previous studies suggested the possible link between autoimmune diseases and malignancy. Therefore, we aimed to examine whether there is a link between the EGFR genetic polymorphisms and the RA. Our study gauged the effects of EGFR (rs11543848 and rs17337023) single-nucleotide polymorphisms (SNPs) on RA among Taiwan's Han Chinese population. Polymorphism of EGFR gene was analyzed in 188 RA patients and 128 control subjects. Genotyping for EGFR SNPs was performed by restriction fragment length polymorphism (RFLP) assay. Our data confirmed statistically significant increased risk of RA development in subjects with A carrier at rs17337023 SNP (P < 0.0001), and subjects with A allele at rs17337023 SNP (odds ratio [OR] = 1.52; 95% confidence interval [CI] = 1.10-2.09). Furthermore, comparison of haplotype frequencies between patients and controls suggested GA and AT haplotypes were more "at-risk" for RA development (P < 0.0001 and P < 0.01, respectively). However, comparisons of the clinical features of RA patients according to different genotypes and haplotypes revealed no significant difference. In conclusion, our data yield the new information on EGFR polymorphisms (rs11543848 and rs17337023) with the susceptibility of RA development and polymorphism revealed by this study merit further investigation.
21529308 How should impaired morning function in rheumatoid arthritis be treated? 2011 Patients with rheumatoid arthritis (RA) commonly experience morning symptoms of joint stiffness and pain that result in impaired function. However, current treatment options are limited. The management of impaired morning function is based primarily on non-pharmacological approaches, including simple or short exercises, application of heat or a hot shower or bath, and delaying activities until later in the day. Although it seems that the majority of patients follow the management advice they are given by rheumatologists, symptoms persist. In recent years, only a minority of clinical studies have assessed the impact on morning symptoms of pharmacological treatments for RA. The paucity of data makes it difficult to evaluate systematically the ability of current treatments to improve morning function. However, treatment seems to be suboptimal; in a pan-European survey of 518 rheumatologists, 61% considered that current treatment options do not address impaired morning function specifically, and 68% considered there is a need for new treatment options. Understanding the pathophysiology of circadian symptoms may provide the key to improving treatment of impaired morning function. In patients with morning symptoms of RA, there may be insufficient endogenous cortisol released during the night to counter elevated levels of the pro-inflammatory cytokine, interleukin (IL)-6. Delivering exogenous glucocorticoid during the night was found to reduce IL-6 levels and reduce morning stiffness, but was inconvenient for patients. However, this chronotherapeutic approach has now been facilitated by the development of modified-release prednisone tablets. Taken at bedtime (approximately 10:00 pm), these tablets give programmed delivery of prednisone around 4 h later, at the optimal time to suppress IL-6. Clinical studies suggest that morning stiffness in patients with RA could be treated successfully with the use of low-dose modified-release prednisone.
22960345 Associations of killer cell immunoglobulin- like receptor genes with rheumatoid arthritis. 2012 OBJECTIVE: Rheumatoid Arthritis (RA) is an autoimmune and chronic inflammatory disease of unknown etiology. Killer cell immunoglobulin-like receptors are expressed on the surface of natural killer cells and CD28null T-cells, both present in synovial membrane of RA. Therefore we evaluated the associations of KIR genes with RA. METHODS: 16 KIR genes were genotyped in 100 healthy subjects (HS) and 100 RA patients from Western Mexico using PCR-SSP. Differences in KIR genotypes and gene frequencies were assessed using the X^{2} test. RESULTS: Gene frequency of KIR2DL3 was lower in RA than in HS (p= 0.0019), whereas KIR2DL2 and KIR2DS2 were higher in RA than HS (p =0.0004 and p = 0.0487, respectively). In addition were identified 38 genotypes (from G1-G38) in both studied groups, and the genotype frequencies of G1, G6 and G14 showed significant differences (p =0.0001, p =0.0208 and p =0.0300, respectively). CONCLUSIONS: The presence of KIR2DL2, KIR2DS2 and absence of KIR2DL3 are associated with RA. Moreover, two genotypes BX are associated with RA. These results suggest that KIRs can be involved in RA susceptibility.
22610975 Occurrence and relative risk of stroke in incident and prevalent contemporary rheumatoid a 2013 Apr OBJECTIVE: In contrast with the wealth of data on ischaemic heart disease in rheumatoid arthritis (RA), data on stroke are scarce and contradictory. Despite the high clinical and aetiological relevance, there is no data regarding when (if ever) after RA diagnosis there is an increased risk. Our objective was to assess the risk of stroke (by subtype) in contemporary patients with RA, particularly in relation to time since RA diagnosis. METHODS: One incident RA cohort diagnosed between 1997 and 2009 (n=8077) and one nationwide prevalent RA cohort followed at Swedish rheumatology clinics between 2005 and 2009 ((n=39 065) were assembled). Each cohort member was matched to a general population comparator. Information on first-time hospitalisations for stroke up to 2009 was retrieved from the Swedish Patient Register. HR and 95% CI were estimated using Cox models. RESULTS: In prevalent unselected RA, the HR of ischaemic stroke was 1.29 (95% CI 1.18 to 1.41). In the incident RA cohort, the overall risk increase was small and non-significant (overall HR 1.11, 95% CI 0.95 to 1.30). When stratified by RA disease duration, an increased risk of ischaemic stroke was indeed detectable but only after 10 or more years since RA diagnosis (HR>10 years: 2.33, 95% CI 1.25 to 4.34). Risk of haemorrhagic stroke was increased in prevalent but not in incident RA. CONCLUSION: The magnitude of stroke risk is lower than for ischaemic heart disease in RA, and the evolvement of this risk from RA diagnosis may be slower. This suggests different driving forces behind these two RA co-morbidities and has implications for the clinical follow-up of patients with RA.
21323703 Host-response: understanding the cellular and molecular mechanisms of host-microbial inter 2011 Mar BACKGROUND: Major challenges in periodontology include understanding the pathophysiology, the interplay between various components of the host response, parallels with other diseases and identifying biomarkers of the disease. OBJECTIVES: Four reviews were compiled with the aim of better understanding: (1) the role of polymorphic nuclear leucocytes (PMNs), i.e. neutrophils; (2) the function of cytokine networks in the host response; (3) whether parallels exist with rheumatoid arthritis (RA); and (4) whether useful biomarkers currently exist to help in the management of periodontal disease. MATERIAL AND METHODS: Based on the focused questions, electronic and manual searches were conducted for human, animal and cellular studies on the above topics. RESULTS: Papers fulfilling the inclusion criteria were selected and reviews were written and reviewed and corrected before the academy meeting to produce consensus statements. CONCLUSION: The following consensus statements were produced. PMNs are important in the pathophysiology of periodontal disease but there is limited evidence on their much quoted destructive potential. Cytokine networks are enormously complex and we are really at the beginning of understanding their role in the disease process. RA has both similarities and marked differences to periodontal disease although the existing utilization of anti-cytokine therapies and other molecules in its treatment may have importance in periodontal disease therapy. Biomarkers for periodontal disease have yet to be completely defined but the ratio of receptor activator of NF-κB ligand to osteoprotegerin appears to be a biomarker test with utility for detecting bone destruction.
21807792 It's good to feel better but it's better to feel good and even better to feel good as soon 2011 Aug The OMERACT patient reported outcomes (PRO) working group evaluated the methodologies for measuring responsiveness to change at the Outcome Measures in Rheumatology (OMERACT) 10 meeting. The outcome measures used in PRO studies are often expressed as continuous data at the group level (e.g., mean change in pain on a 0-100 visual analog scale). This is difficult to interpret and cannot easily be translated to the individual level of response. When interpreting scores at the individual level, it is important to take into account the following 4 main concepts: (1) improvement; (2) status of well-being; (3) onset of action; and (4) sustainability. Information from clinical trials on how many patients showed a response, what the level of response was, and how many patients are doing well, would be extremely useful for physicians. The objective of this article is to outline how continuous data may be reported in a clinically relevant manner. We will describe 5 techniques of reporting continuous variables in clinical studies and discuss the relevance of each.
22104560 Population-based study of incidence and clinical characteristics of rheumatic fever in Abr 2012 May OBJECTIVE: To investigate the incidence and describe the characteristics of acute rheumatic fever (ARF) in the pediatric population in a community-based healthcare delivery system of the central Italy region of Abruzzo during 2000-2009. STUDY DESIGN: A retrospective study was conducted in Abruzzo to identify patients aged <18 years with a diagnosis of ARF between January 1, 2000, and December 31, 2009. Each patient's age, sex, date of diagnosis, age at disease presentation, and fulfilled Jones criteria were recorded. RESULTS: A total of 88 patients meeting the Jones criteria for the diagnosis of ARF were identified, with arthritis in 59.1% of the patients, carditis in 48.9%, erythema marginatum in 11.4%, 5.7% with chorea, and 4.6% with subcutaneous nodules. Residual chronic rheumatic heart disease was present in 44.3% of the children. Age at diagnosis ranged from 2.5 to 17 years (average, 8.7 ± 4.0 years). Twelve children (13.6%) were under age 5 years. The overall incidence rate of ARF was 4.1/100 000. The lowest incidence rate was documented in the year 2000 (2.26/100 000), and the highest in 2006 (5.58/100 000). CONCLUSION: Our data indicate that ARF has not disappeared in industrialized countries and still causes significant residual rheumatic heart disease. Pediatricians should routinely consider the diagnoses of streptococcal pharyngitis and ARF to reduce long-term morbidity and mortality.
22429695 Polymorphism in the vascular endothelial growth factor A (VEGFA) gene is associated with s 2012 Jun OBJECTIVE: To assess the impact of common genetic variants in the vascular endothelial growth factor A (VEGFA) gene on circulating VEGF-A levels and disease activity in patients with rheumatoid arthritis (RA). METHODS: A cohort (n=419) of consecutively recruited RA patients of Caucasian origin was studied. Disease activity (DAS28) was recorded on a regular basis (0, 12 and 24 months). Smoking history (never, past and current) was obtained. PCR-RFLP assays were used to determine the genotypes of VEGFA single-nucleotide polymorphisms (SNP) including VEGFA-2578 (rs699947), -460 (rs833061), +405 (rs2010963) and +936 (rs3025039). Circulating levels of VEGF-A were measured in serum samples using a fluorescent bead-based assay system (Luminex®). Associations were analyzed using univariate and multivariate statistics. RESULTS: VEGFA-2578 AA genotype was associated with lower serum VEGF-A levels, as was the most frequent haplotype (A(-2578)-C(-460)-G(+405), 48.1%) within the 5'-flanking region of the gene. The same genotype and haplotype were also associated with decreased disease activity in RA. This was seen only in patients who had never smoked. In multivariate multiple regression models, the VEGFA-2578 SNP was shown to be associated with disease activity at presentation (p=0.029) and over time (p=0.016) in patients who never smoked, independent of serum VEGF-A levels and other confounding factors. CONCLUSION: Genetic variation in the VEGFA gene is associated with serum VEGF-A levels in RA, and shows an association with disease activity in RA patients who have never smoked, independent of serum VEGF-A levels.