Frequency Of Development Of Connective Tissue Disease In Statin-Users Versus Nonusers

Statins have pleiotropic properties that may affect the development of connective tissue diseases (CTD). The objective of this study was to compare the risk of CTD diagnoses in statin users and nonusers. This study was a propensity score-matched analysis of adult patients (30 to 85 years old) in the San Antonio military medical community. The study was divided into baseline (October 1, 2003 to September 30, 2005), and follow-up (October 1, 2005 to March 5, 2010) periods. Statin users received a statin prescription during fiscal year 2005. Nonusers did not receive a statin at any time during the study. The outcome measure was the occurrence of 3 diagnosis codes of the International Classification of Diseases, 9th Revision, Clinical Modification consistent with CTD. We described co-morbidities during the baseline period using the Charlson Comorbidity Index. We created a propensity score based on 41 variables. We then matched statin users and nonusers 1:1, using a caliper of 0.001. Of 46,488 patients who met study criteria (13,640 statin users and 32,848 nonusers), we matched 6,956 pairs of statin users and nonusers. Matched groups were similar in terms of patient age, gender, incidence of co-morbidities, total Charlson Comorbidity Index, health care use, and medication use. The odds ratio for CTD was lower in statin users than nonusers (odds ratio: 0.80; 95% confidence interval: 0.64 to 0.99; p = 0.05). Secondary analysis and sensitivity analysis confirmed these results. In conclusion, statin use was associated with a lower risk of CTD. Published by Elsevier Inc.Pharmac

Bone control of muscle function

Bone and muscle represent a single functional system and are tightly connected to each other. Indeed, diseases characterized by alterations of muscle physiology have effects on bone remodeling and structure and vice versa. Muscle influence on bone has been deeply studied, and recent studies identified irisin as new molecule involved in this crosstalk. Muscle regulation by bone needs to be extensively investigated since in the last few years osteocalcin was recognized as a key molecule in the bone–muscle interaction. Osteocalcin can exist in two forms with different degrees of carboxylation. The undercarboxylated form of osteocalcin is a hormone released by the bone matrix during the osteoclast bone resorption and can bind its G-protein coupled receptor GPRC6A expressed in the muscle, thus regulating its function. Recently, this hormone was described as an antiaging molecule for its ability to regulate bone, muscle and cognitive functions. Indeed, the features of this bone-related hormone were used to test a new therapeutic approach for sarcopenia, since injection of osteocalcin in older mice induces the acquirement of physical abilities of younger animals. Even if this approach should be tested in humans, osteocalcin represents the most surprising molecule in endocrine regulation by the skeleton

Cost-effectiveness of routine mediastinoscopy in computed tomography– and positron emission tomography–screened patients with stage I lung cancer

ObjectiveAccurate preoperative staging is essential for the optimal management of patients with lung cancer. An important goal of preoperative staging is to identify mediastinal lymph node metastasis. Computed tomography and positron emission tomography may identify mediastinal lymph node metastasis with sufficient sensitivity to allow omission of mediastinoscopy. This study utilizes our experience with patients with clinical stage I lung cancer to perform a decision analysis addressing whether mediastinoscopy should be performed in clinical stage I lung cancer patients staged by computed tomography and positron emission tomography.MethodsWe retrospectively reviewed our thoracic surgery database for cases between May 1999 and May 2004. Patients deemed clinical stage I by computed tomography and positron emission tomography were chosen for further study. Individual computed tomography, positron emission tomography, and operative and pathology reports were reviewed. The postresection pathologic staging and long-term survival were recorded. A decision model was created using TreeAgePro software and our observed data for the prevalence of mediastinal lymph node metastases and for the rate of benign nodules. Data reported in the literature were also utilized to complete the decision analysis model. A sensitivity analysis of key variables was performed.ResultsA total of 248 patients with clinical stage I lung tumors were identified. One hundred seventy-eight patients (72%) underwent mediastinoscopy before resection, and 5/178 (3%) showed N2 disease. An additional 9 patients were found to have N2 metastasis in the final resected specimen, resulting in a total of 14/248 patients (5.6%) with occult mediastinal lymph node metastases. Benign nodules were found in 19/248 (8%) of patients. Decision analysis determined that mediastinoscopy added 0.008 years of life expectancy at a cost of $250,989 per life-year gained. The outcome was sensitive to the prevalence of N2 disease in the population and the benefit of induction versus adjuvant therapy for N2 lung cancer. If the prevalence of N2 disease exceeds 10$100,000 per life-year gained.ConclusionPatients with clinical stage I lung cancer staged by computed tomography and positron emission tomography benefit little from mediastinoscopy. The survival advantage it confers is very small and is dependent on the prevalence of N2 metastasis and the unproven superiority of induction therapy over adjuvant therapy

Long-term survival of methotrexate in psoriatic arthritis

Objective. The purpose of this study was to evaluate the long-term survival rate of Methotrexate (MTX) in the peripheral joint involvement of psoriatic arthritis (PsA) in a setting of everyday clinical practice. Methods. This was an observational restrospective study performed using the data from a dermatological-rheumatological PsA clinic. All of the patients evaluated at this clinic from March 1997 to December 2007 who were started on MTX alone, had a three-year follow-up time or had discontinued the therapy were included into the survey. Results. Of the 174 evaluable patients, 104 (59.8%) were still taking MTX after three years of treament. The reasons of therapy discontinuation in the remaining 70 (40.2%) patients were: 34 (19.5%) lost-to-follow-up, 18 (10.3%) adverse events, 14 (8%) inefficacies, and 4 (2.3%) deaths (none related to the therapy). MTX was effective in controlling joint inflammation but not in preventing their deterioration. Overall, adverse events were recorded in 43 patients (36.4% of the 114 patients with a three-year follow-up). No serious side effect occurred in the study population. Conclusions. The results of this study showed that, in a setting of clinical pratice, MTX had a good three-year performance in patients with peripheral PsA. Almost 60% of them were still taking this drug at the end of the study period and the toxicity was more than acceptable. In our opinion, MTX might be considered the non-biological DMARD of choice for the treatment of this condition. However it should be used earlier and at higher doses

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 \u3c 1 × 10-4) with CIMT and plaque, respectively. The strongest association was observed between CIMT and rs17526722 (SLC17A2 gene) (β ± 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, β ± 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

2015 American College of Rheumatology Workforce Study

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144285/1/art40432_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144285/2/art40432.pd

Vaccinations in patients with immune-mediated inflammatory diseases

Patients with immune-mediated inflammatory diseases (IMID) such as RA, IBD or psoriasis, are at increased risk of infection, partially because of the disease itself, but mostly because of treatment with immunomodulatory or immunosuppressive drugs. In spite of their elevated risk for vaccine-preventable disease, vaccination coverage in IMID patients is surprisingly low. This review summarizes current literature data on vaccine safety and efficacy in IMID patients treated with immunosuppressive or immunomodulatory drugs and formulates best-practice recommendations on vaccination in this population. Especially in the current era of biological therapies, including TNF-blocking agents, special consideration should be given to vaccination strategies in IMID patients. Clinical evidence indicates that immunization of IMID patients does not increase clinical or laboratory parameters of disease activity. Live vaccines are contraindicated in immunocompromized individuals, but non-live vaccines can safely be given. Although the reduced quality of the immune response in patients under immunotherapy may have a negative impact on vaccination efficacy in this population, adequate humoral response to vaccination in IMID patients has been demonstrated for hepatitis B, influenza and pneumococcal vaccination. Vaccination status is best checked and updated before the start of immunomodulatory therapy: live vaccines are not contraindicated at that time and inactivated vaccines elicit an optimal immune response in immunocompetent individuals