Osteoporotic patients treated with bisphosphonates do not show the increased mortality observed in those untreated.

INTRODUCTION: Osteoporosis has been said to be associated with increased mortality. On the other hand, it is debated whether treatment with bisphosphonates may reduce mortality in osteoporotic patients. To contribute to the clarification of these issues, we have studied in a prospective cohort the mortality in people without osteoporosis and in patients with osteoporosis, untreated or treated with bisphosphonates MATERIAL AND METHODS: At their inclusion in the cohort, four groups of participants were identified: (a) people without osteoporosis (group 1); (b) osteoporotic patients treated with bisphosphonates (group 2); (c) osteoporotic patients who refused to be treated (group 3); and (d) patients who met osteoporosis diagnostic criteria but were not treated because their risk of fracture was considered to be low (group 4). To compare all four groups, unadjusted Kaplan-Meier estimates of survivorship were obtained and they were compared using log-rank test. Hazard ratios were then estimated via Cox regression adjusting for the main confounders. A comparison among the osteoporotic groups was made by means of a Cox regression analysis performed using only these three groups, adjusting for propensity scores. RESULTS: Two thousand six hundred and sixty-five people were included. In the unadjusted analysis, mortality in group 3 was higher than in the other groups (p < 0.001). Taking group 1 as a reference, Cox regression analysis showed the following mortality HRs for groups 2, 3, and 4 after adjusting for confounding factors: 0.82 (0.41-1.63), 1.37 (0.90-2.10), and 0.69 (0.46-1.02). In the analysis of the osteoporotic groups with the PS generated for them, and taking group 2 as a reference, the HRs were as follows: group 3, 2.38 (1.34-4.22); group 4, 1.45 (0.61-3.43). CONCLUSION: Mortality in osteoporotic patients who refused treatment is higher than in osteoporotic patients treated with bisphosphonates. In unadjusted analysis, it was also higher than in non-osteoporotic people; however, this difference disappeared after adjustment for confounding factors.

Serum 25-hydroxyvitamin D, parathyroid hormone, calcium intake, and bone mineral density in Spanish adults.

UNLABELLED: Vitamin D insufficiency is very common among Spanish community-dwelling adult subjects. A threshold of serum 25(OH)D around 30 ng/ml would be necessary for the prevention of secondary hyperparathyroidism and hip bone loss in our population, regardless of the dairy calcium ingestion. INTRODUCTION: This study aims to assess 25-hydroxyvitamin D-25(OH)D-status in Spanish adult subjects and to analyze its relationships with serum PTH levels, calcium intake, and bone mineral density (BMD). METHODS: A total of 1811 individuals (1154 postmenopausal women and 657 men) aged 44-93 years participated in the study. Serum 25(OH)D, intact parathyroid hormone (PTH), aminoterminal propeptide of type I collagen (P1NP), and C-terminal telopeptide of type I collagen (ß-CTX) levels were measured by electrochemiluminescence. BMD was determined by dual x-ray absorptiometry (DXA) at lumbar spine, femoral neck, and total hip. RESULTS: Serum 25(OH)D levels were below 10, 20, and 30 ng/ml in 5, 40, and 83 % of participants, respectively. There was a significant seasonal difference in mean serum 25(OH)D, with higher levels in summer-autumn. In multivariate analysis, 25(OH)D levels were negatively correlated with age, serum PTH and creatinine, body mass index, smoking, alcohol intake, and a number of chronic diseases, but positively with dairy calcium intake. The magnitude of the difference in serum PTH according to 25(OH)D quartiles was not influenced by calcium intake. A threshold of serum 25(OH)D around 30 ng/ml was observed for serum PTH and hip BMD. CONCLUSIONS: Vitamin D insufficiency is very common among Spanish community-dwelling adult subjects. A threshold of serum 25(OH)D around 30 ng/ml would be necessary for the prevention of secondary hyperparathyroidism and hip bone loss in our population, regardless of the dairy calcium ingestion. Programs to improve vitamin D status may be required in our country.

Anti-TNF-α therapy reduces retinol-binding protein 4 serum levels in non-diabetic patients with psoriasis: a 6-month prospective study.

BACKGROUND: Retinol-binding protein-4 (RBP4), an adipokine considered as an emerging cardiometabolic risk factor, is increased in patients with moderate-to-severe psoriasis. OBJECTIVE: In this study, we aimed to establish the effect of anti-TNF-α therapy on RBP4 levels in patients with moderate-to-severe psoriasis. We also assessed if RBP4 levels correlate with metabolic syndrome features and disease severity in these patients. METHODS: Prospective study on a series of consecutive non-diabetic patients with moderate-to-severe psoriasis who completed 6 months of therapy with adalimumab. Patients with kidney disease, hypertension or body mass index ≥ 35 kg/m(2) were excluded. Metabolic and clinical evaluation was performed at the onset of treatment (time 0) and at month 6. RESULTS: Twenty-nine patients were assessed. Statistically significant reduction (P = 0.0001) of RBP4 levels was observed after 6 months of therapy (RBP4 at time 0: 55.7 ± 21.4 µg/mL, vs. 35.6 ± 29.9 µg/mL at month 6). No significant correlation between basal RBP4 levels and metabolic syndrome features or disease severity was found. Nevertheless, although RBP4 levels did not correlate with insulin resistance, a negative and significant correlation between RBP4 levels obtained after 6 months of adalimumab therapy and other metabolic syndrome features such as abdominal perimeter and body mass index were observed. At that time, a negative and significant correlation between RBP4 levels and disease activity scores and ultrasensitive CRP levels was also disclosed. CONCLUSION: Our results support an influence of the anti-TNF-α blockade on RBP4 serum levels. This finding is of potential relevance due to increased risk of cardiovascular disease in patients with psoriasis.

Relationship of leptin with adiposity and inflammation and resistin with disease severity in psoriatic patients undergoing anti-TNF-alpha therapy.

BACKGROUND: Altered secretion patterns of proinflammatory adipokines may influence the increased risk of cardiovascular mortality observed in patients with chronic inflammatory diseases. OBJECTIVE: To determine whether two adipokines, leptin and resistin, correlate with metabolic syndrome features and disease severity in psoriatic patients who underwent anti-TNF-α therapy. METHODS: Prospective study of consecutive non-diabetic patients with moderate-to-severe psoriasis who completed 6 months of therapy with anti-TNF-α- adalimumab. Patients with kidney disease, hypertension or body mass index ≥35 Kg/m(2) were excluded. Metabolic and clinical evaluation was performed at the onset of anti-TNF-α treatment and at month 6. RESULTS: Twenty-nine patients were assessed. A correlation between adiposity and leptin was observed (waist circumference and leptin levels after 6 months of therapy: r = 0.43; P = 0.030). Leptin concentration also correlated with blood pressure before adalimumab onset (systolic: r = 0.48; P = 0.013 and diastolic blood pressure: r = 0.50; P = 0.010 ). A marginally significant negative correlation between insulin sensitivity (QUICKI) and leptin levels was also observed. CRP levels correlated with leptin prior to the onset of adalimumab (r = 0.45; P = 0.020) and with resistin both before (r = 0.45; P = 0.020) and after 6 months of therapy (r = 0.55; P = 0.004). A positive association between parameters of disease activity such as BSA (r = 0.60; P = 0.001) and PASI (r = 0.63; P = 0.001) prior to the onset of adalimumab therapy and resistin concentrations was also disclosed. No significant changes in leptin and resistin concentrations following the 6-month treatment with adalimumab were seen. CONCLUSION: In patients with moderate-to-severe psoriasis leptin correlates with metabolic syndrome features and inflammation whereas resistin correlate with inflammation and disease severity.

Anti-TNF-α therapy improves insulin sensitivity in non-diabetic patients with psoriasis: a 6-month prospective study.

OBJECTIVE: Psoriasis is a chronic inflammatory disease associated with increased risk of cardiovascular death. Several studies have shown a beneficial effect of anti-TNF-α therapy on the mechanisms associated with accelerated atherogenesis in patients with inflammatory arthritis, including an improvement of insulin sensitivity. In this study, we aimed to determine for the first time whether the anti-TNF-α monoclonal antibody adalimumab may improve insulin sensitivity in non-diabetic patients with psoriasis. METHODS: Prospective study on a series of consecutive non-diabetic patients with moderate to severe psoriasis seen at the Dermatology Division of Hospital Universitario Marques de Valdecilla (Northern Spain) who completed 6 months of therapy with adalimumab (80 mg at week 0 followed by 40 mg every other week, starting 1 week after the initial dose). Patients with chronic kidney disease, hypertension or body mass index ≥ 35 kg/m(2) were excluded. Metabolic and clinical evaluation including assessment of insulin sensitivity using the Quantitative Insulin Sensitivity Check Index (QUICKI) was performed at the onset of the treatment (time 0) and at month 6. RESULTS: Twenty-nine patients (52% women; 38.6 ± 10.7 years) with moderate to severe psoriasis [body surface area (BSA) 37.9 ± 16.3%], Psoriasis Area and Severity Index [(PASI) 18.9 ± 7.8] were assessed. Statistically significant improvement (P=0.008) of insulin sensitivity was observed after 6 months of adalimumab therapy (QUICKI at time 0: 0.35 ± 0.04 vs. 0.37 ± 0.04 at month 6). Significant improvement of erythrocyte sedimentation rate, ultrasensitive C-reactive protein, BSA, PASI, Nail Psoriasis Severity Index, physician global assessment and psoriatic arthritis screening and evaluation questionnaire was also observed at month 6 (P < 0.05 for each variable). CONCLUSION: Our results support a beneficial effect of the anti-TNF-α blockade on the mechanisms associated with accelerated atherogenesis in patients with psoriasis.

Cardiovascular risk assessment in rheumatoid arthritis: impact of the EULAR recommendations on a national calibrated score risk index.

OBJECTIVES: To evaluate the impact of the application of the EULAR task force recommendations in the cardiovascular (CV) risk assessment of rheumatoid arthritis (RA) patients according to a national calibrated SCORE. METHODS: Two hundred and one consecutive RA patients seen at the rheumatology outpatient clinics of the University Hospital 'San Cecilio', Granada, Southern Spain, were studied. Information on demographic, classic CV risk factors, history of CV events and disease clinical features were obtained. Both the systematic coronary risk evaluation (SCORE) risk index and the modified SCORE (mSCORE) following the EULAR recommendations were performed. RESULTS: Based on the classic CV risk factors the mean ± standard deviation SCORE was 2.2 ± 2.6 (median 2). Twenty-two (11%) patients were above the threshold of high risk for the Spanish population. Following the EULAR recommendations 52 of the 124 patients (41.93%) initially classified as having intermediate risk were reclassified as having high CV risk. Therefore, the mean mSCORE was 3.3 ± 4 (median 3) and, due to this, 74 (36.8%) patients were above the threshold of high CV risk for the Spanish population. As expected, patients who had experienced CV events were older, had more CV risk factors and higher mSCORE than those without CV events. CONCLUSIONS: These observations support the claim that the mSCORE should be specifically adapted to the population to be assessed. However, the use of additional tools should be considered in an attempt to fully identify high-risk RA patients.

Gelsolin levels are decreased in ankylosing spondylitis patients undergoing anti-TNF-alpha therapy.

OBJECTIVES: To determine whether circulating gelsolin (GSN) levels in patients with ankylosing spondylitis (AS) undergoing TNF-α antagonist-infliximab-therapy are altered compared with controls and to establish whether disease activity, systemic inflammation and metabolic syndrome are potential determinants of circulating GSN levels in these patients. METHODS: We assessed GSN serum concentrations in a series of 30 non-diabetic AS patients without cardiovascular (CV) disease undergoing TNF-α antagonist-infliximab therapy and 48 matched controls. GSN levels were measured immediately before and after an infliximab infusion. Correlations of GSN serum levels with disease activity, systemic inflammation and metabolic syndrome were assessed. Potential changes in GSN concentration following an infusion of anti-TNF-α monoclonal antibody-infliximab were also analysed. RESULTS: Although at the time of the study AS patients undergoing anti-TNF-α therapy had adequate control of the disease (mean BASDAI 2.94), they showed lower GSN serum levels than healthy controls (mean±SD: 38660.42±23624.6 ng/ml versus 68975.43±31246.79 ng/ml; p<0.0001). When AS patients were stratified according to sex, we observed that GSN levels were significantly lower in men than in women (p=0.032). However, no differences in GSN levels according to the specific clinical features of the disease were seen. No association was found between GSN concentration and adipokines or biomarkers of endothelial cell activation. However, correlation between basal GSN levels and insulin resistance was observed. A single infliximab infusion did not lead to significant changes in GSN levels. CONCLUSIONS: GSN concentration is reduced in AS patients undergoing periodical anti-TNF-α therapy and low disease activity. Potential association with some metabolic syndrome features seems to exist.

Correlation between two biomarkers of atherosclerosis, osteopontin and angiopoietin-2, in non-diabetic ankylosing spondylitis patients undergoing TNF-α antagonist therapy.

OBJECTIVES: To determine whether circulating osteopontin (OPN) levels in patients with ankylosing spondylitis (AS) undergoing TNF-α antagonist-infliximab-therapy are increased compared with controls and to establish whether disease activity, systemic inflammation, metabolic syndrome, adipokines and biomarkers of atherosclerosis are potential determinants of circulating OPN levels in these patients. METHODS: We assessed OPN serum concentrations in a series of 30 non-diabetic AS patients without cardiovascular disease undergoing TNF-α antagonist-infliximab therapy and 48 matched controls. OPN levels were measured immediately before and after an infliximab infusion, at time 0 and at time 120 minutes respectively. Correlations of OPN serum levels with clinical features, disease activity, systemic inflammation, metabolic syndrome and several biomarkers of atherosclerosis were assessed. Potential changes in OPN concentration following an infusion of anti-TNF-α monoclonal antibody-infliximab were also analysed. RESULTS: At the time of the study AS patients undergoing anti-TNF-α therapy had low disease activity (mean BASDAI 2.94) and they showed similar OPN serum levels to healthy controls. No differences in OPN levels according to the specific clinical features of the disease were seen. Also, no correlation between OPN concentration and insulin resistance and adipokines was observed. However, a positive correlation between OPN and angiopoietin-2 (Angpt-2) serum levels was found (r=0.397; p=0.04). In addition, a single infliximab infusion led to a marginal statistically significant reduction in OPN levels (24112.19±14608.73 pg/ml at time 0 versus 21806.62±11390.83 pg/ml at time 120'; p=0.05). CONCLUSIONS: OPN and Angpt-2 serum levels are correlated in non-diabetic AS patients undergoing TNF-α antagonist therapy.

Additively-manufactured Mg wire-reinforced PLDL-matrix composites for biomedical applications.

Coupons of a medical grade PLDL polymer matrix uniaxially reinforced with a 15% volume fraction of Mg wires have been manufactured by fused filament fabrication for the first time. Two different types of Mg wires, without and with a surface treatment by plasma electrolytic oxidation were used. Both composite materials were subjected to degradation in phosphate buffer solution over a 3-week period, and their degradation and deformation micromechanisms were analysed in detail. Additionally, the materials were subjected to extensive mechanical testing under various loading conditions, and the interface strength was also analysed. It was found that the presence of the Mg wires improves the mechanical behaviour and accelerates the corrosion rate of the composite with respect that of the polymer matrix and these properties can be further tailored through the surface-modification of Mg wires by plasma electrolytic oxidation. The additive manufacturing strategy presented opens the path to fabricate multimaterial implants and scaffolds with complex shape and tailored properties provided by biodegradable polymers reinforced with either Mg and Zn particles and/or wires.

Mechanical properties, in vitro degradation and cytocompatibility of woven textiles manufactured from PLA/PCL commingled yarns.

The mechanical, thermal, and biological performance of fabrics manufactured with hybrid PLA/PCL commingled yarns were studied. Commingled hybrid yarns take advantage of the higher elastic modulus of PLA and the higher ductility and toughness of PCL to produce yarns and fabrics with high strength and ductility that is transferred to the woven textiles. Furthermore, PLA and PCL exhibit different degradation rates and also allow to tailor this property. Degradation of the textiles was carried out in phosphate-buffered saline solution for up to 160 days at 37 °C and 50 °C (accelerated degradation). Neither the thermal nor the mechanical properties were altered by immersion at 37 °C during 80 days and a slight degradation was observed as a result of chain scission of the PLA fibres after 160 days. However, immersion at 50 °C led to a rapid reduction in strength after 40 days due to the hydrolysis of PLA, and the fabric was highly degraded after 160 days as a result of chain scission in PCL. Finally, while indirect tests did not predict optimal biocompatibility, the direct tests provided a different perspective of the cell interaction between the textile and pre-osteoblasts regarding cell attachment and cell morphology. These results show the potential of hybrid commingled yarns to manufacture textile scaffolds of biodegradable polymers with tailored mechanical properties and good ductility for connective tissue engineering (ligaments and tendons).

No evidence of association between functional polymorphisms located within IL6R and IL6ST genes and Henoch-Schönlein purpura.

Henoch-Schönlein purpura (HSP) is the most common type of primary small-sized blood vessel vasculitis in children and an uncommon condition in adults. Interleukin (IL)-6 is a proinflammatory cytokine whose effect is controlled by the IL-6 receptor (IL-6R). IL-6 transducer (IL-6ST/gp130) is the signal-transducing subunit of the IL-6R. Two hundred and eighty five Spanish HSP patients and 877 sex and ethnically matched controls were genotyped for the IL6R rs2228145 and IL6ST/gp130 rs2228044 functional polymorphisms. No significant differences in the genotype and allele frequencies between HSP patients and controls were observed. Moreover, there were no differences between HSP patients according to the age at disease onset, presence of nephritis or gastrointestinal manifestations. Our results do not confirm association of IL6R rs2228145 and IL6ST/gp130 rs2228044 polymorphisms with HSP.

Single-nucleotide polymorphisms at the 9p21.3 genomic region not associated with the risk of cardiovascular disease in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic polygenic inflammatory disease associated with accelerated atherosclerosis and high risk of cardiovascular disease (CVD). In this study, we evaluated the potential association of 9p21.3 single-nucleotide polymorphisms (SNPs) - previously linked to coronary artery disease - and CVD risk in 2001 Spanish RA patients genotyped for 9p21.3 SNPs using TaqMan™ assays. Carotid intima media thickness (cIMT) and presence of carotid plaques were also analyzed. Cox regression model did not disclose significant differences between patients who experienced CVD and those who did not. Neither association was found between cIMT or carotid plaques and SNPs allele distribution. In conclusion, results do not support a role of rs10116277 or rs1537375 SNPs in CVD risk in Spanish RA patients.

The 11q23.3 genomic region-rs964184-is associated with cardiovascular disease in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is an inflammatory disease associated with high risk of cardiovascular (CV) events. Recently, the rs964184 polymorphism has been associated with coronary artery disease in nonrheumatic Caucasian individuals. 2160 Spanish RA patients were genotyped for the rs964184 polymorphism. Sex, age at diagnosis and traditional CV risk factors (diabetes mellitus, dyslipidemia and smoking habit) were associated with increased risk of CV events. Interestingly, RA patients carrying the rs964184 GG genotype had significantly higher risk of CV events than those with CC genotype [hazard ratio (HR) = 2.91, 95% confidence interval (CI): 1.36-6.26, P = 0.006] after adjusting the results for sex, age at diagnosis and traditional CV risk factors. Our results indicate that rs964184 polymorphism is associated with CV disease in RA.

Local implementation of a syndromic influenza surveillance system using emergency department data in Santander, Spain.

BACKGROUND: We assessed the local implementation of syndromic surveillance (SyS) as part of the European project 'System for Information on, Detection and Analysis of Risks and Threats to Health' in Santander, Spain. METHODS: We applied a cumulative sum algorithm on emergency department (ED) chief complaints for influenza-like illness in the seasons 2010-11 and 2011-12. We fine tuned the algorithm using a receiver operating characteristic analysis to identify the optimal trade-off of sensitivity and specificity and defined alert criteria. We assessed the timeliness of the SyS system to detect the onset of the influenza season. RESULTS: The ED data correlated with the sentinel data. With the best algorithm settings we achieved 70/63% sensitivity and 89/95% specificity for 2010-11/2011-12. At least 2 consecutive days of signals defined an alert. In 2010-11 the SyS system alerted 1 week before the sentinel system and in 2011-12 in the same week. The data from the ED is available on a daily basis providing an advantage in timeliness compared with the weekly sentinel data. CONCLUSIONS: ED-based SyS in Santander complements sentinel influenza surveillance by providing timely information. Local fine tuning and definition of alert criteria are recommended to enhance validity.

Cold-related mortality due to cardiovascular diseases, respiratory diseases and cancer: a case-crossover study.

OBJECTIVES: The aim of this study was to identify the relationship between low temperatures in winter and mortality due to cancer, cardiovascular diseases and respiratory diseases. STUDY DESIGN: Case-crossover study. METHODS: A case-crossover study was performed in Cantabria (northern Spain) in the years 2004-2005; 3948 deaths were included. Odds ratios were estimated using conditional logistic regression, stratified by age, sex, and delay of exposure to low temperatures. RESULTS: There was an inverse dose-response relationship between temperature and mortality in the three causes of death studied; this result was consistent across genders and age groups. The higher OR for cancer mortality was seen on the first day of exposure (OR = 4.91; 95% CI: 1.65-13.07 in the whole population), and it decreased when exposure over several days in a row was considered; people aged 75 years or more were especially susceptible to cold temperatures (OR = 17.9; 95% CI: 2.38-134.8). Cardiovascular (OR = 2.63; 95% CI: 1.88-3.67) and respiratory mortality (OR = 2.72; 95% CI: 1.46-5.08) showed a weaker effect. CONCLUSION: There is a striking association between the extreme cold temperatures and mortality from cancer, not previously reported, which is more remarkable in the elderly. These results could be explained by a harvesting effect in which the cold acts as a trigger of death in terminally ill patients at high risk of dying a few days or weeks later.

Influence of the drying mode of support on the properties of Pd/Al2O3-ZrO2 materials used for methane combustion.

This work constitutes a new trial to enhance the properties of palladium supported on alumina modified with zirconium used as catalysts for methane combustion. The effect of the support drying mode is studied. For this aim, Al2O3-ZrO2 binary oxides with zirconium loading of 2 and 5% in weight were prepared using sol-gel process then dried under ordinary or supercritical conditions. Palladium with a loading of 0.5% was deposited on the support by wet impregnation. Several techniques have been used to investigate differences between the two types of the derived catalysts.

Late-onset systemic lupus erythematosus in Northwestern Spain: differences with early-onset systemic lupus erythematosus and literature review.

To further investigate into the epidaemiology of systemic lupus erythematosus (SLE) in Southern Europe, we have assessed the incidence, clinical spectrum and survival of patients diagnosed with late-onset SLE (age ≥ 50 years) according to the 1982 American College of Rheumatology (ACR) classification criteria at the single hospital for a well-defined population of Lugo, Northwestern (NW) Spain. Between January 1987 and December 2006, 51 (39.3%) of the 150 patients diagnosed as having SLE fulfilled definitions for late-onset SLE. The predominance of women among late-onset SLE (4:1) was reduced when compared with that observed in early-onset SLE (7:1). However, the incidence of late-onset SLE was significantly higher in women (4.2 [95% confidence interval (CI): 3.1-5.6] per 100,000 population) than in men (1.3 [95% CI: 0.6-2.2] per 100,000 population) (p < 0.001). As observed in early-onset SLE, the most frequent clinical manifestation in patients with late-onset SLE was arthritis (71.2%). Renal disease was less common in late-onset SLE (13.5%) than in early-onset SLE (26.4%); p = 0.07). In contrast, secondary Sjögren syndrome was more commonly found in the older age-group (27.1% versus 12.1%; p = 0.03). A non-significantly increased incidence of serositis was also observed in late-onset SLE patients (33.9% versus 22.0%; p = 0.13). Hypocomplementaemia (72.9% versus 91.2%) and positive results for anti-DNA and anti-Sm (49.2% and 6.8% versus 68.1% and 23.1, respectively) were significantly less common in late-onset SLE patients than in early-onset SLE. The probability of survival was reduced in late-onset SLE (p < 0.001). With respect to this, the 10-year and 15-year survival probability were 74.9 % and 63.3% in the late-onset SLE group and 96.3% and 91.0% in patients with early-onset SLE, respectively. In conclusion, our results confirm that in NW Spain SLE is not uncommon in individuals 50 years and older. In keeping with earlier studies, late-onset SLE patients from NW Spain have some clinical and laboratory differences with respect to those individuals with early-onset SLE. Our data support the claim of a reduced probability of survival in the older age-group of SLE patients.

Association of the methionine sulfoxide reductase A rs10903323 gene polymorphism with cardiovascular disease in patients with rheumatoid arthritis.

OBJECTIVE: The methionine sulfoxide reductase A (MSRA) gene is related to oxidative stress that has been involved in the susceptibility to rheumatoid arthritis (RA) in genome-wide pathway analysis and replication studies. The aim of the present study was to determine whether the MSRA gene is implicated in susceptibility to cardiovascular (CV) disease in RA patients. METHODS: A total of 1302 patients fulfilling the 1987 American College of Rheumatism classification criteria for RA were genotyped for the MSRA rs10903323 (G/A) polymorphism. Two hundred and thirty-three (17.9%) patients experienced CV events. Human leucocyte antigen (HLA)-DRB1 genotyping was performed using molecular-based methods. Multiple logistic regression models were constructed with adjustments for gender, age at RA diagnosis, follow-up, rheumatoid shared epitope, and traditional CV risk as potential confounders. RESULTS: There were no statistically significant differences in the allele or genotype frequencies for the MSRA rs10903323 polymorphism between RA patients who experienced CV events and those who did not. However, an adjusted logistic regression model disclosed that the minor allele G yielded a marginally significant increased risk of CV events in this series of patients with RA [p = 0.05, odds ratio (OR) 1.68, 95% confidence interval (CI) 1.00-2.85]. When the logistic regression model was adjusted for anti-cyclic citrullinated peptide (anti-CCP) antibody status instead of for shared epitope, an increased risk of having ischaemic heart disease was found in patients carrying the minor allele G (p = 0.04, OR 2.00, 95% CI 1.03-3.88). CONCLUSION: The MSRA rs10903323 gene polymorphism may be implicated in the increased risk to develop CV events, in particular ischaemic heart disease, observed in RA patients.

Sex differences in adherence to highly active antiretroviral therapy: a meta-analysis.

Observational studies have found that women tend to have lower adherence to highly active antiretroviral therapy (HAART) than men do, though no meta-analysis has yet investigated this trend. The aims of the current meta-analysis are to determine if and to what degree the percentage of men versus women maintaining ≥90% adherence to prescribed HAART differs, and if the external variables moderating adherence differs by gender. Eight electronic databases were searched to locate all relevant studies available by May 2011. Fifty-six observational studies were eligible for inclusion in the meta-analysis. A random effect model was assumed for the global percentage estimation and to explain the heterogeneity. Across these studies, the difference between men and women in the proportion of individuals with ≥90% adherence to HAART was marginally significant (p<0.1; 67% and 62%, respectively). A greater proportion of men maintaining ≥90% adherence to HAART was more likely in studies with higher proportions of men who have sex with men (MSM), lower proportions of male alcohol users or lower proportions of men in a methadone program. In women, higher rates of adherence were found in studies conducted in Africa, Asia, and South America, when the sample included more widows or when the sample had a lower basal CD4 count. That both the percentage of adherent individuals and the variables associated with such adherence differ between men and women are suggestive of the need for improving gender-tailored interventions for adherence to HAART.

Influence of MHCIITA rs3087456 and rs4774 polymorphisms in the susceptibility to cardiovascular disease of patients with rheumatoid arthritis.

OBJECTIVES: MHCIITA is a major regulator of MHC expression that has been reported to be involved in the susceptibility to rheumatoid arthritis (RA) and myocardial infarction. In this study we investigated the potential association of two MHCIITA gene polymorphisms with cardiovascular (CV) risk in patients with RA. METHODS: 1302 patients fulfilling the 1987 ACR classification criteria for RA were genotyped for the MHCIITA rs3087456 and rs4774 gene polymorphisms to determine the influence of MHCIITA variants in the development of CV events. The potential influence of these polymorphisms in the development of subclinical atherosclerosis was also analysed in a subgroup of patients with no history of CV events by the assessment of two surrogate markers of atherosclerosis; brachial and carotid ultrasonography to determine endothelial function and carotid artery intima-media thickness, respectively. RESULTS: No statistically significant differences in the allele or genotype frequencies for each individual MHCIITA gene polymorphism between RA patients who experienced CV events, or not, were found. This was also the case when each polymorphism was assessed according to results obtained from surrogate markers of atherosclerosis. Also, in assessing the combined influence of both MHCIITA gene polymorphisms in the risk of CV disease after adjustment for gender, age at time of disease diagnosis, follow-up time, traditional CV risk factors, and shared epitope status, patients with CV events only showed a marginally decreased frequency of the MHCIITA rs3087456-rs4774 G-G allele combination (p=0.08; odds ratio: 0.63 [95% confidence interval: 0.37-1.05]). CONCLUSIONS: Our data do not support an influence of MHCIITA rs3087456 and rs4774 polymorphisms in the increased risk of CV events of patients with RA.