Optimal Tai Chi forms in knee osteoarthritis: An exploration from biomechanical rationale to pain reduction.

Objectives: Tai Chi (TC) shows some beneficial effects in reducing pain in knee osteoarthritis (OA). However, the selection of criteria TC forms in previous studies were unclear and inconsistent, possibly accounting for the varying outcomes and rendering the training effects suboptimal. We have selected four optimal TC (OTC) forms based on the knee joint load and its association with pain. This pilot study sought to examine the effect of the OTC forms on reducing knee pain in individuals with knee OA. Methods: Fifteen knee OA participants were recruited. Their knee joint pain level was rated by using the Visual Analogue Scale before and after two weeks of OTC training and compared between these two assessments. Results: The two-week OTC training course was well accepted by our participants. The knee OA pain showed a significant reduction (median pain score: 5 â€‹cm before training and 1 â€‹cm post-training, Wilcoxon p â€‹< â€‹0.001) after the two-week training program. Conclusions: Our pilot results revealed that the 2-week four-form-based OTC program could significantly reduce the knee pain level in people with knee OA. Additionally, our OTC program appears to be about 50% more effective in reducing knee pain than the existing TC-based program, which uses 10 â€‹TC forms over 12 weeks (1.59 vs. 1.06 in Hedge's g). The findings in this study may inform the development of OTC-based knee pain reduction programs and the design of relevant clinical trials to establish OTC's effectiveness, safety, and dose-response relationship in easing knee OA pain.

Deconstructing dogma: Nonoperative management of small bowel obstruction in the virgin abdomen.

BACKGROUND: Management of small bowel obstruction (SBO) has become more conservative, especially in those patients with previous abdominal surgery (PAS). However, surgical dogma continues to recommend operative exploration for SBO with no PAS. With the increased use of computed tomography imaging resulting in more SBO diagnoses, it is important to reevaluate the role of mandatory operative exploration. Gastrografin (GG) administration decreases the need for operative exploration and may be an option for SBO without PAS. We hypothesized that the use of GG for SBO without PAS will be equally effective in reducing the operative exploration rate compared with that for SBO with PAS. METHODS: A post hoc analysis of prospectively collected data was conducted for patients with SBO from February 2015 through December 2016. Patients younger than 18 years, pregnant patients, and patients with evidence of hypotension, bowel strangulation, peritonitis, closed loop obstruction or pneumatosis intestinalis were excluded. The primary outcome was operative exploration rate for SBO with or without PAS. Rate adjustment was accomplished through multivariate logistic regression. RESULTS: Overall, 601 patients with SBO were included in the study, 500 with PAS and 101 patients without PAS. The two groups were similar except for age, sex, prior abdominal surgery including colon surgery, prior SBO admission, and history of cancer. Multivariate analysis showed that PAS (odds ratio [OR], 0.47; p = 0.03) and the use of GG (OR, 0.11; p < 0.01) were independent predictors of successful nonoperative management, whereas intensive care unit admission (OR, 16.0; p < 0.01) was associated with a higher likelihood of need for operation. The use of GG significantly decreased the need for operation in patients with and without PAS. CONCLUSIONS: Patients with and without PAS who received GG had lower rates of operative exploration for SBO compared with those who did not receive GG. Patients with a diagnosis of SBO without PAS should be considered for the nonoperative management approach using GG. LEVEL OF EVIDENCE: Therapeutic, level IV.

Data on genetic associations of carotid atherosclerosis markers in Mexican American and European American rheumatoid arthritis subjects.

Carotid Intima-media thickness (CIMT) and plaque are well established markers of subclinical atherosclerosis and are widely used for identifying subclinical atherosclerotic disease. We performed association analyses using Metabochip array to identify genetic variants that influence variation in CIMT and plaque, measured using B-mode ultrasonography, in rheumatoid arthritis (RA) patients. Data on genetic associations of common variants associated with both CIMT and plaque in RA subjects involving Mexican Americans (MA) and European Americans (EA) populations are presented in this article. Strong associations were observed after adjusting for covariate effects including baseline clinical characteristics and statin use. Susceptibility loci and genes and/or nearest genes associated with CIMT in MAs and EAs with RA are presented. In addition, common susceptibility loci influencing CIMT and plaque in both MAs and EAs have been presented. Polygenic Risk Score (PRS) plots showing complementary evidence for the observed CIMT and plaque association signals are also shown in this article. For further interpretation and details, please see the research article titled "A Genetic Association Study of Carotid Intima-Media Thickness (CIMT) and Plaque in Mexican Americans and European Americans with Rheumatoid Arthritis" which is being published in Atherosclerosis (Arya et al., 2018) [1].(Arya et al., in press) Thus, common variants in several genes exhibited significant associations with CIMT and plaque in both MAs and EAs as presented in this article. These findings may help understand the genetic architecture of subclinical atherosclerosis in RA populations.

A genetic association study of carotid intima-media thickness (CIMT) and plaque in Mexican Americans and European Americans with rheumatoid arthritis.

BACKGROUND AND AIMS: Little is known about specific genetic determinants of carotid-intima-media thickness (CIMT) and carotid plaque in subjects with rheumatoid arthritis (RA). We have used the Metabochip array to fine map and replicate loci that influence variation in these phenotypes in Mexican Americans (MAs) and European Americans (EAs). METHODS: CIMT and plaque were measured using ultrasound from 700 MA and 415 EA patients with RA and we conducted association analyses with the Metabochip single nucleotide polymorphism (SNP) data using PLINK. RESULTS: In MAs, 12 SNPs from 11 chromosomes and 6 SNPs from 6 chromosomes showed suggestive associations (p < 1 × 10-4) with CIMT and plaque, respectively. The strongest association was observed between CIMT and rs17526722 (SLC17A2 gene) (ß ± SE = -0.84 ± 0.18, p = 3.80 × 10-6). In EAs, 9 SNPs from 7 chromosomes and 7 SNPs from 7 chromosomes showed suggestive associations with CIMT and plaque, respectively. The top association for CIMT was observed with rs1867148 (PPCDC gene, ß ± SE = -0.28 ± 0.06, p = 5.11 × 10-6). We also observed strong association between plaque and two novel loci: rs496916 from COL4A1 gene (OR = 0.51, p = 3.15 × 10-6) in MAs and rs515291 from SLCA13 gene (OR = 0.50, p = 3.09 × 10-5) in EAs. CONCLUSIONS: We identified novel associations between CIMT and variants in SLC17A2 and PPCDC genes, and between plaque and variants from COL4A1 and SLCA13 that may pinpoint new candidate risk loci for subclinical atherosclerosis associated with RA.

Severe traumatic brain injuries in children: Does the type of trauma center matter?

BACKGROUND: Traumatic brain injury (TBI) is the leading cause of death among injured children. Depending on geographic location, and trauma resources, pediatric patients may be treated at pediatric (PTC), adult (ATC), or mixed trauma centers (MTC). The effect of the type of trauma center on outcomes in severe TBI is not known. METHODS: NTDB study (2007-2014), level 1 trauma centers, patients ≤14years with severe isolated TBI (head AIS≥3 and extracranial AIS≤2). Demographic, clinical and injury characteristics were abstracted. Logistic regression was used to compare outcomes between the three types of trauma centers. RESULTS: 10,402 patients met inclusion criteria. 4430 (42.6%) were admitted in PTC, 4044 (38.9%) in ATC and 1928 (18.5%) in MTC. Overall, 39.9% of patients had head AIS 3, 55.5% had AIS 4 and 4.6% AIS 5. Mortality was 3.2% (2.0% in PTC, 4.5% in ATC and 3.3% in MTC). On logistic regression, treatment at ATC was associated with significantly higher mortality than PTC (OR 1.55, p=0.011). There was no significant difference between PTC and MTC (p=0.394). There was no significant difference in mortality between the 3 types of trauma centers in the subgroups of patients with head AIS 3 or 5. However, patients with head AIS 4 treated at MTC had significantly lower mortality (OR 0.163, 95% CI 0.053-0.501, p=0.002). CONCLUSION: Patients with isolated severe TBI treated at PTC have significantly better survival than patients treated at ATC, but not MTC. In the subgroup of patients with isolated TBI and a head AIS score of 4, patients treated at MTC have improved survival than those treated at PTC. LEVEL OF EVIDENCE: III.

Use of Hydroxychloroquine Is Associated With Improved Lipid Profile in Rheumatoid Arthritis Patients.

BACKGROUND/PURPOSE: We examined the association between hydroxychloroquine (HCQ) and plasma lipid and glucose levels in rheumatoid arthritis (RA) cohort. METHODS: This is a retrospective cohort analysis of 1261 RA patients comparing fasting lipid profiles and plasma glucose between patients who were and were not taking HCQ. We divided patients into 3 groups based on HCQ exposure during follow-up: those who had never taken HCQ, those who took it intermittently, and those who took it continuously. We used multivariable models and propensity scoring to compensate for the effect of nonrandom treatment assignment. RESULTS: We followed 1261 RA patients for a total of 4605 observations between 1996 and 2014. After adjusting for age, sex, ethnicity, other disease-modifying antirheumatic drugs (DMARDs), lipid-lowering medications, body mass index (BMI), and smoking, patients taking HCQ at baseline had significantly lower total cholesterol (TC) (P ≤ 0.001), low-density lipoprotein (LDL) (P ≤ 0.001), triglycerides (P = 0.013), and lipid profile ratios TC/high-density lipoprotein (HDL) (P ≤ 0.001) and LDL/HDL (P ≤ 0.001), as well as higher HDL (P ≤ 0.001).In longitudinal analyses, after adjusting for confounders, patients who continuously took HCQ showed significantly lower TC, LDL, TC/HDL, and LDL/HDL and higher HDL (P ≤ 0.01). Fasting plasma glucose levels were not significantly associated with HCQ exposure. CONCLUSIONS: Hydroxychloroquine use was associated with lower lipid levels but not with the plasma glucose in this RA cohort. These findings support the need for a randomized trial to establish the role of HCQ in cardiovascular disease prevention in RA patients.

Novel Protein Glycan-Derived Markers of Systemic Inflammation and C-Reactive Protein in Relation to Glycemia, Insulin Resistance, and Insulin Secretion.

OBJECTIVE: N-acetylglucosamine/galactosamine (GlycA) and sialic acid (GlycB) moieties of glycosylated serum proteins are nonspecific measures of inflammation, but conclusive data on their relationship with insulin resistance or insulin secretion are missing. Therefore, we aimed to examine the relation of GlycA, GlycB, and C-reactive protein (CRP) to direct measures of insulin sensitivity (insulin sensitivity index [SI]) and insulin secretion (acute insulin response [AIR]). RESEARCH DESIGN AND METHODS: This study used cross-sectional analyses and included 1,225 participants with and without type 2 diabetes in the Insulin Resistance Atherosclerosis Study (IRAS). SI and AIR were measured using the frequently sampled intravenous glucose tolerance test, and GlycA and GlycB were measured using nuclear magnetic resonance spectroscopy. RESULTS: GlycA and GlycB had a strong correlation with CRP (r = 0.60 [P < 0.001] and r = 0.46 [P < 0.001], respectively). In a linear regression model with both GlycA and CRP as independent variables, GlycA (ß × 1 SD, -0.04 ± 0.02; P < 0.01) and CRP (-0.06 ± 0.02; P < 0.001) were independently associated with SI even after adjusting for demographics, smoking, physical activity, plasma glucose, and BMI. However, neither CRP nor GlycA had an independent relationship with AIR. CONCLUSIONS: GlycA may complement CRP in evaluating the relationship between inflammation, glucose tolerance, and insulin resistance.

Genetic Variants Influencing Joint Damage in Mexican Americans and European Americans With Rheumatoid Arthritis.

Joint destruction in rheumatoid arthritis (RA) is heritable, but knowledge on specific genetic determinants of joint damage in RA is limited. We have used the Immunochip array to examine whether genetic variants influence variation in joint damage in a cohort of Mexican Americans (MA) and European Americans (EA) with RA. We studied 720 MA and 424 EA patients with RA. Joint damage was quantified using a radiograph of both hands and wrists, scored using Sharp's technique. We conducted association analyses with the transformed Sharp score and the Immunochip single nucleotide polymorphism (SNP) data using PLINK. In MAs, 15 SNPs from chromosomes 1, 5, 9, 17 and 22 associated with joint damage yielded strong p-values (p < 1 × 10(-4) ). The strongest association with joint damage was observed with rs7216796, an intronic SNP located in the MAP3K14 gene, on chromosome 17 (ß ± SE = -0.25 ± 0.05, p = 6.23 × 10(-6) ). In EAs, 28 SNPs from chromosomes 1, 4, 6, 9, and 21 showed associations with joint damage (p-value < 1 × 10(-4) ). The best association was observed on chromosome 9 with rs59902911 (ß ± SE = 0.86 ± 0.17, p = 1.01 × 10(-6) ), a synonymous SNP within the CARD9 gene. We also observed suggestive evidence for some loci influencing joint damage in MAs and EAs. We identified two novel independent loci (MAP3K14 and CARD9) strongly associated with joint damage in MAs and EAs and a few shared loci showing suggestive evidence for association.

Mortality in Rheumatoid Arthritis (RA): factors associated with recording RA on death certificates.

BACKGROUND: Death certificates can be used to assess disease prevalence and incidence; however, rheumatoid arthritis (RA) often remains unreported in death certificates. We sought to determine to what extent RA is underreported and what demographic and clinical characteristics could predict mention of RA in the death certificate. METHODS: We recruited 1328 patients with RA from private, public and military rheumatology practices and followed them prospectively for yearly evaluations. A rheumatologist assessed clinical characteristics of RA and comorbidities at each evaluation. Deaths were identified through family members, other physicians, obituaries and public death databases. All were confirmed with state-issued death certificates. Patients with and without RA in death certificate were compared using bivariate and multivariate analyses. RESULTS: By December 2013, 326 deaths had occurred. We received and reviewed death certificates for all confirmed deaths, of which 58 (17.7 %) mentioned RA on the death certificate. Bivariate analysis revealed that younger age, a greater number of deformities, higher Sharp score and lower socioeconomic status were each associated with recording RA. Multivariable analyses revealed that comorbidity [OR (95 % CI) = 0.84 (0.73, 0.97); P = 0.022] was inversely associated with listing RA on the death certificate, while the number of deformities [OR (95 % CI) = 1.04 (1.00, 1.07); P = 0.033] and a certified physician's signature on the death certificate [OR (95 % CI) = 4.79 (1.35, 16.9); P = 0.015] increased likelihood of reporting RA. CONCLUSION: In this cohort, RA was not listed in over 80 % of death certificates. Younger patients with fewer comorbidities and more joint deformities were more likely to have RA reported. DISCUSSION: RA is often not included in death certificates. The findings of this study suggest that older patients may have a greater number of comorbidities, thus decreasing the likelihood that RA be included when completing the death certificate.

Clinical and laboratory factors associated with interstitial lung disease in rheumatoid arthritis.

OBJECTIVE: The objective of this study is to examine the clinical, genetic, and environmental factors associated with interstitial lung disease (ILD) in rheumatoid arthritis (RA). METHOD: We recruited patients with RA from rheumatology practices at the time of a scheduled visit. Each patient participated in a comprehensive assessment that included ascertainment of age, sex, joint tenderness and swelling, subcutaneous nodules, disease severity, use of methotrexate and prednisone, smoking status, rheumatoid factor (RF), antibodies against cyclic citrullinated peptide (anti-CCP),erythrocyte sedimentation rate (ESR), the 28-joint Disease Activity Score (DAS28), and the presence of the HLA-DRB1 shared epitope (SE). As part of a thorough quantification of comorbidity, we identify all comorbid conditions, including ILD. We examined variables associated with ILD using logistic regression. We tested interaction terms between SE and other covariates. RESULTS: We studied 779 RA patients, among whom, ILD was recognized clinically in 69 (8.8 %). Variables significantly associated with ILD in a multivariable analysis included male sex, RA duration, the ESR, the DAS28, anti-CCP, and RF. There was a significant interaction between the HLA-DRB1 SE and smoking, ILD being associated with smoking only in the presence of SE. The association between ILD and anti-CCP, RF, and the ESR displayed a biological gradient, higher titers being more strongly associated with ILD. CONCLUSION: Anti-CCP antibodies and the RF may be pathogenically related to ILD. The association between ILD and smoking is dependent on the HLA-DRB1 SE, which may reflect gene-environment interaction.

Association of socioeconomic status with treatment delays, disease activity, joint damage, and disability in rheumatoid arthritis.

OBJECTIVE: To examine the association of socioeconomic status (SES) and delays in disease-modifying antirheumatic drug (DMARD) treatment with clinical measures in rheumatoid arthritis (RA) patients. METHODS: RA patients were recruited from rheumatology practices. We assessed SES based on education, occupation, and income, and divided patients into tertiles. The time from RA symptom onset to DMARD initiation (DMARD lag) was determined by self-report of the 2 dates, and distance to the rheumatologist (Distance) was obtained from Google Maps. We examined disease activity, determined by the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR); joint damage, determined from hand radiographs by Sharp scores; and physical disability, determined by the modified Health Assessment Questionnaire (M-HAQ). We used linear regression models to examine the relationship between clinical measures and SES, Distance, and DMARD lag. RESULTS: We recruited 1,209 RA patients, 1,159 of whom had received DMARD treatment. Mean ± SD DMARD lag was 6.9 ± 9.0 years. On average, patients with lower SES waited 8.5 ± 10.2 years after onset of RA symptoms to begin DMARD treatment, compared to those in the middle and upper SES tertiles who waited 6.1 ± 7.9 years (P = 0.002) and 6.1 ± 8.6 years (P = 0.009), respectively. Each year of delayed treatment was associated with a DAS28-ESR increase of 0.02 (P ≤ 0.001), a Sharp score increase of 1.33 (P ≤ 0.001), and an M-HAQ score increase of 0.01 (P ≤ 0.001). CONCLUSION: Low SES was associated with delay in DMARD initiation, and both were independently associated with worse clinical measures in RA. Strategies to reduce treatment delay in low-SES RA patients are needed.

Systemic inflammation and cardiovascular risk factors predict rapid progression of atherosclerosis in rheumatoid arthritis.

OBJECTIVE: To estimate atherosclerosis progression and identify influencing factors in rheumatoid arthritis (RA). METHODS: We used carotid ultrasound to measure intima-media thickness (IMT) in RA patients, and ascertained cardiovascular (CV) risk factors, inflammation markers and medications. A second ultrasound was performed approximately 3 years later. We calculated the progression rate by subtracting the baseline from the follow-up IMT, divided by the time between the two scans. We used logistic regression to identify baseline factors predictive of rapid progression. We tested for interactions of erythrocyte sedimentation rate (ESR) with CV risk factors and medication use. RESULTS: Results were available for 487 RA patients. The mean (SD) common carotid IMT at baseline was 0.571 mm (0.151). After a mean of 2.8 years, the IMT increased by 0.050 mm (0.055), p≤0.001, a progression rate of 0.018 mm/year (95% CI 0.016 to 0.020). Baseline factors associated with rapid progression included the number of CV risk factors (OR 1.27 per risk factor, 95% CI 1.01 to 1.61), and the ESR (OR 1.12 per 10 mm/h, 95% CI 1.02 to 1.23). The ESR×CV risk factor and ESR×medication product terms were significant, suggesting these variables modify the association between the ESR and IMT progression. CONCLUSIONS: Systemic inflammation and CV risk factors were associated with rapid IMT progression. CV risk factors may modify the role of systemic inflammation in determining IMT progression over time. Methotrexate and antitumour necrosis factor agents may influence IMT progression by reducing the effect of the systemic inflammation on the IMT.

Trígono cistohepático: área crítica anatómica para la seguridad quirúrgica / Trigonum cystohepaticum: critical anatomical area for surgical safety

El conocimiento de la anatomía de la vía biliar y sus variantes para la realización de una cirugía segura, resulta fundamental. La extirpación de la vesícula requiere cuidadosa atención, conocer muy bien la anatomía de la región, teniendo en cuenta la posibilidad de variaciones anatómicas. La mala interpretación de la anatomía percibida más que una falta en la destreza técnica es la causa de la lesión de la vía biliar durante la colecistectomía. Diferenciar el límite y el contenido del trígono cistohepático. Diseñar las áreas de Visión Crítica y de Seguridad como medida de seguridad en el paciente quirúrgico. Revisión de 458 partes quirúrgicos de colecistectomías de enero/2010 a octubre/2012, en el Servicio de Cirugía General del Hospital Aeronáutico Central, y disección de 12 cadáveres adultos formolizados al 10% en la III Cátedra de Anatomía - Facultad de Medicina - Universidad de Buenos Aires. De 458 colecistectomías, se clasificaron los partes quirúrgicos, dividiéndose según menciona: triángulo de Calot en 247 (53,93%); triángulo hepatocístico en 59 (12,88%); área de visión crítica en 152 (33,18%); ninguno mencionó al triángulo de Budde o trígono cistohepático. Se disecaron 12 cadáveres adultos donde se identificó: arteria cística originándose de arteria hepática derecha en 9 (75%); originándose de arteria hepática izquierda en 2 (16,66%) y originándose de arteria hepática en 1 (8,34%). En 7 (58,35%) se la visualiza en trígono cistohepático. El conocimiento de la anatomía de la vía biliar y sus variantes para la realización de una cirugía segura, resulta fundamental. El triángulo descrito por Calot corresponde a la mitad inferior del triángulo descrito por Buddé. El sector lateral (Triangulo de Seguridad) es el verdadero área de visión critica a disecar por la menor probabilidad de lesionar estructuras nobles.

Knowing the anatomy of the bile duct and its anatomical variations becomes essential to safely perform any surgery. Gallbladder resection requires careful attention: knowing the region's anatomy by heart and taking into account the possibility of anatomical variations. Misunderstanding the anatomy is not only a failure in technical ability but also a cause of injury to the bile duct during a cholescystectomy. The objectives of this study were, to distinguish the boundaries and content of the trigonum cystohepaticum. Furthermore, to design the areas of Safety and Critical Vision as a safety measure for the patient undergoing surgery. Analysis of 458 surgical reports on cholecystectomies performed from January 2010 to October 2012 by the Hospital Aeronáutico's General Surgery Department, and dissection of 12 adult cadavers preserved in a 10% formalin solution at the IIIrd Chair of Anatomy, School of Medicine, University of Buenos Aires. From 458 cholecystectomies, surgical reports were classified as mentioning: Calot triangle, 247 (53.93%); cystohepatic triangle, 59 (12.88%); critical vision area, 152 (33.18%). None of them mentioned Buddé triangle or trigonum cystohepaticum. Twelve adult cadavers were dissected in which we identified the cystic artery: originating from right hepatic artery, 9 (75%); originating from left hepatic artery, 2 (16.66%); and originating from hepatic artery, 1 (8.34%). Trigonum cystohepaticum is observed in 7 cadavers (58.35%). Knowing the anatomy of the bile duct and its anatomical variations becomes essential to safely perform any surgery. The triangle described by Calot is the lower half of the triangle described by Buddé. The lateral portion (Safety Triangle) is the area of critical vision to be dissected due to the lower probability of injuring noble structures.

Glucocorticoid dose thresholds associated with all-cause and cardiovascular mortality in rheumatoid arthritis.

OBJECTIVE: To delineate daily and cumulative glucocorticoid dose thresholds associated with increased mortality rates in rheumatoid arthritis (RA). METHODS: We studied RA patients recruited from rheumatology clinics. Annually, we assessed the glucocorticoid dose, demographic, socioeconomic, clinical, and laboratory features of RA, cardiovascular (CV) risk factors, and vital status. We used Cox proportional hazards regression to assess associations between the daily or cumulative glucocorticoid dose and death, adjusting for potential confounders and for the propensity to receive glucocorticoids. We tested strata of the glucocorticoid dose to delineate the threshold associated with death. RESULTS: We studied 779 RA patients with a total of 7,203 person-years of observation, during which 237 of them died, yielding a mortality rate of 3.2 per 100 person-years (95% confidence interval [95% CI] 2.8-3.7). One hundred twenty of the deaths were due to CV causes, yielding a CV mortality rate of 1.8 (95% CI 1.5-2.1). Exposure to glucocorticoids was associated with a dose-dependent increase in death from all causes, with a ratio (HR) of 1.07 per mg of prednisone per day (95% CI 1.05-1.08). Compared to patients who were not receiving corticosteroids, the minimum daily prednisone dose threshold associated with an increase in all-cause mortality was 8-15 mg, with an adjusted HR of 1.78 (95% CI 1.22-2.60). For the cumulative dose of glucocorticoids, the minimum dosage associated with all-cause mortality was 40 gm (HR 1.74 [95% CI 1.25-2.44]). CONCLUSION: Glucocorticoid use in RA is associated with a dose-dependent increase in mortality rates, with a daily threshold dose of 8 mg, at which the number of deaths increased in a dose-dependent manner. These findings may assist clinicians in selecting the appropriate glucocorticoid dosage for RA patients who require these agents.

Does the "Hispanic paradox" occur in rheumatoid arthritis? Survival data from a multiethnic cohort.

OBJECTIVE: Despite lower socioeconomic status (SES) and higher disease burden, Hispanics in the US paradoxically display equal or lower mortality on average than non-Hispanic whites. Our objective was to determine if the "Hispanic paradox" occurs among patients with rheumatoid arthritis (RA). METHODS: In a cohort of 706 RA patients, we compared differences in RA severity and comorbidity between Hispanic and non-Hispanic white ethnic groups at baseline. Cox proportional hazards models were used to estimate and compare mortality risk between Hispanics and non-Hispanic whites. RESULTS: We studied 706 patients with RA, of whom 434 were Hispanic and 272 were non-Hispanic white. Hispanics had significantly lower SES, greater inflammation, as well as higher tender and swollen joint counts. Patients were observed for 6,639 patient-years, during which time 229 deaths occurred by the censoring date (rate 3.4 per 100 person-years; 95% confidence interval 3.0, 3.9). Age- and sex-adjusted mortality was not significantly different between the 2 ethnic groups (hazard ratio [HR] 0.96). After adjustment for comorbidities, RA severity, and level of acculturation, mortality among Hispanics was lower (HR 0.56, P = 0.004). CONCLUSION: Despite greater severity in most clinical manifestations and lower SES among Hispanics, paradoxically, their mortality was not increased. Further research is needed to understand the mechanisms underlying this survival paradox.

Medical decision-making among Hispanics and non-Hispanic Whites with chronic back and knee pain: a qualitative study.

BACKGROUND: Musculoskeletal disorders affect all racial and ethnic groups, including Hispanics. Because these disorders are not life-threatening, decision-making is generally preference-based. Little is known about whether Hispanics in the U.S. differ from non-Hispanic Whites with respect to key decision making preferences. METHODS: We assembled six focus groups of Hispanic and non-Hispanic White patients with chronic back or knee pain at an urban medical center to discuss management of their conditions and the roles they preferred in medical decision-making. Hispanic groups were further stratified by socioeconomic status, using neighborhood characteristics as proxy measures. Discussions were led by a moderator, taped, transcribed and analyzed using a grounded theory approach. RESULTS: The analysis revealed ethnic differences in several areas pertinent to medical decision-making. Specifically, Hispanic participants were more likely to permit their physician to take the predominant role in making health decisions. Also, Hispanics of lower socioeconomic status generally preferred to use non-internet sources of health information to make medical decisions and to rely on advice obtained by word of mouth. Hispanics emphasized the role of faith and religion in coping with musculoskeletal disability. The analysis also revealed broad areas of concordance across ethnic strata including the primary role that pain and achieving pain relief play in patients' experiences and decisions. CONCLUSIONS: These findings suggest differences between Hispanics and non-Hispanic Whites in preferred information sources and decision-making roles. These findings are hypothesis-generating. If confirmed in further research, they may inform the development of interventions to enhance preference-based decision-making among Hispanics.

Carotid atherosclerosis predicts incident acute coronary syndromes in rheumatoid arthritis.

OBJECTIVE: The role of atherosclerosis in the acute coronary syndromes (ACS) that occur in patients with rheumatoid arthritis (RA) has not been quantified in detail. We undertook this study to determine the extent to which ACS are associated with carotid atherosclerosis in RA. METHODS: We prospectively ascertained ACS, defined as myocardial infarction, unstable angina, cardiac arrest, or death due to ischemic heart disease, in an RA cohort. We measured carotid atherosclerosis using high-resolution ultrasound. We used Cox proportional hazards models to estimate the association between ACS and atherosclerosis, adjusting for demographic features, cardiovascular (CV) risk factors, and RA manifestations. RESULTS: We performed carotid ultrasound on 636 patients whom we followed up for 3,402 person-years. During this time, 84 patients experienced 121 new or recurrent ACS events, a rate of 3.5 ACS events per 100 patient-years (95% confidence interval [95% CI] 3.0-4.3). Among the 599 patients without a history of ACS, 66 incident ACS events occurred over 3,085 person-years, an incidence of 2.1 ACS events per 100 person-years (95% CI 1.7-2.7). The incidence of new ACS events per 100 patient-years was 1.1 (95% CI 0.6-1.7) among patients without plaque, 2.5 (95% CI 1.7-3.8) among patients with unilateral plaque, and 4.3 (95% CI 2.9-6.3) among patients with bilateral plaque. Covariates associated with incident ACS events independent of atherosclerosis included male sex, diabetes mellitus, and a cumulative glucocorticoid dose of ≥ 20 gm. CONCLUSION: Atherosclerosis is strongly associated with ACS in RA. RA patients with carotid plaque, multiple CV risk factors (particularly diabetes mellitus or hypertension), many swollen joints, and a high cumulative dose of glucocorticoids, as well as RA patients who are men, are at high risk of ACS.

Effects of covariates and interactions on a genome-wide association analysis of rheumatoid arthritis.

While genetic and environmental factors and their interactions influence susceptibility to rheumatoid arthritis (RA), causative genetic variants have not been identified. The purpose of the present study was to assess the effects of covariates and genotype x sex interactions on the genome-wide association analysis (GWAA) of RA using Genetic Analysis Workshop 16 Problem 1 data and a logistic regression approach as implemented in PLINK. After accounting for the effects of population stratification, effects of covariates and genotype x sex interactions on the GWAA of RA were assessed by conducting association and interaction analyses. We found significant allelic associations, covariate, and genotype x sex interaction effects on RA. Several top single-nucleotide polymorphisms (SNPs) (~22 SNPs) showed significant associations with strong p-values (p < 1 x 10-4 - p < 1 x 10-24). Only three SNPs on chromosomes 4, 13, and 20 were significant after Bonferroni correction, and none of these three SNPs showed significant genotype x sex interactions. Of the 30 top SNPs with significant (p < 1 x 10-4 - p < 1 x 10-6) interactions, ~23 SNPs showed additive interactions and ~5 SNPs showed only dominance interactions. Those SNPs showing significant associations in the regular logistic regression failed to show significant interactions. In contrast, the SNPs that showed significant interactions failed to show significant associations in models that did not incorporate interactions. It is important to consider interactions of genotype x sex in addition to associations in a GWAA of RA. Furthermore, the association between SNPs and RA susceptibility varies significantly between men and women.

Impaired arterial function associated with thinning of cortical bone in rheumatoid arthritis.

OBJECTIVE: To evaluate the association between peripheral arterial function and cortical bone thickness in rheumatoid arthritis (RA). METHODS: In a cross-sectional study, we measured the combined cortical thickness (CCT) of the second metacarpal bone from hand radiographs, and the ankle-to-arm systolic blood pressure ratio, also known as ankle-brachial index (ABI), in RA patients. We evaluated the association between the 2 using multinomial logistic regression. RESULTS: We obtained CCT and ABI measurements in 588 RA patients. The mean +/- SD CCT was 3.62 +/- 1.16 mm. The proportion of patients with > or =1 ABI value < or =0.9, indicating obstructed lower limb arteries, increased from 18 (9.2%) of 191 patients in the highest CCT tertile to 25 (12.5%) of 200 in the middle CCT tertile to 38 (19.2%) of 198 in the lowest CCT tertile (P for trend 0.005). We noted a similar pattern for ABI values >1.3, indicative of arterial incompressibility (frequencies in high, middle, and low CCT tertiles were 4.7%, 9.5%, and 19.9%, respectively; P for trend < or =0.001). These trends remained significant after multivariable adjustment for potential confounders. After adjustment for the manifestations of RA and cumulative glucocorticoid dose, the association between CCT and arterial obstruction remained significant, but that with arterial incompressibility weakened considerably. CONCLUSION: There is an association between metacarpal cortical bone thinning and obstruction or incompressibility of the peripheral arteries in RA. The association with incompressibility may be mediated by systemic inflammation and/or glucocorticoids, but that with obstruction is independent of a wide array of potential confounders. Clinicians should be alert to the possibility of impaired arterial function RA patients with thinned metacarpal cortical bone.