Safety of Etoricoxib, Celecoxib, and Nonselective Nonsteroidal Antiinflammatory Drugs in Ankylosing Spondylitis and Other Spondyloarthritis Patients: A Swedish National Population-Based Cohort Study.

OBJECTIVE: Safety data regarding the use of etoricoxib and other nonsteroidal antiinflammatory drugs (NSAIDs) in ankylosing spondylitis (AS) and other spondyloarthritis (SpA) patients are rather limited. Our objective was to estimate and compare rates of gastrointestinal, renovascular, and cardiovascular adverse events in patients exposed to etoricoxib, celecoxib, or nonselective NSAIDs or totally unexposed to NSAIDs. METHODS: We performed a national register-based cohort study on patients with AS or SpA (n = 21,872) identified in the Swedish national patient register from 1987-2009. Treatment exposure was assessed time dependently based on the prescription drug register from 2006-2009, adjusting for sociodemographics and comorbidities derived from national population-based registers. RESULTS: Exposure to etoricoxib, celecoxib, and nonselective NSAIDs was 7.6%, 3.9%, and 71.2%, respectively. No major risk differences for serious cardiovascular, gastrointestinal, or renal adverse events were seen among the 3 exposure groups. Patients unexposed to NSAIDs had more baseline comorbidities and an increased relative risk for congestive heart failure events during the study period (2.0, 95% confidence interval [95% CI] 1.3-3.2). The relative risk for atherosclerotic events was nonsignificant when compared to the nonselective NSAID group (1.0, 95% CI 0.7-1.5), while the relative risk for gastrointestinal events was lower for unexposed patients (0.5, 95% CI 0.4-0.7). CONCLUSION: Overall, serious adverse events related to nonselective NSAIDs, etoricoxib, and celecoxib were similar and in the range of what would be expected in a group of SpA patients. Patients unexposed to NSAIDs had considerably more baseline comorbidities and increased risk for congestive heart failure, reflecting a selection of patients being prescribed NSAIDs in clinical practice.

The number needed to treat for second-generation biologics when treating established rheumatoid arthritis: a systematic quantitative review of randomized controlled trials.

OBJECTIVE: To evaluate the number needed to treat (NNT) and the number needed to harm (NNH) of the second-generation biologics abatacept, certolizumab, golimumab, rituximab, and tocilizumab in patients with established rheumatoid arthritis (RA) taking concomitant methotrexate (MTX). METHODS: A systematic literature search of MEDLINE, EMBASE, Web of Science, and the Cochrane Register of Controlled Trials was conducted up to 1 November 2009. We selected any published randomized, double-blind, MTX-controlled study including RA patients with a mean disease duration of at least 5 years before entering a pivotal trial on second-generation biological therapy. Studies eligible for inclusion involved patients, who had previously shown inadequate response to conventional disease-modifying anti-rheumatic drug (DMARD) therapy. Pre-specified binary outcomes were extracted with a preference for 1-year data (6-month data were used if no data were available for 1 year). Two reviewers independently extracted the data necessary to estimate the absolute measures in a non-responder intention-to-treat (ITT) analysis. RESULTS: Five randomized controlled trials, one for each of the drugs, were selected and data extracted according to published data at endpoint for American College of Rheumatology 50% (ACR50)-responding patients, and withdrawals due to adverse events. NNT ranged from four to six treated patients to achieve one ACR50 response, while withdrawals due to adverse events were few and non-significant compared to the placebo group, except for rituximab administered as 1000 mg. CONCLUSION: Comparable efficacy was shown by the five biological agents studied, with few adverse events. However, for rituximab, tocilizumab, and golimumab, only 6-month data were available, hampering the external validity with regard to long-term efficacy and tolerability. A low dose (500 mg) of rituximab may be as effective as the recommended dose of 1000 mg.

Muscle size, neuromuscular activation, and rapid force characteristics in elderly men and women: effects of unilateral long-term disuse due to hip-osteoarthritis.

Substantial evidence exists for the age-related decline in muscle strength and neural function, but the effect of long-term disuse in the elderly is largely unexplored. The present study examined the effect of unilateral long-term limb disuse on maximal voluntary quadriceps contraction (MVC), lean quadriceps muscle cross-sectional area (LCSA), contractile rate of force development (RFD, Delta force/Delta time), impulse (integral force dt), muscle activation deficit (interpolated twitch technique), maximal neuromuscular activity [electromyogram (EMG)], and antagonist muscle coactivation in elderly men (M: 60-86 yr; n = 19) and women (W: 60-86 yr; n = 20) with unilateral chronic hip-osteoarthritis. Both sides were examined to compare the effect of long-term decreased activity on the affected (AF) leg with the unaffected (UN) side. AF had a significant lower MVC (W: 20%; M: 20%), LCSA (W: 8%; M: 10%), contractile RFD (W: 17-26%; M: 15-24%), impulse (W: 10-19%, M: 19-20%), maximal EMG amplitude (W: 22-25%, M: 22-28%), and an increased muscle activation deficit (-18%) compared with UN. Furthermore, women were less strong (AF: 40%; UN: 39%), had less muscle mass (AF: 33%; UN: 34%), and had a lower RFD (AF: 38-50%; UN: 41-48%) compared with men. Similarly, maximum EMG amplitude was smaller for both agonists (AF: 51-63%; UN: 35-61%) and antagonist (AF: 49-64%; UN: 36-56%) muscles in women compared with men. However, when MVC and RFD were normalized to LCSA, there were no differences between genders. The present data demonstrate that disuse leads to a marked loss of muscle strength and muscle mass in elderly individuals. Furthermore, the data indicate that neuromuscular activation and contractile RFD are more affected by long-term disuse than maximal muscle strength, which may increase the future risk for falls.

[Patients with early stages of endometrial cancer should be spared adjuvant radiotherapy. Danish Endometrial Cancer Group]. / Patienter med tidlige stadier af endometriecancer bør skånes for adjuverende strålebehandling.

In an attempt to create uniform nationwide guidelines for the management of all stages of endometrial carcinoma, and to limit the use of adjuvant radiation therapy in stage I disease to high-risk patients only, a protocol was developed by the Danish Endometrial Cancer group (DEMCA). From September 1986 through August 1988, 1214 women in Denmark with newly diagnosed carcinoma of the endometrium have been treated according to this protocol. This figure represents all endometrial carcinomas diagnosed in Denmark during this two-year period. The primary treatment was total abdominal hysterectomy and bilateral salpingo-oophorectomy, no preoperative radiation therapy was delivered. In 1039 cases no macroscopic residual tumour and/or microscopic tumor tissue in the resection margins was found following surgery. Based on surgery and histopathology, these patients were classified as: P-stage I low risk (n = 641), P-stage I high risk (n = 235), P-stage II (n = 105) and P-stage III, Group 1 (n = 58). No postoperative radiation therapy was given to P-I low risk cases. P-I high risk, P-II, and P-III (Group 1) cases received external radiation therapy. Recurrence rate at 68-92 months follow-up was 45/641 (7%) in P-I low risk, 36/235 (15%) in P-I high risk, 30/105 (29%) in P-II, and 27/58 (47%) in P-III (Group 1) cases. Fifteen of 17 vaginal recurrences in P-I low risk cases were salvaged (mean observation time 61 months). In this population-based investigation it has been shown that P-stage low-risk patients are adequately treated by total abdominal hysterectomy and bilateral salpingo-oophorectomy, and that no pre- or postoperative radiation therapy is necessary.

The role of serum tetranectin, CA 125, and a combined index as tumor markers in women with pelvic tumors.

Serum tetranectin (Se-TN) and CA-125 were measured in 315 patients with a pelvic tumor and 458 healthy females. At a false-positive rate of 0.7% the sensitivity for ovarian cancer stage 1 and 2 was 33% for Se-TN and 76% for both CA 125 and an index based on Se-TN and CA 125 (Index 1). At a false-positive rate of 0.4% the sensitivity was 29% for Se-TN, 62% for CA 125 (35 U/ml), and 76% for Index 1. A negative correlation was found between the Se-TN level and the stage of cancer. The sensitivity for benign tumors was 6% for Se-TN, 17% for CA 125, and 21% for Index 1 at a false-positive rate of 0.4%. In the present study the sensitivity and specificity levels of Se-TN were not sufficiently high to warrant the use of Se-TN as an individual marker for ovarian cancer. The sensitivity rose with the index-based Se-TN and CA 125 without causing a concomitant increase in the rate of false-positive results. None of the markers rose to levels that would allow their use in clinical diagnosis to discriminate between localized cancer and benign tumors.

[Treatment of cervix cancer in Denmark]. / Behandlingen af cancer cervicis uteri i Danmark.

The current status of cervical cancer treatment in Denmark is discussed. Diagnostic aspects and problems of classification are presented briefly supplemented with a comment on new prognostic parameters based on a semiquantitative score system and flow cytometry. Surgery is the treatment of election for the early stages whereas radiotherapy is the treatment of choice in advanced stages. Chemotherapy should only be employed in the framework of clinical trials. It is concluded that centralised treatment should be maintained.