Tolerance and effectiveness of anti-tumor necrosis factor alpha therapies in elderly patients with rheumatoid arthritis: a population-based cohort study

OBJECTIVE: Limited data have been published on tolerance to and efficacy of classic or biologic disease-modifying antirheumatic drugs in elderly patients with rheumatoid arthritis (RA). The goal of the present study was to evaluate the tolerance to and effectiveness of anti-tumor necrosis factor (anti-TNF) agents in elderly patients (> or =65 years old) with RA (ERA) in comparison with younger patients (YRA). METHODS: The Swiss Clinical Quality Management program for RA is a longitudinal population-based cohort. All patients who had received at least 1 dose of anti-TNF agents between January 1997 and November 2005 were included and categorized according to their age. Tolerance was assessed by analyzing discontinuation rates of anti-TNF agents. Effectiveness of these agents was assessed by analyzing RA disease activity (Disease Activity Score in 28 joints [DAS28]) and functional disability (Health Assessment Questionnaire [HAQ]) after anti-TNF initiation. RESULTS: Among 1,571 patients with RA treated with anti-TNF agents, 344 were > or =65 years of age at treatment initiation. Drug discontinuation rates (median time 3 years) and mean change in DAS28 scores at 2 years (-0.65 versus -0.58) were identical in ERA and YRA. However, HAQ score improved significantly less in ERA (-0.02) than in YRA (-0.1) and a subsequent analysis revealed that this finding was essentially due to patients >75 years of age. CONCLUSION: Age in itself should not interfere with the decision to treat elderly patients with RA with anti-TNF agents. In a subset of patients ages >75 years, no functional improvement according to HAQ should be expected despite improvements in disease activity.     

Genetic variation in 1253 immune and inflammation genes and risk of non-Hodgkin lymphoma

Smaller-scale evaluations suggest that common genetic variation in candidate genes related to immune function may predispose to the development of non-Hodgkin lymphoma (NHL). We report an analysis of variants within genes associated with immunity and inflammation and risk of NHL using a panel of 9412 single-nucleotide polymorphisms (SNPs) from 1253 genes in a study of 458 patients with NHL and 484 frequency-matched controls. We modeled haplotypes and risk of NHL, as well as the main effects for all independent SNPs from a gene in multivariate logistic regression models; we separately report results for nonsynonymous (ns) SNPs. In gene-level analyses, the strongest findings (P < or = .001) were for CREB1, FGG, MAP3K5, RIPK3, LSP1, TRAF1, DUSP2, and ITGB3. In nsSNP analyses, the strongest findings (P < or = .01) were for ITGB3 L59P (odds ratio [OR] = 0.66; 95% confidence interval [CI] 0.52-0.85), TLR6 V427A (OR = 5.20; CI 1.77-15.3), SELPLG M264V (OR = 3.20; CI 1.48-6.91), UNC84B G671S (OR = 1.50; CI 1.12-2.00), B3GNT3 H328R (OR = 0.74; CI 0.59-0.93), and BAT2 V1883L (OR = 0.64; CI 0.45-0.90). Our results suggest that genetic variation in genes associated with immune response (TRAF1, RIPK3, BAT2, and TLR6), mitogen-activated protein kinase (MAPK) signaling (MAP3K5, DUSP2, and CREB1), lymphocyte trafficking and migration (B3GNT3, SELPLG, and LSP1), and coagulation pathways (FGG and ITGB3) may be important in the etiology of NHL, and should be prioritized in replication studies.     

Angioimmunoblastic T-cell lymphoma: histological progression associates with EBV and HHV6B viral load

The clinical and histological presentations of angioimmunoblastic T-cell lymphoma (AITL) often mimic an infectious process. Epstein-Barr virus (EBV) and human herpes virus (HHV6) are known to be associated with AITL, but whether these viral infections play a role in its pathogenesis is unclear. It also remains to be investigated whether there might be other viruses associated with AITL. We first screened 26 well-characterised cases of AITL for herpesvirus by polymerase chain reaction (PCR) with universal primers and found evidence of only EBV and HHV6B infection. Subsequent PCR using virus-specific primers demonstrated EBV and HHV6B infection in 40/49 biopsies (36/42 cases) and 21/49 biopsies (19/42 cases) of AITL respectively with both viral infections found in 17/49 specimens (15/42 cases). Importantly, simultaneous infection with both viruses was found only in specimens showing histological pattern II (n = 2) or III (n = 15). Interestingly, among specimens containing both viruses, there was a tendency towards an inverse correlation between the EBV and HHV6B viral load as shown by quantitative PCR. In specimens positive only for EBV, the viral load was significantly higher in specimens with histological pattern III than those with pattern II. High EBV load was also significantly associated with B-cell monoclonality. Double EBV encoded small RNA (EBER) in situ hybridisation and immunohistochemistry indicated that EBV-infected B cells had a late postgerminal centre immunophenotype. Our results demonstrate an association between EBV and HHV6B infection and the histological progression of AITL, suggesting that these viruses may play a role in the pathogenesis of this lymphoma.     

Atrial fibrillation after percutaneous coronary intervention: predictive importance of clinical, angiographic features and P-wave dispersion

Atrial fibrillation (AF) may occur during or after percutaneous coronary interventions (PCI). The purpose of the study was to determine the clinical, angiographic and electrophysiological predictors of AF after PCI. 225 patients undergoing PCI (mean age of 65 +/- 11 years) who had sinus rhythm (SR) before balloon inflation were taken to study. Of these 22 developed AF in catheterization laboratory after balloon inflation or in 24 h following PCI (AF group), 203 did not (SR group). The patients in AF group were older (67 +/- 9 vs. 63 +/- 8 years, p < 0.05) and their ventricular ejection fraction was lower than SR group (56 +/- 5 vs. 45 +/- 7%, p < 0.05). The P-wave dispersion was significantly higher in AF group than SR group (53 +/- 8 vs. 29 +/- 10 ms, p < 0.001). For the patients with ST elevation myocardial infarction, the time from the onset of symptoms to balloon inflation was 3.7 +/- 1.7 h in SR group. It was longer in AF group (4.1 +/- 1.8 h, p < 0.05). TIMI perfusion grades 2 and 3 were achieved in 23 of 27 patients in SR group, and 5 of 8 patients in AF group. Multivessel disease was documented in 93 of the patients in SR group, and 12 in AF group. Clinical reperfusion was thought to be established in 20 in SR group, and 4 in AF group. In conclusion, our results show the importance of clinical factors, angiographic results and P-wave analysis in prediction of AF following PCI.     

Relation of body mass index (BMI) to disease free (DFS) and distant disease free survivals (DDFS) among Turkish women with operable breast carcinoma

BACKGROUND: The correlation between body mass index (BMI) and patient and tumor characteristics related to prognosis has not been well explored and may help to elucidate the mechanisms involved in the carcinogenesis. Because of the equivocal, inconsistent and uncertain research results as well as racial and ethnic differences, we aimed to evaluate the prognostic significance of high BMI in Turkish women with operable breast carcinoma. METHODS: Two hundred and sixty-six patients who had operable invasive breast carcinoma diagnosed from 2000 through 2004 in a single institution were evaluated for their demographic features, BMI, histopathological/immunohistochemical examinations and treatments. Quetelet BMI [weight (kg)/height (m)2] categories were selected according to the World Health Organization definition. Disease free survival (DSF) as well as distant disease free survival (DDSF) analyses were performed to identify independent prognostic factors. RESULTS: Post-menopausal patients were significantly in the higher quartile of BMI than pre-menopausal patients (P = 0.003). While post-menopausal obese patients had worse DSF and DDFS (P = 0.001), vascular invasion was the independent prognostic factor for both survival indices (P = 0.031). CONCLUSIONS: Post-menopausal obese Turkish women are at increased risk of developing breast tumors with aggressive phenotype and obesity is a strong predictor of poor DSF and DDFS. Preventive strategies to reduce not only the prevalence of obesity and breast cancer but also the mortality must be recognized as the cost-effective public-health policy for Turkey.     

Evaluation of sexual function in women with overactive bladder syndrome

INTRODUCTION: Of late, little data is available concerning factors affecting female sexual function. In the present study, we evaluated the effects of overactive bladder (OAB) syndrome symptoms on female sexual function. MATERIALS AND METHODS: 40 patients with OAB symptoms and 40 age-matched women as a control group were evaluated using the Female Sexual Function Index (FSFI) for sexual function. According to the presence of urge incontinence, women with OAB were also divided into wet and dry groups. After completion of the forms, groups were compared. RESULTS: Although scores of all domains of FSFI (desire, arousal, lubrication, orgasm, satisfaction, pain and total) in the OAB group were found to be lower than in the control group, only 'desire' was found to be significantly different (p = 0.035). The FSFI scores of the OAB-dry and OAB-wet group were similar to each other. CONCLUSION: The results indicate that there is a trend toward lower sexual function scores in women with OAB compared to controls.